Comparison of the Oral Microbiomes of Canines and Their Owners Using Next-Generation Sequencing

PubMed Central

Oh, Changin; Lee, Kunkyu; Cheong, Yeotaek; Lee, Sang-Won; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Lee, Joong-Bok

2015-01-01

The oral microbiome, which is closely associated with many diseases, and the resident pathogenic oral bacteria, which can be transferred by close physical contact, are important public health considerations. Although the dog is the most common companion animal, the composition of the canine oral microbiome, which may include human pathogenic bacteria, and its relationship with that of their owners are unclear. In this study, 16S rDNA pyrosequencing was used to compare the oral microbiomes of 10 dogs and their owners and to identify zoonotic pathogens. Pyrosequencing revealed 246 operational taxonomic units in the 10 samples, representing 57 genera from eight bacterial phyla. Firmicutes (57.6%), Proteobacteria (21.6%), Bacteroidetes (9.8%), Actinobacteria (7.1%), and Fusobacteria (3.9%) were the predominant phyla in the human oral samples, whereas Proteobacteria (25.7%), Actinobacteria (21%), Bacteroidetes (19.7%), Firmicutes (19.3%), and Fusobacteria (12.3%) were predominant in the canine oral samples. The predominant genera in the human samples were Streptococcus (43.9%), Neisseria (10.3%), Haemophilus (9.6%), Prevotella (8.4%), and Veillonella (8.1%), whereas the predominant genera in the canine samples were Actinomyces (17.2%), Unknown (16.8), Porphyromonas (14.8), Fusobacterium (11.8), and Neisseria (7.2%). The oral microbiomes of dogs and their owners were appreciably different, and similarity in the microbiomes of canines and their owners was not correlated with residing in the same household. Oral-to-oral transfer of Neisseria shayeganii, Porphyromonas canigingivalis, Tannerella forsythia, and Streptococcus minor from dogs to humans was suspected. The finding of potentially zoonotic and periodontopathic bacteria in the canine oral microbiome may be a public health concern. PMID:26134411

Oral Microbiome Metabolism: From "Who Are They?" to "What Are They Doing?".

PubMed

Takahashi, N

2015-12-01

Recent advances in molecular biology have facilitated analyses of the oral microbiome ("Who are they?"); however, its functions (e.g., metabolic activities) are poorly understood ("What are they doing?"). This review aims to summarize our current understanding of the metabolism of the oral microbiome. Saccharolytic bacteria-including Streptococcus, Actinomyces, and Lactobacillus species-degrade carbohydrates into organic acids via the Embden-Meyerhof-Parnas pathway and several of its branch pathways, resulting in dental caries, while alkalization and acid neutralization via the arginine deiminase system, urease, and so on, counteract acidification. Proteolytic/amino acid-degrading bacteria, including Prevotella and Porphyromonas species, break down proteins and peptides into amino acids and degrade them further via specific pathways to produce short-chain fatty acids, ammonia, sulfur compounds, and indole/skatole, which act as virulent and modifying factors in periodontitis and oral malodor. Furthermore, it is suggested that ethanol-derived acetaldehyde can cause oral cancer, while nitrate-derived nitrite can aid caries prevention and systemic health. Microbial metabolic activity is influenced by the oral environment; however, it can also modify the oral environment, enhance the pathogenicity of bacteria, and induce microbial selection to create more pathogenic microbiome. Taking a metabolomic approach to analyzing the oral microbiome is crucial to improving our understanding of the functions of the oral microbiome. © International & American Associations for Dental Research 2015.

The Oral Microbiome in Health and Its Implication in Oral and Systemic Diseases.

PubMed

Sampaio-Maia, B; Caldas, I M; Pereira, M L; Pérez-Mongiovi, D; Araujo, R

2016-01-01

The oral microbiome can alter the balance between health and disease, locally and systemically. Within the oral cavity, bacteria, archaea, fungi, protozoa, and viruses may all be found, each having a particular role, but strongly interacting with each other and with the host, in sickness or in health. A description on how colonization occurs and how the oral microbiome dynamically evolves throughout the host's life is given. In this chapter the authors also address oral and nonoral conditions in which oral microorganisms may play a role in the etiology and progression, presenting the up-to-date knowledge on oral dysbiosis as well as the known underlying pathophysiologic mechanisms involving oral microorganisms in each condition. In oral pathology, oral microorganisms are associated with several diseases, namely dental caries, periodontal diseases, endodontic infections, and also oral cancer. In systemic diseases, nonoral infections, adverse pregnancy outcomes, cardiovascular diseases, and diabetes are among the most prevalent pathologies linked with oral cavity microorganisms. The knowledge on how colonization occurs, how oral microbiome coevolves with the host, and how oral microorganisms interact with each other may be a key factor to understand diseases etiology and progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Understanding Caries From the Oral Microbiome Perspective.

PubMed

Tanner, Anne C R; Kressirer, Christine A; Faller, Lina L

2016-07-01

Dental caries is a major disease of the oral cavity with profound clinical significance. Caries results from a transition of a healthy oral microbiome into an acidogenic community of decreased microbial diversity in response to excessive dietary sugar intake. Microbiological cultivation, molecular identification, gene expression and metabolomic analyses show the importance of the entire microbial community in understanding the role of the microbiome in the pathology of caries.

Progress in oral personalized medicine: contribution of ‘omics’

PubMed Central

Glurich, Ingrid; Acharya, Amit; Brilliant, Murray H.; Shukla, Sanjay K.

2015-01-01

Background Precision medicine (PM), representing clinically applicable personalized medicine, proactively integrates and interprets multidimensional personal health data, including clinical, ‘omics’, and environmental profiles, into clinical practice. Realization of PM remains in progress. Objective The focus of this review is to provide a descriptive narrative overview of: 1) the current status of oral personalized medicine; and 2) recent advances in genomics and related ‘omic’ and emerging research domains contributing to advancing oral-systemic PM, with special emphasis on current understanding of oral microbiomes. Design A scan of peer-reviewed literature describing oral PM or ‘omic’-based research conducted on humans/data published in English within the last 5 years in journals indexed in the PubMed database was conducted using mesh search terms. An evidence-based approach was used to report on recent advances with potential to advance PM in the context of historical critical and systematic reviews to delineate current state-of-the-art technologies. Special focus was placed on oral microbiome research associated with health and disease states, emerging research domains, and technological advances, which are positioning realization of PM. Results This review summarizes: 1) evolving conceptualization of personalized medicine; 2) emerging insight into roles of oral infectious and inflammatory processes as contributors to both oral and systemic diseases; 3) community shifts in microbiota that may contribute to disease; 4) evidence pointing to new uncharacterized potential oral pathogens; 5) advances in technological approaches to ‘omics’ research that will accelerate PM; 6) emerging research domains that expand insights into host–microbe interaction including inter-kingdom communication, systems and network analysis, and salivaomics; and 7) advances in informatics and big data analysis capabilities to facilitate interpretation of host and microbiome-associated datasets. Furthermore, progress in clinically applicable screening assays and biomarker definition to inform clinical care are briefly explored. Conclusion Advancement of oral PM currently remains in research and discovery phases. Although substantive progress has been made in advancing the understanding of the role of microbiome dynamics in health and disease and is being leveraged to advance early efforts at clinical translation, further research is required to discern interpretable constituency patterns in the complex interactions of these microbial communities in health and disease. Advances in biotechnology and bioinformatics facilitating novel approaches to rapid analysis and interpretation of large datasets are providing new insights into oral health and disease, potentiating clinical application and advancing realization of PM within the next decade. PMID:26344171

The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

PubMed Central

Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

2015-01-01

Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

The $100 Genome: Implications for the DoD

DTIC Science & Technology

2010-12-15

Phenotypes Influenced by the Microbiome In a recent study (Vijay-Kumar et al. 2010), gut microbes from obese mice were transferred to thin mice whose gut ...extraordinary genetic diversity of the gut microbiome , it is expected that these organisms (which usually have the first chance to interact with orally...Human Microbiome . In some cases it may be useful to sequence metagenomic samples of the microbiomes that colonize the human gut . oral cavity or other

Human Microbiome and HIV/AIDS

PubMed Central

Li, Yihong; Yang, Liying; Pei, Zhiheng; Poles, Michael; Abrams, William R.; Malamud, Daniel

2013-01-01

Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of “crosstalk” between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection. PMID:22193889

Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease

PubMed Central

Ghodsi, Mohammad; Sommer, Daniel D.; Gibbons, Theodore R.; Treangen, Todd J.; Chang, Yi-Chien; Li, Shan; Stine, O. Colin; Hasturk, Hatice; Kasif, Simon; Segrè, Daniel; Pop, Mihai; Amar, Salomon

2012-01-01

The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (∼2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ∼90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes. PMID:22675498

Cigarette smoking and the oral microbiome in a large study of American adults

PubMed Central

Wu, Jing; Peters, Brandilyn A; Dominianni, Christine; Zhang, Yilong; Pei, Zhiheng; Yang, Liying; Ma, Yingfei; Purdue, Mark P; Jacobs, Eric J; Gapstur, Susan M; Li, Huilin; Alekseyenko, Alexander V; Hayes, Richard B; Ahn, Jiyoung

2016-01-01

Oral microbiome dysbiosis is associated with oral disease and potentially with systemic diseases; however, the determinants of these microbial imbalances are largely unknown. In a study of 1204 US adults, we assessed the relationship of cigarette smoking with the oral microbiome. 16S rRNA gene sequencing was performed on DNA from oral wash samples, sequences were clustered into operational taxonomic units (OTUs) using QIIME and metagenomic content was inferred using PICRUSt. Overall oral microbiome composition differed between current and non-current (former and never) smokers (P<0.001). Current smokers had lower relative abundance of the phylum Proteobacteria (4.6%) compared with never smokers (11.7%) (false discovery rate q=5.2 × 10−7), with no difference between former and never smokers; the depletion of Proteobacteria in current smokers was also observed at class, genus and OTU levels. Taxa not belonging to Proteobacteria were also associated with smoking: the genera Capnocytophaga, Peptostreptococcus and Leptotrichia were depleted, while Atopobium and Streptococcus were enriched, in current compared with never smokers. Functional analysis from inferred metagenomes showed that bacterial genera depleted by smoking were related to carbohydrate and energy metabolism, and to xenobiotic metabolism. Our findings demonstrate that smoking alters the oral microbiome, potentially leading to shifts in functional pathways with implications for smoking-related diseases. PMID:27015003

Dysbiosis as a determinant factor of systemic and oral pathology: importance of microbiome.

PubMed

Chimenos-Küstner, Eduardo; Giovannoni, María Laura; Schemel-Suárez, Mayra

2017-10-11

Advances in genetic and epigenetic studies modified some concepts of health and disease that had been kept intact for decades. In this respect, in the last few years, microorganisms that have evolved with superior life forms for millions of years have taken an increased prominence. The genes of organisms and their microbiota constitute a microbiome that intervenes in health maintenance. The oral cavity is inhabited by a variety of microorganisms, their control aids in stabilising oral and systemic disease. The objective of this article is to update some concepts related to oral microbiome and its correlation with general and oral health. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Ecological therapeutic opportunities for oral diseases

PubMed Central

Hoare, Anilei; Marsh, Philip D.; Diaz, Patricia I.

2017-01-01

SUMMARY The three main oral diseases of humans, that is caries, periodontal diseases and oral candidiasis, are associated with microbiome shifts initiated by changes in the oral environment and/or decreased effectiveness of mucosal immune surveillance. In this review we discuss the role that microbial-based therapies may have in the control of these conditions. Most investigations on the use of microorganisms for management of oral disease have been conducted with probiotic strains with some positive but very discrete clinical outcomes. Other strategies such as whole oral microbiome transplantation or modification of community function by enrichment with health-promoting indigenous oral strains may offer more promise but research in this field is still in its infancy. Any microbial-based therapeutics for oral conditions, however, are likely to be only one component within a holistic preventive strategy that should also aim at modification of the environmental influences responsible for the initiation and perpetuation of microbiome shifts associated with oral dysbiosis. PMID:28840820

Ecological Therapeutic Opportunities for Oral Diseases.

PubMed

Hoare, Anilei; Marsh, Philip D; Diaz, Patricia I

2017-08-01

The three main oral diseases of humans, that is, caries, periodontal diseases, and oral candidiasis, are associated with microbiome shifts initiated by changes in the oral environment and/or decreased effectiveness of mucosal immune surveillance. In this review, we discuss the role that microbial-based therapies may have in the control of these conditions. Most investigations on the use of microorganisms for management of oral disease have been conducted with probiotic strains with some positive but very discrete clinical outcomes. Other strategies such as whole oral microbiome transplantation or modification of community function by enrichment with health-promoting indigenous oral strains may offer more promise, but research in this field is still in its infancy. Any microbial-based therapeutics for oral conditions, however, are likely to be only one component within a holistic preventive strategy that should also aim at modification of the environmental influences responsible for the initiation and perpetuation of microbiome shifts associated with oral dysbiosis.

Characterization of the salivary microbiome in people with obesity

PubMed Central

Zhang, Qian

2018-01-01

Background The interactions between the gut microbiome and obesity have been extensively studied. Although the oral cavity is the gateway to the gut, and is extensively colonized with microbes, little is known about the oral microbiome in people with obesity. In the present study, we investigated the salivary microbiome in obese and normal weight healthy participants using metagenomic analysis. The subjects were categorized into two groups, obesity and normal weight, based on their BMIs. Methods We characterized the salivary microbiome of 33 adults with obesity and 29 normal weight controls using high-throughput sequencing of the V3–V4 region of the 16S rRNA gene (Illumina MiSeq). None of the selected participants had systemic, oral mucosal, or periodontal diseases. Results The salivary microbiome of the obesity group was distinct from that of the normal weight group. The salivary microbiome of periodontally healthy people with obesity had both significantly lower bacterial diversity and richness compared with the controls. The genus Prevotella, Granulicatella, Peptostreptococcus, Solobacterium, Catonella, and Mogibacterium were significantly more abundant in the obesity group; meanwhile the genus Haemophilus, Corynebacterium, Capnocytophaga, and Staphylococcus were less abundant in the obesity group. We also performed a functional analysis of the inferred metagenomes, and showed that the salivary community associated with obesity had a stronger signature of immune disease and a decreased functional signature related to environmental adaptation and Xenobiotics biodegradation compared with the normal weight controls. Discussion Our study demonstrates that the microbial diversity and structure of the salivary microbiome in people with obesity are significantly different from those of normal weight controls. These results suggested that changes in the structure and function of salivary microbiome in people with obesity might reflect their susceptibility to oral diseases. PMID:29576948

HuMiChip: Development of a Functional Gene Array for the Study of Human Microbiomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tu, Q.; Deng, Ye; Lin, Lu

Microbiomes play very important roles in terms of nutrition, health and disease by interacting with their hosts. Based on sequence data currently available in public domains, we have developed a functional gene array to monitor both organismal and functional gene profiles of normal microbiota in human and mouse hosts, and such an array is called human and mouse microbiota array, HMM-Chip. First, seed sequences were identified from KEGG databases, and used to construct a seed database (seedDB) containing 136 gene families in 19 metabolic pathways closely related to human and mouse microbiomes. Second, a mother database (motherDB) was constructed withmore » 81 genomes of bacterial strains with 54 from gut and 27 from oral environments, and 16 metagenomes, and used for selection of genes and probe design. Gene prediction was performed by Glimmer3 for bacterial genomes, and by the Metagene program for metagenomes. In total, 228,240 and 801,599 genes were identified for bacterial genomes and metagenomes, respectively. Then the motherDB was searched against the seedDB using the HMMer program, and gene sequences in the motherDB that were highly homologous with seed sequences in the seedDB were used for probe design by the CommOligo software. Different degrees of specific probes, including gene-specific, inclusive and exclusive group-specific probes were selected. All candidate probes were checked against the motherDB and NCBI databases for specificity. Finally, 7,763 probes covering 91.2percent (12,601 out of 13,814) HMMer confirmed sequences from 75 bacterial genomes and 16 metagenomes were selected. This developed HMM-Chip is able to detect the diversity and abundance of functional genes, the gene expression of microbial communities, and potentially, the interactions of microorganisms and their hosts.« less

Divergent Effects of Dendritic Cells on Pancreatitis

DTIC Science & Technology

2013-09-01

may possibly be a role for endogenous LPS derived from gut bacteria in modulating pancreatic carcinogenesis. Indeed, a role for the microbiome in... microbiome via TLR4 requires more exact investigation. An equally compelling discovery in this study is that MyD88 blockade vigorously accelerates pancreatic...Oral microbiome and oral and gastrointestinal cancer risk. Cancer Causes Control. 23:399–404. http:// dx.doi.org/10.1007/s10552-011-9892-7 Ammann, R.W

Oral Health and the Oral Microbiome in Pancreatic Cancer: An Overview of Epidemiological Studies.

PubMed

Bracci, Paige M

The aim was to provide a cohesive overview of epidemiological studies of periodontal disease, oral microbiome profiles, and pancreatic cancer risk. A PubMed search of articles published in English through July 2017 with additional review of bibliographies of identified articles. Risk estimates for periodontal disease associated with pancreatic cancer consistently ranged from 1.5 to 2, aligning with a meta-analysis summary relative risk of 1.74. Analyses of antibodies to pathogenic and/or commensal oral bacteria in prediagnostic blood provided evidence that some oral bacteria and oral microbial diversity may be related to pancreatic cancer. Overall, the data present a plausible but complex relationship among pancreatic cancer, the oral microbiome, periodontal disease, and other risk factors that might be explained by systemic effects on immune and inflammatory processes. Larger comprehensive studies that examine serially collected epidemiological/clinical data and blood, tissue, and various microbial samples are needed to definitively determine how and whether oral health-related factors contribute to pancreatic cancer risk.

The Effect of Fixed Orthodontic Appliances and Fluoride Mouthwash on the Oral Microbiome of Adolescents – A Randomized Controlled Clinical Trial

PubMed Central

Buijs, Mark J.; Elyassi, Yassaman; van der Veen, Monique H.; Crielaard, Wim; ten Cate, Jacob M.; Zaura, Egija

2015-01-01

While the aesthetic effect of orthodontic treatment is clear, the knowledge on how it influences the oral microbiota and the consequential effects on oral health are limited. In this randomized controlled clinical trial we investigated the changes introduced in the oral ecosystem, during and after orthodontic treatment with fixed appliances in combination with or without a fluoride mouthwash, of 10–16.8 year old individuals (N = 91). We followed several clinical parameters in time, in combination with microbiome changes using next-generation sequencing of the bacterial 16S rRNA gene. During the course of our study, the oral microbial community displayed remarkable resilience towards the disturbances it was presented with. The effects of the fluoride mouthwash on the microbial composition were trivial. More pronounced microbial changes were related to gingival health status, orthodontic treatment and time. Periodontal pathogens (e.g. Selenomonas and Porphyromonas) were highest in abundance during the orthodontic treatment, while the health associated Streptococcus, Rothia and Haemophilus gained abundance towards the end and after the orthodontic treatment. Only minor compositional changes remained in the oral microbiome after the end of treatment. We conclude that, provided proper oral hygiene is maintained, changes in the oral microbiome composition resulting from orthodontic treatment are minimal and do not negatively affect oral health. PMID:26332408

The Effect of Fixed Orthodontic Appliances and Fluoride Mouthwash on the Oral Microbiome of Adolescents - A Randomized Controlled Clinical Trial.

PubMed

Koopman, Jessica E; van der Kaaij, Nicoline C W; Buijs, Mark J; Elyassi, Yassaman; van der Veen, Monique H; Crielaard, Wim; Ten Cate, Jacob M; Zaura, Egija

2015-01-01

While the aesthetic effect of orthodontic treatment is clear, the knowledge on how it influences the oral microbiota and the consequential effects on oral health are limited. In this randomized controlled clinical trial we investigated the changes introduced in the oral ecosystem, during and after orthodontic treatment with fixed appliances in combination with or without a fluoride mouthwash, of 10-16.8 year old individuals (N = 91). We followed several clinical parameters in time, in combination with microbiome changes using next-generation sequencing of the bacterial 16S rRNA gene. During the course of our study, the oral microbial community displayed remarkable resilience towards the disturbances it was presented with. The effects of the fluoride mouthwash on the microbial composition were trivial. More pronounced microbial changes were related to gingival health status, orthodontic treatment and time. Periodontal pathogens (e.g. Selenomonas and Porphyromonas) were highest in abundance during the orthodontic treatment, while the health associated Streptococcus, Rothia and Haemophilus gained abundance towards the end and after the orthodontic treatment. Only minor compositional changes remained in the oral microbiome after the end of treatment. We conclude that, provided proper oral hygiene is maintained, changes in the oral microbiome composition resulting from orthodontic treatment are minimal and do not negatively affect oral health.

Defining the healthy "core microbiome" of oral microbial communities

PubMed Central

2009-01-01

Background Most studies examining the commensal human oral microbiome are focused on disease or are limited in methodology. In order to diagnose and treat diseases at an early and reversible stage an in-depth definition of health is indispensible. The aim of this study therefore was to define the healthy oral microbiome using recent advances in sequencing technology (454 pyrosequencing). Results We sampled and sequenced microbiomes from several intraoral niches (dental surfaces, cheek, hard palate, tongue and saliva) in three healthy individuals. Within an individual oral cavity, we found over 3600 unique sequences, over 500 different OTUs or "species-level" phylotypes (sequences that clustered at 3% genetic difference) and 88 - 104 higher taxa (genus or more inclusive taxon). The predominant taxa belonged to Firmicutes (genus Streptococcus, family Veillonellaceae, genus Granulicatella), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Corynebacterium, Rothia, Actinomyces), Bacteroidetes (genus Prevotella, Capnocytophaga, Porphyromonas) and Fusobacteria (genus Fusobacterium). Each individual sample harboured on average 266 "species-level" phylotypes (SD 67; range 123 - 326) with cheek samples being the least diverse and the dental samples from approximal surfaces showing the highest diversity. Principal component analysis discriminated the profiles of the samples originating from shedding surfaces (mucosa of tongue, cheek and palate) from the samples that were obtained from solid surfaces (teeth). There was a large overlap in the higher taxa, "species-level" phylotypes and unique sequences among the three microbiomes: 84% of the higher taxa, 75% of the OTUs and 65% of the unique sequences were present in at least two of the three microbiomes. The three individuals shared 1660 of 6315 unique sequences. These 1660 sequences (the "core microbiome") contributed 66% of the reads. The overlapping OTUs contributed to 94% of the reads, while nearly all reads (99.8%) belonged to the shared higher taxa. Conclusions We obtained the first insight into the diversity and uniqueness of individual oral microbiomes at a resolution of next-generation sequencing. We showed that a major proportion of bacterial sequences of unrelated healthy individuals is identical, supporting the concept of a core microbiome at health. PMID:20003481

A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome.

PubMed

Warinner, Christina; Speller, Camilla; Collins, Matthew J

2015-01-19

The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes.

Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

PubMed Central

Gupta, Vinod K.; Paul, Sandip; Dutta, Chitra

2017-01-01

One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering. PMID:28690602

Oral microbiome in HIV-associated periodontitis.

PubMed

Noguera-Julian, Marc; Guillén, Yolanda; Peterson, Jessica; Reznik, David; Harris, Erica V; Joseph, Sandeep J; Rivera, Javier; Kannanganat, Sunil; Amara, Rama; Nguyen, Minh Ly; Mutembo, Simon; Paredes, Roger; Read, Timothy D; Marconi, Vincent C

2017-03-01

HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV- individuals at different levels of PD severity.This cross-sectional study included both HIV+ and HIV- patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations.Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV-) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P < 0.001). HIV status and PD severity showed a statistically significant impact on microbiome composition but only accounted for a combined 2% of variation. HIV+ samples were enriched in genera Abiotrophia, Neisseria, Kingella, and unclassified Neisseriaceae and depleted in Leptotrichia and Selenomonas. The Neisseria genus was consistently enriched in HIV+ participants regardless of sampling site and PD level. Immune markers were altered in HIV+ participants but did not show association with the oral microbiome.HIV-associated changes in oral microbiome result in subtle microbial signatures along different stages of PD that are common in independent oral anatomic sites.

Oral microbiome in HIV-associated periodontitis

PubMed Central

Noguera-Julian, Marc; Guillén, Yolanda; Peterson, Jessica; Reznik, David; Harris, Erica V.; Joseph, Sandeep J.; Rivera, Javier; Kannanganat, Sunil; Amara, Rama; Nguyen, Minh Ly; Mutembo, Simon; Paredes, Roger; Read, Timothy D.; Marconi, Vincent C.

2017-01-01

Abstract HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV– individuals at different levels of PD severity. This cross-sectional study included both HIV+ and HIV– patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations. Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV–) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P < 0.001). HIV status and PD severity showed a statistically significant impact on microbiome composition but only accounted for a combined 2% of variation. HIV+ samples were enriched in genera Abiotrophia, Neisseria, Kingella, and unclassified Neisseriaceae and depleted in Leptotrichia and Selenomonas. The Neisseria genus was consistently enriched in HIV+ participants regardless of sampling site and PD level. Immune markers were altered in HIV+ participants but did not show association with the oral microbiome. HIV-associated changes in oral microbiome result in subtle microbial signatures along different stages of PD that are common in independent oral anatomic sites. PMID:28328799

The influence of the intestinal microbiome on vaccine responses.

PubMed

Zimmermann, Petra; Curtis, Nigel

2018-06-13

There is substantial variation between individuals in the immune response to vaccinations. The intestinal microbiome plays a crucial rule in the development and regulation of the immune system and therefore its composition might affect how individuals respond to vaccinations. In this review, we summarise studies that investigated the influence of the intestinal microbiome on humoral and cellular vaccine responses. To date, only four studies (three in infants and one in adults) have investigated the influence of the intestinal microbiome on vaccine responses. All found an association between the intestinal microbiome and vaccine responses. Despite the heterogeneity in study designs (including different vaccines, schedules, timing of collection of stool and blood samples, analysis methods and reporting of results on different taxonomic levels), findings across studies were consistent: a higher relative abundance of the phylum Actinobacteria (oral and parenteral vaccines) and Firmicutes (oral vaccines) was associated with both higher humoral and higher cellular vaccine responses, while a higher relative abundance of the phylum Proteobacteria (oral and parenteral vaccines) and Bacteroidetes (oral vaccines) was associated with lower responses. Further, well-designed, adequately powered studies using whole-genome sequencing (to include the influence of viruses, fungi and parasites) are needed to investigate in more detail the influence of the intestinal microbiome on vaccine responses. This will help identify strategies to improve vaccine efficacy and duration of protection, particularly in infancy when the intestinal microbiome is more amenable to external influences and plays an important role in the development of the immune system. Copyright © 2018 Elsevier Ltd. All rights reserved.

Re-discovering periodontal butyric acid: New insights on an old metabolite.

PubMed

Cueno, Marni E; Ochiai, Kuniyasu

2016-05-01

The oral microbiome is composed of detrimental and beneficial microbial communities producing several microbial factors that could contribute to the development of the oral microbiome and, likewise, may lead to the development of host diseases. Metabolites, like short-chain fatty acids, are commonly produced by the oral microbiome and serve various functions. Among the periodontal short-chain fatty acids, butyric acid is mainly produced by periodontopathic bacteria and, attributable to the butyrate paradox, is postulated to exhibit a dual function depending on butyric acid concentration. A better understanding of the interconnecting networks that would influence butyric acid function in the oral cavity may shed a new light on the current existing knowledge and view regarding butyric acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Towards microbiome transplant as a therapy for periodontitis: an exploratory study of periodontitis microbial signature contrasted by oral health, caries and edentulism.

PubMed

Pozhitkov, Alex E; Leroux, Brian G; Randolph, Timothy W; Beikler, Thomas; Flemmig, Thomas F; Noble, Peter A

2015-10-14

Conventional periodontal therapy aims at controlling supra- and subgingival biofilms. Although periodontal therapy was shown to improve periodontal health, it does not completely arrest the disease. Almost all subjects compliant with periodontal maintenance continue to experience progressive clinical attachment loss and a fraction of them loses teeth. An oral microbial transplant may be a new alternative for treating periodontitis (inspired by fecal transplant). First, it must be established that microbiomes of oral health and periodontitis are distinct. In that case, the health-associated microbiome could be introduced into the oral cavity of periodontitis patients. This relates to the goals of our study: (i) to assess if microbial communities of the entire oral cavity of subjects with periodontitis were different from or oral health contrasted by microbiotas of caries and edentulism patients; (ii) to test in vitro if safe concentration of sodium hypochlorite could be used for initial eradication of the original oral microbiota followed by a safe neutralization of the hypochlorite prior transplantation. Sixteen systemically healthy white adults with clinical signs of one of the following oral conditions were enrolled: periodontitis, established caries, edentulism, and oral health. Oral biofilm samples were collected from sub- and supra-gingival sites, and oral mucosae. DNA was extracted and 16S rRNA genes were amplified. Amplicons from the same patient were pooled, sequenced and quantified. Volunteer's oral plaque was treated with saline, 16 mM NaOCl and NaOCl neutralized by ascorbate buffer followed by plating on blood agar. Ordination plots of rRNA gene abundances revealed distinct groupings for the oral microbiomes of subjects with periodontitis, edentulism, or oral health. The oral microbiome in subjects with periodontitis showed the greatest diversity harboring 29 bacterial species at significantly higher abundance compared to subjects with the other assessed conditions. Healthy subjects had significantly higher abundance in 10 microbial species compared to the other conditions. NaOCl showed strong antimicrobial properties; nontoxic ascorbate was capable of neutralizing the hypochlorite. Distinct oral microbial signatures were found in subjects with periodontitis, edentulism, or oral health. This finding opens up a potential for a new therapy, whereby a health-related entire oral microbial community would be transplanted to the diseased patient.

Insights of the dental calculi microbiome of pre-Columbian inhabitants from Puerto Rico

PubMed Central

Narganes-Storde, Yvonne; Toranzos, Gary A.; Cano, Raul J.

2017-01-01

Background The study of ancient microorganisms in mineralized dental plaque or calculi is providing insights into microbial evolution, as well as lifestyles and disease states of extinct cultures; yet, little is still known about the oral microbial community structure and function of pre-Columbian Caribbean cultures. In the present study, we investigated the dental calculi microbiome and predicted function of one of these cultures, known as the Saladoid. The Saladoids were horticulturalists that emphasized root-crop production. Fruits, as well as small marine and terrestrial animals were also part of the Saladoid diet. Methods Dental calculi samples were recovered from the archaeological site of Sorcé, in the municipal island of Vieques, Puerto Rico, characterized using 16S rRNA gene high-throughput sequencing, and compared to the microbiome of previously characterized coprolites of the same culture, as well modern plaque, saliva and stool microbiomes available from the Human Microbiome Project. Results Actinobacteria, Proteobacteria and Firmicutes comprised the majority of the Saladoid dental calculi microbiome. The Saladoid dental calculi microbiome was distinct when compared to those of modern saliva and dental plaque, but showed the presence of common inhabitants of modern oral cavities including Streptococcus sp., Veillonella dispar and Rothia mucilaginosa. Cell motility, signal transduction and biosynthesis of other secondary metabolites may be unique features of the Saladoid microbiome. Discussion Results suggest that the Saladoid dental calculi microbiome structure and function may possibly reflect a horticulturalist lifestyle and distinct dietary habits. Results also open the opportunity to further elucidate oral disease states in extinct Caribbean cultures and extinct indigenous cultures with similar lifestyles. PMID:28480145

Insights of the dental calculi microbiome of pre-Columbian inhabitants from Puerto Rico.

PubMed

Santiago-Rodriguez, Tasha M; Narganes-Storde, Yvonne; Chanlatte-Baik, Luis; Toranzos, Gary A; Cano, Raul J

2017-01-01

The study of ancient microorganisms in mineralized dental plaque or calculi is providing insights into microbial evolution, as well as lifestyles and disease states of extinct cultures; yet, little is still known about the oral microbial community structure and function of pre-Columbian Caribbean cultures. In the present study, we investigated the dental calculi microbiome and predicted function of one of these cultures, known as the Saladoid. The Saladoids were horticulturalists that emphasized root-crop production. Fruits, as well as small marine and terrestrial animals were also part of the Saladoid diet. Dental calculi samples were recovered from the archaeological site of Sorcé, in the municipal island of Vieques, Puerto Rico, characterized using 16S rRNA gene high-throughput sequencing, and compared to the microbiome of previously characterized coprolites of the same culture, as well modern plaque, saliva and stool microbiomes available from the Human Microbiome Project. Actinobacteria, Proteobacteria and Firmicutes comprised the majority of the Saladoid dental calculi microbiome. The Saladoid dental calculi microbiome was distinct when compared to those of modern saliva and dental plaque, but showed the presence of common inhabitants of modern oral cavities including Streptococcus sp., Veillonella dispar and Rothia mucilaginosa . Cell motility, signal transduction and biosynthesis of other secondary metabolites may be unique features of the Saladoid microbiome. Results suggest that the Saladoid dental calculi microbiome structure and function may possibly reflect a horticulturalist lifestyle and distinct dietary habits. Results also open the opportunity to further elucidate oral disease states in extinct Caribbean cultures and extinct indigenous cultures with similar lifestyles.

Changes in Abundance of Oral Microbiota Associated with Oral Cancer

PubMed Central

Schmidt, Brian L.; Kuczynski, Justin; Bhattacharya, Aditi; Huey, Bing; Corby, Patricia M.; Queiroz, Erica L. S.; Nightingale, Kira; Kerr, A. Ross; DeLacure, Mark D.; Veeramachaneni, Ratna; Olshen, Adam B.; Albertson, Donna G.

2014-01-01

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence. PMID:24887397

Mouthguards: does the indigenous microbiome play a role in maintaining oral health?

PubMed

Kumar, Purnima S; Mason, Matthew R

2015-01-01

The existence of symbiotic relationships between bacteria and their hosts in various ecosystems have long been known to science. The human body also hosts vast numbers of bacteria in several habitats. Emerging evidence from the gastro-intestinal tract, genito-urinary tract and respiratory indicates that there are several health benefits to hosting a complex and diverse microbial community. Bacteria colonize the oral cavity within a few minutes after birth and form stable communities. Our knowledge of the oral microbiome has expanded exponentially with development of novel exploratory methods that allow us to examine diversity, structure, function, and topography without the need to cultivate the individual components of the biofilm. The purpose of this perspective, therefore, is to examine the strength of current evidence supporting a role for the oral microbiome in maintaining oral health. While several lines of evidence are emerging to suggest that indigenous oral microbiota may have a role in immune education and preventing pathogen expansion, much more work is needed to definitively establish whether oral bacteria do indeed contribute to sustaining oral health, and if so, the mechanisms underlying this role.

A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome

PubMed Central

Warinner, Christina; Speller, Camilla; Collins, Matthew J.

2015-01-01

The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes. PMID:25487328

Betel nut chewing, oral premalignant lesions, and the oral microbiome

PubMed Central

Hernandez, Brenda Y.; Zhu, Xuemei; Goodman, Marc T.; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C.

2017-01-01

Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes are involved in betel nut-induced oral carcinogenesis is only speculative. Further research is needed to discern the clinical significance of an altered oral microbiome and the mechanisms of oral cancer development in betel nut chewers. PMID:28225785

Betel nut chewing, oral premalignant lesions, and the oral microbiome.

PubMed

Hernandez, Brenda Y; Zhu, Xuemei; Goodman, Marc T; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C

2017-01-01

Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes are involved in betel nut-induced oral carcinogenesis is only speculative. Further research is needed to discern the clinical significance of an altered oral microbiome and the mechanisms of oral cancer development in betel nut chewers.

Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules.

PubMed

Edlund, Anna; Garg, Neha; Mohimani, Hosein; Gurevich, Alexey; He, Xuesong; Shi, Wenyuan; Dorrestein, Pieter C; McLean, Jeffrey S

2017-01-01

Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential influences from a wide diversity of bacterium-derived compounds that are illy defined. Here, we present the analysis of peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal perspective. Through comparative analysis of mass spectral profiles from a collection of cultured oral isolates and an established in vitro multispecies oral community, we found that the production of SMs both delineates a temporal expression pattern and allows discrimination between bacterial isolates at the species level. Importantly, the majority of the identified molecules were of unknown identity, and only ~2.2% could be annotated and classified. The catalogue of bacterially produced SMs we obtained in this study reveals an undiscovered molecular world for which compound isolation and ecosystem testing will facilitate a better understanding of their roles in human health and disease. IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug Discov 45:473-484, 2016, https://doi.org/10.1038/nrd.2016.32). This is a great advance over studying genes alone, which only inform about metabolic potential. Approximately 25,000 compounds have been chemically characterized thus far; however, the richness of metabolites such as SMs has been estimated to be as high as 1 × 10 30 in the biosphere (K. Garber, Nat Biotechnol 33:228-231, 2015, https://doi.org/10.1038/nbt.3161). Our classical, one-at-a-time activity-guided approach to compound identification continues to find the same known compounds and is also incredibly tedious, which represents a major bottleneck for global SM identification. These challenges have prompted new developments of databases and analysis tools that provide putative classifications of SMs by mass spectral alignments to already characterized tandem mass spectrometry spectra and databases containing structural information (e.g., PubChem and AntiMarin). In this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial isolates and a complex oral in vitro biofilm community of >100 species by using the Global Natural Products Social molecular Networking and the DEREPLICATOR infrastructures, which are methodologies that allow automated and putative annotation of PSMs. These approaches enabled the identification of an untapped resource of PSMs from oral bacteria showing species-unique patterns of secretion with putative matches to known bioactive compounds.

Acquisition and maturation of oral microbiome throughout childhood: An update

PubMed Central

Sampaio-Maia, Benedita; Monteiro-Silva, Filipa

2014-01-01

Traditional microbiology concepts are being renewed since the development of new microbiological technologies, such as, sequencing and large-scale genome analysis. Since the entry into the new millennium, a lot of new information has emerged regarding the oral microbiome. This revision presents an overview of this renewed knowledge on oral microbial community acquisition in the newborn and on the evolution of this microbiome to adulthood. Throughout childhood, the oral microbial load increases, but the microbial diversity decreases. The initial colonizers are related to the type of delivery, personal relationships, and living environment. These first colonizers seem to condition the subsequent colonization, which will lead to more complex and stable ecosystems in adulthood. These early oral microbial communities, therefore, play a major role in the development of the adult oral microbiota and may represent a source of both pathogenic and protective microorganisms in a very early stage of human life. The implications of this knowledge on the daily clinical practice of odontopediatrics are highlighted. PMID:25097637

The impact of horizontal gene transfer on the adaptive ability of the human oral microbiome.

PubMed

Roberts, Adam P; Kreth, Jens

2014-01-01

The oral microbiome is composed of a multitude of different species of bacteria, each capable of occupying one or more of the many different niches found within the human oral cavity. This community exhibits many types of complex interactions which enable it to colonize and rapidly respond to changes in the environment in which they live. One of these interactions is the transfer, or acquisition, of DNA within this environment, either from co-resident bacterial species or from exogenous sources. Horizontal gene transfer in the oral cavity gives some of the resident bacteria the opportunity to sample a truly enormous metagenome affording them considerable adaptive potential which may be key to survival in such a varying environment. In this review the underlying mechanisms of HGT are discussed in relation to the oral microbiome with numerous examples described where the direct acquisition of exogenous DNA has contributed to the fitness of the bacterial host within the human oral cavity.

Biological approach of dental caries management.

PubMed

Grigalauskienė, Rūta; Slabšinskienė, Eglė; Vasiliauskienė, Ingrida

2015-01-01

Dental caries is a disease induced by dental plaque, which can be described as a community of microorganisms (biofilm). Because of genetic and environmental factors a number of changes in the oral microbiome takes place; in case of commensalism and mutualism between biofilm microorganisms and the host, homeostasis in oral microbiome is maintained. However, when a risk factor occurs parasitic relationship starts prevailing and activity of the pathogenic cariogenic microorganisms increases leading to a dental caries. According to the newest technologies of molecular microbiology new cariogenic microorganisms species have been determined. Each individual's oral microbiome is as unique as his/her immune system; therefore, commonly taken caries prevention measures cannot be of the same effectiveness for all individuals. Each person has his own caries risk which is determined by the oral microbiome and immune system influenced by the environmental and genetic factors. Early caries diagnostic, risk assessment and individualized caries prevention plan will allow us to control the disease and achieve a desirable effect. For the dentist the most important thing is not to treat the consequences of the disease - cavities - but be aware of the dental caries as a biological phenomenon.

Microbiota, cirrhosis, and the emerging oral-gut-liver axis

PubMed Central

Acharya, Chathur; Bajaj, Jasmohan S.

2017-01-01

Cirrhosis is a prevalent cause of morbidity and mortality, especially for those at an advanced decompensated stage. Cirrhosis development and progression involves several important interorgan communications, and recently, the gut microbiome has been implicated in pathophysiology of the disease. Dysbiosis, defined as a pathological change in the microbiome, has a variable effect on the compensated versus decompensated stage of cirrhosis. Adverse microbial changes, both in composition and function, can act at several levels within the gut (stool and mucosal) and have also been described in the blood and oral cavity. While dysbiosis in the oral cavity could be a source of systemic inflammation, current cirrhosis treatment modalities are targeted toward the gut-liver axis and do not address the oral microbiome. As interventions designed to modulate oral dysbiosis may delay progression of cirrhosis, a better understanding of this process is of the utmost importance. The concept of oral microbiota dysbiosis in cirrhosis is relatively new; therefore, this review will highlight the emerging role of the oral-gut-liver axis and introduce perspectives for future research. PMID:28978799

The placenta harbors a unique microbiome.

PubMed

Aagaard, Kjersti; Ma, Jun; Antony, Kathleen M; Ganu, Radhika; Petrosino, Joseph; Versalovic, James

2014-05-21

Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001). Copyright © 2014, American Association for the Advancement of Science.

Human gut microbiota plays a role in the metabolism of drugs.

PubMed

Jourova, Lenka; Anzenbacher, Pavel; Anzenbacherova, Eva

2016-09-01

The gut microbiome, an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract, is now known to play a critical role in human health and predisposition to disease. It is also involved in the biotransformation of xenobiotics and several recent studies have shown that the gut microbiota can affect the pharmacokinetics of orally taken drugs with implications for their oral bioavailability. Review of Pubmed, Web of Science and Science Direct databases for the years 1957-2016. Recent studies make it clear that the human gut microbiota can play a major role in the metabolism of xenobiotics and, the stability and oral bioavailability of drugs. Over the past 50 years, more than 30 drugs have been identified as a substrate for intestinal bacteria. Questions concerning the impact of the gut microbiota on drug metabolism, remain unanswered or only partially answered, namely (i) what are the molecular mechanisms and which bacterial species are involved? (ii) What is the impact of host genotype and environmental factors on the composition and function of the gut microbiota, (iii) To what extent is the composition of the intestinal microbiome stable, transmissible, and resilient to perturbation? (iv) Has past exposure to a given drug any impact on future microbial response, and, if so, for how long? Answering such questions should be an integral part of pharmaceutical research and personalised health care.

Oral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure.

PubMed

Bryan, Nathan S; Tribble, Gena; Angelov, Nikola

2017-04-01

Having high blood pressure puts you at risk for heart disease and stroke, which are leading causes of death in the USA and worldwide. One out of every three Americans has hypertension, and it is estimated that despite aggressive treatment with medications, only about half of those medicated have managed blood pressure. Recent discoveries of the oral microbiome that reduces inorganic nitrate to nitrite and nitric oxide provide a new therapeutic target for the management of hypertension. The presence or absence of select and specific bacteria may determine steady-state blood pressure levels. Eradication of oral bacteria through antiseptic mouthwash or overuse of antibiotics causes blood pressure to increase. Allowing recolonization of nitrate- and nitrite-reducing bacteria can normalize blood pressure. This review will provide evidence of the link between oral microbiota and the production of nitric oxide and regulation of systemic blood pressure. Management of systemic hypertension through maintenance of the oral microbiome is a completely new paradigm in cardiovascular medicine.

The microbiome in prostate inflammation and prostate cancer.

PubMed

Porter, Corey M; Shrestha, Eva; Peiffer, Lauren B; Sfanos, Karen S

2018-05-23

The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response. We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer. Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease. In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.

Preliminary characterization of the oral microbiota of Chinese adults with and without gingivitis

PubMed Central

2011-01-01

Background Microbial communities inhabiting human mouth are associated with oral health and disease. Previous studies have indicated the general prevalence of adult gingivitis in China to be high. The aim of this study was to characterize in depth the oral microbiota of Chinese adults with or without gingivitis, by defining the microbial phylogenetic diversity and community-structure using highly paralleled pyrosequencing. Methods Six non-smoking Chinese, three with and three without gingivitis (age range 21-39 years, 4 females and 2 males) were enrolled in the present cross-sectional study. Gingival parameters of inflammation and bleeding on probing were characterized by a clinician using the Mazza Gingival Index (MGI). Plaque (sampled separately from four different oral sites) and salivary samples were obtained from each subject. Sequences and relative abundance of the bacterial 16 S rDNA PCR-amplicons were determined via pyrosequencing that produced 400 bp-long reads. The sequence data were analyzed via a computational pipeline customized for human oral microbiome analyses. Furthermore, the relative abundances of selected microbial groups were validated using quantitative PCR. Results The oral microbiomes from gingivitis and healthy subjects could be distinguished based on the distinct community structures of plaque microbiomes, but not the salivary microbiomes. Contributions of community members to community structure divergence were statistically accessed at the phylum, genus and species-like levels. Eight predominant taxa were found associated with gingivitis: TM7, Leptotrichia, Selenomonas, Streptococcus, Veillonella, Prevotella, Lautropia, and Haemophilus. Furthermore, 98 species-level OTUs were identified to be gingivitis-associated, which provided microbial features of gingivitis at a species resolution. Finally, for the two selected genera Streptococcus and Fusobacterium, Real-Time PCR based quantification of relative bacterial abundance validated the pyrosequencing-based results. Conclusions This methods study suggests that oral samples from this patient population of gingivitis can be characterized via plaque microbiome by pyrosequencing the 16 S rDNA genes. Further studies that characterize serial samples from subjects (longitudinal study design) with a larger population size may provide insight into the temporal and ecological features of oral microbial communities in clinically-defined states of gingivitis. PMID:22152152

Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

PubMed Central

Diaz, Patricia I.; Strausbaugh, Linda D.; Dongari-Bagtzoglou, Anna

2014-01-01

High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases. PMID:25120959

Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

PubMed

Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

2014-01-01

High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans.

PubMed

Vanhatalo, Anni; Blackwell, Jamie R; L'Heureux, Joanna; Williams, David W; Smith, Ann; van der Giezen, Mark; Winyard, Paul G; Kelly, James; Jones, Andrew M

2018-05-25

Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO 3 - )-nitrite (NO 2 - )-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO 3 - to NO 2 - . NO (generated from both NO 2 - and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO 3 - (12mmol/d) and placebo supplementation in young (18-22yrs) and old (70-79yrs) normotensive humans (n=18). NO 3 - supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (-46%; P<0.05). After NO 3 - supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (-60%) and Veillonella (-65%) were lower than in the placebo condition (all P<0.05). NO 3 - supplementation increased plasma concentration of NO 2 - and reduced systemic blood pressure in old (70-79yrs), but not young (18-22yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO 2 - ] in response to NO 3 - supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO 3 - , and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

REPRODUCIBLE RESEARCH WORKFLOW IN R FOR THE ANALYSIS OF PERSONALIZED HUMAN MICROBIOME DATA.

PubMed

Callahan, Benjamin; Proctor, Diana; Relman, David; Fukuyama, Julia; Holmes, Susan

2016-01-01

This article presents a reproducible research workflow for amplicon-based microbiome studies in personalized medicine created using Bioconductor packages and the knitr markdown interface.We show that sometimes a multiplicity of choices and lack of consistent documentation at each stage of the sequential processing pipeline used for the analysis of microbiome data can lead to spurious results. We propose its replacement with reproducible and documented analysis using R packages dada2, knitr, and phyloseq. This workflow implements both key stages of amplicon analysis: the initial filtering and denoising steps needed to construct taxonomic feature tables from error-containing sequencing reads (dada2), and the exploratory and inferential analysis of those feature tables and associated sample metadata (phyloseq). This workow facilitates reproducible interrogation of the full set of choices required in microbiome studies. We present several examples in which we leverage existing packages for analysis in a way that allows easy sharing and modification by others, and give pointers to articles that depend on this reproducible workflow for the study of longitudinal and spatial series analyses of the vaginal microbiome in pregnancy and the oral microbiome in humans with healthy dentition and intra-oral tissues.

A Characterization of the Oral Microbiome in Allogeneic Stem Cell Transplant Patients

PubMed Central

Ames, Nancy J.; Sulima, Pawel; Ngo, Thoi; Barb, Jennifer; Munson, Peter J.; Paster, Bruce J.; Hart, Thomas C.

2012-01-01

Background The mouth is a complex biological structure inhabited by diverse bacterial communities. The purpose of this study is to describe the effects of allogeneic stem cell transplantation on the oral microbiota and to examine differences among those patients who acquired respiratory complications after transplantation. Methodology/Principal Findings All patients were consented at the National Institutes of Health, Clinical Center. Bacterial DNA was analyzed from patients' oral specimens using the Human Oral Microbe Identification Microarray. The specimens were collected from four oral sites in 45 allogeneic transplantation patients. Specimens were collected at baseline prior to transplantation, after transplantation at the nadir of the neutrophil count and after myeloid engraftment. If respiratory signs and symptoms developed, additional specimens were obtained. Patients were followed for 100 days post transplantation. Eleven patients' specimens were subjected to further statistical analysis. Many common bacterial genera, such as Streptococcus, Veillonella, Gemella, Granulicatella and Camplyobacter were identified as being present before and after transplantation. Five of 11 patients developed respiratory complications following transplantation and there was preliminary evidence that the oral microbiome changed in their oral specimens. Cluster analysis and principal component analysis revealed this change in the oral microbiota. Conclusions/Significance After allogeneic transplantation, the oral bacterial community's response to a new immune system was not apparent and many of the most common core oral taxa remained unaffected. However, the oral microbiome was affected in patients who developed respiratory signs and symptoms after transplantation. The association related to the change in the oral microbiota and respiratory complications after transplantation will be validated by future studies using high throughput molecular methods. PMID:23144704

Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer.

PubMed

Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou; Peters, Brandilyn A; Ma, Yingfei; Yang, Liying; Agalliu, Ilir; Burk, Robert D; Ganly, Ian; Purdue, Mark P; Freedman, Neal D; Gapstur, Susan M; Pei, Zhiheng

2018-03-01

Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. To prospectively examine associations between the oral microbiome and incident HNSCC. This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Incident HNSCC. The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use. This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.

The role of the cutaneous microbiome in skin cancer: lessons learned from the gut.

PubMed

Yu, Yang; Champer, Jackson; Beynet, David; Kim, Jenny; Friedman, Adam J

2015-05-01

The human microbiome has recently gained prominence as a major factor in health and disease. Here we review the literature regarding the microbiome and cancer and suggest how the microbiome may be manipulated for improved health outcomes. The gut microbiome has been relatively well studied, and the mechanisms of how it may increase or decrease the risk of certain cancers may apply to the skin microbiome. Additionally, the gut microbiome may directly impact the risk of cancer in the skin and other organs by promoting systemic inflammation. The skin microbiome itself is as diverse as the gut microbiome, but research has just begun to unravel its influence on the host. Like the gut microbiome, it affects the risk for several diseases, including cancer. By using healthpromoting strains from the microbiome in oral or topical probiotics, it may be possible to reduce the risk of skin cancer and perhaps even increase the likelihood of successful treatment.

Association of coffee and tea intake with the oral microbiome: results from a large cross-sectional study.

PubMed

Peters, Brandilyn A; McCullough, Marjorie L; Purdue, Mark P; Freedman, Neal D; Um, Caroline Y; Gapstur, Susan M; Hayes, Richard B; Ahn, Jiyoung

2018-04-27

The oral microbiota play a central role in oral health, and possibly in carcinogenesis. Research suggests coffee and tea consumption may have beneficial health effects. We examined the associations of these common beverages with the oral ecosystem in a large cross-sectional study. We assessed oral microbiota in mouthwash samples from 938 participants in two U.S. cohorts using 16S rRNA gene sequencing. Coffee and tea intake were assessed from food frequency questionnaires. We examined associations of coffee and tea intake with overall oral microbiota diversity and composition using linear regression and permutational MANOVA, respectively, and with taxon abundance using negative binomial generalized linear models; all models adjusted for age, sex, cohort, BMI, smoking, ethanol intake, and energy intake. Higher tea intake was associated with greater oral microbiota richness (P=0.05) and diversity (P=0.006), and shifts in overall community composition (P=0.002); coffee was not associated with these microbiome parameters. Tea intake was associated with altered abundance of several oral taxa; these included Fusobacteriales, Clostridiales, and Shuttleworthia satelles (higher with increasing tea) and Bifidobacteriaceae, Bergeyella, Lactobacillales, and Kingella oralis (lower with increasing tea). Higher coffee intake was only associated with greater abundance of Granulicatella and Synergistetes. In the largest study to date of tea and coffee consumption in relation to the oral microbiota, the microbiota of tea drinkers differed in several ways from non-drinkers. Tea-driven changes to the oral microbiome may contribute to previously observed associations between tea and oral and systemic diseases, including cancers. Copyright ©2018, American Association for Cancer Research.

Characterisation of the human oral microbiome in patients with coronary artery disease using next-generation sequencing of 16SrRNA amplicons.

PubMed

Menon, Thangam; Gopalakrishnan, Sathya Narayanan; Balasubramanian, Rayvathy; Justin, Stalin Roy

2017-01-01

Oral health is suspected to be linked to heart disease since species of bacteria that cause periodontitis and dental caries have been found in the atherosclerotic plaque in arteries in the heart. The aim of this study was to characterize the oral microbiome in patients with coronary artery disease (CAD) and in a patient with dental caries (DC) without any clinical symptoms of CAD. DNA was extracted from the oral swabs collected from the patients and sequencing was performed by next generation sequencing method using Illumina (MiSeq) platform. The resulting sequencing data set was analysed using QIIME. A total of 31 phyla were found in all the samples. The predominant phylum found in both CAD and DC was Firmicutes (46.09% & 38.98%), Proteobacteria (17.73% & 9.79%), Fusobacteria (13.44% & 17.95%), Bacteroidetes (11.82% & 22.73%), Actinobacteria (8.33% & 7.71%) and TM7 (2.25% & 2.71%). We found a similarity in the bacterial diversity in the two groups of patients. A comparison of the oral microbiome in patients with CAD and DC shows a similarity in the composition of the oral microbiota with variations in the proportion of a few genera.

A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome

PubMed Central

Yao, Jiangwei; Carter, Robert A.; Vuagniaux, Grégoire; Barbier, Maryse; Rosch, Jason W.

2016-01-01

Broad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome. PMID:27161626

Microbiome Associated with Severe Caries in Canadian First Nations Children.

PubMed

Agnello, M; Marques, J; Cen, L; Mittermuller, B; Huang, A; Chaichanasakul Tran, N; Shi, W; He, X; Schroth, R J

2017-11-01

Young Indigenous children in North America suffer from a higher degree of severe early childhood caries (S-ECC) than the general population, leading to speculation that the etiology and characteristics of the disease may be distinct in this population. To address this knowledge gap, we conducted the first microbiome analysis of an Indigenous population using modern molecular techniques. We investigated the caries-associated microbiome among Canadian First Nations children with S-ECC. Thirty First Nations children <72 mo of age with S-ECC and 20 caries-free children were recruited in Winnipeg, Canada. Parents or caregivers completed a questionnaire on general and dental health, diet, and demographics. The plaque microbiome was investigated by sequencing the 16S rRNA gene. Sequences were clustered into operational taxonomic units and taxonomy assigned via the Human Oral Microbiome Database, then analyzed at the community level with alpha and beta diversity measures. Compared with those who were caries free, children with S-ECC came from households with lower income; they were more likely to live in First Nations communities and were more likely to be bottle-fed; and they were weaned from the bottle at a later age. The microbial communities of the S-ECC and caries-free groups did not differ in terms of species richness or phylogenetic diversity. Beta diversity analysis showed that the samples significantly clustered into groups based on caries status. Twenty-eight species-level operational taxonomic units were significantly different between the groups, including Veillonella HOT 780 and Porphyromonas HOT 284, which were 4.6- and 9-fold higher, respectively, in the S-ECC group, and Streptococcus gordonii and Streptococcus sanguinis, which were 5- and 2-fold higher, respectively, in the caries-free group. Extremely high levels of Streptococcus mutans were detected in the S-ECC group. Overall, First Nations children with S-ECC have a significantly different plaque microbiome than their caries-free counterparts, with the S-ECC group containing higher levels of known cariogenic organisms.

Periodontitis, Microbiomes and their Role in Alzheimer’s Disease

PubMed Central

Pritchard, Anna B.; Crean, StJohn; Olsen, Ingar; Singhrao, Sim K.

2017-01-01

As far back as the eighteenth and early nineteenth centuries, microbial infections were responsible for vast numbers of deaths. The trend reversed with the introduction of antibiotics coinciding with longer life. Increased life expectancy however, accompanied the emergence of age related chronic inflammatory states including the sporadic form of Alzheimer’s disease (AD). Taken together, the true challenge of retaining health into later years of life now appears to lie in delaying and/or preventing the progression of chronic inflammatory diseases, through identifying and influencing modifiable risk factors. Diverse pathogens, including periodontal bacteria have been associated with AD brains. Amyloid-beta (Aβ) hallmark protein of AD may be a consequence of infection, called upon due to its antimicrobial properties. Up to this moment in time, a lack of understanding and knowledge of a microbiome associated with AD brain has ensured that the role pathogens may play in this neurodegenerative disease remains unresolved. The oral microbiome embraces a range of diverse bacterial phylotypes, which especially in vulnerable individuals, will excite and perpetuate a range of inflammatory conditions, to a wide range of extra-oral body tissues and organs specific to their developing pathophysiology, including the brain. This offers the tantalizing opportunity that by controlling the oral-specific microbiome; clinicians may treat or prevent a range of chronic inflammatory diseases orally. Evolution has equipped the human host to combat infection/disease by providing an immune system, but Porphyromonas gingivalis and selective spirochetes, have developed immune avoidance strategies threatening the host-microbe homeostasis. It is clear from longitudinal monitoring of patients that chronic periodontitis contributes to declining cognition. The aim here is to discuss the contribution from opportunistic pathogens of the periodontal microbiome, and highlight the challenges, the host faces, when dealing with unresolvable oral infections that may lead to clinical manifestations that are characteristic for AD. PMID:29114218

Potential Role of the Microbiome in Barrett's Esophagus and Esophageal Adenocarcinoma.

PubMed

Snider, Erik J; Freedberg, Daniel E; Abrams, Julian A

2016-08-01

Esophageal adenocarcinoma and its precursor Barrett's esophagus have been rapidly increasing in incidence for half a century, for reasons not adequately explained by currently identified risk factors such as gastroesophageal reflux disease and obesity. The upper gastrointestinal microbiome may represent another potential cofactor. The distal esophagus has a distinct microbiome of predominantly oral-derived flora, which is altered in Barrett's esophagus and reflux esophagitis. Chronic low-grade inflammation or direct carcinogenesis from this altered microbiome may combine with known risk factors to promote Barrett's metaplasia and progression to adenocarcinoma.

Review: Maternal health and the placental microbiome.

PubMed

Pelzer, Elise; Gomez-Arango, Luisa F; Barrett, Helen L; Nitert, Marloes Dekker

2017-06-01

Over the past decade, the role of the microbiome in regulating metabolism, immune function and behavior in humans has become apparent. It has become clear that the placenta is not a sterile organ, but rather has its own endogenous microbiome. The composition of the placental microbiome is distinct from that of the vagina and has been reported to resemble the oral microbiome. Compared to the gut microbiome, the placental microbiome exhibits limited microbial diversity. This review will focus on the current understanding of the placental microbiota in normal healthy pregnancy and also in disease states including preterm birth, chorioamnionitis and maternal conditions such as obesity, gestational diabetes mellitus and preeclampsia. Factors known to alter the composition of the placental microbiota will be discussed in the final part of this review. Copyright © 2016. Published by Elsevier Ltd.

Microbiome in parturition and preterm birth.

PubMed

Mysorekar, Indira U; Cao, Bin

2014-01-01

Preterm parturition is a one of the most significant global maternal-child health problem. In recent years, there has been an explosion in reports on a role for microbiomes (i.e., a microbial biomass) on a plethora of physiologic and pathologic human conditions. This review aims to describe our current understanding of the microbiome and its impact on parturition, with particular emphasis on preterm birth. We will focus on the roles of vaginal and oral mucosal microbiomes in premature parturition and describe the state-of-the-art methodologies used in microbiome studies. Next, we will present new studies on a potential microbiome in the placenta and how it may affect pregnancy outcomes. Finally, we will propose that host genetic factors can perturb the normal "pregnancy microbiome" and trigger adverse pregnancy outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces

PubMed Central

Brandt, Bernd W.; Teixeira de Mattos, M. Joost; Buijs, Mark J.; Caspers, Martien P. M.; Rashid, Mamun-Ur; Weintraub, Andrej; Nord, Carl Erik; Savell, Ann; Hu, Yanmin; Coates, Antony R.; Hubank, Mike; Spratt, David A.; Wilson, Michael; Keijser, Bart J. F.; Crielaard, Wim

2015-01-01

ABSTRACT Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health-associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body. PMID:26556275

The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters

PubMed Central

Aagaard, Kjersti; Petrosino, Joseph; Keitel, Wendy; Watson, Mark; Katancik, James; Garcia, Nathalia; Patel, Shital; Cutting, Mary; Madden, Tessa; Hamilton, Holli; Harris, Emily; Gevers, Dirk; Simone, Gina; McInnes, Pamela; Versalovic, James

2013-01-01

The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m2, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.—Aagaard, K., Petrosino, J., Keitel, W., Watson, M., Katancik, J., Garcia, N., Patel, S., Cutting, M., Madden, T., Hamilton, H., Harris, E., Gevers, D., Simone, G., McInnes, P., Versalovic, J. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. PMID:23165986

Alcohol and tobacco consumption affects bacterial richness in oral cavity mucosa biofilms.

PubMed

Thomas, Andrew Maltez; Gleber-Netto, Frederico Omar; Fernandes, Gustavo Ribeiro; Amorim, Maria; Barbosa, Luisa Fernanda; Francisco, Ana Lúcia Noronha; de Andrade, Arthur Guerra; Setubal, João Carlos; Kowalski, Luiz Paulo; Nunes, Diana Noronha; Dias-Neto, Emmanuel

2014-10-03

Today there are more than 2 billion alcohol users and about 1.3 billion tobacco users worldwide. The chronic and heavy use of these two substances is at the heart of numerous diseases and may wreak havoc on the human oral microbiome. This study delves into the changes that alcohol and tobacco may cause on biofilms of the human oral microbiome. To do so, we used swabs to sample the oral biofilm of 22 subjects; including 9 control-individuals with no or very low consumption of alcohol and no consumption of tobacco, 7 who were chronic and heavy users of both substances and 6 active smokers that reported no significant alcohol consumption. DNA was extracted from swabs and the V1 region of the 16S rRNA gene was PCR amplified and sequenced using the Ion Torrent PGM platform, generating 3.7 million high quality reads. DNA sequences were clustered and OTUs were assigned using the ARB SILVA database and Qiime. We found no differences in species diversity and evenness among the groups. However, we found a significant decrease in species richness in only smokers and in smokers/drinkers when compared to controls. We found that Neisseria abundance was significantly decreased in both groups when compared to controls. Smokers had significant increases in Prevotella and Capnocytophaga and reductions in Granulicatella, Staphylococcus, Peptostreptococcus and Gemella when compared to the two other groups. Controls showed higher abundance of Aggregibacter, whilst smokers/drinkers had lower abundances of Fusobacteria. Samples from only smokers clustered closer together than to controls and smokers/drinkers, and also had a significant reduction in inter-group dissimilarity distances, indicating a more homogenous group than controls. Our results indicate that the continued use of tobacco or alcohol plus tobacco significantly reduces bacterial richness, which apparently leads to a reduction in inter-group variability, turning the respective biofilms into a more homogenous microenvironment in terms of bacterial community composition, with possible consequences for human oral diseases.

Distinct Ecological Niche of Anal, Oral, and Cervical Mucosal Microbiomes in Adolescent Women.

PubMed

Smith, Benjamin C; Zolnik, Christine P; Usyk, Mykhaylo; Chen, Zigui; Kaiser, Katherine; Nucci-Sack, Anne; Peake, Ken; Diaz, Angela; Viswanathan, Shankar; Strickler, Howard D; Schlecht, Nicolas F; Burk, Robert D

2016-09-01

Human body sites represent ecological niches for microorganisms, each providing variations in microbial exposure, nutrient availability, microbial competition, and host immunological responses. In this study, we investigated the oral, anal, and cervical microbiomes from the same 20 sexually active adolescent females, using culture-independent, next-generation sequencing. DNA from each sample was amplified for the bacterial 16S rRNA gene and sequenced on an Illumina platform using paired-end reads. Across the three anatomical niches, we found significant differences in bacterial community composition and diversity. Overall anal samples were dominated with Prevotella and Bacteriodes , oral samples with Streptococcus and Prevotella , and cervical samples with Lactobacillus . The microbiomes of a few cervical samples clustered with anal samples in weighted principal coordinate analyses, due in part to a higher proportion of Prevotella in those samples. Additionally, cervical samples had the lowest alpha diversity. Our results demonstrate the occurrence of distinct microbial communities across body sites within the same individual.

Role of oral microbiome on oral cancers, a review.

PubMed

Gholizadeh, Pourya; Eslami, Hosein; Yousefi, Mehdi; Asgharzadeh, Mohammad; Aghazadeh, Mohammad; Kafil, Hossein Samadi

2016-12-01

The oral cavity is inhibited by many of the bacterial species. Some of them have a key role in the development of oral disease. Interrelationships between oral microbiome and systemic conditions such as head-and-neck cancer have become increasingly appreciated in recent years. Emerging evidence also suggests a link between periodontal disease and oral cancer, and the explanation being that chronic inflammation could be a major factor in both diseases. Squamous cell carcinoma is that the most frequently occurring malignancy of the oral cavity and adjacent sites, representing over 90% of all cancers. The incidence of oral cancer is increasing, significantly among young people and women. Worldwide there are 350,000-400,000 new cases diagnosed every year. Bacteria, viruses, and fungi are strongly implicated as etiological factors in certain cancers. In this review we will discuss the association between the development of oral cancer in potentially malignant oral lesions with chronic periodontitis, chronic Porphyromonas gingivalis, Fusobacterium nucleatum, candida, other microbes and described mechanisms which may be involved in these carcinoma. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The microbiome of a striped dolphin (Stenella coeruleoalba) stranded in Portugal.

PubMed

Godoy-Vitorino, Filipa; Rodriguez-Hilario, Arnold; Alves, Ana Luísa; Gonçalves, Filipa; Cabrera-Colon, Beatriz; Mesquita, Cristina Sousa; Soares-Castro, Pedro; Ferreira, Marisa; Marçalo, Ana; Vingada, José; Eira, Catarina; Santos, Pedro Miguel

2017-01-01

Infectious diseases with epizootic consequences have not been fully studied in marine mammals. Presently, the unprecedented depth of sequencing, made available by high-throughput approaches, allows detailed comparisons of the microbiome in health and disease. This is the first report of the striped dolphin microbiome in different body sites. Samples from one striped female edematous dolphin were acquired from a variety of body niches, including the blowhole, oral cavity, oral mucosa, tongue, stomach, intestines and genital mucosa. Detailed 16S rRNA analysis of over half a million sequences identified 235 OTUs. Beta diversity analyses indicated that microbial communities vary in structure and cluster by sample origin. Pathogenic, Gram-negative, facultative and obligate anaerobic taxa were significantly detected, including Cetobacterium, Fusobacterium and Ureaplasma. Phocoenobacter and Arcobacter dominated the oral-type samples, while Cardiobacteriaceae and Vibrio were associated with the blowhole and Photobacterium were abundant in the gut. We report for the first time the association of Epulopiscium with a marine mammal gut. The striped dolphin microbiota shows variation in structure and diversity according to the organ type. The high dominance of Gram-negative anaerobic pathogens evidences a cetacean microbiome affected by human-related bacteria. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Global diversity in the human salivary microbiome.

