Science.gov

Sample records for core gut microbiome

  1. The core gut microbiome, energy balance and obesity.

    PubMed

    Turnbaugh, Peter J; Gordon, Jeffrey I

    2009-09-01

    Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.

  2. A core gut microbiome in obese and lean twins

    PubMed Central

    Turnbaugh, Peter J.; Hamady, Micah; Yatsunenko, Tanya; Cantarel, Brandi L.; Duncan, Alexis; Ley, Ruth E.; Sogin, Mitchell L.; Jones, William J.; Roe, Bruce A.; Affourtit, Jason P.; Egholm, Michael; Henrissat, Bernard; Heath, Andrew C.; Knight, Rob; Gordon, Jeffrey I.

    2008-01-01

    The human distal gut harbors a vast ensemble of microbes (the microbiota) that provide us with important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides1–6. Studies of a small number of unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes6–8, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is utilized and stored3–5. To address the question of how host genotype, environmental exposures, and host adiposity influence the gut microbiome, we have characterized the fecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person’s gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable ‘core microbiome’ at the gene, rather than at the organismal lineage level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this

  3. The Core Gut Microbiome of the American Cockroach, Periplaneta americana, Is Stable and Resilient to Dietary Shifts

    PubMed Central

    Tinker, Kara A.

    2016-01-01

    ABSTRACT The omnivorous cockroach Periplaneta americana hosts a diverse hindgut microbiota encompassing hundreds of microbial species. In this study, we used 16S rRNA gene sequencing to examine the effect of diet on the composition of the P. americana hindgut microbial community. Results show that the hindgut microbiota of P. americana exhibit a highly stable core microbial community with low variance in compositions between individuals and minimal community change in response to dietary shifts. This core hindgut microbiome is shared between laboratory-hosted and wild-caught individuals, although wild-caught specimens exhibited a higher diversity of low-abundance microbes that were lost following extended cultivation under laboratory conditions. This taxonomic stability strongly contrasts with observations of the gut microbiota of mammals, which have been shown to be highly responsive to dietary change. A comparison of P. americana hindgut samples with human fecal samples indicated that the cockroach hindgut community exhibited higher alpha diversity but a substantially lower beta diversity than the human gut microbiome. This suggests that cockroaches have evolved unique mechanisms for establishing and maintaining a diverse and stable core microbiome. IMPORTANCE The gut microbiome plays an important role in the overall health of its host. A healthy gut microbiota typically assists with defense against pathogens and the digestion and absorption of nutrients from food, while dysbiosis of the gut microbiota has been associated with reduced health. In this study, we examined the composition and stability of the gut microbiota from the omnivorous cockroach Periplaneta americana. We found that P. americana hosts a diverse core gut microbiome that remains stable after drastic long-term changes in diet. While other insects, notably ant and bee species, have evolved mechanisms for maintaining a stable association with specific gut microbiota, these insects typically host

  4. The gut microbiome.

    PubMed

    Sidhu, Mayenaaz; van der Poorten, David

    2017-01-01

    More than a trillion, mostly good, microbes live within our gastrointestinal tract and are responsible for vital metabolic, immune and nutritional functions. Dysbiosis, meaning a maladaptive imbalance of the microbiome, is associated with many common diseases and is a target for therapy. This article provides an overview of the gut microbiome in health and disease, highlighting conditions such as Clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, obesity and non-alcoholic fatty liver disease, with which dysbiosis is associated. Information about treatments that affect the gut microbiome, including probiotics and faecal microbiota transplant, are discussed. As our knowledge of the microbiome increases, we are likely to better understand the complex interactions that cause disease, and develop new and more effective treatments for many common conditions.

  5. The gut microbiome.

    PubMed

    Actis, Giovanni C

    2014-01-01

    Since the discovery and use of the microscope in the 17(th) century, we know that we host trillions of micro-organisms mostly in the form of bacteria indwelling the "barrier organs" skin, gut, and airways. They exert regulatory functions, are in a continuous dialogue with the intestinal epithelia, influence energy handling, produce nutrients, and may cause diabetes and obesity. The human microbiome has developed by modulating or avoiding inflammatory responses; the host senses bacterial presence through cell surface sensors (the Toll-like receptors) as well as by refining mucous barriers as passive defense mechanisms. The cell density and composition of the microbiome are variable and multifactored. The way of delivery establishes the type of initial flora; use of antibiotics is another factor; diet composition after weaning will shape the adult's microbiome composition, depending on the subject's life-style. Short-chain fatty acids participate in the favoring action exerted by microbiome in the pathogenesis of type-2 diabetes and obesity. Clinical observation has pinpointed a sharp rise of various dysimmune conditions in the last decades, including IBD and rheumatoid arthritis, changes that outweigh the input of simple heritability. It is nowadays proposed that the microbiome, incapable to keep up with the changes of our life-style and feeding sources in the past few decades might have contributed to these immune imbalances, finding itself inadequate to handle the changed gut environment. Another pathway to pathology is the rise of directly pathogenic phyla within a given microbiome: growth of adherent E. coli, of C. concisus, and of C. jejuni, might be examples of causes of local enteropathy, whereas the genus Prevotella copri is now suspected to be linked to rise of arthritic disorders. Inflammasomes are required to shape a non colitogenic flora. Treatment of IBD and infectious enteritides by the use of fecal transplant is warranted by this knowledge.