PubMed

Nasidze, Ivan; Li, Jing; Quinque, Dominique; Tang, Kun; Stoneking, Mark

2009-04-01

The human salivary microbiome may play a role in diseases of the oral cavity and interact with microbiomes from other parts of the human body (in particular, the intestinal tract), but little is known about normal variation in the salivary microbiome. We analyzed 14,115 partial ( approximately 500 bp) 16S ribosomal RNA (rRNA) sequences from saliva samples from 120 healthy individuals (10 individuals from each of 12 worldwide locations). These sequences could be assigned to 101 known bacterial genera, of which 39 were not previously reported from the human oral cavity; phylogenetic analysis suggests that an additional 64 unknown genera are present. There is high diversity in the salivary microbiome within and between individuals, but little geographic structure. Overall, approximately 13.5% of the total variance in the composition of genera is due to differences among individuals, which is remarkably similar to the fraction of the total variance in neutral genetic markers that can be attributed to differences among human populations. Investigation of some environmental variables revealed a significant association between the genetic distances among locations and the distance of each location from the equator. Further characterization of the enormous diversity revealed here in the human salivary microbiome will aid in elucidating the role it plays in human health and disease, and in the identification of potentially informative species for studies of human population history.

Salivary Microbiota Reflects Changes in Gut Microbiota in Cirrhosis with Hepatic Encephalopathy

PubMed Central

Bajaj, Jasmohan S; Betrapally, Naga S; Hylemon, Phillip B; Heuman, Douglas M; Daita, Kalyani; White, Melanie B; Unser, Ariel; Thacker, Leroy R; Sanyal, Arun J; Kang, Dae Joong; Sikaroodi, Masoumeh; Gillevet, Patrick M

2015-01-01

Background Altered gut microbiome is associated with systemic inflammation and cirrhosis decompensation. However, the correlation of the oral microbiome with inflammation in cirrhosis is unclear. Aim Evaluate the oral microbiome in cirrhosis and compare with stool microbiome. Methods Cirrhotic outpatients [with/without hepatic encephalopathy (HE)] and controls underwent stool/saliva microbiome analysis (for composition and function) and also systemic inflammatory evaluation. 90-day liver-related hospitalizations were recorded. Salivary inflammation was studied using Th1 cytokines/secretory IgA, histatins and lysozyme in a subsequent group. Results 102 cirrhotics (43 prior-HE) and 32 age-matched controls were included. On PCO, stool and saliva microbiome clustered far apart showing differences between sites as a whole. Salivary microbiome With prior-HE, relative abundance of autochthonous families decreased while potentially pathogenic ones (Enterobacteriaceae, Enterococcaceae) increased in saliva. Endotoxin-related predicted functions were significantly higher in cirrhotic saliva. Stool microbiome Relative autochthonous taxa abundance reduced in prior-HE, along with increased Enterobacteriaceae and Enterococcaceae. Cirrhotic stool microbiota demonstrated a significantly higher correlation with systemic inflammation compared to saliva microbiota on correlation networks. Outcomes 38 patients were hospitalized within 90 days. Their salivary dysbiosis was significantly worse and predicted this outcome independent of cirrhosis severity. Salivary inflammation was studied in an additional 86 age-matched subjects (43 controls/43 cirrhotics); significantly higher IL-6/IL-1β, secretory IgA and lower lysozyme, and histatins 1 and 5 were found in cirrhotics compared to controls. Conclusions Dysbiosis, represented by reduction in autochthonous bacteria, is present in both saliva and stool in cirrhosis patients compared to controls. Cirrhotic patients have impaired salivary defenses and worse inflammation. Salivary dysbiosis was greater in cirrhotics who developed 90-day hospitalizations. These findings could represent a global mucosal-immune interface change in cirrhosis. PMID:25820757

Visibiome: an efficient microbiome search engine based on a scalable, distributed architecture.

PubMed

Azman, Syafiq Kamarul; Anwar, Muhammad Zohaib; Henschel, Andreas

2017-07-24

Given the current influx of 16S rRNA profiles of microbiota samples, it is conceivable that large amounts of them eventually are available for search, comparison and contextualization with respect to novel samples. This process facilitates the identification of similar compositional features in microbiota elsewhere and therefore can help to understand driving factors for microbial community assembly. We present Visibiome, a microbiome search engine that can perform exhaustive, phylogeny based similarity search and contextualization of user-provided samples against a comprehensive dataset of 16S rRNA profiles environments, while tackling several computational challenges. In order to scale to high demands, we developed a distributed system that combines web framework technology, task queueing and scheduling, cloud computing and a dedicated database server. To further ensure speed and efficiency, we have deployed Nearest Neighbor search algorithms, capable of sublinear searches in high-dimensional metric spaces in combination with an optimized Earth Mover Distance based implementation of weighted UniFrac. The search also incorporates pairwise (adaptive) rarefaction and optionally, 16S rRNA copy number correction. The result of a query microbiome sample is the contextualization against a comprehensive database of microbiome samples from a diverse range of environments, visualized through a rich set of interactive figures and diagrams, including barchart-based compositional comparisons and ranking of the closest matches in the database. Visibiome is a convenient, scalable and efficient framework to search microbiomes against a comprehensive database of environmental samples. The search engine leverages a popular but computationally expensive, phylogeny based distance metric, while providing numerous advantages over the current state of the art tool.

Oral microbiota reveals signs of acculturation in Mexican American women

PubMed Central

Hutchinson, Diane S.; Fowler, Jerry; Smith, Daniel P.; Ajami, Nadim J.; Zhao, Hua; Scheet, Paul; Chow, Wong-Ho; Petrosino, Joseph F.; Daniel, Carrie R.

2018-01-01

The oral microbiome has been linked to a number of chronic inflammatory conditions, including obesity, diabetes, periodontitis, and cancers of the stomach and liver. These conditions disproportionately affect Mexican American women, yet few studies have examined the oral microbiota in this at-risk group. We characterized the 16S rDNA oral microbiome in 369 non-smoking women enrolled in the MD Anderson Mano a Mano Mexican American Cohort Study. Lower bacterial diversity, a potential indicator of oral health, was associated with increased age and length of US residency among recent immigrants. Grouping women by overarching bacterial community type (e.g., “Streptococcus,” “Fusobacterium,” and “Prevotella” clusters), we observed differences across a number of acculturation-related variables, including nativity, age at immigration, time in the US, country of longest residence, and a multi-dimensional acculturation scale. Participants in the cluster typified by higher abundance of Streptococcus spp. exhibited the lowest bacterial diversity and appeared the most acculturated as compared to women in the “Prevotella” group. Computationally-predicted functional analysis suggested the Streptococcus-dominated bacterial community had greater potential for carbohydrate metabolism while biosynthesis of essential amino acids and nitrogen metabolism prevailed among the Prevotella-high group. Findings suggest immigration and adaption to life in the US, a well-established mediator of disease risk, is associated with differences in oral microbial profiles in Mexican American women. These results warrant further investigation into the joint and modifying effects of acculturation and oral bacteria on the health of Mexican American women and other immigrant populations. The oral microbiome presents an easily accessible biomarker of disease risk, spanning biological, behavioral, and environmental factors. PMID:29694348

On the ecosystemic network of saliva in healthy young adults

PubMed Central

Zaura, Egija; Brandt, Bernd W; Prodan, Andrei; Teixeira de Mattos, Maarten Joost; Imangaliyev, Sultan; Kool, Jolanda; Buijs, Mark J; Jagers, Ferry LPW; Hennequin-Hoenderdos, Nienke L; Slot, Dagmar E; Nicu, Elena A; Lagerweij, Maxim D; Janus, Marleen M; Fernandez-Gutierrez, Marcela M; Levin, Evgeni; Krom, Bastiaan P; Brand, Henk S; Veerman, Enno CI; Kleerebezem, Michiel; Loos, Bruno G; van der Weijden, G A; Crielaard, Wim; Keijser, Bart JF

2017-01-01

A dysbiotic state is believed to be a key factor in the onset of oral disease. Although oral diseases have been studied for decades, our understanding of oral health, the boundaries of a healthy oral ecosystem and ecological shift toward dysbiosis is still limited. Here, we present the ecobiological heterogeneity of the salivary ecosystem and relations between the salivary microbiome, salivary metabolome and host-related biochemical salivary parameters in 268 healthy adults after overnight fasting. Gender-specific differences in the microbiome and metabolome were observed and were associated with salivary pH and dietary protein intake. Our analysis grouped the individuals into five microbiome and four metabolome-based clusters that significantly related to biochemical parameters of saliva. Low salivary pH and high lysozyme activity were associated with high proportions of streptococcal phylotypes and increased membrane-lipid degradation products. Samples with high salivary pH displayed increased chitinase activity, higher abundance of Veillonella and Prevotella species and higher levels of amino acid fermentation products, suggesting proteolytic adaptation. An over-specialization toward either a proteolytic or a saccharolytic ecotype may indicate a shift toward a dysbiotic state. Their prognostic value and the degree to which these ecotypes are related to increased disease risk remains to be determined. PMID:28072421

Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome

PubMed Central

Poole, Angela C.; Pischel, Lauren; Ley, Catherine; Suh, Gina; Goodrich, Julia K.; Haggerty, Thomas D.; Ley, Ruth E.

2016-01-01

ABSTRACT Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans. PMID:27303746

The oral microbiome and the immunobiology of periodontal disease and caries

PubMed Central

Costalonga, Massimo; Herzberg, Mark C.

2015-01-01

The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth. Caries is a unique infection of the dental hard tissues. The initiation of both diseases is marked by an increase in the complexity of the microbiome. In periodontitis, pathobionts and keystone pathogens such as Porphyromonas gingivalis appear in greater proportion than in health. As a keystone pathogen, P. gingivalis impairs host immune responses and appears necessary but not sufficient to cause periodontitis. Historically, dental caries had been causally linked to Streptococcus mutans. Contemporary microbiome studies now indicate that singular pathogens are not obvious in either caries or periodontitis. Both diseases appear to result from a perturbation among relatively minor constituents in local microbial communities resulting in dysbiosis. Emergent consortia of the minor members of the respective microbiomes act synergistically to stress the ability of the host to respond and protect. In periodontal disease, host protection first occurs at the level of innate gingival epithelial immunity. Secretory IgA antibody and other salivary antimicrobial systems also act against periodontopathic and cariogenic consortia. When the gingival immune response is impaired, periodontal tissue pathology results when matrix metalloproteinases are released from neutrophils and T cells mediate alveolar bone loss. In caries, several species are acidogenic and aciduric and appear to work synergistically to promote demineralization of the enamel and dentin. Whereas technically possible, particularly for caries, vaccines are unlikely to be commercialized in the near future because of the low morbidity of caries and periodontitis. PMID:25447398

The oral microbiome and the immunobiology of periodontal disease and caries.

PubMed

Costalonga, Massimo; Herzberg, Mark C

2014-12-01

The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth. Caries is a unique infection of the dental hard tissues. The initiation of both diseases is marked by an increase in the complexity of the microbiome. In periodontitis, pathobionts and keystone pathogens such as Porphyromonas gingivalis appear in greater proportion than in health. As a keystone pathogen, P. gingivalis impairs host immune responses and appears necessary but not sufficient to cause periodontitis. Historically, dental caries had been causally linked to Streptococcus mutans. Contemporary microbiome studies now indicate that singular pathogens are not obvious in either caries or periodontitis. Both diseases appear to result from a perturbation among relatively minor constituents in local microbial communities resulting in dysbiosis. Emergent consortia of the minor members of the respective microbiomes act synergistically to stress the ability of the host to respond and protect. In periodontal disease, host protection first occurs at the level of innate gingival epithelial immunity. Secretory IgA antibody and other salivary antimicrobial systems also act against periodontopathic and cariogenic consortia. When the gingival immune response is impaired, periodontal tissue pathology results when matrix metalloproteinases are released from neutrophils and T cells mediate alveolar bone loss. In caries, several species are acidogenic and aciduric and appear to work synergistically to promote demineralization of the enamel and dentin. Whereas technically possible, particularly for caries, vaccines are unlikely to be commercialized in the near future because of the low morbidity of caries and periodontitis. Copyright © 2014. Published by Elsevier B.V.

Pathogens and host immunity in the ancient human oral cavity

PubMed Central

Warinner, Christina; Matias Rodrigues, João F.; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y.; Tito, Raul Y.; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C.; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars; Samaniego Castruita, José Alfredo; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian; Olsen, Jesper V.; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M.; Collins, Matthew J.; Gilbert, M. Thomas P.; Rühli, Frank; Cappellini, Enrico

2014-01-01

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, “red-complex” pathogens, and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity, and diet, thereby extending the direct investigation of common diseases into the human evolutionary past. PMID:24562188

Metagenomics of prebiotic and probiotic supplemented broilers gastrointestinal tract microbiome

USDA-ARS?s Scientific Manuscript database

Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) is a recently developed computational approach for prediction of functional composition of a microbiome comparing marker gene data with a reference genome database. The procedure established significant link ...

Application of a neutral community model to assess structuring of the human lung microbiome.

PubMed

Venkataraman, Arvind; Bassis, Christine M; Beck, James M; Young, Vincent B; Curtis, Jeffrey L; Huffnagle, Gary B; Schmidt, Thomas M

2015-01-20

DNA from phylogenetically diverse microbes is routinely recovered from healthy human lungs and used to define the lung microbiome. The proportion of this DNA originating from microbes adapted to the lungs, as opposed to microbes dispersing to the lungs from other body sites and the atmosphere, is not known. We use a neutral model of community ecology to distinguish members of the lung microbiome whose presence is consistent with dispersal from other body sites and those that deviate from the model, suggesting a competitive advantage to these microbes in the lungs. We find that the composition of the healthy lung microbiome is consistent with predictions of the neutral model, reflecting the overriding role of dispersal of microbes from the oral cavity in shaping the microbial community in healthy lungs. In contrast, the microbiome of diseased lungs was readily distinguished as being under active selection. We also assessed the viability of microbes from lung samples by cultivation with a variety of media and incubation conditions. Bacteria recovered by cultivation from healthy lungs represented species that comprised 61% of the 16S rRNA-encoding gene sequences derived from bronchoalveolar lavage samples. Neutral distribution of microbes is a distinguishing feature of the microbiome in healthy lungs, wherein constant dispersal of bacteria from the oral cavity overrides differential growth of bacteria. No bacterial species consistently deviated from the model predictions in healthy lungs, although representatives of many of the dispersed species were readily cultivated. In contrast, bacterial populations in diseased lungs were identified as being under active selection. Quantification of the relative importance of selection and neutral processes such as dispersal in shaping the healthy lung microbiome is a first step toward understanding its impacts on host health. Copyright © 2015 Venkataraman et al.

High Diversity of the Saliva Microbiome in Batwa Pygmies

PubMed Central

Schroeder, Roland; Creasey, Jean L.; Li, Mingkun; Stoneking, Mark

2011-01-01

We describe the saliva microbiome diversity in Batwa Pygmies, a former hunter-gatherer group from Uganda, using next-generation sequencing of partial 16S rRNA sequences. Microbial community diversity in the Batwa is significantly higher than in agricultural groups from Sierra Leone and the Democratic Republic of Congo. We found 40 microbial genera in the Batwa, which have previously not been described in the human oral cavity. The distinctive composition of the salvia microbiome of the Batwa may have been influenced by their recent different lifestyle and diet. PMID:21858083

Dynamics of the oral microbiota as a tool to estimate time since death.

PubMed

Adserias-Garriga, J; Quijada, N M; Hernandez, M; Rodríguez Lázaro, D; Steadman, D; Garcia-Gil, L J

2017-06-27

The oral cavity harbors one of the most diverse microbiomes in the human body. It has been shown to be the second most complex in the body after the gastrointestinal tract. Upon death, the indigenous microorganisms lead to the decomposition of the carcass. Therefore, the oral cavity and gastrointestinal tract microbiomes play a key role in human decomposition. The aim of the present study is to monitor the microbiome of decaying bodies on a daily basis and to identify signature bacterial taxa, that can improve postmortem interval estimation. Three individuals (one male and two female) donated to the University of Tennessee Forensic Anthropology Center for the W.M. Bass Donated Skeletal Collection were studied. Oral swab samples were taken daily throughout the different stages of cadaveric putrefaction. DNA was extracted and analyzed by next-generation sequencing techniques. The three cadavers showed similar overall successional changes during the decomposition process. Firmicutes and Actinobacteria are the predominant phyla in the fresh stage. The presence of Tenericutes corresponds to bloat stage. Firmicutes is the predominant phylum in advanced decay, but the Firmicutes community is a different one from the predominant Firmicutes of the fresh stage. This study depicts the thanatomicrobiome successional changes in the oral cavity, and highlights its potential use in forensic cases as a quantitative and objective approach to estimate postmortem interval, from an ecological rationale. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral yeast colonization throughout pregnancy.

PubMed

Rio, R; Simões-Silva, L; Garro, S; Silva, M-J; Azevedo, Á; Sampaio-Maia, B

2017-03-01

Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment.

Breaking down the gut microbiome composition in multiple sclerosis.

PubMed

Budhram, Adrian; Parvathy, Seema; Kremenchutzky, Marcelo; Silverman, Michael

2017-04-01

The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS. A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS. Controlled studies examining the gut microbiome in patients with MS were included for review. Identified studies were predominantly case-control in their design and consistently found differences in the gut microbiome of MS patients compared to controls. We examine plausible mechanistic links between these differences and MS immunopathogenesis, and discuss the therapeutic implications of these findings. Review of the available literature reveals potential immunopathogenic links between the gut microbiome and MS, identifies avenues for therapeutic advancement, and emphasizes the need for further systematic study in this emerging field.

The relation between oral Candida load and bacterial microbiome profiles in Dutch older adults.

PubMed

Kraneveld, Eefje A; Buijs, Mark J; Bonder, Marc J; Visser, Marjolein; Keijser, Bart J F; Crielaard, Wim; Zaura, Egija

2012-01-01

Currently there are no evidence-based ecological measures for prevention of overgrowth and subsequent infection by fungi in the oral cavity. The aim of this study was to increase our knowledge on fungal-bacterial ecological interactions. Salivary Candida abundance of 82 Dutch adults aged 58-80 years was established relative to the bacterial load by quantitative PCR analysis of the Internal Transcribed (ITS) region (Candida) and 16S rDNA gene (bacteria). The salivary microbiome was assessed using barcoded pyrosequencing of the bacterial hypervariable regions V5-V7 of 16S rDNA. Sequencing data was preprocessed by denoising and chimera removal, clustered in Operational Taxonomic Units (OTUs) and assigned to taxonomy. Both OTU-based (PCA, diversity statistics) and phylogeny-based analyses (UniFrac, PCoA) were performed. Saliva of Dutch older adults contained 0-4 × 10(8) CFU/mL Candida with a median Candida load of 0.06%. With increased Candida load the diversity of the salivary microbiome decreased significantly (p<0.001). Increase in the Candida load correlated positively with class Bacilli, and negatively with class Fusobacteria, Flavobacteria, and Bacteroidia. Microbiomes with high Candida load were less diverse and had a distinct microbial composition towards dominance by saccharolytic and acidogenic bacteria--streptococci. The control of the acidification of the oral environment may be a potential preventive measure for Candida outgrowth that should be evaluated in longitudinal clinical intervention trials.

The Relation between Oral Candida Load and Bacterial Microbiome Profiles in Dutch Older Adults

PubMed Central

Kraneveld, Eefje A.; Buijs, Mark J.; Bonder, Marc J.; Visser, Marjolein; Keijser, Bart J. F.; Crielaard, Wim; Zaura, Egija

2012-01-01

Currently there are no evidence-based ecological measures for prevention of overgrowth and subsequent infection by fungi in the oral cavity. The aim of this study was to increase our knowledge on fungal–bacterial ecological interactions. Salivary Candida abundance of 82 Dutch adults aged 58–80 years was established relative to the bacterial load by quantitative PCR analysis of the Internal Transcribed (ITS) region (Candida) and 16S rDNA gene (bacteria). The salivary microbiome was assessed using barcoded pyrosequencing of the bacterial hypervariable regions V5–V7 of 16S rDNA. Sequencing data was preprocessed by denoising and chimera removal, clustered in Operational Taxonomic Units (OTUs) and assigned to taxonomy. Both OTU-based (PCA, diversity statistics) and phylogeny-based analyses (UniFrac, PCoA) were performed. Saliva of Dutch older adults contained 0–4 × 108 CFU/mL Candida with a median Candida load of 0.06%. With increased Candida load the diversity of the salivary microbiome decreased significantly (p<0.001). Increase in the Candida load correlated positively with class Bacilli, and negatively with class Fusobacteria, Flavobacteria, and Bacteroidia. Microbiomes with high Candida load were less diverse and had a distinct microbial composition towards dominance by saccharolytic and acidogenic bacteria - streptococci. The control of the acidification of the oral environment may be a potential preventive measure for Candida outgrowth that should be evaluated in longitudinal clinical intervention trials. PMID:22900048

From microbiome to infectome in autoimmunity.

PubMed

Bogdanos, Dimitrios P; Sakkas, Lazaros I

2017-07-01

The current review discusses the pros and cons of the microbiome studies conducted in search of the association between microbiota and autoimmunity. We focus on the role of infectome and autoinfectome as a bridge to link the findings of microbiome studies with those emerging from investigations of the role of specific viruses and antiviral responses as triggers of autoimmunity (through various mechanisms such as molecular mimicry). The 'usual suspects', such as herpetoviruses and Escherichia coli, are thoroughly discussed in light of the data emerged by the microbiome studies, using as examples specific autoimmune rheumatic diseases and inflammatory bowel diseases. We conclude that the studies of the oral cavity, gastrointestinal, and urinary tract microbiome are informative but can only be useful if further explored from the infectome perspective. This means that the plethora of bacteria associated with autoimmune diseases from microbiome studies can be and must be tested experimentally. If certain bacteria are associated directly or indirectly with autoimmune diseases, specific immunological mechanisms must be identified.

Oral yeast colonization throughout pregnancy

PubMed Central

Rio, Rute; Simões-Silva, Liliana; Garro, Sofia; Silva, Mário-Jorge; Azevedo, Álvaro

2017-01-01

Background Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. Material and Methods The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Results Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Conclusions Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment. Key words:Oral yeast, fungi, pregnancy, saliva pH. PMID:28160578

Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology.

PubMed

Guo, Lihong; McLean, Jeffrey S; Yang, Youngik; Eckert, Randal; Kaplan, Christopher W; Kyme, Pierre; Sheikh, Omid; Varnum, Brian; Lux, Renate; Shi, Wenyuan; He, Xuesong

2015-06-16

One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans' natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome.

Identifying Low pH Active and Lactate-Utilizing Taxa within Oral Microbiome Communities from Healthy Children Using Stable Isotope Probing Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

McLean, Jeffrey S.; Fansler, Sarah J.; Majors, Paul D.

Many human microbial infectious diseases including dental caries are polymicrobial in nature and how these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral microbes have been characterized in vitro, their physiology in vivo in the presence of the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these oral species remain uncultivated to date and little is known except their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated microorganisms will remain enigmatic despite their apparent disease correlation.more » To start addressing these knowledge gaps, we applied a novel combination of in vivo Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for temporal monitoring of carbohydrate utilization, organic acid production and identification of metabolically active and inactive bacterial species.« less

Matrix metalloproteinases outside vertebrates.

PubMed

Marino-Puertas, Laura; Goulas, Theodoros; Gomis-Rüth, F Xavier

2017-11-01

The matrix metalloproteinase (MMP) family belongs to the metzincin clan of zinc-dependent metallopeptidases. Due to their enormous implications in physiology and disease, MMPs have mainly been studied in vertebrates. They are engaged in extracellular protein processing and degradation, and present extensive paralogy, with 23 forms in humans. One characteristic of MMPs is a ~165-residue catalytic domain (CD), which has been structurally studied for 14 MMPs from human, mouse, rat, pig and the oral-microbiome bacterium Tannerella forsythia. These studies revealed close overall coincidence and characteristic structural features, which distinguish MMPs from other metzincins and give rise to a sequence pattern for their identification. Here, we reviewed the literature available on MMPs outside vertebrates and performed database searches for potential MMP CDs in invertebrates, plants, fungi, viruses, protists, archaea and bacteria. These and previous results revealed that MMPs are widely present in several copies in Eumetazoa and higher plants (Tracheophyta), but have just token presence in eukaryotic algae. A few dozen sequences were found in Ascomycota (within fungi) and in double-stranded DNA viruses infecting invertebrates (within viruses). In contrast, a few hundred sequences were found in archaea and >1000 in bacteria, with several copies for some species. Most of the archaeal and bacterial phyla containing potential MMPs are present in human oral and gut microbiomes. Overall, MMP-like sequences are present across all kingdoms of life, but their asymmetric distribution contradicts the vertical descent model from a eubacterial or archaeal ancestor. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional sequencing read annotation for high precision microbiome analysis

PubMed Central

Zhu, Chengsheng; Miller, Maximilian; Marpaka, Srinayani; Vaysberg, Pavel; Rühlemann, Malte C; Wu, Guojun; Heinsen, Femke-Anouska; Tempel, Marie; Zhao, Liping; Lieb, Wolfgang; Franke, Andre; Bromberg, Yana

2018-01-01

Abstract The vast majority of microorganisms on Earth reside in often-inseparable environment-specific communities—microbiomes. Meta-genomic/-transcriptomic sequencing could reveal the otherwise inaccessible functionality of microbiomes. However, existing analytical approaches focus on attributing sequencing reads to known genes/genomes, often failing to make maximal use of available data. We created faser (functional annotation of sequencing reads), an algorithm that is optimized to map reads to molecular functions encoded by the read-correspondent genes. The mi-faser microbiome analysis pipeline, combining faser with our manually curated reference database of protein functions, accurately annotates microbiome molecular functionality. mi-faser’s minutes-per-microbiome processing speed is significantly faster than that of other methods, allowing for large scale comparisons. Microbiome function vectors can be compared between different conditions to highlight environment-specific and/or time-dependent changes in functionality. Here, we identified previously unseen oil degradation-specific functions in BP oil-spill data, as well as functional signatures of individual-specific gut microbiome responses to a dietary intervention in children with Prader–Willi syndrome. Our method also revealed variability in Crohn's Disease patient microbiomes and clearly distinguished them from those of related healthy individuals. Our analysis highlighted the microbiome role in CD pathogenicity, demonstrating enrichment of patient microbiomes in functions that promote inflammation and that help bacteria survive it. PMID:29194524

Oral Microbiome of Deep and Shallow Dental Pockets In Chronic Periodontitis

PubMed Central

Ge, Xiuchun; Rodriguez, Rafael; Trinh, My; Gunsolley, John; Xu, Ping

2013-01-01

We examined the subgingival bacterial biodiversity in untreated chronic periodontitis patients by sequencing 16S rRNA genes. The primary purpose of the study was to compare the oral microbiome in deep (diseased) and shallow (healthy) sites. A secondary purpose was to evaluate the influences of smoking, race and dental caries on this relationship. A total of 88 subjects from two clinics were recruited. Paired subgingival plaque samples were taken from each subject, one from a probing site depth >5 mm (deep site) and the other from a probing site depth ≤3mm (shallow site). A universal primer set was designed to amplify the V4–V6 region for oral microbial 16S rRNA sequences. Differences in genera and species attributable to deep and shallow sites were determined by statistical analysis using a two-part model and false discovery rate. Fifty-one of 170 genera and 200 of 746 species were found significantly different in abundances between shallow and deep sites. Besides previously identified periodontal disease-associated bacterial species, additional species were found markedly changed in diseased sites. Cluster analysis revealed that the microbiome difference between deep and shallow sites was influenced by patient-level effects such as clinic location, race and smoking. The differences between clinic locations may be influenced by racial distribution, in that all of the African Americans subjects were seen at the same clinic. Our results suggested that there were influences from the microbiome for caries and periodontal disease and these influences are independent. PMID:23762384

Distinct composition of the oral indigenous microbiota in South Korean and Japanese adults

PubMed Central

Takeshita, Toru; Matsuo, Kazuki; Furuta, Michiko; Shibata, Yukie; Fukami, Kaoru; Shimazaki, Yoshihiro; Akifusa, Sumio; Han, Dong-Hung; Kim, Hyun-Duck; Yokoyama, Takeshi; Ninomiya, Toshiharu; Kiyohara, Yutaka; Yamashita, Yoshihisa

2014-01-01

A comparison of national surveys on oral health suggested that the population of South Korea has a better periodontal health status than that of Japan, despite their similar inherent backgrounds. Here, we investigated differences in oral bacterial assemblages between individuals from those two countries. To exclude potential effects of oral health condition on the microbiota, we selected 52 Korean and 88 Japanese orally healthy adults (aged 40–79 years) from the participants of two cohort studies, the Yangpyeong study in South Korea and the Hisayama study in Japan, and compared the salivary microbiomes. The microbiota of the Japanese individuals comprised a more diverse community, with greater proportions of 17 bacterial genera, including Veillonella, Prevotella, and Fusobacterium, compared to the microbiota of the Korean individuals. Conversely, Neisseria and Haemophilus species were present in much lower proportions in the microbiota of the Japanese individuals than the Korean individuals. Because higher proportions of Prevotella and Veillonella and lower proportions of Neisseria and Haemophilus in the salivary microbiome were implicated in periodontitis, the results of this study suggest that the greater proportion of dysbiotic oral microbiota in the Japanese individuals is associated with their higher susceptibility to periodontitis compared to the Korean individuals. PMID:25384884

Microbiome and pancreatic cancer: A comprehensive topic review of literature

PubMed Central

Ertz-Archambault, Natalie; Keim, Paul; Von Hoff, Daniel

2017-01-01

AIM To review microbiome alterations associated with pancreatic cancer, its potential utility in diagnostics, risk assessment, and influence on disease outcomes. METHODS A comprehensive literature review was conducted by all-inclusive topic review from PubMed, MEDLINE, and Web of Science. The last search was performed in October 2016. RESULTS Diverse microbiome alterations exist among several body sites including oral, gut, and pancreatic tissue, in patients with pancreatic cancer compared to healthy populations. CONCLUSION Pilot study successes in non-invasive screening strategies warrant further investigation for future translational application in early diagnostics and to learn modifiable risk factors relevant to disease prevention. Pre-clinical investigations exist in other tumor types that suggest microbiome manipulation provides opportunity to favorably transform cancer response to existing treatment protocols and improve survival. PMID:28348497

A geographically-diverse collection of 418 human gut microbiome pathway genome databases

PubMed Central

Hahn, Aria S.; Altman, Tomer; Konwar, Kishori M.; Hanson, Niels W.; Kim, Dongjae; Relman, David A.; Dill, David L.; Hallam, Steven J.

2017-01-01

Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools. PMID:28398290

Metagenomic sequencing reveals microbiota and its functional potential associated with periodontal disease

PubMed Central

Wang, Jinfeng; Qi, Ji; Zhao, Hui; He, Shu; Zhang, Yifei; Wei, Shicheng; Zhao, Fangqing

2013-01-01

Although attempts have been made to reveal the relationships between bacteria and human health, little is known about the species and function of the microbial community associated with oral diseases. In this study, we report the sequencing of 16 metagenomic samples collected from dental swabs and plaques representing four periodontal states. Insights into the microbial community structure and the metabolic variation associated with periodontal health and disease were obtained. We observed a strong correlation between community structure and disease status, and described a core disease-associated community. A number of functional genes and metabolic pathways including bacterial chemotaxis and glycan biosynthesis were over-represented in the microbiomes of periodontal disease. A significant amount of novel species and genes were identified in the metagenomic assemblies. Our study enriches the understanding of the oral microbiome and sheds light on the contribution of microorganisms to the formation and succession of dental plaques and oral diseases. PMID:23673380

The microbiome of uncontacted Amerindians.

PubMed

Clemente, Jose C; Pehrsson, Erica C; Blaser, Martin J; Sandhu, Kuldip; Gao, Zhan; Wang, Bin; Magris, Magda; Hidalgo, Glida; Contreras, Monica; Noya-Alarcón, Óscar; Lander, Orlana; McDonald, Jeremy; Cox, Mike; Walter, Jens; Oh, Phaik Lyn; Ruiz, Jean F; Rodriguez, Selena; Shen, Nan; Song, Se Jin; Metcalf, Jessica; Knight, Rob; Dantas, Gautam; Dominguez-Bello, M Gloria

2015-04-03

Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a microbiome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that westernization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mobilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized populations before globalization of modern practices affects potentially beneficial bacteria harbored in the human body.

The microbiome of uncontacted Amerindians

PubMed Central

Clemente, Jose C.; Pehrsson, Erica C.; Blaser, Martin J.; Sandhu, Kuldip; Gao, Zhan; Wang, Bin; Magris, Magda; Hidalgo, Glida; Contreras, Monica; Noya-Alarcón, Óscar; Lander, Orlana; McDonald, Jeremy; Cox, Mike; Walter, Jens; Oh, Phaik Lyn; Ruiz, Jean F.; Rodriguez, Selena; Shen, Nan; Song, Se Jin; Metcalf, Jessica; Knight, Rob; Dantas, Gautam; Dominguez-Bello, M. Gloria

2015-01-01

Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a microbiome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that westernization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mobilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized populations before globalization of modern practices affects potentially beneficial bacteria harbored in the human body. PMID:26229982

From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease

PubMed Central

2016-01-01

Abstract The oral microbiome is established within a few minutes after birth and consists of stable multi‐species communities that engage in a dynamic equilibrium with the host immune system. Dental caries, endodontic infections and periodontal diseases are bacterially driven diseases that are caused by dysbiotic microbiomes. Over a century ago, the focal infection theory implicated these infections in the aetiology of several systemic diseases, ranging from arthritis to neurodegenerative diseases. However, a lack of concrete evidence, combined with the urgency with which clinicians embraced this approach without regard for appropriate case selection, led to its demise within 30 years. In the last decade of the 20th century, the concept of periodontal medicine was introduced to explain the correlations that were being observed between periodontitis and cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, pulmonary disease, pre‐term delivery of low birth weight infants and metabolic disease. It was proposed that periodontal pathobionts played a causal role in the initiating or exacerbating certain diseases either by direct invasion or by stimulating a florid immune‐inflammatory response that extended into the systemic circulation. This review will examine the strength of current evidence in establishing a causal link between oral pathobionts and systemic disease. PMID:27426277

Bacterial diversity in saliva and oral health-related conditions: the Hisayama Study

NASA Astrophysics Data System (ADS)

Takeshita, Toru; Kageyama, Shinya; Furuta, Michiko; Tsuboi, Hidenori; Takeuchi, Kenji; Shibata, Yukie; Shimazaki, Yoshihiro; Akifusa, Sumio; Ninomiya, Toshiharu; Kiyohara, Yutaka; Yamashita, Yoshihisa

2016-02-01

This population-based study determined the salivary microbiota composition of 2,343 adult residents of Hisayama town, Japan, using 16S rRNA gene next-generation high-throughput sequencing. Of 550 identified species-level operational taxonomic units (OTUs), 72 were common, in ≥75% of all individuals, as well as in ≥75% of the individuals in the lowest quintile of phylogenetic diversity (PD). These “core” OTUs constituted 90.9 ± 6.1% of each microbiome. The relative abundance profiles of 22 of the core OTUs with mean relative abundances ≥1% were stratified into community type I and community type II by partitioning around medoids clustering. Multiple regression analysis revealed that a lower PD was associated with better conditions for oral health, including a lower plaque index, absence of decayed teeth, less gingival bleeding, shallower periodontal pockets and not smoking, and was also associated with tooth loss. By contrast, multiple Poisson regression analysis demonstrated that community type II, as characterized by a higher ratio of the nine dominant core OTUs, including Neisseria flavescens, was implicated in younger age, lower body mass index, fewer teeth with caries experience, and not smoking. Our large-scale data analyses reveal variation in the salivary microbiome among Japanese adults and oral health-related conditions associated with the salivary microbiome.

Changes in the oral ecosystem induced by the use of 8% arginine toothpaste.

PubMed

Koopman, Jessica E; Hoogenkamp, Michel A; Buijs, Mark J; Brandt, Bernd W; Keijser, Bart J F; Crielaard, Wim; Ten Cate, Jacob M; Zaura, Egija

2017-01-01

Bacterial metabolism of arginine in the oral cavity has a pH-raising and thus, potential anti-caries effect. However, the influence of arginine on the oral microbial ecosystem remains largely unresolved. In this pilot study, nine healthy individuals used toothpaste containing 8% arginine for eight weeks. Saliva was collected to determine arginolytic potential and sucrose metabolic activity at the Baseline, Week 4, Week 8 and after a two weeks Wash-out period. To follow the effects on microbial ecology, 16S rDNA sequencing on saliva and plaque samples at Baseline and Week 8 and metagenome sequencing on selected saliva samples of the same time-points was performed. During the study period, the arginolytic potential of saliva increased, while the sucrose metabolism in saliva decreased. These effects were reversed during the Wash-out period. Although a few operational taxonomic units (OTUs) in plaque changed in abundance during the study period, there was no real shift in the plaque microbiome. In the saliva microbiome there was a significant compositional shift, specifically the genus Veillonella had increased significantly in abundance at Week 8. Indeed, the presence of arginine in toothpaste affects the arginolytic capacity of saliva and reduces its sucrose metabolic activity. Additionally, it leads to a shift in the salivary microbiome composition towards a healthy ecology from a caries point of view. Therefore, arginine can be regarded as a genuine oral prebiotic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

PubMed

Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

2016-05-01

SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

Salivary inflammatory markers and microbiome in normoglycemic lean and obese children compared to obese children with type 2 diabetes.

PubMed

Janem, Waleed F; Scannapieco, Frank A; Sabharwal, Amarpeet; Tsompana, Maria; Berman, Harvey A; Haase, Elaine M; Miecznikowski, Jeffrey C; Mastrandrea, Lucy D

2017-01-01

There is emerging evidence linking diabetes with periodontal disease. Diabetes is a well-recognized risk factor for periodontal disease. Conversely, pro-inflammatory molecules released by periodontally-diseased tissues may enter the circulation to induce insulin resistance. While this association has been demonstrated in adults, there is little information regarding periodontal status in obese children with and without type 2 diabetes (T2D). We hypothesized that children with T2D have higher rates of gingivitis, elevated salivary inflammatory markers, and an altered salivary microbiome compared to children without T2D. Three pediatric cohorts ages 10-19 years were studied: lean (normal weight-C), obese (Ob), and obese with T2D (T2D). Each subject completed an oral health survey, received a clinical oral examination, and provided unstimulated saliva for measurement of inflammatory markers and microbiome analysis. The diabetes group was less likely to have had a dental visit within the last six months. Body mass index (BMI) Z-scores and waist circumference/height ratios were similar between Ob and T2D cohorts. The number of carious lesions and fillings were similar for all three groups. The gingival index was greater in the T2D group compared to the Ob and C groups. Although salivary microbial diversity was minimal between groups, a few differences in bacterial genus composition were noted. Obese children with T2D show a trend toward poorer oral health compared to normal weight and obese children without T2D. This study characterizes the salivary microbiome of children with and without obesity and T2D. This study supports a modest link between T2D and periodontal inflammation in the pediatric population.

An assessment of US microbiome research.

PubMed

Stulberg, Elizabeth; Fravel, Deborah; Proctor, Lita M; Murray, David M; LoTempio, Jonathan; Chrisey, Linda; Garland, Jay; Goodwin, Kelly; Graber, Joseph; Harris, M Camille; Jackson, Scott; Mishkind, Michael; Porterfield, D Marshall; Records, Angela

2016-01-11

Genome-enabled technologies have supported a dramatic increase in our ability to study microbial communities in environments and hosts. Taking stock of previously funded microbiome research can help to identify common themes, under-represented areas and research priorities to consider moving forward. To assess the status of US microbiome research, a team of government scientists conducted an analysis of federally funded microbiome research. Microbiomes were defined as host-, ecosystem- or habitat-associated communities of microorganisms, and microbiome research was defined as those studies that emphasize community-level analyses using 'omics technologies. Single pathogen, single strain and culture-based studies were not included, except symbiosis studies that served as models for more complex communities. Fourteen governmental organizations participated in the data call. The analysis examined three broad research themes, eight environments and eight microbial categories. Human microbiome research was larger than any other environment studied, and the basic biology research theme accounted for half of the total research activities. Computational biology and bioinformatics, reference databases and biorepositories, standardized protocols and high-throughput tools were commonly identified needs. Longitudinal and functional studies and interdisciplinary research were also identified as needs. This study has implications for the funding of future microbiome research, not only in the United States but beyond.

Dynamics and associations of microbial community types across the human body.

PubMed

Ding, Tao; Schloss, Patrick D

2014-05-15

A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point. Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.

Oral microbiota in youth with perinatally acquired HIV infection.

PubMed

Starr, Jacqueline R; Huang, Yanmei; Lee, Kyu Ha; Murphy, C M; Moscicki, Anna-Barbara; Shiboski, Caroline H; Ryder, Mark I; Yao, Tzy-Jyun; Faller, Lina L; Van Dyke, Russell B; Paster, Bruce J

2018-05-31

Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth. We compared oral microbiome levels and associations with caries or periodontitis in 154 PHIV and 100 PHEU youth. Species richness and alpha diversity differed little between PHIV and PHEU youth. Group differences in average counts met the significance threshold for six taxa; two Corynebacterium species were lower in PHIV and met thresholds for noteworthiness. Several known periodontitis-associated organisms (Prevotella nigrescens, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Filifactor alocis) exhibited expected associations with periodontitis in PHEU youth, associations not observed in PHIV youth. In both groups, odds of caries increased with counts of taxa in four genera, Streptococcus, Scardovia, Bifidobacterium, and Lactobacillus. The microbiomes of PHIV and PHEU youth were similar, although PHIV youth seemed to have fewer "health"-associated taxa such as Corynebacterium species. These results are consistent with the hypothesis that HIV infection, or its treatment, may contribute to oral dysbiosis.

The subgingival periodontal microbiota in the aging mouth

PubMed Central

FERES, Magda; TELES, Flavia; TELES, Ricardo; FIGUEIREDO, Luciene Cristina; FAVERI, Marcelo

2016-01-01

Different mechanisms have been hypothesized to explain the increase in prevalence and severity of periodontitis in older adults, including shifts in the periodontal microbiota. However, the actual impact of aging in the composition of subgingival biofilms remains unclear. In the present article, we provide an overview of the composition of the subgingival biofilm in older adults and the potential effects of age on the oral microbiome. In particular, this review covers the following topics: (i) the oral microbiota of an aging mouth, (ii) the effects of age and time on the human oral microbiome, (iii) the potential impact of inflammaging and immunosenescence in the host-oral microbiota interactions, and (iv) the relationship of the aging oral microbiota and Alzheimer’s disease. Finally, in order to explore in greater breadth the potential effects of aging on the periodontal microbiota, we present analyses of data compiled from large clinical studies that evaluated the subgingival microbiota of periodontally healthy subjects and periodontitis patients from a wide age spectrum (20–83 years old). Those studies were conducted at Guarulhos University (São Paulo, SP, Brazil) and at The Forsyth Institute (Cambridge, USA), from 1999 to 2014. PMID:27501490

Biodiversity of the Human Oral Mycobiome in Health and Disease.

PubMed

Bandara, H M H N; Panduwawala, C P; Samaranayake, L P

2018-05-22

The organisms that colonize the human body over a lifetime are diverse, extensive and gargantuan. A fair proportion of the microbiota that constitutes this human microbiome live within our oral cavities mostly as harmonious associates causing only sporadic disease. An important core constituent of the microbiome is the mycobiome, representing various fungal genera. Up until recently, only a few species of fungi, mainly Candida species, were thought to constitute the human oral mycobiome. The reasons for this are manifold, although the uncultivable nature of many fungi in conventional laboratory media, and their complex genetic composition seem to be the major factors which eluded their detection over the years. Nevertheless, recent advances in computing and high throughput sequencing such as next generation sequencing (NGS) platforms have provided us a panoramic view of a totally new world of fungi that are human oral co-habitués. Their diversity is perplexing, and functionality yet to be deciphered. Here we provide a glimpse of what is currently known of the oral mycobiome, in health and disease, with some future perspectives. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract.

PubMed

Le Bars, Pierre; Matamoros, Sébastien; Montassier, Emmanuel; Le Vacon, Françoise; Potel, Gilles; Soueidan, Assem; Jordana, Fabienne; de La Cochetière, Marie-France

2017-06-01

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

PubMed

Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

2017-07-01

Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

Do you kiss your mother with that mouth? An authentic large-scale undergraduate research experience in mapping the human oral microbiome.

PubMed

Wang, Jack T H; Daly, Joshua N; Willner, Dana L; Patil, Jayee; Hall, Roy A; Schembri, Mark A; Tyson, Gene W; Hugenholtz, Philip

2015-05-01

Clinical microbiology testing is crucial for the diagnosis and treatment of community and hospital-acquired infections. Laboratory scientists need to utilize technical and problem-solving skills to select from a wide array of microbial identification techniques. The inquiry-driven laboratory training required to prepare microbiology graduates for this professional environment can be difficult to replicate within undergraduate curricula, especially in courses that accommodate large student cohorts. We aimed to improve undergraduate scientific training by engaging hundreds of introductory microbiology students in an Authentic Large-Scale Undergraduate Research Experience (ALURE). The ALURE aimed to characterize the microorganisms that reside in the healthy human oral cavity-the oral microbiome-by analyzing hundreds of samples obtained from student volunteers within the course. Students were able to choose from selective and differential culture media, Gram-staining, microscopy, as well as polymerase chain reaction (PCR) and 16S rRNA gene sequencing techniques, in order to collect, analyze, and interpret novel data to determine the collective oral microbiome of the student cohort. Pre- and postsurvey analysis of student learning gains across two iterations of the course (2012-2013) revealed significantly higher student confidence in laboratory skills following the completion of the ALURE (p < 0.05 using the Mann-Whitney U-test). Learning objectives on effective scientific communication were also met through effective student performance in laboratory reports describing the research outcomes of the project. The integration of undergraduate research in clinical microbiology has the capacity to deliver authentic research experiences and improve scientific training for large cohorts of undergraduate students.

The nasal microbiota of dairy farmers is more complex than oral microbiota, reflects occupational exposure, and provides competition for staphylococci

PubMed Central

Sandberg, Scott; Reyes, Iris; Fritsche, Thomas R.

2017-01-01

Allergic and autoimmune diseases had been attributed to lack of exposure to biodiversity, an important factor in regulating immune homeostasis in a healthy host. We posit that the microbiome of healthy dairy farmers (DF) will be richer than non-farmers (NF) living in urban settings due to exposure to a greater biodiversity in the dairy environment. However, no studies have investigated the relationships between microbiota of dairy farmers (DF) compared with urban non-farmers (NF). We compared the nasal and oral microbiota of dairy farmers (N_DF, O_DF, respectively) with nasal and oral microbiota of NF in the same geographical area. The N_DF showed high microbial diversity with hundreds of unique genera that reflected environmental/occupational exposures. The nasal and oral microbiomes clustered separately from each other using Principal Coordinate Analysis, and with DF harboring two-fold and 1.5-fold greater exclusive genera in their nose and mouth respectively, than did non-farmers. Additionally, the N_DF group had a lower burden of Staphylococcus spp. suggesting a correlation between higher microbial diversity and competition for colonization by staphylococci. The N_DF samples were negative for the mecA gene, a marker of methicillin-resistance in staphylococci. The lower burden of staphylococci was found to be independent of the abundance of Corynebacterium spp. Exposure to greater biodiversity could enhance microbial competition, thereby reducing colonization with opportunistic pathogens. Future studies will analyze whether exposure to livestock microbiomes offers protection from acute and chronic diseases. PMID:28850578

The nasal microbiota of dairy farmers is more complex than oral microbiota, reflects occupational exposure, and provides competition for staphylococci.

PubMed

Shukla, Sanjay K; Ye, Zhan; Sandberg, Scott; Reyes, Iris; Fritsche, Thomas R; Keifer, Matthew

2017-01-01

Allergic and autoimmune diseases had been attributed to lack of exposure to biodiversity, an important factor in regulating immune homeostasis in a healthy host. We posit that the microbiome of healthy dairy farmers (DF) will be richer than non-farmers (NF) living in urban settings due to exposure to a greater biodiversity in the dairy environment. However, no studies have investigated the relationships between microbiota of dairy farmers (DF) compared with urban non-farmers (NF). We compared the nasal and oral microbiota of dairy farmers (N_DF, O_DF, respectively) with nasal and oral microbiota of NF in the same geographical area. The N_DF showed high microbial diversity with hundreds of unique genera that reflected environmental/occupational exposures. The nasal and oral microbiomes clustered separately from each other using Principal Coordinate Analysis, and with DF harboring two-fold and 1.5-fold greater exclusive genera in their nose and mouth respectively, than did non-farmers. Additionally, the N_DF group had a lower burden of Staphylococcus spp. suggesting a correlation between higher microbial diversity and competition for colonization by staphylococci. The N_DF samples were negative for the mecA gene, a marker of methicillin-resistance in staphylococci. The lower burden of staphylococci was found to be independent of the abundance of Corynebacterium spp. Exposure to greater biodiversity could enhance microbial competition, thereby reducing colonization with opportunistic pathogens. Future studies will analyze whether exposure to livestock microbiomes offers protection from acute and chronic diseases.

From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease.

PubMed

Kumar, Purnima S

2017-01-15

The oral microbiome is established within a few minutes after birth and consists of stable multi-species communities that engage in a dynamic equilibrium with the host immune system. Dental caries, endodontic infections and periodontal diseases are bacterially driven diseases that are caused by dysbiotic microbiomes. Over a century ago, the focal infection theory implicated these infections in the aetiology of several systemic diseases, ranging from arthritis to neurodegenerative diseases. However, a lack of concrete evidence, combined with the urgency with which clinicians embraced this approach without regard for appropriate case selection, led to its demise within 30 years. In the last decade of the 20th century, the concept of periodontal medicine was introduced to explain the correlations that were being observed between periodontitis and cardiovascular disease, rheumatoid arthritis, Alzheimer's disease, pulmonary disease, pre-term delivery of low birth weight infants and metabolic disease. It was proposed that periodontal pathobionts played a causal role in the initiating or exacerbating certain diseases either by direct invasion or by stimulating a florid immune-inflammatory response that extended into the systemic circulation. This review will examine the strength of current evidence in establishing a causal link between oral pathobionts and systemic disease. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The Airplane Cabin Microbiome.

PubMed

Weiss, Howard; Hertzberg, Vicki Stover; Dupont, Chris; Espinoza, Josh L; Levy, Shawn; Nelson, Karen; Norris, Sharon

2018-06-06

Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics. Over two dozen cases of in-flight transmissions have been documented. To understand these risks, a characterization of the airplane cabin microbiome is necessary. Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing. We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria. We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces. We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples. There was no systematic pattern of microbial community change from pre- to post-flight. Our findings are similar to those of other recent studies of the microbiome of built environments. In summary, the airplane cabin microbiome has immense airplane to airplane variability. The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions.

Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection.

PubMed

Morris, Alison; Paulson, Joseph N; Talukder, Hisham; Tipton, Laura; Kling, Heather; Cui, Lijia; Fitch, Adam; Pop, Mihai; Norris, Karen A; Ghedin, Elodie

2016-07-08

Longitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre-infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing. We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease. This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease.

Dynamics and associations of microbial community types across the human body

PubMed Central

Ding, Tao; Schloss, Patrick D.

2014-01-01

A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S rRNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health 1. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point 2,3. Using additional data collected over the course of 12–18 months, we used Dirichlet multinomial mixture models 4 to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether they had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, while those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and inter-personal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are likely the result of life history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies. PMID:24739969

The Human Microbiome in the Fight Against Tuberculosis

PubMed Central

Wood, Madeleine R.; Yu, Elaine A.; Mehta, Saurabh

2017-01-01

The human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study (N = 1), case report (N = 1), and case–control studies (N = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case–control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance. PMID:28719264

Maternal–Child Microbiome: Specimen Collection, Storage and Implications for Research and Practice

PubMed Central

Jordan, Sheila; Baker, Brenda; Dunn, Alexis; Edwards, Sara; Ferranti, Erin; Mutic, Abby D.; Yang, Irene; Rodriguez, Jeannie

2017-01-01

Background The maternal microbiome is a key contributor to the development and outcomes of pregnancy and the health status of both mother and infant. Significant advances are occurring in the science of the maternal and child microbiome and hold promise in improving outcomes related to pregnancy complications, child development, and chronic health conditions of mother and child. Objectives The purpose of the paper is to review site-specific considerations in the collection and storage of maternal and child microbiome samples and its implications for nursing research and practice. Approach Microbiome sampling protocols were reviewed and synthesized. Precautions across sampling protocols were also noted. Results Oral, vaginal, gut, placental, and breastmilk are viable sources for sampling the maternal and/or child microbiome. Prior to sampling special considerations need to be addressed related to various factors including current medications, health status, and hygiene practices. Proper storage of samples will avoid degradation of cellular and DNA structures vital for analysis. Discussion Changes in the microbiome throughout the perinatal, postpartum and childhood periods are dramatic and significant to outcomes of the pregnancy and the long-term health of mother and child. Proper sampling techniques are required to produce reliable results from which evidence-based practice recommendations will be built. Ethical and practical issues surrounding study design and protocol development must also be considered when researching vulnerable groups such as pregnant women and infants. Nurses hold the responsibility to both perform the research and to translate findings from microbiome investigations for clinical use. PMID:28252577

Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma.

PubMed

Pérez-Losada, Marcos; Castro-Nallar, Eduardo; Bendall, Matthew L; Freishtat, Robert J; Crandall, Keith A

2015-01-01

High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for variation in clinical metadata. Transcriptomic (host) and metatranscriptomic (microbiota) sequences from the nasal epithelium of 8 asthmatics and 6 healthy controls were separated in silico and mapped to available human and NCBI-NR protein reference databases. Human genes differentially expressed in asthmatics and controls were then used to infer upstream regulators involved in immune and inflammatory responses. Concomitantly, microbial genes were mapped to metabolic databases (COG, SEED, and KEGG) to infer microbial functions differentially expressed in asthmatics and controls. Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation. Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested. Enrichment analysis of 499 differentially expressed host genes for inflammatory and immune responses revealed 43 upstream regulators differentially activated in asthma. Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.

Salivary Gluten Degradation and Oral Microbial Profiles in Healthy Individuals and Celiac Disease Patients.

PubMed

Tian, Na; Faller, Lina; Leffler, Daniel A; Kelly, Ciaran P; Hansen, Joshua; Bosch, Jos A; Wei, Guoxian; Paster, Bruce J; Schuppan, Detlef; Helmerhorst, Eva J

2017-03-15

Celiac disease (CD) is a chronic immune-mediated enteropathy induced by dietary gluten in genetically predisposed individuals. Saliva harbors the second highest bacterial load of the gastrointestinal (GI) tract after the colon. We hypothesized that enzymes produced by oral bacteria may be involved in gluten processing in the intestine and susceptibility to celiac disease. The aim of this study was to investigate salivary enzymatic activities and oral microbial profiles in healthy subjects versus patients with classical and refractory CD. Stimulated whole saliva was collected from patients with CD in remission ( n = 21) and refractory CD (RCD; n = 8) and was compared to healthy controls (HC; n = 20) and subjects with functional GI complaints ( n = 12). Salivary gluten-degrading activities were monitored with the tripeptide substrate Z-Tyr-Pro-Gln-pNA and the α-gliadin-derived immunogenic 33-mer peptide. The oral microbiome was profiled by 16S rRNA-based MiSeq analysis. Salivary glutenase activities were higher in CD patients compared to controls, both before and after normalization for protein concentration or bacterial load. The oral microbiomes of CD and RCD patients showed significant differences from that of healthy subjects, e.g., higher salivary levels of lactobacilli ( P < 0.05), which may partly explain the observed higher gluten-degrading activities. While the pathophysiological link between the oral and gut microbiomes in CD needs further exploration, the presented data suggest that oral microbe-derived enzyme activities are elevated in subjects with CD, which may impact gluten processing and the presentation of immunogenic gluten epitopes to the immune system in the small intestine. IMPORTANCE Ingested gluten proteins are the triggers of intestinal inflammation in celiac disease (CD). Certain immunogenic gluten domains are resistant to intestinal proteases but can be hydrolyzed by oral microbial enzymes. Very little is known about the endogenous proteolytic processing of gluten proteins in the oral cavity. Given that this occurs prior to gluten reaching the small intestine, such enzymes are likely to contribute to the composition of the gluten digest that ultimately reaches the small intestine and causes CD. We demonstrated that endogenous salivary protease activities are incomplete, likely liberating peptides from larger gluten proteins. The potentially responsible microbes were identified. The study included refractory CD patients, who have been studied less with regard to CD pathogenesis. Copyright © 2017 American Society for Microbiology.

Oral Biofilms from Symbiotic to Pathogenic Interactions and Associated Disease –Connection of Periodontitis and Rheumatic Arthritis by Peptidylarginine Deiminase

PubMed Central

Kriebel, Katja; Hieke, Cathleen; Müller-Hilke, Brigitte; Nakata, Masanobu; Kreikemeyer, Bernd

2018-01-01

A wide range of bacterial species are harbored in the oral cavity, with the resulting complex network of interactions between the microbiome and host contributing to physiological as well as pathological conditions at both local and systemic levels. Bacterial communities inhabit the oral cavity as primary niches in a symbiotic manner and form dental biofilm in a stepwise process. However, excessive formation of biofilm in combination with a corresponding deregulated immune response leads to intra-oral diseases, such as dental caries, gingivitis, and periodontitis. Moreover, oral commensal bacteria, which are classified as so-called “pathobionts” according to a now widely accepted terminology, were recently shown to be present in extra-oral lesions with distinct bacterial species found to be involved in the onset of various pathophysiological conditions, including cancer, atherosclerosis, chronic infective endocarditis, and rheumatoid arthritis. The present review focuses on oral pathobionts as commensal and healthy members of oral biofilms that can turn into initiators of disease. We will shed light on the processes involved in dental biofilm formation and also provide an overview of the interactions of P. gingivalis, as one of the most prominent oral pathobionts, with host cells, including epithelial cells, phagocytes, and dental stem cells present in dental tissues. Notably, a previously unknown interaction of P. gingivalis bacteria with human stem cells that has impact on human immune response is discussed. In addition to this very specific interaction, the present review summarizes current knowledge regarding the immunomodulatory effect of P. gingivalis and other oral pathobionts, members of the oral microbiome, that pave the way for systemic and chronic diseases, thereby showing a link between periodontitis and rheumatoid arthritis. PMID:29441048

Composition and development of oral bacterial communities.

PubMed

Palmer, Robert J

2014-02-01

The oral bacterial microbiome encompasses approximately 700 commonly occurring phylotypes, approximately half of which can be present at any time in any individual. These bacteria are largely indigenous to the oral cavity; this limited habitat range suggests that interactions between the various phylotypes, and between the phylotypes and their environment, are crucial for their existence. Molecular cataloging has confirmed many basic observations on the composition of the oral microbiome that were formulated well before ribosomal RNA-based systematics, but the power and the scope of molecular taxonomy have resulted in the discovery of new phylotypes and, more importantly, have made possible a level of bacterial community analysis that was unachievable with classical methods. Bacterial community structure varies with location within the mouth, and changes in community structure are related to disease initiation and disease progression. Factors that influence the formation and the evolution of communities include selective adherence to epithelial or tooth surfaces, specific cell-to-cell binding as a driver of early community composition, and interorganismal interaction leading to alteration of the local environment, which represents the first step on the road to oral disease. A comprehensive understanding of how these factors interact to drive changes in the composition of the oral microbial community can lead to new strategies for the inhibition of periodontal diseases and dental caries. Published 2013. This article is a US Government work and is in the public domain in the USA.

The oral microbiome in human immunodeficiency virus (HIV)-positive individuals.

PubMed

Kistler, James O; Arirachakaran, Pratanporn; Poovorawan, Yong; Dahlén, Gunnar; Wade, William G

2015-09-01

Human immunodeficiency virus (HIV) infection is associated with a range of oral conditions, and increased numbers of disease-associated microbial species have previously been found in HIV-positive subjects. The aim of this study was to use next-generation sequencing to compare the composition of the oral microbiome in HIV-positive and -negative individuals. Plaque and saliva were collected from 37 HIV-positive individuals and 37 HIV-negative individuals, and their bacterial composition determined by pyrosequencing of partial 16S rRNA genes. A total of 855,222 sequences were analysed. The number of species-level operational taxonomic units (OTUs) detected was significantly lower in the saliva of HIV-positive individuals (mean = 303.3) than in that of HIV-negative individuals (mean = 365.5) (P < 0.0003). Principal coordinates analysis (PCoA) based on community membership (Jaccard index) and structure (Yue and Clayton measure of dissimilarity) showed significant separation of plaque and saliva samples [analysis of molecular variance (AMOVA), P < 0.001]. PCoA plots did not show any clear separation based on HIV status. However, AMOVA indicated that there was a significant difference in the community membership of saliva between HIV-positive and -negative groups (P = 0.001). Linear discriminant analysis effect size revealed an OTU identified as Haemophilus parainfluenzae to be significantly associated with HIV-positive individuals, whilst Streptococcus mitis/HOT473 was most significantly associated with HIV-negative individuals. In conclusion, this study has confirmed that the microbial composition of saliva and plaque is different. The oral microbiomes of HIV-positive and -negative individuals were found to be similar overall, although there were minor but significant differences in the composition of the salivary microbiota of the two groups.

The microbiome associated with equine periodontitis and oral health.

PubMed

Kennedy, Rebekah; Lappin, David Francis; Dixon, Padraic Martin; Buijs, Mark Johannes; Zaura, Egija; Crielaard, Wim; O'Donnell, Lindsay; Bennett, David; Brandt, Bernd Willem; Riggio, Marcello Pasquale

2016-04-14

Equine periodontal disease is a common and painful condition and its severe form, periodontitis, can lead to tooth loss. Its aetiopathogenesis remains poorly understood despite recent increased awareness of this disorder amongst the veterinary profession. Bacteria have been found to be causative agents of the disease in other species, but current understanding of their role in equine periodontitis is extremely limited. The aim of this study was to use high-throughput sequencing to identify the microbiome associated with equine periodontitis and oral health. Subgingival plaque samples from 24 horses with periodontitis and gingival swabs from 24 orally healthy horses were collected. DNA was extracted from samples, the V3-V4 region of the bacterial 16S rRNA gene amplified by PCR and amplicons sequenced using Illumina MiSeq. Data processing was conducted using USEARCH and QIIME. Diversity analyses were performed with PAST v3.02. Linear discriminant analysis effect size (LEfSe) was used to determine differences between the groups. In total, 1308 OTUs were identified and classified into 356 genera or higher taxa. Microbial profiles at health differed significantly from periodontitis, both in their composition (p < 0.0001, F = 12.24; PERMANOVA) and in microbial diversity (p < 0.001; Mann-Whitney test). Samples from healthy horses were less diverse (1.78, SD 0.74; Shannon diversity index) and were dominated by the genera Gemella and Actinobacillus, while the periodontitis group samples showed higher diversity (3.16, SD 0.98) and were dominated by the genera Prevotella and Veillonella. It is concluded that the microbiomes associated with equine oral health and periodontitis are distinct, with the latter displaying greater microbial diversity.

Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection.

PubMed

Kaleko, Michael; Bristol, J Andrew; Hubert, Steven; Parsley, Todd; Widmer, Giovanni; Tzipori, Saul; Subramanian, Poorani; Hasan, Nur; Koski, Perrti; Kokai-Kun, John; Sliman, Joseph; Jones, Annie; Connelly, Sheila

2016-10-01

The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

In vitro Increased Respiratory Activity of Selected Oral Bacteria May Explain Competitive and Collaborative Interactions in the Oral Microbiome

PubMed Central

Hernandez-Sanabria, Emma; Slomka, Vera; Herrero, Esteban R.; Kerckhof, Frederiek-Maarten; Zaidel, Lynette; Teughels, Wim; Boon, Nico

2017-01-01

Understanding the driving forces behind the shifts in the ecological balance of the oral microbiota will become essential for the future management and treatment of periodontitis. As the use of competitive approaches for modulating bacterial outgrowth is unexplored in the oral ecosystem, our study aimed to investigate both the associations among groups of functional compounds and the impact of individual substrates on selected members of the oral microbiome. We employed the Phenotype Microarray high-throughput technology to analyse the microbial cellular phenotypes of 15 oral bacteria. Multivariate statistical analysis was used to detect respiratory activity triggers and to assess similar metabolic activities. Carbon and nitrogen were relevant for the respiration of health-associated bacteria, explaining competitive interactions when grown in biofilms. Carbon, nitrogen, and peptides tended to decrease the respiratory activity of all pathobionts, but not significantly. None of the evaluated compounds significantly increased activity of pathobionts at both 24 and 48 h. Additionally, metabolite requirements of pathobionts were dissimilar, suggesting that collective modulation of their respiratory activity may be challenging. Flow cytometry indicated that the metabolic activity detected in the Biolog plates may not be a direct result of the number of bacterial cells. In addition, damage to the cell membrane may not influence overall respiratory activity. Our methodology confirmed previously reported competitive and collaborative interactions among bacterial groups, which could be used either as marker of health status or as targets for modulation of the oral environment. PMID:28638806

Antibiotic resistance genes across a wide variety of metagenomes.

PubMed

Fitzpatrick, David; Walsh, Fiona

2016-02-01

The distribution of potential clinically relevant antibiotic resistance (AR) genes across soil, water, animal, plant and human microbiomes is not well understood. We aimed to investigate if there were differences in the distribution and relative abundances of resistance genes across a variety of ecological niches. All sequence reads (human, animal, water, soil, plant and insect metagenomes) from the MG-RAST database were downloaded and assembled into a local sequence database. We show that there are many reservoirs of the basic form of resistance genes e.g. blaTEM, but the human and mammalian gut microbiomes contain the widest diversity of clinically relevant resistance genes using metagenomic analysis. The human microbiomes contained a high relative abundance of resistance genes, while the relative abundances varied greatly in the marine and soil metagenomes, when datasets with greater than one million genes were compared. While these results reflect a bias in the distribution of AR genes across the metagenomes, we note this interpretation with caution. Metagenomics analysis includes limits in terms of detection and identification of AR genes in complex and diverse microbiome population. Therefore, if we do not detect the AR gene is it in fact not there or just below the limits of our techniques? © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis.

PubMed Central

Lasica, Anna M.; Goulas, Theodoros; Mizgalska, Danuta; Zhou, Xiaoyan; de Diego, Iñaki; Ksiazek, Mirosław; Madej, Mariusz; Guo, Yonghua; Guevara, Tibisay; Nowak, Magdalena; Potempa, Barbara; Goel, Apoorv; Sztukowska, Maryta; Prabhakar, Apurva T.; Bzowska, Monika; Widziolek, Magdalena; Thøgersen, Ida B.; Enghild, Jan J.; Simonian, Mary; Kulczyk, Arkadiusz W.; Nguyen, Ky-Anh; Potempa, Jan; Gomis-Rüth, F. Xavier

2016-01-01

Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T9SS carry a recognition signal in the conserved C-terminal domain (CTD), which is removed by sortase PorU during translocation. Here, we identified a novel component of T9SS, PorZ, which is essential for surface exposure of PorU and posttranslational modification of T9SS cargo proteins. These include maturation of enzyme precursors, CTD removal and attachment of anionic lipopolysaccharide for anchorage in the outer membrane. The crystal structure of PorZ revealed two β-propeller domains and a C-terminal β-sandwich domain, which conforms to the canonical CTD architecture. We further documented that PorZ is itself transported to the cell surface via T9SS as a full-length protein with its CTD intact, independently of the presence or activity of PorU. Taken together, our results shed light on the architecture and possible function of a novel component of the T9SS. Knowledge of how T9SS operates will contribute to our understanding of protein secretion as part of host-microbiome interactions by dysbiotic members of the human oral cavity. PMID:27883039

Exploring the Association between Alzheimer's Disease, Oral Health, Microbial Endocrinology and Nutrition.

PubMed

Harding, Alice; Gonder, Ulrike; Robinson, Sarita J; Crean, StJohn; Singhrao, Sim K

2017-01-01

Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer's disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis , a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host's inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual's diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns. This review suggests healthy diet based interventions that together with improved life style/behavioral changes may reduce and/or delay the incidence of AD.

Exploring the Association between Alzheimer’s Disease, Oral Health, Microbial Endocrinology and Nutrition

PubMed Central

Harding, Alice; Gonder, Ulrike; Robinson, Sarita J.; Crean, StJohn; Singhrao, Sim K.

2017-01-01

Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer’s disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host’s inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual’s diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns. This review suggests healthy diet based interventions that together with improved life style/behavioral changes may reduce and/or delay the incidence of AD. PMID:29249963

Second Era of OMICS in Caries Research: Moving Past the Phase of Disillusionment.

PubMed

Nascimento, M M; Zaura, E; Mira, A; Takahashi, N; Ten Cate, J M

2017-07-01

Novel approaches using OMICS techniques enable a collective assessment of multiple related biological units, including genes, gene expression, proteins, and metabolites. In the past decade, next-generation sequencing ( NGS) technologies were improved by longer sequence reads and the development of genome databases and user-friendly pipelines for data analysis, all accessible at lower cost. This has generated an outburst of high-throughput data. The application of OMICS has provided more depth to existing hypotheses as well as new insights in the etiology of dental caries. For example, the determination of complete bacterial microbiomes of oral samples rather than selected species, together with oral metatranscriptome and metabolome analyses, supports the viewpoint of dysbiosis of the supragingival biofilms. In addition, metabolome studies have been instrumental in disclosing the contributions of major pathways for central carbon and amino acid metabolisms to biofilm pH homeostasis. New, often noncultured, oral streptococci have been identified, and their phenotypic characterization has revealed candidates for probiotic therapy. Although findings from OMICS research have been greatly informative, problems related to study design, data quality, integration, and reproducibility still need to be addressed. Also, the emergence and continuous updates of these computationally demanding technologies require expertise in advanced bioinformatics for reliable interpretation of data. Despite the obstacles cited above, OMICS research is expected to encourage the discovery of novel caries biomarkers and the development of next-generation diagnostics and therapies for caries control. These observations apply equally to the study of other oral diseases.

Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes - A Randomized Controlled Trial.

PubMed

Timby, Niklas; Domellöf, Magnus; Holgerson, Pernilla Lif; West, Christina E; Lönnerdal, Bo; Hernell, Olle; Johansson, Ingegerd

2017-01-01

In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age. The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk. In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria. Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups. Supplementation of infant formula with MFGM yielded moderate effects on the oral microbiome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.

The Sphagnum microbiome: New insights from an ancient plant lineage

DOE PAGES

Kostka, Joel E.; Weston, David J.; Glass, Jennifer B.; ...

2016-05-13

Here, peat mosses of the genus Sphagnum play a major role in global carbon storage and dominate many northern peatland ecosystems, which are currently being subjected to some of the most rapid climate changes on Earth. A rapidly expanding database indicates that a diverse community of microorganisms is intimately associated with Sphagnum, inhabiting the tissues and surface of the plant. Here we summarize the current state of knowledge regarding the Sphagnum microbiome and provide a perspective for future research directions. Although the majority of the microbiome remains uncultivated and its metabolic capabilities uncharacterized, prokaryotes and fungi have the potential tomore » act as mutualists, symbionts, or antagonists of Sphagnum. For example, methanotrophic and nitrogen-fixing bacteria may benefit the plant host by providing up to 20–30% of Sphagnum carbon and nitrogen, respectively. Next-generation sequencing approaches have enabled the detailed characterization of microbiome community composition in peat mosses. However, as with other ecologically or economically important plants, our knowledge of Sphagnum–microbiome associations is in its infancy. In order to attain a predictive understanding of the role of the microbiome in Sphagnum productivity and ecosystem function, the mechanisms of plant–microbiome interactions and the metabolic potential of constituent microbial populations must be revealed.« less

The Sphagnum microbiome: New insights from an ancient plant lineage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kostka, Joel E.; Weston, David J.; Glass, Jennifer B.

Here, peat mosses of the genus Sphagnum play a major role in global carbon storage and dominate many northern peatland ecosystems, which are currently being subjected to some of the most rapid climate changes on Earth. A rapidly expanding database indicates that a diverse community of microorganisms is intimately associated with Sphagnum, inhabiting the tissues and surface of the plant. Here we summarize the current state of knowledge regarding the Sphagnum microbiome and provide a perspective for future research directions. Although the majority of the microbiome remains uncultivated and its metabolic capabilities uncharacterized, prokaryotes and fungi have the potential tomore » act as mutualists, symbionts, or antagonists of Sphagnum. For example, methanotrophic and nitrogen-fixing bacteria may benefit the plant host by providing up to 20–30% of Sphagnum carbon and nitrogen, respectively. Next-generation sequencing approaches have enabled the detailed characterization of microbiome community composition in peat mosses. However, as with other ecologically or economically important plants, our knowledge of Sphagnum–microbiome associations is in its infancy. In order to attain a predictive understanding of the role of the microbiome in Sphagnum productivity and ecosystem function, the mechanisms of plant–microbiome interactions and the metabolic potential of constituent microbial populations must be revealed.« less

Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome.

PubMed

Maldonado-Gómez, María X; Martínez, Inés; Bottacini, Francesca; O'Callaghan, Amy; Ventura, Marco; van Sinderen, Douwe; Hillmann, Benjamin; Vangay, Pajau; Knights, Dan; Hutkins, Robert W; Walter, Jens

2016-10-12

Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral Microbiome: A New Biomarker Reservoir for Oral and Oropharyngeal Cancers

PubMed Central

Lim, Yenkai; Totsika, Makrina; Morrison, Mark; Punyadeera, Chamindie

2017-01-01

Current biomarkers (DNA, RNA and protein) for oral cavity and oropharyngeal cancers demonstrate biological variations between individuals, rendering them impractical for clinical translation. Whilst these biomarkers originate from the host, there is not much information in the literature about the influence of oral microbiota on cancer pathogenesis, especially in oral cancers. Oral microbiotas are known to participate in disease initiation and progression not only limited to the oral cavity, but also at other distant sites. Due to the close proximity of oral microbiota and oral cavity and oropharyngeal tumours, abundance changes in oral microbiota may provide useful information on tumourigenesis. This review aims to highlight information on the role of oral microbiota in oral cavity and oropharyngeal cancers. An in-depth analysis into the oral microbiota may provide a new avenue to diagnose and treat these patients. PMID:29158828

COREMIC: a web-tool to search for a niche associated CORE MICrobiome.

PubMed

Rodrigues, Richard R; Rodgers, Nyle C; Wu, Xiaowei; Williams, Mark A

2018-01-01

Microbial diversity on earth is extraordinary, and soils alone harbor thousands of species per gram of soil. Understanding how this diversity is sorted and selected into habitat niches is a major focus of ecology and biotechnology, but remains only vaguely understood. A systems-biology approach was used to mine information from databases to show how it can be used to answer questions related to the core microbiome of habitat-microbe relationships. By making use of the burgeoning growth of information from databases, our tool "COREMIC" meets a great need in the search for understanding niche partitioning and habitat-function relationships. The work is unique, furthermore, because it provides a user-friendly statistically robust web-tool (http://coremic2.appspot.com or http://core-mic.com), developed using Google App Engine, to help in the process of database mining to identify the "core microbiome" associated with a given habitat. A case study is presented using data from 31 switchgrass rhizosphere community habitats across a diverse set of soil and sampling environments. The methodology utilizes an outgroup of 28 non-switchgrass (other grasses and forbs) to identify a core switchgrass microbiome. Even across a diverse set of soils (five environments), and conservative statistical criteria (presence in more than 90% samples and FDR q -val <0.05% for Fisher's exact test) a core set of bacteria associated with switchgrass was observed. These included, among others, closely related taxa from Lysobacter spp., Mesorhizobium spp , and Chitinophagaceae . These bacteria have been shown to have functions related to the production of bacterial and fungal antibiotics and plant growth promotion. COREMIC can be used as a hypothesis generating or confirmatory tool that shows great potential for identifying taxa that may be important to the functioning of a habitat (e.g. host plant). The case study, in conclusion, shows that COREMIC can identify key habitat-specific microbes across diverse samples, using currently available databases and a unique freely available software.

The Microbiome in Populations with a Low and High Prevalence of Caries.

PubMed

Johansson, I; Witkowska, E; Kaveh, B; Lif Holgerson, P; Tanner, A C R

2016-01-01

The oral microbiota was compared between Romanian adolescents with a high prevalence of caries and no dental care and Swedish caries-active and caries-free adolescents in caries prevention programs and with a low prevalence of caries. Biofilm samples were analyzed by FLX+ pyrosequencing of the V1 to V4 hypervariable regions of the 16S rRNA gene and polymerase chain reaction (PCR)/quantitative PCR (qPCR) for Streptococcus mutans and Streptococcus sobrinus. Sequences obtained blasted to 9 phyla, 66 genera, and 401 human oral taxa (HOT) in the 16S rRNA Human Oral Microbiome Database, of which 295 were represented by ≥20 sequences. The Romanian adolescents had more sequences in Firmicutes and fewer in Actinobacteria phyla and more sequences in the genera Bacteroidetes [G-3], Porphyromonas, Abiotrophia, Filifactor, Peptostreptococcaceae [11][G-4], Pseudoramibacter, Streptococcus, and Neisseria and fewer in Actinomyces, Selenomonas, Veillonella, Campylobacter, and TM7 [G-1] than the Swedish groups. Multivariate modeling employing HOT, S. sobrinus and S. mutans (PCR/qPCR), and sugar snacks separated Romanian from Swedish adolescents. The Romanian adolescents' microbiota was characterized by a panel of streptococci, including S. mutans, S. sobrinus, and Streptococcus australis, and Alloprevotella, Leptotrichia, Neisseria, Porphyromonas, and Prevotella. The Swedish adolescents were characterized by sweet snacks, and those with caries activity were also characterized by Prevotella, Actinomyces, and Capnocytophaga species and those free of caries by Actinomyces, Prevotella, Selenomonas, Streptococcus, and Mycoplasma. Eight species including Streptococcus mitis and Streptococcus species HOT070 were prevalent in Romanian and Swedish caries-active subjects but not caries-free subjects. In conclusion, S. mutans and S. sobrinus correlated with Romanian adolescents with caries and with limited access to dental care, whereas S. mutans and S. sobrinus were detected infrequently in Swedish adolescents in dental care programs. Swedish caries-active adolescents were typically colonized by Actinomyces, Selenomonas, Prevotella, and Capnocytophaga. Hence, the role of mutans streptococci as a primary caries pathogen appears less pronounced in populations with prevention programs compared to populations lacking caries treatment and prevention strategies. © International & American Associations for Dental Research 2015.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackrel, Sara L.; Owens, Sarah M.; Gilbert, Jack A.

Plants in terrestrial and aquatic environments contain a diverse microbiome. Yet, the chloroplast and mitochondria organelles of the plant eukaryotic cell originate from free-living cyanobacteria and Rickettsiales. This represents a challenge for sequencing the plant microbiome with universal primers, as ~99% of 16S rRNA sequences may consist of chloroplast and mitochondrial sequences. Peptide nucleic acid clamps offer a potential solution by blocking amplification of host-associated sequences. We assessed the efficacy of chloroplast and mitochondria-blocking clamps against a range of microbial taxa from soil, freshwater and marine environments. While we found that the mitochondrial blocking clamps appear to be a robustmore » method for assessing animal-associated microbiota, Proteobacterial 16S rRNA binds to the chloroplast-blocking clamp, resulting in a strong sequencing bias against this group. We attribute this bias to a conserved 14-bp sequence in the Proteobacteria that matches the 17-bp chloroplast-blocking clamp sequence. By scanning the Greengenes database, we provide a reference list of nearly 1500 taxa that contain this 14-bp sequence, including 48 families such as the Rhodobacteraceae, Phyllobacteriaceae, Rhizobiaceae, Kiloniellaceae and Caulobacteraceae. To determine where these taxa are found in nature, we mapped this taxa reference list against the Earth Microbiome Project database. These taxa are abundant in a variety of environments, particularly aquatic and semiaquatic freshwater and marine habitats. To facilitate informed decisions on effective use of organelle-blocking clamps, we provide a searchable database of microbial taxa in the Greengenes and Silva databases matching various n-mer oligonucleotides of each PNA sequence.« less

Ecology of the oral microbiome: beyond bacteria

PubMed Central

Baker, Jonathon L.; Bor, Batbileg; Agnello, Melissa; Shi, Wenyuan; He, Xuesong

2017-01-01

Although great strides have been made in understanding the complex bacterial community inhabiting the human oral cavity, for a variety of (mainly technical) reasons the ecological contributions of oral fungi, viruses, phages, and the candidate phyla radiation (CPR) group of ultra-small bacteria have remained understudied. Several recent reports have illustrated the diversity and importance of these organisms in the oral cavity, while TM7x and Candida albicans have served as crucial paradigms for CPR species and oral fungi, respectively. A comprehensive understanding of the oral microbiota and its influence on host health and disease will require a holistic view that emphasizes interactions among different residents within the oral community, as well as their interaction with the host. PMID:28089325

GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.

PubMed

Brittnacher, Mitchell J; Heltshe, Sonya L; Hayden, Hillary S; Radey, Matthew C; Weiss, Eli J; Damman, Christopher J; Zisman, Timothy L; Suskind, David L; Miller, Samuel I

2016-01-01

Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking. We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT. Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome.

Exploration of bacterial species associated with the salivary microbiome of individuals with a low susceptibility to dental caries.

PubMed

Yasunaga, Haruna; Takeshita, Toru; Shibata, Yukie; Furuta, Michiko; Shimazaki, Yoshihiro; Akifusa, Sumio; Ninomiya, Toshiharu; Kiyohara, Yutaka; Takahashi, Ichiro; Yamashita, Yoshihisa

2017-11-01

Dental caries is caused by acidogenic plaque microbiota formed on saliva-bathed tooth surfaces, in which multiple organisms act collectively to initiate and expand a cavity. We explored bacterial species associated with the salivary microbiome of individuals with low susceptibility to dental caries. The bacterial composition of saliva from 19 young adults was analyzed using barcoded pyrosequencing of the 16S rRNA gene; we compared 10 caries-experienced (CE) and nine caries-free (CF) individuals. A quantitative PCR assay of saliva from 139 orally healthy adults aged 40-59 years was carried out to confirm the result obtained by pyrosequencing analysis. The microbiomes of CF individuals showed more diverse communities with a significantly greater proportion of the genus Porphyromonas. Among operational taxonomic units (OTUs) corresponding to the genus Porphyromonas, the OTU corresponding to P. pasteri was the most predominant and its relative abundance in CF individuals was significantly greater than in CE individuals (P < 0.001, Wilcoxon rank sum test). A quantitative PCR assay of saliva confirmed that the amounts of P. pasteri were significantly higher in individuals with lower caries experience (filled teeth <15, n = 67) than in those with higher caries experience (filled teeth ≥15, n = 72) (P < 0.001, Student's t test). These results revealed an association between a greater abundance of P. pasteri and lower susceptibility to dental caries. P. pasteri may be a bacterial species that could potentially be used as a marker for maintaining a healthy oral microbiome against dental caries.

Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice.

PubMed

Brown, Kirsty; Godovannyi, Artem; Ma, Caixia; Zhang, YiQun; Ahmadi-Vand, Zahra; Dai, Chaunbin; Gorzelak, Monika A; Chan, YeeKwan; Chan, Justin M; Lochner, Arion; Dutz, Jan P; Vallance, Bruce A; Gibson, Deanna L

2016-02-01

Accumulating evidence supports that the intestinal microbiome is involved in Type 1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse model played a role in T1D through the gut. To examine the effect of the intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2) the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes onset, quantified CD4+T cells in the Peyer's patches, profiled the microbiome and measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice harbored more pathobionts and fewer beneficial microbes in comparison with NOR mice. Fecal transplantation of NOD microbes induced insulitis in NOR hosts suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1 (Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic microbiome was characterized by a metagenome altered in several metabolic gene clusters. Furthermore, diabetes susceptibility correlated with reduced fecal SCFAs. In an attempt to correct the diabetogenic microbiome, we administered VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly and did not delay diabetes. We conclude that NOD mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. Protective microbes like VSL#3 are insufficient to overcome the effects of a diabetogenic microbiome.

The Tasmanian devil microbiome-implications for conservation and management.

PubMed

Cheng, Yuanyuan; Fox, Samantha; Pemberton, David; Hogg, Carolyn; Papenfuss, Anthony T; Belov, Katherine

2015-12-21

The Tasmanian devil, the world's largest carnivorous marsupial, is at risk of extinction due to devil facial tumour disease (DFTD), a fatal contagious cancer. The Save the Tasmanian Devil Program has established an insurance population, which currently holds over 600 devils in captive facilities across Australia. Microbes are known to play a crucial role in the health and well-being of humans and other animals, and increasing evidence suggests that changes in the microbiota can influence various aspects of host physiology and development. To improve our understanding of devils and facilitate management and conservation of the species, we characterised the microbiome of wild devils and investigated differences in the composition of microbial community between captive and wild individuals. A total of 1,223,550 bacterial 16S ribosomal RNA (rRNA) sequences were generated via Roche 454 sequencing from 56 samples, including 17 gut, 15 skin, 18 pouch and 6 oral samples. The devil's gut microbiome was dominated by Firmicutes and showed a high Firmicutes-to-Bacteroidetes ratio, which appears to be a common feature of many carnivorous mammals. Metabolisms of carbohydrates, amino acids, energy, cofactors and vitamins, nucleotides and lipids were predicted as the most prominent metabolic pathways that the devil's gut flora contributed to. The microbiota inside the female's pouch outside lactation was highly similar to that of the skin, both co-dominated by Firmicutes and Proteobacteria. The oral microbiome had similar proportions of Proteobacteria, Bacteroidetes, Firmicutes and Fusobacteria. Compositional differences were observed in all four types of microbiota between devils from captive and wild populations. Certain captive devils had significantly lower levels of gut bacterial diversity than wild individuals, and the two groups differed in the proportion of gut bacteria accounting for the metabolism of glycan, amino acids and cofactors and vitamins. Further studies are underway to investigate whether alterations in the microbiome of captive devils can have impacts on their ability to adapt and survive following re-introduction to the wild.

Gut Microbiota and Salivary Diagnostics: The Mouth Is Salivating to Tell Us Something.

PubMed

Kodukula, Krishna; Faller, Douglas V; Harpp, David N; Kanara, Iphigenia; Pernokas, Julie; Pernokas, Mark; Powers, Whitney R; Soukos, Nikolaos S; Steliou, Kosta; Moos, Walter H

2017-01-01

The microbiome of the human body represents a symbiosis of microbial networks spanning multiple organ systems. Bacteria predominantly represent the diversity of human microbiota, but not to be forgotten are fungi, viruses, and protists. Mounting evidence points to the fact that the "microbial signature" is host-specific and relatively stable over time. As our understanding of the human microbiome and its relationship to the health of the host increases, it is becoming clear that many and perhaps most chronic conditions have a microbial involvement. The oral and gastrointestinal tract microbiome constitutes the bulk of the overall human microbial load, and thus presents unique opportunities for advancing human health prognosis, diagnosis, and therapy development. This review is an attempt to catalog a broad diversity of recent evidence and focus it toward opportunities for prevention and treatment of debilitating illnesses.

[Microbiocenosis of subgingival biofilm and intestinal content in chronic periodontal disease in patients with metabolic syndrome].

PubMed

Petrukhina, N B; Zorina, O A; Shikh, E V; Kartysheva, E V

The aim of the study was to assess correlations of subgingival biofilm and intestinal microbiota in patients with chronic periodontal disease (CPD) and metabolic syndrome (MS). The study included 80 patients divided in 2 groups: 40 healthy individuals with no signs of periodontal disease and 40 patients with CPD and MS. Oral and intestinal microbial consortia compositions were revealed using deep sequencing libraries of 16S rDNA. The study showed than the qualitative composition of the intestinal microbiome in patients with CPD differ significantly from the microbiome of controls. Real-time PCR of subgingival microflora in CPD patients revealed high content of P. gingivalis, T. forsythia and T. denticola, while in intestinal microbiome dominated representatives of Enterobacteriaceae and Eubacteriaceae families with signs of intestinal dysbiosis mostly associated with the decrease of protective species.

Effects of Specimen Collection Methodologies and Storage Conditions on the Short-Term Stability of Oral Microbiome Taxonomy.

PubMed

Luo, Ting; Srinivasan, Usha; Ramadugu, Kirtana; Shedden, Kerby A; Neiswanger, Katherine; Trumble, Erika; Li, Jiean J; McNeil, Daniel W; Crout, Richard J; Weyant, Robert J; Marazita, Mary L; Foxman, Betsy

2016-09-15

Community profiling of the oral microbiome requires the recovery of quality sequences in order to accurately describe microbial community structure and composition. Our objective was to assess the effects of specimen collection method, storage medium, and storage conditions on the relative abundance of taxa in saliva and plaque identified using 16S rRNA genes. We also assessed short-term changes in taxon composition and relative abundance and compared the salivary and dental plaque communities in children and adults. Over a 2-week period, four successive saliva and dental plaque specimens were collected from four adults with no dental decay (108 samples), and two successive specimens were collected from six children with four or more erupted teeth (48 samples). There were minimal differences in community composition at the phylum and operational taxonomic unit levels between dental plaque collection using a scaler and collection using a CytoSoft brush. Plaque samples stored in OMNIgene medium showed higher within-sample Shannon diversity, were compositionally different, and were more similar to each other than plaque stored in liquid dental transport medium. Saliva samples stored in OMNIgene recovered similar communities for at least a week following storage at room temperature. However, the microbial communities recovered from plaque and saliva stored in OMNIgene were significantly different in composition from their counterparts stored in liquid dental transport medium. Dental plaque communities collected from the same tooth type over four successive visits from the same adult did not significantly differ in structure or composition. Large-scale epidemiologic studies require collection over time and space, often with multiple teams collecting, storing, and processing data. Therefore, it is essential to understand how sensitive study results are to modest changes in collection and storage protocols that may occur with variation in personnel, resources available at a study site, and shipping requirements. The research presented in this paper measures the effects of multiple storage parameters and collection methodologies on the measured ecology of the oral microbiome from healthy adults and children. These results will potentially enable investigators to conduct oral microbiome studies at maximal efficiency by guiding informed administrative decisions pertaining to the necessary field or clinical work. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effects of Specimen Collection Methodologies and Storage Conditions on the Short-Term Stability of Oral Microbiome Taxonomy

PubMed Central

Luo, Ting; Srinivasan, Usha; Ramadugu, Kirtana; Shedden, Kerby A.; Neiswanger, Katherine; Trumble, Erika; Li, Jiean J.; McNeil, Daniel W.; Crout, Richard J.; Weyant, Robert J.; Marazita, Mary L.

2016-01-01

ABSTRACT Community profiling of the oral microbiome requires the recovery of quality sequences in order to accurately describe microbial community structure and composition. Our objective was to assess the effects of specimen collection method, storage medium, and storage conditions on the relative abundance of taxa in saliva and plaque identified using 16S rRNA genes. We also assessed short-term changes in taxon composition and relative abundance and compared the salivary and dental plaque communities in children and adults. Over a 2-week period, four successive saliva and dental plaque specimens were collected from four adults with no dental decay (108 samples), and two successive specimens were collected from six children with four or more erupted teeth (48 samples). There were minimal differences in community composition at the phylum and operational taxonomic unit levels between dental plaque collection using a scaler and collection using a CytoSoft brush. Plaque samples stored in OMNIgene medium showed higher within-sample Shannon diversity, were compositionally different, and were more similar to each other than plaque stored in liquid dental transport medium. Saliva samples stored in OMNIgene recovered similar communities for at least a week following storage at room temperature. However, the microbial communities recovered from plaque and saliva stored in OMNIgene were significantly different in composition from their counterparts stored in liquid dental transport medium. Dental plaque communities collected from the same tooth type over four successive visits from the same adult did not significantly differ in structure or composition. IMPORTANCE Large-scale epidemiologic studies require collection over time and space, often with multiple teams collecting, storing, and processing data. Therefore, it is essential to understand how sensitive study results are to modest changes in collection and storage protocols that may occur with variation in personnel, resources available at a study site, and shipping requirements. The research presented in this paper measures the effects of multiple storage parameters and collection methodologies on the measured ecology of the oral microbiome from healthy adults and children. These results will potentially enable investigators to conduct oral microbiome studies at maximal efficiency by guiding informed administrative decisions pertaining to the necessary field or clinical work. PMID:27371581

The Sphagnum microbiome: new insights from an ancient plant lineage.

PubMed

Kostka, Joel E; Weston, David J; Glass, Jennifer B; Lilleskov, Erik A; Shaw, A Jonathan; Turetsky, Merritt R

2016-07-01

57 I. 57 II. 58 III. 59 IV. 59 V. 61 VI. 62 63 References 63 SUMMARY: Peat mosses of the genus Sphagnum play a major role in global carbon storage and dominate many northern peatland ecosystems, which are currently being subjected to some of the most rapid climate changes on Earth. A rapidly expanding database indicates that a diverse community of microorganisms is intimately associated with Sphagnum, inhabiting the tissues and surface of the plant. Here we summarize the current state of knowledge regarding the Sphagnum microbiome and provide a perspective for future research directions. Although the majority of the microbiome remains uncultivated and its metabolic capabilities uncharacterized, prokaryotes and fungi have the potential to act as mutualists, symbionts, or antagonists of Sphagnum. For example, methanotrophic and nitrogen-fixing bacteria may benefit the plant host by providing up to 20-30% of Sphagnum carbon and nitrogen, respectively. Next-generation sequencing approaches have enabled the detailed characterization of microbiome community composition in peat mosses. However, as with other ecologically or economically important plants, our knowledge of Sphagnum-microbiome associations is in its infancy. In order to attain a predictive understanding of the role of the microbiome in Sphagnum productivity and ecosystem function, the mechanisms of plant-microbiome interactions and the metabolic potential of constituent microbial populations must be revealed. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Oral Metagenomic Biomarkers in Rheumatoid Arthritis

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0320 TITLE: Oral Metagenomic Biomarkers in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Edward K Chan CONTRACTING...Biomarkers in Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0320 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Edward K Chan 5d...significant difference in the oral  microbiome at the subspecies level of individuals with  rheumatoid   arthritis  (RA). The goal is to test the

Denitrification potential of the eastern oyster microbiome using a 16S rRNA gene based metabolic inference approach

PubMed Central

Bowman, Jeff S.; Piehler, Michael

2017-01-01

The eastern oyster (Crassostrea virginica) is a foundation species providing significant ecosystem services. However, the roles of oyster microbiomes have not been integrated into any of the services, particularly nitrogen removal through denitrification. We investigated the composition and denitrification potential of oyster microbiomes with an approach that combined 16S rRNA gene analysis, metabolic inference, qPCR of the nitrous oxide reductase gene (nosZ), and N2 flux measurements. Microbiomes of the oyster digestive gland, the oyster shell, and sediments adjacent to the oyster reef were examined based on next generation sequencing (NGS) of 16S rRNA gene amplicons. Denitrification potentials of the microbiomes were determined by metabolic inferences using a customized denitrification gene and genome database with the paprica (PAthway PRediction by phylogenetIC plAcement) bioinformatics pipeline. Denitrification genes examined included nitrite reductase (nirS and nirK) and nitrous oxide reductase (nosZ), which was further subdivided by genotype into clade I (nosZI) or clade II (nosZII). Continuous flow through experiments measuring N2 fluxes were conducted with the oysters, shells, and sediments to compare denitrification activities. Paprica properly classified the composition of microbiomes, showing similar classification results from Silva, Greengenes and RDP databases. Microbiomes of the oyster digestive glands and shells were quite different from each other and from the sediments. The relative abundance of denitrifying bacteria inferred by paprica was higher in oysters and shells than in sediments suggesting that oysters act as hotspots for denitrification in the marine environment. Similarly, the inferred nosZI gene abundances were also higher in the oyster and shell microbiomes than in the sediment microbiome. Gene abundances for nosZI were verified with qPCR of nosZI genes, which showed a significant positive correlation (F1,7 = 14.7, p = 6.0x10-3, R2 = 0.68). N2 flux rates were significantly higher in the oyster (364.4 ± 23.5 μmol N-N2 m-2 h-1) and oyster shell (355.3 ± 6.4 μmol N-N2 m-2 h-1) compared to the sediment (270.5 ± 20.1 μmol N-N2 m-2 h-1). Thus, bacteria carrying nosZI genes were found to be an important denitrifier, facilitating nitrogen removal in oyster reefs. In addition, this is the first study to validate the use of 16S gene based metabolic inference as a method for determining microbiome function, such as denitrification, by comparing inference results with qPCR gene quantification and rate measurements. PMID:28934286

Denitrification potential of the eastern oyster microbiome using a 16S rRNA gene based metabolic inference approach.

PubMed

Arfken, Ann; Song, Bongkeun; Bowman, Jeff S; Piehler, Michael

2017-01-01

The eastern oyster (Crassostrea virginica) is a foundation species providing significant ecosystem services. However, the roles of oyster microbiomes have not been integrated into any of the services, particularly nitrogen removal through denitrification. We investigated the composition and denitrification potential of oyster microbiomes with an approach that combined 16S rRNA gene analysis, metabolic inference, qPCR of the nitrous oxide reductase gene (nosZ), and N2 flux measurements. Microbiomes of the oyster digestive gland, the oyster shell, and sediments adjacent to the oyster reef were examined based on next generation sequencing (NGS) of 16S rRNA gene amplicons. Denitrification potentials of the microbiomes were determined by metabolic inferences using a customized denitrification gene and genome database with the paprica (PAthway PRediction by phylogenetIC plAcement) bioinformatics pipeline. Denitrification genes examined included nitrite reductase (nirS and nirK) and nitrous oxide reductase (nosZ), which was further subdivided by genotype into clade I (nosZI) or clade II (nosZII). Continuous flow through experiments measuring N2 fluxes were conducted with the oysters, shells, and sediments to compare denitrification activities. Paprica properly classified the composition of microbiomes, showing similar classification results from Silva, Greengenes and RDP databases. Microbiomes of the oyster digestive glands and shells were quite different from each other and from the sediments. The relative abundance of denitrifying bacteria inferred by paprica was higher in oysters and shells than in sediments suggesting that oysters act as hotspots for denitrification in the marine environment. Similarly, the inferred nosZI gene abundances were also higher in the oyster and shell microbiomes than in the sediment microbiome. Gene abundances for nosZI were verified with qPCR of nosZI genes, which showed a significant positive correlation (F1,7 = 14.7, p = 6.0x10-3, R2 = 0.68). N2 flux rates were significantly higher in the oyster (364.4 ± 23.5 μmol N-N2 m-2 h-1) and oyster shell (355.3 ± 6.4 μmol N-N2 m-2 h-1) compared to the sediment (270.5 ± 20.1 μmol N-N2 m-2 h-1). Thus, bacteria carrying nosZI genes were found to be an important denitrifier, facilitating nitrogen removal in oyster reefs. In addition, this is the first study to validate the use of 16S gene based metabolic inference as a method for determining microbiome function, such as denitrification, by comparing inference results with qPCR gene quantification and rate measurements.

Analyses of the Stability and Core Taxonomic Memberships of the Human Microbiome

PubMed Central

Li, Kelvin; Bihan, Monika; Methé, Barbara A.

2013-01-01

Analyses of the taxonomic diversity associated with the human microbiome continue to be an area of great importance. The study of the nature and extent of the commonly shared taxa (“core”), versus those less prevalent, establishes a baseline for comparing healthy and diseased groups by quantifying the variation among people, across body habitats and over time. The National Institutes of Health (NIH) sponsored Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine and better define what constitutes the taxonomic core within and across body habitats and individuals through pyrosequencing-based profiling of 16S rRNA gene sequences from oral, skin, distal gut (stool), and vaginal body habitats from over 200 healthy individuals. A two-parameter model is introduced to quantitatively identify the core taxonomic members of each body habitat’s microbiota across the healthy cohort. Using only cutoffs for taxonomic ubiquity and abundance, core taxonomic members were identified for each of the 18 body habitats and also for the 4 higher-level body regions. Although many microbes were shared at low abundance, they exhibited a relatively continuous spread in both their abundance and ubiquity, as opposed to a more discretized separation. The numbers of core taxa members in the body regions are comparatively small and stable, reflecting the relatively high, but conserved, interpersonal variability within the cohort. Core sizes increased across the body regions in the order of: vagina, skin, stool, and oral cavity. A number of “minor” oral taxonomic core were also identified by their majority presence across the cohort, but with relatively low and stable abundances. A method for quantifying the difference between two cohorts was introduced and applied to samples collected on a second visit, revealing that over time, the oral, skin, and stool body regions tended to be more transient in their taxonomic structure than the vaginal body region. PMID:23671663

Dysbiosis and Ecotypes of the Salivary Microbiome Associated With Inflammatory Bowel Diseases and the Assistance in Diagnosis of Diseases Using Oral Bacterial Profiles

PubMed Central

Xun, Zhe; Zhang, Qian; Xu, Tao; Chen, Ning; Chen, Feng

2018-01-01

Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3–V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn’s disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of Streptococcaceae (Streptococcus) and Enterobacteriaceae in UC and Veillonellaceae (Veillonella) in CD, accompanied by depletion of Lachnospiraceae and [Prevotella] in UC and Neisseriaceae (Neisseria) and Haemophilus in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively. PMID:29899737

The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions

PubMed Central

Kwong, Waldan K.; McFrederick, Quinn; Anderson, Kirk E.; Barribeau, Seth Michael; Chandler, James Angus; Cornman, R. Scott; Dainat, Jacques; Doublet, Vincent; Emery, Olivier; Evans, Jay D.; Farinelli, Laurent; Flenniken, Michelle L.; Granberg, Fredrik; Grasis, Juris A.; Gauthier, Laurent; Hayer, Juliette; Koch, Hauke; Kocher, Sarah; Martinson, Vincent G.; Moran, Nancy; Munoz-Torres, Monica; Newton, Irene; Paxton, Robert J.; Powell, Eli; Sadd, Ben M.; Schmid-Hempel, Paul; Schmid-Hempel, Regula; Schwarz, Ryan S.; vanEngelsdorp, Dennis

2016-01-01

ABSTRACT As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health. PMID:27118586

The bee microbiome: Impact on bee health and model for evolution and ecology of host-microbe interactions

USGS Publications Warehouse

Engel, Philipp; Kwong, Waldan K.; McFrederick, Quinn; Anderson, Kirk E.; Barribeau, Seth Michael; Chandler, James Angus; Cornman, Robert S.; Dainat, Jacques; de Miranda, Joachim R.; Doublet, Vincent; Emery, Olivier; Evans, Jay D.; Farinelli, Laurent; Flenniken, Michelle L.; Granberg, Fredrik; Grasis, Juris A.; Gauthier, Laurent; Hayer, Juliette; Koch, Hauke; Kocher, Sarah; Martinson, Vincent G.; Moran, Nancy; Munoz-Torres, Monica; Newton, Irene; Paxton, Robert J.; Powell, Eli; Sadd, Ben M.; Schmid-Hempel, Paul; Schmid-Hempel, Regula; Song, Se Jin; Schwarz, Ryan S.; vanEngelsdorp, Dennis; Dainat, Benjamin

2016-01-01

As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.

The Neonatal Microbiome and Its Partial Role in Mediating the Association between Birth by Cesarean Section and Adverse Pediatric Outcomes.

PubMed

Montoya-Williams, Diana; Lemas, Dominick J; Spiryda, Lisa; Patel, Keval; Carney, O'neshia Olivia; Neu, Josef; Carson, Tiffany L

2018-05-22

Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers' vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as Lactobacillus, Bifidobacterium, and Bacteroides. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as Klebsiella, Enterococcus, and Clostridium. Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted. © 2018 S. Karger AG, Basel.

The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions.

PubMed

Engel, Philipp; Kwong, Waldan K; McFrederick, Quinn; Anderson, Kirk E; Barribeau, Seth Michael; Chandler, James Angus; Cornman, R Scott; Dainat, Jacques; de Miranda, Joachim R; Doublet, Vincent; Emery, Olivier; Evans, Jay D; Farinelli, Laurent; Flenniken, Michelle L; Granberg, Fredrik; Grasis, Juris A; Gauthier, Laurent; Hayer, Juliette; Koch, Hauke; Kocher, Sarah; Martinson, Vincent G; Moran, Nancy; Munoz-Torres, Monica; Newton, Irene; Paxton, Robert J; Powell, Eli; Sadd, Ben M; Schmid-Hempel, Paul; Schmid-Hempel, Regula; Song, Se Jin; Schwarz, Ryan S; vanEngelsdorp, Dennis; Dainat, Benjamin

2016-04-26

As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health. Copyright © 2016 Engel et al.

Targeting of Streptococcus mutans Biofilms by a Novel Small Molecule Prevents Dental Caries and Preserves the Oral Microbiome.

PubMed

Garcia, S S; Blackledge, M S; Michalek, S; Su, L; Ptacek, T; Eipers, P; Morrow, C; Lefkowitz, E J; Melander, C; Wu, H

2017-07-01

Dental caries is a costly and prevalent disease characterized by the demineralization of the tooth's enamel. Disease outcome is influenced by host factors, dietary intake, cariogenic bacteria, and other microbes. The cariogenic bacterial species Streptococcus mutans metabolizes sucrose to initiate biofilm formation on the tooth surface and consequently produces lactic acid to degrade the tooth's enamel. Persistence of S. mutans biofilms in the oral cavity can lead to tooth decay. To date, no anticaries therapies that specifically target S. mutans biofilms but do not disturb the overall oral microbiome are available. We screened a library of 2-aminoimidazole antibiofilm compounds with a biofilm dispersion assay and identified a small molecule that specifically targets S. mutans biofilms. At 5 µM, the small molecule annotated 3F1 dispersed 50% of the established S. mutans biofilm but did not disperse biofilms formed by the commensal species Streptococcus sanguinis or Streptococcus gordonii. 3F1 dispersed S. mutans biofilms independently of biofilm-related factors such as antigen I/II and glucosyltransferases. 3F1 treatment effectively prevented dental caries by controlling S. mutans in a rat caries model without perturbing the oral microbiota. Our study demonstrates that selective targeting of S. mutans biofilms by 3F1 was able to effectively reduce dental caries in vivo without affecting the overall oral microbiota shaped by the intake of dietary sugars, suggesting that the pathogenic biofilm-specific treatment is a viable strategy for disease prevention.

Differences in carbon source usage by dental plaque in children with and without early childhood caries

PubMed Central

Zhao, Yan; Zhong, Wen-Jie; Xun, Zhe; Zhang, Qian; Song, Ye-Qing; Liu, Yun-Song; Chen, Feng

2017-01-01

Early childhood caries (ECC) is a considerable pediatric and public health problem worldwide. Preceding studies have focused primarily on bacterial diversity at the taxonomic level. Although these studies have provided significant information regarding the connection between dental caries and oral microbiomes, further comprehension of this microbial community’s ecological relevance is limited. This study identified the carbon source metabolic differences in dental plaque between children with and without ECC. We compared the microbial community functional diversity in 18 caries-free subjects with 18 severe ECC patients based on sole carbon source usage using a Biolog assay. The anaerobic microbial community in the ECC patients displayed greater metabolic activity than that of the control group. Specific carbon source metabolism differed significantly between the two groups. Subjects from the two groups were well distinguished by cluster and principal component analyses based on discriminative carbon sources. Our results implied that the microbial functional diversity between the ECC patients and healthy subjects differed significantly. In addition, the Biolog assay furthered our understanding of oral microbiomes as a composite of functional abilities, thus enabling us to identify the ecologically relevant functional differences among oral microbial communities.

Community analysis of dental plaque and endotracheal tube biofilms from mechanically ventilated patients.

PubMed

Marino, Poala J; Wise, Matt P; Smith, Ann; Marchesi, Julian R; Riggio, Marcello P; Lewis, Michael A O; Williams, David W

2017-06-01

Mechanically ventilated patients are at risk for developing ventilator-associated pneumonia, and it has been reported that dental plaque provides a reservoir of respiratory pathogens that may aspirate to the lungs and endotracheal tube (ETT) biofilms. For the first time, metataxonomics was used to simultaneously characterize the microbiome of dental plaque, ETTs, and non-directed bronchial lavages (NBLs) in mechanically ventilated patients to determine similarities in respective microbial communities and therefore likely associations. Bacterial 16S rRNA gene sequences from 34 samples of dental plaque, NBLs, and ETTs from 12 adult mechanically ventilated patients were analyzed. No significant differences in the microbial communities of these samples were evident. Detected bacteria were primarily oral species (e.g., Fusobacterium nucleatum, Streptococcus salivarius, Prevotella melaninogenica) with respiratory pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcuspneumoniae, and Haemophilus influenzae) also in high abundance. The high similarity between the microbiomes of dental plaque, NBLs, and ETTs suggests that the oral cavity is indeed an important site involved in microbial aspiration to the lower airway and ETT. As such, maintenance of good oral hygiene is likely to be highly important in limiting aspiration of bacteria in this vulnerable patient group. Copyright © 2017 Elsevier Inc. All rights reserved.

Biogeography of a human oral microbiome at the micron scale

PubMed Central

Mark Welch, Jessica L.; Rossetti, Blair J.; Rieken, Christopher W.; Dewhirst, Floyd E.; Borisy, Gary G.

2016-01-01

The spatial organization of complex natural microbiomes is critical to understanding the interactions of the individual taxa that comprise a community. Although the revolution in DNA sequencing has provided an abundance of genomic-level information, the biogeography of microbiomes is almost entirely uncharted at the micron scale. Using spectral imaging fluorescence in situ hybridization as guided by metagenomic sequence analysis, we have discovered a distinctive, multigenus consortium in the microbiome of supragingival dental plaque. The consortium consists of a radially arranged, nine-taxon structure organized around cells of filamentous corynebacteria. The consortium ranges in size from a few tens to a few hundreds of microns in radius and is spatially differentiated. Within the structure, individual taxa are localized at the micron scale in ways suggestive of their functional niche in the consortium. For example, anaerobic taxa tend to be in the interior, whereas facultative or obligate aerobes tend to be at the periphery of the consortium. Consumers and producers of certain metabolites, such as lactate, tend to be near each other. Based on our observations and the literature, we propose a model for plaque microbiome development and maintenance consistent with known metabolic, adherence, and environmental considerations. The consortium illustrates how complex structural organization can emerge from the micron-scale interactions of its constituent organisms. The understanding that plaque community organization is an emergent phenomenon offers a perspective that is general in nature and applicable to other microbiomes. PMID:26811460

Impact of humic acids on the colonic microbiome in healthy volunteers.

PubMed

Swidsinski, Alexander; Dörffel, Yvonne; Loening-Baucke, Vera; Gille, Christoph; Reißhauer, Anne; Göktas, Onder; Krüger, Monika; Neuhaus, Jürgen; Schrödl, Wieland

2017-02-07

To test the effects of humic acids on innate microbial communities of the colon. We followed the effects of oral supplementation with humic acids (Activomin ® ) on concentrations and composition of colonic microbiome in 14 healthy volunteers for 45 d. 3 × 800 mg Activomin ® were taken orally for 10 d followed by 3 × 400 mg for 35 d. Colonic microbiota were investigated using multicolor fluorescence in situ hybridization (FISH) of Carnoy fixated and paraffin embedded stool cylinders. Two stool samples were collected a week prior to therapy and one stool sample on days 10, 31 and 45. Forty-one FISH probes representing different bacterial groups were used. The sum concentration of colonic microbiota increased from 20% at day 10 to 30% by day 31 and remained stable until day 45 (32%) of humic acid supplementation ( P < 0.001). The increase in the concentrations in each person was due to growth of preexisting groups. The individual microbial profile of the patients remained unchanged. Similarly, the bacterial diversity remained stable. Concentrations of 24 of the 35 substantial groups increased from 20% to 96%. Two bacterial groups detected with Bac303 ( Bacteroides ) and Myc657 (mycolic acid-containing Actinomycetes ) FISH probes decreased ( P > 0.05). The others remained unaffected. Bacterial groups with initially marginal concentrations (< 0.1 × 10 9 /mL) demonstrated no response to humic acids. The concentrations of pioneer groups of Bifidobacteriaceae , Enterobacteriaceae and Clostridium difficile increased but the observed differences were statistically not significant. Humic acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome.

Impact of humic acids on the colonic microbiome in healthy volunteers

PubMed Central

Swidsinski, Alexander; Dörffel, Yvonne; Loening-Baucke, Vera; Gille, Christoph; Reißhauer, Anne; Göktas, Onder; Krüger, Monika; Neuhaus, Jürgen; Schrödl, Wieland

2017-01-01

AIM To test the effects of humic acids on innate microbial communities of the colon. METHODS We followed the effects of oral supplementation with humic acids (Activomin®) on concentrations and composition of colonic microbiome in 14 healthy volunteers for 45 d. 3 × 800 mg Activomin® were taken orally for 10 d followed by 3 × 400 mg for 35 d. Colonic microbiota were investigated using multicolor fluorescence in situ hybridization (FISH) of Carnoy fixated and paraffin embedded stool cylinders. Two stool samples were collected a week prior to therapy and one stool sample on days 10, 31 and 45. Forty-one FISH probes representing different bacterial groups were used. RESULTS The sum concentration of colonic microbiota increased from 20% at day 10 to 30% by day 31 and remained stable until day 45 (32%) of humic acid supplementation (P < 0.001). The increase in the concentrations in each person was due to growth of preexisting groups. The individual microbial profile of the patients remained unchanged. Similarly, the bacterial diversity remained stable. Concentrations of 24 of the 35 substantial groups increased from 20% to 96%. Two bacterial groups detected with Bac303 (Bacteroides) and Myc657 (mycolic acid-containing Actinomycetes) FISH probes decreased (P > 0.05). The others remained unaffected. Bacterial groups with initially marginal concentrations (< 0.1 × 109/mL) demonstrated no response to humic acids. The concentrations of pioneer groups of Bifidobacteriaceae, Enterobacteriaceae and Clostridium difficile increased but the observed differences were statistically not significant. CONCLUSION Humic acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome. PMID:28223733

Microbiomes of Site-Specific Dental Plaques from Children with Different Caries Status.

PubMed

Richards, Vincent P; Alvarez, Andres J; Luce, Amy R; Bedenbaugh, Molly; Mitchell, Mary Lyn; Burne, Robert A; Nascimento, Marcelle M

2017-08-01

The oral microbiota associated with the initiation and progression of dental caries has yet to be fully characterized. The Human Oral Microbe Identification Using Next-Generation Sequencing (HOMI NGS ) approach was used to analyze the microbiomes of site-specific supragingival dental plaques from children with different caries status. Fifty-five children (2 to 7 years of age) were assessed at baseline and at 12 months and grouped as caries free (CF), caries active with enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE) and dentin carious lesions (PD) were collected. 16S community profiles were obtained by HOMI NGS , and 408 bacterial species and 84 genus probes were assigned. Plaque bacterial communities showed temporal stability, as there was no significant difference in beta diversity values between the baseline and 12-month samples. Irrespective of collection time points, the microbiomes of healthy tooth surfaces differed substantially from those found during caries activity. All pairwise comparisons of beta diversity values between groups were significantly different ( P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most frequently detected taxa across the plaque groups, followed by Streptococcus sanguinis , which was highly abundant in CF-PF. Well-known acidogenic/aciduric species such as Streptococcus mutans , Scardovia wiggsiae , Parascardovia denticolens , and Lactobacillus salivarius were found almost exclusively in CA-PD. The microbiomes of supragingival dental plaque differ substantially among tooth surfaces and children of different caries activities. In support of the ecological nature of caries etiology, a steady transition in community species composition was observed with disease progression. Copyright © 2017 American Society for Microbiology.

Microbiomes of Site-Specific Dental Plaques from Children with Different Caries Status

PubMed Central

Alvarez, Andres J.; Luce, Amy R.; Bedenbaugh, Molly; Mitchell, Mary Lyn

2017-01-01

ABSTRACT The oral microbiota associated with the initiation and progression of dental caries has yet to be fully characterized. The Human Oral Microbe Identification Using Next-Generation Sequencing (HOMINGS) approach was used to analyze the microbiomes of site-specific supragingival dental plaques from children with different caries status. Fifty-five children (2 to 7 years of age) were assessed at baseline and at 12 months and grouped as caries free (CF), caries active with enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE) and dentin carious lesions (PD) were collected. 16S community profiles were obtained by HOMINGS, and 408 bacterial species and 84 genus probes were assigned. Plaque bacterial communities showed temporal stability, as there was no significant difference in beta diversity values between the baseline and 12-month samples. Irrespective of collection time points, the microbiomes of healthy tooth surfaces differed substantially from those found during caries activity. All pairwise comparisons of beta diversity values between groups were significantly different (P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most frequently detected taxa across the plaque groups, followed by Streptococcus sanguinis, which was highly abundant in CF-PF. Well-known acidogenic/aciduric species such as Streptococcus mutans, Scardovia wiggsiae, Parascardovia denticolens, and Lactobacillus salivarius were found almost exclusively in CA-PD. The microbiomes of supragingival dental plaque differ substantially among tooth surfaces and children of different caries activities. In support of the ecological nature of caries etiology, a steady transition in community species composition was observed with disease progression. PMID:28507066

Gut Microbiota and Salivary Diagnostics: The Mouth Is Salivating to Tell Us Something

PubMed Central

Kodukula, Krishna; Faller, Douglas V.; Harpp, David N.; Kanara, Iphigenia; Pernokas, Julie; Pernokas, Mark; Powers, Whitney R.; Soukos, Nikolaos S.; Steliou, Kosta; Moos, Walter H.

2017-01-01

Abstract The microbiome of the human body represents a symbiosis of microbial networks spanning multiple organ systems. Bacteria predominantly represent the diversity of human microbiota, but not to be forgotten are fungi, viruses, and protists. Mounting evidence points to the fact that the “microbial signature” is host-specific and relatively stable over time. As our understanding of the human microbiome and its relationship to the health of the host increases, it is becoming clear that many and perhaps most chronic conditions have a microbial involvement. The oral and gastrointestinal tract microbiome constitutes the bulk of the overall human microbial load, and thus presents unique opportunities for advancing human health prognosis, diagnosis, and therapy development. This review is an attempt to catalog a broad diversity of recent evidence and focus it toward opportunities for prevention and treatment of debilitating illnesses. PMID:29098118

Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoEnull Mice

PubMed Central

Chukkapalli, Sasanka S.; Velsko, Irina M.; Rivera-Kweh, Mercedes F.; Zheng, Donghang; Lucas, Alexandra R.; Kesavalu, Lakshmyya

2015-01-01

Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoEnull mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoEnull hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p < 0.05), nitric oxide (p < 0.01), altered lipid profiles (cholesterol, triglycerides, Chylomicrons, VLDL) (p < 0.05) as well as accelerated aortic plaque formation in ApoEnull mice (p < 0.05). Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model. PMID:26619277

Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoE null Mice.

PubMed

Chukkapalli, Sasanka S; Velsko, Irina M; Rivera-Kweh, Mercedes F; Zheng, Donghang; Lucas, Alexandra R; Kesavalu, Lakshmyya

2015-01-01

Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoE null mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoE null hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p < 0.05), nitric oxide (p < 0.01), altered lipid profiles (cholesterol, triglycerides, Chylomicrons, VLDL) (p < 0.05) as well as accelerated aortic plaque formation in ApoE null mice (p < 0.05). Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model.

Oral Metagenomic Biomarkers in Rheumatoid Arthritis

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-15-1-0320 TITLE: Oral Metagenomic Biomarkers in Rheumatoid Arthritis PRINCIPAL INVESTIGATOR: Edward K Chan CONTRACTING... Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0320 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Edward K Chan 5d. PROJECT NUMBER...individuals with  rheumatoid   arthritis  (RA). The goal is to test the  hypothesis that oral microbiome and metagenomic analyses will allow us to identify new

Incontinence medication response relates to the female urinary microbiota.

PubMed

Thomas-White, Krystal J; Hilt, Evann E; Fok, Cynthia; Pearce, Meghan M; Mueller, Elizabeth R; Kliethermes, Stephanie; Jacobs, Kristin; Zilliox, Michael J; Brincat, Cynthia; Price, Travis K; Kuffel, Gina; Schreckenberger, Paul; Gai, Xiaowu; Brubaker, Linda; Wolfe, Alan J

2016-05-01

Many adult women have resident urinary bacteria (urinary microbiome/microbiota). In adult women affected by urinary urgency incontinence (UUI), the etiologic and/or therapeutic role of the urinary microbiome/microbiota remains unknown. We hypothesized that microbiome/microbiota characteristics would relate to clinically relevant treatment response to UUI medication per os. Adult women initiating medication treatment orally for UUI and a comparator group of unaffected women were recruited in a tertiary care health-care system. All participants provided baseline clinical data and urine samples. Women with UUI were given 5 mg solifenacin, with potential dose escalation to 10 mg for inadequate UUI symptom control at 4 weeks. Additional data and urine samples were collected from women with UUI at 4 and 12 weeks. The samples were assessed using 16S ribosomal RNA (rRNA) gene sequencing and enhanced quantitative urine culturing. The primary outcome was treatment response as measured by the validated Patient Global Symptom Control (PGSC) questionnaire. Clinically relevant UUI symptom control was defined as a 4 or 5 score on the PGSC. Diversity and composition of the urinary microbiome/microbiota of women with and without UUI differed at baseline. Women with UUI had more bacteria and a more diverse microbiome/microbiota. The clinical response to solifenacin in UUI participants was related to baseline microbiome/microbiota, with responders more likely to have fewer bacteria and a less diverse community at baseline. Nonresponders had a more diverse community that often included bacteria not typically found in responders. Knowledge of an individual's urinary microbiome/microbiota may help refine UUI treatment. Complementary tools, DNA sequencing, and expanded urine culture provide information about bacteria that appear to be related to UUI incontinence status and treatment response in this population of adult women.

Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer.

PubMed

Rajpoot, Meenakshi; Sharma, Anil K; Sharma, Anil; Gupta, Girish Kumar

2018-02-06

The human body is a home to more than 1 trillion microbes with a diverse variety of commensal microbes that play a crucial role towards the health of the individual. These microbes occupy different habitats such as gut, skin, vagina, oral etc. Not only the types and abundance of microbes are different in different organs, but also these may differ in different individuals. The genome of these microbiota and their ecosystem constitute to form a microbiome. Factors such as diet, environment, host genetics etc. may be the reason behind the wide microbial diversity. A number of studies performed on human microbiome have revealed that microbiota present in healthy and diseased individuals are distinct. Altered microbiome is many a times the reason behind the overexpression of genes which may cause complex diseases including cancer. Manipulation of the human microbiome can be done by microbial supplements such as probiotics or synbiotics, diet or prebiotics and microbial suppression strategies using antibiotics. Recent advances in genome sequencing technologies and metagenomic analysis provide us the broader understanding of these commensal microbes and highlighting the distinctive features of microbiome during healthy and disease states. Molecular pathological epidemiology (MPE) studies have been very helpful in providing insights into the pathological process behind disease evolution and progression by determining the specific etiological factors. New emerging field of research targets the microbiome for therapeutic purposes by which personalized medicines can be made for treating various types of tumors. Screening programmes might be helpful in identifying patients who are at the verge of developing cancer and in delivering appropriate approaches according to individual risk modes so that disease could be prevented. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health.

PubMed

Koch, Carl D; Gladwin, Mark T; Freeman, Bruce A; Lundberg, Jon O; Weitzberg, Eddie; Morris, Alison

2017-04-01

Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases. Once thought to be the inert, end-products of endothelial-derived nitric oxide (NO) heme-oxidation, nitrate and nitrite are now considered major sources of exogenous NO that exhibit enhanced vasoactive signaling activity under conditions of hypoxia and stress. The bioavailability of nitrate and nitrite depend on the enzymatic reduction of nitrate to nitrite by a unique set of bacterial nitrate reductase enzymes possessed by specific bacterial populations in the mammalian mouth and gut. The pathogenesis of pulmonary hypertension (PH), obesity, hypertension and CVD are linked to defects in NO signaling, suggesting a role for commensal oral bacteria to shape the development of PH through the formation of nitrite, NO and other bioactive nitrogen oxides. Oral supplementation with inorganic nitrate or nitrate-containing foods exert pleiotropic, beneficial vascular effects in the setting of inflammation, endothelial dysfunction, ischemia-reperfusion injury and in pre-clinical models of PH, while traditional high-nitrate dietary patterns are associated with beneficial outcomes in hypertension, obesity and CVD. These observations highlight the potential of the microbiome in the development of novel nitrate- and nitrite-based therapeutics for PH, CVD and their risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Salivary Microbiome Diversity in Caries-Free and Caries-Affected Children.

PubMed

Jiang, Shan; Gao, Xiaoli; Jin, Lijian; Lo, Edward C M

2016-11-25

Dental caries (tooth decay) is an infectious disease. Its etiology is not fully understood from the microbiological perspective. This study characterizes the diversity of microbial flora in the saliva of children with and without dental caries. Children (3-4 years old) with caries ( n = 20) and without caries ( n = 20) were recruited. Unstimulated saliva (2 mL) was collected from each child and the total microbial genomic DNA was extracted. DNA amplicons of the V3-V4 hypervariable region of the bacterial 16S rRNA gene were generated and subjected to Illumina Miseq sequencing. A total of 17 phyla, 26 classes, 40 orders, 80 families, 151 genera, and 310 bacterial species were represented in the saliva samples. There was no significant difference in the microbiome diversity between caries-affected and caries-free children ( p > 0.05). The relative abundance of several species ( Rothia dentocariosa , Actinomyces graevenitzii , Veillonella sp. oral taxon 780 , Prevotella salivae , and Streptococcus mutans ) was higher in the caries-affected group than in the caries-free group ( p < 0.05). Fusobacterium periodonticum and Leptotrichia sp. oral clone FP036 were more abundant in caries-free children than in caries-affected children ( p < 0.05). The salivary microbiome profiles of caries-free and caries-affected children were similar. Salivary counts of certain bacteria such as R. dentocariosa and F. periodonticum may be useful for screening/assessing children's risk of developing caries.

ReprDB and panDB: minimalist databases with maximal microbial representation.

PubMed

Zhou, Wei; Gay, Nicole; Oh, Julia

2018-01-18

Profiling of shotgun metagenomic samples is hindered by a lack of unified microbial reference genome databases that (i) assemble genomic information from all open access microbial genomes, (ii) have relatively small sizes, and (iii) are compatible to various metagenomic read mapping tools. Moreover, computational tools to rapidly compile and update such databases to accommodate the rapid increase in new reference genomes do not exist. As a result, database-guided analyses often fail to profile a substantial fraction of metagenomic shotgun sequencing reads from complex microbiomes. We report pipelines that efficiently traverse all open access microbial genomes and assemble non-redundant genomic information. The pipelines result in two species-resolution microbial reference databases of relatively small sizes: reprDB, which assembles microbial representative or reference genomes, and panDB, for which we developed a novel iterative alignment algorithm to identify and assemble non-redundant genomic regions in multiple sequenced strains. With the databases, we managed to assign taxonomic labels and genome positions to the majority of metagenomic reads from human skin and gut microbiomes, demonstrating a significant improvement over a previous database-guided analysis on the same datasets. reprDB and panDB leverage the rapid increases in the number of open access microbial genomes to more fully profile metagenomic samples. Additionally, the databases exclude redundant sequence information to avoid inflated storage or memory space and indexing or analyzing time. Finally, the novel iterative alignment algorithm significantly increases efficiency in pan-genome identification and can be useful in comparative genomic analyses.

A Longitudinal Study of the Feline Faecal Microbiome Identifies Changes into Early Adulthood Irrespective of Sexual Development

PubMed Central

Deusch, Oliver; O’Flynn, Ciaran; Colyer, Alison; Swanson, Kelly S.; Allaway, David; Morris, Penelope

2015-01-01

Companion animals provide an excellent model for studies of the gut microbiome because potential confounders such as diet and environment can be more readily controlled for than in humans. Additionally, domestic cats and dogs are typically neutered early in life, enabling an investigation into the potential effect of sex hormones on the microbiome. In a longitudinal study to investigate the potential effects of neutering, neutering age and gender on the gut microbiome during growth, the faeces of kittens (16 male, 14 female) were sampled at 18, 30 and 42 weeks of age. DNA was shotgun sequenced on the Illumina platform and sequence reads were annotated for taxonomy and function by comparison to a database of protein coding genes. In a statistical analysis of diversity, taxonomy and functional potential of the microbiomes, age was identified as the only factor with significant associations. No significant effects were detected for gender, neutering, or age when neutered (19 or 31 weeks). At 18 weeks of age the microbiome was dominated by the genera Lactobacillus and Bifidobacterium (35% and 20% average abundance). Structural and functional diversity was significantly increased by week 30 but there was no further significant increase. At 42 weeks of age the most abundant genera were Bacteroides (16%), Prevotella (14%) and Megasphaera (8%). Significant differences in functional potential included an enrichment for genes in energy metabolism (carbon metabolism and oxidative phosphorylation) and depletion in cell motility (flagella and chemotaxis). We conclude that the feline faecal microbiome is predominantly determined by age when diet and environment are controlled for. We suggest this finding may also be informative for studies of the human microbiome, where control over such factors is usually limited. PMID:26659594

A Pilot Study to Evaluate the Oral Microbiome and Dental Health in Primary Open-Angle Glaucoma.

PubMed

Polla, Daniel; Astafurov, Konstantin; Hawy, Eman; Hyman, Leslie; Hou, Wei; Danias, John

2017-04-01

To evaluate possible associations between primary open-angle glaucoma (POAG), dental health, and the oral microbiome. Case-control study was conducted at SUNY Downstate. Adult subjects (40 to 87 y) were recruited as POAG cases (n=119) and controls without glaucoma (n=78) based on visual field and optic nerve criteria. Overall 74.6% were African Americans (AA). Information on medical history and oral health was collected and ophthalmologic examinations were performed. Mouthwash specimens (28 AA cases and 17 controls) were analyzed for bacterial DNA amounts. Analyses were limited to AAs as the predominant racial group. Outcome measures included number of natural teeth, self-reported periodontal health parameters, and amounts and prevalence of oral bacterial species. Logistic regression was used to evaluate associated factors and potential interactions. Cases and controls had similar age (mean: 62.2 and 60.9 y, respectively, P>0.48), and frequency of hypertension, diabetes, but cases had a higher proportion of men (P<0.04). On average (±SD), cases had fewer natural teeth than controls [18.0 (±11.1) vs. 20.7 (±9.4)]. Having more natural teeth was inversely associated with POAG, in multivariable analyses, at older ages [eg, odds ratio (95% confidence interval) at age 55: 1.0 (0.95-1.06), P=0.98 vs. at age 85: 0.87 (0.79-0.96), P=0.007]. Amounts of Streptococci were higher in cases than controls (P<0.03) in samples from the subset of subjects analyzed. The number of teeth (an oral health indicator) and alterations in the amounts of oral bacteria may be associated with glaucoma pathology. Further investigation of the association between dental health and glaucoma is warranted.

The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science.

PubMed

Ames, Nancy J; Ranucci, Alexandra; Moriyama, Brad; Wallen, Gwenyth R

As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and healthcare practitioners to analyze these microbial communities and their role in health and disease. 16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings. The objectives of this review are to (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung, and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science. Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists-individuals uniquely positioned to utilize these techniques in future studies in clinical settings.

Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome

PubMed Central

Lee, Heetae; Ko, GwangPyo

2016-01-01

The effect and underlying mechanism of vitamin A on norovirus infection are largely unknown. This study aimed to investigate how vitamin A administration affects the gut microbiome after norovirus infection. Here, we demonstrate that treatment with either retinol or retinoic acid (RA) inhibits murine norovirus (MNV) replication using both in vitro and in vivo models. Compositional changes in the gut microbiome associated with RA administration and/or norovirus infection were also investigated. Oral administration of RA and/or MNV significantly altered intestinal microbiome profiles. Particularly, bacterial species belonging to the Lactobacillaceae families were remarkably increased by MNV inoculation and RA administration, suggesting that the antiviral effects of RA occur via the modulation of specific microbiota. The antiviral causal effect of Lactobacillus was identified and demonstrated using in vitro models in RAW264.7 cells. The antiviral immune response to MNV was mediated by IFN-β upregulation. This study represents the first comprehensive profiling of gut microbiota in response to RA treatment against norovirus infection. Moreover, we conclude that the abundance of Lactobacillus through gut microbiota modulation by RA is at least partially responsible for norovirus inhibition. PMID:27180604

The microbiome and HIV prevention strategies in women.

PubMed

Abdool Karim, Salim S; Passmore, Jo-Ann S; Baxter, Cheryl

2018-01-01

HIV prevention approaches that women can use and control are a priority. Results from topical and oral preexposure prophylaxis (PrEP) HIV prevention trials have produced inconsistent results in women. One of the main behavioural factors impacting effectiveness of PrEP has been suboptimal adherence. In this review, we examine biological factors that modulate topical PrEP efficacy, with particular focus on the vaginal microbiome. Genital inflammation is an independent risk factor for HIV acquisition in women. Using 16S rRNA sequencing of the vaginal microbiota, anaerobic bacteria linked with bacterial vaginosis have been shown to be associated with both genital inflammation and HIV risk. Using proteomics, it was recently discovered that a dysbiotic vaginal microbiome, comprising less than 50% Lactobacillus spp., directly influenced topical PrEP efficacy. Gardnerella vaginalis, the dominant vaginal species in dysbiotic women, was able to directly degrade tenofovir, but not dapivirine, an antiretroviral also being developed for topical PrEP. The link between bacterial vaginosis-associated organisms with HIV risk and altered tenofovir gel effectiveness underscores the importance of good vaginal health and good adherence for women to benefit maximally from topical PrEP. Altering the vaginal microbiome is one of the new directions being pursued for HIV prevention.

Lung Microbiome for Clinicians. New Discoveries about Bugs in Healthy and Diseased Lungs

PubMed Central

Rom, William N.; Weiden, Michael D.

2014-01-01

Microbes are readily cultured from epithelial surfaces of the skin, mouth, and colon. In the last 10 years, culture-independent DNA-based techniques demonstrated that much more complex microbial communities reside on most epithelial surfaces; this includes the lower airways, where bacterial culture had failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial environment is important for adequate immunological development. The most common microbes found in the lower airways are also found in the upper airways. Increasing abundance of oral characteristic taxa is associated with increased inflammatory cells and exhaled nitric oxide, suggesting that the airway microbiome induces an immunological response in the lung. Furthermore, rhinovirus infection leads to outgrowth of Haemophilus in patients with chronic obstructive pulmonary disease, and human immunodeficiency virus–infected subjects have more Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction in which the host immune defenses also influence the microbial niche. Quantitative and/or qualitative changes in the lung microbiome may be relevant for disease progression and exacerbations in a number of pulmonary diseases. Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. PMID:24460444

Proton pump inhibitors affect the gut microbiome

PubMed Central

Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Tigchelaar, Ettje F; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

2016-01-01

Background and aims Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. Methods The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. Results 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10−38). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. Conclusions The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs. PMID:26657899

Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding.