  6. The Core Gut Microbiome of the American Cockroach, Periplaneta americana, Is Stable and Resilient to Dietary Shifts.

    PubMed

    Tinker, Kara A; Ottesen, Elizabeth A

    2016-11-15

    The omnivorous cockroach Periplaneta americana hosts a diverse hindgut microbiota encompassing hundreds of microbial species. In this study, we used 16S rRNA gene sequencing to examine the effect of diet on the composition of the P. americana hindgut microbial community. Results show that the hindgut microbiota of P. americana exhibit a highly stable core microbial community with low variance in compositions between individuals and minimal community change in response to dietary shifts. This core hindgut microbiome is shared between laboratory-hosted and wild-caught individuals, although wild-caught specimens exhibited a higher diversity of low-abundance microbes that were lost following extended cultivation under laboratory conditions. This taxonomic stability strongly contrasts with observations of the gut microbiota of mammals, which have been shown to be highly responsive to dietary change. A comparison of P. americana hindgut samples with human fecal samples indicated that the cockroach hindgut community exhibited higher alpha diversity but a substantially lower beta diversity than the human gut microbiome. This suggests that cockroaches have evolved unique mechanisms for establishing and maintaining a diverse and stable core microbiome.

  7. 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

  8. The alligator gut microbiome and implications for archosaur symbioses.

    PubMed

    Keenan, Sarah W; Engel, Annette Summers; Elsey, Ruth M

    2013-10-07

    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.

  9. The Gut Microbiome and Obesity.

    PubMed

    John, George Kunnackal; Mullin, Gerard E

    2016-07-01

    The gut microbiome consists of trillions of bacteria which play an important role in human metabolism. Animal and human studies have implicated distortion of the normal microbial balance in obesity and metabolic syndrome. Bacteria causing weight gain are thought to induce the expression of genes related to lipid and carbohydrate metabolism thereby leading to greater energy harvest from the diet. There is a large body of evidence demonstrating that alteration in the proportion of Bacteroidetes and Firmicutes leads to the development of obesity, but this has been recently challenged. It is likely that the influence of gut microbiome on obesity is much more complex than simply an imbalance in the proportion of these phyla of bacteria. Modulation of the gut microbiome through diet, pre- and probiotics, antibiotics, surgery, and fecal transplantation has the potential to majorly impact the obesity epidemic.

  10. Gut microbiome and metabolic syndrome.

    PubMed

    Mazidi, Mohsen; Rezaie, Peyman; Kengne, Andre Pascal; Mobarhan, Majid Ghayour; Ferns, Gordon A

    2016-01-01

    The gut microbiome contributes approximately 2kg of the whole body weight, and recent studies suggest that gut microbiota has a profound effect on human metabolism, potentially contributing to several features of the metabolic syndrome. Metabolic syndrome is defined by a clustering of metabolic disorders that include central adiposity with visceral fat accumulation, dyslipidemia, insulin resistance, dysglycemia and non-optimal blood pressure levels. Metabolic syndrome is associated with an increased risk of cardiovascular diseases and type 2 diabetes. It is estimated that around 20-25 percent of the world's adult population has metabolic syndrome. In this manuscript, we have reviewed the existing data linking gut microbiome with metabolic syndrome. Existing evidence from studies both in animals and humans support a link between gut microbiome and various components of metabolic syndrome. Possible pathways include involvement with energy homeostasis and metabolic processes, modulation of inflammatory signaling pathways, interferences with the immune system, and interference with the renin-angiotensin system. Modification of gut microbiota via prebiotics, probiotics or other dietary interventions has provided evidence to support a possible beneficial effect of interventions targeting gut microbiota modulation to treat components or complications of metabolic syndrome.

  11. Xenobiotic Metabolism and Gut Microbiomes

    PubMed Central

    Das, Anubhav; Srinivasan, Meenakshi; Ghosh, Tarini Shankar; Mande, Sharmila S.

    2016-01-01

    Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends. PMID:27695034

  12. 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/.

  13. High-throughput sequencing reveals the core gut microbiome of Bar-headed goose (Anser indicus) in different wintering areas in Tibet.

    PubMed

    Wang, Wen; Cao, Jian; Yang, Fang; Wang, Xuelian; Zheng, Sisi; Sharshov, Kirill; Li, Laixing

    2016-04-01

    Elucidating the spatial dynamic and core gut microbiome related to wild bar-headed goose is of crucial importance for probiotics development that may meet the demands of bar-headed goose artificial breeding industries and accelerate the domestication of this species. However, the core microbial communities in the wild bar-headed geese remain totally unknown. Here, for the first time, we present a comprehensive survey of bar-headed geese gut microbial communities by Illumina high-throughput sequencing technology using nine individuals from three distinct wintering locations in Tibet. A total of 236,676 sequences were analyzed, and 607 OTUs were identified. We show that the gut microbial communities of bar-headed geese have representatives of 14 phyla and are dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The additive abundance of these four most dominant phyla was above 96% across all the samples. At the genus level, the sequences represented 150 genera. A set of 19 genera were present in all samples and considered as core gut microbiome. The top seven most abundant core genera were distributed in that four dominant phyla. Among them, four genera (Lactococcus, Bacillus, Solibacillus, and Streptococcus) belonged to Firmicutes, while for other three phyla, each containing one genus, such as Proteobacteria (genus Pseudomonas), Actinobacteria (genus Arthrobacter), and Bacteroidetes (genus Bacteroides). This broad survey represents the most in-depth assessment, to date, of the gut microbes that associated with bar-headed geese. These data create a baseline for future bar-headed goose microbiology research, and make an original contribution to probiotics development for bar-headed goose artificial breeding industries. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  14. Seasonal Variation in Human Gut Microbiome Composition

    PubMed Central

    Davenport, Emily R.; Mizrahi-Man, Orna; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2014-01-01

    The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i) the abundance of particular taxa (false discovery rate <0.05), including highly abundant phyla Bacteroidetes and Firmicutes, and (ii) overall gut microbiome diversity (by Shannon diversity; P = 0.001). It is likely that the dietary fluctuations between seasons with respect to produce availability explain, at least in part, these differences in microbiome composition. For example, high levels of produce containing complex carbohydrates consumed during the summer months might explain increased abundance of Bacteroidetes, which contain complex carbohydrate digesters, and decreased levels of Actinobacteria, which have been negatively correlated to fiber content in food questionnaires. Our observations demonstrate the plastic nature of the human gut microbiome in response to variation in diet. PMID:24618913

  15. Human gut microbiome: the second genome of human body.

    PubMed

    Zhu, Baoli; Wang, Xin; Li, Lanjuan

    2010-08-01

    The human body is actually a super-organism that is composed of 10 times more microbial cells than our body cells. Metagenomic study of the human microbiome has demonstrated that there are 3.3 million unique genes in human gut, 150 times more genes than our own genome, and the bacterial diversity analysis showed that about 1000 bacterial species are living in our gut and a majority of them belongs to the divisions of Firmicutes and Bacteriodetes. In addition, most people share a core microbiota that comprises 50-100 bacterial species when the frequency of abundance at phylotype level is not considered, and a core microbiome harboring more than 6000 functional gene groups is present in the majority of human gut surveyed till now. Gut bacteria are not only critical for regulating gut metabolism, but also important for host immune system as revealed by animal studies.

  16. Gut inflammation and microbiome in spondyloarthritis.

    PubMed

    Kabeerdoss, Jayakanthan; Sandhya, Pulukool; Danda, Debashish

    2016-04-01

    Spondyloarthritis (SpA) is chronic inflammatory disease involving joints and the spine. Bowel inflammation is common in SpA, which may be classified as acute or chronic. Chronic gut inflammation is most common in SpA patients with axial involvement as compared to those presenting with peripheral involvement alone. The pathogenesis of gut inflammation in SpA could be explained by two factors-over-activation of immunological cells and altered gut microbiome. This is exemplified by SpA animal models, namely HLA-B27-expressing transgenic animals and SKG mice models. Immunological mechanisms include homing of activated T cells from gut into synovium, excess pro-inflammatory cytokines secretion by immune cells such as IL-23 and genetic variations in immunological genes. The evidence for role of gut microbiome in SpA is gradually emerging. Recently, metagenomic study of gut microbiome by sequencing of microbial nucleic acids has enabled identification of new microbial taxa and their functions in gut of patients with SpA. In SpA, the gut microbiome could emerge as diagnostic and prognostic marker of disease. Modulation of gut microbiome is slated to have therapeutic potential as well.

  17. The gut microbiome modulates colon tumorigenesis.

    PubMed

    Zackular, Joseph P; Baxter, Nielson T; Iverson, Kathryn D; Sadler, William D; Petrosino, Joseph F; Chen, Grace Y; Schloss, Patrick D

    2013-11-05

    Recent studies have shown that individuals with colorectal cancer have an altered gut microbiome compared to healthy controls. It remains unclear whether these differences are a response to tumorigenesis or actively drive tumorigenesis. To determine the role of the gut microbiome in the development of colorectal cancer, we characterized the gut microbiome in a murine model of inflammation-associated colorectal cancer that mirrors what is seen in humans. We followed the development of an abnormal microbial community structure associated with inflammation and tumorigenesis in the colon. Tumor-bearing mice showed enrichment in operational taxonomic units (OTUs) affiliated with members of the Bacteroides, Odoribacter, and Akkermansia genera and decreases in OTUs affiliated with members of the Prevotellaceae and Porphyromonadaceae families. Conventionalization of germfree mice with microbiota from tumor-bearing mice significantly increased tumorigenesis in the colon compared to that for animals colonized with a healthy gut microbiome from untreated mice. Furthermore, at the end of the model, germfree mice colonized with microbiota from tumor-bearing mice harbored a higher relative abundance of populations associated with tumor formation in conventional animals. Manipulation of the gut microbiome with antibiotics resulted in a dramatic decrease in both the number and size of tumors. Our results demonstrate that changes in the gut microbiome associated with inflammation and tumorigenesis directly contribute to tumorigenesis and suggest that interventions affecting the composition of the microbiome may be a strategy to prevent the development of colon cancer. The trillions of bacteria that live in the gut, known collectively as the gut microbiome, are important for normal functioning of the intestine. There is now growing evidence that disruptive changes in the gut microbiome are strongly associated with the development colorectal cancer. However, how the gut microbiome

  18. Bile Acids and the Gut Microbiome

    PubMed Central

    Ridlon, Jason M.; Kang, Dae Joong; Hylemon, Phillip B.; Bajaj, Jasmohan S.