PubMed

Ilhan, Zehra Esra; DiBaise, John K; Isern, Nancy G; Hoyt, David W; Marcus, Andrew K; Kang, Dae-Wook; Crowell, Michael D; Rittmann, Bruce E; Krajmalnik-Brown, Rosa

2017-09-01

Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are anatomically different bariatric operations. RYGB achieves greater weight loss compared with LAGB. Changes in the gut microbiome have been documented after RYGB, but not LAGB, and the microbial contribution to sustainable surgical weight loss warrants further evaluation. We hypothesized that RYGB imposes greater changes on the microbiota and its metabolism than LAGB, and that the altered microbiota may contribute to greater weight loss. Using multi-omic approaches, we analyzed fecal microbial community structure and metabolites of pre-bariatric surgery morbidly obese (PreB-Ob), normal weight (NW), post-RYGB, and post-LAGB participants. RYGB microbiomes were significantly different from those from NW, LAGB and PreB-Ob. Microbiome differences between RYGB and PreB-Ob populations were mirrored in their metabolomes. Diversity was higher in RYGB compared with LAGB, possibly because of an increase in the abundance of facultative anaerobic, bile-tolerant and acid-sensible microorganisms in the former. Possibly because of lower gastric acid exposure, phylotypes from the oral cavity, such as Escherichia, Veillonella and Streptococcus, were in greater abundance in the RYGB group, and their abundances positively correlated with percent excess weight loss. Many of these post-RYGB microorganisms are capable of amino-acid fermentation. Amino-acid and carbohydrate fermentation products-isovalerate, isobutyrate, butyrate and propionate-were prevalent in RYGB participants, but not in LAGB participants. RYGB resulted in greater alteration of the gut microbiome and metabolome than LAGB, and RYGB group exhibited unique microbiome composed of many amino-acid fermenters, compared with nonsurgical controls.

[Salivary microbiome in people with obesity: a pilot study].

PubMed

Wu, Y J; Chi, X P; Chen, F; Deng, X L

2018-02-18

To investigate the characterization of the salivary microbiome in people with obesity and the differences in microbial composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight controls. The study was carried out in people with obesity and age- and sex-matched normal weight controls. None of these selected participants had the systemic disease, oral mucosal disease or periodontal disease. Unstimulated saliva samples were collected and oral examination was conducted. DNAs from saliva samples were extracted and sequenced in an Illumina NextSeq 500 platform. Community composition, linear discriminant analysis of taxonomic differences,gene prediction, gene set construction and annotation of gene function were performed. The classified bacterial reads of the samples were 2 630 428 for each sample. A total of 11 phyla, 19 classes, 26 orders, 41 families, 62 genera and 164 species were detected ultimately. All samples had the same predominant phyla (Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria). There were statistical differences between the groups at the class, order, family, genus and species levels. At the class level, Negativicutes and Erysipelotrichia were more abundant in the obesity group, while Flavobacteriia and Bateroidetes dominated in normal weight group (P<0.05). At the species level, 16 showed significant differences in relative abundance among the groups, in which Prevotella melaninogenica,Prevotella salivae,Solobacterium moorei and Atopobium parvulum ware more abundant in the obesity group, whereas Streptococcus sanguinis dominated in normal weight group (P<0.05). The people with obesity had a higher number of salivary microbial genes (P<0.05). We produced statistics on gene prediction and found salivary microbiome of obesity group had a higher number of genes (P < 0.05). Genes associated with the pathways of metabolism and environmental information processing and human diseases were significantly enriched in the saliva samples of people with obesity (P < 0.01). Significant differences were seen in composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight people. We hope to go on further study with larger sample size in the near future.

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD.

PubMed

Kortman, Guus A M; Reijnders, Dorien; Swinkels, Dorine W

2017-06-01

Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota. © 2017 International Society for Hemodialysis.

Bacterial DNA detected on pathologically changed heart valves using 16S rRNA gene amplification.

PubMed

Chalupova, Miroslava; Skalova, Anna; Hajek, Tomas; Geigerova, Lenka; Kralova, Dana; Liska, Pavel; Hecova, Hana; Molacek, Jiri; Hrabak, Jaroslav

2018-05-22

Nowadays, dental diseases are one of the most common illnesses in the world. Some of them can lead to translocation of oral bacteria to the bloodstream causing intermittent bacteraemia. Therefore, a potential association between oral infection and cardiovascular diseases has been discussed in recent years as a result of adhesion of oral microbes to the heart valves. The aim of this study was to detect oral bacteria on pathologically changed heart valves not caused by infective endocarditis. In the study, patients with pathologically changed heart valves were involved. Samples of heart valves removed during heart valve replacement surgery were cut into two parts. One aliquot was cultivated aerobically and anaerobically. Bacterial DNA was extracted using Ultra-Deep Microbiome Prep (Molzym GmbH, Bremen, Germany) followed by a 16S rRNA gene PCR amplification using Mastermix 16S Complete kit (Molzym GmbH, Bremen, Germany). Positive PCR products were sequenced and the sequences were analyzed using BLAST database ( http://www.ncbi.nlm.nih/BLAST ). During the study period, 41 samples were processed. Bacterial DNA of the following bacteria was detected in 21 samples: Cutibacterium acnes (formerly Propionibacterium acnes) (n = 11; 52.38% of patients with positive bacterial DNA detection), Staphylococcus sp. (n = 9; 42.86%), Streptococcus sp. (n = 1; 4.76%), Streptococcus sanguinis (n = 4; 19.05%), Streptococcus oralis (n = 1; 4.76%), Carnobacterium sp. (n = 1; 4.76%), Bacillus sp. (n = 2; 9.52%), and Bergeyella sp. (n = 1; 4.76%). In nine samples, multiple bacteria were found. Our results showed significant appearance of bacteria on pathologically changed heart valves in patients with no symptoms of infective endocarditis.

Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial.

PubMed

Kamamoto, C S L; Nishikaku, A S; Gompertz, O F; Melo, A S; Hassun, K M; Bagatin, E

2017-01-01

Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non- Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs.

Microbial profiling of dental plaque from mechanically ventilated patients

PubMed Central

Twigg, Joshua A.; Lewis, Michael A. O.; Wise, Matt P.; Marchesi, Julian R.; Smith, Ann; Wilson, Melanie J.; Williams, David W.

2016-01-01

Micro-organisms isolated from the oral cavity may translocate to the lower airways during mechanical ventilation (MV) leading to ventilator-associated pneumonia (VAP). Changes within the dental plaque microbiome during MV have been documented previously, primarily using culture-based techniques. The aim of this study was to use community profiling by high throughput sequencing to comprehensively analyse suggested microbial changes within dental plaque during MV. Bacterial 16S rDNA gene sequences were obtained from 38 samples of dental plaque sampled from 13 mechanically ventilated patients and sequenced using the Illumina platform. Sequences were processed using Mothur, applying a 97 % gene similarity cut-off for bacterial species level identifications. A significant ‘microbial shift’ occurred in the microbial community of dental plaque during MV for nine out of 13 patients. Following extubation, or removal of the endotracheal tube that facilitates ventilation, sampling revealed a decrease in the relative abundance of potential respiratory pathogens and a compositional change towards a more predominantly (in terms of abundance) oral microbiota including Prevotella spp., and streptococci. The results highlight the need to better understand microbial shifts in the oral microbiome in the development of strategies to reduce VAP, and may have implications for the development of other forms of pneumonia such as community-acquired infection. PMID:26690690

Microbial profiling of dental plaque from mechanically ventilated patients.

PubMed

Sands, Kirsty M; Twigg, Joshua A; Lewis, Michael A O; Wise, Matt P; Marchesi, Julian R; Smith, Ann; Wilson, Melanie J; Williams, David W

2016-02-01

Micro-organisms isolated from the oral cavity may translocate to the lower airways during mechanical ventilation (MV) leading to ventilator-associated pneumonia (VAP). Changes within the dental plaque microbiome during MV have been documented previously, primarily using culture-based techniques. The aim of this study was to use community profiling by high throughput sequencing to comprehensively analyse suggested microbial changes within dental plaque during MV. Bacterial 16S rDNA gene sequences were obtained from 38 samples of dental plaque sampled from 13 mechanically ventilated patients and sequenced using the Illumina platform. Sequences were processed using Mothur, applying a 97% gene similarity cut-off for bacterial species level identifications. A significant 'microbial shift' occurred in the microbial community of dental plaque during MV for nine out of 13 patients. Following extubation, or removal of the endotracheal tube that facilitates ventilation, sampling revealed a decrease in the relative abundance of potential respiratory pathogens and a compositional change towards a more predominantly (in terms of abundance) oral microbiota including Prevotella spp., and streptococci. The results highlight the need to better understand microbial shifts in the oral microbiome in the development of strategies to reduce VAP, and may have implications for the development of other forms of pneumonia such as community-acquired infection.

Has the use of molecular methods for the characterization of the human oral microbiome changed our understanding of the role of bacteria in the pathogenesis of periodontal disease?

PubMed

Wade, William Geoffrey

2011-03-01

Only around half of oral bacteria can be grown in the laboratory using conventional culture methods. Molecular methods based on 16S rRNA gene sequence are now available and are being used to characterize the periodontal microbiota in its entirety. This review describes the cultural characterization of the oral and periodontal microbiotas and explores the influence of the additional data now available from culture-independent molecular analyses on current thinking on the role of bacteria in periodontitis. Culture-independent molecular analysis of the periodontal microbiota has shown it to be far more diverse than previously thought. A number of species including some that have yet to be cultured are as strongly associated with disease as those organisms traditionally regarded as periodontal pathogens. Sequencing of bacterial genomes has revealed a high degree of intra-specific genetic diversity. The use of molecular methods for the characterization of the periodontal microbiome has greatly expanded the range of bacterial species known to colonize this habitat. Understanding the interactions between the human host and its commensal bacterial community at the functional level is a priority. © 2011 John Wiley & Sons A/S.

A Bayesian taxonomic classification method for 16S rRNA gene sequences with improved species-level accuracy.

PubMed

Gao, Xiang; Lin, Huaiying; Revanna, Kashi; Dong, Qunfeng

2017-05-10

Species-level classification for 16S rRNA gene sequences remains a serious challenge for microbiome researchers, because existing taxonomic classification tools for 16S rRNA gene sequences either do not provide species-level classification, or their classification results are unreliable. The unreliable results are due to the limitations in the existing methods which either lack solid probabilistic-based criteria to evaluate the confidence of their taxonomic assignments, or use nucleotide k-mer frequency as the proxy for sequence similarity measurement. We have developed a method that shows significantly improved species-level classification results over existing methods. Our method calculates true sequence similarity between query sequences and database hits using pairwise sequence alignment. Taxonomic classifications are assigned from the species to the phylum levels based on the lowest common ancestors of multiple database hits for each query sequence, and further classification reliabilities are evaluated by bootstrap confidence scores. The novelty of our method is that the contribution of each database hit to the taxonomic assignment of the query sequence is weighted by a Bayesian posterior probability based upon the degree of sequence similarity of the database hit to the query sequence. Our method does not need any training datasets specific for different taxonomic groups. Instead only a reference database is required for aligning to the query sequences, making our method easily applicable for different regions of the 16S rRNA gene or other phylogenetic marker genes. Reliable species-level classification for 16S rRNA or other phylogenetic marker genes is critical for microbiome research. Our software shows significantly higher classification accuracy than the existing tools and we provide probabilistic-based confidence scores to evaluate the reliability of our taxonomic classification assignments based on multiple database matches to query sequences. Despite its higher computational costs, our method is still suitable for analyzing large-scale microbiome datasets for practical purposes. Furthermore, our method can be applied for taxonomic classification of any phylogenetic marker gene sequences. Our software, called BLCA, is freely available at https://github.com/qunfengdong/BLCA .

Microbiomes: unifying animal and plant systems through the lens of community ecology theory

PubMed Central

Christian, Natalie; Whitaker, Briana K.; Clay, Keith

2015-01-01

The field of microbiome research is arguably one of the fastest growing in biology. Bacteria feature prominently in studies on animal health, but fungi appear to be the more prominent functional symbionts for plants. Despite the similarities in the ecological organization and evolutionary importance of animal-bacterial and plant–fungal microbiomes, there is a general failure across disciplines to integrate the advances made in each system. Researchers studying bacterial symbionts in animals benefit from greater access to efficient sequencing pipelines and taxonomic reference databases, perhaps due to high medical and veterinary interest. However, researchers studying plant–fungal symbionts benefit from the relative tractability of fungi under laboratory conditions and ease of cultivation. Thus each system has strengths to offer, but both suffer from the lack of a common conceptual framework. We argue that community ecology best illuminates complex species interactions across space and time. In this synthesis we compare and contrast the animal-bacterial and plant–fungal microbiomes using six core theories in community ecology (i.e., succession, community assembly, metacommunities, multi-trophic interactions, disturbance, restoration). The examples and questions raised are meant to spark discussion amongst biologists and lead to the integration of these two systems, as well as more informative, manipulatory experiments on microbiomes research. PMID:26441846

Pathophysiology of diverticular disease.

PubMed

Schieffer, Kathleen M; Kline, Bryan P; Yochum, Gregory S; Koltun, Walter A

2018-06-07

Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

The oral bacterial microbiome of occlusal surfaces in children and its association with diet and caries.

PubMed

Ribeiro, Apoena Aguiar; Azcarate-Peril, Maria Andrea; Cadenas, Maria Belen; Butz, Natasha; Paster, Bruce J; Chen, Tsute; Bair, Eric; Arnold, Roland R

2017-01-01

Dental caries is the most prevalent disease in humans globally. Efforts to control it have been invigorated by an increasing knowledge of the oral microbiome composition. This study aimed to evaluate the bacterial diversity in occlusal biofilms and its relationship with clinical surface diagnosis and dietary habits. Anamneses were recorded from thirteen 12-year-old children. Biofilm samples collected from occlusal surfaces of 46 permanent second molars were analyzed by 16S rRNA amplicon sequencing combined with the BLASTN-based search algorithm for species identification. The overall mean decayed, missing and filled surfaces modified index [DMFSm Index, including active white spot lesions (AWSL)] value was 8.77±7.47. Biofilm communities were highly polymicrobial collectively, representing 10 bacterial phyla, 25 classes, 29 orders, 58 families, 107 genera, 723 species. Streptococcus sp_Oral_Taxon_065, Corynebacterium matruchotii, Actinomyces viscosus, Actinomyces sp_Oral_Taxon_175, Actinomyces sp_Oral_Taxon_178, Actinomyces sp_Oral_Taxon_877, Prevotella nigrescens, Dialister micraerophilus, Eubacterium_XI G 1 infirmum were more abundant among surfaces with AWSL, and Streptococcus gordonii, Streptococcus sp._Oral_Taxon_058, Enterobacter sp._str._638 Streptococcus australis, Yersinia mollaretii, Enterobacter cloacae, Streptococcus sp._Oral_Taxon_71, Streptococcus sp._Oral_Taxon_F11, Centipeda sp._Oral_Taxon_D18 were more abundant among sound surfaces. Streptococcus mutans was detected on all surfaces in all patients, while Streptococcus sobrinus was detected only in three patients (mean relative abundances 7.1% and 0.6%, respectively). Neither species differentiated healthy from diseased sites. Diets of nine of the subjects were scored as high in fermentable carbohydrates (≧2X/day between meals). A direct association between relative abundances of bacteria and carbohydrate consumption was observed among 18 species. High consumption of fermentable carbohydrates and sound surfaces were associated with a reduction in bacterial diversity. PCoA plots displayed differences in bacterial community profiles between sound and diseased surfaces. Our study showed that, in addition to mutans streptococci, other species may be associated with the initiation of dental caries on occlusal surfaces, and that biofilm diversity of tooth surfaces is influenced by carbohydrate consumption and a surface's health status.

The oral bacterial microbiome of occlusal surfaces in children and its association with diet and caries

PubMed Central

Azcarate-Peril, Maria Andrea; Cadenas, Maria Belen; Butz, Natasha; Paster, Bruce J.; Chen, Tsute; Bair, Eric

2017-01-01

Dental caries is the most prevalent disease in humans globally. Efforts to control it have been invigorated by an increasing knowledge of the oral microbiome composition. This study aimed to evaluate the bacterial diversity in occlusal biofilms and its relationship with clinical surface diagnosis and dietary habits. Anamneses were recorded from thirteen 12-year-old children. Biofilm samples collected from occlusal surfaces of 46 permanent second molars were analyzed by 16S rRNA amplicon sequencing combined with the BLASTN-based search algorithm for species identification. The overall mean decayed, missing and filled surfaces modified index [DMFSm Index, including active white spot lesions (AWSL)] value was 8.77±7.47. Biofilm communities were highly polymicrobial collectively, representing 10 bacterial phyla, 25 classes, 29 orders, 58 families, 107 genera, 723 species. Streptococcus sp_Oral_Taxon_065, Corynebacterium matruchotii, Actinomyces viscosus, Actinomyces sp_Oral_Taxon_175, Actinomyces sp_Oral_Taxon_178, Actinomyces sp_Oral_Taxon_877, Prevotella nigrescens, Dialister micraerophilus, Eubacterium_XI G 1 infirmum were more abundant among surfaces with AWSL, and Streptococcus gordonii, Streptococcus sp._Oral_Taxon_058, Enterobacter sp._str._638 Streptococcus australis, Yersinia mollaretii, Enterobacter cloacae, Streptococcus sp._Oral_Taxon_71, Streptococcus sp._Oral_Taxon_F11, Centipeda sp._Oral_Taxon_D18 were more abundant among sound surfaces. Streptococcus mutans was detected on all surfaces in all patients, while Streptococcus sobrinus was detected only in three patients (mean relative abundances 7.1% and 0.6%, respectively). Neither species differentiated healthy from diseased sites. Diets of nine of the subjects were scored as high in fermentable carbohydrates (≧2X/day between meals). A direct association between relative abundances of bacteria and carbohydrate consumption was observed among 18 species. High consumption of fermentable carbohydrates and sound surfaces were associated with a reduction in bacterial diversity. PCoA plots displayed differences in bacterial community profiles between sound and diseased surfaces. Our study showed that, in addition to mutans streptococci, other species may be associated with the initiation of dental caries on occlusal surfaces, and that biofilm diversity of tooth surfaces is influenced by carbohydrate consumption and a surface’s health status. PMID:28678838

The microbiota and microbiome in aging: potential implications in health and age-related diseases.

PubMed

Zapata, Heidi J; Quagliarello, Vincent J

2015-04-01

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Microbiomes associated with bovine periodontitis and oral health.

PubMed

Borsanelli, Ana C; Lappin, David F; Viora, Lorenzo; Bennett, David; Dutra, Iveraldo S; Brandt, Bernd W; Riggio, Marcello P

2018-05-01

Periodontitis is an infectious polymicrobial, immuno-inflammatory disease of multifactorial aetiology that has an impact on the health, production and welfare of ruminants. The objective of the present study was to determine the microbial profiles present in the gingival sulcus of cattle considered periodontally healthy and in the periodontal pocket of animals with periodontitis lesions using high-throughput bacterial 16S rRNA gene sequencing. Subgingival biofilm samples were collected from 40 cattle with periodontitis and 38 periodontally healthy animals. In total, 1923 OTUs were identified and classified into 395 genera or higher taxa. Microbial profiles in health differed significantly from periodontitis in their composition (p < 0.0001, F = 5.30; PERMANOVA) but no statistically significant differences were observed in the diversity of healthy and periodontitis microbiomes. The most prevalent taxa in health were Pseudomonas, Burkholderia and Actinobacteria, whereas in disease these were Prevotella, Fusobacterium and Porphyromonas. The most discriminative taxa in health were Gastranaerophilales, Planifilum and Burkholderia, and in disease these were Elusimicrobia, Synergistes and Propionivibrio. In conclusion, statistically significant difference exists between the microbiome in bovine oral health and periodontitis, with populations showing 72.6% dissimilarity. The diversity of the bacteria found in health and periodontitis were similar and bacteria recognised as periodontal pathogens showed increased abundance in disease. In this context, the main components of bacterial homeostasis in the biofilm of healthy sites and of dysbiosis in periodontal lesions provide unprecedented indicators for the evolution of knowledge about bovine periodontitis. Copyright © 2018 Elsevier B.V. All rights reserved.

Salivary Microbiome Diversity in Caries-Free and Caries-Affected Children

PubMed Central

Jiang, Shan; Gao, Xiaoli; Jin, Lijian; Lo, Edward C. M.

2016-01-01

Dental caries (tooth decay) is an infectious disease. Its etiology is not fully understood from the microbiological perspective. This study characterizes the diversity of microbial flora in the saliva of children with and without dental caries. Children (3–4 years old) with caries (n = 20) and without caries (n = 20) were recruited. Unstimulated saliva (2 mL) was collected from each child and the total microbial genomic DNA was extracted. DNA amplicons of the V3-V4 hypervariable region of the bacterial 16S rRNA gene were generated and subjected to Illumina Miseq sequencing. A total of 17 phyla, 26 classes, 40 orders, 80 families, 151 genera, and 310 bacterial species were represented in the saliva samples. There was no significant difference in the microbiome diversity between caries-affected and caries-free children (p > 0.05). The relative abundance of several species (Rothia dentocariosa, Actinomyces graevenitzii, Veillonella sp. oral taxon 780, Prevotella salivae, and Streptococcus mutans) was higher in the caries-affected group than in the caries-free group (p < 0.05). Fusobacterium periodonticum and Leptotrichia sp. oral clone FP036 were more abundant in caries-free children than in caries-affected children (p < 0.05). The salivary microbiome profiles of caries-free and caries-affected children were similar. Salivary counts of certain bacteria such as R. dentocariosa and F. periodonticum may be useful for screening/assessing children’s risk of developing caries. PMID:27898021

In Silico Screening of the Human Gut Metaproteome Identifies Th17-Promoting Peptides Encrypted in Proteins of Commensal Bacteria

PubMed Central

Hidalgo-Cantabrana, Claudio; Moro-García, Marco A.; Blanco-Míguez, Aitor; Fdez-Riverola, Florentino; Lourenço, Anália; Alonso-Arias, Rebeca; Sánchez, Borja

2017-01-01

Scientific studies focused on the role of the human microbiome over human health have generated billions of gigabits of genetic information during the last decade. Nowadays integration of all this information in public databases and development of pipelines allowing us to biotechnologically exploit this information are urgently needed. Prediction of the potential bioactivity of the products encoded by the human gut microbiome, or metaproteome, is the first step for identifying proteins responsible for the molecular interaction between microorganisms and the immune system. We have recently published the Mechanism of Action of the Human Microbiome (MAHMI) database (http://www.mahmi.org), conceived as a resource compiling peptide sequences with a potential immunomodulatory activity. Fifteen out of the 300 hundred million peptides contained in the MAHMI database were synthesized. These peptides were identified as being encrypted in proteins produced by gut microbiota members, they do not contain cleavage points for the major intestinal endoproteases and displayed high probability to have immunomodulatory bioactivity. The bacterial peptides FR-16 and LR-17 encrypted in proteins from Bifidobacterium longum DJ010A and Bifidobacterium fragilis YCH46 respectively, showed the higher immune modulation capability over human peripheral blood mononuclear cells. Both peptides modulated the immune response toward increases in the Th17 and decreases in the Th1 cell response, together with an induction of IL-22 production. These results strongly suggest the combined use of bioinformatics and in vitro tools as a first stage in the screening of bioactive peptides encrypted in the human gut metaproteome. PMID:28943872

Dynamic Alterations in Salivary Microbiota Related to Dental Caries and Age in Preschool Children With Deciduous Dentition: A 2-Year Follow-Up Study

PubMed Central

Xu, Lei; Chen, Xi; Wang, Yuan; Jiang, Wen; Wang, Sa; Ling, Zongxin; Chen, Hui

2018-01-01

Dynamic alterations in oral microbiota are closely related to the development of dental caries;however, changes in salivary microbiota during this process have not been extensively studied. In addition, increasing evidence suggests that oral microbiome profiles differ according to dentition stages, but it is unclear whether they change with age during the same dentition, such as deciduous dentition. These two aspects were investigated in a 2-year follow-up study, and caries-free preschool children with complete deciduous dentition were enrolled. Saliva was collected and oral examination was conducted at the beginning of this trial, and then every subsequent 6 months for a total of five time points (T0, T1, T2, T3, and T4). Based on the clinical examination of teeth at the end of the trial, subjects were divided into health-to-health (H-H, N = 11) and health-to-caries (H-C, N = 12) groups at every time point. A total of 115 saliva samples from 23 subjects was detected by sequencing 16S rDNA V3-V4 hypervariable regions with the Illumina MiSeq platform to obtain microbiome profiles, and 100 samples finally passed quality control for further analyses. A total of 4,328,852 high-quality sequencing reads passed quality-control testing, representing 14 phyla, 27 classes, 43 orders, 67 families, and 127 genera. An α diversity analysis showed that salivary microbial diversity was similar in all groups, and a β diversity analysis showed that salivary microbial community structure changed with dental caries. Linear discriminant analysis effect size (LEfSe) analysis revealed that the abundance of the genera Atopobium, Megasphaera, and Veillonella increased significantly, while that of the genera Shuttleworthia and Rothia decreased significantly with the development of dental caries. Megasphaera and Veillonella were enriched at the early stage of deciduous dentition whereas Peptococcus, Rothia, and Treponema were enriched at the later stage. The core microbiome in the H-H and H-C groups comprised 26 and 29 genera, respectively, with statistical differences observed in 11 shared core genera. These results provide new insights into variations in the salivary microbiome related to dental caries and age in the deciduous dentition period. PMID:29670544

Dynamic Alterations in Salivary Microbiota Related to Dental Caries and Age in Preschool Children With Deciduous Dentition: A 2-Year Follow-Up Study.

PubMed

Xu, Lei; Chen, Xi; Wang, Yuan; Jiang, Wen; Wang, Sa; Ling, Zongxin; Chen, Hui

2018-01-01

Dynamic alterations in oral microbiota are closely related to the development of dental caries;however, changes in salivary microbiota during this process have not been extensively studied. In addition, increasing evidence suggests that oral microbiome profiles differ according to dentition stages, but it is unclear whether they change with age during the same dentition, such as deciduous dentition. These two aspects were investigated in a 2-year follow-up study, and caries-free preschool children with complete deciduous dentition were enrolled. Saliva was collected and oral examination was conducted at the beginning of this trial, and then every subsequent 6 months for a total of five time points (T0, T1, T2, T3, and T4). Based on the clinical examination of teeth at the end of the trial, subjects were divided into health-to-health (H-H, N = 11) and health-to-caries (H-C, N = 12) groups at every time point. A total of 115 saliva samples from 23 subjects was detected by sequencing 16S rDNA V3-V4 hypervariable regions with the Illumina MiSeq platform to obtain microbiome profiles, and 100 samples finally passed quality control for further analyses. A total of 4,328,852 high-quality sequencing reads passed quality-control testing, representing 14 phyla, 27 classes, 43 orders, 67 families, and 127 genera. An α diversity analysis showed that salivary microbial diversity was similar in all groups, and a β diversity analysis showed that salivary microbial community structure changed with dental caries. Linear discriminant analysis effect size (LEfSe) analysis revealed that the abundance of the genera Atopobium, Megasphaera , and Veillonella increased significantly, while that of the genera Shuttleworthia and Rothia decreased significantly with the development of dental caries. Megasphaera and Veillonella were enriched at the early stage of deciduous dentition whereas Peptococcus, Rothia , and Treponema were enriched at the later stage. The core microbiome in the H-H and H-C groups comprised 26 and 29 genera, respectively, with statistical differences observed in 11 shared core genera. These results provide new insights into variations in the salivary microbiome related to dental caries and age in the deciduous dentition period.

Proton pump inhibitors affect the gut microbiome.

PubMed

Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Tigchelaar, Ettje F; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

2016-05-01

Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli. The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.

PubMed

Prince, Amanda L; Ma, Jun; Kannan, Paranthaman S; Alvarez, Manuel; Gisslen, Tate; Harris, R Alan; Sweeney, Emma L; Knox, Christine L; Lambers, Donna S; Jobe, Alan H; Chougnet, Claire A; Kallapur, Suhas G; Aagaard, Kjersti M

2016-05-01

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/or funisitis using state-of-the-science whole-genome shotgun metagenomics. This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either betamethasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative metagenomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis. Copyright © 2016. Published by Elsevier Inc.

The placental microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis

PubMed Central

Kannan, Paranthaman S.; Alvarez, Manuel; Gisslen, Tate; Harris, R. Alan; Sweeney, Emma L.; Knox, Christine L.; Lambers, Donna S.; Jobe, Alan H.; Chougnet, Claire A.; Kallapur, Suhas G.; Aagaard, Kjersti M.

2016-01-01

BACKGROUND Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. OBJECTIVE In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/ or funisitis using state-of-the-science whole-genome shotgun metagenomics. STUDY DESIGN This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9–15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. RESULTS Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either beta-methasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). CONCLUSION Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative meta-genomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis. PMID:26965447

Influences of pH and Iron Concentration on the Salivary Microbiome in Individual Humans with and without Caries

PubMed Central

Zhou, Jianye; Jiang, Nan; Wang, Zhenzhen; Li, Longqing; Zhang, Jumei; Ma, Rui; Nie, Hongbing

2016-01-01

ABSTRACT This study aimed to identify the differences in the oral microbial communities in saliva from patients with and without caries by performing sequencing with the Illumina MiSeq platform, as well as to further assess their relationships with environmental factors (salivary pH and iron concentration). Forty-three volunteers were selected, including 21 subjects with and 22 without caries, from one village in Gansu, China. Based on 966,255 trimmed sequences and clustering at the 97% similarity level, 1,303 species-level operational taxonomic units were generated. The sequencing data for the two groups revealed that (i) particular distribution patterns (synergistic effects or competition) existed in the subjects with and without caries at both the genus and species levels and (ii) both the salivary pH and iron concentration had significant influences on the microbial community structure. IMPORTANCE The significant influences of the oral environment observed in this study increase the current understanding of the salivary microbiome in caries. These results will be useful for expanding research directions and for improving disease diagnosis, prognosis, and therapy. PMID:27940544

Influences of pH and Iron Concentration on the Salivary Microbiome in Individual Humans with and without Caries.

PubMed

Zhou, Jianye; Jiang, Nan; Wang, Zhenzhen; Li, Longqing; Zhang, Jumei; Ma, Rui; Nie, Hongbing; Li, Zhiqiang

2017-02-15

This study aimed to identify the differences in the oral microbial communities in saliva from patients with and without caries by performing sequencing with the Illumina MiSeq platform, as well as to further assess their relationships with environmental factors (salivary pH and iron concentration). Forty-three volunteers were selected, including 21 subjects with and 22 without caries, from one village in Gansu, China. Based on 966,255 trimmed sequences and clustering at the 97% similarity level, 1,303 species-level operational taxonomic units were generated. The sequencing data for the two groups revealed that (i) particular distribution patterns (synergistic effects or competition) existed in the subjects with and without caries at both the genus and species levels and (ii) both the salivary pH and iron concentration had significant influences on the microbial community structure. The significant influences of the oral environment observed in this study increase the current understanding of the salivary microbiome in caries. These results will be useful for expanding research directions and for improving disease diagnosis, prognosis, and therapy. Copyright © 2017 Zhou et al.

Analyses of the Microbial Diversity across the Human Microbiome

PubMed Central

Li, Kelvin; Bihan, Monika; Yooseph, Shibu; Methé, Barbara A.

2012-01-01

Analysis of human body microbial diversity is fundamental to understanding community structure, biology and ecology. The National Institutes of Health Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine microbial diversity within and across body habitats and individuals through pyrosequencing-based profiling of 16 S rRNA gene sequences (16 S) from habits of the oral, skin, distal gut, and vaginal body regions from over 200 healthy individuals enabling the application of statistical techniques. In this study, two approaches were applied to elucidate the nature and extent of human microbiome diversity. First, bootstrap and parametric curve fitting techniques were evaluated to estimate the maximum number of unique taxa, Smax, and taxa discovery rate for habitats across individuals. Next, our results demonstrated that the variation of diversity within low abundant taxa across habitats and individuals was not sufficiently quantified with standard ecological diversity indices. This impact from low abundant taxa motivated us to introduce a novel rank-based diversity measure, the Tail statistic, (“τ”), based on the standard deviation of the rank abundance curve if made symmetric by reflection around the most abundant taxon. Due to τ’s greater sensitivity to low abundant taxa, its application to diversity estimation of taxonomic units using taxonomic dependent and independent methods revealed a greater range of values recovered between individuals versus body habitats, and different patterns of diversity within habitats. The greatest range of τ values within and across individuals was found in stool, which also exhibited the most undiscovered taxa. Oral and skin habitats revealed variable diversity patterns, while vaginal habitats were consistently the least diverse. Collectively, these results demonstrate the importance, and motivate the introduction, of several visualization and analysis methods tuned specifically for next-generation sequence data, further revealing that low abundant taxa serve as an important reservoir of genetic diversity in the human microbiome. PMID:22719823

Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial.

PubMed

Doan, Thuy; Arzika, Ahmed M; Ray, Kathryn J; Cotter, Sun Y; Kim, Jessica; Maliki, Ramatou; Zhong, Lina; Zhou, Zhaoxia; Porco, Travis C; Vanderschelden, Benjamin; Keenan, Jeremy D; Lietman, Thomas M

2017-05-01

Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger. A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The prespecified outcome was α-diversity (inverse Simpson's α-diversity index), with secondary outcomes of β and γ Simpson's and Shannon's diversities. At 5 days after treatment, 40 children aged 1-60 months were analyzed in the azithromycin-treated group and 40 children in the placebo-treated group. Diversity of the gut microbiome was significantly lower in the treated group (inverse Simpson's α-diversity, 5.03; 95% confidence interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P = .03). Similarly, the Shannon's α-diversity was lower in the treated group (10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P = .004). Simpson's community-level (γ) diversity decreased with azithromycin exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P = .00008), although β-diversity was not significantly reduced (2.56, 95% CI, 1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26). Oral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community. NCT02048007. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Persistence of the Oral Probiotic Streptococcus salivarius M18 Is Dose Dependent and Megaplasmid Transfer Can Augment Their Bacteriocin Production and Adhesion Characteristics

PubMed Central

Burton, Jeremy P.; Wescombe, Philip A.; Macklaim, Jean M.; Chai, Melissa H. C.; MacDonald, Kyle; Hale, John D. F.; Tagg, John; Reid, Gregor; Gloor, Gregory B.; Cadieux, Peter A.

2013-01-01

Bacteriocin-producing probiotic Streptococcus salivarius M18 offers beneficial modulatory capabilities within the oral microbiome, apparently through potent inhibitory activity against potentially deleterious bacteria, such as Streptococcus pyogenes. The oral cavity persistence of S. salivarius M18 was investigated in 75 subjects receiving four different doses for 28 days. Sixty per cent of the subjects already had some inhibitor-producing S. salivarius in their saliva prior to probiotic intervention. Strain M18’s persistence was dependent upon the dose, but not the period of administration. Culture analysis indicated that in some individuals the introduced strain had almost entirely replaced the indigenous S. salivarius, though the total numbers of the species did not increase. Selected subjects showing either high or low probiotic persistence had their salivary populations profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Analysis indicated that while certain bacterial phenotypes were markedly modulated, the overall composition of the oral microbiome was not modified by the probiotic treatment. Megaplasmids encoding bacteriocins and adhesion factors were transferred in vitro to generate a transconjugant S. salivarius exhibiting enhanced antimicrobial production and binding capabilities to HEp-2 cells. Since no widespread perturbation of the existing indigenous microbiota was associated with oral instillation and given its antimicrobial activity against potentially pathogenic streptococci, it appears that application of probiotic strain M18 offers potential low impact alternative to classical antibiotic prophylaxis. For candidate probiotic strains having relatively poor antimicrobial or adhesive properties, unique derivatives displaying improved probiotic performance may be engineered in vitro by megaplasmid transfer. PMID:23785463

Persistence of the oral probiotic Streptococcus salivarius M18 is dose dependent and megaplasmid transfer can augment their bacteriocin production and adhesion characteristics.

PubMed

Burton, Jeremy P; Wescombe, Philip A; Macklaim, Jean M; Chai, Melissa H C; Macdonald, Kyle; Hale, John D F; Tagg, John; Reid, Gregor; Gloor, Gregory B; Cadieux, Peter A

2013-01-01

Bacteriocin-producing probiotic Streptococcus salivarius M18 offers beneficial modulatory capabilities within the oral microbiome, apparently through potent inhibitory activity against potentially deleterious bacteria, such as Streptococcus pyogenes. The oral cavity persistence of S. salivarius M18 was investigated in 75 subjects receiving four different doses for 28 days. Sixty per cent of the subjects already had some inhibitor-producing S. salivarius in their saliva prior to probiotic intervention. Strain M18's persistence was dependent upon the dose, but not the period of administration. Culture analysis indicated that in some individuals the introduced strain had almost entirely replaced the indigenous S. salivarius, though the total numbers of the species did not increase. Selected subjects showing either high or low probiotic persistence had their salivary populations profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Analysis indicated that while certain bacterial phenotypes were markedly modulated, the overall composition of the oral microbiome was not modified by the probiotic treatment. Megaplasmids encoding bacteriocins and adhesion factors were transferred in vitro to generate a transconjugant S. salivarius exhibiting enhanced antimicrobial production and binding capabilities to HEp-2 cells. Since no widespread perturbation of the existing indigenous microbiota was associated with oral instillation and given its antimicrobial activity against potentially pathogenic streptococci, it appears that application of probiotic strain M18 offers potential low impact alternative to classical antibiotic prophylaxis. For candidate probiotic strains having relatively poor antimicrobial or adhesive properties, unique derivatives displaying improved probiotic performance may be engineered in vitro by megaplasmid transfer.

Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential.

PubMed

Carrion, Julio; Scisci, Elizabeth; Miles, Brodie; Sabino, Gregory J; Zeituni, Amir E; Gu, Ying; Bear, Adam; Genco, Caroline A; Brown, David L; Cutler, Christopher W

2012-09-15

The low-grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. In this study, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19(-)BDCA-1(+)DC-SIGN(+) blood myeloid DCs (mDCs) were analyzed in CP subjects with or without existing acute coronary syndrome and in healthy controls. FACS analysis revealed a significant increase in blood mDCs in the following order: healthy controls < CP < acute coronary syndrome/CP. Analysis of the blood mDC microbiome by 16S rDNA sequencing showed Porphyromonas gingivalis and other species, including (cultivable) Burkholderia cepacia. The mDC carriage rate with P. gingivalis correlated with oral carriage rate and with serologic exposure to P. gingivalis in CP subjects. Intervention (local debridement) to elicit a bacteremia increased the mDC carriage rate and frequency in vivo. In vitro studies established that P. gingivalis enhanced by 28% the differentiation of monocytes into immature mDCs; moreover, mDCs secreted high levels of matrix metalloproteinase-9 and upregulated C1q, heat shock protein 60, heat shock protein 70, CCR2, and CXCL16 transcripts in response to P. gingivalis in a fimbriae-dependent manner. Moreover, the survival of the anaerobe P. gingivalis under aerobic conditions was enhanced when within mDCs. Immunofluorescence analysis of oral mucosa and atherosclerotic plaques demonstrate infiltration with mDCs, colocalized with P. gingivalis. Our results suggest a role for blood mDCs in harboring and disseminating pathogens from oral mucosa to atherosclerosis plaques, which may provide key signals for mDC differentiation and atherogenic conversion.

Oligotyping reveals differences between gut microbiomes of free-ranging sympatric Namibian carnivores (Acinonyx jubatus, Canis mesomelas) on a bacterial species-like level

PubMed Central

Menke, Sebastian; Wasimuddin; Meier, Matthias; Melzheimer, Jörg; Mfune, John K. E.; Heinrich, Sonja; Thalwitzer, Susanne; Wachter, Bettina; Sommer, Simone

2014-01-01

Recent gut microbiome studies in model organisms emphasize the effects of intrinsic and extrinsic factors on the variation of the bacterial composition and its impact on the overall health status of the host. Species occurring in the same habitat might share a similar microbiome, especially if they overlap in ecological and behavioral traits. So far, the natural variation in microbiomes of free-ranging wildlife species has not been thoroughly investigated. The few existing studies exploring microbiomes through 16S rRNA gene reads clustered sequencing reads into operational taxonomic units (OTUs) based on a similarity threshold (e.g., 97%). This approach, in combination with the low resolution of target databases, generally limits the level of taxonomic assignments to the genus level. However, distinguishing natural variation of microbiomes in healthy individuals from “abnormal” microbial compositions that affect host health requires knowledge of the “normal” microbial flora at a high taxonomic resolution. This gap can now be addressed using the recently published oligotyping approach, which can resolve closely related organisms into distinct oligotypes by utilizing subtle nucleotide variation. Here, we used Illumina MiSeq to sequence amplicons generated from the V4 region of the 16S rRNA gene to investigate the gut microbiome of two free-ranging sympatric Namibian carnivore species, the cheetah (Acinonyx jubatus) and the black-backed jackal (Canis mesomelas). Bacterial phyla with proportions >0.2% were identical for both species and included Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria and Actinobacteria. At a finer taxonomic resolution, black-backed jackals exhibited 69 bacterial taxa with proportions ≥0.1%, whereas cheetahs had only 42. Finally, oligotyping revealed that shared bacterial taxa consisted of distinct oligotype profiles. Thus, in contrast to 3% OTUs, oligotyping can detect fine-scale taxonomic differences between microbiomes. PMID:25352837

The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science

PubMed Central

Ames, Nancy J.; Ranucci, Alexandra; Moriyama, Brad; Wallen, Gwenyth R.

2017-01-01

Background As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and health care practitioners to analyze these microbial communities and their role in health and disease.16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings. Objectives The objectives of this review are to: (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science. Discussion Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists—individuals uniquely positioned to utilize these techniques in future studies in clinical settings. PMID:28252578

Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification.

PubMed

Ziesemer, Kirsten A; Mann, Allison E; Sankaranarayanan, Krithivasan; Schroeder, Hannes; Ozga, Andrew T; Brandt, Bernd W; Zaura, Egija; Waters-Rist, Andrea; Hoogland, Menno; Salazar-García, Domingo C; Aldenderfer, Mark; Speller, Camilla; Hendy, Jessica; Weston, Darlene A; MacDonald, Sandy J; Thomas, Gavin H; Collins, Matthew J; Lewis, Cecil M; Hofman, Corinne; Warinner, Christina

2015-11-13

To date, characterization of ancient oral (dental calculus) and gut (coprolite) microbiota has been primarily accomplished through a metataxonomic approach involving targeted amplification of one or more variable regions in the 16S rRNA gene. Specifically, the V3 region (E. coli 341-534) of this gene has been suggested as an excellent candidate for ancient DNA amplification and microbial community reconstruction. However, in practice this metataxonomic approach often produces highly skewed taxonomic frequency data. In this study, we use non-targeted (shotgun metagenomics) sequencing methods to better understand skewed microbial profiles observed in four ancient dental calculus specimens previously analyzed by amplicon sequencing. Through comparisons of microbial taxonomic counts from paired amplicon (V3 U341F/534R) and shotgun sequencing datasets, we demonstrate that extensive length polymorphisms in the V3 region are a consistent and major cause of differential amplification leading to taxonomic bias in ancient microbiome reconstructions based on amplicon sequencing. We conclude that systematic amplification bias confounds attempts to accurately reconstruct microbiome taxonomic profiles from 16S rRNA V3 amplicon data generated using universal primers. Because in silico analysis indicates that alternative 16S rRNA hypervariable regions will present similar challenges, we advocate for the use of a shotgun metagenomics approach in ancient microbiome reconstructions.

Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification

PubMed Central

Ziesemer, Kirsten A.; Mann, Allison E.; Sankaranarayanan, Krithivasan; Schroeder, Hannes; Ozga, Andrew T.; Brandt, Bernd W.; Zaura, Egija; Waters-Rist, Andrea; Hoogland, Menno; Salazar-García, Domingo C.; Aldenderfer, Mark; Speller, Camilla; Hendy, Jessica; Weston, Darlene A.; MacDonald, Sandy J.; Thomas, Gavin H.; Collins, Matthew J.; Lewis, Cecil M.; Hofman, Corinne; Warinner, Christina

2015-01-01

To date, characterization of ancient oral (dental calculus) and gut (coprolite) microbiota has been primarily accomplished through a metataxonomic approach involving targeted amplification of one or more variable regions in the 16S rRNA gene. Specifically, the V3 region (E. coli 341–534) of this gene has been suggested as an excellent candidate for ancient DNA amplification and microbial community reconstruction. However, in practice this metataxonomic approach often produces highly skewed taxonomic frequency data. In this study, we use non-targeted (shotgun metagenomics) sequencing methods to better understand skewed microbial profiles observed in four ancient dental calculus specimens previously analyzed by amplicon sequencing. Through comparisons of microbial taxonomic counts from paired amplicon (V3 U341F/534R) and shotgun sequencing datasets, we demonstrate that extensive length polymorphisms in the V3 region are a consistent and major cause of differential amplification leading to taxonomic bias in ancient microbiome reconstructions based on amplicon sequencing. We conclude that systematic amplification bias confounds attempts to accurately reconstruct microbiome taxonomic profiles from 16S rRNA V3 amplicon data generated using universal primers. Because in silico analysis indicates that alternative 16S rRNA hypervariable regions will present similar challenges, we advocate for the use of a shotgun metagenomics approach in ancient microbiome reconstructions. PMID:26563586

[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].

PubMed

Krajewska-Włodarczyk, Magdalena

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.

[Oral microbiota: a promising predictor of human oral and systemic diseases].

PubMed

Xin, Xu; Junzhi, He; Xuedong, Zhou

2015-12-01

A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.

As-yet-uncultivated oral bacteria: breadth and association with oral and extra-oral diseases

PubMed Central

Siqueira, José F.; Rôças, Isabela N.

2013-01-01

It has been shown that 40–60% of the bacteria found in different healthy and diseased oral sites still remain to be grown in vitro, phenotypically characterized, and formally named as species. The possibility exists that these as-yet-uncultivated bacteria play important ecological roles in oral bacterial communities and may participate in the pathogenesis of several oral infectious diseases. There is also a potential for these as-yet-uncultivated oral bacteria to take part in extra-oral infections. For a comprehensive characterization of physiological and pathogenic properties as well as antimicrobial susceptibility of individual bacterial species, strains need to be grown in pure culture. Advances in culturing techniques have allowed the cultivation of several oral bacterial taxa only previously known by a 16S rRNA gene sequence signature, and novel species have been proposed. There is a growing need for developing improved methods to cultivate and characterize the as-yet-uncultivated portion of the oral microbiome so as to unravel its role in health and disease. PMID:23717756

COREMIC: a web-tool to search for a niche associated CORE MICrobiome

PubMed Central

Rodgers, Nyle C.; Wu, Xiaowei; Williams, Mark A.

2018-01-01

Microbial diversity on earth is extraordinary, and soils alone harbor thousands of species per gram of soil. Understanding how this diversity is sorted and selected into habitat niches is a major focus of ecology and biotechnology, but remains only vaguely understood. A systems-biology approach was used to mine information from databases to show how it can be used to answer questions related to the core microbiome of habitat-microbe relationships. By making use of the burgeoning growth of information from databases, our tool “COREMIC” meets a great need in the search for understanding niche partitioning and habitat-function relationships. The work is unique, furthermore, because it provides a user-friendly statistically robust web-tool (http://coremic2.appspot.com or http://core-mic.com), developed using Google App Engine, to help in the process of database mining to identify the “core microbiome” associated with a given habitat. A case study is presented using data from 31 switchgrass rhizosphere community habitats across a diverse set of soil and sampling environments. The methodology utilizes an outgroup of 28 non-switchgrass (other grasses and forbs) to identify a core switchgrass microbiome. Even across a diverse set of soils (five environments), and conservative statistical criteria (presence in more than 90% samples and FDR q-val <0.05% for Fisher’s exact test) a core set of bacteria associated with switchgrass was observed. These included, among others, closely related taxa from Lysobacter spp., Mesorhizobium spp, and Chitinophagaceae. These bacteria have been shown to have functions related to the production of bacterial and fungal antibiotics and plant growth promotion. COREMIC can be used as a hypothesis generating or confirmatory tool that shows great potential for identifying taxa that may be important to the functioning of a habitat (e.g. host plant). The case study, in conclusion, shows that COREMIC can identify key habitat-specific microbes across diverse samples, using currently available databases and a unique freely available software. PMID:29473009

Oral biology in middle age: a history of the University at Buffalo Oral Biology PhD Program.

PubMed

Scannapieco, F A

2014-05-01

In 1960, the first Department of Oral Biology in the United States dedicated to the conduct of research, graduate biomedical research education, and the provision of basic oral science education for the DDS curriculum was established at the University at Buffalo. In 1963, the Department organized the first PhD Program in Oral Biology in the United States. This PhD program has produced a large cadre of oral health researchers, many of whom have gone on to make major contributions to dental research and education. This article provides a brief history of the program, the context within which the program was organized and developed, and a description of some of the many faculty, students, and fellows associated with the program. Additionally, to celebrate the 50th anniversary of this program, a symposium, entitled "The Oral Microbiome, Immunity and Chronic Disease", was held on June 12-14, 2013, in Buffalo, New York. The proceedings are published online in Advances in Dental Research (2014, Vol. 26).

Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial

PubMed Central

Kamamoto, C. S. L.; Nishikaku, A. S.; Gompertz, O. F.; Melo, A. S.; Hassun, K. M.; Bagatin, E.

2017-01-01

ABSTRACT Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non-Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs. PMID:29484095

The Inflammasome and Danger Molecule Signaling: At the Crossroads of Inflammation and Pathogen Persistence in the Oral Cavity

PubMed Central

Yilmaz, Özlem; Lee, Kyu Lim

2014-01-01

Inflammasomes are an oligomeric assembly of multiprotein complexes that activate the caspase-1-dependent maturation and the subsequent secretion of inflammatory interleukin-1β and interleukin-18 cytokines in response to a ‘danger signal’ in vertebrates. The assessment of their significance continues to grow rapidly as the complex biology of various chronic inflammatory conditions are better dissected. Increasing evidence links inflammasomes and host-derived small ‘danger molecule ATP’-signaling strongly with the modulation of the host immune response by microbial colonizers as well as potential altering of the microbiome structure and inter-microbial interactions in host. All of these factors eventually lead to the destructive chronic inflammatory disease state. In the oral cavity, a highly dynamic and multifaceted interplay takes place between the endogenous danger molecule signaling and colonizing microbes on the mucosal surfaces. This interaction may redirect the local microenvironment to favor the conversion of the resident microbiome towards pathogenicity. This review outlines the major components of the known inflammasome complexes/mechanisms and highlights their regulation, in particular, by oral microorganisms in relation to the periodontal disease pathology. Better characterizations of the cellular and molecular biology of the inflammasome will likely present important potential therapeutic targets in the treatment and prevention of periodontal disease as well as other debilitating chronic diseases. PMID:26252403

The oral microbiome in dental caries.

PubMed

Struzycka, Izabela

2014-01-01

Dental caries is one of the most common chronic and multifactorial diseases affecting the human population. The appearance of a caries lesion is determined by the coexistence of three main factors: acidogenic and acidophilic microorganisms, carbohydrates derived from the diet, and host factors. Socio-economic and behavioral factors also play an important role in the etiology of the disease. Caries develops as a result of an ecological imbalance in the stable oral microbiom. Oral microorganisms form dental plaque on the surfaces of teeth, which is the cause of the caries process, and shows features of the classic biofilm. Biofilm formation appears to be influenced by large scale changes in protein expression over time and under genetic control Cariogenic microorganisms produce lactic, formic, acetic and propionic acids, which are a product of carbohydrate metabolism. Their presence causes a decrease in pH level below 5.5, resulting in demineralization of enamel hydroxyapatite crystals and proteolytic breakdown of the structure of tooth hard tissues. Streptococcus mutans, other streptococci of the so-called non-mutans streptococci group, Actinomyces and Lactobacillus play a key role in this process. Dental biofilm is a dynamic, constantly active metabolically structure. The alternating processes of decrease and increase of biofilm pH occur, which are followed by the respective processes of de- and remineralisation of the tooth surface. In healthy conditions, these processes are in balance and no permanent damage to the tooth enamel surface occurs.

A comprehensive and scalable database search system for metaproteomics.

PubMed

Chatterjee, Sandip; Stupp, Gregory S; Park, Sung Kyu Robin; Ducom, Jean-Christophe; Yates, John R; Su, Andrew I; Wolan, Dennis W

2016-08-16

Mass spectrometry-based shotgun proteomics experiments rely on accurate matching of experimental spectra against a database of protein sequences. Existing computational analysis methods are limited in the size of their sequence databases, which severely restricts the proteomic sequencing depth and functional analysis of highly complex samples. The growing amount of public high-throughput sequencing data will only exacerbate this problem. We designed a broadly applicable metaproteomic analysis method (ComPIL) that addresses protein database size limitations. Our approach to overcome this significant limitation in metaproteomics was to design a scalable set of sequence databases assembled for optimal library querying speeds. ComPIL was integrated with a modified version of the search engine ProLuCID (termed "Blazmass") to permit rapid matching of experimental spectra. Proof-of-principle analysis of human HEK293 lysate with a ComPIL database derived from high-quality genomic libraries was able to detect nearly all of the same peptides as a search with a human database (~500x fewer peptides in the database), with a small reduction in sensitivity. We were also able to detect proteins from the adenovirus used to immortalize these cells. We applied our method to a set of healthy human gut microbiome proteomic samples and showed a substantial increase in the number of identified peptides and proteins compared to previous metaproteomic analyses, while retaining a high degree of protein identification accuracy and allowing for a more in-depth characterization of the functional landscape of the samples. The combination of ComPIL with Blazmass allows proteomic searches to be performed with database sizes much larger than previously possible. These large database searches can be applied to complex meta-samples with unknown composition or proteomic samples where unexpected proteins may be identified. The protein database, proteomic search engine, and the proteomic data files for the 5 microbiome samples characterized and discussed herein are open source and available for use and additional analysis.

Menopause and the vaginal microbiome.

PubMed

Muhleisen, Alicia L; Herbst-Kralovetz, Melissa M

2016-09-01

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assembly of 913 microbial genomes from metagenomic sequencing of the cow rumen.

PubMed

Stewart, Robert D; Auffret, Marc D; Warr, Amanda; Wiser, Andrew H; Press, Maximilian O; Langford, Kyle W; Liachko, Ivan; Snelling, Timothy J; Dewhurst, Richard J; Walker, Alan W; Roehe, Rainer; Watson, Mick

2018-02-28

The cow rumen is adapted for the breakdown of plant material into energy and nutrients, a task largely performed by enzymes encoded by the rumen microbiome. Here we present 913 draft bacterial and archaeal genomes assembled from over 800 Gb of rumen metagenomic sequence data derived from 43 Scottish cattle, using both metagenomic binning and Hi-C-based proximity-guided assembly. Most of these genomes represent previously unsequenced strains and species. The draft genomes contain over 69,000 proteins predicted to be involved in carbohydrate metabolism, over 90% of which do not have a good match in public databases. Inclusion of the 913 genomes presented here improves metagenomic read classification by sevenfold against our own data, and by fivefold against other publicly available rumen datasets. Thus, our dataset substantially improves the coverage of rumen microbial genomes in the public databases and represents a valuable resource for biomass-degrading enzyme discovery and studies of the rumen microbiome.

Diversity and homogeneity of oral microbiota in healthy Korean pre-school children using pyrosequencing.

PubMed

Lee, Soo Eon; Nam, Ok Hyung; Lee, Hyo-Seol; Choi, Sung Chul

2016-07-01

Objectives The purpose of this study was designed to identify the oral microbiota in healthy Korean pre-school children using pyrosequencing. Materials and methods Dental plaque samples were obtained form 10 caries-free pre-school children. The samples were analysed using pyrosequencing. Results The pyrosequencing analysis revealed that, at the phylum level, Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria showed high abundance. Also, predominant genera were identified as core microbiome, such as Streptococcus, Neisseria, Capnocytophaga, Haemophilus and Veilonella. Conclusions The diversity and homogeneity was shown in the dental plaque microbiota in healthy Korean pre-school children.

Acetaldehyde production and microbial colonization in oral squamous cell carcinoma and oral lichenoid disease.

PubMed

Marttila, Emilia; Uittamo, Johanna; Rusanen, Peter; Lindqvist, Christian; Salaspuro, Mikko; Rautemaa, Riina

2013-07-01

The main aim of this prospective study was to explore the ability of the oral microbiome to produce acetaldehyde in ethanol incubation. A total of 90 patients [30 oral squamous cell carcinoma (OSCC); 30 oral lichenoid disease (OLD); 30 healthy controls (CO)] were enrolled in the study. Microbial samples were taken from the mucosa using a filter paper method. The density of microbial colonization was calculated and the spectrum analyzed. Microbial acetaldehyde production was measured by gas chromatography. The majority (68%) of cultures produced carcinogenic levels of acetaldehyde (>100 μM) when incubated with ethanol (22 mM). The mean acetaldehyde production by microbes cultured from smoker samples was significantly higher (213 μM) than from non-smoker samples (141 μM) (P=.0326). The oral microbiota from OSCC, OLD patients and healthy individuals are able to produce carcinogenic levels of acetaldehyde. The present provisional study suggests smoking may increase the production of acetaldehyde. Copyright © 2013 Elsevier Inc. All rights reserved.

Oral Bacterial and Fungal Microbiome Impacts Colorectal Carcinogenesis.

PubMed

Klimesova, Klara; Jiraskova Zakostelska, Zuzana; Tlaskalova-Hogenova, Helena

2018-01-01

Host's physiology is significantly influenced by microbiota colonizing the epithelial surfaces. Complex microbial communities contribute to proper mucosal barrier function, immune response, and prevention of pathogen invasion and have many other crucial functions. The oral cavity and large intestine are distant parts of the digestive tract, both heavily colonized by commensal microbiota. Nevertheless, they feature different proportions of major bacterial and fungal phyla, mostly due to distinct epithelial layers organization and different oxygen levels. A few obligate anaerobic strains inhabiting the oral cavity are involved in the pathogenesis of oral diseases. Interestingly, these microbiota components are also enriched in gut inflammatory and tumor tissue. An altered microbiota composition - dysbiosis - and formation of polymicrobial biofilms seem to play important roles in the development of oral diseases and colorectal cancer. In this review, we describe the differences in composition of commensal microbiota in the oral cavity and large intestine and the mechanisms by which microbiota affect the inflammatory and carcinogenic response of the host.

Circadian oscillations of microbial and functional composition in the human salivary microbiome

PubMed Central

Takayasu, Lena; Suda, Wataru; Takanashi, Kageyasu; Iioka, Erica; Kurokawa, Rina; Shindo, Chie; Hattori, Yasue; Yamashita, Naoko; Nishijima, Suguru; Oshima, Kenshiro

2017-01-01

Abstract The human microbiomes across the body evidently interact with various signals in response to biogeographical physiological conditions. To understand such interactions in detail, we investigated how the salivary microbiome in the oral cavity would be regulated by host-related signals. Here, we show that the microbial abundance and gene participating in keeping the human salivary microbiome exhibit global circadian rhythm. Analysis of the 16S rRNA sequences of salivary microbial samples of six healthy adults collected at 4-h intervals for three days revealed that the microbial genera accounting for 68.4–89.6% of the total abundance were observed to significantly oscillate with the periodicity of ∼24 h. These oscillation patterns showed high variations amongst individuals, and the extent of circadian variations in individuals was generally lower than that of interindividual variations. Of the microbial categories oscillated, those classified by aerobic/anaerobic growth and Gram staining, Firmicutes including Streptococcus and Gemella, and Bacteroidetes including Prevotella showed high association with the circadian oscillation. The circadian oscillation was completely abolished by incubating the saliva in vitro, suggesting that host’s physiological changes mostly contributed to the microbial oscillation. Further metagenomic analysis showed that circadian oscillation enriched the functions of environmental responses such as various transporters and two-component regulatory systems in the evening, and those of metabolisms such as the biosynthesis of vitamins and fatty acids in the morning. PMID:28338745

Deeper insight into the structure of the anaerobic digestion microbial community; the biogas microbiome database is expanded with 157 new genomes.

PubMed

Treu, Laura; Kougias, Panagiotis G; Campanaro, Stefano; Bassani, Ilaria; Angelidaki, Irini

2016-09-01

This research aimed to better characterize the biogas microbiome by means of high throughput metagenomic sequencing and to elucidate the core microbial consortium existing in biogas reactors independently from the operational conditions. Assembly of shotgun reads followed by an established binning strategy resulted in the highest, up to now, extraction of microbial genomes involved in biogas producing systems. From the 236 extracted genome bins, it was remarkably found that the vast majority of them could only be characterized at high taxonomic levels. This result confirms that the biogas microbiome is comprised by a consortium of unknown species. A comparative analysis between the genome bins of the current study and those extracted from a previous metagenomic assembly demonstrated a similar phylogenetic distribution of the main taxa. Finally, this analysis led to the identification of a subset of common microbes that could be considered as the core essential group in biogas production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioconductor Workflow for Microbiome Data Analysis: from raw reads to community analyses

PubMed Central

Callahan, Ben J.; Sankaran, Kris; Fukuyama, Julia A.; McMurdie, Paul J.; Holmes, Susan P.

2016-01-01

High-throughput sequencing of PCR-amplified taxonomic markers (like the 16S rRNA gene) has enabled a new level of analysis of complex bacterial communities known as microbiomes. Many tools exist to quantify and compare abundance levels or OTU composition of communities in different conditions. The sequencing reads have to be denoised and assigned to the closest taxa from a reference database. Common approaches use a notion of 97% similarity and normalize the data by subsampling to equalize library sizes. In this paper, we show that statistical models allow more accurate abundance estimates. By providing a complete workflow in R, we enable the user to do sophisticated downstream statistical analyses, whether parametric or nonparametric. We provide examples of using the R packages dada2, phyloseq, DESeq2, ggplot2 and vegan to filter, visualize and test microbiome data. We also provide examples of supervised analyses using random forests and nonparametric testing using community networks and the ggnetwork package. PMID:27508062

The human urinary microbiome and how it relates to urogynecology.

PubMed

Schneeweiss, Jenifer; Koch, Marianne; Umek, Wolfgang

2016-09-01

Recent studies applying molecular techniques have demonstrated the presence of a urinary microbiota not detected by standard microbiological techniques. These have been found in the urine of healthy individuals and in those suffering from clinical symptoms. The present article reviews the findings of these studies to date, describing the molecular techniques, and specifically outlining any differences in microbiomes in relation to urogynecological disease. Further, the role of commensal bacteria in the lower urinary tract is considered. An extensive literature search was conducted to identify articles on the microbiome of the female urinary tract in health and disease. We searched the electronic meta-databases Ovid MEDLINE® 1946-2015 and Embase 1974-2015. The keywords "microbiome, microbiota, bacterial colonization, microbiology, commensal bacteria, and bacteriuria" were searched in combination with "lower urinary tract symptoms, urogenital symptoms, urinary tract infection, overactive bladder and urinary incontinence." A total of 426 papers were retrieved; 33 were included in this paper. The microbiome of the female lower urinary tract shows variance between individuals and between age groups. There are significant differences between the microbiota in the lower urinary tract of individuals with urological symptoms and those without, relating to type and proportion of commensal Lactobacillus spp. There is only weak evidence to suggest that Lactobacillus might be applied as a therapeutic measure. It is still unclear what role microbiota plays in female urinary tract health. The discovery of bacteria in the urine of healthy individuals may have implications for future therapies for lower urinary tract symptoms.

Potential Role of the Gut Microbiome in ALS: A Systematic Review.

PubMed

Wright, Michelle L; Fournier, Christina; Houser, Madelyn C; Tansey, Malú; Glass, Jonathan; Hertzberg, Vicki Stover

2018-01-01

Amyotrophic lateral sclerosis (ALS) etiology and pathophysiology are not well understood. Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. This review aims to explore evidence of associations between gut microbiota and ALS etiology and pathophysiology. Databases were searched for publications relevant to the gut microbiome in ALS. Three publications provided primary evidence of changes in microbiome profiles in ALS. An ALS mouse model revealed damaged tight junction structure and increased permeability in the intestine versus controls along with a shifted microbiome profile, including decreased levels of butyrate-producing bacteria. In a subsequent publication, again using an ALS mouse model, researchers showed that dietary supplementation with butyrate relieved symptoms and lengthened both time to onset of weight loss and survival time. In a small study of ALS patients and healthy controls, investigators also found decreased levels of butyrate-producing bacteria. Essential for maintaining gut barrier integrity, butyrate is the preferred energy source of intestinal epithelial cells. Ten other articles were reviews and commentaries providing indirect support for a role of gut microbiota in ALS pathophysiology. Thus, these studies provide a modicum of evidence implicating gut microbiota in ALS disease, although more research is needed to confirm the connection and determine pathophysiologic mechanisms. Nurses caring for these patients need to understand the gut microbiome and its potential role in ALS in order to effectively counsel patients and their families about emerging therapies (e.g., prebiotics, probiotics, and fecal microbial transplant) and their off-label uses.

[Construction and application of the tissue bank and database of oral mucosa precancerous lesions in the Yangtze delta].

PubMed

Huang, Ji-yan; Zhao, Hou-ming; Zhou, Hai-wen

2014-04-01

To construct a database and a tissue bank of oral mucosa precancerous lesions and to estimate the application values. Patients in the Yangtze delta suffering oral mucosa precancerous lesions were enrolled into this study. The patients' clinical data and samples of oral precancerous mucosa, salivary and blood were collected to create a tissue bank, based on which a database was constructed using Microsoft Access software, Brower/Server structure and ASP language. The tissue bank and database of oral mucosa precancerous lesions were successfully built. The procedure to harvest, store and transport the samples had been standardized. The database showed good interactive interface, convenient for data collection, query and share in the internet. We constructed the tissue bank and database of oral mucosa precancerous lesions for the first time, which not only help preserve the biological resource of oral mucosa precancerous lesions, but also provide enormous convenience in clinical work, researching and teaching. Supported by Research Fund of Science and Technology Committee of Shanghai Municipality (08ZR1416700).

Mobile Microbiome

PubMed Central

Han, Y.W.; Wang, X.

2013-01-01

The link between oral infections and adverse systemic conditions has attracted much attention in the research community. Several mechanisms have been proposed, including spread of the oral infection due to transient bacteremia resulting in bacterial colonization in extra-oral sites, systemic injury by free toxins of oral pathogens, and systemic inflammation caused by soluble antigens of oral pathogens. Mounting evidence supports a major role of the systemic spread of oral commensals and pathogens to distant body sites causing extra-oral infections and inflammation. We review here the most recent findings on systemic infections and inflammation complicated by oral bacteria, including cardiovascular disease, adverse pregnancy outcomes, rheumatoid arthritis, inflammatory bowel disease and colorectal cancer, respiratory tract infections, and organ inflammations and abscesses. The recently identified virulence mechanisms of oral species Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Campylobacter rectus are also reviewed. A pattern emerges indicating that only select subtype(s) of a given species, e.g., F. nucleatum subspecies animalis and polymorphum and S. mutans non-c serotypes, are prone to extra-oral translocation. These findings advocate the importance of identification and quantification of potential pathogens at the subtype levels for accurate prediction of disease potential. PMID:23625375

Association between tobacco use and the upper gastrointestinal microbiome among Chinese men.