    2014-01-01

    Purpose of the review We examine the latest research on the emerging bile acid-gut microbiome axis and its role in health and disease. Our focus revolves around two key microbial pathways for degrading bile salts, and the impact of bile acid composition in the gut on the gut microbiome and host physiology. Recent findings Bile acid pool size has recently been shown to be a function of microbial metabolism of bile acids in the intestines. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. Bile acids are emerging as regulators of the gut microbiome at the highest taxomic levels. The role of bile acids as hormones and potentiators of liver cancer are also emerging. Summary The host and microbiome appear to regulate bile acid pool size. The host produces a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of FXR in intestine and liver. Members of the microbiome utilize bile acids and their conjugates resulting in agonism of FXR in intestine and liver resulting in a smaller, unconjugated hydrophobic bile acid pool. Hydrophilicity of the bile acid pool is associated with disease states. Reduced bile acid levels in the gut are associated with bacterial overgrowth and inflammation. Diet, antibiotic therapy, and disease states affect the balance of the microbiome-bile acid pool. PMID:24625896

  19. 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

  20. Analysis of Stomach and Gut Microbiomes of the Eastern Oyster (Crassostrea virginica) from Coastal Louisiana, USA

    SciTech Connect

    King, Gary M.; Judd, Craig; Kuske, Cheryl R.; Smith, Conor

    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 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. 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.

  1. 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

  2. Gut Microbiome in Down Syndrome

    PubMed Central

    Biagi, Elena; Candela, Marco; Centanni, Manuela; Consolandi, Clarissa; Rampelli, Simone; Turroni, Silvia; Severgnini, Marco; Peano, Clelia; Ghezzo, Alessandro; Scurti, Maria; Salvioli, Stefano; Franceschi, Claudio; Brigidi, Patrizia

    2014-01-01

    Background Premature aging seriously compromises the health status of Down Syndrome (DS) persons. Since human aging has been associated with a deterioration of the gut microbiota (GM)-host mutualism, here we investigated the composition of GM in DS. Methods The observational study presented involved 17 adult DS persons. We characterized the GM structure by 454 pyrosequencing of the V4 region of the 16S rRNA gene. DS microbiome was compared with that of age-matched healthy non-trisomic adults enrolled in the same geographic area. Results and Conclusions The dominant GM fraction of DS persons showed an overall mutualistic immune-modulatory layout, comparable to that of healthy controls. This makes GM a possible factor counteracting the genetic determined acceleration of immune senescence in DS persons. However, we also found detectable signatures specific for DS among subdominant GM components, such as the increase of Parasporobacterium and Sutterella. In particular, the abundance of this last microorganism significantly correlated with the Aberrant Behavior Checklist (ABC) total score, allowing us to hypothesize a possible role for this microbial genus in behavioral features in DS. PMID:25386941

  3. Shrinkage of the human core microbiome and a proposal for launching microbiome biobanks.

    PubMed

    Barzegari, Abolfazl; Saeedi, Nazli; Saei, Amir Ata

    2014-01-01

    The Human Microbiome Project (HMP) revealed the significance of the gut microbiome in promoting health. Disruptions in microbiome composition are associated with the pathogenesis of numerous diseases. The indigenous microflora has co-evolved with humans for millions of years and humans have preserved the inherited microbiomes through consumption of fermented foods and interactions with environmental microbes. Through modernization, traditional foods were abandoned, native food starters were substituted with industrial products, vaccines and antibiotics were used, extreme hygiene measures were taken, the rate of cesarean section increased, and breast feeding changed into formula. These factors have reduced human exposure to microbial symbionts and led to shrinkage of the core microbiome. Reduction in microbiome biodiversity can compromise the human immune system and predispose individuals to several modern diseases. This article suggests launching microbiome biobanks for archiving native microbiomes, supervising antibiotic use, probiotic design and native starter production, as well as advertising a revisit to native lifestyles.

  4. Convergence of gut microbiomes in myrmecophagous mammals.

    PubMed

    Delsuc, Frédéric; Metcalf, Jessica L; Wegener Parfrey, Laura; Song, Se Jin; González, Antonio; Knight, Rob

    2014-03-01

    Mammals have diversified into many dietary niches. Specialized myrmecophagous (ant- and termite-eating) placental mammals represent a textbook example of evolutionary convergence driven by extreme diet specialization. Armadillos, anteaters, aardvarks, pangolins and aardwolves thus provide a model system for understanding the potential role of gut microbiota in the convergent adaptation to myrmecophagy. Here, we expand upon previous mammalian gut microbiome studies by using high-throughput barcoded Illumina sequencing of the 16S rRNA gene to characterize the composition of gut microbiota in 15 species representing all placental myrmecophagous lineages and their close relatives from zoo- and field-collected samples. We confirm that both diet and phylogeny drive the evolution of mammalian gut microbiota, with cases of convergence in global composition, but also examples of phylogenetic inertia. Our results reveal specialized placental myrmecophages as a spectacular case of large-scale convergence in gut microbiome composition. Indeed, neighbour-net networks and beta-diversity plots based on UniFrac distances show significant clustering of myrmecophagous species (anteaters, aardvarks and aardwolves), even though they belong to phylogenetically distant lineages representing different orders. The aardwolf, which diverged from carnivorous hyenas only in the last 10 million years, experienced a convergent shift in the composition of its gut microbiome to become more similar to other myrmecophages. These results confirm diet adaptation to be a major driving factor of convergence in gut microbiome composition over evolutionary timescales. This study sets the scene for future metagenomic studies aiming at evaluating potential convergence in functional gene content in the microbiomes of specialized mammalian myrmecophages. © 2013 John Wiley & Sons Ltd.

  5. Gut Microbiomes of Indian Children of Varying Nutritional Status

    PubMed Central

    Bhattacharya, Tanudeep; Yadav, Deepak; Barik, Anamitra; Chowdhury, Abhijit; Das, Bhabatosh; Mande, Sharmila S.; Nair, G. Balakrish

    2014-01-01

    Background Malnutrition is a global health problem affecting more than 300 million pre-school children worldwide. It is one of the major health concerns in India since around 50% of children below the age of two suffer from various forms of malnutrition. The gut microbiome plays an important role in nutrient pre-processing, assimilation and energy harvest from food. Consequently, dysbiosis of the gut microbiota has been implicated in malnutrition. Methodology/Principal Findings Metagenomics approach was adopted to investigate the gut microbiome sampled from 20 rural Indian children with varying nutritional status. The changes in the abundances of various taxonomic and functional groups were investigated across these gut microbiomes. A core set of 23 genera were observed across samples, with some showing differential abundances with varying nutritional status. One of the findings of the current study is the positive/negative associations of specific taxonomic and functional groups with the nutritional status of the children. Notable alterations in the architecture of the inter-microbial co-occurrence networks were also observed with changes in nutritional status. A key example is the clustering of potentially pathogenic groups into a distinct hub in severely malnourished gut. Our data does not demonstrate causality with the microbiome patterns that we observed, rather a description of some interesting patterns, whose underlying mechanism remains to be uncovered. Conclusions The present study envisioned interrelationships between the pattern of gut microbiome and the nutritional status of children. The cause of this pattern needs to be explored. However, insights obtained from the present study form the basis for further metagenomic investigations on larger population of children. Results of such studies will be useful in identifying the key microbial groups that can be utilized for targeted therapeutic interventions for managing severe acute malnutrition. PMID

  6. Gut microbiomes of Indian children of varying nutritional status.

    PubMed

    Ghosh, Tarini Shankar; Gupta, Sourav Sen; Bhattacharya, Tanudeep; Yadav, Deepak; Barik, Anamitra; Chowdhury, Abhijit; Das, Bhabatosh; Mande, Sharmila S; Nair, G Balakrish

    2014-01-01

    Malnutrition is a global health problem affecting more than 300 million pre-school children worldwide. It is one of the major health concerns in India since around 50% of children below the age of two suffer from various forms of malnutrition. The gut microbiome plays an important role in nutrient pre-processing, assimilation and energy harvest from food. Consequently, dysbiosis of the gut microbiota has been implicated in malnutrition. Metagenomics approach was adopted to investigate the gut microbiome sampled from 20 rural Indian children with varying nutritional status. The changes in the abundances of various taxonomic and functional groups were investigated across these gut microbiomes. A core set of 23 genera were observed across samples, with some showing differential abundances with varying nutritional status. One of the findings of the current study is the positive/negative associations of specific taxonomic and functional groups with the nutritional status of the children. Notable alterations in the architecture of the inter-microbial co-occurrence networks were also observed with changes in nutritional status. A key example is the clustering of potentially pathogenic groups into a distinct hub in severely malnourished gut. Our data does not demonstrate causality with the microbiome patterns that we observed, rather a description of some interesting patterns, whose underlying mechanism remains to be uncovered. The present study envisioned interrelationships between the pattern of gut microbiome and the nutritional status of children. The cause of this pattern needs to be explored. However, insights obtained from the present study form the basis for further metagenomic investigations on larger population of children. Results of such studies will be useful in identifying the key microbial groups that can be utilized for targeted therapeutic interventions for managing severe acute malnutrition.

  7. Insights from Characterizing Extinct Human Gut Microbiomes

    PubMed Central

    Tito, Raul Y.; Knights, Dan; Metcalf, Jessica; Obregon-Tito, Alexandra J.; Cleeland, Lauren; Najar, Fares; Roe, Bruce; Reinhard, Karl; Sobolik, Kristin; Belknap, Samuel; Foster, Morris; Spicer, Paul; Knight, Rob; Lewis, Cecil M.