PubMed

Vogtmann, Emily; Flores, Roberto; Yu, Guoqin; Freedman, Neal D; Shi, Jianxin; Gail, Mitchell H; Dye, Bruce A; Wang, Guo-Qing; Klepac-Ceraj, Vanja; Paster, Bruce J; Wei, Wen-Qiang; Guo, Hui-Qin; Dawsey, Sanford M; Qiao, You-Lin; Abnet, Christian C

2015-04-01

Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men. We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses. Of the 278 men in this study, 46.8% were current smokers and 12.6% were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95% CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95% CI 0.51-0.87; PCoA2 OR 0.73; 95% CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers. Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases.

Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilhan, Zehra Esra; DiBaise, John K.; Isern, Nancy G.

Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are anatomically different bariatric operations. RYGB achieves greater weight loss compared with LAGB. Changes in the gut microbiome have been documented after RYGB, but not LAGB, and the microbial contribution to sustainable surgical weight loss warrants further evaluation. We hypothesized that RYGB imposes greater changes on the microbiota and its metabolism than LAGB, and that the altered microbiota may contribute to greater weight loss. Using multi-omic approaches, we analyzed fecal microbial community structure and metabolites of pre-bariatric surgery morbidly obese (PreB-Ob), normal weight (NW), post-RYGB, and post-LAGB participants. RYGB microbiomesmore » were significantly different from those from NW, LAGB and PreB-Ob. Microbiome differences between RYGB and PreB- Ob populations were mirrored in their metabolomes. Diversity was higher in RYGB compared with LAGB, possibly because of an increase in the abundance of facultative anaerobic, bile-tolerant and acid-sensible microorganisms in the former. Possibly because of lower gastric acid exposure, phylotypes from the oral cavity, such as Escherichia, Veillonella and Streptococcus, were in greater abundance in the RYGB group, and their abundances positively correlated with percent excess weight loss. Many of these post-RYGB microorganisms are capable of amino-acid fermentation. Amino-acid and carbohydrate fermentation products—isovalerate, isobutyrate, butyrate and propionate—were prevalent in RYGB participants, but not in LAGB participants. RYGB resulted in greater alteration of the gut microbiome and metabolome than LAGB, and RYGB group exhibited unique microbiome composed of many amino-acid fermenters, compared with nonsurgical controls.« less

The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery.

PubMed

Cabrera-Rubio, Raul; Collado, M Carmen; Laitinen, Kirsi; Salminen, Seppo; Isolauri, Erika; Mira, Alex

2012-09-01

Breast milk is recognized as the most important postpartum element in metabolic and immunologic programming of health of neonates. The factors influencing the milk microbiome and the potential impact of microbes on infant health have not yet been uncovered. Our objective was to identify pre- and postnatal factors that can potentially influence the bacterial communities inhabiting human milk. We characterized the milk microbial community at 3 different time points by pyrosequencing and quantitative polymerase chain reaction in mothers (n = 18) who varied in BMI, weight gain, and mode of delivery. We found that the human milk microbiome changes over lactation. Weisella, Leuconostoc, Staphylococcus, Streptococcus, and Lactococcus were predominant in colostrum samples, whereas in 1- and 6-mo milk samples the typical inhabitants of the oral cavity (eg, Veillonella, Leptotrichia, and Prevotella) increased significantly. Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal-weight mothers. Milk samples from elective but not from nonelective mothers who underwent cesarean delivery contained a different bacterial community than did milk samples from individuals giving birth by vaginal delivery, suggesting that it is not the operation per se but rather the absence of physiological stress or hormonal signals that could influence the microbial transmission process to milk. Our results indicate that milk bacteria are not contaminants and suggest that the milk microbiome is influenced by several factors that significantly skew its composition. Because bacteria present in breast milk are among the very first microbes entering the human body, our data emphasize the necessity to understand the biological role that the milk microbiome could potentially play for human health.

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denner, Darcy R.; Sangwan, Naseer; Becker, Julia B.

The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencingmore » was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.« less

High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation

PubMed Central

Guerrero-Preston, Rafael; White, James Robert; Godoy-Vitorino, Filipa; Rodríguez-Hilario, Arnold; Navarro, Kelvin; González, Herminio; Michailidi, Christina; Jedlicka, Anne; Canapp, Sierra; Bondy, Jessica; Dziedzic, Amanda; Mora-Lagos, Barbara; Rivera-Alvarez, Gustavo; Ili-Gangas, Carmen; Brebi-Mieville, Priscilla; Westra, William; Koch, Wayne; Kang, Hyunseok; Marchionni, Luigi; Kim, Young; Sidransky, David

2017-01-01

Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients. PMID:29340028

High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation.

PubMed

Guerrero-Preston, Rafael; White, James Robert; Godoy-Vitorino, Filipa; Rodríguez-Hilario, Arnold; Navarro, Kelvin; González, Herminio; Michailidi, Christina; Jedlicka, Anne; Canapp, Sierra; Bondy, Jessica; Dziedzic, Amanda; Mora-Lagos, Barbara; Rivera-Alvarez, Gustavo; Ili-Gangas, Carmen; Brebi-Mieville, Priscilla; Westra, William; Koch, Wayne; Kang, Hyunseok; Marchionni, Luigi; Kim, Young; Sidransky, David

2017-12-19

Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum , an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.

Computational prediction of CRISPR cassettes in gut metagenome samples from Chinese type-2 diabetic patients and healthy controls.

PubMed

Mangericao, Tatiana C; Peng, Zhanhao; Zhang, Xuegong

2016-01-11

CRISPR has been becoming a hot topic as a powerful technique for genome editing for human and other higher organisms. The original CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats coupled with CRISPR-associated proteins) is an important adaptive defence system for prokaryotes that provides resistance against invading elements such as viruses and plasmids. A CRISPR cassette contains short nucleotide sequences called spacers. These unique regions retain a history of the interactions between prokaryotes and their invaders in individual strains and ecosystems. One important ecosystem in the human body is the human gut, a rich habitat populated by a great diversity of microorganisms. Gut microbiomes are important for human physiology and health. Metagenome sequencing has been widely applied for studying the gut microbiomes. Most efforts in metagenome study has been focused on profiling taxa compositions and gene catalogues and identifying their associations with human health. Less attention has been paid to the analysis of the ecosystems of microbiomes themselves especially their CRISPR composition. We conducted a preliminary analysis of CRISPR sequences in a human gut metagenomic data set of Chinese individuals of type-2 diabetes patients and healthy controls. Applying an available CRISPR-identification algorithm, PILER-CR, we identified 3169 CRISPR cassettes in the data, from which we constructed a set of 1302 unique repeat sequences and 36,709 spacers. A more extensive analysis was made for the CRISPR repeats: these repeats were submitted to a more comprehensive clustering and classification using the web server tool CRISPRmap. All repeats were compared with known CRISPRs in the database CRISPRdb. A total of 784 repeats had matches in the database, and the remaining 518 repeats from our set are potentially novel ones. The computational analysis of CRISPR composition based contigs of metagenome sequencing data is feasible. It provides an efficient approach for finding potential novel CRISPR arrays and for analysing the ecosystem and history of human microbiomes.

Mycoplasma salivarium as a Dominant Coloniser of Fanconi Anaemia Associated Oral Carcinoma

PubMed Central

Henrich, Birgit; Rumming, Madis; Sczyrba, Alexander; Velleuer, Eunike; Dietrich, Ralf; Gerlach, Wolfgang; Gombert, Michael; Rahn, Sebastian; Stoye, Jens; Borkhardt, Arndt; Fischer, Ute

2014-01-01

Mycoplasma salivarium belongs to the class of the smallest self-replicating Tenericutes and is predominantly found in the oral cavity of humans. In general it is considered as a non-pathogenic commensal. However, some reports point to an association with human diseases. M. salivarium was found e.g. as causative agent of a submasseteric abscess, in necrotic dental pulp, in brain abscess and clogged biliary stent. Here we describe the detection of M. salivarium on the surface of a squamous cell carcinoma of the tongue of a patient with Fanconi anaemia (FA). FA is an inherited bone marrow failure syndrome based on defective DNA-repair that increases the risk of carcinomas especially oral squamous cell carcinoma. Employing high coverage, massive parallel Roche/454-next-generation-sequencing of 16S rRNA gene amplicons we analysed the oral microbiome of this FA patient in comparison to that of an FA patient with a benign leukoplakia and five healthy individuals. The microbiota of the FA patient with leukoplakia correlated well with that of the healthy controls. A dominance of Streptococcus, Veillonella and Neisseria species was typically observed. In contrast, the microbiome of the cancer bearing FA patient was dominated by Pseudomonas aeruginosa at the healthy sites, which changed to a predominance of 98% M. salivarium on the tumour surface. Quantification of the mycoplasma load in five healthy, two tumour- and two leukoplakia-FA patients by TaqMan-PCR confirmed the prevalence of M. salivarium at the tumour sites. These new findings suggest that this mycoplasma species with its reduced coding capacity found ideal breeding grounds at the tumour sites. Interestingly, the oral cavity of all FA patients and especially samples at the tumour sites were in addition positive for Candida albicans. It remains to be elucidated in further studies whether M. salivarium can be used as a predictive biomarker for tumour development in these patients. PMID:24642836

Identifying low pH active and lactate-utilizing taxa within oral microbiome communities from healthy children using stable isotope probing techniques.

PubMed

McLean, Jeffrey S; Fansler, Sarah J; Majors, Paul D; McAteer, Kathleen; Allen, Lisa Z; Shirtliff, Mark E; Lux, Renate; Shi, Wenyuan

2012-01-01

Many human microbial infectious diseases including dental caries are polymicrobial in nature. How these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral bacteria have been characterized in vitro, their physiology within the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these species remain uncultivated to date with little known besides their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated species will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for in vitro temporal monitoring of metabolites and identification of metabolically active and inactive bacterial species. Supragingival plaque samples from caries-free children incubated with (13)C-substrates under imposed healthy (buffered, pH 7) and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic acid from glucose metabolism. Rapid lactate utilization upon glucose depletion was observed under pH 7 conditions. SIP analyses revealed a number of genera containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5. The diversity of active species decreased significantly at pH 4.5 and was dominated by Lactobacillus and Propionibacterium species, both of which have been previously found within carious lesions from children. Our approach allowed for identification of species that metabolize carbohydrates under different pH conditions and supports the importance of Lactobacilli and Propionibacterium in the development of childhood caries. Identification of species within healthy subjects that are active at low pH can lead to a better understanding of oral caries onset and generate appropriate targets for preventative measures in the early stages.

The salivary microbiome is altered in the presence of a high salivary glucose concentration

PubMed Central

Hartman, Mor-Li; Shi, Ping; Hasturk, Hatice; Yaskell, Tina; Vargas, Jorel; Song, Xiaoqing; Cugini, Maryann; Barake, Roula; Alsmadi, Osama; Al-Mutawa, Sabiha; Ariga, Jitendra; Soparkar, Pramod; Behbehani, Jawad; Behbehani, Kazem

2017-01-01

Background Type II diabetes (T2D) has been associated with changes in oral bacterial diversity and frequency. It is not known whether these changes are part of the etiology of T2D, or one of its effects. Methods We measured the glucose concentration, bacterial counts, and relative frequencies of 42 bacterial species in whole saliva samples from 8,173 Kuwaiti adolescents (mean age 10.00 ± 0.67 years) using DNA probe analysis. In addition, clinical data related to obesity, dental caries, and gingivitis were collected. Data were compared between adolescents with high salivary glucose (HSG; glucose concentration ≥ 1.0 mg/d, n = 175) and those with low salivary glucose (LSG, glucose concentration < 0.1 mg/dL n = 2,537). Results HSG was associated with dental caries and gingivitis in the study population. The overall salivary bacterial load in saliva decreased with increasing salivary glucose concentration. Under HSG conditions, the bacterial count for 35 (83%) of 42 species was significantly reduced, and relative bacterial frequencies in 27 species (64%) were altered, as compared with LSG conditions. These alterations were stronger predictors of high salivary glucose than measures of oral disease, obesity, sleep or fitness. Conclusions HSG was associated with a reduction in overall bacterial load and alterations to many relative bacterial frequencies in saliva when compared with LSG in samples from adolescents. We propose that hyperglycemia due to obesity and/or T2D results in HSG and subsequent acidification of the oral environment, leading to a generalized perturbation in the oral microbiome. This suggests a basis for the observation that hyperglycemia is associated with an increased risk of dental erosion, dental caries, and gingivitis. We conclude that HSG in adolescents may be predicted from salivary microbial diversity or frequency, and that the changes in the oral microbial composition seen in adolescents with developing metabolic disease may the consequence of hyperglycemia. PMID:28249034

Porphyromonas gingivalis: Major Periodontopathic Pathogen Overview

PubMed Central

Mysak, Jaroslav; Podzimek, Stepan; Sommerova, Pavla; Lyuya-Mi, Yelena; Bartova, Jirina; Janatova, Tatjana; Prochazkova, Jarmila; Duskova, Jana

2014-01-01

Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis and is a member of more than 500 bacterial species that live in the oral cavity. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions: this is attributed to its arsenal of specialized virulence factors. The purpose of this review is to provide an overview of one of the main periodontal pathogens—Porphyromonas gingivalis. This bacterium, along with Treponema denticola and Tannerella forsythia, constitute the “red complex,” a prototype polybacterial pathogenic consortium in periodontitis. This review outlines Porphyromonas gingivalis structure, its metabolism, its ability to colonize the epithelial cells, and its influence upon the host immunity. PMID:24741603

Feasibility of Providing Safe Mouth Care and Collecting Oral and Fecal Microbiome Samples from Nursing Home Residents with Dysphagia: Proof of Concept Study.

PubMed

Jablonski, Rita A; Winstead, Vicki; Azuero, Andres; Ptacek, Travis; Jones-Townsend, Corteza; Byrd, Elizabeth; Geisinger, Maria L; Morrow, Casey

2017-09-01

Individuals with dysphagia who reside in nursing homes often receive inadequate mouth care and experience poor oral health. From a policy perspective, the combination of absent evidence-based mouth care protocols coupled with insufficient dental coverage create a pool of individuals at great risk for preventable infectious illnesses that contribute to high health care costs. The purpose of the current study was to determine (a) the safety of a mouth care protocol tailored for individuals with dysphagia residing in nursing homes without access to suction equipment, and (b) the feasibility of collecting oral and fecal samples for microbiota analyses. The mouth care protocol resulted in improved oral hygiene without aspiration, and oral and fecal samples were safely collected from participants. Policies supporting ongoing testing of evidence-based mouth care protocols for individuals with dysphagia are important to improve quality, demonstrate efficacy, and save health care costs. [Journal of Gerontological Nursing, 43(9), 9-15.]. Copyright 2017, SLACK Incorporated.

The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease

PubMed Central

Schwarzberg, Karen; Le, Rosalin; Bharti, Balambal; Lindsay, Suzanne; Casaburi, Giorgio; Salvatore, Francesco; Saber, Mohamed H.; Alonaizan, Faisal; Slots, Jørgen; Gottlieb, Roberta A.; Caporaso, J. Gregory; Kelley, Scott T.

2014-01-01

Periodontitis is a progressive disease of the periodontium with a complex, polymicrobial etiology. Recent Next-Generation Sequencing (NGS) studies of the microbial diversity associated with periodontitis have revealed strong, community-level differences in bacterial assemblages associated with healthy or diseased periodontal sites. In this study, we used NGS approaches to characterize changes in periodontal pocket bacterial diversity after standard periodontal treatment. Despite consistent changes in the abundance of certain taxa in individuals whose condition improved with treatment, post-treatment samples retained the highest similarity to pre-treatment samples from the same individual. Deeper phylogenetic analysis of periodontal pathogen-containing genera Prevotella and Fusobacterium found both unexpected diversity and differential treatment response among species. Our results highlight how understanding interpersonal variability among microbiomes is necessary for determining how polymicrobial diseases respond to treatment and disturbance. PMID:24489772

The Sphagnum microbiome: new insights from an ancient plant lineage

Treesearch

Joel E. Kostka; David J. Weston; Jennifer B. Glass; Erik A. Lilleskov; A. Jonathan Shaw; Merritt Turetsky

2016-01-01

Peat mosses of the genus Sphagnum play a major role in global carbon storage and dominate many northern peatland ecosystems, which are currently being subjected to some of the most rapid climate changes on Earth.Arapidly expanding database indicates that a diverse community of microorganisms is intimately associated with Sphagnum...

Differential Establishment of Bifidobacteria in the Breastfed Infant Gut

PubMed Central

Lewis, Zachery T.; Mills, David A.

2017-01-01

The composition of an infant’s gut microbiome can impact their immediate and long-term health. Bifdobacteria play a major role in structuring the gut microbiome of breastfed infants due to their ability to consume oligosaccharides found in human milk. However, recent studies have revealed that bifidobacteria are often absent in the gut microbiome of breastfed infants in some locations. This lack of colonization may be due either to differences in the environmental conditions in the gastrointestinal tract of uncolonized infants which prohibit the growth of bifidobacteria or a dearth of sources from which infants may acquire these specialized bacterial species. Potential mechanisms by which these broad factors may lead to lower colonization of infants by bifidobacteria are discussed herein. Environmental conditions which may select against bifidobacteria include low rates/duration of breastfeeding, milk glycan composition, and antimicrobial use. Routes of colonization by bifidobacteria which may be disrupted include maternal transfer via vaginal birth, fecal-oral routes, or via breast milk itself. A careful contemplation of the conditions experienced by bifidobacteria over human evolutionary history may lead to further hypotheses as to the causative factors of the differential colonization by this foundation genus in some contemporary locations. PMID:28346936

Dysbiosis of the microbiome in gastric carcinogenesis.

PubMed

Castaño-Rodríguez, Natalia; Goh, Khean-Lee; Fock, Kwong Ming; Mitchell, Hazel M; Kaakoush, Nadeem O

2017-11-21

The gastric microbiome has been proposed as an etiological factor in gastric carcinogenesis. We compared the gastric microbiota in subjects presenting with gastric cancer (GC, n = 12) and controls (functional dyspepsia (FD), n = 20) from a high GC risk population in Singapore and Malaysia. cDNA from 16S rRNA transcripts were amplified (515F-806R) and sequenced using Illumina MiSeq 2 × 250 bp chemistry. Increased richness and phylogenetic diversity but not Shannon's diversity was found in GC as compared to controls. nMDS clustered GC and FD subjects separately, with PERMANOVA confirming a significant difference between the groups. H. pylori serological status had a significant impact on gastric microbiome α-diversity and composition. Several bacterial taxa were enriched in GC, including Lactococcus, Veilonella, and Fusobacteriaceae (Fusobacterium and Leptotrichia). Prediction of bacterial metabolic contribution indicated that serological status had a significant impact on metabolic function, while carbohydrate digestion and pathways were enriched in GC. Our findings highlight three mechanisms of interest in GC, including enrichment of pro-inflammatory oral bacterial species, increased abundance of lactic acid producing bacteria, and enrichment of short chain fatty acid production pathways.

Biogeography of the ecosystems of the healthy human body.

PubMed

Zhou, Yanjiao; Gao, Hongyu; Mihindukulasuriya, Kathie A; La Rosa, Patricio S; Wylie, Kristine M; Vishnivetskaya, Tatiana; Podar, Mircea; Warner, Barb; Tarr, Phillip I; Nelson, David E; Fortenberry, J Dennis; Holland, Martin J; Burr, Sarah E; Shannon, William D; Sodergren, Erica; Weinstock, George M

2013-01-14

Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. Previous studies mainly focused on a single body habitat from a limited set of subjects. Here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans. We identified 929 genera from more than 24 million 16S rRNA gene sequences of 22 habitats, and we provide a baseline of inter-subject variation for healthy adults. The oral habitat has the most stable microbiota with the highest alpha diversity, while the skin and vaginal microbiota are less stable and show lower alpha diversity. The level of biodiversity in one habitat is independent of the biodiversity of other habitats in the same individual. The abundances of a given genus at a body site in which it dominates do not correlate with the abundances at body sites where it is not dominant. Additionally, we observed the human microbiota exhibit both cosmopolitan and endemic features. Finally, comparing datasets of different projects revealed a project-based clustering pattern, emphasizing the significance of standardization of metagenomic studies. The data presented here extend the definition of the human microbiome by providing a more complete and accurate picture of human microbiome biogeography, addressing questions best answered by a large dataset of subjects and body sites that are deeply sampled by sequencing.

Biogeography of the ecosystems of the healthy human body

PubMed Central

2013-01-01

Background Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. Previous studies mainly focused on a single body habitat from a limited set of subjects. Here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans. Results We identified 929 genera from more than 24 million 16S rRNA gene sequences of 22 habitats, and we provide a baseline of inter-subject variation for healthy adults. The oral habitat has the most stable microbiota with the highest alpha diversity, while the skin and vaginal microbiota are less stable and show lower alpha diversity. The level of biodiversity in one habitat is independent of the biodiversity of other habitats in the same individual. The abundances of a given genus at a body site in which it dominates do not correlate with the abundances at body sites where it is not dominant. Additionally, we observed the human microbiota exhibit both cosmopolitan and endemic features. Finally, comparing datasets of different projects revealed a project-based clustering pattern, emphasizing the significance of standardization of metagenomic studies. Conclusions The data presented here extend the definition of the human microbiome by providing a more complete and accurate picture of human microbiome biogeography, addressing questions best answered by a large dataset of subjects and body sites that are deeply sampled by sequencing. PMID:23316946

The Earth Microbiome Project and Global Systems Biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbert, Jack A.; Jansson, Janet K.; Knight, Rob

Recently, we published the first large-scale analysis of data from the Earth Microbiome Project (1, 2), a truly multidisciplinary research program involving more than 500 scientists and 27,751 samples acquired from 43 countries. These samples represent myriad specimen types and span a wide range of biotic and abiotic factors, geographic locations, and physicochemical properties. The database (https://qiita.ucsd.edu/emp/) is still growing, with over 90,000 amplicon datasets, >500 metagenomic runs, and metabolomics datasets from a similar number of samples. Importantly, the techniques, data and analytical tools are all standardized and publicly accessible, providing a framework to support research at a scale ofmore » integration that just 7 years ago seemed impossible.« less

Oral Microbiota Shift after 12-Week Supplementation with Lactobacillus reuteri DSM 17938 and PTA 5289; A Randomized Control Trial

PubMed Central

Romani Vestman, Nelly; Chen, Tsute; Lif Holgerson, Pernilla; Öhman, Carina; Johansson, Ingegerd

2015-01-01

Background Lactobacillus spp. potentially contribute to health by modulating bacterial biofilm formation, but their effects on the overall oral microbiota remain unclear. Methods and Findings Oral microbiota was characterized via 454-pyrosequencing of the 16S rDNA hypervariable region V3-V4 after 12 weeks of daily Lactobacillus reuteri DSM 17938 and PTA 5289 consumption. Forty-four adults were assigned to a test group (n = 22) that received lactobacilli lozenges (108 CFU of each strain/lozenge) or a control group that received placebo (n = 22). Presence of L. reuteri was confirmed by cultivation and species specific PCR. Tooth biofilm samples from 16 adults before, during, and after exposure were analyzed by pyrosequencing. A total of 1,310,292 sequences were quality filtered. After removing single reads, 257 species or phylotypes were identified at 98.5% identity in the Human Oral Microbiome Database. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria, and Actinobacteria were the most abundant phyla. Streptococcus was the most common genus and the S. oralis/S. mitis/S. mitis bv2/S. infantis group comprised the dominant species. The number of observed species was unaffected by L. reuteri exposure. However, subjects who had consumed L. reuteri were clustered in a principal coordinates analysis relative to scattering at baseline, and multivariate modeling of pyrosequencing microbiota, and culture and PCR detected L. reuteri separated baseline from 12-week samples in test subjects. L. reuteri intake correlated with increased S. oralis/S. mitis/S. mitis bv2/S. infantis group and Campylobacter concisus, Granulicatella adiacens, Bergeyella sp. HOT322, Neisseria subflava, and SR1 [G-1] sp. HOT874 detection and reduced S. mutans, S. anginosus, N. mucosa, Fusobacterium periodicum, F. nucleatum ss vincentii, and Prevotella maculosa detection. This effect had disappeared 1 month after exposure was terminated. Conclusions L. reuteri consumption did not affect species richness but induced a shift in the oral microbiota composition. The biological relevance of this remains to be elucidated. Trial Registration ClinicalTrials.gov NCT02311218 PMID:25946126

The oral microbiome and human health.

PubMed

Yamashita, Yoshihisa; Takeshita, Toru

2017-01-01

In this brief review, we discuss our previous research on the relationship between the bacterial composition of salivary microbiota and periodontal disease. Analysis using a terminal restriction fragment length polymorphism method and an international comparison suggest that the predominance of the genera Prevotella and Veillonella in the salivary microbiota is attributable to periodontal disease conditions, and that the predominance of the genus Neisseria indicates healthy periodontal conditions. Furthermore, we recently used next-generation sequencing technology to perform a detailed large-scale analysis of the salivary microbiota. An important finding of that study was that high bacterial richness in the salivary microbiota was significantly associated with poor oral health, as indicated by decayed teeth, periodontitis, and poor oral hygiene. Another important result was that relative abundance of predominant bacteria in saliva was significantly associated with oral health-related conditions. Of the two different cohabiting groups of bacteria found in the salivary microbiota, a greater relative abundance of group I bacteria, which include Prevotella and Veillonella species, was associated with poor oral health, high body mass index, and old age. These findings suggest that the salivary microbiota reflects oral and systemic conditions.

What could you do with 400 years of biological history on african americans? Evaluating the potential scientific benefit of systematic studies of dental and skeletal materials on African Americans from the 17th through 20th centuries

PubMed Central

Jackson, Latifa; Cross, Christopher; Clarke, Cameron

2016-01-01

Objectives How important is it to be able to reconstruct the lives of a highly diverse, historically recent macroethnic group over the course of 400 years? How many insights into human evolutionary biology and disease susceptibilities could be gained, even with this relatively recent window into the past? In this article, we explore the potential ramifications of a newly constructed dataset of Four Centuries of African American Biological Variation (4Cs). Methods This article provides initial lists of digitized variables formatted as SQL tables for the 17th and 18th century samples and for the 19th and 20th century samples. Results This database is dynamic and new information is added yearly. The database provides novel opportunities for significant insights into the past biological history of this group and three case study applications are detailed for comparative computational systems biology studies of (1) hypertension, (2) the oral microbiome, and (3) mental health disorders. Conclusions The 4Cs dataset is ideal for interdisciplinary “next generation” science research and these data represent a unique step toward the accumulation of historically contextualized Big Data on an underrepresented group known to have experienced differential survival over time. Am. J. Hum. Biol. 28:510–513, 2016. © 2016 The Authors American Journal of Human Biology Published byWiley Periodicals, Inc. PMID:26749025

Endophyte Microbiome Diversity in Micropropagated Atriplex canescens and Atriplex torreyi var griffithsii

PubMed Central

Lucero, Mary E.; Unc, Adrian; Cooke, Peter; Dowd, Scot; Sun, Shulei

2011-01-01

Microbial diversity associated with micropropagated Atriplex species was assessed using microscopy, isolate culturing, and sequencing. Light, electron, and confocal microscopy revealed microbial cells in aseptically regenerated leaves and roots. Clone libraries and tag-encoded FLX amplicon pyrosequencing (TEFAP) analysis amplified sequences from callus homologous to diverse fungal and bacterial taxa. Culturing isolated some seed borne endophyte taxa which could be readily propagated apart from the host. Microbial cells were observed within biofilm-like residues associated with plant cell surfaces and intercellular spaces. Various universal primers amplified both plant and microbial sequences, with different primers revealing different patterns of fungal diversity. Bacterial and fungal TEFAP followed by alignment with sequences from curated databases revealed 7 bacterial and 17 ascomycete taxa in A. canescens, and 5 bacterial taxa in A. torreyi. Additional diversity was observed among isolates and clone libraries. Micropropagated Atriplex retains a complex, intimately associated microbiome which includes diverse strains well poised to interact in manners that influence host physiology. Microbiome analysis was facilitated by high throughput sequencing methods, but primer biases continue to limit recovery of diverse sequences from even moderately complex communities. PMID:21437280

CowPI: A Rumen Microbiome Focussed Version of the PICRUSt Functional Inference Software.

PubMed

Wilkinson, Toby J; Huws, Sharon A; Edwards, Joan E; Kingston-Smith, Alison H; Siu-Ting, Karen; Hughes, Martin; Rubino, Francesco; Friedersdorff, Maximillian; Creevey, Christopher J

2018-01-01

Metataxonomic 16S rDNA based studies are a commonplace and useful tool in the research of the microbiome, but they do not provide the full investigative power of metagenomics and metatranscriptomics for revealing the functional potential of microbial communities. However, the use of metagenomic and metatranscriptomic technologies is hindered by high costs and skills barrier necessary to generate and interpret the data. To address this, a tool for Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was developed for inferring the functional potential of an observed microbiome profile, based on 16S data. This allows functional inferences to be made from metataxonomic 16S rDNA studies with little extra work or cost, but its accuracy relies on the availability of completely sequenced genomes of representative organisms from the community being investigated. The rumen microbiome is an example of a community traditionally underrepresented in genome and sequence databases, but recent efforts by projects such as the Global Rumen Census and Hungate 1000 have resulted in a wide sampling of 16S rDNA profiles and almost 500 fully sequenced microbial genomes from this environment. Using this information, we have developed "CowPI," a focused version of the PICRUSt tool provided for use by the wider scientific community in the study of the rumen microbiome. We evaluated the accuracy of CowPI and PICRUSt using two 16S datasets from the rumen microbiome: one generated from rDNA and the other from rRNA where corresponding metagenomic and metatranscriptomic data was also available. We show that the functional profiles predicted by CowPI better match estimates for both the meta-genomic and transcriptomic datasets than PICRUSt, and capture the higher degree of genetic variation and larger pangenomes of rumen organisms. Nonetheless, whilst being closer in terms of predictive power for the rumen microbiome, there were differences when compared to both the metagenomic and metatranscriptome data and so we recommend, where possible, functional inferences from 16S data should not replace metagenomic and metatranscriptomic approaches. The tool can be accessed at http://www.cowpi.org and is provided to the wider scientific community for use in the study of the rumen microbiome.

Community-Level Differences in the Microbiome of Healthy Wild Mallards and Those Infected by Influenza A Viruses

PubMed Central

Doroud, Ladan; Firl, Alana J.; Hird, Sarah M.; Eisen, Jonathan A.

2017-01-01

ABSTRACT Waterfowl, especially ducks and geese, are primary reservoirs for influenza A viruses (IAVs) that evolve and emerge as important pathogens in domestic animals and humans. In contrast to humans, where IAVs infect the respiratory tract and cause significant morbidity and mortality, IAVs infect the gastrointestinal tract of waterfowl and cause little or no pathology and are spread by fecal-oral transmission. For this reason, we examined whether IAV infection is associated with differences in the cloacal microbiome of mallards (Anas platyrhyncos), an important host of IAVs in North America and Eurasia. We characterized bacterial community composition by sequencing the V4 region of 16S rRNA genes. IAV-positive mallards had lower species diversity, richness, and evenness than IAV-negative mallards. Operational taxonomic unit (OTU) cooccurrence patterns were also distinct depending on infection status. Network analysis showed that IAV-positive mallards had fewer significant cooccurring OTUs and exhibited fewer coassociation patterns among those OTUs than IAV-negative mallards. These results suggest that healthy mallards have a more robust and complex cloacal microbiome. By combining analytical approaches, we identified 41 bacterial OTUs, primarily representatives of Streptococcus spp., Veillonella dispar, and Rothia mucilaginosa, contributing to the observed differences. This study found that IAV-infected wild mallards exhibited strong differences in microbiome composition relative to noninfected mallards and identified a concise set of putative biomarker OTUs. Using Random Forest, a supervised machine learning method, we verified that these 41 bacterial OTUs are highly predictive of infection status. IMPORTANCE Seasonal influenza causes 3 to 5 million severe illnesses and 250,000 to 500,000 human deaths each year. While pandemic influenza viruses emerge only periodically, they can be devastating—for example, the 1918 H1N1 pandemic virus killed more than 20 million people. IAVs infect the respiratory tract and cause significant morbidity and mortality in humans. In contrast, IAVs infect the gastrointestinal tract of waterfowl, producing little pathology. Recent studies indicated that viruses can alter the microbiome at the respiratory and gastrointestinal mucosa, but there are no reports of how the microbiota of the natural host of influenza is affected by infection. Here we find that the mallard microbiome is altered during IAV infection. Our results suggest that detailed examination of humans and animals infected with IAVs may reveal individualized microbiome profiles that correspond to health and disease. Moreover, future studies should explore whether the altered microbiome facilitates maintenance and transmission of IAVs in waterfowl populations. PMID:28293681

Subgingival Microbiome Colonization and Cytokine Production during Early Dental Implant Healing.

PubMed

Payne, Jeffrey B; Johnson, Paul G; Kok, Car Reen; Gomes-Neto, João C; Ramer-Tait, Amanda E; Schmid, Marian J; Hutkins, Robert W

2017-01-01

Little is known about longitudinal development of the peri-implant subgingival microbiome and cytokine production as a new sulcus forms after dental implant placement. Therefore, the purpose of this observational study was to evaluate simultaneous longitudinal changes in the oral microbiome and cytokine production in the developing peri-implant sulcus compared to control natural teeth. Four and 12 weeks after implant placement and abutment connection, a dental implant and a natural tooth were sampled in 25 patients for subgingival plaque and gingival crevicular fluid (GCF [around teeth] and peri-implant crevicular fluid [PICF] around implants). DNA from plaque samples was extracted and sequenced using Illumina-based 16S rRNA sequencing. GCF and PICF samples were analyzed using a customized Milliplex human cytokine and chemokine magnetic bead panel. Beta diversity analysis revealed that natural teeth and implants had similar subgingival microbiomes, while teeth had greater alpha diversity than implants. At the genus level, however, few differences were noted between teeth and dental implants over 12 weeks. Specifically, Actinomyces and Selenomonas were significantly elevated around teeth versus dental implants at both 4 weeks and 12 weeks, while Corynebacterium and Campylobacter were significantly elevated only at 4 weeks around teeth. The only difference between PICF and GCF biomarkers was significantly elevated granulocyte-macrophage colony-stimulating factor levels around teeth versus dental implants at the 4-week visit. The subgingival microbiome and cytokine production were similar between teeth and implants during early healing, suggesting that these profiles are driven by the patient following dental implant placement and are not determined by anatomical niche. IMPORTANCE Dental implants are a common treatment option offered to patients for tooth replacement. However, little is known regarding initial colonization of the subgingival microbiome and simultaneous longitudinal cytokine production in humans during the early healing phase following implant placement. We report findings from an in vivo study that assessed initial colonization of the subgingival microbiome and concomitant early cytokine production in a newly formed anatomical space, namely, an implant sulcus. This approach may be useful in future interventional studies to influence dental implant success. Our data showed that the subgingival microbiome and cytokine profile were similar for control natural teeth and dental implants at both 4 and 12 weeks after implant placement. These data suggest that these profiles are driven by the patient and not by anatomical location (i.e., tooth versus dental implant).

Potential NICU Environmental Influences on the Neonate's Microbiome: A Systematic Review.

PubMed

Hartz, Lacey E; Bradshaw, Wanda; Brandon, Debra H

2015-10-01

To identify how the neonatal intensive care unit (NICU) environment potentially influences the microbiome high-risk term and preterm infants. Electronic databases utilized to identify studies published in English included PubMed, Google Scholar, Cumulative Index for Nursing and Allied Health Literature, and BioMedSearcher. Date of publication did not limit inclusion in the review. Two hundred fifty articles were assessed for relevance to the research question through title and abstract review. Further screening resulted in full review of 60 articles. An in-depth review of all 60 articles resulted in 39 articles that met inclusion criteria. Twenty-eight articles were eliminated on the basis of the type of study and subject of interest. Studies were reviewed for information related to environmental factors that influence microbial colonization of the neonatal microbiome. Environment was later defined as the physical environment of the NICU and nursery caregiving activities. Studies were characterized into factors that impacted the infant's microbiome—parental skin, feeding type, environmental surfaces and caregiving equipment, health care provider skin, and antibiotic use. Literature revealed that various aspects of living within the NICU environment do influence the microbiome of infants. Caregivers can implement strategies to prevent environment-associated nosocomial infection in the NICU such as implementing infection control measures, encouraging use of breast milk, and decreasing the empirical use of antibiotics.

The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists

PubMed Central

Lerner, Aaron; Neidhöfer, Sandra; Matthias, Torsten

2017-01-01

Objectives: To comprehensively review the scientific knowledge on the gut–brain axis. Methods: Various publications on the gut–brain axis, until 31 July 2017, were screened using the Medline, Google, and Cochrane Library databases. The search was performed using the following keywords: “gut-brain axis”, “gut-microbiota-brain axis”, “nutrition microbiome/microbiota”, “enteric nervous system”, “enteric glial cells/network”, “gut-brain pathways”, “microbiome immune system”, “microbiome neuroendocrine system” and “intestinal/gut/enteric neuropeptides”. Relevant articles were selected and reviewed. Results: Tremendous progress has been made in exploring the interactions between nutrients, the microbiome, and the intestinal, epithelium–enteric nervous, endocrine and immune systems and the brain. The basis of the gut–brain axis comprises of an array of multichannel sensing and trafficking pathways that are suggested to convey the enteric signals to the brain. These are mediated by neuroanatomy (represented by the vagal and spinal afferent neurons), the neuroendocrine–hypothalamic–pituitary–adrenal (HPA) axis (represented by the gut hormones), immune routes (represented by multiple cytokines), microbially-derived neurotransmitters, and finally the gate keepers of the intestinal and brain barriers. Their mutual and harmonious but intricate interaction is essential for human life and brain performance. However, a failure in the interaction leads to a number of inflammatory-, autoimmune-, neurodegenerative-, metabolic-, mood-, behavioral-, cognitive-, autism-spectrum-, stress- and pain-related disorders. The limited availability of information on the mechanisms, pathways and cause-and-effect relationships hinders us from translating and implementing the knowledge from the bench to the clinic. Implications: Further understanding of this intricate field might potentially shed light on novel preventive and therapeutic strategies to combat these disorders. Nutritional approaches, microbiome manipulations, enteric and brain barrier reinforcement and sensing and trafficking modulation might improve physical and mental health outcomes. PMID:29023380

An accurate and efficient experimental approach for characterization of the complex oral microbiota.

PubMed

Zheng, Wei; Tsompana, Maria; Ruscitto, Angela; Sharma, Ashu; Genco, Robert; Sun, Yijun; Buck, Michael J

2015-10-05

Currently, taxonomic interrogation of microbiota is based on amplification of 16S rRNA gene sequences in clinical and scientific settings. Accurate evaluation of the microbiota depends heavily on the primers used, and genus/species resolution bias can arise with amplification of non-representative genomic regions. The latest Illumina MiSeq sequencing chemistry has extended the read length to 300 bp, enabling deep profiling of large number of samples in a single paired-end reaction at a fraction of the cost. An increasingly large number of researchers have adopted this technology for various microbiome studies targeting the 16S rRNA V3-V4 hypervariable region. To expand the applicability of this powerful platform for further descriptive and functional microbiome studies, we standardized and tested an efficient, reliable, and straightforward workflow for the amplification, library construction, and sequencing of the 16S V1-V3 hypervariable region using the new 2 × 300 MiSeq platform. Our analysis involved 11 subgingival plaque samples from diabetic and non-diabetic human subjects suffering from periodontitis. The efficiency and reliability of our experimental protocol was compared to 16S V3-V4 sequencing data from the same samples. Comparisons were based on measures of observed taxonomic richness and species evenness, along with Procrustes analyses using beta(β)-diversity distance metrics. As an experimental control, we also analyzed a total of eight technical replicates for the V1-V3 and V3-V4 regions from a synthetic community with known bacterial species operon counts. We show that our experimental protocol accurately measures true bacterial community composition. Procrustes analyses based on unweighted UniFrac β-diversity metrics depicted significant correlation between oral bacterial composition for the V1-V3 and V3-V4 regions. However, measures of phylotype richness were higher for the V1-V3 region, suggesting that V1-V3 offers a deeper assessment of population diversity and community ecology for the complex oral microbiota. This study provides researchers with valuable experimental evidence for the selection of appropriate 16S amplicons for future human oral microbiome studies. We expect that the tested 16S V1-V3 framework will be widely applicable to other types of microbiota, allowing robust, time-efficient, and inexpensive examination of thousands of samples for population, phylogenetic, and functional crossectional and longitutidal studies.

Human neutrophils and oral microbiota: a constant tug-of-war between a harmonious and a discordant coexistence

PubMed Central

Uriarte, Silvia M.; Edmisson, Jacob S.; Jimenez-Flores, Emeri

2017-01-01

Summary Neutrophils are a major component of the innate host response, and the outcome of the interaction between the oral microbiota and neutrophils is a key determinant of oral health status. The composition of the oral microbiome is very complex and different in health and disease. Neutrophils are constantly recruited to the oral cavity, and their protective role is highlighted in cases where their number or functional responses are impeded, resulting in different forms of periodontal disease. Periodontitis, one of the more severe and irreversible forms of periodontal disease, is a microbial-induced chronic inflammatory disease that affects the gingival tissues supporting the tooth. This chronic inflammatory disease is the result of a shift of the oral bacterial symbiotic community to a dysbiotic more complex community. Chronic inflammatory infectious diseases such as periodontitis can occur because the pathogens are able to evade or disable the innate immune system. In this review, we discuss how human neutrophils interact with both the symbiotic and the dysbiotic oral community; an understanding of which is essential to increase our knowledge of the periodontal disease process. PMID:27558341

Research on oral microbiota of monozygotic twins with discordant caries experience - in vitro and in vivo study.

PubMed

Wu, Hongle; Zeng, Benhua; Li, Bolei; Ren, Biao; Zhao, Jianhua; Li, Mingyun; Peng, Xian; Feng, Mingye; Li, Jiyao; Wei, Hong; Cheng, Lei; Zhou, Xuedong

2018-05-08

Oral microbiome is potentially correlated with many diseases, such as dental caries, periodontitis, oral cancer and some systemic diseases. Twin model, as an effective method for studying human microbiota, is widely used in research of relationship between oral microbiota and dental caries. However, there were few researches focusing on caries discordant twins. In this study, in vitro assays were conducted combined with 16S rRNA sequencing analysis on oral microbiota sampled from twins who presented discordant caries experience and mice model was developed as well. Results showed that oral microbiota from caries-active twin possessed higher metabolic activity and produced more lactic production. 16S rRNA sequencing analysis showed that more than 80% of family taxa could be transferred into gnotobiotic-mice. Key caries-associated genera were significantly different between twins and the same difference in genus level could be found in mice as well (p < 0.05). This study suggested that oral microbiota of twins could be distinguished from each other despite the similarities in genetic make-up, living environment, and lifestyle. The difference in microbiota was applied to develop a mice model which may facilitate the investigation of core microbiota of dental caries.

Activation of the TREM-1 pathway in human monocytes by periodontal pathogens and oral commensal bacteria.

PubMed

Varanat, M; Haase, E M; Kay, J G; Scannapieco, F A

2017-08-01

Periodontitis is a highly prevalent disease caused in part by an aberrant host response to the oral multi-species biofilm. A balance between the oral bacteria and host immunity is essential for oral health. Imbalances in the oral microbiome lead to an uncontrolled host inflammatory response and subsequent periodontal disease (i.e. gingivitis and periodontitis). TREM-1 is a signaling receptor present on myeloid cells capable of acting synergistically with other pattern recognition receptors leading to amplification of inflammatory responses. The aim of this study was to investigate the activation of the TREM-1 pathway in the human monocyte-like cell line THP-1 exposed to both oral pathogens and commensals. The relative expression of the genes encoding TREM-1 and its adapter protein DAP12 were determined by quantitative real-time polymerase chain reaction. The surface expression of TREM-1 was determined by flow cytometry. Soluble TREM-1 and cytokines were measured by enzyme-linked immunosorbent assay. The results demonstrate that both commensal and pathogenic oral bacteria activate the TREM-1 pathway, resulting in a proinflammatory TREM-1 activity-dependent increase in proinflammatory cytokine production. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Potential benefits of chewing gum for the delivery of oral therapeutics and its possible role in oral healthcare.

PubMed

Wessel, Stefan W; van der Mei, Henny C; Maitra, Amarnath; Dodds, Michael W J; Busscher, Henk J

2016-10-01

Over the years, chewing gum has developed from a candy towards an oral health-promoting nutraceutical. This review summarizes evidence for the oral health benefits of chewing gum, emphasizing identification of active ingredients in gum that facilitate prevention and removal of oral biofilm. Chewing of sugar-free gum yields oral health benefits that include clearance of food debris, reduction in oral dryness, increase of biofilm pH and remineralization of enamel. These basic effects of chewing gum are attributed to increased mastication and salivation. Active ingredients incorporated in chewing gums aim to expand these effects to inhibition of extrinsic tooth stain and calculus formation, enhanced enamel remineralization, reduction of the numbers of bacteria in saliva and amount of oral biofilm, neutralization of biofilm pH, and reduction of volatile sulfur compounds. Evidence for oral-health benefits of chewing gum additives is hard to obtain due to their relatively low concentrations and rapid wash-out. Clinical effects of gum additives are overshadowed by effects of increased mastication and salivation due to the chewing of gum and require daily chewing of gum for prolonged periods of time. Future studies on active ingredients should focus on specifically targeting pathogenic bacteria, whilst leaving the healthy microbiome unaffected.

Is There a Role for Probiotics in the Prevention of Preterm Birth?

PubMed Central

Yang, Siwen; Reid, Gregor; Challis, John R. G.; Kim, Sung O.; Gloor, Gregory B.; Bocking, Alan D.

2015-01-01

Preterm birth (PTB) continues to be a global health challenge. An over-production of inflammatory cytokines and chemokines, as well as an altered maternal vaginal microbiome has been implicated in the pathogenesis of inflammation/infection-associated PTB. Lactobacillus represents the dominant species in the vagina of most healthy pregnant women. The depletion of Lactobacillus in women with bacterial vaginosis (BV) has been associated with an increased risk of PTB. It remains unknown at what point an aberrant vaginal microbiome composition specifically induces the cascade leading to PTB. The ability of oral or vaginal lactobacilli probiotics to reduce BV occurrence and/or dampen inflammation is being considered as a means to prevent PTB. Certain anti-inflammatory properties of lactobacilli suggest potential mechanisms. To date, clinical studies have not been powered with sufficiently high rates of PTB, but overall, there is merit in examining this promising area of clinical science. PMID:25741339

The microbiome of New World vultures.

PubMed

Roggenbuck, Michael; Bærholm Schnell, Ida; Blom, Nikolaj; Bælum, Jacob; Bertelsen, Mads Frost; Sicheritz-Pontén, Thomas; Pontén, Thomas Sicheritz; Sørensen, Søren Johannes; Gilbert, M Thomas P; Graves, Gary R; Hansen, Lars H

2014-11-25

Vultures are scavengers that fill a key ecosystem niche, in which they have evolved a remarkable tolerance to bacterial toxins in decaying meat. Here we report the first deep metagenomic analysis of the vulture microbiome. Through face and gut comparisons of 50 vultures representing two species, we demonstrate a remarkably conserved low diversity of gut microbial flora. The gut samples contained an average of 76 operational taxonomic units (OTUs) per specimen, compared with 528 OTUs on the facial skin. Clostridia and Fusobacteria, widely pathogenic to other vertebrates, dominate the vulture's gut microbiota. We reveal a likely faecal-oral-gut route for their origin. DNA of prey species detectable on facial swabs was completely degraded in the gut samples from most vultures, suggesting that the gastrointestinal tracts of vultures are extremely selective. Our findings show a strong adaption of vultures and their bacteria to their food source, exemplifying a specialized host-microbial alliance.

Demonstration of vaginal colonization with GusA-expressing Lactobacillus jensenii following oral delivery in rhesus macaques

PubMed Central

Lagenaur, Laurel A; Lee, Peter P; Hamer, Dean H; Sanders-Beer, Brigitte E

2012-01-01

The vaginal microbiome, which harbors beneficial Lactobacillus strains, is believed to be a major host defense mechanism for preventing infections of the urogenital tract. It has been suggested that the gastrointestinal tract serves as a reservoir for lactobacilli that colonize the vagina. Using rhesus macaques, we examined whether oral delivery of human vaginal Lactobacillus jensenii-1153-1646, a GusA-producing strain, would result in colonization of the rectum and the vagina. Lactobacilli were identified from the vagina tracts of three macaques on the basis of β-glucuronidase enzyme production, 16S rRNA gene sequence and DNA homology using a repetitive sequence-based polymerase chain reaction. PMID:21907793

Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis.

PubMed

Song, Han; Yoo, Young; Hwang, Junghyun; Na, Yun-Cheol; Kim, Heenam Stanley

2016-03-01

Atopic dermatitis (AD) is a serious global epidemic associated with a modern lifestyle. Although aberrant interactions between gut microbes and the intestinal immune system have been implicated in this skin disease, the nature of the microbiome dysfunction underlying the disease remains unclear. The gut microbiome from 132 subjects, including 90 patients with AD, was analyzed by using 16S rRNA gene and metagenome sequence analyses. Reference genomes from the Human Microbiome Project and the KEGG Orthology database were used for metagenome analyses. Short-chain fatty acids in fecal samples were compared by using gas chromatographic-mass spectrometric analyses. We show that enrichment of a subspecies of the major gut species Faecalibacterium prausnitzii is strongly associated with AD. In addition, the AD microbiome was enriched in genes encoding the use of various nutrients that could be released from damaged gut epithelium, reflecting a bloom of auxotrophic bacteria. Fecal samples from patients with AD showed decreased levels of butyrate and propionate, which have anti-inflammatory effects. This is likely a consequence of an intraspecies compositional change in F prausnitzii that reduces the number of high butyrate and propionate producers, including those related to the strain A2-165, a lack of which has been implicated in patients with Crohn disease. The data suggest that feedback interactions between dysbiosis in F prausnitzii and dysregulation of gut epithelial inflammation might underlie the chronic progression of AD by resulting in impairment of the gut epithelial barrier, which ultimately leads to aberrant TH2-type immune responses to allergens in the skin. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children

PubMed Central

Florez de Sessions, Paola; Jie, Song; Pham Thanh, Duy; Thompson, Corinne N.; Nguyen Ngoc Minh, Chau; Chu, Collins Wenhan; Tran, Tuan-Anh; Thomson, Nicholas R.; Thwaites, Guy E.; Rabaa, Maia A.; Hibberd, Martin; Baker, Stephen

2018-01-01

ABSTRACT Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions. PMID:28767339

Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

PubMed Central

Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A.; Lynch, Susan V.

2014-01-01

Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome. PMID:24850358

Microbiome Disturbances and Autism Spectrum Disorders.

PubMed

Rosenfeld, Cheryl S

2015-10-01

Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

PubMed Central

Fennema, Diede; Phillips, Ian R.

2016-01-01

Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. On a daily basis, however, we are exposed to one of the most abundant substrates of the enzyme trimethylamine (TMA), which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous TMA to nonodorous TMA N-oxide (TMAO), which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria (TMAU). Affected individuals cannot produce TMAO and, consequently, excrete large amounts of TMA. A dysbiosis in gut bacteria can give rise to secondary TMAU. Recently, there has been much interest in FMO3 and its catalytic product, TMAO, because TMAO has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport, and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to TMA, the gut bacteria involved in the production of TMA from dietary precursors, the metabolic reactions by which bacteria produce and use TMA, and the enzymes that catalyze the reactions. Also included is information on bacteria that produce TMA in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the TMA/TMAO microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of TMA, the involvement of TMAO and FMO3 in disease, and the implications of the host-microbiome axis for management of TMAU. PMID:27190056

Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children.

PubMed

The, Hao Chung; Florez de Sessions, Paola; Jie, Song; Pham Thanh, Duy; Thompson, Corinne N; Nguyen Ngoc Minh, Chau; Chu, Collins Wenhan; Tran, Tuan-Anh; Thomson, Nicholas R; Thwaites, Guy E; Rabaa, Maia A; Hibberd, Martin; Baker, Stephen

2018-01-02

Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.

The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation

PubMed Central

Abusleme, Loreto; Dupuy, Amanda K; Dutzan, Nicolás; Silva, Nora; Burleson, Joseph A; Strausbaugh, Linda D; Gamonal, Jorge; Diaz, Patricia I

2013-01-01

The goals of this study were to better understand the ecology of oral subgingival communities in health and periodontitis and elucidate the relationship between inflammation and the subgingival microbiome. Accordingly, we used 454-pyrosequencing of 16S rRNA gene libraries and quantitative PCR to characterize the subgingival microbiome of 22 subjects with chronic periodontitis. Each subject was sampled at two sites with similar periodontal destruction but differing in the presence of bleeding, a clinical indicator of increased inflammation. Communities in periodontitis were also compared with those from 10 healthy individuals. In periodontitis, presence of bleeding was not associated with different α-diversity or with a distinct microbiome, however, bleeding sites showed higher total bacterial load. In contrast, communities in health and periodontitis largely differed, with higher diversity and biomass in periodontitis. Shifts in community structure from health to periodontitis resembled ecological succession, with emergence of newly dominant taxa in periodontitis without replacement of primary health-associated species. That is, periodontitis communities had higher proportions of Spirochetes, Synergistetes, Firmicutes and Chloroflexi, among other taxa, while the proportions of Actinobacteria, particularly Actinomyces, were higher in health. Total Actinomyces load, however, remained constant from health to periodontitis. Moreover, an association existed between biomass and community structure in periodontitis, with the proportion of specific taxa correlating with bacterial load. Our study provides a global-scale framework for the ecological events in subgingival communities that underline the development of periodontitis. The association, in periodontitis, between inflammation, community biomass and community structure and their role in disease progression warrant further investigation. PMID:23303375

Host-Microbiome Cross-talk in Oral Mucositis

PubMed Central

Vasconcelos, R.M.; Sanfilippo, N.; Paster, B.J.; Kerr, A.R.; Li, Y.; Ramalho, L.; Queiroz, E.L.; Smith, B.; Sonis, S.T.; Corby, P.M.

2016-01-01

Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen–related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention. PMID:27053118

The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay

PubMed Central

Yilmaz, Özlem

2009-01-01

The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues. PMID:18832296

The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplay.

PubMed

Yilmaz, Ozlem

2008-10-01

The microbiota of the human oral mucosa consists of a myriad of bacterial species that normally exist in commensal harmony with the host. Porphyromonas gingivalis, an aetiological agent in severe forms of periodontitis (a chronic inflammatory disease), is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. This Gram-negative anaerobe can also exist within the host epithelium without the existence of overt disease. Gingival epithelial cells, the outer lining of the gingival mucosa, which function as an important part of the innate immune system, are among the first host cells colonized by P. gingivalis. This review describes recent studies implicating the co-existence and intracellular adaptation of the organism in these target host cells. Specifically, recent findings on the putative mechanisms of persistence, intercellular dissemination and opportunism are highlighted. These new findings may also represent an original and valuable model for mechanistic characterization of other successful host-adapted, self-limiting, persistent intracellular bacteria in human epithelial tissues.

Chemokine Function in Periodontal Disease and Oral Cavity Cancer

PubMed Central

Sahingur, Sinem Esra; Yeudall, W. Andrew

2015-01-01

The chemotactic cytokines, or chemokines, comprise a superfamily of polypeptides with a wide range of activities that include recruitment of immune cells to sites of infection and inflammation, as well as stimulation of cell proliferation. As such, they function as antimicrobial molecules and play a central role in host defenses against pathogen challenge. However, their ability to recruit leukocytes and potentiate or prolong the inflammatory response may have profound implications for the progression of oral diseases such as chronic periodontitis, where tissue destruction may be widespread. Moreover, it is increasingly recognized that chronic inflammation is a key component of tumor progression. Interaction between cancer cells and their microenvironment is mediated in large part by secreted factors such as chemokines, and serves to enhance the malignant phenotype in oral and other cancers. In this article, we will outline the biological and biochemical mechanisms of chemokine action in host–microbiome interactions in periodontal disease and in oral cancer, and how these may overlap and contribute to pathogenesis. PMID:25999952

Evidence to Support Tooth Brushing in Critically Ill Patients

PubMed Central

Ames, Nancy J.

2012-01-01

Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully. PMID:21532045

Evidence to support tooth brushing in critically ill patients.

PubMed

Ames, Nancy J

2011-05-01

Tooth brushing in critically ill patients has been advocated by many as a standard of care despite the limited evidence to support this practice. Attention has been focused on oral care as the evidence accumulates to support an association between the bacteria in the oral microbiome and those respiratory pathogens that cause pneumonia. It is plausible to assume that respiratory pathogens originating in the oral cavity are aspirated into the lungs, causing infection. A recent study of the effects of a powered toothbrush on the incidence of ventilator-associated pneumonia was stopped early because of a lack of effect in the treatment group. This review summarizes the evidence that supports the effectiveness of tooth brushing in critically ill adults and children receiving mechanical ventilation. Possible reasons for the lack of benefit of tooth brushing demonstrated in clinical trials are discussed. Recommendations for future trials in critically ill patients are suggested. With increased emphasis being placed on oral care, the evidence that supports this intervention must be evaluated carefully.

Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections.

PubMed

Zawadzki, Paweł J; Perkowski, Konrad; Padzik, Marcin; Mierzwińska-Nastalska, Elżbieta; Szaflik, Jacek P; Conn, David Bruce; Chomicz, Lidia

2017-01-01

The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

Cultivable Anaerobic Microbiota of Severe Early Childhood Caries▿¶

PubMed Central

Tanner, A. C. R.; Mathney, J. M. J.; Kent, R. L.; Chalmers, N. I.; Hughes, C. V.; Loo, C. Y.; Pradhan, N.; Kanasi, E.; Hwang, J.; Dahlan, M. A.; Papadopolou, E.; Dewhirst, F. E.

2011-01-01

Severe early childhood caries (ECC), while strongly associated with Streptococcus mutans using selective detection (culture, PCR), has also been associated with a widely diverse microbiota using molecular cloning approaches. The aim of this study was to evaluate the microbiota of severe ECC using anaerobic culture. The microbial composition of dental plaque from 42 severe ECC children was compared with that of 40 caries-free children. Bacterial samples were cultured anaerobically on blood and acid (pH 5) agars. Isolates were purified, and partial sequences for the 16S rRNA gene were obtained from 5,608 isolates. Sequence-based analysis of the 16S rRNA isolate libraries from blood and acid agars of severe ECC and caries-free children had >90% population coverage, with greater diversity occurring in the blood isolate library. Isolate sequences were compared with taxon sequences in the Human Oral Microbiome Database (HOMD), and 198 HOMD taxa were identified, including 45 previously uncultivated taxa, 29 extended HOMD taxa, and 45 potential novel groups. The major species associated with severe ECC included Streptococcus mutans, Scardovia wiggsiae, Veillonella parvula, Streptococcus cristatus, and Actinomyces gerensceriae. S. wiggsiae was significantly associated with severe ECC children in the presence and absence of S. mutans detection. We conclude that anaerobic culture detected as wide a diversity of species in ECC as that observed using cloning approaches. Culture coupled with 16S rRNA identification identified over 74 isolates for human oral taxa without previously cultivated representatives. The major caries-associated species were S. mutans and S. wiggsiae, the latter of which is a candidate as a newly recognized caries pathogen. PMID:21289150

The dormant blood microbiome in chronic, inflammatory diseases.

PubMed

Potgieter, Marnie; Bester, Janette; Kell, Douglas B; Pretorius, Etheresia

2015-07-01

Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as 'dysbiosis'). Another source is microbes translocated from the oral cavity. 'Dysbiosis' is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term 'atopobiosis' for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. © FEMS 2015.

Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis.

PubMed

Sandhya, Pulukool; Danda, Debashish; Sharma, Disha; Scaria, Vinod

2016-01-01

The human body is an environmental niche which is home to diverse co-habiting microbes collectively referred as the human microbiome. Recent years have seen the in-depth characterization of the human microbiome and associations with diseases. Linking of the composition or number of the human microbiota with diseases and traits date back to the original work of Elie Metchnikoff. Recent advances in genomic technologies have opened up finer details and dynamics of this new science with higher precision. Microbe-rheumatoid arthritis connection, largely related to the gut and oral microbiomes, has showed up as a result - apart from several other earlier, well-studied candidate autoimmune diseases. Although evidence favouring roles of specific microbial species, including Porphyromonas, Prevotella and Leptotricha, has become clearer, mechanistic insights still continue to be enigmatic. Manipulating the microbes by traditional dietary modifications, probiotics, and antibiotics and by currently employed disease-modifying agents seems to modulate the disease process and its progression. In the present review, we appraise the existing information as well as the gaps in knowledge in this challenging field. We also discuss the future directions for potential clinical applications, including prevention and management of rheumatoid arthritis using microbial modifications. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Illumina MiSeq Sequencing for Preliminary Analysis of Microbiome Causing Primary Endodontic Infections in Egypt

PubMed Central

Azab, Marwa Mohamed; Fayyad, Dalia Mukhtar

2018-01-01

The use of high throughput next generation technologies has allowed more comprehensive analysis than traditional Sanger sequencing. The specific aim of this study was to investigate the microbial diversity of primary endodontic infections using Illumina MiSeq sequencing platform in Egyptian patients. Samples were collected from 19 patients in Suez Canal University Hospital (Endodontic Department) using sterile # 15K file and paper points. DNA was extracted using Mo Bio power soil DNA isolation extraction kit followed by PCR amplification and agarose gel electrophoresis. The microbiome was characterized on the basis of the V3 and V4 hypervariable region of the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device. MOTHUR software was used in sequence filtration and analysis of sequenced data. A total of 1858 operational taxonomic units at 97% similarity were assigned to 26 phyla, 245 families, and 705 genera. Four main phyla Firmicutes, Bacteroidetes, Proteobacteria, and Synergistetes were predominant in all samples. At genus level, Prevotella, Bacillus, Porphyromonas, Streptococcus, and Bacteroides were the most abundant. Illumina MiSeq platform sequencing can be used to investigate oral microbiome composition of endodontic infections. Elucidating the ecology of endodontic infections is a necessary step in developing effective intracanal antimicrobials. PMID:29849646

The dormant blood microbiome in chronic, inflammatory diseases

PubMed Central

Potgieter, Marnie; Bester, Janette; Kell, Douglas B.; Pretorius, Etheresia

2015-01-01

Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. PMID:25940667

Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line

PubMed Central

How, Kah Yan; Song, Keang Peng; Chan, Kok Gan

2016-01-01

Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity. PMID:26903954

Review: Pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction.

PubMed

Santoro, Domenico; Marsella, Rosanna; Pucheu-Haston, Cherie M; Eisenschenk, Melissa N C; Nuttall, Tim; Bizikova, Petra

2015-04-01

Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The pathogenesis of canine AD is incompletely understood. The aim of this review is to provide an in-depth update on the involvement of skin barrier and host-microbiome interaction in the pathogenesis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to skin barrier and host-microbiome interaction (e.g. bacteria, yeast, antimicrobial peptides). A total of 126 publications were identified. This review article focuses on epidermal barrier dysfunction and the interaction between cutaneous microbes (bacteria and yeasts) and the host (antimicrobial peptides). Epidemiological updates on the presence of pathogenic organisms and canine AD are also provided. Major advances have been made in the investigation of skin barrier dysfunction in canine AD, although many questions still remain. Skin barrier dysfunction and host-microbiome interactions are emerging as primary alterations in canine AD. Based on this review, it is clear that future studies focused on the development of drugs able to restore the skin barrier and increase the natural defences against pathogenic organisms are needed. © 2015 ESVD and ACVD.

Determining the culturability of the rumen bacterial microbiome

PubMed Central

Creevey, Christopher J; Kelly, William J; Henderson, Gemma; Leahy, Sinead C

2014-01-01

The goal of the Hungate1000 project is to generate a reference set of rumen microbial genome sequences. Toward this goal we have carried out a meta-analysis using information from culture collections, scientific literature, and the NCBI and RDP databases and linked this with a comparative study of several rumen 16S rRNA gene-based surveys. In this way we have attempted to capture a snapshot of rumen bacterial diversity to examine the culturable fraction of the rumen bacterial microbiome. Our analyses have revealed that for cultured rumen bacteria, there are many genera without a reference genome sequence. Our examination of culture-independent studies highlights that there are few novel but many uncultured taxa within the rumen bacterial microbiome. Taken together these results have allowed us to compile a list of cultured rumen isolates that are representative of abundant, novel and core bacterial species in the rumen. In addition, we have identified taxa, particularly within the phylum Bacteroidetes, where further cultivation efforts are clearly required. This information is being used to guide the isolation efforts and selection of bacteria from the rumen microbiota for sequencing through the Hungate1000. PMID:24986151

Periodontal disease and breast cancer: Prospective cohort study of postmenopausal women

PubMed Central

Freudenheim, Jo L; Genco, Robert J; LaMonte, Michael J; Millen, Amy E; Hovey, Kathleen M; Mai, Xiaodan; Nwizu, Ngozi; Andrews, Christopher A; Wactawski-Wende, Jean

2015-01-01

Background Periodontal disease (PD) has been consistently associated with chronic disease; there are no large studies of breast cancer although oral-associated microbes are present in breast tumors. Methods In the Women’s Health Initiative Observational Study, a prospective cohort of postmenopausal women, 73,737 women without previous breast cancer were followed. Incident, primary, invasive breast tumors were verified by physician adjudication. PD was by self-report. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards, adjusted for breast cancer risk factors. Because the oral microbiome of those with PD differs with smoking status, we examined associations stratified by smoking. Results 2,124 incident, invasive breast cancer cases were identified after mean follow-up of 6.7 years. PD, reported by 26.1% of women, was associated with increased breast cancer risk (HR 1.14, 95% CI 1.03 to 1.26), particularly among former smokers who quit within 20 years (HR 1.36; 95% CI 1.05 to 1.77). Among current smokers, the trend was similar (HR 1.32; 95% CI 0.83 to 2.11); there were few cases (n=74) and the CI included the null. The population attributable fraction was 12.06% (95% CI 1.12 to 21.79) and 10.90% (95% CI 10.31 to 28.94) for PD among former smokers quitting within 20 years and current smokers, respectively. Conclusion PD, a common chronic inflammatory disorder, was associated with increased risk of postmenopausal breast cancer, particularly among former smokers who quit in the past 20 years. Impact Understanding a possible role of the oral microbiome in breast carcinogenesis could impact prevention. PMID:26689418

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism

PubMed Central

Oancea, I; Movva, R; Das, I; Aguirre de Cárcer, D; Schreiber, V; Yang, Y; Purdon, A; Harrington, B; Proctor, M; Wang, R; Sheng, Y; Lobb, M; Lourie, R; Ó Cuív, P; Duley, J A; Begun, J; Florin, T H J

2017-01-01

Objective Mercaptopurine (MP) and pro-drug azathioprine are ‘first-line’ oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). Design C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. Results Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt−/− fibroblast cell lines and augmented epithelial intracellular bacterial killing. Conclusions Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation. PMID:27411368

The microbiome in PTEN hamartoma tumor syndrome.