    2012-01-01

    In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (∼8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome. PMID:23251439

  8. Insights from characterizing extinct human gut microbiomes.

    PubMed

    Tito, Raul Y; Knights, Dan; Metcalf, Jessica; Obregon-Tito, Alexandra J; Cleeland, Lauren; Najar, Fares; Roe, Bruce; Reinhard, Karl; Sobolik, Kristin; Belknap, Samuel; Foster, Morris; Spicer, Paul; Knight, Rob; Lewis, Cecil M

    2012-01-01

    In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (~8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome.

  9. Gut Microbiome of the Canadian Arctic Inuit

    PubMed Central

    Tromas, Nicolas; Amyot, Marc

    2017-01-01

    ABSTRACT Diet is a major determinant of community composition in the human gut microbiome, and “traditional” diets have been associated with distinct and highly diverse communities, compared to Western diets. However, most traditional diets studied have been those of agrarians and hunter-gatherers consuming fiber-rich diets. In contrast, the Inuit of the Canadian Arctic have been consuming a traditional diet low in carbohydrates and rich in animal fats and protein for thousands of years. We hypothesized that the Inuit diet and lifestyle would be associated with a distinct microbiome. We used deep sequencing of the 16S rRNA gene to compare the gut microbiomes of Montrealers with a Western diet to those of the Inuit consuming a range of traditional and Western diets. At the overall microbial community level, the gut microbiomes of Montrealers and Inuit were indistinguishable and contained similar levels of microbial diversity. However, we observed significant differences in the relative abundances of certain microbial taxa down to the subgenus level using oligotyping. For example, Prevotella spp., which have been previously associated with high-fiber diets, were enriched in Montrealers and among the Inuit consuming a Western diet. The gut microbiomes of Inuit consuming a traditional diet also had significantly less genetic diversity within the Prevotella genus, suggesting that a low-fiber diet might not only select against Prevotella but also reduce its diversity. Other microbes, such as Akkermansia, were associated with geography as well as diet, suggesting limited dispersal to the Arctic. Our report provides a snapshot of the Inuit microbiome as Western-like in overall community structure but distinct in the relative abundances and diversity of certain genera and strains. IMPORTANCE Non-Western populations have been shown to have distinct gut microbial communities shaped by traditional diets. The hitherto-uncharacterized microbiome of the Inuit may help us to

  10. Human genetic variation and the gut microbiome in disease.

    PubMed

    Hall, Andrew Brantley; Tolonen, Andrew C; Xavier, Ramnik J

    2017-08-21

    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.

  11. Gut microbiome and metabolic diseases.

    PubMed

    Fukuda, Shinji; Ohno, Hiroshi

    2014-01-01

    The prevalence of obesity and obesity-related disorders is increasing worldwide. In the last decade, the gut microbiota has emerged as an important factor in the development of obesity and metabolic syndrome, through its interactions with dietary, environmental, and host genetic factors. Various studies have shown that alteration of the gut microbiota, shifting it toward increased energy harvest, is associated with an obese phenotype. However, the molecular mechanisms by which the gut microbiota affects host metabolism are still obscure. In this review, we discuss the complexity of the gut microbiota and its relationship to obesity and obesity-related diseases. Furthermore, we discuss the anti-obesity potential of probiotics and prebiotics.

  12. 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

  13. The giant panda gut microbiome.

    PubMed

    Wei, Fuwen; Wang, Xiao; Wu, Qi

    2015-08-01

    Giant pandas (Ailuropoda melanoleuca) are bamboo specialists that evolved from carnivores. Their gut microbiota probably aids in the digestion of cellulose and this is considered an example of gut microbiota adaptation to a bamboo diet. However, this issue remains unresolved and further functional and compositional studies are needed.

  14. Global Profiling of Carbohydrate Active Enzymes in Human Gut Microbiome

    PubMed Central

    Mande, Sharmila S.

    2015-01-01

    Motivation Carbohydrate Active enzyme (CAZyme) families, encoded by human gut microflora, play a crucial role in breakdown of complex dietary carbohydrates into components that can be absorbed by our intestinal epithelium. Since nutritional wellbeing of an individual is dependent on the nutrient harvesting capability of the gut microbiome, it is important to understand how CAZyme repertoire in the gut is influenced by factors like age, geography and food habits. Results This study reports a comprehensive in-silico analysis of CAZyme profiles in the gut microbiomes of 448 individuals belonging to different geographies, using similarity searches of the corresponding gut metagenomic contigs against the carbohydrate active enzymes database. The study identifies a core group of 89 CAZyme families that are present across 85% of the gut microbiomes. The study detects several geography/age-specific trends in gut CAZyme repertoires of the individuals. Notably, a group of CAZymes having a positive correlation with BMI has been identified. Further this group of BMI-associated CAZymes is observed to be specifically abundant in the Firmicutes phyla. One of the major findings from this study is identification of three distinct groups of individuals, referred to as 'CAZotypes', having similar CAZyme profiles. Distinct taxonomic drivers for these CAZotypes as well as the probable dietary basis for such trends have also been elucidated. The results of this study provide a global view of CAZyme profiles across individuals of various geographies and age-groups. These results re-iterate the need of a more precise understanding of the role of carbohydrate active enzymes in human nutrition. PMID:26544883

  15. The Gut Microbiome and the Brain

    PubMed Central

    Galland, Leo

    2014-01-01

    Abstract The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics. PMID:25402818

  16. Obesity and the gut microbiome: pathophysiological aspects.

    PubMed

    Bradlow, H Leon

    2014-01-01

    While there is a large volume of literature describing a role for obesity as a risk factor for breast cancer and many other cancers, in the main a causal relationship has not been established. If the study is limited to breast cancer risk, it has been suggested that the increase in sex steroid formation that occurs in postmenopausal women plays a role. Obesity is known to be associated with chronic low grade inflammation, but no reason for this association has been offered in the past. The gut microbiome, while known to be enormous, has not in the past been considered as a metabolic role player in the body. This is now recognized to be the case. Recent studies have found the obesity is correlated with an alteration in the gut microbiome. In obese individual there is a change in the relative proportions of the two major classes of bacteria - bacteroides and firmacutes - with the latter dominant in obesity and resulting in the formation of increased amounts of metabolic endotoxins like deoxycholic acid and lipopolysaccharides (LPS). Obese individuals show a decrease in the concentration of Akkermansia muciniphila in the mucus that lines the intestinal wall, resulting in thinner mucus and a weakened intestinal lining and permitting metabolic endotoxins formed by other bacterial flora like LPS to enter the blood steam and cause the chronic inflammation associated with obesity. The change in the microbiome profile results in increases in bacterial strains that are more efficient at generating energy, leading to increased obesity. In mice, it has been shown that introducing gut bacterial flora from the cecum of obese mice into germ-free mice results in increased obesity with lesser food consumption while the reverse, introducing bacterial flora from lean mice results in a loss in weight. This raises the attractive possibility that manipulating the gut microbiome could facilitate weight loss or prevent obesity in humans.

  17. Gut microbiome, surgical complications and probiotics

    PubMed Central

    Stavrou, George; Kotzampassi, Katerina

    2017-01-01

    The trigger for infectious complications in patients following major abdominal operations is classically attributed to endogenous enteral bacterial translocation, due to the critical condition of the gut. Today, extensive gut microbiome analysis has enabled us to understand that almost all “evidence-based” surgical or medical intervention (antibiotics, bowel preparation, opioids, deprivation of nutrition), in addition to stress-released hormones, could affect the relative abundance and diversity of the enteral microbiome, allowing harmful bacteria to proliferate in the place of depressed beneficial species. Furthermore, these bacteria, after tight sensing of host stress and its consequent humoral alterations, can and do switch their virulence accordingly, towards invasion of the host. Probiotics are the exogenously given, beneficial clusters of live bacteria that, upon digestion, seem to succeed in partially restoring the distorted microbial diversity, thus reducing the infectious complications occurring in surgical and critically ill patients. This review presents the latest data on the interrelationship between the gut microbiome and the occurrence of complications after colon surgery, and the efficacy of probiotics as therapeutic instruments for changing the bacterial imbalance. PMID:28042237

  18. Arthritis susceptibility and the Gut Microbiome

    PubMed Central

    Taneja, Veena

    2014-01-01

    Summary Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors like smoking have been studies extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system that leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means. PMID:24873878

  19. Arthritis susceptibility and the gut microbiome.

    PubMed

    Taneja, Veena

    2014-11-17

    Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors (e.g. smoking) have been studied extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system, which leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means.

  20. Development of the Preterm Gut Microbiome in Twins at Risk of Necrotising Enterocolitis and Sepsis

    PubMed Central

    Stewart, Christopher J.; Marrs, Emma C. L.; Nelson, Andrew; Lanyon, Clare; Perry, John D.; Embleton, Nicholas D.; Cummings, Stephen P.; Berrington, Janet E.

    2013-01-01

    The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics. PMID:24023682

  1. Metabolic tinkering by the gut microbiome

    PubMed Central

    Selkrig, Joel; Wong, Peiyan; Zhang, Xiaodong; Pettersson, Sven

    2014-01-01

    Brain development is an energy demanding process that relies heavily upon diet derived nutrients. Gut microbiota enhance the host’s ability to extract otherwise inaccessible energy from the diet via fermentation of complex oligosaccharides in the colon. This nutrient yield is estimated to contribute up to 10% of the host’s daily caloric requirement in humans and fluctuates in response to environmental variations. Research over the past decade has demonstrated a surprising role for the gut microbiome in normal brain development and function. In this review we postulate that perturbations in the gut microbial-derived nutrient supply, driven by environmental variation, profoundly impacts upon normal brain development and function. PMID:24685620

  2. Diet effects in gut microbiome and obesity.

    PubMed

    Chen, Jia; He, Xianzhi; Huang, Jinhai

    2014-04-01

    The 100 trillion microbes in human gut coevolve with the host and exert significant influences on human health. The gut microbial composition presents dynamic changes correlated with various factors including host genotypes, age, and external environment. Effective manipulation of the gut microbiota through diets (both long-term and short-term diet patterns), probiotics and/or prebiotics, and antibiotics has been proved being potential to prevent from metabolic disorders such as obesity in many studies. The dietary regulation exerts influences on microbial metabolism and host immune functions through several pathways, of which may include selectively bacterial fermentation of nutrients, lower intestinal barrier function, overexpression of genes associated with disorders, and disruptions to both innate and adaptive immunity. Discoveries in the interrelationship between diet, intestinal microbiome, and body immune system provide us novel perceptions to the specific action mechanisms and will promote the development of therapeutic approaches for obesity. © 2014 Institute of Food Technologists®