PubMed

Byrd, Victoria; Getz, Ted; Padmanabhan, Roshan; Arora, Hans; Eng, Charis

2018-03-01

Germline PTEN mutations defining PTEN hamartoma tumor syndrome (PHTS) confer heritable predisposition to breast, endometrial, thyroid and other cancers with known age-related risks, but it remains impossible to predict if any individual will develop cancer. In the general population, gut microbial dysbiosis has been linked to cancer, yet is unclear whether these are associated in PHTS patients. In this pilot study, we aimed to characterize microbial composition of stool, urine, and oral wash from 32 PTEN mutation-positive individuals using 16S rRNA gene sequencing. PCoA revealed clustering of the fecal microbiome by cancer history ( P  = 0.03, R 2  = 0.04). Fecal samples from PHTS cancer patients had relatively more abundant operational taxonomic units (OTUs) from family Rikenellaceae and unclassified members of Clostridia compared to those from non-cancer patients, whereas families Peptostreptococcaceae, Enterobacteriaceae, and Bifidobacteriaceae represented relatively more abundant OTUs among fecal samples from PHTS non-cancer patients. Functional metagenomic prediction revealed enrichment of the folate biosynthesis, genetic information processing and cell growth and death pathways among fecal samples from PHTS cancer patients compared to non-cancer patients. We found no major shifts in overall diversity and no clustering by cancer history among oral wash or urine samples. Our observations suggest the utility of an expanded study to interrogate gut dysbiosis as a potential cancer risk modifier in PHTS patients. © 2018 The authors.

Co-occurrence of anaerobic bacteria in colorectal carcinomas.

PubMed

Warren, René L; Freeman, Douglas J; Pleasance, Stephen; Watson, Peter; Moore, Richard A; Cochrane, Kyla; Allen-Vercoe, Emma; Holt, Robert A

2013-05-15

Numerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic studies have shown an association between Fusobacterium species and colorectal carcinoma. Here, we have extended these studies with deeper sequencing of a much larger number (n = 130) of colorectal carcinoma and matched normal control tissues. We analyzed these data using co-occurrence networks in order to identify microbe-microbe and host-microbe associations specific to tumors. We confirmed tumor over-representation of Fusobacterium species and observed significant co-occurrence within individual tumors of Fusobacterium, Leptotrichia and Campylobacter species. This polymicrobial signature was associated with over-expression of numerous host genes, including the gene encoding the pro-inflammatory chemokine Interleukin-8. The tumor-associated bacteria we have identified are all Gram-negative anaerobes, recognized previously as constituents of the oral microbiome, which are capable of causing infection. We isolated a novel strain of Campylobacter showae from a colorectal tumor specimen. This strain is substantially diverged from a previously sequenced oral Campylobacter showae isolate, carries potential virulence genes, and aggregates with a previously isolated tumor strain of Fusobacterium nucleatum. A polymicrobial signature of Gram-negative anaerobic bacteria is associated with colorectal carcinoma tissue.

Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis

PubMed Central

Armingohar, Zahra; Jørgensen, Jørgen J.; Kristoffersen, Anne Karin; Abesha-Belay, Emnet; Olsen, Ingar

2014-01-01

Background Several studies have reported an association between chronic periodontitis (CP) and cardiovascular diseases. Detection of periodontopathogens, including red complex bacteria (RCB), in vascular lesions has suggested these bacteria to be involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysms. Objective In this study, we investigate bacteria and their DNA in vascular biopsies from patients with vascular diseases (VD; i.e. abdominal aortic aneurysms, atherosclerotic carotid, and common femoral arteries), with and without CP. Methods DNA was extracted from vascular biopsies selected from 40 VD patients: 30 with CP and 10 without CP. The V3-V5 region of the 16S rDNA (V3-V5) was polymerase chain reaction (PCR)-amplified, and the amplicons were cloned into Escherichia coli, sequenced, and classified (GenBank and the Human Oral Microbiome database). Species-specific primers were used for the detection of Porphyromonas gingivalis. In addition, 10 randomly selected vascular biopsies from the CP group were subjected to scanning electron microscopy (SEM) for visualization of bacteria. Checkerboard DNA–DNA hybridization was performed to assess the presence of RCB in 10 randomly selected subgingival plaque samples from CP patients. Results A higher load and mean diversity of bacteria were detected in vascular biopsies from VD patients with CP compared to those without CP. Enterobacteriaceae were frequently detected in vascular biopsies together with cultivable, commensal oral, and not-yet-cultured bacterial species. While 70% of the subgingival plaque samples from CP patients showed presence of RCB, only P. gingivalis was detected in one vascular biopsy. Bacterial cells were seen in all 10 vascular biopsies examined by SEM. Conclusions A higher bacterial load and more diverse colonization were detected in VD lesions of CP patients as compared to patients without CP. This indicated that a multitude of bacterial species both from the gut and the oral cavity, rather than exclusively periodontopathogens, may be involved as additional risk factors in the pathogenesis of VD. PMID:25006361

What could you do with 400 years of biological history on african americans? Evaluating the potential scientific benefit of systematic studies of dental and skeletal materials on African Americans from the 17th through 20th centuries.

PubMed

Jackson, Fatimah; Jackson, Latifa; Cross, Christopher; Clarke, Cameron

2016-07-01

How important is it to be able to reconstruct the lives of a highly diverse, historically recent macroethnic group over the course of 400 years? How many insights into human evolutionary biology and disease susceptibilities could be gained, even with this relatively recent window into the past? In this article, we explore the potential ramifications of a newly constructed dataset of Four Centuries of African American Biological Variation (4Cs). This article provides initial lists of digitized variables formatted as SQL tables for the 17th and 18th century samples and for the 19th and 20th century samples. This database is dynamic and new information is added yearly. The database provides novel opportunities for significant insights into the past biological history of this group and three case study applications are detailed for comparative computational systems biology studies of (1) hypertension, (2) the oral microbiome, and (3) mental health disorders. The 4Cs dataset is ideal for interdisciplinary "next generation" science research and these data represent a unique step toward the accumulation of historically contextualized Big Data on an underrepresented group known to have experienced differential survival over time. Am. J. Hum. Biol. 28:510-513, 2016. © 2016 The Authors American Journal of Human Biology Published byWiley Periodicals, Inc. © 2016 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.

Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges.

PubMed

Deng, Ping; Swanson, Kelly S

2015-01-01

High-throughput DNA sequencing techniques allow for the identification and characterisation of microbes and their genes (microbiome). Using these new techniques, microbial populations in several niches of the human body, including the oral and nasal cavities, skin, urogenital tract and gastrointestinal tract, have been described recently. Very little data on the microbiome of companion animals exist, and most of the data have been derived from the analysis of the faeces of healthy laboratory animals. High-throughput assays provide opportunities to study the complex and dense populations of the gut microbiota, including bacteria, archaea, fungi, protozoa and viruses. Our laboratory and others have recently described the predominant microbial taxa and genes of healthy dogs and cats and how these respond to dietary interventions. In general, faecal microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) and functional capacity (e.g. major functional groups related to carbohydrate, protein, DNA and vitamin metabolism; virulence factors; and cell wall and capsule) of the canine and feline gut are similar to those of the human gut. Initial sequencing projects have provided a glimpse of the microbial super-organism that exists within the canine and feline gut, but leaves much to be explored and discovered. As DNA provides information only about potential functions, studies that focus on the microbial transcriptome, metabolite profiles, and how microbiome changes affect host physiology and health are clearly required. Future studies must determine how diet composition, antibiotics and other drug therapies, breed and disease affect or are affected by the gut microbiome and how this information may be used to improve diets, identify disease biomarkers and develop targeted disease therapies.

CRISPR-Cas systems target a diverse collection of invasive mobile genetic elements in human microbiomes

PubMed Central

2013-01-01

Background Bacteria and archaea develop immunity against invading genomes by incorporating pieces of the invaders' sequences, called spacers, into a clustered regularly interspaced short palindromic repeats (CRISPR) locus between repeats, forming arrays of repeat-spacer units. When spacers are expressed, they direct CRISPR-associated (Cas) proteins to silence complementary invading DNA. In order to characterize the invaders of human microbiomes, we use spacers from CRISPR arrays that we had previously assembled from shotgun metagenomic datasets, and identify contigs that contain these spacers' targets. Results We discover 95,000 contigs that are putative invasive mobile genetic elements, some targeted by hundreds of CRISPR spacers. We find that oral sites in healthy human populations have a much greater variety of mobile genetic elements than stool samples. Mobile genetic elements carry genes encoding diverse functions: only 7% of the mobile genetic elements are similar to known phages or plasmids, although a much greater proportion contain phage- or plasmid-related genes. A small number of contigs share similarity with known integrative and conjugative elements, providing the first examples of CRISPR defenses against this class of element. We provide detailed analyses of a few large mobile genetic elements of various types, and a relative abundance analysis of mobile genetic elements and putative hosts, exploring the dynamic activities of mobile genetic elements in human microbiomes. A joint analysis of mobile genetic elements and CRISPRs shows that protospacer-adjacent motifs drive their interaction network; however, some CRISPR-Cas systems target mobile genetic elements lacking motifs. Conclusions We identify a large collection of invasive mobile genetic elements in human microbiomes, an important resource for further study of the interaction between the CRISPR-Cas immune system and invaders. PMID:23628424

Metabolomics evaluation of the impact of smokeless tobacco exposure on the oral bacterium Capnocytophaga sputigena

PubMed Central

Sun, Jinchun; Jin, Jinshan; Beger, Richard D.; Cerniglia, Carl E.; Yang, Maocheng; Chen, Huizhong

2017-01-01

The association between exposure to smokeless tobacco products (STP) and oral diseases is partially due to the physiological and pathological changes in the composition of the oral microbiome and its metabolic profile. However, it is not clear how STPs affect the physiology and ecology of oral microbiota. A UPLC/QTof-MS-based metabolomics study was employed to analyze metabolic alterations in oral bacterium, Capnocytophaga sputigena as a result of smokeless tobacco exposure and to assess the capability of the bacterium to metabolize nicotine. Pathway analysis of the metabolome profiles indicated that smokeless tobacco extracts caused oxidative stress in the bacterium. The metabolomics data also showed that the argininenitric oxide pathway was perturbed by the smokeless tobacco treatment. Results also showed that LC/MS was useful in identifying STP constituents and additives, including caffeine and many flavoring compounds. No significant changes in levels of nicotine and its major metabolites were found when C. sputigena was cultured in a nutrient rich medium, although hydroxylnicotine and cotinine N-oxide were detected in the bacterial metabolites suggesting that nicotine metabolism might be present as a minor degradation pathway in the bacterium. Study results provide new insights regarding the physiological and toxicological effects of smokeless tobacco on oral bacterium C. sputigena and associated oral health as well as measuring the ability of the oral bacterium to metabolize nicotine. PMID:27480511

Metabolomics evaluation of the impact of smokeless tobacco exposure on the oral bacterium Capnocytophaga sputigena.

PubMed

Sun, Jinchun; Jin, Jinshan; Beger, Richard D; Cerniglia, Carl E; Yang, Maocheng; Chen, Huizhong

2016-10-01

The association between exposure to smokeless tobacco products (STP) and oral diseases is partially due to the physiological and pathological changes in the composition of the oral microbiome and its metabolic profile. However, it is not clear how STPs affect the physiology and ecology of oral microbiota. A UPLC/QTof-MS-based metabolomics study was employed to analyze metabolic alterations in oral bacterium, Capnocytophaga sputigena as a result of smokeless tobacco exposure and to assess the capability of the bacterium to metabolize nicotine. Pathway analysis of the metabolome profiles indicated that smokeless tobacco extracts caused oxidative stress in the bacterium. The metabolomics data also showed that the arginine-nitric oxide pathway was perturbed by the smokeless tobacco treatment. Results also showed that LC/MS was useful in identifying STP constituents and additives, including caffeine and many flavoring compounds. No significant changes in levels of nicotine and its major metabolites were found when C. sputigena was cultured in a nutrient rich medium, although hydroxylnicotine and cotinine N-oxide were detected in the bacterial metabolites suggesting that nicotine metabolism might be present as a minor degradation pathway in the bacterium. Study results provide new insights regarding the physiological and toxicological effects of smokeless tobacco on oral bacterium C. sputigena and associated oral health as well as measuring the ability of the oral bacterium to metabolize nicotine. Published by Elsevier Ltd.

Successional changes in the chicken cecal microbiome during 42 days of growth are independent of organic acid feed additives.

PubMed

Oakley, Brian B; Buhr, R Jeff; Ritz, Casey W; Kiepper, Brian H; Berrang, Mark E; Seal, Bruce S; Cox, Nelson A

2014-11-27

Poultry remains a major source of foodborne bacterial infections. A variety of additives with presumed anti-microbial and/or growth-promoting effects are commonly added to poultry feed during commercial grow-out, yet the effects of these additives on the gastrointestinal microbial community (the GI microbiome) as the bird matures remain largely unknown. Here we compared temporal changes in the cecal microbiome to the effects of formic acid, propionic acid, and medium-chain fatty acids (MCFA) added to feed and/or drinking water. Cecal bacterial communities at day of hatch (n = 5 birds), 7d (n = 32), 21d (n = 27), and 42d (n = 36) post-hatch were surveyed using direct 454 sequencing of 16S rRNA gene amplicons from each bird in combination with cultivation-based recovery of a Salmonella Typhimurium marker strain and quantitative-PCR targeting Clostridium perfringens. Treatment effects on specific pathogens were generally non-significant. S. Typhimurium introduced by oral gavage at day of hatch was recovered by cultivation from nearly all birds sampled across treatments at 7d and 21d, but by 42d, S. Typhimurium was only recovered from ca. 25% of birds, regardless of treatment. Sequencing data also revealed non-significant treatment effects on genera containing known pathogens and on the cecal microbiome as a whole. In contrast, temporal changes in the cecal microbiome were dramatic, highly significant, and consistent across treatments. At 7d, the cecal community was dominated by three genera (Flavonifractor, Pseudoflavonifractor, and a Lachnospiracea sequence type) that accounted for more than half of sequences. By 21d post-hatch, a single genus (Faecalibacterium) accounted for 23-55% of sequences, and the number of Clostridium 16S rRNA gene copies detected by quantitative-PCR reached a maximum. Over the 42 d experiment, the cecal bacterial community changed significantly as measured by a variety of ecological metrics and increases in the complexity of co-occurrence networks. Management of poultry to improve animal health, nutrition, or food safety may need to consider the interactive effects of any treatments with the dramatic temporal shifts in the taxonomic composition of the cecal microbiome as described here.

Towards understanding oral health.

PubMed

Zaura, Egija; ten Cate, Jacob M

2015-01-01

During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term 'oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain microbial community stability in health. However, the oral ecosystem itself is not stable: throughout life an individual undergoes multiple physiological changes while progressing through infancy, childhood, adolescence, adulthood and old age. Recent discussions on the definition of general health have led to the proposal that health is the ability of the individual to adapt to physiological changes, a condition known as allostasis. In this paper the allostasis principle is applied to the oral ecosystem. The multidimensionality of the host factors contributing to allostasis in the oral cavity is illustrated with an example on changes occurring in puberty. The complex phenomenon of oral health and the processes that prevent the ecosystem from collapsing during allostatic changes in the entire body are far from being understood. As yet individual components (e.g. hard tissues, microbiome, saliva, host response) have been investigated, while only by consolidating these and assessing their multidimensional interactions should we be able to obtain a comprehensive understanding of the ecosystem, which in turn could serve to develop rational schemes to maintain health. Adapting such a 'system approach' comes with major practical challenges for the entire research field and will require vast resources and large-scale multidisciplinary collaborations. 2015 S. Karger AG, Basel

Hearing impairment associated with oral terbinafine use: a case series and case/non-case analysis in the Netherlands Pharmacovigilance Centre Lareb database and VigiBase™.

PubMed

Scholl, Joep H G; van Puijenbroek, Eugene P

2012-08-01

The Netherlands Pharmacovigilance Centre Lareb received reports of six cases of hearing impairment in association with oral terbinafine use. This study describes these cases and provides support for this association from the Lareb database for spontaneous adverse drug reaction (ADR) reporting and from Vigibase™, the ADR database of the WHO Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre. The objective of the current study was to identify whether the observed association between oral terbinafine use and hearing impairment, based on cases received by Lareb, constitutes a safety signal. Cases of hearing impairment in oral terbinafine users are described. In a case/non-case analysis, the strength of the association in Vigibase™ and the Lareb database was determined (date of analysis August 2011) by calculating the reporting odds ratios (RORs), adjusted for possible confounding by age, sex and ototoxic concomitant medication. For the purpose of this study, RORs were calculated for deafness, hypoacusis and the combination of both, defined as hearing impairment. In the Lareb database, six reports concerning individuals aged 31-82 years, who developed hearing impairment after starting oral terbinafine, were present. The use of oral terbinafine was disproportionally associated with hypoacusis in both the Lareb database (adjusted ROR 3.9; 95% CI 1.7, 9.0) and in Vigibase™ (adjusted ROR 1.7; 95% CI 1.0, 2.8). Deafness was not disproportionally present in either of the databases. Based on the described cases and the statistical analyses from both databases, a causal relationship between the use of oral terbinafine and hearing impairment is possible. The mechanism by which terbinafine could cause hearing impairment has not been elucidated yet. The pharmacological action of terbinafine is based on the inhibition of squalene epoxidase, an enzyme present in both fungal and human cells. This inhibition might result in a decrease in cholesterol levels in human cells, among which are the outer hair cells of the cochlea. It may be possible that the reduction in cochlear cholesterol levels leads to impaired cochlear function and possibly hearing impairment. In this study we describe hearing impairment as a possible ADR of oral terbinafine, based on six case reports and statistical support from Vigibase™ and the Lareb database. To our knowledge this association has not been described before.

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications.

PubMed

Baba, Yoshifumi; Iwatsuki, Masaaki; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

2017-06-01

Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum , which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

Microbial Community Profiling of Human Saliva Using Shotgun Metagenomic Sequencing

PubMed Central

Hasan, Nur A.; Young, Brian A.; Minard-Smith, Angela T.; Saeed, Kelly; Li, Huai; Heizer, Esley M.; McMillan, Nancy J.; Isom, Richard; Abdullah, Abdul Shakur; Bornman, Daniel M.; Faith, Seth A.; Choi, Seon Young; Dickens, Michael L.; Cebula, Thomas A.; Colwell, Rita R.

2014-01-01

Human saliva is clinically informative of both oral and general health. Since next generation shotgun sequencing (NGS) is now widely used to identify and quantify bacteria, we investigated the bacterial flora of saliva microbiomes of two healthy volunteers and five datasets from the Human Microbiome Project, along with a control dataset containing short NGS reads from bacterial species representative of the bacterial flora of human saliva. GENIUS, a system designed to identify and quantify bacterial species using unassembled short NGS reads was used to identify the bacterial species comprising the microbiomes of the saliva samples and datasets. Results, achieved within minutes and at greater than 90% accuracy, showed more than 175 bacterial species comprised the bacterial flora of human saliva, including bacteria known to be commensal human flora but also Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Gamma proteobacteria. Basic Local Alignment Search Tool (BLASTn) analysis in parallel, reported ca. five times more species than those actually comprising the in silico sample. Both GENIUSand BLAST analyses of saliva samples identified major genera comprising the bacterial flora of saliva, but GENIUS provided a more precise description of species composition, identifying to strain in most cases and delivered results at least 10,000 times faster. Therefore, GENIUS offers a facile and accurate system for identification and quantification of bacterial species and/or strains in metagenomic samples. PMID:24846174

Gut microbiome and liver diseases.

PubMed

Tilg, Herbert; Cani, Patrice D; Mayer, Emeran A

2016-12-01

The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell types. Whereas few results from clinical metagenomic studies in liver disease are available, evidence is accumulating that in liver cirrhosis an oral microbiome is overrepresented in the lower intestinal tract, potentially contributing to disease process and severity. A major role for the gut microbiota in liver disorders is also supported by the accumulating evidence that several complications of severe liver disease such as hepatic encephalopathy are efficiently treated by various prebiotics, probiotics and antibiotics. A better understanding of the gut microbiota and its components in liver diseases might provide a more complete picture of these complex disorders and also form the basis for novel therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review.

PubMed

Paganini, Daniela; Zimmermann, Michael B

2017-12-01

In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA) is common, and many complementary foods are low in bioavailable iron. In-home fortification of complementary foods using iron-containing micronutrient powders (MNPs) and oral iron supplementation are both effective strategies to increase iron intakes and reduce IDA at this age. However, these interventions produce large increases in colonic iron because the absorption of their high iron dose (≥12.5 mg) is typically <20%. We reviewed studies in infants and young children on the effects of iron supplements and iron fortification with MNPs on the gut microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly increase diarrhea risk, and in vitro and in vivo studies have suggested that this occurs because increases in colonic iron adversely affect the gut microbiome in that they decrease abundances of beneficial barrier commensal gut bacteria (e.g., bifidobacteria and lactobacilli) and increase the abundance of enterobacteria including entropathogenic Escherichia coli These changes are associated with increased gut inflammation. Therefore, safer formulations of iron-containing supplements and MNPs are needed. To improve MNP safety, the iron dose of these formulations should be reduced while maximizing absorption to retain efficacy. Also, the addition of prebiotics to MNPs is a promising approach to mitigate the adverse effects of iron on the infant gut. © 2017 American Society for Nutrition.

Three distinct pneumotypes characterize the microbiome of the lung in BALB/cJ mice.

PubMed

Scheiermann, Julia; Klinman, Dennis M

2017-01-01

Bacteria can rarely be isolated from normal healthy lungs using conventional culture techniques, supporting the traditional belief that the lungs are sterile. Yet recent studies using next generation sequencing report that bacterial DNA commonly found in the upper respiratory tract (URT) is present at lower levels in the lungs. Interpretation of that finding is complicated by the technical limitations and potential for contamination introduced when dealing with low biomass samples. The current work sought to overcome those limitations to clarify the number, type and source of bacteria present in the lungs of normal mice. Results showed that the oral microbiome is diverse and highly conserved whereas murine lung samples fall into three distinct patterns. 33% of the samples were sterile, as they lacked culturable bacteria and their bacterial DNA content did not differ from background. 9% of samples contained comparatively higher amounts of bacterial DNA whose composition mimicked that detected in the URT. A final group (58%) contained smaller amounts of microbial DNA whose composition was correlating to that of rodent chow and cage bedding, likely acquired by inspiration of food and bedding fragments. By analyzing each sample independently rather than working with group averages, this work eliminated the bias introduced by aspiration-contaminated samples to establish that three distinct microbiome pneumotypes are present in normal murine lungs.

Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association.

PubMed

Atanasova, K R; Yilmaz, O

2014-04-01

The past decades of biomedical research have yielded massive evidence for the contribution of the microbiome in the development of a variety of chronic human diseases. There is emerging evidence that Porphyromonas gingivalis, a well-adapted opportunistic pathogen of the oral mucosa and prominent constituent of oral biofilms, best known for its involvement in periodontitis, may be an important mediator in the development of a number of multifactorial and seemingly unrelated chronic diseases, such as rheumatoid arthritis and orodigestive cancers. Orodigestive cancers represent a large proportion of the total malignancies worldwide, and include cancers of the oral cavity, gastrointestinal tract and pancreas. For prevention and/or enhanced prognosis of these diseases, a good understanding of the pathophysiological mechanisms and the interaction between P. gingivalis and host is much needed. With this review, we introduce the currently accumulated knowledge on P. gingivalis's plausible association with cancer as a risk modifier, and present the putative cancer-promoting cellular and molecular mechanisms that this organism may influence in the oral mucosa. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BMPOS: a Flexible and User-Friendly Tool Sets for Microbiome Studies.

PubMed

Pylro, Victor S; Morais, Daniel K; de Oliveira, Francislon S; Dos Santos, Fausto G; Lemos, Leandro N; Oliveira, Guilherme; Roesch, Luiz F W

2016-08-01

Recent advances in science and technology are leading to a revision and re-orientation of methodologies, addressing old and current issues under a new perspective. Advances in next generation sequencing (NGS) are allowing comparative analysis of the abundance and diversity of whole microbial communities, generating a large amount of data and findings at a systems level. The current limitation for biologists has been the increasing demand for computational power and training required for processing of NGS data. Here, we describe the deployment of the Brazilian Microbiome Project Operating System (BMPOS), a flexible and user-friendly Linux distribution dedicated to microbiome studies. The Brazilian Microbiome Project (BMP) has developed data analyses pipelines for metagenomic studies (phylogenetic marker genes), conducted using the two main high-throughput sequencing platforms (Ion Torrent and Illumina MiSeq). The BMPOS is freely available and possesses the entire requirement of bioinformatics packages and databases to perform all the pipelines suggested by the BMP team. The BMPOS may be used as a bootable live USB stick or installed in any computer with at least 1 GHz CPU and 512 MB RAM, independent of the operating system previously installed. The BMPOS has proved to be effective for sequences processing, sequences clustering, alignment, taxonomic annotation, statistical analysis, and plotting of metagenomic data. The BMPOS has been used during several metagenomic analyses courses, being valuable as a tool for training, and an excellent starting point to anyone interested in performing metagenomic studies. The BMPOS and its documentation are available at http://www.brmicrobiome.org .

Glycemic Status Affects the Subgingival Microbiome of Diabetic Patients.

PubMed

Longo, Priscila Larcher; Dabdoub, Shareef; Kumar, Purnima; Artese, Hilana Paula Carillo; Dib, Sergio Atala; Romito, Giuseppe Alexandre; Mayer, Marcia Pinto Alves

2018-05-09

Periodontitis is correlated with type 2 diabetes mellitus (T2DM), but little is known about glycemic status effect on subgingival microbiota associated with periodontitis. This study evaluated if periodontal microbiome of T2DM patients is affected by glycemic status. 21 T2DM non-smoking patients with chronic periodontitis and body mass index ≤40kg/m 2 were allocated into two groups according to systemic glycemic status: inadequate (DMI- HbA1c≥8%) and adequate (DMA- HbA1c<7.8%). Subgingival biofilm was collected from sites with moderate (PD=4-6mm) and severe disease (PD≥7mm) in two quadrants. The V5-V6 hypervariable region of the 16SrRNA was sequenced using the GS-FLX-454Titanium platform. Sequences were compared to HOMD database using QIIME and PhyloToAST pipelines. Statistical comparisons were made using 2-sample t-tests. DMA microbiome presented higher diversity than DMI. Inadequate glycemic control favored fermenting species, especially those associated with propionate/succinate production, whereas those forming butyrate/pyruvate were decreased in DMI. Higher abundances of anginosus group and Streptococcus agalactiae in DMI may indicate that subgingival sites can be reservoir of potentially invasive pathogens. Altered subgingival microbiome in DMI may represent an additional challenge in the periodontal treatment of these patients and in the prevention of more invasive infections. Glycemic status in T2DM patients seems to modulate subgingival biofilm composition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis

PubMed Central

Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh

2015-01-01

Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer. PMID:25797243

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

PubMed

Mitsuhashi, Kei; Nosho, Katsuhiko; Sukawa, Yasutaka; Matsunaga, Yasutaka; Ito, Miki; Kurihara, Hiroyoshi; Kanno, Shinichi; Igarashi, Hisayoshi; Naito, Takafumi; Adachi, Yasushi; Tachibana, Mami; Tanuma, Tokuma; Maguchi, Hiroyuki; Shinohara, Toshiya; Hasegawa, Tadashi; Imamura, Masafumi; Kimura, Yasutoshi; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

2015-03-30

Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

Glycosyltransferase-mediated Sweet Modification in Oral Streptococci.

PubMed

Zhu, F; Zhang, H; Wu, H

2015-05-01

Bacterial glycosyltransferases play important roles in bacterial fitness and virulence. Oral streptococci have evolved diverse strategies to survive and thrive in the carbohydrate-rich oral cavity. In this review, we discuss 2 important biological processes mediated by 2 distinct groups of glycosyltransferases in oral streptococci that are important for bacterial colonization and virulence. The first process is the glycosylation of highly conserved serine-rich repeat adhesins by a series of glycosyltransferases. Using Streptococcus parasanguinis as a model, we highlight new features of several glycosyltransferases that sequentially modify the serine-rich glycoprotein Fap1. Distinct features of a novel glycosyltransferase fold from a domain of unknown function 1792 are contrasted with common properties of canonical glycosyltransferases. The second biological process we cover is involved in building sticky glucan matrix to establish cariogenic biofilms by an important opportunistic pathogen Streptococcus mutans through the action of a family of 3 glucosyltransferases. We focus on discussing the structural feature of this family as a glycoside hydrolase family of enzymes. While the 2 processes are distinct, they all produce carbohydrate-coated biomolecules, which enable bacteria to stick better in the complex oral microbiome. Understanding the making of the sweet modification presents a unique opportunity to develop novel antiadhesion and antibiofilm strategies to fight infections by oral streptococci and beyond. © International & American Associations for Dental Research 2015.

Glycosyltransferase-mediated Sweet Modification in Oral Streptococci

PubMed Central

Zhu, F.; Zhang, H.

2015-01-01

Bacterial glycosyltransferases play important roles in bacterial fitness and virulence. Oral streptococci have evolved diverse strategies to survive and thrive in the carbohydrate-rich oral cavity. In this review, we discuss 2 important biological processes mediated by 2 distinct groups of glycosyltransferases in oral streptococci that are important for bacterial colonization and virulence. The first process is the glycosylation of highly conserved serine-rich repeat adhesins by a series of glycosyltransferases. Using Streptococcus parasanguinis as a model, we highlight new features of several glycosyltransferases that sequentially modify the serine-rich glycoprotein Fap1. Distinct features of a novel glycosyltransferase fold from a domain of unknown function 1792 are contrasted with common properties of canonical glycosyltransferases. The second biological process we cover is involved in building sticky glucan matrix to establish cariogenic biofilms by an important opportunistic pathogen Streptococcus mutans through the action of a family of 3 glucosyltransferases. We focus on discussing the structural feature of this family as a glycoside hydrolase family of enzymes. While the 2 processes are distinct, they all produce carbohydrate-coated biomolecules, which enable bacteria to stick better in the complex oral microbiome. Understanding the making of the sweet modification presents a unique opportunity to develop novel antiadhesion and antibiofilm strategies to fight infections by oral streptococci and beyond. PMID:25755271

Disbiome database: linking the microbiome to disease.

PubMed

Janssens, Yorick; Nielandt, Joachim; Bronselaer, Antoon; Debunne, Nathan; Verbeke, Frederick; Wynendaele, Evelien; Van Immerseel, Filip; Vandewynckel, Yves-Paul; De Tré, Guy; De Spiegeleer, Bart

2018-06-04

Recent research has provided fascinating indications and evidence that the host health is linked to its microbial inhabitants. Due to the development of high-throughput sequencing technologies, more and more data covering microbial composition changes in different disease types are emerging. However, this information is dispersed over a wide variety of medical and biomedical disciplines. Disbiome is a database which collects and presents published microbiota-disease information in a standardized way. The diseases are classified using the MedDRA classification system and the micro-organisms are linked to their NCBI and SILVA taxonomy. Finally, each study included in the Disbiome database is assessed for its reporting quality using a standardized questionnaire. Disbiome is the first database giving a clear, concise and up-to-date overview of microbial composition differences in diseases, together with the relevant information of the studies published. The strength of this database lies within the combination of the presence of references to other databases, which enables both specific and diverse search strategies within the Disbiome database, and the human annotation which ensures a simple and structured presentation of the available data.

Isolation of Propionibacterium acnes among the microbiota of primary endodontic infections with and without intraoral communication.

PubMed

Niazi, Sadia Ambreen; Al Kharusi, Hana Suleiman; Patel, Shanon; Bruce, Kenneth; Beighton, David; Foschi, Federico; Mannocci, Francesco

2016-11-01

The presence of opportunistic pathogens such as Propionibacterium acnes (P. acnes) may contribute to the endodontic pathology. The presence of P. acnes may be influenced by different endodontic conditions. The aims of the study were firstly, to identify P. acnes within the whole cultivable microbiota of primary endodontic infections, to investigate which P. acnes phylotypes predominate in such infections and secondly to determine if the presence of an "open" communication (e.g. a sinus) can be associated with the isolation of P. acnes from the root canal. The predominant cultivable microbiota of 15 primary endodontic lesions (7 without communication with the oral environment and 8 with an open communication) were identified using partial 16S ribosomal RNA (rRNA) gene sequence analysis. The identification of the organism was determined by interrogating the Human Oral Microbiome Database. The P. acnes isolates were typed on the basis of the recA gene sequence comparison. A neighbor-joining tree was constructed using MEGA 4.1 with the inclusion of known recA sequences. There was no difference in the number of species identified from lesions without communication (5.86 ± 3.7) and those with communication (5.37 ± 3.6) (P > 0.05). PCR-based 16S rRNA gene sequencing revealed P. acnes as the most prevalent isolate recovered from lesions with communication. recA gene sequencing revealed two phylogenetic lineages present in lesion with communication, with mainly type I (further split into type IA and type IB) and type II. The presence of P. acnes as opportunistic pathogens has been confirmed and may sustain the traits observed in specific clinical presentations. Clinical management of open lesions may require further disinfection to eliminate opportunistic bacteria.

Oral microbiome and peri-implant diseases: where are we now?

PubMed Central

Pokrowiecki, Rafał; Mielczarek, Agnieszka; Zaręba, Tomasz; Tyski, Stefan

2017-01-01

Peri-implant infective diseases (PIIDs) in oral implantology are commonly known as peri-implant mucositis (PIM) and periimplantitis (PI). While PIM is restricted to the peri-implant mucosa and is reversible, PI also affects implant-supporting bone and, therefore, is very difficult to eradicate. PIIDs in clinical outcome may resemble gingivitis and periodontitis, as they share similar risk factors. However, recent study in the field of proteomics and other molecular studies indicate that PIIDs exhibit significant differences when compared to periodontal diseases. This review aims to elucidate the current knowledge of PIIDs, their etiopathology and diversified microbiology as well as the role of molecular studies, which may be a key to personalized diagnostic and treatment protocols of peri-implant infections in the near future. PMID:29238198

Probiotic treatment restores protection against lethal fungal infection lost during amphibian captivity.

PubMed

Kueneman, Jordan G; Woodhams, Douglas C; Harris, Reid; Archer, Holly M; Knight, Rob; McKenzie, Valerie J

2016-09-28

Host-associated microbiomes perform many beneficial functions including resisting pathogens and training the immune system. Here, we show that amphibians developing in captivity lose substantial skin bacterial diversity, primarily due to reduced ongoing input from environmental sources. We combined studies of wild and captive amphibians with a database of over 1 000 strains that allows us to examine antifungal function of the skin microbiome. We tracked skin bacterial communities of 62 endangered boreal toads, Anaxyrus boreas, across 18 time points, four probiotic treatments, and two exposures to the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd) in captivity, and compared these to 33 samples collected from wild populations at the same life stage. As the amphibians in captivity lost the Bd-inhibitory bacteria through time, the proportion of individuals exposed to Bd that became infected rose from 33% to 100% in subsequent exposures. Inoculations of the Bd-inhibitory probiotic Janthinobacterium lividum resulted in a 40% increase in survival during the second Bd challenge, indicating that the effect of microbiome depletion was reversible by restoring Bd-inhibitory bacteria. Taken together, this study highlights the functional role of ongoing environmental inputs of skin-associated bacteria in mitigating a devastating amphibian pathogen, and that long-term captivity decreases this defensive function. © 2016 The Author(s).

Probiotic treatment restores protection against lethal fungal infection lost during amphibian captivity

PubMed Central

Kueneman, Jordan G.; Woodhams, Douglas C.; Harris, Reid; Archer, Holly M.; Knight, Rob

2016-01-01

Host-associated microbiomes perform many beneficial functions including resisting pathogens and training the immune system. Here, we show that amphibians developing in captivity lose substantial skin bacterial diversity, primarily due to reduced ongoing input from environmental sources. We combined studies of wild and captive amphibians with a database of over 1 000 strains that allows us to examine antifungal function of the skin microbiome. We tracked skin bacterial communities of 62 endangered boreal toads, Anaxyrus boreas, across 18 time points, four probiotic treatments, and two exposures to the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd) in captivity, and compared these to 33 samples collected from wild populations at the same life stage. As the amphibians in captivity lost the Bd-inhibitory bacteria through time, the proportion of individuals exposed to Bd that became infected rose from 33% to 100% in subsequent exposures. Inoculations of the Bd-inhibitory probiotic Janthinobacterium lividum resulted in a 40% increase in survival during the second Bd challenge, indicating that the effect of microbiome depletion was reversible by restoring Bd-inhibitory bacteria. Taken together, this study highlights the functional role of ongoing environmental inputs of skin-associated bacteria in mitigating a devastating amphibian pathogen, and that long-term captivity decreases this defensive function. PMID:27655769

Do we treat our patients or rather periodontal microbes with adjunctive antibiotics in periodontal therapy? A 16S rDNA microbial community analysis.

PubMed

Hagenfeld, Daniel; Koch, Raphael; Jünemann, Sebastian; Prior, Karola; Harks, Inga; Eickholz, Peter; Hoffmann, Thomas; Kim, Ti-Sun; Kocher, Thomas; Meyle, Jörg; Kaner, Doğan; Schlagenhauf, Ulrich; Ehmke, Benjamin; Harmsen, Dag

2018-01-01

Empiric antibiotics are often used in combination with mechanical debridement to treat patients suffering from periodontitis and to eliminate disease-associated pathogens. Until now, only a few next generation sequencing 16S rDNA amplicon based publications with rather small sample sizes studied the effect of those interventions on the subgingival microbiome. Therefore, we studied subgingival samples of 89 patients with chronic periodontitis (solely non-smokers) before and two months after therapy. Forty-seven patients received mechanical periodontal therapy only, whereas 42 patients additionally received oral administered amoxicillin plus metronidazole (500 and 400 mg, respectively; 3x/day for 7 days). Samples were sequenced with Illumina MiSeq 300 base pairs paired end technology (V3 and V4 hypervariable regions of the 16S rDNA). Inter-group differences before and after therapy of clinical variables (percentage of sites with pocket depth ≥ 5mm, percentage of sites with bleeding on probing) and microbiome variables (diversity, richness, evenness, and dissimilarity) were calculated, a principal coordinate analysis (PCoA) was conducted, and differential abundance of agglomerated ribosomal sequence variants (aRSVs) classified on genus level was calculated using a negative binomial regression model. We found statistically noticeable decreased richness, and increased dissimilarity in the antibiotic, but not in the placebo group after therapy. The PCoA revealed a clear compositional separation of microbiomes after therapy in the antibiotic group, which could not be seen in the group receiving mechanical therapy only. This difference was even more pronounced on aRSV level. Here, adjunctive antibiotics were able to induce a microbiome shift by statistically noticeably reducing aRSVs belonging to genera containing disease-associated species, e.g., Porphyromonas, Tannerella, Treponema, and Aggregatibacter, and by noticeably increasing genera containing health-associated species. Mechanical therapy alone did not statistically noticeably affect any disease-associated taxa. Despite the difference in microbiome modulation both therapies improved the tested clinical parameters after two months. These results cast doubt on the relevance of the elimination and/or reduction of disease-associated taxa as a main goal of periodontal therapy.

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

PubMed

Villar-García, Judit; Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P; Artacho, Alejandro; D Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target.

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

PubMed Central

Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J.; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P.; Artacho, Alejandro; D´Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target. PMID:28388647

Comparison of Bacterial Community Composition of Primary and Persistent Endodontic Infections Using Pyrosequencing.

PubMed

Tzanetakis, Giorgos N; Azcarate-Peril, M Andrea; Zachaki, Sophia; Panopoulos, Panos; Kontakiotis, Evangelos G; Madianos, Phoebus N; Divaris, Kimon

2015-08-01

Elucidating the microbial ecology of endodontic infections (EIs) is a necessary step in developing effective intracanal antimicrobials. The aim of the present study was to investigate the bacterial composition of symptomatic and asymptomatic primary and persistent infections in a Greek population using high-throughput sequencing methods. 16S amplicon pyrosequencing of 48 root canal bacterial samples was conducted, and sequencing data were analyzed using an oral microbiome-specific and a generic (Greengenes) database. Bacterial abundance and diversity were examined by EI type (primary or persistent), and statistical analysis was performed by using non-parametric and parametric tests accounting for clustered data. Bacteroidetes was the most abundant phylum in both infection groups. Significant, albeit weak associations of bacterial diversity were found, as measured by UniFrac distances with infection type (analyses of similarity, R = 0.087, P = .005) and symptoms (analyses of similarity, R = 0.055, P = .047). Persistent infections were significantly enriched for Proteobacteria and Tenericutes compared with primary ones; at the genus level, significant differences were noted for 14 taxa, including increased enrichment of persistent infections for Lactobacillus, Streptococcus, and Sphingomonas. More but less abundant phyla were identified using the Greengenes database; among those, Cyanobacteria (0.018%) and Acidobacteria (0.007%) were significantly enriched among persistent infections. Persistent infections showed higher phylogenetic diversity (PD) (asymptomatic: PD = 9.2, standard error [SE] = 1.3; symptomatic: PD = 8.2, SE = 0.7) compared with primary infections (asymptomatic: PD = 5.9, SE = 0.8; symptomatic: PD = 7.4, SE = 1.0). The present study revealed a high bacterial diversity of EI and suggests that persistent infections may have more diverse bacterial communities than primary infections. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Pathogenesis of Escherichia coli O157:H7 Strain 86-24 Following Oral Infection of BALB/c Mice with an Intact Commensal Flora

DTIC Science & Technology

2010-01-01

microbiome for resources. On the other hand, in a mouse model in which the normal gut flora is suppressed, the infecting E. coli 0157:H7 strain may...producing E. coli (STEC) [ 10- 121. This toxin is produced by the infecting bacteria in the gut , as evidenced by the presence of Stx in the feces...intestinal barrier to target small vessel endothelial cells in the lamina propria of the gut {thought to be a primary event in the manifestation of

Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes and exhibit different in situ growth rates

PubMed Central

Olm, Matthew R.; Brown, Christopher T.; Brooks, Brandon; Firek, Brian; Baker, Robyn; Burstein, David; Soenjoyo, Karina; Thomas, Brian C.; Morowitz, Michael; Banfield, Jillian F.

2017-01-01

The initial microbiome impacts the health and future development of premature infants. Methodological limitations have led to gaps in our understanding of the habitat range and subpopulation complexity of founding strains, as well as how different body sites support microbial growth. Here, we used metagenomics to reconstruct genomes of strains that colonized the skin, mouth, and gut of two hospitalized premature infants during the first month of life. Seven bacterial populations, considered to be identical given whole-genome average nucleotide identity of >99.9%, colonized multiple body sites, yet none were shared between infants. Gut-associated Citrobacter koseri genomes harbored 47 polymorphic sites that we used to define 10 subpopulations, one of which appeared in the gut after 1 wk but did not spread to other body sites. Differential genome coverage was used to measure bacterial population replication rates in situ. In all cases where the same bacterial population was detected in multiple body sites, replication rates were faster in mouth and skin compared to the gut. The ability of identical strains to colonize multiple body sites underscores the habit flexibility of initial colonists, whereas differences in microbial replication rates between body sites suggest differences in host control and/or resource availability. Population genomic analyses revealed microdiversity within bacterial populations, implying initial inoculation by multiple individual cells with distinct genotypes. Overall, however, the overlap of strains across body sites implies that the premature infant microbiome can exhibit very low microbial diversity. PMID:28073918

Antibiotic use and microbiome function.

PubMed

Ferrer, Manuel; Méndez-García, Celia; Rojo, David; Barbas, Coral; Moya, Andrés

2017-06-15

Our microbiome should be understood as one of the most complex components of the human body. The use of β-lactam antibiotics is one of the microbiome covariates that influence its composition. The extent to which our microbiota changes after an antibiotic intervention depends not only on the chemical nature of the antibiotic or cocktail of antibiotics used to treat specific infections, but also on the type of administration, duration and dose, as well as the level of resistance that each microbiota develops. We have begun to appreciate that not all bacteria within our microbiota are vulnerable or reactive to different antibiotic interventions, and that their influence on both microbial composition and metabolism may differ. Antibiotics are being used worldwide on a huge scale and the prescription of antibiotics is continuing to rise; however, their effects on our microbiota have been reported for only a limited number of them. This article presents a critical review of the antibiotics or antibiotic cocktails whose use in humans has been linked to changes in the composition of our microbial communities, with a particular focus on the gut, oral, respiratory, skin and vaginal microbiota, and on their molecular agents (genes, proteins and metabolites). We review the state of the art as of June 2016, and cover a total of circa 68 different antibiotics. The data herein are the first to compile information about the bacteria, fungi, archaea and viruses most influenced by the main antibiotic treatments prescribed nowadays. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical and microbiological parameters of naturally occurring periodontitis in the non-human primate Macaca mulatta

PubMed Central

Colombo, A. P. V.; Paster, B. J.; Grimaldi, G.; Lourenço, T. G. B.; Teva, A.; Campos-Neto, A.; McCluskey, J.; Kleanthous, H.; Van Dyke, T. E.; Stashenko, P.

2017-01-01

ABSTRACT Background: Non-human primates appear to represent the most faithful model of human disease, but to date the oral microbiome in macaques has not been fully characterized using next-generation sequencing. Objective: In the present study, we characterized the clinical and microbiological features of naturally occurring periodontitis in non-human primates (Macaca mulatta). Design: Clinical parameters of periodontitis including probing pocket depth (PD) and bleeding on probing (BOP) were measured in 40 adult macaques (7–22 yrs), at six sites per tooth. Subgingival plaque was collected from diseased and healthy sites, and subjected to 16S rDNA sequencing and identification at the species or higher taxon level. Results: All macaques had mild periodontitis at minimum, with numerous sites of PD ≥ 4 mm and BOP. A subset (14/40) had moderate-severe disease, with >2 sites with PD ≥ 5mm, deeper mean PD, and more BOP. Animals with mild vs moderate-severe disease were identical in age, suggesting genetic heterogeneity. 16S rDNA sequencing revealed that all macaques had species that were identical to those in humans or closely related to human counterparts, including Porphyromonas gingivalis which was present in all animals. Diseased and healthy sites harboured distinct microbiomes; however there were no significant differences in the microbiomes in moderate-severe vs. mild periodontitis. Conclusions: Naturally occurring periodontitis in older macaques closely resembles human adult periodontitis, thus validating a useful model to evaluate novel anti-microbial therapies. PMID:29805776

Interplay between the Gastric Bacterial Microbiota and Candida albicans during Postantibiotic Recolonization and Gastritis

PubMed Central

Mason, Katie L.; Erb Downward, John R.; Falkowski, Nicole R.; Young, Vincent B.; Kao, John Y.

2012-01-01

The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent. PMID:21986629

Interplay between the gastric bacterial microbiota and Candida albicans during postantibiotic recolonization and gastritis.

PubMed

Mason, Katie L; Erb Downward, John R; Falkowski, Nicole R; Young, Vincent B; Kao, John Y; Huffnagle, Gary B

2012-01-01

The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent.

Preventive effects of a phospholipid polymer coating on PMMA on biofilm formation by oral streptococci

NASA Astrophysics Data System (ADS)

Shibata, Yukie; Yamashita, Yoshihisa; Tsuru, Kanji; Ishihara, Kazuhiko; Fukazawa, Kyoko; Ishikawa, Kunio

2016-12-01

The regulation of biofilm formation on dental materials such as denture bases is key to oral health. Recently, a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) coating, was reported to inhibit sucrose-dependent biofilm formation by Streptococcus mutans, a cariogenic bacterium, on the surface of poly(methyl methacrylate) (PMMA) denture bases. However, S. mutans is a minor component of the oral microbiome and does not play an important role in biofilm formation in the absence of sucrose. Other, more predominant oral streptococci must play an indispensable role in sucrose-independent biofilm formation. In the present study, the effect of PMB coating on PMMA was evaluated using various oral streptococci that are known to be initial colonizers during biofilm formation on tooth surfaces. PMB coating on PMMA drastically reduced sucrose-dependent tight biofilm formation by two cariogenic bacteria (S. mutans and Streptococcus sobrinus), among seven tested oral streptococci, as described previously [N. Takahashi, F. Iwasa, Y. Inoue, H. Morisaki, K. Ishihara, K. Baba, J. Prosthet. Dent. 112 (2014) 194-203]. Streptococci other than S. mutans and S. sobrinus did not exhibit tight biofilm formation even in the presence of sucrose. On the other hand, all seven species of oral streptococci exhibited distinctly reduced glucose-dependent soft biofilm retention on PMB-coated PMMA. We conclude that PMB coating on PMMA surfaces inhibits biofilm attachment by initial colonizer oral streptococci, even in the absence of sucrose, indicating that PMB coating may help maintain clean conditions on PMMA surfaces in the oral cavity.

Dysbiosis of oral buccal mucosa microbiota in patients with oral lichen planus.

PubMed

He, Y; Gong, D; Shi, C; Shao, F; Shi, J; Fei, J

2017-07-01

The bacterial community structure of buccal mucosa in patients with oral lichen planus was evaluated and compared with healthy control. Buccal scraping samples have been taken on 43 oral lichen planus patients (21 erosive and 22 non-erosive) and 21 mucosal healthy volunteers. The V3 hypervariable 16S rDNA region was amplified and sequenced by high-throughput 454 pyrosequencing. 94.26% of the total buccal bacteria were classified into 15 abundant genera. Eight of these abundant genera could be detected in all cases, namely Streptococcus, Prevotella, Haemophilu, Neisseria, Fusobacterium, Leptotrichia, Veillonella and Actinomyces. Four abundant bacteria showed significantly different prevalence at the genus level: Streptococcus was more abundant (P < 0.01) in healthy control group, while Fusobacterium (P < 0.01), Leptotrichia (P < 0.001) and Lautropia (P < 0.001) showed higher abundance in OLP group. Few differences can be found between erosive and non-erosive OLP. In general, 19 'core' OTUs at three levels were defined to be OLP specific, comparing with healthy control group. These results suggest that OLP is associated with dysbiosis of the oral microbiome. Further studies should be taken to elucidate the inner relationship between these observed changes and OLP development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral Microbiome Link to Neurodegeneration in Glaucoma

PubMed Central

Astafurov, Konstantin; Elhawy, Eman; Ren, Lizhen; Dong, Cecilia Q.; Igboin, Christina; Hyman, Leslie; Griffen, Ann; Mittag, Thomas; Danias, John

2014-01-01

Background Glaucoma is a progressive optic nerve degenerative disease that often leads to blindness. Local inflammatory responses are implicated in the pathology of glaucoma. Although inflammatory episodes outside the CNS, such as those due to acute systemic infections, have been linked to central neurodegeneration, they do not appear to be relevant to glaucoma. Based on clinical observations, we hypothesized that chronic subclinical peripheral inflammation contributes to neurodegeneration in glaucoma. Methods Mouthwash specimens from patients with glaucoma and control subjects were analyzed for the amount of bacteria. To determine a possible pathogenic mechanism, low-dose subcutaneous lipopolysaccharide (LPS) was administered in two separate animal models of glaucoma. Glaucomatous neurodegeneration was assessed in the retina and optic nerve two months later. Changes in gene expression of toll-like receptor 4 (TLR4) signaling pathway and complement as well as changes in microglial numbers and morphology were analyzed in the retina and optic nerve. The effect of pharmacologic blockade of TLR4 with naloxone was determined. Findings Patients with glaucoma had higher bacterial oral counts compared to control subjects (p<0.017). Low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage. Conclusions The above findings suggest that the oral microbiome contributes to glaucoma pathophysiology. A plausible mechanism by which increased bacterial loads can lead to neurodegeneration is provided by experiments in animal models of the disease and involves activation of microglia in the retina and optic nerve, mediated through TLR4 signaling and complement upregulation. The finding that commensal bacteria may play a role in the development and/or progression of glaucomatous pathology may also be relevant to other chronic neurodegenerative disorders. PMID:25180891

Oral microbial community assembly under the influence of periodontitis.

PubMed

Chen, Hongju; Peng, Shuting; Dai, Lin; Zou, Quan; Yi, Bin; Yang, Xianghong; Ma, Zhanshan Sam

2017-01-01

Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation.

Oral microbial community assembly under the influence of periodontitis

PubMed Central

Chen, Hongju; Peng, Shuting; Dai, Lin; Zou, Quan; Yi, Bin; Yang, Xianghong

2017-01-01

Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell’s neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.’s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher’s exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or ‘phenotype’ of community assembly), it does not seem to cause the ‘mutation’ of the ‘genotype” (mechanism) of community assembly. We argue that the ‘phenotypic’ changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation. PMID:28813450

Applying the design-build-test paradigm in microbiome engineering.

PubMed

Pham, Hoang Long; Ho, Chun Loong; Wong, Adison; Lee, Yung Seng; Chang, Matthew Wook

2017-12-01

The recently discovered roles of human microbiome in health and diseases have inspired research efforts across many disciplines to engineer microbiome for health benefits. In this review, we highlight recent progress in human microbiome research and how modifications to the microbiome could result in implications to human health. Furthermore, we discuss the application of a 'design-build-test' framework to expedite microbiome engineering efforts by reviewing current literature on three key aspects: design principles to engineer the human microbiome, methods to engineer microbiome with desired functions, and analytical techniques to examine complex microbiome samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Probiotics, antibiotics and the immune responses to vaccines

PubMed Central

Praharaj, Ira; John, Sushil M.; Bandyopadhyay, Rini; Kang, Gagandeep

2015-01-01

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. PMID:25964456

Management of inflammatory bowel disease-related anemia and iron deficiency with specific reference to the role of intravenous iron in current practice.

PubMed

Stein, Jürgen; Aksan, Ayşegül; Farrag, Karima; Dignass, Axel; Radeke, Heinfried H

2017-11-01

Anemia is a common extraintestinal manifestation in patients with inflammatory bowel disease, impacting disease prognosis, morbidity, hospitalization rates and time lost from work. While iron deficiency anemia and anemia of chronic inflammation predominate, combinations of hematimetric and biochemical markers facilitate the diagnosis and targeted therapy of other etiologies according to their underlying pathophysiological causes. Intravenous iron replacement is currently recommended in IBD patients with moderate to severe anemia or intolerance to oral iron. Areas covered: This review examines the impact, pathophysiology and diagnostics of iron deficiency and anemia, compares the characteristics and safety profiles of available oral and intravenous iron preparations, and highlights issues which require consideration in decision making for therapy administration and monitoring. Expert opinion: Modern intravenous iron formulations have been shown to be safe and effective in IBD patients, allowing rapid anemia correction and repletion of iron stores. While traditional oral iron preparations are associated with increased inflammation, negative effects on the microbiome, and poor tolerance and compliance, first clinical trial data indicate that newer oral compounds such as ferric maltol and sucrosomial iron offer improved tolerability and may thus offer a viable alternative for the future.

Personalized microbial network inference via co-regularized spectral clustering.

PubMed

Imangaliyev, Sultan; Keijser, Bart; Crielaard, Wim; Tsivtsivadze, Evgeni

2015-07-15

We use Human Microbiome Project (HMP) cohort (Peterson et al., 2009) to infer personalized oral microbial networks of healthy individuals. To determine clustering of individuals with similar microbial profiles, co-regularized spectral clustering algorithm is applied to the dataset. For each cluster we discovered, we compute co-occurrence relationships among the microbial species that determine microbial network per cluster of individuals. The results of our study suggest that there are several differences in microbial interactions on personalized network level in healthy oral samples acquired from various niches. Based on the results of co-regularized spectral clustering we discover two groups of individuals with different topology of their microbial interaction network. The results of microbial network inference suggest that niche-wise interactions are different in these two groups. Our study shows that healthy individuals have different microbial clusters according to their oral microbiota. Such personalized microbial networks open a better understanding of the microbial ecology of healthy oral cavities and new possibilities for future targeted medication. The scripts written in scientific Python and in Matlab, which were used for network visualization, are provided for download on the website http://learning-machines.com/. Copyright © 2015 Elsevier Inc. All rights reserved.

Multispecies Biofilms and Host Responses: “Discriminating the Trees from the Forest”

PubMed Central

Peyyala, R.; Ebersole, J.L.

2014-01-01

Periodontal diseases reflect a tissue destructive process of the hard and soft tissues of the periodontium that are initiated by the accumulation of multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in both quantity and quality of bacteria, results in a chronic immunoinflammatory response of the host to control this noxious challenge, leading to collateral damage of the tissues. As knowledge of the characteristics of the host-bacterial interactions in the oral cavity has expanded, new knowledge has become available on the complexity of the microbial challenge and the repertoire of host responses to this challenge. Recent results from the Human Microbiome Project continue to extend the array of taxa, genera, and species of bacteria that inhabit the multiple niches in the oral cavity; however, there is rather sparse information regarding variations in how host cells discriminate commensal from pathogenic species, as well as how the host response is affected by the 3-dimensional architecture and interbacterial interactions that occur in the oral biofilms. This review provides some insights into thes- processes by including existing literature on the biology of nonoral bacterial biofilms, and the more recent literature just beginning to document how the oral cavity responds to multispecies biofilms. PMID:23141757

Molecular Biomarkers for Detecting, Monitoring and Quantifying Reductive Microbial Processes

DTIC Science & Technology

2013-07-01

Microbiomes   database   (IMG/M)   versions   2.5...Termite   Gut  Metagenome,  IMG/M  ID  2005608198   5.6%   [FeFe]  Hydrogenase  from  Termite   Gut  Metagenome,  IMG/M  ID...2005622586   5.0%   [FeFe]  Hydrogenase  from  Termite   Gut  Metagenome,  IMG/M  ID  2005599188   4.2%   [FeFe

Microbial Ecology along the Gastrointestinal Tract

PubMed Central

Hillman, Ethan T.; Lu, Hang; Yao, Tianming; Nakatsu, Cindy H.

2017-01-01

The ecosystem of the human gastrointestinal (GI) tract traverses a number of environmental, chemical, and physical conditions because it runs from the oral cavity to the anus. These differences in conditions along with food or other ingested substrates affect the composition and density of the microbiota as well as their functional roles by selecting those that are the most suitable for that environment. Previous studies have mostly focused on Bacteria, with the number of studies conducted on Archaea, Eukarya, and Viruses being limited despite their important roles in this ecosystem. Furthermore, due to the challenges associated with collecting samples directly from the inside of humans, many studies are still exploratory, with a primary focus on the composition of microbiomes. Thus, mechanistic studies to investigate functions are conducted using animal models. However, differences in physiology and microbiomes need to be clarified in order to aid in the translation of animal model findings into the context of humans. This review will highlight Bacteria, Archaea, Fungi, and Viruses, discuss differences along the GI tract of healthy humans, and perform comparisons with three common animal models: rats, mice, and pigs. PMID:29129876

Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.

PubMed

Rentea, Rebecca M; Lam, Vy; Biesterveld, Ben; Fredrich, Katherine M; Callison, Jennifer; Fish, Brian L; Baker, John E; Komorowski, Richard; Gourlay, David M; Otterson, Mary F

2016-10-01

Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP. WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant. Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome. Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome. Copyright © 2016 Elsevier Inc. All rights reserved.

Tongue coating microbiome regulates the changes in tongue texture and coating in patients with post-menopausal osteoporosis of Gan-shen deficiency syndrome type.

PubMed

Liang, Wenna; Li, Xihai; Li, Yachan; Li, Candong; Gao, Bizheng; Gan, Huijuan; Li, Sumin; Shen, Jianying; Kang, Jie; Ding, Shanshan; Lin, Xuejuan; Liao, Linghong

2013-11-01

Tongue inspection is a unique and important method of diagnosis in traditional Chinese medicine (TCM). It is a diagnostic approach which involves observing the changes in the tongue proper and tongue coating in order to understand the physiological functions and pathological changes of the body. However, the biological basis of TCM tongue diagnosis remains to be poorly understood and lacks systematic investigation at the molecular level. In this study, we evaluated the effects of tongue coating microbiome on changes in the tongue texture and coating in patients with post-menopausal osteoporosis (PMO) of Gan‑shen deficiency syndrome type. Our aim was to delineate the mechanisms of tongue coating microbiome-induced changes in the tongue texture and coating by investigating the histomorphological changes and performing a bacterial analysis of the tongue coating. We found that the number of intermediate cells in the red tongue with a thin coating was higher, while the number of superficial cells in the red tongue with a thin coating was lower. The maturation value (MV) of tongue exfoliated cells in the red tongue with a thin coating decreased, compared with that in the pale red tongue with a thin white coating. Furthermore, the total bacterial count, oral streptococcus, Gram‑positive (G+) and Gram‑negative (G-) anaerobic bacteria in the red tongue with a thin coating was significantly decreased compared with the pale red tongue with a thin white coating. The results of ultrastructural examination demonstrated that the number of epithelial cells and bacteria in the red tongue with a thin coating decreased compared with that in the pale red tongue with a thin white coating. These observations indicate that the tongue coating microbiome may be an important factor contributing to changes in the tongue in patients with PMO of Gan‑shen deficiency syndrome type.

Local Acetaldehyde—An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis

PubMed Central

Salaspuro, Mikko

2018-01-01

The resident microbiome plays a key role in exposure of the upper gastrointestinal (GI) tract mucosa to acetaldehyde (ACH), a carcinogenic metabolite of ethanol. Poor oral health is a significant risk factor for oral and esophageal carcinogenesis and is characterized by a dysbiotic microbiome. Dysbiosis leads to increased growth of opportunistic pathogens (such as Candida yeasts) and may cause an up to 100% increase in the local ACH production, which is further modified by organ-specific expression and gene polymorphisms of ethanol-metabolizing and ACH-metabolizing enzymes. A point mutation in the aldehyde dehydrogenase 2 gene has randomized millions of alcohol consumers to markedly increased local ACH exposure via saliva and gastric juice, which is associated with a manifold risk for upper GI tract cancers. This human cancer model proves conclusively the causal relationship between ACH and upper GI tract carcinogenesis and provides novel possibilities for the quantitative assessment of ACH carcinogenicity in the human oropharynx. ACH formed from ethanol present in “non-alcoholic” beverages, fermented food, or added during food preparation forms a significant epidemiologic bias in cancer epidemiology. The same also concerns “free” ACH present in mutagenic concentrations in multiple beverages and foodstuffs. Local exposure to ACH is cumulative and can be reduced markedly both at the population and individual level. At best, a person would never consume tobacco, alcohol, or both. However, even smoking cessation and moderation of alcohol consumption are associated with a marked decrease in local ACH exposure and cancer risk, especially among established risk groups. PMID:29303995

The dental calculus metabolome in modern and historic samples.

PubMed

Velsko, Irina M; Overmyer, Katherine A; Speller, Camilla; Klaus, Lauren; Collins, Matthew J; Loe, Louise; Frantz, Laurent A F; Sankaranarayanan, Krithivasan; Lewis, Cecil M; Martinez, Juan Bautista Rodriguez; Chaves, Eros; Coon, Joshua J; Larson, Greger; Warinner, Christina

2017-01-01

Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss. Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples. The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies.

Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota.

PubMed

Staley, Christopher; Vaughn, Byron P; Graiziger, Carolyn T; Singroy, Stephanie; Hamilton, Matthew J; Yao, Dan; Chen, Chi; Khoruts, Alexander; Sadowsky, Michael J

2017-05-04

Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.

Nasopharyngeal Microbiome Diversity Changes over Time in Children with Asthma.

PubMed

Pérez-Losada, Marcos; Alamri, Lamia; Crandall, Keith A; Freishtat, Robert J

2017-01-01

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome of infants and adults during health and disease; less is known, however, about the composition and temporal dynamics (i.e., longitudinal variation) of microbiotas from children and adolescents. Here we use NGS technology to characterize the nasopharyngeal microbiomes of asthmatic children and adolescents (6 to 18 years) and determine their stability over time. Two nasopharyngeal washes collected 5.5 to 6.5 months apart were taken from 40 children and adolescents with asthma living in the Washington D.C. area. Sequence data from the 16S-V4 rRNA gene region (~250 bp) were collected from the samples using the MiSeq platform. Raw data were processed in mothur (SILVA123 reference database) and Operational Taxonomic Units (OTU)-based alpha- and beta-diversity metrics were estimated. Relatedness among samples was assessed using PCoA ordination and Procrustes analyses. Differences in microbial diversity and taxon mean relative proportions were assessed using linear mixed effects models. Core microbiome analyses were also performed to identify stable and consistent microbes of the nasopharynx. A total of 2,096,584 clean 16S sequences corresponding to an average of 167 OTUs per sample were generated. Representatives of Moraxella*, Staphylococcus*, Dolosigranulum, Corynebacterium, Prevotella, Streptococcus*, Haemophilus*, Fusobacterium* and a Neisseriaceae genus accounted for 86% of the total reads. These nine genera have been previously found in the nasopharynxes of both infants and adults, but in different proportions. OTUs from the five genera highlighted (*) above defined the nasopharyngeal core microbiome at the 95% level. No significant differences in alpha- and beta-diversity were observed between seasons, but bacterial mean relative proportions of Haemophilus, Moraxella, Staphylococcus and Corynebacterium varied significantly between summer-fall and age groups (inter-patient variation). Additionally, OTUs varied significantly within patients between time points in 35 of the 40 patients analyzed. Future cross-sectional studies should be mindful of the temporal dynamics of the nasopharyngeal microbiota.

The saliva microbiome of Pan and Homo

PubMed Central

2013-01-01

Background It is increasingly recognized that the bacteria that live in and on the human body (the microbiome) can play an important role in health and disease. The composition of the microbiome is potentially influenced by both internal factors (such as phylogeny and host physiology) and external factors (such as diet and local environment), and interspecific comparisons can aid in understanding the importance of these factors. Results To gain insights into the relative importance of these factors on saliva microbiome diversity, we here analyze the saliva microbiomes of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) from two sanctuaries in Africa, and from human workers at each sanctuary. The saliva microbiomes of the two Pan species are more similar to one another, and the saliva microbiomes of the two human groups are more similar to one another, than are the saliva microbiomes of human workers and apes from the same sanctuary. We also looked for the existence of a core microbiome and find no evidence for a taxon-based core saliva microbiome for Homo or Pan. In addition, we studied the saliva microbiome from apes from the Leipzig Zoo, and found an extraordinary diversity in the zoo ape saliva microbiomes that is not found in the saliva microbiomes of the sanctuary animals. Conclusions The greater similarity of the saliva microbiomes of the two Pan species to one another, and of the two human groups to one another, are in accordance with both the phylogenetic relationships of the hosts as well as with host physiology. Moreover, the results from the zoo animals suggest that novel environments can have a large impact on the microbiome, and that microbiome analyses based on captive animals should be viewed with caution as they may not reflect the microbiome of animals in the wild. PMID:24025115

The oral cavity is not a primary source for implantable pacemaker or cardioverter defibrillator infections

PubMed Central

2013-01-01

Background To test the hypothesis that the oral cavity is a potential source for implantable pacemaker and cardioverter defibrillators infections, the bacterial diversity on explanted rhythm heart management devices was investigated and compared to the oral microbiome. Methods A metagenomic approach was used to analyze the bacterial diversity on the surfaces of non-infected and infected pacemakers. The DNA from surfaces swaps of 24 non-infected and 23 infected pacemaker were isolated and subjected to bacterial-specific DNA amplification, single strand conformation polymorphism- (SSCP) and sequencing analysis. Species-specific primer sets were used to analyze for any correlation between bacterial diversity on pacemakers and in the oral cavity. Results DNA of bacterial origin was detected in 21 cases on infected pacemakers and assigned to the bacterial phylotypes Staphylococcus epidermidis, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus schleiferi and Stapyhlococcus. In 17 cases bacterial DNA was found on pacemakers with no clinical signs of infections. On the basis of the obtained sequence data, the phylotypes Propionibacterium acnes, Staphylococcus and an uncultured bacterium were identified. Propionibacterium acnes and Staphylococcus epidermidis were the only bacteria detected in pacemeaker (n = 25) and oral samples (n = 11). Conclusions The frequency of the coincidental detection of bacteria on infected devices and in the oral cavity is low and the detected bacteria are highly abundant colonizers of non-oral human niches. The transmission of oral bacteria to the lead or device of implantable pacemaker or cardioverter defibrillators is unlikely relevant for the pathogenesis of pacemaker or cardioverter defibrillators infections. PMID:23575037

Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Lei; Hao, Ke; Yang, Ting; Wang, Chen

2017-09-05

The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals. With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD. This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis. Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD. The search terms were "microbiome" and "chronic obstructive pulmonary disease", or "microbiome" and "lung/pulmonary". The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited. The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health. The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process. Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD.

Personal microbiome analysis improves student engagement and interest in Immunology, Molecular Biology, and Genomics undergraduate courses

PubMed Central

Bridgewater, Laura C.; Jensen, Jamie L.; Breakwell, Donald P.; Nielsen, Brent L.; Johnson, Steven M.

2018-01-01

A critical area of emphasis for science educators is the identification of effective means of teaching and engaging undergraduate students. Personal microbiome analysis is a means of identifying the microbial communities found on or in our body. We hypothesized the use of personal microbiome analysis in the classroom could improve science education by making courses more applied and engaging for undergraduate students. We determined to test this prediction in three Brigham Young University undergraduate courses: Immunology, Advanced Molecular Biology Laboratory, and Genomics. These three courses have a two-week microbiome unit and students during the 2016 semester students could submit their own personal microbiome kit or use the demo data, whereas during the 2017 semester students were given access to microbiome data from an anonymous individual. The students were surveyed before, during, and after the human microbiome unit to determine whether analyzing their own personal microbiome data, compared to analyzing demo microbiome data, impacted student engagement and interest. We found that personal microbiome analysis significantly enhanced the engagement and interest of students while completing microbiome assignments, the self-reported time students spent researching the microbiome during the two week microbiome unit, and the attitudes of students regarding the course overall. Thus, we found that integrating personal microbiome analysis in the classroom was a powerful means of improving student engagement and interest in undergraduate science courses. PMID:29641525

Metabolome of human gut microbiome is predictive of host dysbiosis.

PubMed

Larsen, Peter E; Dai, Yang

2015-01-01

Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome's interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome-host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

Personal microbiome analysis improves student engagement and interest in Immunology, Molecular Biology, and Genomics undergraduate courses.

PubMed

Weber, K Scott; Bridgewater, Laura C; Jensen, Jamie L; Breakwell, Donald P; Nielsen, Brent L; Johnson, Steven M

2018-01-01

A critical area of emphasis for science educators is the identification of effective means of teaching and engaging undergraduate students. Personal microbiome analysis is a means of identifying the microbial communities found on or in our body. We hypothesized the use of personal microbiome analysis in the classroom could improve science education by making courses more applied and engaging for undergraduate students. We determined to test this prediction in three Brigham Young University undergraduate courses: Immunology, Advanced Molecular Biology Laboratory, and Genomics. These three courses have a two-week microbiome unit and students during the 2016 semester students could submit their own personal microbiome kit or use the demo data, whereas during the 2017 semester students were given access to microbiome data from an anonymous individual. The students were surveyed before, during, and after the human microbiome unit to determine whether analyzing their own personal microbiome data, compared to analyzing demo microbiome data, impacted student engagement and interest. We found that personal microbiome analysis significantly enhanced the engagement and interest of students while completing microbiome assignments, the self-reported time students spent researching the microbiome during the two week microbiome unit, and the attitudes of students regarding the course overall. Thus, we found that integrating personal microbiome analysis in the classroom was a powerful means of improving student engagement and interest in undergraduate science courses.

Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions

PubMed Central

Bingham, Clifton O.; Moni, Malini

2015-01-01

Purpose of review This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. Recent findings There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. Summary Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions. PMID:23455329

The Intestinal Microbiome in Infectious Diseases: The Clinical Relevance of a Rapidly Emerging Field.

PubMed

Harris, Vanessa C; Haak, Bastiaan W; Boele van Hensbroek, Michaël; Wiersinga, Willem J

2017-01-01

The field of infectious disease is undergoing a paradigm shift as the intestinal microbiome is becoming understood. The aim of this review is to inform infectious disease physicians of the potential relevance of the intestinal microbiome to their practice. We searched Medline using both index and text words relating to infectious diseases, microbiome, and probiotics. Relevant articles published up through 2017 were reviewed within Rayyan. The review illustrates pathophysiologic concepts linking the microbiome and infectious diseases; specifically, the intestinal microbiome's relevance to early immune development, the microbiome and enteric infections, the microbiome's relevance in compromised hosts, and antimicrobial resistance. Within each subject, there are specific examples of diseases and at-risk patient populations where a role for the microbiome has been strongly established. This provides an overview of the significance of the intestinal microbiome to microbiology, pediatric and adult infectious diseases with an underpinning of concepts useful for the practicing clinician.

Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics.

PubMed

ElRakaiby, Marwa; Dutilh, Bas E; Rizkallah, Mariam R; Boleij, Annemarie; Cole, Jason N; Aziz, Ramy K

2014-07-01

The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug-microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed.

Pharmacomicrobiomics: The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics

PubMed Central

ElRakaiby, Marwa; Dutilh, Bas E.; Rizkallah, Mariam R.; Boleij, Annemarie; Cole, Jason N.

2014-01-01

Abstract The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug–microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed. PMID:24785449

Critical Problems Stalling Progress in Natural Bioactive Polysaccharide Research and Development.

PubMed

Han, Quan-Bin

2018-05-09

Natural polysaccharides are attracting increasing attention from food and pharmaceutical industries for their wide range of valuable biological activities. However, the poor repeatability of the methods used in sample preparation and chemical characterization is hampering both research and product development. The unstandardized quality, in turn, undermines efforts to understand the mechanism by which they work via oral dose, which is essential to realize the full beneficial potential of polysaccharides. Some scientists believe polysaccharides work by direct gut absorption; however, increasing evidence points to the gut microbiome and intestinal Peyer's patches as holding the keys to how they work.

Emerging technologies for the prevention of dental caries. Are current methods of prevention sufficient for the high risk patient?

PubMed Central

Bretz, Walter A; Rosa, Odila P S

2011-01-01

Fluorides and chlorhexidine are technologies that are 65 and 40 yeas old, respectively. This overview argues that current methods of caries prevention are not effective for the high caries risk patient. In this review examples, arguments and recommendations are provided to address the high caries risk patient that include: failure of comprehensive chemical modalities treatments to address the high caries risk patient; ecological alteration - would this be an effective approach?; and biomaterials and oral microbiome research to address the high caries risk patient. PMID:21726223

Subgingival Microbial Communities in Leukocyte Adhesion Deficiency and Their Relationship with Local Immunopathology

PubMed Central

Moutsopoulos, Niki M.; Abusleme, Loreto; Greenwell-Wild, Teresa; Dutzan, Nicolas; Paster, Bruce J.; Munson, Peter J.; Fine, Daniel H.; Uzel, Gulbu; Holland, Steven M.

2015-01-01

Leukocyte Adhesion Deficiency I (LAD-I) is a primary immunodeficiency caused by single gene mutations in the CD18 subunit of β2 integrins which result in defective transmigration of neutrophils into the tissues. Affected patients suffer from recurrent life threatening infections and severe oral disease (periodontitis). Microbial communities in the local environment (subgingival plaque) are thought to be the triggers for inflammatory periodontitis, yet little is known regarding the microbial communities associated with LAD-I periodontitis. Here we present the first comprehensive characterization of the subgingival communities in LAD-I, using a 16S rRNA gene-based microarray, and investigate the relationship of this tooth adherent microbiome to the local immunopathology of periodontitis. We show that the LAD subgingival microbiome is distinct from that of health and Localized Aggressive Periodontitits. Select periodontitis-associated species in the LAD microbiome included Parvimonas micra, Porphyromonas endodontalis, Eubacterium brachy and Treponema species. Pseudomonas aeruginosa, a bacterium not typically found in subgingival plaque is detected in LAD-I. We suggest that microbial products from LAD-associated communities may have a role in stimulating the local inflammatory response. We demonstrate that bacterial LPS translocates into the lesions of LAD-periodontitis potentially triggering immunopathology. We also show in in vitro assays with human macrophages and in vivo in animal models that microbial products from LAD-associated subgingival plaque trigger IL-23-related immune responses, which have been shown to dominate in patient lesions. In conclusion, our current study characterizes the subgingival microbial communities in LAD-periodontitis and supports their role as triggers of disease pathogenesis. PMID:25741691

Subgingival microbial communities in Leukocyte Adhesion Deficiency and their relationship with local immunopathology.

PubMed

Moutsopoulos, Niki M; Chalmers, Natalia I; Barb, Jennifer J; Abusleme, Loreto; Greenwell-Wild, Teresa; Dutzan, Nicolas; Paster, Bruce J; Munson, Peter J; Fine, Daniel H; Uzel, Gulbu; Holland, Steven M

2015-03-01

Leukocyte Adhesion Deficiency I (LAD-I) is a primary immunodeficiency caused by single gene mutations in the CD18 subunit of β2 integrins which result in defective transmigration of neutrophils into the tissues. Affected patients suffer from recurrent life threatening infections and severe oral disease (periodontitis). Microbial communities in the local environment (subgingival plaque) are thought to be the triggers for inflammatory periodontitis, yet little is known regarding the microbial communities associated with LAD-I periodontitis. Here we present the first comprehensive characterization of the subgingival communities in LAD-I, using a 16S rRNA gene-based microarray, and investigate the relationship of this tooth adherent microbiome to the local immunopathology of periodontitis. We show that the LAD subgingival microbiome is distinct from that of health and Localized Aggressive Periodontitits. Select periodontitis-associated species in the LAD microbiome included Parvimonas micra, Porphyromonas endodontalis, Eubacterium brachy and Treponema species. Pseudomonas aeruginosa, a bacterium not typically found in subgingival plaque is detected in LAD-I. We suggest that microbial products from LAD-associated communities may have a role in stimulating the local inflammatory response. We demonstrate that bacterial LPS translocates into the lesions of LAD-periodontitis potentially triggering immunopathology. We also show in in vitro assays with human macrophages and in vivo in animal models that microbial products from LAD-associated subgingival plaque trigger IL-23-related immune responses, which have been shown to dominate in patient lesions. In conclusion, our current study characterizes the subgingival microbial communities in LAD-periodontitis and supports their role as triggers of disease pathogenesis.

The Hygiene Hypothesis in the Age of the Microbiome.

PubMed

Ege, Markus J

2017-11-01

The original version of the hygiene hypothesis suggested that infections transmitted early in life by "unhygienic contact" prevented allergies. Examples were endemic fecal-oral infections by viral, bacterial, or protozoic pathogens, such as hepatitis A virus, Helicobacter pylori, or Toxoplasma gondii. Later, this concept also included microorganisms beyond pathogens, such as commensals and symbionts, and the hygiene hypothesis was extended to inflammatory diseases in general. An impressive illustration of the hygiene hypothesis was found in the consistent farm effect on asthma and allergies, which has partly been attributed to immunomodulatory properties of endotoxin as emitted by livestock. Assessment of environmental microorganisms by molecular techniques suggested an additional protective effect of microbial diversity on asthma beyond atopy. Whether microbial diversity stands for a higher probability to encounter protective clusters of microorganisms or whether it is a proxy of a balanced environmental exposure remains elusive. Diversity of the mucosal microbiome of the upper airways probably reflects an undisturbed balance of beneficial microorganisms and pathogens, such as Moraxella catarrhalis, which has been associated with subsequent development of asthma and pneumonia. In addition, specific fermenters of plant fibers, such as the genera Ruminococcus and Bacteroides, have been implied in asthma protection through production of short-chain fatty acids, volatile substances with the capability to reduce T-helper cell type 2-mediated allergic airway inflammation. Evolutionary thinking may offer a key to understanding noncommunicable inflammatory diseases as delayed adaptation to a world of fast and profound environmental changes. Better adaptation may be fostered by growing insight into the interplay between man and microbiome and an adequate choice of the environmental exposure.

A Stoichioproteomic Analysis of Samples from the Human Microbiome Project

PubMed Central

Vecchio-Pagan, Briana; Bewick, Sharon; Mainali, Kumar; Karig, David K.; Fagan, William F.

2017-01-01

Ecological stoichiometry (ES) uses organism-specific elemental content to explain differences in species life histories, species interactions, community organization, environmental constraints and even ecosystem function. Although ES has been successfully applied to a range of different organisms, most emphasis on microbial ecological stoichiometry focuses on lake, ocean, and soil communities. With the recent advances in human microbiome research, however, large amounts of data are being generated that describe differences in community composition across body sites and individuals. We suggest that ES may provide a framework for beginning to understand the structure, organization, and function of human microbial communities, including why certain organisms exist at certain locations, and how they interact with both the other microbes in their environment and their human host. As a first step, we undertake a stoichioproteomic analysis of microbial communities from different body sites. Specifically, we compare and contrast the elemental composition of microbial protein samples using annotated sequencing data from 690 gut, vaginal, oral, nares, and skin samples currently available through the Human Microbiome Project. Our results suggest significant differences in both the median and variance of the carbon, oxygen, nitrogen, and sulfur contents of microbial protein samples from different locations. For example, whereas proteins from vaginal sites are high in carbon, proteins from skin and nasal sites are high in nitrogen and oxygen. Meanwhile, proteins from stool (the gut) are particularly high in sulfur content. We interpret these differences in terms of the local environments at different human body sites, including atmospheric exposure and food intake rates. PMID:28769875

Rhizosphere Microbiomes Modulated by Pre-crops Assisted Plants in Defense Against Plant-Parasitic Nematodes

PubMed Central

Elhady, Ahmed; Adss, Shimaa; Hallmann, Johannes; Heuer, Holger

2018-01-01

Plant-parasitic nematodes cause considerable damage to crop plants. The rhizosphere microbiome can affect invasion and reproductive success of plant-parasitic nematodes, thus affecting plant damage. In this study, we investigated how the transplanted rhizosphere microbiome from different crops affect plant-parasitic nematodes on soybean or tomato, and whether the plant’s own microbiome from the rhizosphere protects it better than the microbiome from fallow soil. Soybean plants growing in sterilized substrate were inoculated with the microbiome extracted from the rhizosphere of soybean, maize, or tomato. Controls were inoculated with extracts from bulk soil, or not inoculated. After the microbiome was established, the root lesion nematode Pratylenchus penetrans was added. Root invasion of P. penetrans was significantly reduced on soybean plants inoculated with the microbiome from maize or soybean compared to tomato or bulk soil, or the uninoculated control. In the analogous experiment with tomato plants inoculated with either P. penetrans or the root knot nematode Meloidogyne incognita, the rhizosphere microbiomes of maize and tomato reduced root invasion by P. penetrans and M. incognita compared to microbiomes from soybean or bulk soil. Reproduction of M. incognita on tomato followed the same trend, and it was best suppressed by the tomato rhizosphere microbiome. In split-root experiments with soybean and tomato plants, a systemic effect of the inoculated rhizosphere microbiomes on root invasion of P. penetrans was shown. Furthermore, some transplanted microbiomes slightly enhanced plant growth compared to uninoculated plants. The microbiomes from maize rhizosphere and bulk soil increased the fresh weights of roots and shoots of soybean plants, and microbiomes from soybean rhizosphere and bulk soil increased the fresh weights of roots and shoots of tomato plants. Nematode invasion did not affect plant growth in these short-term experiments. In conclusion, this study highlights the importance of the rhizosphere microbiome in protecting crops against plant-parasitic nematodes. An effect of pre-crops on the rhizosphere microbiome might be harnessed to enhance the resistance of crops towards plant-parasitic nematodes. However, nematode-suppressive effects of a particular microbiome may not necessarily coincide with improvement of plant growth in the absence of plant-parasitic nematodes. PMID:29915566

Hot topic: 16S rRNA gene sequencing reveals the microbiome of the virgin and pregnant bovine uterus.

PubMed

Moore, S G; Ericsson, A C; Poock, S E; Melendez, P; Lucy, M C

2017-06-01

We tested the hypothesis that the uterus of virgin heifers and pregnant cows possessed a resident microbiome by 16S rRNA gene sequencing of the virgin and pregnant bovine uterus. The endometrium of 10 virgin heifers in estrus and the amniotic fluid, placentome, intercotyledonary placenta, cervical lumen, and external cervix surface (control) of 5 pregnant cows were sampled using aseptic techniques. The DNA was extracted, the V4 hypervariable region of the 16S rRNA gene was amplified, and amplicons were sequenced using Illumina MiSeq technology (Illumina Inc., San Diego, CA). Operational taxonomic units (OTU) were generated from the sequences using Qiime v1.8 software, and taxonomy was assigned using the Greengenes database. The effect of tissue on the microbial composition within the pregnant uterus was tested using univariate (mixed model) and multivariate (permutational multivariate ANOVA) procedures. Amplicons of 16S rRNA gene were generated in all samples, supporting the contention that the uterus of virgin heifers and pregnant cows contained a microbiome. On average, 53, 199, 380, 382, 525, and 13,589 reads annotated as 16, 35, 43, 63, 48, and 176 OTU in the placentome, virgin endometrium, amniotic fluid, cervical lumen, intercotyledonary placenta, and external surface of the cervix, respectively, were generated. The 3 most abundant phyla in the uterus of the virgin heifers and pregnant cows were Firmicutes, Bacteroidetes, and Proteobacteria, and they accounted for approximately 40, 35, and 10% of the sequences, respectively. Phyla abundance was similar between the tissues of the pregnant uterus. Principal component analysis, one-way PERMANOVA analysis of the Bray-Curtis similarity index, and mixed model analysis of the Shannon diversity index and Chao1 index demonstrated that the microbiome of the control tissue (external surface of the cervix) was significantly different from that of the amniotic fluid, intercotyledonary placenta, and placentome tissues. Interestingly, many bacterial species associated with postpartum uterine disease (i.e., Trueperella spp., Acinetobacter spp., Fusobacteria spp., Proteus spp., Prevotella spp., and Peptostreptococcus spp.) were also present in the uterus of virgin heifers and of pregnant cows. The presence of 16S rRNA gene sequence reads in the samples from the current study suggests that the uterine microbiome is established by the time a female reaches reproductive maturity, and that pregnancies are established and maintained in the presence of a uterine microbiome. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

In Vitro Cultivation of 'Unculturable' Oral Bacteria, Facilitated by Community Culture and Media Supplementation with Siderophores.

PubMed

Vartoukian, Sonia R; Adamowska, Aleksandra; Lawlor, Megan; Moazzez, Rebecca; Dewhirst, Floyd E; Wade, William G

2016-01-01

Over a third of oral bacteria are as-yet-uncultivated in-vitro. Siderophores have been previously shown to enable in-vitro growth of previously uncultivated bacteria. The objective of this study was to cultivate novel oral bacteria in siderophore-supplemented culture media. Various compounds with siderophore activity, including pyoverdines-Fe-complex, desferricoprogen and salicylic acid, were found to stimulate the growth of difficult-to-culture strains Prevotella sp. HOT-376 and Fretibacterium fastidiosum. Furthermore, pyrosequencing analysis demonstrated increased proportions of the as-yet-uncultivated phylotypes Dialister sp. HOT-119 and Megasphaera sp. HOT-123 on mixed culture plates supplemented with siderophores. Therefore a culture model was developed, which incorporated 15 μg siderophore (pyoverdines-Fe-complex or desferricoprogen) or 150 μl neat subgingival-plaque suspension into a central well on agar plates that were inoculated with heavily-diluted subgingival-plaque samples from subjects with periodontitis. Colonies showing satellitism were passaged onto fresh plates in co-culture with selected helper strains. Five novel strains, representatives of three previously-uncultivated taxa (Anaerolineae bacterium HOT-439, the first oral taxon from the Chloroflexi phylum to have been cultivated; Bacteroidetes bacterium HOT-365; and Peptostreptococcaceae bacterium HOT-091) were successfully isolated. All novel isolates required helper strains for growth, implying dependence on a biofilm lifestyle. Their characterisation will further our understanding of the human oral microbiome.

Microbiome engineering: Current applications and its future.

PubMed

Foo, Jee Loon; Ling, Hua; Lee, Yung Seng; Chang, Matthew Wook

2017-03-01

Microbiomes exist in all ecosystems and are composed of diverse microbial communities. Perturbation to microbiomes brings about undesirable phenotypes in the hosts, resulting in diseases and disorders, and disturbs the balance of the associated ecosystems. Engineering of microbiomes can be used to modify structures of the microbiota and restore ecological balance. Consequently, microbiome engineering has been employed for improving human health and agricultural productivity. The importance and current applications of microbiome engineering, particularly in humans, animals, plants and soil is reviewed. Furthermore, we explore the challenges in engineering microbiome and the future of this field, thus providing perspectives and outlook of microbiome engineering. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The alligator gut microbiome and implications for archosaur symbioses

PubMed Central

Keenan, Sarah W.; Engel, Annette Summers; Elsey, Ruth M.

2013-01-01

Among vertebrate gastrointestinal microbiome studies, complete representation of taxa is limited, particularly among reptiles. Here, we provide evidence for previously unrecognized host-microbiome associations along the gastrointestinal tract from the American alligator, a crown archosaur with shared ancestry to extinct taxa, including dinosaurs. Microbiome compositional variations reveal that the digestive system consists of multiple, longitudinally heterogeneous microbiomes that strongly correlate to specific gastrointestinal tract organs, regardless of rearing histories or feeding status. A core alligator gut microbiome comprised of Fusobacteria, but depleted in Bacteroidetes and Proteobacteria common to mammalians, is compositionally unique from other vertebrate gut microbiomes, including other reptiles, fish, and herbivorous and carnivorous mammals. As such, modern alligator gut microbiomes advance our understanding of archosaur gut microbiome evolution, particularly if conserved host ecology has retained archosaur-specific symbioses over geologic time. PMID:24096888

Oral cancer databases: A comprehensive review.

PubMed

Sarode, Gargi S; Sarode, Sachin C; Maniyar, Nikunj; Anand, Rahul; Patil, Shankargouda

2017-11-29

Cancer database is a systematic collection and analysis of information on various human cancers at genomic and molecular level that can be utilized to understand various steps in carcinogenesis and for therapeutic advancement in cancer field. Oral cancer is one of the leading causes of morbidity and mortality all over the world. The current research efforts in this field are aimed at cancer etiology and therapy. Advanced genomic technologies including microarrays, proteomics, transcrpitomics, and gene sequencing development have culminated in generation of extensive data and subjection of several genes and microRNAs that are distinctively expressed and this information is stored in the form of various databases. Extensive data from various resources have brought the need for collaboration and data sharing to make effective use of this new knowledge. The current review provides comprehensive information of various publicly accessible databases that contain information pertinent to oral squamous cell carcinoma (OSCC) and databases designed exclusively for OSCC. The databases discussed in this paper are Protein-Coding Gene Databases and microRNA Databases. This paper also describes gene overlap in various databases, which will help researchers to reduce redundancy and focus on only those genes, which are common to more than one databases. We hope such introduction will promote awareness and facilitate the usage of these resources in the cancer research community, and researchers can explore the molecular mechanisms involved in the development of cancer, which can help in subsequent crafting of therapeutic strategies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The roles of the outdoors and occupants in contributing to a potential pan-microbiome of the built environment: a review.

PubMed

Leung, Marcus H Y; Lee, Patrick K H

2016-05-24

Recent high-throughput sequencing technology has led to an expansion of knowledge regarding the microbial communities (microbiome) across various built environments (BEs). The microbiome of the BE is dependent upon building factors and conditions that govern how outdoor microbes enter and persist in the BE. Additionally, occupants are crucial in shaping the microbiome of the BE by releasing human-associated microorganisms and resuspending microbes on floors and surfaces. Therefore, both the outdoors and occupants act as major sources of microorganisms found in the BE. However, most characterizations of the microbiome of the BE have been conducted in the Western world. Notably, outdoor locations and population groups present geographical variations in outdoor and human microbiomes, respectively. Given the influences of the outdoor and human microbiomes on BE microbiology, and the geographical variations in outdoor and human microbiomes, it is likely that the microbiomes of BEs also vary by location. The summation of microbiomes between BEs contribute to a potential BE pan-microbiome, which will both consist of microbes that are ubiquitous in indoor environments around the world, and microbes that appear to be endemic to particular geographical locations. Importantly, the BE pan-microbiome can potentially question the global application of our current views on indoor microbiology. In this review, we first provide an assessment on the roles of building and occupant properties on shaping the microbiome of the BE. This is then followed by a description of geographical variations in the microbiomes of the outdoors and humans, the two main sources of microbes in BEs. We present evidence of differences in microbiomes of BEs around the world, demonstrating the existence of a global pan-microbiome of the BE that is larger than the microbiome of any single indoor environment. Finally, we discuss the significance of understanding the BE pan-microbiome and identifying universal and location-specific relationships between building and occupant characteristics and indoor microbiology. This review highlights the much needed efforts towards determining the pan-microbiome of the BE, thereby identifying general and location-specific links between the microbial communities of the outdoors, human, and BE ecosystems, ultimately improving the health, comfort, and productivity of occupants around the world.

Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

PubMed Central

Kumar, Rohitashw; Saraswat, Darpan; Tati, Swetha

2015-01-01

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a Δsap8 strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6 strain was attenuated. These hypervirulent strains had highly aggregative colony structure in vitro and higher secreted proteinase activity; however, the levels of proteinase activity of C. albicans Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and Δsap8 cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis. PMID:25870228

Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis.

PubMed

Kumar, Rohitashw; Saraswat, Darpan; Tati, Swetha; Edgerton, Mira

2015-07-01

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a Δsap8 strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6 strain was attenuated. These hypervirulent strains had highly aggregative colony structure in vitro and higher secreted proteinase activity; however, the levels of proteinase activity of C. albicans Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and Δsap8 cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

Bacteriome and mycobiome associations in oral tongue cancer.

PubMed

Mukherjee, Pranab K; Wang, Hannah; Retuerto, Mauricio; Zhang, Huan; Burkey, Brian; Ghannoum, Mahmoud A; Eng, Charis

2017-11-14

Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P <0.006). Firmicutes was the most abundant bacterial phylum, which was significantly increased in TT compared to NTT (48% vs. 40%, respectively; P =0.004). Abundance of Bacteroidetes and Fusobacteria were significantly decreased in TT compared to matched NTT ( P ≤0.003 for both). Abundance of 22 bacterial and 7 fungal genera was significantly different between the TT and NTT, including Streptococcus , which was the most abundant and significantly increased in the tumor group (34% vs. 22%, P <0.001). Abundance of fungal genus Aspergillus in TT correlated negatively with bacteria ( Actinomyces, Prevotella , Streptococcus) , but positively with Aggregatibacter . Patients with high T-stage disease had lower mean differences between TT and NTT compared with patients with low T-stage disease (0.07 vs. 0.21, P =0.04). Our results demonstrate differences in bacteriome and mycobiome between OMTC and their matched normal oral epithelium, and their association with T-stage.

The human gut microbiome of Latin America populations: a landscape to be discovered.

PubMed

Magne, Fabien; O'Ryan, Miguel L; Vidal, Roberto; Farfan, Mauricio

2016-10-01

The gut microbiome is critical for human health, and its alteration is associated with intestinal, autoimmune and metabolic diseases. Numerous studies have focused on prevention or treatment of dysbiotic microbiome to reduce the risk or effect of these diseases. A key issue is to define the microbiome associated with the state of good health. The purpose of this review is to describe factors influencing the gut microbiome with special emphasis on contributions from Latin America. In addition, we will highlight opportunities for future studies on gut microbiome in Latin America. A relevant factor influencing gut microbiome composition is geographical location associated with specific genetic, dietary and lifestyle factors. Geographical specificities suggest that a universal 'healthy microbiome' is unlikely. Several research programs, mostly from Europe and North America, are extensively sequencing gut microbiome of healthy people, whereas data from Latin America remain scarce yet slowly increasing. Few studies have shown difference in the composition of gut microbiome between their local populations with that of other industrialized countries (North American populations). Latin America is composed of countries with a myriad of lifestyles, traditions, genetic backgrounds and socioeconomic conditions, which may determine differences in gut microbiome of individuals from different countries. This represents an opportunity to better understand the relationship between these factors and gut microbiome.

Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis

PubMed Central

Ryan, Lisa K.; Freeman, Katie B.; Masso-Silva, Jorge A.; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G.; Fatahzadeh, Mahnaz; Scott, Richard W.

2014-01-01

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis. PMID:24752272

Ancient DNA analysis of dental calculus.

PubMed

Weyrich, Laura S; Dobney, Keith; Cooper, Alan

2015-02-01

Dental calculus (calcified tartar or plaque) is today widespread on modern human teeth around the world. A combination of soft starchy foods, changing acidity of the oral environment, genetic pre-disposition, and the absence of dental hygiene all lead to the build-up of microorganisms and food debris on the tooth crown, which eventually calcifies through a complex process of mineralisation. Millions of oral microbes are trapped and preserved within this mineralised matrix, including pathogens associated with the oral cavity and airways, masticated food debris, and other types of extraneous particles that enter the mouth. As a result, archaeologists and anthropologists are increasingly using ancient human dental calculus to explore broad aspects of past human diet and health. Most recently, high-throughput DNA sequencing of ancient dental calculus has provided valuable insights into the evolution of the oral microbiome and shed new light on the impacts of some of the major biocultural transitions on human health throughout history and prehistory. Here, we provide a brief historical overview of archaeological dental calculus research, and discuss the current approaches to ancient DNA sampling and sequencing. Novel applications of ancient DNA from dental calculus are discussed, highlighting the considerable scope of this new research field for evolutionary biology and modern medicine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Probiotics, antibiotics and the immune responses to vaccines.

PubMed

Praharaj, Ira; John, Sushil M; Bandyopadhyay, Rini; Kang, Gagandeep

2015-06-19

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Looking in the Porphyromonas gingivalis’ Cabinet of Curiosities: The Microbium, the Host and Cancer Association

PubMed Central

Atanasova, Kalina R; Yilmaz, Özlem

2014-01-01

Summary The past decades of biomedical research have yielded massive evidence for the contribution of microbiome in the development of a variety of chronic human diseases. There is emerging evidence that Porphyromonas gingivalis, a well-adapted opportunistic pathogen of the oral mucosa and prominent constituent of oral biofilms, best known for its involvement in periodontitis, may be an important mediator in the development of a number of multifactorial and seemingly unrelated chronic diseases, such as rheumatoid arthritis and orodigestive cancers. Orodigestive cancers represent a big portion of the total malignancies worldwide, and include cancers of the oral cavity, gastro-intestinal tract, and pancreas. For prevention and/or enhanced prognosis of these diseases, a good understanding of the pathophysiological mechanisms and the interaction between P. gingivalis and host is much needed. With this review, we introduce the currently accumulated knowledge on P. gingivalis’ plausible association with cancer as a risk modifier, and present the putative cancer promoting cellular and molecular mechanisms that this organism may influence in the oral mucosa. “Knowledge is made by oblivion, and to purchase a clear and warrantable body of truth, we must forget and part with much we know”Sir Thomas Browne (1605–1682) PMID:24506890

Composition and variation of respiratory microbiota in healthy military personnel.

PubMed

Hang, Jun; Zavaljevski, Nela; Yang, Yu; Desai, Valmik; Ruck, Richard C; Macareo, Louis R; Jarman, Richard G; Reifman, Jaques; Kuschner, Robert A; Keiser, Paul B

2017-01-01

Certain occupational and geographical exposures have been associated with an increased risk of lung disease. As a baseline for future studies, we sought to characterize the upper respiratory microbiomes of healthy military personnel in a garrison environment. Nasal, oropharyngeal, and nasopharyngeal swabs were collected from 50 healthy active duty volunteers eight times over the course of one year (1107 swabs, completion rate = 92.25%) and subjected to pyrosequencing of the V1-V3 region of 16S rDNA. Respiratory bacterial taxa were characterized at the genus level, using QIIME 1.8 and the Ribosomal Database Project classifier. High levels of Staphylococcus, Corynebacterium, and Propionibacterium were observed among both nasal and nasopharyngeal microbiota, comprising more than 75% of all operational taxonomical units (OTUs). In contrast, Streptococcus was the sole dominant bacterial genus (approximately 50% of all OTUs) in the oropharynx. The average bacterial diversity was greater in the oropharynx than in the nasal or nasopharyngeal region at all time points. Diversity analysis indicated a significant overlap between nasal and nasopharyngeal samples, whereas oropharyngeal samples formed a cluster distinct from these two regions. The study produced a large set of pyrosequencing data on the V1-V3 region of bacterial 16S rDNA for the respiratory microbiomes of healthy active duty Service Members. Pre-processing of sequencing reads showed good data quality. The derived microbiome profiles were consistent both internally and with previous reports, suggesting their utility for further analyses and association studies based on sequence and demographic data.

Metabolome of human gut microbiome is predictive of host dysbiosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, Peter E.; Dai, Yang

Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent onmore » its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

Metabolome of human gut microbiome is predictive of host dysbiosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, Peter E.; Dai, Yang

Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependentmore » on its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

Metabolome of human gut microbiome is predictive of host dysbiosis

DOE PAGES

Larsen, Peter E.; Dai, Yang

2015-09-14

Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent onmore » its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.« less

Host and Aquatic Environment Shape the Amphibian Skin Microbiome but Effects on Downstream Resistance to the Pathogen Batrachochytrium dendrobatidis Are Variable

PubMed Central

Jani, Andrea J.; Briggs, Cheryl J.

2018-01-01

Symbiotic microbial communities play key roles in the health and development of their multicellular hosts. Understanding why microbial communities vary among different host species or individuals is an important step toward understanding the diversity and function of the microbiome. The amphibian skin microbiome may affect resistance to the fungal pathogen Batrachochytrium dendrobatidis (Bd). Still, the factors that determine the diversity and composition of the amphibian skin microbiome, and therefore may ultimately contribute to disease resistance, are not well understood. We conducted a two-phase experiment to first test how host and environment shape the amphibian skin microbiome, and then test if the microbiome affects or is affected by Bd infection. Most lab experiments testing assembly of the amphibian skin microbiome so far have compared sterile to non-sterile environments or heavily augmented to non-augmented frogs. A goal of this study was to evaluate, in an experimental setting, realistic potential drivers of microbiome assembly that would be relevant to patterns observed in nature. We tested effects of frog genetic background (2 source populations) and 6 natural lake water sources in shaping the microbiome of the frog Rana sierrae. Water in which frogs were housed affected the microbiome in a manner that partially mimicked patterns observed in natural populations. In particular, frogs housed in water from disease-resistant populations had greater bacterial richness than frogs housed in water from populations that died out due to Bd. However, in the experiment this difference in microbiomes did not lead to differences in host mortality or rates of pathogen load increase. Frog source population also affected the microbiome and, although none of the frogs in this study showed true resistance to infection, host source population had a small effect on the rate of pathogen load increase. This difference in infection trajectories could be due to the observed differences in the microbiome, but could also be due to other traits that differ between frogs from the two populations. In addition to examining effects of the microbiome on Bd, we tested the effect of Bd infection severity on the microbiome. Specifically, we studied a time series of the microbiome over the course of infection to test if the effects of Bd on the microbiome are dependent on Bd infection severity. Although limited to a small subset of frogs, time series analysis suggested that relative abundances of several bacterial phylotypes changed as Bd loads increased through time, indicating that Bd-induced disturbance of the R. sierrae microbiome is not a binary effect but instead is dependent on infection severity. We conclude that both host and aquatic environment help shape the R. sierrae skin microbiome, with links to small changes in disease resistance in some cases, but in this study the effect of Bd on the microbiome was greater than the effect of the microbiome on Bd. Assessment of the microbiome differences between more distantly related populations than those studied here is needed to fully understand the role of the microbiome in resistance to Bd. PMID:29619014

16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment.

PubMed

Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne; Rodríguez-Hilario, Arnold; González, Herminio; Bondy, Jessica; Lawson, Fahcina; Folawiyo, Oluwasina; Michailidi, Christina; Dziedzic, Amanda; Thangavel, Rajagowthamee; Hadar, Tal; Noordhuis, Maartje G; Westra, William; Koch, Wayne; Sidransky, David

2016-08-09

Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection.The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors.

16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment

PubMed Central

Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne; Rodríguez-Hilario, Arnold; González, Herminio; Bondy, Jessica; Lawson, Fahcina; Folawiyo, Oluwasina; Michailidi, Christina; Dziedzic, Amanda; Thangavel, Rajagowthamee; Hadar, Tal; Noordhuis, Maartje G.; Westra, William; Koch, Wayne; Sidransky, David

2016-01-01

Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection. The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors. PMID:27259999

Microbiomes of Endodontic-Periodontal Lesions before and after Chemomechanical Preparation.

PubMed

Gomes, Brenda P F A; Berber, Vanessa B; Kokaras, Alexis S; Chen, Tsute; Paster, Bruce J

2015-12-01

This study was conducted to evaluate the microbiomes of endodontic-periodontal lesions before and after chemomechanical preparation (CMP). Clinical samples were taken from 15 root canals (RCs) with necrotic pulp tissues and from their associated periodontal pockets (PPs) (n = 15) of teeth with endodontic-periodontal lesions before and after CMP. The Human Oral Microbe Identification using Next Generation Sequencing (NGS) protocol and viable culture were used to analyze samples from RCs and PPs. The Mann-Whitney U test and Benjamini-Hochberg corrections were performed to correlate the clinical and radiographic findings with microbial findings (P < .05). Bacteria were detected in 100% of the samples in both sites (15/15) using NGS. Firmicutes was the most predominant phylum in both sites using both methods. The most frequently detected species in the RCs before and after CMP using NGS were Enterococcus faecalis, Parvimonas micra, Mogibacterium timidum, Filifactor alocis, and Fretibacterium fastidiosum. The species most frequently detected in the PPs before and after CMP using NGS were P. micra, E. faecalis, Streptococcus constellatus, Eubacterium brachy, Tannerella forsythia, and F. alocis. Associations were found between periapical lesions ≤ 2 mm and Desulfobulbus sp oral taxon 041 and with periodontal pockets ≥ 6 mm and Dialister invisius and Peptostreptococcus stomatis (all P < .05, found in the RCs before CMP). It is concluded that the microbial community present in combined endodontic-periodontal lesions is complex and more diverse than previously reported. It is important to note that bacteria do survive in some root canals after CMP. Finally, the similarity between the microbiota of both sites, before and after CMP, suggests there may be a pathway of infection between the pulp and periodontium. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The Challenge of Maintaining a Healthy Microbiome During Long-Duration Space Missions.

NASA Astrophysics Data System (ADS)

Voorhies, Alexander; Lorenzi, Hernan

2016-07-01

Astronauts will face a host of challenges on long-duration space missions like a human expedition to Mars, including the difficulty of maintaining a balanced and healthy microbiome. The human microbiome is the collection of all microorganisms residing in and on a human host, and it plays an essential role in keeping humans healthy. However, imbalances in the microbiome have also been linked to many human diseases. Space travel has been shown to alter the microbiome of astronauts in ways that are not yet completely understood. Here we review past and current microbiology and microbiome research with the aim of determining the extent of change to the human microbiome caused by space travel and implications for astronaut health. We also address several challenges that will need to be overcome in order to facilitate long-duration human exploration missions. These challenges include maintaining environmental conditions that favor healthy microbiomes, controlling the microbial organisms astronauts are exposed to, the impact of galactic cosmic radiation on the microbiome, and medical interventions that can potentially damage the microbiome.

Disseminating Metaproteomic Informatics Capabilities and Knowledge Using the Galaxy-P Framework

PubMed Central

Easterly, Caleb; Gruening, Bjoern; Johnson, James; Kolmeder, Carolin A.; Kumar, Praveen; May, Damon; Mehta, Subina; Mesuere, Bart; Brown, Zachary; Elias, Joshua E.; Hervey, W. Judson; McGowan, Thomas; Muth, Thilo; Rudney, Joel; Griffin, Timothy J.

2018-01-01

The impact of microbial communities, also known as the microbiome, on human health and the environment is receiving increased attention. Studying translated gene products (proteins) and comparing metaproteomic profiles may elucidate how microbiomes respond to specific environmental stimuli, and interact with host organisms. Characterizing proteins expressed by a complex microbiome and interpreting their functional signature requires sophisticated informatics tools and workflows tailored to metaproteomics. Additionally, there is a need to disseminate these informatics resources to researchers undertaking metaproteomic studies, who could use them to make new and important discoveries in microbiome research. The Galaxy for proteomics platform (Galaxy-P) offers an open source, web-based bioinformatics platform for disseminating metaproteomics software and workflows. Within this platform, we have developed easily-accessible and documented metaproteomic software tools and workflows aimed at training researchers in their operation and disseminating the tools for more widespread use. The modular workflows encompass the core requirements of metaproteomic informatics: (a) database generation; (b) peptide spectral matching; (c) taxonomic analysis and (d) functional analysis. Much of the software available via the Galaxy-P platform was selected, packaged and deployed through an online metaproteomics “Contribution Fest“ undertaken by a unique consortium of expert software developers and users from the metaproteomics research community, who have co-authored this manuscript. These resources are documented on GitHub and freely available through the Galaxy Toolshed, as well as a publicly accessible metaproteomics gateway Galaxy instance. These documented workflows are well suited for the training of novice metaproteomics researchers, through online resources such as the Galaxy Training Network, as well as hands-on training workshops. Here, we describe the metaproteomics tools available within these Galaxy-based resources, as well as the process by which they were selected and implemented in our community-based work. We hope this description will increase access to and utilization of metaproteomics tools, as well as offer a framework for continued community-based development and dissemination of cutting edge metaproteomics software. PMID:29385081

Disseminating Metaproteomic Informatics Capabilities and Knowledge Using the Galaxy-P Framework.

PubMed

Blank, Clemens; Easterly, Caleb; Gruening, Bjoern; Johnson, James; Kolmeder, Carolin A; Kumar, Praveen; May, Damon; Mehta, Subina; Mesuere, Bart; Brown, Zachary; Elias, Joshua E; Hervey, W Judson; McGowan, Thomas; Muth, Thilo; Nunn, Brook; Rudney, Joel; Tanca, Alessandro; Griffin, Timothy J; Jagtap, Pratik D

2018-01-31

The impact of microbial communities, also known as the microbiome, on human health and the environment is receiving increased attention. Studying translated gene products (proteins) and comparing metaproteomic profiles may elucidate how microbiomes respond to specific environmental stimuli, and interact with host organisms. Characterizing proteins expressed by a complex microbiome and interpreting their functional signature requires sophisticated informatics tools and workflows tailored to metaproteomics. Additionally, there is a need to disseminate these informatics resources to researchers undertaking metaproteomic studies, who could use them to make new and important discoveries in microbiome research. The Galaxy for proteomics platform (Galaxy-P) offers an open source, web-based bioinformatics platform for disseminating metaproteomics software and workflows. Within this platform, we have developed easily-accessible and documented metaproteomic software tools and workflows aimed at training researchers in their operation and disseminating the tools for more widespread use. The modular workflows encompass the core requirements of metaproteomic informatics: (a) database generation; (b) peptide spectral matching; (c) taxonomic analysis and (d) functional analysis. Much of the software available via the Galaxy-P platform was selected, packaged and deployed through an online metaproteomics "Contribution Fest" undertaken by a unique consortium of expert software developers and users from the metaproteomics research community, who have co-authored this manuscript. These resources are documented on GitHub and freely available through the Galaxy Toolshed, as well as a publicly accessible metaproteomics gateway Galaxy instance. These documented workflows are well suited for the training of novice metaproteomics researchers, through online resources such as the Galaxy Training Network, as well as hands-on training workshops. Here, we describe the metaproteomics tools available within these Galaxy-based resources, as well as the process by which they were selected and implemented in our community-based work. We hope this description will increase access to and utilization of metaproteomics tools, as well as offer a framework for continued community-based development and dissemination of cutting edge metaproteomics software.

Analysis of oral microbiota in children with dental caries by PCR-DGGE and barcoded pyrosequencing.

PubMed

Ling, Zongxin; Kong, Jianming; Jia, Peng; Wei, Chaochun; Wang, Yuezhu; Pan, Zhiwen; Huang, Wujing; Li, Lanjuan; Chen, Hui; Xiang, Charlie

2010-10-01

Oral microbiota plays a vital role in maintaining the homeostasis of oral cavity. Dental caries are among the most common oral diseases in children and pathogenic bacteria contribute to the development of the disease. However, the overall structure of bacterial communities in the oral cavity from children with dental caries has not been explored deeply heretofore. We used high-throughput barcoded pyrosequencing and PCR-denaturing gradient gel electrophoresis (DGGE) to examine bacterial diversity of oral microbiota in saliva and supragingival plaques from 60 children aged 3 to 6 years old with and without dental caries from China. The multiplex barcoded pyrosequencing was performed in a single run, with multiple samples tagged uniquely by multiplex identifiers. As PCR-DGGE analysis is a conventional molecular ecological approach, this analysis was also performed on the same samples and the results of both approaches were compared. A total of 186,787 high-quality sequences were obtained for evaluating bacterial diversity and 41,905 unique sequences represented all phylotypes. We found that the oral microbiota in children was far more diverse than previous studies reported, and more than 200 genera belonging to ten phyla were found in the oral cavity. The phylotypes in saliva and supragingival plaques were significantly different and could be divided into two distinct clusters (p < 0.05). The bacterial diversity in oral microbiome analyzed by PCR-DGGE and barcoded pyrosequencing was employed to cross validate the data sets. The genera of Streptococcus, Veillonella, Actinomyces, Granulicatella, Leptotrichia, and Thiomonas in plaques were significantly associated with dental caries (p < 0.05). The results showed that there was no one specific pathogen but rather pathogenic populations in plaque that significantly correlated with dental caries. The enormous diversity of oral microbiota allowed for a better understanding of oral microecosystem, and these pathogenic populations in plaque provide new insights into the etiology of dental caries and suggest new targets for interventions of the disease.

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.

PubMed

Gopalakrishnan, Vancheswaran; Helmink, Beth A; Spencer, Christine N; Reuben, Alexandre; Wargo, Jennifer A

2018-04-09

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses. Copyright © 2018 Elsevier Inc. All rights reserved.

Mining virulence genes using metagenomics.

PubMed

Belda-Ferre, Pedro; Cabrera-Rubio, Raúl; Moya, Andrés; Mira, Alex

2011-01-01

When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

Fundamentals of precision medicine

PubMed Central

Divaris, Kimon

2018-01-01

Imagine a world where clinicians make accurate diagnoses and provide targeted therapies to their patients according to well-defined, biologically-informed disease subtypes, accounting for individual differences in genetic make-up, behaviors, cultures, lifestyles and the environment. This is not as utopic as it may seem. Relatively recent advances in science and technology have led to an explosion of new information on what underlies health and what constitutes disease. These novel insights emanate from studies of the human genome and microbiome, their associated transcriptomes, proteomes and metabolomes, as well as epigenomics and exposomics—such ‘omics data can now be generated at unprecedented depth and scale, and at rapidly decreasing cost. Making sense and integrating these fundamental information domains to transform health care and improve health remains a challenge—an ambitious, laudable and high-yield goal. Precision dentistry is no longer a distant vision; it is becoming part of the rapidly evolving present. Insights from studies of the human genome and microbiome, their associated transcriptomes, proteomes and metabolomes, and epigenomics and exposomics have reached an unprecedented depth and scale. Much more needs to be done, however, for the realization of precision medicine in the oral health domain. PMID:29227115

Proceedings of the 11th Congress of the International Society of Nutrigenetics and Nutrigenomics (ISNN 2017).

PubMed

Barrington, William T; Salvador, Anna C; Hartiala, Jaana A; De Caterina, Raffaele; Kohlmeier, Martin; Martinez, J Alfredo; Kreutzer, Carin B; Heber, David; Lusis, Aldons J; Li, Zhaoping; Allayee, Hooman

2017-01-01

The International Society of Nutrigenetics and Nutrigenomics (ISNN) held its 11th annual Congress in Los Angeles, California, between September 16 and 19, 2017. In addition to 2 keynote lectures, 4 plenary sessions included presentations by internationally renowned speakers on cutting-edge areas of research and new discoveries in genetics/genomics, the microbiome, and nutrition. Scientific topics included multi-omics approaches; diet and the microbiome; cancer, longevity, and metabolism; moving the field forward; and translational/educational aspects and the future of medicine. There was also an accepted oral abstracts session designed specifically to provide young investigators and trainees with the opportunity to present their work, as well as a session focused on industry-academic partnerships, which included a roundtable discussion afterwards. Overall, the 11th ISNN Congress was an exciting and intellectually stimulating meeting focused on understanding the impact of biological interactions between genes and nutrients on health and disease. These efforts continued the decade-long tradition of the annual ISNN Congress to provide an interdisciplinary platform for scientists from various disciplines to discuss research ideas and advance the fields of nutrigenetics and nutrigenomics. © 2018 S. Karger AG, Basel.

A snapshot of gut microbiota of an adult urban population from Western region of India.

PubMed

Tandon, Disha; Haque, Mohammed Monzoorul; R, Saravanan; Shaikh, Shafiq; P, Sriram; Dubey, Ashok Kumar; Mande, Sharmila S

2018-01-01

The human gut microbiome contributes to a broad range of biochemical and metabolic functions that directly or indirectly affect human physiology. Several recent studies have indicated that factors like age, geographical location, genetic makeup, and individual health status significantly influence the diversity, stability, and resilience of the gut microbiome. Of the mentioned factors, geographical location (and related dietary/socio-economic context) appears to explain a significant portion of microbiome variation observed in various previously conducted base-line studies on human gut microbiome. Given this context, we have undertaken a microbiome study with the objective of cataloguing the taxonomic diversity of gut microbiomes sampled from an urban cohort from Ahmedabad city in Western India. Computational analysis of microbiome sequence data corresponding to 160 stool samples (collected from 80 healthy individuals at two time-points, 60 days apart) has indicated a Prevotella-dominated microbial community. Given that the typical diet of participants included carbohydrate and fibre-rich components (predominantly whole grains and legume-based preparations), results appear to validate the proposed correlation between diet/geography and microbiome composition. Comparative analysis of obtained gut microbiome profiles with previously published microbiome profiles from US, China, Finland, and Japan additionally reveals a distinct taxonomic and (inferred) functional niche for the sampled microbiomes.

Academic Oral History: Life Review in Spite of Itself.

ERIC Educational Resources Information Center

Ryant, Carl

The process and content of the life review should not be separated from the creation of an oral history. Several projects, undertaken at the University of Louisville Oral History Center, support the therapeutic aspects of reminiscence. The dichotomy between oral history, as an historical database, and life review, as a therapeutic exercise, breaks…

Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

PubMed Central

Newberry, Fiona; Hsieh, Shen-Yuan; Wileman, Tom; Carding, Simon R.

2018-01-01

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed. PMID:29523751

The Perinatal Microbiome and Pregnancy: Moving Beyond the Vaginal Microbiome

PubMed Central

Prince, Amanda L.; Chu, Derrick M.; Seferovic, Maxim D.; Antony, Kathleen M.; Ma, Jun; Aagaard, Kjersti M.

2015-01-01

The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition. PMID:25775922

The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition.

PubMed

Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm

2014-01-01

Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge. Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers. Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.

Bioinformatics tools for quantitative and functional metagenome and metatranscriptome data analysis in microbes.

PubMed

Niu, Sheng-Yong; Yang, Jinyu; McDermaid, Adam; Zhao, Jing; Kang, Yu; Ma, Qin

2017-05-08

Metagenomic and metatranscriptomic sequencing approaches are more frequently being used to link microbiota to important diseases and ecological changes. Many analyses have been used to compare the taxonomic and functional profiles of microbiota across habitats or individuals. While a large portion of metagenomic analyses focus on species-level profiling, some studies use strain-level metagenomic analyses to investigate the relationship between specific strains and certain circumstances. Metatranscriptomic analysis provides another important insight into activities of genes by examining gene expression levels of microbiota. Hence, combining metagenomic and metatranscriptomic analyses will help understand the activity or enrichment of a given gene set, such as drug-resistant genes among microbiome samples. Here, we summarize existing bioinformatics tools of metagenomic and metatranscriptomic data analysis, the purpose of which is to assist researchers in deciding the appropriate tools for their microbiome studies. Additionally, we propose an Integrated Meta-Function mapping pipeline to incorporate various reference databases and accelerate functional gene mapping procedures for both metagenomic and metatranscriptomic analyses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Market Integration Predicts Human Gut Microbiome Attributes across a Gradient of Economic Development

PubMed Central

Cepon-Robins, Tara J.; Liebert, Melissa A.; Gildner, Theresa E.; Urlacher, Samuel S.; Madimenos, Felicia C.; Guillemin, Karen; Snodgrass, J. Josh; Sugiyama, Lawrence S.; Bohannan, Brendan J. M.

2018-01-01

ABSTRACT Economic development is marked by dramatic increases in the incidence of microbiome-associated diseases, such as autoimmune diseases and metabolic syndromes, but the lifestyle changes that drive alterations in the human microbiome are not known. We measured market integration as a proxy for economically related lifestyle attributes, such as ownership of specific market goods that index degree of market integration and components of traditional and nontraditional (more modern) house structure and infrastructure, and profiled the fecal microbiomes of 213 participants from a contiguous, indigenous Ecuadorian population. Despite relatively modest differences in lifestyle across the population, greater economic development correlated with significantly lower within-host diversity, higher between-host dissimilarity, and a decrease in the relative abundance of the bacterium Prevotella. These microbiome shifts were most strongly associated with more modern housing, followed by reduced ownership of traditional subsistence lifestyle-associated items. IMPORTANCE Previous research has reported differences in the gut microbiome between populations residing in wealthy versus poorer countries, leading to the assertion that lifestyle changes associated with economic development promote changes in the gut microbiome that promote the proliferation of microbiome-associated diseases. However, a direct relationship between economic development and the gut microbiome has not previously been shown. We surveyed the gut microbiomes of a single indigenous population undergoing economic development and found significant associations between features of the gut microbiome and lifestyle changes associated with economic development. These findings suggest that even the earliest stages of economic development can drive changes in the gut microbiome, which may provide a warning sign for the development of microbiome-associated diseases. PMID:29507896

Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

PubMed

Kang, Dae-Wook; Adams, James B; Gregory, Ann C; Borody, Thomas; Chittick, Lauren; Fasano, Alessio; Khoruts, Alexander; Geis, Elizabeth; Maldonado, Juan; McDonough-Means, Sharon; Pollard, Elena L; Roux, Simon; Sadowsky, Michael J; Lipson, Karen Schwarzberg; Sullivan, Matthew B; Caporaso, J Gregory; Krajmalnik-Brown, Rosa

2017-01-23

Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10 13 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. This trial was registered on the ClinicalTrials.gov, with the registration number  NCT02504554.

Analysis of Stomach and Gut Microbiomes of the Eastern Oyster (Crassostrea virginica) from Coastal Louisiana, USA

PubMed Central

King, Gary M.; Judd, Craig; Kuske, Cheryl R.; Smith, Conor

2012-01-01

We used high throughput pyrosequencing to characterize stomach and gut content microbiomes of Crassostrea virginica, the Easter oyster, obtained from two sites, one in Barataria Bay (Hackberry Bay) and the other in Terrebonne Bay (Lake Caillou), Louisiana, USA. Stomach microbiomes in oysters from Hackberry Bay were overwhelmingly dominated by Mollicutes most closely related to Mycoplasma; a more rich community dominated by Planctomyctes occurred in Lake Caillou oyster stomachs. Gut communities for oysters from both sites differed from stomach communities, and harbored a relatively diverse assemblage of phylotypes. Phylotypes most closely related to Shewanella and a Chloroflexi strain dominated the Lake Caillou and Hackberry Bay gut microbiota, respectively. While many members of the stomach and gut microbiomes appeared to be transients or opportunists, a putative core microbiome was identified based on phylotypes that occurred in all stomach or gut samples only. The putative core stomach microbiome comprised 5 OTUs in 3 phyla, while the putative core gut microbiome contained 44 OTUs in 12 phyla. These results collectively revealed novel microbial communities within the oyster digestive system, the functions of the oyster microbiome are largely unknown. A comparison of microbiomes from Louisiana oysters with bacterial communities reported for other marine invertebrates and fish indicated that molluscan microbiomes were more similar to each other than to microbiomes of polychaetes, decapods and fish. PMID:23251548

Analysis of Stomach and Gut Microbiomes of the Eastern Oyster (Crassostrea virginica) from Coastal Louisiana, USA

DOE PAGES

King, Gary M.; Judd, Craig; Kuske, Cheryl R.; ...

2012-12-12

In this paper, we used high throughput pyrosequencing to characterize stomach and gut content microbiomes of Crassostrea virginica, the Easter oyster, obtained from two sites, one in Barataria Bay (Hackberry Bay) and the other in Terrebonne Bay (Lake Caillou), Louisiana, USA. Stomach microbiomes in oysters from Hackberry Bay were overwhelmingly dominated by Mollicutes most closely related to Mycoplasma; a more rich community dominated by Planctomyctes occurred in Lake Caillou oyster stomachs. Gut communities for oysters from both sites differed from stomach communities, and harbored a relatively diverse assemblage of phylotypes. Phylotypes most closely related to Shewanella and a Chloroflexi strainmore » dominated the Lake Caillou and Hackberry Bay gut microbiota, respectively. While many members of the stomach and gut microbiomes appeared to be transients or opportunists, a putative core microbiome was identified based on phylotypes that occurred in all stomach or gut samples only. The putative core stomach microbiome comprised 5 OTUs in 3 phyla, while the putative core gut microbiome contained 44 OTUs in 12 phyla. These results collectively revealed novel microbial communities within the oyster digestive system, the functions of the oyster microbiome are largely unknown. Finally, a comparison of microbiomes from Louisiana oysters with bacterial communities reported for other marine invertebrates and fish indicated that molluscan microbiomes were more similar to each other than to microbiomes of polychaetes, decapods and fish.« less

The role of microbiome in central nervous system disorders

PubMed Central

Wang, Yan; Kasper, Lloyd H.

2014-01-01

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation

PubMed Central

Heron, Samantha E.; Elahi, Shokrollah

2017-01-01

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to “inflammaging” that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore, unraveling how HIV compromises the integrity of the oral mucosal tissues and innate immune components of the oral cavity and its association with induction of chronic inflammation are critical for the development of effective preventive interventions and therapeutic strategies. PMID:28326084

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation.

PubMed

Heron, Samantha E; Elahi, Shokrollah

2017-01-01

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to "inflammaging" that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore, unraveling how HIV compromises the integrity of the oral mucosal tissues and innate immune components of the oral cavity and its association with induction of chronic inflammation are critical for the development of effective preventive interventions and therapeutic strategies.

A personal digital assistant application (MobilDent) for dental fieldwork data collection, information management and database handling.

PubMed

Forsell, M; Häggström, M; Johansson, O; Sjögren, P

2008-11-08

To develop a personal digital assistant (PDA) application for oral health assessment fieldwork, including back-office and database systems (MobilDent). System design, construction and implementation of PDA, back-office and database systems. System requirements for MobilDent were collected, analysed and translated into system functions. User interfaces were implemented and system architecture was outlined. MobilDent was based on a platform with. NET (Microsoft) components, using an SQL Server 2005 (Microsoft) for data storage with Windows Mobile (Microsoft) operating system. The PDA devices were Dell Axim. System functions and user interfaces were specified for MobilDent. User interfaces for PDA, back-office and database systems were based on. NET programming. The PDA user interface was based on Windows suitable to a PDA display, whereas the back-office interface was designed for a normal-sized computer screen. A synchronisation module (MS Active Sync, Microsoft) was used to enable download of field data from PDA to the database. MobilDent is a feasible application for oral health assessment fieldwork, and the oral health assessment database may prove a valuable source for care planning, educational and research purposes. Further development of the MobilDent system will include wireless connectivity with download-on-demand technology.

Rapid changes in the gut microbiome during human evolution

PubMed Central

Moeller, Andrew H.; Li, Yingying; Mpoudi Ngole, Eitel; Ahuka-Mundeke, Steve; Lonsdorf, Elizabeth V.; Pusey, Anne E.; Peeters, Martine; Hahn, Beatrice H.; Ochman, Howard

2014-01-01

Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan. PMID:25368157

Rapid changes in the gut microbiome during human evolution.

PubMed

Moeller, Andrew H; Li, Yingying; Mpoudi Ngole, Eitel; Ahuka-Mundeke, Steve; Lonsdorf, Elizabeth V; Pusey, Anne E; Peeters, Martine; Hahn, Beatrice H; Ochman, Howard

2014-11-18

Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan.

The Subgingival Microbiome of Periodontal Pockets With Different Probing Depths in Chronic and Aggressive Periodontitis: A Pilot Study.

PubMed

Shi, Meng; Wei, Yiping; Hu, Wenjie; Nie, Yong; Wu, Xiaolei; Lu, Ruifang

2018-01-01

Periodontitis is a kind of infectious disease initiated by colonization of subgingival periodontal pathogens, which cause destruction of tooth-supporting tissues, and is a predominant threat to oral health as the most common cause of loss of teeth. The aim of this pilot study was to characterize the subgingival bacterial biodiversity of periodontal pockets with different probing depths in patients with different forms of periodontitis. Twenty-one subgingival plaque samples were collected from three patients with chronic periodontitis (ChP), three patients with aggressive periodontitis (AgP) and three periodontally healthy subjects (PH). Each patient with periodontitis was sampled at three sites, at different probing depths (PDs, one each at 4 mm, 5-6 mm, and ≥ 7 mm). Using 16S rRNA gene high-throughput sequencing and bioinformatic analysis, we found that subgingival communities in health and periodontitis samples largely differed. Meanwhile, Acholeplasma, Fretibacterium, Porphyromonas, Peptococcus, Treponema_2, Defluviitaleaceae_UCG_011, Filifactor , and Mycoplasma increased with the deepening of the pockets in ChP, whilst only Corynebacterium was negatively associated with PD. In AgP, Corynebacterium and Klebsiella were positively associated with PD, while Serratia, Pseudoramibacter, Defluviitaleaceae_UCG_011 , and Desulfobulbus were negatively associated with PD. And among these two groups, Corynebacterium shifted differently. Moreover, in subgingival plaque, the unweighted UniFrac distances between samples from pockets with different PD in the same patients were significantly lower than those from pockets within the same PD category from different patients. This study demonstrated the shift of the subgingival microbiome in individual teeth sites during disease development. Within the limitation of the relative small sample size, this pilot study shed new light on the dynamic relationship between the extent of periodontal destruction and the subgingival microbiome.

Final Report: The Human Microbiome as a Multipurpose Biomarker

DTIC Science & Technology

2015-11-23

Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 microbiome, biomarker, microbial forensics, microbial ecology , identifiability REPORT...temporal variation in the ecology of the human microbiome, this work demonstrated the feasibility of microbiome-based identifiability for the first time...a result with important ethical implications for microbiome study design. In order to construct metagenomic codes that are stable over time, we

Metagenomic Analysis of the Dynamic Changes in the Gut Microbiome of the Participants of the MARS-500 Experiment, Simulating Long Term Space Flight

PubMed Central

Mardanov, A.V.; Babykin, M.M.; Beletsky, A.V.; Grigoriev, A.I.; Zinchenko, V.V.; Kadnikov, V.V.; Kirpichnikov, M.P.; Mazur, A.M.; Nedoluzhko, A.V.; Novikova, N.D.; Prokhortchouk, E.B.; Ravin, N.V.; Skryabin, K.G.; Shestakov, S.V.

2013-01-01

A metagenomic analysis of the dynamic changes of the composition of the intestinal microbiome of five participants of the MARS-500 experiment was performed. DNA samples were isolated from the feces of the participants taken just before the experiment, upon 14, 30, 210, 363 and 510 days of isolation in the experimental module, and two weeks upon completion of the experiment. The taxonomic composition of the microbiome was analyzed by pyrosequencing of 16S rRNA gene fragments. Both the taxonomic and functional gene content of the microbiome of one participant were analyzed by whole metagenome sequencing using the SOLiD technique. Each participant had a specific microbiome that could be assigned to one of three recognized enterotypes. Two participants had enterotype I microbiomes characterized by the prevalence of Bacteroides, while the microbiomes of two others, assigned to type II, were dominated by Prevotella. One participant had a microbiome of mixed type. It was found that (1) changes in the taxonimic composition of the microbiomes occurred in the course of the experiment, but the enterotypes remained the same; (2) significant changes in the compositions of the microbiomes occurred just 14-30 days after the beginning of the experiment, presumably indicating the influence of stress factors in the first stage of the experiment; (3) a tendency toward a reversion of the microbiomes to their initial composition was observed two weeks after the end of the experiment, but complete recovery was not achieved. The metagenomic analysis of the microbiome of one of the participants showed that in spite of variations in the taxonomic compositions of microbiomes, the “functional” genetic composition was much more stable for most of the functional gene categories. Probably in the course of the experiment the taxonomic composition of the gut microbiome was adaptively changed to reflect the individual response to the experimental conditions. A new, balanced taxonomic composition of the microbiome was formed to ensure a stable gene content of the community as a whole without negative consequences for the health of the participants. PMID:24303207

Extensive Core Microbiome in Drone-Captured Whale Blow Supports a Framework for Health Monitoring

PubMed Central

Miller, Carolyn A.; Moore, Michael J.; Durban, John W.; Fearnbach, Holly; Barrett-Lennard, Lance G.

2017-01-01

ABSTRACT The pulmonary system is a common site for bacterial infections in cetaceans, but very little is known about their respiratory microbiome. We used a small, unmanned hexacopter to collect exhaled breath condensate (blow) from two geographically distinct populations of apparently healthy humpback whales (Megaptera novaeangliae), sampled in the Massachusetts coastal waters off Cape Cod (n = 17) and coastal waters around Vancouver Island (n = 9). Bacterial and archaeal small-subunit rRNA genes were amplified and sequenced from blow samples, including many of sparse volume, as well as seawater and other controls, to characterize the associated microbial community. The blow microbiomes were distinct from the seawater microbiomes and included 25 phylogenetically diverse bacteria common to all sampled whales. This core assemblage comprised on average 36% of the microbiome, making it one of the more consistent animal microbiomes studied to date. The closest phylogenetic relatives of 20 of these core microbes were previously detected in marine mammals, suggesting that this core microbiome assemblage is specialized for marine mammals and may indicate a healthy, noninfected pulmonary system. Pathogen screening was conducted on the microbiomes at the genus level, which showed that all blow and few seawater microbiomes contained relatives of bacterial pathogens; no known cetacean respiratory pathogens were detected in the blow. Overall, the discovery of a shared large core microbiome in humpback whales is an important advancement for health and disease monitoring of this species and of other large whales. IMPORTANCE The conservation and management of large whales rely in part upon health monitoring of individuals and populations, and methods generally necessitate invasive sampling. Here, we used a small, unmanned hexacopter drone to noninvasively fly above humpback whales from two populations, capture their exhaled breath (blow), and examine the associated microbiome. In the first extensive examination of the large-whale blow microbiome, we present surprising results about the discovery of a large core microbiome that was shared across individual whales from geographically separated populations in two ocean basins. We suggest that this core microbiome, in addition to other microbiome characteristics, could be a useful feature for health monitoring of large whales worldwide. PMID:29034331

Laboratory colonization stabilizes the naturally dynamic microbiome composition of field collected Dermacentor andersoni ticks.

PubMed

Gall, Cory A; Scoles, Glen A; Magori, Krisztian; Mason, Kathleen L; Brayton, Kelly A

2017-10-04

Nearly a quarter of emerging infectious diseases identified in the last century are arthropod-borne. Although ticks and insects can carry pathogenic microorganisms, non-pathogenic microbes make up the majority of their microbial communities. The majority of tick microbiome research has had a focus on discovery and description; very few studies have analyzed the ecological context and functional responses of the bacterial microbiome of ticks. The goal of this analysis was to characterize the stability of the bacterial microbiome of Dermacentor andersoni ticks between generations and two populations within a species. The bacterial microbiome of D. andersoni midguts and salivary glands was analyzed from populations collected at two different ecologically distinct sites by comparing field (F1) and lab-reared populations (F1-F3) over three generations. The microbiome composition of pooled and individual samples was analyzed by sequencing nearly full-length 16S rRNA gene amplicons using a Pacific Biosciences CCS platform that allows identification of bacteria to the species level. In this study, we found that the D. andersoni microbiome was distinct in different geographic populations and was tissue specific, differing between the midgut and the salivary gland, over multiple generations. Additionally, our study showed that the microbiomes of laboratory-reared populations were not necessarily representative of their respective field populations. Furthermore, we demonstrated that the microbiome of a few individual ticks does not represent the microbiome composition at the population level. We demonstrated that the bacterial microbiome of D. andersoni was complex over three generations and specific to tick tissue (midgut vs. salivary glands) as well as geographic location (Burns, Oregon vs. Lake Como, Montana vs. laboratory setting). These results provide evidence that habitat of the tick population is a vital component of the complexity of the bacterial microbiome of ticks, and that the microbiome of lab colonies may not allow for comparative analyses with field populations. A broader understanding of microbiome variation will be required if we are to employ manipulation of the microbiome as a method for interfering with acquisition and transmission of tick-borne pathogens.

Metagenomic Analysis of the Dynamic Changes in the Gut Microbiome of the Participants of the MARS-500 Experiment, Simulating Long Term Space Flight.

PubMed

Mardanov, A V; Babykin, M M; Beletsky, A V; Grigoriev, A I; Zinchenko, V V; Kadnikov, V V; Kirpichnikov, M P; Mazur, A M; Nedoluzhko, A V; Novikova, N D; Prokhortchouk, E B; Ravin, N V; Skryabin, K G; Shestakov, S V

2013-07-01

A metagenomic analysis of the dynamic changes of the composition of the intestinal microbiome of five participants of the MARS-500 experiment was performed. DNA samples were isolated from the feces of the participants taken just before the experiment, upon 14, 30, 210, 363 and 510 days of isolation in the experimental module, and two weeks upon completion of the experiment. The taxonomic composition of the microbiome was analyzed by pyrosequencing of 16S rRNA gene fragments. Both the taxonomic and functional gene content of the microbiome of one participant were analyzed by whole metagenome sequencing using the SOLiD technique. Each participant had a specific microbiome that could be assigned to one of three recognized enterotypes. Two participants had enterotype I microbiomes characterized by the prevalence of Bacteroides, while the microbiomes of two others, assigned to type II, were dominated by Prevotella. One participant had a microbiome of mixed type. It was found that (1) changes in the taxonimic composition of the microbiomes occurred in the course of the experiment, but the enterotypes remained the same; (2) significant changes in the compositions of the microbiomes occurred just 14-30 days after the beginning of the experiment, presumably indicating the influence of stress factors in the first stage of the experiment; (3) a tendency toward a reversion of the microbiomes to their initial composition was observed two weeks after the end of the experiment, but complete recovery was not achieved. The metagenomic analysis of the microbiome of one of the participants showed that in spite of variations in the taxonomic compositions of microbiomes, the "functional" genetic composition was much more stable for most of the functional gene categories. Probably in the course of the experiment the taxonomic composition of the gut microbiome was adaptively changed to reflect the individual response to the experimental conditions. A new, balanced taxonomic composition of the microbiome was formed to ensure a stable gene content of the community as a whole without negative consequences for the health of the participants.

Extensive Core Microbiome in Drone-Captured Whale Blow Supports a Framework for Health Monitoring.

PubMed

Apprill, Amy; Miller, Carolyn A; Moore, Michael J; Durban, John W; Fearnbach, Holly; Barrett-Lennard, Lance G

2017-01-01

The pulmonary system is a common site for bacterial infections in cetaceans, but very little is known about their respiratory microbiome. We used a small, unmanned hexacopter to collect exhaled breath condensate (blow) from two geographically distinct populations of apparently healthy humpback whales ( Megaptera novaeangliae ), sampled in the Massachusetts coastal waters off Cape Cod ( n = 17) and coastal waters around Vancouver Island ( n = 9). Bacterial and archaeal small-subunit rRNA genes were amplified and sequenced from blow samples, including many of sparse volume, as well as seawater and other controls, to characterize the associated microbial community. The blow microbiomes were distinct from the seawater microbiomes and included 25 phylogenetically diverse bacteria common to all sampled whales. This core assemblage comprised on average 36% of the microbiome, making it one of the more consistent animal microbiomes studied to date. The closest phylogenetic relatives of 20 of these core microbes were previously detected in marine mammals, suggesting that this core microbiome assemblage is specialized for marine mammals and may indicate a healthy, noninfected pulmonary system. Pathogen screening was conducted on the microbiomes at the genus level, which showed that all blow and few seawater microbiomes contained relatives of bacterial pathogens; no known cetacean respiratory pathogens were detected in the blow. Overall, the discovery of a shared large core microbiome in humpback whales is an important advancement for health and disease monitoring of this species and of other large whales. IMPORTANCE The conservation and management of large whales rely in part upon health monitoring of individuals and populations, and methods generally necessitate invasive sampling. Here, we used a small, unmanned hexacopter drone to noninvasively fly above humpback whales from two populations, capture their exhaled breath (blow), and examine the associated microbiome. In the first extensive examination of the large-whale blow microbiome, we present surprising results about the discovery of a large core microbiome that was shared across individual whales from geographically separated populations in two ocean basins. We suggest that this core microbiome, in addition to other microbiome characteristics, could be a useful feature for health monitoring of large whales worldwide.

The effect of arginine on oral biofilm communities.

PubMed

Nascimento, M M; Browngardt, C; Xiaohui, X; Klepac-Ceraj, V; Paster, B J; Burne, R A

2014-02-01

Alkali production by oral bacteria via the arginine deiminase system (ADS) increases the pH of oral biofilms and reduces the risk for development of carious lesions. This study tested the hypothesis that increased availability of arginine in the oral environment through an exogenous source enhances the ADS activity levels in saliva and dental plaque. Saliva and supra-gingival plaque samples were collected from 19 caries-free (CF) individuals (DMFT = 0) and 19 caries-active (CA) individuals (DMFT ≥ 2) before and after treatment, which comprised the use of a fluoride-free toothpaste containing 1.5% arginine, or a regular fluoride-containing toothpaste twice daily for 4 weeks. ADS activity was measured by quantification of ammonia produced from arginine by oral samples at baseline, after washout period, 4 weeks of treatment, and 2 weeks post-treatment. Higher ADS activity levels were observed in plaque samples from CF compared to those of CA individuals (P = 0.048) at baseline. The use of the arginine toothpaste significantly increased ADS activity in plaque of CA individuals (P = 0.026). The plaque microbial profiles of CA treated with the arginine toothpaste showed a shift in bacterial composition to a healthier community, more similar to that of CF individuals. Thus, an anti-caries effect may be expected from arginine-containing formulations due in large part to the enhancement of ADS activity levels and potential favorable modification to the composition of the oral microbiome. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

PubMed

Newberry, Fiona; Hsieh, Shen-Yuan; Wileman, Tom; Carding, Simon R

2018-03-15

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed. © 2018 The Author(s).

Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial.

PubMed

Pallav, Kumar; Dowd, Scot E; Villafuerte, Javier; Yang, Xiaotong; Kabbani, Toufic; Hansen, Joshua; Dennis, Melinda; Leffler, Daniel A; Newburg, David S; Kelly, Ciarán P

2014-07-01

Interactions between the microbial flora of the intestine and the human host play a critical role inmaintaining intestinal health and in the pathophysiology of a wide variety of disorders such as antibiotic associated diarrhea, Clostridium difficile infection, and inflammatory bowel disease. Prebiotics can confer health benefits by beneficial effects on the intestinal microbiome, whereas antibiotics can disrupt the microbiome leading to diarrhea andother side effects. To compare the effects of the prebiotic, polysaccharopeptide from Trametes versicolor, to those of the antibiotic,amoxicillin, on the human gut microbiome Twenty-four healthy volunteers were randomized to receive PSP, amoxicillin, or no treatment (control).Stool specimens were analyzed using bTEFAP microbial ecology methods on seven occasions over 8 weeks from each participant in the active treatment groups and on three occasions for the controls. Twenty-two of 24 participants completed the protocol. PSP led to clear and consistent microbiome changes consistent with its activity as a prebiotic. Despite the diversity of the human microbiome we noted strong microbiome clustering among subjects. Baseline microbiomes tended to remain stable and to overshadow the treatment effects.Amoxicillin treatment caused substantial microbiome changes most notably an increase in Escherichia/Shigella. Antibiotic associated changes persisted to the end of the study, 42 days after antibiotic therapy ended. The microbiomes of healthy individuals show substantial diversity but remain stable over time.The antibiotic amoxicillin alters the microbiome and recovery from this disruption can take several weeks. PSP from T. versicolor acts as a prebiotic to modulate human intestinal microbiome composition.

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes

PubMed Central

Abeles, Shira R.; Ly, Melissa; Santiago-Rodriguez, Tasha M.; Pride, David T.

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

PubMed

Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

Effect of an oxygenating agent on oral bacteria in vitro and on dental plaque composition in healthy young adults.

PubMed

Fernandez y Mostajo, Mercedes; van der Reijden, Wil A; Buijs, Mark J; Beertsen, Wouter; Van der Weijden, Fridus; Crielaard, Wim; Zaura, Egija

2014-01-01

Oral bacteria live in symbiosis with the host. Therefore, when mouthwashes are indicated, selective inhibition of taxa contributing to disease is preferred instead of broad-spectrum antimicrobials. The potential selectivity of an oxygenating mouthwash, Ardox-X® (AX), has not been assessed. The aim of this study was to determine the antimicrobial potential of AX and the effects of a twice-daily oral rinse on dental plaque composition. In vitro, 16 oral bacterial strains were tested using agar diffusion susceptibility, minimum inhibitory and minimum bactericidal concentration tests. A pilot clinical study was performed with 25 healthy volunteers. Clinical assessments and microbiological sampling of supragingival plaque were performed at 1 month before the experiment (Pre-exp), at the start of the experiment (Baseline) and after the one-week experimental period (Post-exp). During the experiment individuals used AX mouthwash twice daily in absence of other oral hygiene measures. The microbiological composition of plaque was assessed by 16S rRNA gene amplicon sequencing. AX showed high inter-species variation in microbial growth inhibition. The tested Prevotella strains and Fusobacterium nucleatum showed the highest sensitivity, while streptococci and Lactobacillus acidophilus were most resistant to AX. Plaque scores at Pre-exp and Baseline visits did not differ significantly (p = 0.193), nor did the microbial composition of plaque. During a period of 7-days non-brushing but twice daily rinsing plaque scores increased from 2.21 (0.31) at Baseline to 2.43 (0.39) Post-exp. A significant microbial shift in composition was observed: genus Streptococcus and Veillonella increased while Corynebacterium, Haemophilus, Leptotrichia, Cardiobacterium and Capnocytophaga decreased (p ≤ 0.001). AX has the potential for selective inhibition of oral bacteria. The shift in oral microbiome after 1 week of rinsing deserves further research.

The microbiome and HIV persistence: implications for viral remission and cure.

PubMed

Koay, Wei Li A; Siems, Lilly V; Persaud, Deborah

2018-01-01

This article discusses the interaction between HIV infection, the gut microbiome, inflammation and immune activation, and HIV reservoirs, along with interventions to target the microbiome and their implications for HIV remission and cure. Most studies show that HIV-infected adults have a gut microbiome associated with decreased bacterial richness and diversity, and associated systemic inflammation and immune activation. A unique set of individuals, elite controllers, who spontaneously control HIV replication, have a similar microbiome to HIV-uninfected individuals. Conversely, exposure to maternal HIV in infants was shown to alter the gut microbiome, even in infants who escaped perinatal infection. Emerging research highlights the importance of the metabolomics and metaproteomics of the gut microbiome, which may have relevance for HIV remission and cure. Together, these studies illustrate the complexity of the relationship between HIV infection, the gut microbiome, and its systemic effects. Understanding the association of HIV with the microbiome, metabolome, and metaproteome may lead to novel therapies to decrease inflammation and immune activation, and impact HIV reservoir size and vaccine responses. Further research in this area is important to inform HIV remission and cure treatments.

Problem Solving with Guided Repeated Oral Reading Instruction

ERIC Educational Resources Information Center

Conderman, Greg; Strobel, Debra

2006-01-01

Many students with disabilities require specialized instructional interventions and frequent progress monitoring in reading. The guided repeated oral reading technique promotes oral reading fluency while providing a reliable data-based monitoring system. This article emphasizes the importance of problem-solving when using this reading approach.

Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors.

PubMed

Velasquez, Daniel E; Parashar, Umesh; Jiang, Baoming

2018-02-01

Numerous studies have shown that the oral rotavirus vaccines are less effective in infants born in low income countries compared to those born in developed countries. Identifying the specific factors in developing countries that decrease and/or compromise the protection that rotavirus vaccines offer, could lead to a path for designing new strategies for the vaccines' improvement. Areas covered: We accessed PubMed to identify rotavirus vaccine performance studies (i.e., efficacy, effectiveness and immunogenicity) and correlated performance with several risk factors. Here, we review the factors that might contribute to the low vaccine efficacy, including passive transfer of maternal rotavirus antibodies, rotavirus seasonality, oral polio vaccine (OPV) administered concurrently, microbiome composition and concomitant enteric pathogens, malnutrition, environmental enteropathy, HIV, and histo blood group antigens. Expert commentary: We highlight two major factors that compromise rotavirus vaccines' efficacy: the passive transfer of rotavirus IgG antibodies to infants and the  co-administration of rotavirus vaccines with OPV. We also identify other potential risk factors that require further research because the data about their interference with the efficacy of rotavirus vaccines are inconclusive and at times conflicting.

Human genetic variation and the gut microbiome in disease.

PubMed

Hall, Andrew Brantley; Tolonen, Andrew C; Xavier, Ramnik J

2017-11-01

Taxonomic and functional changes to the composition of the gut microbiome have been implicated in multiple human diseases. Recent microbiome genome-wide association studies reveal that variants in many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome. Although many factors can affect the microbial organisms residing in the gut, a number of recent findings support the hypothesis that certain host genetic variants predispose an individual towards microbiome dysbiosis. This condition, in which the normal microbiome population structure is disturbed, is a key feature in disorders of metabolism and immunity.

Exploring the diversity-stability paradigm using sponge microbial communities.

PubMed

Glasl, Bettina; Smith, Caitlin E; Bourne, David G; Webster, Nicole S

2018-05-30

A key concept in theoretical ecology is the positive correlation between biodiversity and ecosystem stability. When applying this diversity-stability concept to host-associated microbiomes, the following questions emerge: (1) Does microbial diversity influence the stability of microbiomes upon environmental fluctuations? (2) Do hosts that harbor high versus low microbial diversity differ in their stress response? To test the diversity-stability concept in host-associated microbiomes, we exposed six marine sponge species with varying levels of microbial diversity to non-lethal salinity disturbances and followed their microbial composition over time using 16S rRNA gene amplicon sequencing. No signs of sponge stress were evident following salinity amendment and microbiomes exhibited compositional resistance irrespective of their microbial diversity. Compositional stability of the sponge microbiome manifests itself at distinct host taxonomic and host microbial diversity groups, with (1) stable host genotype-specific microbiomes at oligotype-level; (2) stable host species-specific microbiomes at genus-level; and (3) stable and specific microbiomes at phylum-level for hosts with high versus low microbial diversity. The resistance of sponge microbiomes together with the overall stability of sponge holobionts upon salinity fluctuations suggest that the stability-diversity concept does not appear to hold for sponge microbiomes and provides further evidence for the widely recognized environmental tolerance of sponges.

Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian.

PubMed

Griffiths, Sarah M; Harrison, Xavier A; Weldon, Ché; Wood, Michael D; Pretorius, Abigail; Hopkins, Kevin; Fox, Graeme; Preziosi, Richard F; Antwis, Rachael E

2018-06-25

Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases.

Novel ITS1 Fungal Primers for Characterization of the Mycobiome

PubMed Central

Usyk, Mykhaylo; Zolnik, Christine P.; Patel, Hitesh; Levi, Michael H.

2017-01-01

ABSTRACT Studies of the human microbiome frequently omit characterization of fungal communities (the mycobiome), which limits our ability to investigate how fungal communities influence human health. The internal transcribed spacer 1 (ITS1) region of the eukaryotic ribosomal cluster has features allowing for wide taxonomic coverage and has been recognized as a suitable barcode region for species-level identification of fungal organisms. We developed custom ITS1 primer sets using iterative alignment refinement. Primer performance was evaluated using in silico testing and experimental testing of fungal cultures and human samples. Using an expanded novel reference database, SIS (18S-ITS1-5.8S), the newly designed primers showed an average in silico taxonomic coverage of 79.9% ± 7.1% compared to a coverage of 44.6% ± 13.2% using previously published primers (P = 0.05). The newly described primer sets recovered an average of 21,830 ± 225 fungal reads from fungal isolate culture samples, whereas the previously published primers had an average of 3,305 ± 1,621 reads (P = 0.03). Of note was an increase in the taxonomic coverage of the Candida genus, which went from a mean coverage of 59.5% ± 13% to 100.0% ± 0.0% (P = 0.0015) comparing the previously described primers to the new primers, respectively. The newly developed ITS1 primer sets significantly improve general taxonomic coverage of fungal communities infecting humans and increased read depth by an order of magnitude over the best-performing published primer set tested. The overall best-performing primer pair in terms of taxonomic coverage and read recovery, ITS1-30F/ITS1-217R, will aid in advancing research in the area of the human mycobiome. IMPORTANCE The mycobiome constitutes all the fungal organisms within an environment or biological niche. The fungi are eukaryotes, are extremely heterogeneous, and include yeasts and molds that colonize humans as part of the microbiome. In addition, fungi can also infect humans and cause disease. Characterization of the bacterial component of the microbiome was revolutionized by 16S rRNA gene fragment amplification, next-generation sequencing technologies, and bioinformatics pipelines. Characterization of the mycobiome has often not been included in microbiome studies because of limitations in amplification systems. This report revisited the selection of PCR primers that amplify the fungal ITS1 region. We have identified primers with superior identification of fungi present in the database. We have compared the new primer sets against those previously used in the literature and show a significant improvement in read count and taxon identification. These primers should facilitate the study of fungi in human physiology and disease states. PMID:29242834

Host genetic variation impacts microbiome composition across human body sites.

PubMed

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

The Gut Microbiome: A New Frontier in Autism Research

PubMed Central

Mulle, Jennifer G.; Sharp, William G.; Cubells, Joseph F.

2013-01-01

The human gut harbors a complex community of microbes that profoundly influence many aspects of growth and development, including development of the nervous system. Advances in high-throughput DNA sequencing methods have led to rapidly expanding knowledge about this gut microbiome. Here, we review fundamental emerging data on the human gut microbiome, with a focus on potential interactions between the microbiome and autism spectrum disorders (ASD) and consider research on atypical patterns of feeding and nutrition in ASD and how they might interact with the microbiome. Finally we selectively survey results from studies in rodents on the impact of the microbiome on neurobehavioral development. The evidence reviewed here suggests that a deeper understanding of the gut microbiome could open up new avenues of research on ASD, including potential novel treatment strategies. PMID:23307560

Bespoke microbiome therapy to manage plant diseases.

PubMed

Gopal, Murali; Gupta, Alka; Thomas, George V

2013-01-01

Information gathered with advanced nucleotide sequencing technologies, small molecule detection systems and computational biology is revealing that a community of microbes and their genes, now termed "the microbiome," located in gut and rhizosphere, is responsible for maintaining the health of human beings and plants, respectively. Within the complete microbiome a "core-microbiome" exists that plays the pivotal role in well being of humans and plants. Recent studies in medicine have shown that an artificial mixture of bacteria representing the core gut microbiome of healthy person when transferred into gut of diseased person results in re-establishment of normal microflora in the latter leading to alleviation from diseased condition. In agriculture, though not exactly in similar manner as in medicine, success in plant disease management has been achieved through transfer of microbiome by mixing disease suppressive soils with disease conducive soils. A study more similar to artificial gut microbiome transfer in medical field has been recently reported in agriculture, in which transfer of microbiome via soil solutions (filtered and unfiltered) has shown ability to alleviate drought stress in Arabidopsis thaliana. However, the exact practice of transferring artificially cultivated core-microbiome as in medicine has not thus far been attempted in plant disease management. Nonetheless, as the gut and rhizosphere microbiome are known to share many common traits, there exists a good scope for accomplishing similar studies in agriculture. Based upon the information drawn from all recent works in microbiome studies of gut and rhizosphere, we propose that tailor-made core-microbiome transfer therapy can be a success in agriculture too and it could become a viable strategy for management of plant diseases in future.

Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

PubMed

Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

2017-02-01

There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

Elevated temperature drives kelp microbiome dysbiosis, while elevated carbon dioxide induces water microbiome disruption

PubMed Central

Morris, Megan M.; Brown, Matt; Doane, Michael; Edwards, Matthew S.; Michael, Todd P.; Dinsdale, Elizabeth A.

2018-01-01

Global climate change includes rising temperatures and increased pCO2 concentrations in the ocean, with potential deleterious impacts on marine organisms. In this case study we conducted a four-week climate change incubation experiment, and tested the independent and combined effects of increased temperature and partial pressure of carbon dioxide (pCO2), on the microbiomes of a foundation species, the giant kelp Macrocystis pyrifera, and the surrounding water column. The water and kelp microbiome responded differently to each of the climate stressors. In the water microbiome, each condition caused an increase in a distinct microbial order, whereas the kelp microbiome exhibited a reduction in the dominant kelp-associated order, Alteromondales. The water column microbiomes were most disrupted by elevated pCO2, with a 7.3 fold increase in Rhizobiales. The kelp microbiome was most influenced by elevated temperature and elevated temperature in combination with elevated pCO2. Kelp growth was negatively associated with elevated temperature, and the kelp microbiome showed a 5.3 fold increase Flavobacteriales and a 2.2 fold increase alginate degrading enzymes and sulfated polysaccharides. In contrast, kelp growth was positively associated with the combination of high temperature and high pCO2 ‘future conditions’, with a 12.5 fold increase in Planctomycetales and 4.8 fold increase in Rhodobacteriales. Therefore, the water and kelp microbiomes acted as distinct communities, where the kelp was stabilizing the microbiome under changing pCO2 conditions, but lost control at high temperature. Under future conditions, a new equilibrium between the kelp and the microbiome was potentially reached, where the kelp grew rapidly and the commensal microbes responded to an increase in mucus production. PMID:29474389

Deciphering composition and function of the root microbiome of a legume plant.

PubMed

Hartman, Kyle; van der Heijden, Marcel Ga; Roussely-Provent, Valexia; Walser, Jean-Claude; Schlaeppi, Klaus

2017-01-17

Diverse assemblages of microbes colonize plant roots and collectively function as a microbiome. Earlier work has characterized the root microbiomes of numerous plant species, but little information is available for legumes despite their key role in numerous ecosystems including agricultural systems. Legumes form a root nodule symbiosis with nitrogen-fixing Rhizobia bacteria and thereby account for large, natural nitrogen inputs into soils. Here, we describe the root bacteria microbiome of the legume Trifolium pratense combining culture-dependent and independent methods. For a functional understanding of individual microbiome members and their impact on plant growth, we began to inoculate root microbiome members alone or in combination to Trifolium roots. At a whole-root scale, Rhizobia bacteria accounted for ~70% of the root microbiome. Other enriched members included bacteria from the genera Pantoea, Sphingomonas, Novosphingobium, and Pelomonas. We built a reference stock of 200 bacteria isolates, and we found that they corresponded to ~20% of the abundant root microbiome members. We developed a microcosm system to conduct simplified microbiota inoculation experiments with plants. We observed that while an abundant root microbiome member reduced plant growth when inoculated alone, this negative effect was alleviated if this Flavobacterium was co-inoculated with other root microbiome members. The Trifolium root microbiome was dominated by nutrient-providing Rhizobia bacteria and enriched for bacteria from genera that may provide disease protection. First microbiota inoculation experiments indicated that individual community members can have plant growth compromising activities without being apparently pathogenic, and a more diverse root community can alleviate plant growth compromising activities of its individual members. A trait-based characterization of the reference stock bacteria will permit future microbiota manipulation experiments to decipher overall microbiome functioning and elucidate the biological mechanisms and interactions driving the observed effects. The presented reductionist experimental approach offers countless opportunities for future systematic and functional examinations of the plant root microbiome.

Metagenomic Insights into the RDX-Degrading Potential of the Ovine Rumen Microbiome

PubMed Central

Li, Robert W.; Giarrizzo, Juan Gabriel; Wu, Sitao; Li, Weizhong; Duringer, Jennifer M.; Craig, A. Morrie

2014-01-01

The manufacturing processes of royal demolition explosive (RDX), or hexahydro-1,3,5-trinitro-1,3,5-triazine, have resulted in serious water contamination. As a potential carcinogen, RDX can cause a broad range of harmful effects to humans and animals. The ovine rumen is capable of rapid degradation of nitroaromatic compounds, including RDX. While ruminal RDX-degrading bacteria have been identified, the genes and pathways responsible for RDX degradation in the rumen have yet to be characterized. In this study, we characterized the metabolic potential of the ovine rumen using metagenomic approaches. Sequences homologous to at least five RDX-degrading genes cloned from environmental samples (diaA, xenA, xenB, xplA, and xplB) were present in the ovine rumen microbiome. Among them, diaA was the most abundant, likely reflective of the predominance of the genus Clostridium in the ovine rumen. At least ten genera known to harbor RDX-degrading microorganisms were detectable. Metagenomic sequences were also annotated using public databases, such as Pfam, COG, and KEGG. Five of the six Pfam protein families known to be responsible for RDX degradation in environmental samples were identified in the ovine rumen. However, increased substrate availability did not appear to enhance the proliferation of RDX-degrading bacteria and alter the microbial composition of the ovine rumen. This implies that the RDX-degrading capacity of the ovine rumen microbiome is likely regulated at the transcription level. Our results provide metagenomic insights into the RDX-degrading potential of the ovine rumen, and they will facilitate the development of novel and economic bioremediation strategies. PMID:25383623

Composition and variation of respiratory microbiota in healthy military personnel

PubMed Central

Zavaljevski, Nela; Yang, Yu; Desai, Valmik; Ruck, Richard C.; Macareo, Louis R.; Jarman, Richard G.; Reifman, Jaques; Kuschner, Robert A.; Keiser, Paul B.

2017-01-01

Certain occupational and geographical exposures have been associated with an increased risk of lung disease. As a baseline for future studies, we sought to characterize the upper respiratory microbiomes of healthy military personnel in a garrison environment. Nasal, oropharyngeal, and nasopharyngeal swabs were collected from 50 healthy active duty volunteers eight times over the course of one year (1107 swabs, completion rate = 92.25%) and subjected to pyrosequencing of the V1–V3 region of 16S rDNA. Respiratory bacterial taxa were characterized at the genus level, using QIIME 1.8 and the Ribosomal Database Project classifier. High levels of Staphylococcus, Corynebacterium, and Propionibacterium were observed among both nasal and nasopharyngeal microbiota, comprising more than 75% of all operational taxonomical units (OTUs). In contrast, Streptococcus was the sole dominant bacterial genus (approximately 50% of all OTUs) in the oropharynx. The average bacterial diversity was greater in the oropharynx than in the nasal or nasopharyngeal region at all time points. Diversity analysis indicated a significant overlap between nasal and nasopharyngeal samples, whereas oropharyngeal samples formed a cluster distinct from these two regions. The study produced a large set of pyrosequencing data on the V1–V3 region of bacterial 16S rDNA for the respiratory microbiomes of healthy active duty Service Members. Pre-processing of sequencing reads showed good data quality. The derived microbiome profiles were consistent both internally and with previous reports, suggesting their utility for further analyses and association studies based on sequence and demographic data. PMID:29216202

The relationship between prior antimicrobial prescription and meningitis: a case-control study.

PubMed

Armstrong, David; Ashworth, Mark; Dregan, Alex; White, Patrick

2016-04-01

Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials. The association with bacterial and viral meningitis following antimicrobial prescription during the previous year was investigated to determine whether antimicrobials have a deleterious effect on the nasopharyngeal microbiome. A case-control study (1:4 cases to controls) was conducted examining the rate of previous antimicrobial exposure in cases of meningitis and in a matched control group. Data from a UK primary care clinical database were analysed using conditional logistic regression. A total of 7346 cases of meningitis were identified, 3307 (45%) viral, 1812 (25%) bacterial, and 2227 (30%) unspecified. The risks of viral (adjusted odds ratio [AOR] 2.45; 95% confidence interval [CI] = 2.24 to 2.68) or bacterial (AOR 1.98; 95% CI = 1.71 to 2.30) meningitis were both increased following antimicrobial prescription in the preceding year. Patients who received ≥4 antimicrobial prescriptions in the preceding year were at significantly increased risk of all types of meningitis (AOR 2.85; 95% CI = 2.44 to 3.34), bacterial meningitis (AOR 3.06; 95% CI = 2.26 to 4.15) and viral meningitis (AOR 3.23; 95% CI = 2.55 to 4.08) compared to their matched controls. There was an increased risk of meningitis following antimicrobial prescription in the previous year. It is possible that this increase was due to an effect of antimicrobials on the microbiome or reflected an increased general susceptibility to infections in these patients. © British Journal of General Practice 2016.

The relationship between prior antimicrobial prescription and meningitis: a case–control study

PubMed Central

Armstrong, David; Ashworth, Mark; Dregan, Alex; White, Patrick

2016-01-01

Background Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials. Aim The association with bacterial and viral meningitis following antimicrobial prescription during the previous year was investigated to determine whether antimicrobials have a deleterious effect on the nasopharyngeal microbiome. Design and setting A case-control study (1:4 cases to controls) was conducted examining the rate of previous antimicrobial exposure in cases of meningitis and in a matched control group. Data from a UK primary care clinical database were analysed using conditional logistic regression. Results A total of 7346 cases of meningitis were identified, 3307 (45%) viral, 1812 (25%) bacterial, and 2227 (30%) unspecified. The risks of viral (adjusted odds ratio [AOR] 2.45; 95% confidence interval [CI] = 2.24 to 2.68) or bacterial (AOR 1.98; 95% CI = 1.71 to 2.30) meningitis were both increased following antimicrobial prescription in the preceding year. Patients who received ≥4 antimicrobial prescriptions in the preceding year were at significantly increased risk of all types of meningitis (AOR 2.85; 95% CI = 2.44 to 3.34), bacterial meningitis (AOR 3.06; 95% CI = 2.26 to 4.15) and viral meningitis (AOR 3.23; 95% CI = 2.55 to 4.08) compared to their matched controls. Conclusion There was an increased risk of meningitis following antimicrobial prescription in the previous year. It is possible that this increase was due to an effect of antimicrobials on the microbiome or reflected an increased general susceptibility to infections in these patients. PMID:26965030

Gut microbiomes of wild great apes fluctuate seasonally in response to diet.

PubMed

Hicks, Allison L; Lee, Kerry Jo; Couto-Rodriguez, Mara; Patel, Juber; Sinha, Rohini; Guo, Cheng; Olson, Sarah H; Seimon, Anton; Seimon, Tracie A; Ondzie, Alain U; Karesh, William B; Reed, Patricia; Cameron, Kenneth N; Lipkin, W Ian; Williams, Brent L

2018-05-03

The microbiome is essential for extraction of energy and nutrition from plant-based diets and may have facilitated primate adaptation to new dietary niches in response to rapid environmental shifts. Here we use 16S rRNA sequencing to characterize the microbiota of wild western lowland gorillas and sympatric central chimpanzees and demonstrate compositional divergence between the microbiotas of gorillas, chimpanzees, Old World monkeys, and modern humans. We show that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and frugivory. Metagenomic sequencing of gorilla microbiomes demonstrates distinctions in functional metabolic pathways, archaea, and dietary plants among enterotypes, suggesting that dietary seasonality dictates shifts in the microbiome and its capacity for microbial plant fiber digestion versus growth on mucus glycans. These data indicate that great ape microbiomes are malleable in response to dietary shifts, suggesting a role for microbiome plasticity in driving dietary flexibility, which may provide fundamental insights into the mechanisms by which diet has driven the evolution of human gut microbiomes.

Specific microbiome-dependent mechanisms underlie the energy harvest efficiency of ruminants

PubMed Central

Shabat, Sheerli Kruger Ben; Sasson, Goor; Doron-Faigenboim, Adi; Durman, Thomer; Yaacoby, Shamay; Berg Miller, Margret E; White, Bryan A; Shterzer, Naama; Mizrahi, Itzhak

2016-01-01

Ruminants have the remarkable ability to convert human-indigestible plant biomass into human-digestible food products, due to a complex microbiome residing in the rumen compartment of their upper digestive tract. Here we report the discovery that rumen microbiome components are tightly linked to cows' ability to extract energy from their feed, termed feed efficiency. Feed efficiency was measured in 146 milking cows and analyses of the taxonomic composition, gene content, microbial activity and metabolomic composition was performed on the rumen microbiomes from the 78 most extreme animals. Lower richness of microbiome gene content and taxa was tightly linked to higher feed efficiency. Microbiome genes and species accurately predicted the animals' feed efficiency phenotype. Specific enrichment of microbes and metabolic pathways in each of these microbiome groups resulted in better energy and carbon channeling to the animal, while lowering methane emissions to the atmosphere. This ecological and mechanistic understanding of the rumen microbiome could lead to an increase in available food resources and environmentally friendly livestock agriculture. PMID:27152936

The gut microbiome of nonhuman primates: Lessons in ecology and evolution.

PubMed

Clayton, Jonathan B; Gomez, Andres; Amato, Katherine; Knights, Dan; Travis, Dominic A; Blekhman, Ran; Knight, Rob; Leigh, Steven; Stumpf, Rebecca; Wolf, Tiffany; Glander, Kenneth E; Cabana, Francis; Johnson, Timothy J

2018-06-01

The mammalian gastrointestinal (GI) tract is home to trillions of bacteria that play a substantial role in host metabolism and immunity. While progress has been made in understanding the role that microbial communities play in human health and disease, much less attention has been given to host-associated microbiomes in nonhuman primates (NHPs). Here we review past and current research exploring the gut microbiome of NHPs. First, we summarize methods for characterization of the NHP gut microbiome. Then we discuss variation in gut microbiome composition and function across different NHP taxa. Finally, we highlight how studying the gut microbiome offers new insights into primate nutrition, physiology, and immune system function, as well as enhances our understanding of primate ecology and evolution. Microbiome approaches are useful tools for studying relevant issues in primate ecology. Further study of the gut microbiome of NHPs will offer new insight into primate ecology and evolution as well as human health. © 2018 Wiley Periodicals, Inc.

Environment dominates over host genetics in shaping human gut microbiota.

PubMed

Rothschild, Daphna; Weissbrod, Omer; Barkan, Elad; Kurilshikov, Alexander; Korem, Tal; Zeevi, David; Costea, Paul I; Godneva, Anastasia; Kalka, Iris N; Bar, Noam; Shilo, Smadar; Lador, Dar; Vila, Arnau Vich; Zmora, Niv; Pevsner-Fischer, Meirav; Israeli, David; Kosower, Noa; Malka, Gal; Wolf, Bat Chen; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Weinberger, Adina; Halpern, Zamir; Carmi, Shai; Fu, Jingyuan; Wijmenga, Cisca; Zhernakova, Alexandra; Elinav, Eran; Segal, Eran

2018-03-08

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Specific microbiome-dependent mechanisms underlie the energy harvest efficiency of ruminants.

PubMed

Shabat, Sheerli Kruger Ben; Sasson, Goor; Doron-Faigenboim, Adi; Durman, Thomer; Yaacoby, Shamay; Berg Miller, Margret E; White, Bryan A; Shterzer, Naama; Mizrahi, Itzhak

2016-12-01

Ruminants have the remarkable ability to convert human-indigestible plant biomass into human-digestible food products, due to a complex microbiome residing in the rumen compartment of their upper digestive tract. Here we report the discovery that rumen microbiome components are tightly linked to cows' ability to extract energy from their feed, termed feed efficiency. Feed efficiency was measured in 146 milking cows and analyses of the taxonomic composition, gene content, microbial activity and metabolomic composition was performed on the rumen microbiomes from the 78 most extreme animals. Lower richness of microbiome gene content and taxa was tightly linked to higher feed efficiency. Microbiome genes and species accurately predicted the animals' feed efficiency phenotype. Specific enrichment of microbes and metabolic pathways in each of these microbiome groups resulted in better energy and carbon channeling to the animal, while lowering methane emissions to the atmosphere. This ecological and mechanistic understanding of the rumen microbiome could lead to an increase in available food resources and environmentally friendly livestock agriculture.

Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer.

PubMed

Dominguez-Bello, Maria G; De Jesus-Laboy, Kassandra M; Shen, Nan; Cox, Laura M; Amir, Amnon; Gonzalez, Antonio; Bokulich, Nicholas A; Song, Se Jin; Hoashi, Marina; Rivera-Vinas, Juana I; Mendez, Keimari; Knight, Rob; Clemente, Jose C

2016-03-01

Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section-delivered babies.

Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.

PubMed

Fan, Xiaozhou; Alekseyenko, Alexander V; Wu, Jing; Peters, Brandilyn A; Jacobs, Eric J; Gapstur, Susan M; Purdue, Mark P; Abnet, Christian C; Stolzenberg-Solomon, Rachael; Miller, George; Ravel, Jacques; Hayes, Richard B; Ahn, Jiyoung

2018-01-01

A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans , were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study. This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Host Immune Selection of Rumen Bacteria through Salivary Secretory IgA

PubMed Central

Fouhse, Janelle M.; Smiegielski, Luke; Tuplin, Melanie; Guan, Le Luo; Willing, Benjamin P.

2017-01-01

The rumen microbiome is integral to efficient production in cattle and shows strong host specificity, yet little is known about what host factors shape rumen microbial composition. Secretory immunoglobulin A (SIgA) is produced in large amounts in the saliva, can coat both commensal and pathogenic microbes within the gut, and presents a plausible mechanism of host specificity. However, the role salivary SIgA plays in commensal bacteria selection in ruminants remains elusive. The main objectives of this study were to develop an immuno-affinity benchtop method to isolate SIgA-tagged microbiota and to determine if salivary SIgA preferentially binds selected bacteria. We hypothesized that SIgA-tagged bacteria would differ from total bacteria, thus supporting a potential host-derived mechanism in commensal bacterial selection. Whole rumen (n = 9) and oral secretion samples (n = 10) were incubated with magnetic beads conjugated with anti-secretory IgA antibodies to enrich SIgA-tagged microbiota. Microbial DNA from the oral secretion, whole rumen, SIgA-tagged oral secretion, and SIgA-tagged rumen was isolated for amplicon sequencing of V1–V3 region of 16S rDNA genes. Whole rumen and oral secretion had distinctive (P < 0.05) bacterial compositions indicated by the non-parametric multidimensional scaling plot using Euclidean distance metrics. The SIgA-tagged microbiota from rumen and oral secretion had similar abundance of Bacteroidetes, Actinobacteria, Fibrobacter, candidate phyla TM7, and Tenericutes and are clustered tightly. Composition of SIgA-tagged oral secretion microbiota was more similar to whole rumen microbiota than whole oral secretion due to enrichment of rumen bacteria (Lachnospiraceae) and depletion of oral taxa (Streptococcus, Rothia, Neisseriaceae, and Lactobacillales). In conclusion, SIgA-tagged oral secretion microbiota had an increased resemblance to whole rumen microbiota, suggesting salivary SIgA-coating may be one host-derived mechanism impacting commensal colonization. Further studies, to explore the variations in antibody affinity between different animals as a driver of microbial composition are warranted. PMID:28553275

The genetic predisposition and the interplay of host genetics and gut microbiome in Crohn disease.

PubMed

Jianzhong, Hu

2014-12-01

Extensive genetic studies have identified more than 140 loci predisposing to Crohn disease (CD). Several major CD susceptibility genes have been shown to impair biological function with regard to immune response to recognizing and clearance of bacterial infection. Recent human microbiome studies suggest that the gut microbiome composition is differentiated in carriers of many risk variants of major CD susceptibility genes. This interplay between host genetics and its associated gut microbiome may play an essential role in the pathogenesis of CD. The ongoing microbiome research is aimed to investigate the detailed host genetics-microbiome interacting mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.

PubMed

Gundogdu, Aycan; Nalbantoglu, Ufuk

2017-04-01

A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.

Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

PubMed Central

Nalbantoglu, Ufuk

2017-01-01

A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome–human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis. PMID:28785422

Gut microbiome and dietary patterns in different Saudi populations and monkeys.

PubMed

Angelakis, Emmanouil; Yasir, Muhammad; Bachar, Dipankar; Azhar, Esam I; Lagier, Jean-Christophe; Bibi, Fehmida; Jiman-Fatani, Asif A; Alawi, Maha; Bakarman, Marwan A; Robert, Catherine; Raoult, Didier

2016-08-31

Host genetics, environment, lifestyle and proximity between hosts strongly influence the composition of the gut microbiome. To investigate the association of dietary variables with the gut microbiota, we used 16S rDNA sequencing to test the fecal microbiome of Bedouins and urban Saudis and we compared it to the gut microbiome of baboons living in close contact with Bedouins and eating their leftovers. We also analyzed fermented dairy products commonly consumed by Bedouins in order to investigate their impact on the gut microbiome of this population. We found that the gut microbiomes of westernized urban Saudis had significantly lower richness and biodiversity than the traditional Bedouin population. The gut microbiomes of baboons were more similar to that of Bedouins compared to urban Saudis, probably due the dietary overlap between baboons and Bedouins. Moreover, we found clusters that were compositionally similar to clusters identified in humans and baboons, characterized by differences in Acinetobacter, Turicibacter and Collinsella. The fermented food presented significantly more bacteria genera common to the gut microbiome of Bedouins compared to urban Saudis. These results support the hypothesis that dietary habits influence the composition of the gut microbiome.

Comparisons of microbiomes in conventional and alternative poultry production systems

USDA-ARS?s Scientific Manuscript database

With the advent of new sequencing technologies and platforms, entire microbiomes are more easily characterized than ever before, while initially used more as a surveying tool to determine what microbial taxa (and their relative abundance) comprise various microbiomes, using microbiome data in a more...

Microbiomes of Muricea californica and M. fruticosa: Comparative Analyses of Two Co-occurring Eastern Pacific Octocorals.

PubMed

Holm, Johanna B; Heidelberg, Karla B

2016-01-01

Octocorals are sources of novel but understudied microbial diversity. Conversely, scleractinian or reef-building coral microbiomes have been heavily examined in light of the threats of climate change. Muricea californica and Muricea fruticosa are two co-occurring species of gorgonian octocoral abundantly found in the kelp forests of southern California, and thus provide an excellent basis to determine if octocoral microbiomes are host specific. Using Illumina MiSeq amplicon sequencing and replicate samples, we evaluated the microbiomes collected from multiple colonies of both species of Muricea to measure both inter- and intra-colony microbiome variabilities. In addition, microbiomes from overlying sea water and nearby zoanthids (another benthic invertebrate) were also included in the analysis to evaluate whether bacterial taxa specifically associate with octocorals. This is also the first report of microbiomes from these species of Muricea. We show that microbiomes isolated from each sample type are distinct, and specifically, that octocoral species type had the greatest effect on predicting the composition of the Muricea microbiome. Bacterial taxa contributing to compositional differences include distinct strains of Mycoplasma associated with either M. californica or M. fruticosa, an abundance of Spirochaetes observed on M. californica, and a greater diversity of γ-Proteobacteria associated with M. fruticosa. Many of the bacterial taxa contributing to these differences are known for their presence in photosymbiont-containing invertebrate microbiomes.

Microbiomes of Muricea californica and M. fruticosa: Comparative Analyses of Two Co-occurring Eastern Pacific Octocorals

PubMed Central

Holm, Johanna B.; Heidelberg, Karla B.

2016-01-01

Octocorals are sources of novel but understudied microbial diversity. Conversely, scleractinian or reef-building coral microbiomes have been heavily examined in light of the threats of climate change. Muricea californica and Muricea fruticosa are two co-occurring species of gorgonian octocoral abundantly found in the kelp forests of southern California, and thus provide an excellent basis to determine if octocoral microbiomes are host specific. Using Illumina MiSeq amplicon sequencing and replicate samples, we evaluated the microbiomes collected from multiple colonies of both species of Muricea to measure both inter- and intra-colony microbiome variabilities. In addition, microbiomes from overlying sea water and nearby zoanthids (another benthic invertebrate) were also included in the analysis to evaluate whether bacterial taxa specifically associate with octocorals. This is also the first report of microbiomes from these species of Muricea. We show that microbiomes isolated from each sample type are distinct, and specifically, that octocoral species type had the greatest effect on predicting the composition of the Muricea microbiome. Bacterial taxa contributing to compositional differences include distinct strains of Mycoplasma associated with either M. californica or M. fruticosa, an abundance of Spirochaetes observed on M. californica, and a greater diversity of γ-Proteobacteria associated with M. fruticosa. Many of the bacterial taxa contributing to these differences are known for their presence in photosymbiont-containing invertebrate microbiomes. PMID:27445997

Parasite Microbiome Project: Systematic Investigation of Microbiome Dynamics within and across Parasite-Host Interactions.

PubMed

Dheilly, Nolwenn M; Bolnick, Daniel; Bordenstein, Seth; Brindley, Paul J; Figuères, Cédric; Holmes, Edward C; Martínez Martínez, Joaquín; Phillips, Anna J; Poulin, Robert; Rosario, Karyna

2017-01-01

Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and allow reliable comparative analyses across model systems. It is also an invitation to foundations and national funding agencies to propel the field of parasitology into the microbiome/metagenomic era.

The gut microbiome: a clinically significant player in transplantation?

PubMed

Vindigni, Stephen M; Surawicz, Christina M

2015-01-01

The intestinal microbiome is critical to digestion, metabolism and protection from pathogenic organisms. Dysbiosis, or alteration of this microbiome, can result in Clostridium difficile infection and may play a role in other conditions. Patients undergoing solid organ transplantation (e.g., kidney, lung, liver, small bowel) and hematopoietic stem cell transplantation have a shift in the gut microbiome with a decrease in predominant organisms, a loss of bacterial diversity and emergence of a new dominant population. This translates into increased morbidity and mortality with risk of infection and rejection. We discuss the changes seen in the microbiome and its possible consequences. It may be important to develop strategies to restore the normal microbiome in such patients.

Tick microbiome: the force within

PubMed Central

Narasimhan, Sukanya; Fikrig, Erol

2015-01-01

Ticks are obligate blood-feeders and serve as vectors of human and livestock pathogens worldwide. Defining the tick microbiome and deciphering the interactions between the tick and its symbiotic bacteria in the context of tick development and pathogen transmission, will likely reveal new insights and spawn new paradigms to control tick-borne diseases. Descriptive observations on the tick microbiome that began almost a century ago serve as forerunners to the gathering momentum to define the tick microbiome in greater detail. This review will focus on the current efforts to address the microbiomes of diverse ticks, and the evolving understanding of tick microbiomes. There is hope that these efforts will bring a holistic understanding of pathogen transmission by ticks. PMID:25936226

Emerging Technologies for Gut Microbiome Research

PubMed Central

Arnold, Jason W.; Roach, Jeffrey; Azcarate-Peril, M. Andrea

2016-01-01

Understanding the importance of the gut microbiome on modulation of host health has become a subject of great interest for researchers across disciplines. As an intrinsically multidisciplinary field, microbiome research has been able to reap the benefits of technological advancements in systems and synthetic biology, biomaterials engineering, and traditional microbiology. Gut microbiome research has been revolutionized by high-throughput sequencing technology, permitting compositional and functional analyses that were previously an unrealistic undertaking. Emerging technologies including engineered organoids derived from human stem cells, high-throughput culturing, and microfluidics assays allowing for the introduction of novel approaches will improve the efficiency and quality of microbiome research. Here, we will discuss emerging technologies and their potential impact on gut microbiome studies. PMID:27426971

The Maternal Microbiome and Pregnancy Outcomes that Impact Infant Health: A Review

PubMed Central

Mulle, Jennifer G.; Ferranti, Erin P.; Edwards, Sara; Dunn, Alexis B.; Corwin, Elizabeth J.

2015-01-01

The maternal microbiome is recognized as a key determinant of a range of important maternal and child health outcomes, and together with perinatal factors influences the infant microbiome. This manuscript provides a summary review of research investigating: (1) the role of the maternal microbiome in pregnancy outcomes known to adversely influence neonatal and infant health, including preterm birth, cardiometabolic complications of pregnancy such as preeclampsia and gestational diabetes, and excessive gestational weight gain; (2) factors with an established link to adverse pregnancy outcomes that are known to influence the composition of the maternal microbiome; and (3) strategies for promoting a healthy maternal microbiome, recognizing that much more research is needed in this area. PMID:26317856

The evidence for microbiome manipulation in inflammatory arthritis.

PubMed

Jethwa, Hannah; Abraham, Sonya

2017-09-01

The human body consists of millions of commensal bacteria (the microbiome), with the intestinal tract being the most prevalent site of colonization. This colonization process begins at birth, and despite numerous factors such as ageing, diet and drug use affecting the microbiome make-up, by adulthood the composition of the gut bacteria is relatively consistent across local populations. The recent advent of new scientific techniques has enabled us to explore how the microbiome affects health and, in particular, has shed light on the involvement of the microbiome in the pathogenesis of inflammatory disease. In this review we highlight the current evidence for microbiome manipulation in inflammatory arthritis in animal and human models and discuss potential therapeutics targeting the microbiome as treatment for these diseases. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microbiome sharing between children, livestock and household surfaces in western Kenya.

PubMed

Mosites, Emily; Sammons, Matt; Otiang, Elkanah; Eng, Alexander; Noecker, Cecilia; Manor, Ohad; Hilton, Sarah; Thumbi, Samuel M; Onyango, Clayton; Garland-Lewis, Gemina; Call, Douglas R; Njenga, M Kariuki; Wasserheit, Judith N; Zambriski, Jennifer A; Walson, Judd L; Palmer, Guy H; Montgomery, Joel; Borenstein, Elhanan; Omore, Richard; Rabinowitz, Peter M

2017-01-01

The gut microbiome community structure and development are associated with several health outcomes in young children. To determine the household influences of gut microbiome structure, we assessed microbial sharing within households in western Kenya by sequencing 16S rRNA libraries of fecal samples from children and cattle, cloacal swabs from chickens, and swabs of household surfaces. Among the 156 households studied, children within the same household significantly shared their gut microbiome with each other, although we did not find significant sharing of gut microbiome across host species or household surfaces. Higher gut microbiome diversity among children was associated with lower wealth status and involvement in livestock feeding chores. Although more research is necessary to identify further drivers of microbiota development, these results suggest that the household should be considered as a unit. Livestock activities, health and microbiome perturbations among an individual child may have implications for other children in the household.

MetaCoMET: a web platform for discovery and visualization of the core microbiome

USDA-ARS?s Scientific Manuscript database

A key component of the analysis of microbiome datasets is the identification of OTUs shared between multiple experimental conditions, commonly referred to as the core microbiome. Results: We present a web platform named MetaCoMET that enables the discovery and visualization of the core microbiome an...

Exploring Relationships between Host Genome and Microbiome: New Insights from Genome-Wide Association Studies

PubMed Central

Abdul-Aziz, Muslihudeen A.; Cooper, Alan; Weyrich, Laura S.

2016-01-01

As our understanding of the human microbiome expands, impacts on health and disease continue to be revealed. Alterations in the microbiome can result in dysbiosis, which has now been linked to subsequent autoimmune and metabolic diseases, highlighting the need to identify factors that shape the microbiome. Research has identified that the composition and functions of the human microbiome can be influenced by diet, age, sex, and environment. More recently, studies have explored how human genetic variation may also influence the microbiome. Here, we review several recent analytical advances in this new research area, including those that use genome-wide association studies to examine host genome–microbiome interactions, while controlling for the influence of other factors. We find that current research is limited by small sample sizes, lack of cohort replication, and insufficient confirmatory mechanistic studies. In addition, we discuss the importance of understanding long-term interactions between the host genome and microbiome, as well as the potential impacts of disrupting this relationship, and explore new research avenues that may provide information about the co-evolutionary history of humans and their microorganisms. PMID:27785127

The lung microbiome in health and disease.

PubMed

Moffatt, Miriam F; Cookson, William Ocm

2017-12-01

The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics. © Royal College of Physicians 2017. All rights reserved.

Human and rat gut microbiome composition is maintained following sleep restriction

PubMed Central

Zhang, Shirley L.; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J.; Bushman, Frederic D.; Meerlo, Peter; Dinges, David F.; Sehgal, Amita

2017-01-01

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction. PMID:28179566

Human and rat gut microbiome composition is maintained following sleep restriction.

PubMed

Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

2017-02-21

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

The Microbiome: a Revolution in Treatment for Rheumatic Diseases?

PubMed

Rosenbaum, James T; Asquith, Mark J

2016-10-01

The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple. The clinical implications from observations on the microbiome and disease are broad. A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease. The microbiome has a marked effect on the immune system. Our understanding of immune pathways modulated by the microbiota such as the induction of T helper 17 (Th17) cells and secretory immunoglobulin A (IgA) responses to segmented filamentous bacteria continues to expand. In addition to the gut microbiome, bacterial communities of other sites such as the mouth, lung, and skin have also been associated with the pathogenesis of rheumatic diseases. Strategies to alter the microbiome or to alter the immune activation from the microbiome might play a role in the future therapy for rheumatic diseases.

Development of the Human Mycobiome over the First Month of Life and across Body Sites.

PubMed

Ward, Tonya L; Dominguez-Bello, Maria Gloria; Heisel, Tim; Al-Ghalith, Gabriel; Knights, Dan; Gale, Cheryl A

2018-01-01

With the advent of next-generation sequencing and microbial community characterization, we are beginning to understand the key factors that shape early-life microbial colonization and associated health outcomes. Studies characterizing infant microbial colonization have focused mostly on bacteria in the microbiome and have largely neglected fungi (the mycobiome), despite their relevance to mucosal infections in healthy infants. In this pilot study, we characterized the skin, oral, and anal mycobiomes of infants over the first month of life ( n = 17) and the anal and vaginal mycobiomes of mothers ( n = 16) by internal transcribed spacer 2 (ITS2) amplicon sequencing. We found that infant mycobiomes differed by body site, with the infant mycobiomes at the anal sites being different from those at the skin and oral sites. The relative abundances of body site-specific taxa differed by birth mode, with significantly more Candida albicans fungi present on the skin of vaginally born infants on day 30 and significantly more Candida orthopsilosis fungi present in the oral cavity of caesarean section-born infants throughout the first month of life. We found the mycobiomes within individual infants to be variable over the first month of life, and vaginal birth did not result in infant mycobiomes that were more similar to the mother's vaginal mycobiome. Therefore, although vertical transmission of specific fungal isolates from mother to infant has been reported, it is likely that other sources (environment, other caregivers) also contribute to early-life mycobiome establishment. Thus, future longitudinal studies of mycobiome and bacterial microbiome codevelopment, with dense sampling from birth to beyond the first month of life, are warranted. IMPORTANCE Humans are colonized by diverse fungi (mycobiome), which have received much less study to date than colonizing bacteria. We know very little about the succession of fungal colonization in early life and whether it may relate to long-term health. To better understand fungal colonization and its sources, we studied the skin, oral, and anal mycobiomes of healthy term infants and the vaginal and anal mycobiomes of their mothers. Generally, infants were colonized by few fungal taxa, and fungal alpha diversity did not increase over the first month of life. There was no clear community maturation over the first month of life, regardless of body site. Key body-site-specific taxa, but not overall fungal community structures, were impacted by birth mode. Thus, additional studies to characterize mycobiome acquisition and succession throughout early life are needed to form a foundation for research into the relationship between mycobiome development and human disease.

Mobile Technologies for the Discovery, Analysis, and Engineering of the Global Microbiome.

PubMed

Ballard, Zachary S; Brown, Calvin; Ozcan, Aydogan

2018-04-24

The microbiome has been heralded as a gauge of and contributor to both human health and environmental conditions. Current challenges in probing, engineering, and harnessing the microbiome stem from its microscopic and nanoscopic nature, diversity and complexity of interactions among its members and hosts, as well as the spatiotemporal sampling and in situ measurement limitations induced by the restricted capabilities and norm of existing technologies, leaving some of the constituents of the microbiome unknown. To facilitate significant progress in the microbiome field, deeper understanding of the constituents' individual behavior, interactions with others, and biodiversity are needed. Also crucial is the generation of multimodal data from a variety of subjects and environments over time. Mobile imaging and sensing technologies, particularly through smartphone-based platforms, can potentially meet some of these needs in field-portable, cost-effective, and massively scalable manners by circumventing the need for bulky, expensive instrumentation. In this Perspective, we outline how mobile sensing and imaging technologies could lead the way to unprecedented insight into the microbiome, potentially shedding light on various microbiome-related mysteries of today, including the composition and function of human, animal, plant, and environmental microbiomes. Finally, we conclude with a look at the future, propose a computational microbiome engineering and optimization framework, and discuss its potential impact and applications.

Microbiome assembly of avian eggshells and their potential as transgenerational carriers of maternal microbiota.

PubMed

van Veelen, H Pieter J; Salles, Joana Falcão; Tieleman, B Irene

2018-05-01

The microbiome is essential for development, health and homeostasis throughout an animal's life. Yet, the origins and transmission processes governing animal microbiomes remain elusive for non-human vertebrates, oviparous vertebrates in particular. Eggs may function as transgenerational carriers of the maternal microbiome, warranting characterisation of egg microbiome assembly. Here, we investigated maternal and environmental contributions to avian eggshell microbiota in wild passerine birds: woodlark Lullula arborea and skylark Alauda arvensis. Using 16S rRNA gene sequencing, we demonstrated in both lark species, at the population and within-nest levels, that bacterial communities of freshly laid eggs were distinct from the female cloacal microbiome. Instead, soil-borne bacteria appeared to thrive on freshly laid eggs, and eggshell microbiota composition strongly resembled maternal skin, body feather and nest material communities, sources in direct contact with laid eggs. Finally, phylogenetic structure analysis and microbial source tracking underscored species sorting from directly contacting sources rather than in vivo-transferred symbionts. The female-egg-nest system allowed an integrative assessment of avian egg microbiome assembly, revealing mixed modes of symbiont acquisition not previously documented for vertebrate eggs. Our findings illuminated egg microbiome origins, which suggested a limited potential of eggshells for transgenerational transmission, encouraging further investigation of eggshell microbiome functions in vertebrates.

Structure, variation, and assembly of the root-associated microbiomes of rice

PubMed Central

Edwards, Joseph; Johnson, Cameron; Santos-Medellín, Christian; Lurie, Eugene; Podishetty, Natraj Kumar; Bhatnagar, Srijak; Eisen, Jonathan A.; Sundaresan, Venkatesan

2015-01-01

Plants depend upon beneficial interactions between roots and microbes for nutrient availability, growth promotion, and disease suppression. High-throughput sequencing approaches have provided recent insights into root microbiomes, but our current understanding is still limited relative to animal microbiomes. Here we present a detailed characterization of the root-associated microbiomes of the crop plant rice by deep sequencing, using plants grown under controlled conditions as well as field cultivation at multiple sites. The spatial resolution of the study distinguished three root-associated compartments, the endosphere (root interior), rhizoplane (root surface), and rhizosphere (soil close to the root surface), each of which was found to harbor a distinct microbiome. Under controlled greenhouse conditions, microbiome composition varied with soil source and genotype. In field conditions, geographical location and cultivation practice, namely organic vs. conventional, were factors contributing to microbiome variation. Rice cultivation is a major source of global methane emissions, and methanogenic archaea could be detected in all spatial compartments of field-grown rice. The depth and scale of this study were used to build coabundance networks that revealed potential microbial consortia, some of which were involved in methane cycling. Dynamic changes observed during microbiome acquisition, as well as steady-state compositions of spatial compartments, support a multistep model for root microbiome assembly from soil wherein the rhizoplane plays a selective gating role. Similarities in the distribution of phyla in the root microbiomes of rice and other plants suggest that conclusions derived from this study might be generally applicable to land plants. PMID:25605935

Community assembly of a euryhaline fish microbiome during salinity acclimation.

PubMed

Schmidt, Victor T; Smith, Katherine F; Melvin, Donald W; Amaral-Zettler, Linda A

2015-05-01

Microbiomes play a critical role in promoting a range of host functions. Microbiome function, in turn, is dependent on its community composition. Yet, how microbiome taxa are assembled from their regional species pool remains unclear. Many possible drivers have been hypothesized, including deterministic processes of competition, stochastic processes of colonization and migration, and physiological 'host-effect' habitat filters. The contribution of each to assembly in nascent or perturbed microbiomes is important for understanding host-microbe interactions and host health. In this study, we characterized the bacterial communities in a euryhaline fish and the surrounding tank water during salinity acclimation. To assess the relative influence of stochastic versus deterministic processes in fish microbiome assembly, we manipulated the bacterial species pool around each fish by changing the salinity of aquarium water. Our results show a complete and repeatable turnover of dominant bacterial taxa in the microbiomes from individuals of the same species after acclimation to the same salinity. We show that changes in fish microbiomes are not correlated with corresponding changes to abundant taxa in tank water communities and that the dominant taxa in fish microbiomes are rare in the aquatic surroundings, and vice versa. Our results suggest that bacterial taxa best able to compete within the unique host environment at a given salinity appropriate the most niche space, independent of their relative abundance in tank water communities. In this experiment, deterministic processes appear to drive fish microbiome assembly, with little evidence for stochastic colonization. © 2015 John Wiley & Sons Ltd.

Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension.

PubMed

Lan, Jiarong; Zhao, Yanyun; Dong, Feixia; Yan, Ziyou; Zheng, Wenjie; Fan, Jinping; Sun, Guoli

2015-02-23

Berberine, extracted from Coptis Root and Phellodendron Chinese, has been frequently used for the adjuvant treatment of type 2 diabetes mellitus, hyperlipidemia, and hypertension in China. Safety and efficacy studies in terms of evidence-based medical practice have become more prevalent in application to Chinese Herbal Medicine. It is necessary to assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipidemia and hypertension by conducting a systematic review and meta-analysis of available clinical data. We searched the English databases PubMed, ScienceDirect, Cochrane library, EMbase, etc., and Chinese databases including China biomedical literature database (CBM), Chinese Technology Journal Full-text Database, Chinese journal full text database (CNKI), and Wanfang digital periodical full text database. Relevant studies were selected based on the inclusion and exclusion criteria. Meta-analysis was performed with RevMan5.0 software after data extraction and the quality of studies assessment. Twenty-seven randomized controlled clinical trials were included with 2569 patients. There are seven subgroups in our meta-analysis: berberine versus placebo or berberine with intensive lifestyle intervention versus intensive lifestyle intervention alone; berberine combined with oral hypoglycemic versus hypoglycemic alone; berberine versus oral hypoglycemic; berberine combined with oral lipid lowering drugs versus lipid lowering drugs alone; berberine versus oral lipid lowering drugs; berberine combined with oral hypotensor versus hypotensive medications; berberine versus oral hypotensive medications. In the treatment of type 2 diabetes mellitus, we found that berberine with lifestyle intervention tended to lower the level of FPG, PPG and HbA1c than lifestyle intervention alone or placebo; the same as berberine combined with oral hypoglycaemics to the same hypoglycaemics; but there was no statistical significance between berberine and oral hypoglycaemics. As for the treatment of hyperlipidemia, berberine with lifestyle intervention was better than lifestyle intervention, berberine with oral lipid lowering drugs was better than lipid lowering drugs alone in reducing the level of TC and LDL-C, and raising the level of HDL-C. In the comparative study between berberine and oral lipid lowering drugs, there was no statistical significance in reducing the level of TC and LDL-C, but berberine shows better effect in lowering the level of TG and raising the level of HDL-C. In the treatment of hypertension, berberine with lifestyle intervention tended to lower the level of blood pressure more than the lifestyle intervention alone or placebo did; The same occurred when berberine combined with oral hypotensor was compared to the same hypotensor. Notably, no serious adverse reaction was reported in the 27 experiments. This study indicates that berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension with no serious side effect. Considering the relatively low cost compared with other first-line medicine and treatment, berberine might be a good alternative for low socioeconomic status patients to treat type 2 DM, hyperlipidemia, hypertension over long time period. Due to overall limited quality of the included studies, the therapeutic benefit of berberine can be substantiated to a limited degree. Better methodological quality, large controlled trials using standardized preparation are expected to further quantify the therapeutic effect of berberine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Season, but not symbiont state, drives microbiome structure in the temperate coral Astrangia poculata.

PubMed

Sharp, Koty H; Pratte, Zoe A; Kerwin, Allison H; Rotjan, Randi D; Stewart, Frank J

2017-09-15

Understanding the associations among corals, their photosynthetic zooxanthella symbionts (Symbiodinium), and coral-associated prokaryotic microbiomes is critical for predicting the fidelity and strength of coral symbioses in the face of growing environmental threats. Most coral-microbiome associations are beneficial, yet the mechanisms that determine the composition of the coral microbiome remain largely unknown. Here, we characterized microbiome diversity in the temperate, facultatively symbiotic coral Astrangia poculata at four seasonal time points near the northernmost limit of the species range. The facultative nature of this system allowed us to test seasonal influence and symbiotic state (Symbiodinium density in the coral) on microbiome community composition. Change in season had a strong effect on A. poculata microbiome composition. The seasonal shift was greatest upon the winter to spring transition, during which time A. poculata microbiome composition became more similar among host individuals. Within each of the four seasons, microbiome composition differed significantly from that of surrounding seawater but was surprisingly uniform between symbiotic and aposymbiotic corals, even in summer, when differences in Symbiodinium density between brown and white colonies are the highest, indicating that the observed seasonal shifts are not likely due to fluctuations in Symbiodinium density. Our results suggest that symbiotic state may not be a primary driver of coral microbial community organization in A. poculata, which is a surprise given the long-held assumption that excess photosynthate is of importance to coral-associated microbes. Rather, other environmental or host factors, in this case, seasonal changes in host physiology associated with winter quiescence, may drive microbiome diversity. Additional studies of A. poculata and other facultatively symbiotic corals will provide important comparisons to studies of reef-building tropical corals and therefore help to identify basic principles of coral microbiome assembly, as well as functional relationships among holobiont members.

American Gut: an Open Platform for Citizen Science Microbiome Research

PubMed Central

2018-01-01

ABSTRACT Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples. PMID:29795809

American Gut: an Open Platform for Citizen Science Microbiome Research.

PubMed

McDonald, Daniel; Hyde, Embriette; Debelius, Justine W; Morton, James T; Gonzalez, Antonio; Ackermann, Gail; Aksenov, Alexander A; Behsaz, Bahar; Brennan, Caitriona; Chen, Yingfeng; DeRight Goldasich, Lindsay; Dorrestein, Pieter C; Dunn, Robert R; Fahimipour, Ashkaan K; Gaffney, James; Gilbert, Jack A; Gogul, Grant; Green, Jessica L; Hugenholtz, Philip; Humphrey, Greg; Huttenhower, Curtis; Jackson, Matthew A; Janssen, Stefan; Jeste, Dilip V; Jiang, Lingjing; Kelley, Scott T; Knights, Dan; Kosciolek, Tomasz; Ladau, Joshua; Leach, Jeff; Marotz, Clarisse; Meleshko, Dmitry; Melnik, Alexey V; Metcalf, Jessica L; Mohimani, Hosein; Montassier, Emmanuel; Navas-Molina, Jose; Nguyen, Tanya T; Peddada, Shyamal; Pevzner, Pavel; Pollard, Katherine S; Rahnavard, Gholamali; Robbins-Pianka, Adam; Sangwan, Naseer; Shorenstein, Joshua; Smarr, Larry; Song, Se Jin; Spector, Timothy; Swafford, Austin D; Thackray, Varykina G; Thompson, Luke R; Tripathi, Anupriya; Vázquez-Baeza, Yoshiki; Vrbanac, Alison; Wischmeyer, Paul; Wolfe, Elaine; Zhu, Qiyun; Knight, Rob

2018-01-01

Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.