  3. 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

  4. The gut microbiome in autoimmunity: sex matters

    PubMed Central

    Gomez, Andres; Luckey, David; Taneja, Veena

    2015-01-01

    Autoimmune diseases like rheumatoid arthritis are multifactorial in nature, requiring both genetic and environmental factors for onset. Increased predisposition of females to a wide range of autoimmune diseases points to a gender bias in the multifactorial etiology of these disorders. However, the existing evidence tol date has not provided any conclusive mechanism of gender- bias beyond the role of hormones and sex chromosomes. The gut microbiome, which impacts the innate and adaptive branches of immunity, not only influences the development of autoimmune disorders but may interact with sex-hormones to modulate disease progression and sex-bias. Here, we review the current information on gender bias in autoimmunity and discuss the potential of microbiome-derived biomarkers to help unravel the complex interplay between genes, environment and hormones in rheumatoid arthritis. PMID:25956531

  5. Caterpillars lack a resident gut microbiome.

    PubMed

    Hammer, Tobin J; Janzen, Daniel H; Hallwachs, Winnie; Jaffe, Samuel P; Fierer, Noah

    2017-09-05

    Many animals are inhabited by microbial symbionts that influence their hosts' development, physiology, ecological interactions, and evolutionary diversification. However, firm evidence for the existence and functional importance of resident microbiomes in larval Lepidoptera (caterpillars) is lacking, despite the fact that these insects are enormously diverse, major agricultural pests, and dominant herbivores in many ecosystems. Using 16S rRNA gene sequencing and quantitative PCR, we characterized the gut microbiomes of wild leaf-feeding caterpillars in the United States and Costa Rica, representing 124 species from 15 families. Compared with other insects and vertebrates assayed using the same methods, the microbes that we detected in caterpillar guts were unusually low-density and variable among individuals. Furthermore, the abundance and composition of leaf-associated microbes were reflected in the feces of caterpillars consuming the same plants. Thus, microbes ingested with food are present (although possibly dead or dormant) in the caterpillar gut, but host-specific, resident symbionts are largely absent. To test whether transient microbes might still contribute to feeding and development, we conducted an experiment on field-collected caterpillars of the model species Manduca sexta Antibiotic suppression of gut bacterial activity did not significantly affect caterpillar weight gain, development, or survival. The high pH, simple gut structure, and fast transit times that typify caterpillar digestive physiology may prevent microbial colonization. Moreover, host-encoded digestive and detoxification mechanisms likely render microbes unnecessary for caterpillar herbivory. Caterpillars illustrate the potential ecological and evolutionary benefits of independence from symbionts, a lifestyle that may be widespread among animals.

  6. Biomass utilization by gut microbiomes.

    PubMed

    White, Bryan A; Lamed, Raphael; Bayer, Edward A; Flint, Harry J

    2014-01-01

    Mammals rely entirely on symbiotic microorganisms within their digestive tract to gain energy from plant biomass that is resistant to mammalian digestive enzymes. Especially in herbivorous animals, specialized organs (the rumen, cecum, and colon) have evolved that allow highly efficient fermentation of ingested plant biomass by complex anaerobic microbial communities. We consider here the two most intensively studied, representative gut microbial communities involved in degradation of plant fiber: those of the rumen and the human large intestine. These communities are dominated by bacteria belonging to the Firmicutes and Bacteroidetes phyla. In Firmicutes, degradative capacity is largely restricted to the cell surface and involves elaborate cellulosome complexes in specialized cellulolytic species. By contrast, in the Bacteroidetes, utilization of soluble polysaccharides, encoded by gene clusters (PULs), entails outer membrane binding proteins, and degradation is largely periplasmic or intracellular. Biomass degradation involves complex interplay between these distinct groups of bacteria as well as (in the rumen) eukaryotic microorganisms.

  7. Dynamic Gut Microbiome across Life History of the Malaria Mosquito Anopheles gambiae in Kenya

    PubMed Central

    Kukutla, Phanidhar; Yan, Guiyun; Xu, Jiannong

    2011-01-01

    The mosquito gut represents an ecosystem that accommodates a complex, intimately associated microbiome. It is increasingly clear that the gut microbiome influences a wide variety of host traits, such as fitness and immunity. Understanding the microbial community structure and its dynamics across mosquito life is a prerequisite for comprehending the symbiotic relationship between the mosquito and its gut microbial residents. Here we characterized gut bacterial communities across larvae, pupae and adults of Anopheles gambiae reared in semi-natural habitats in Kenya by pyrosequencing bacterial 16S rRNA fragments. Immatures and adults showed distinctive gut community structures. Photosynthetic Cyanobacteria were predominant in the larval and pupal guts while Proteobacteria and Bacteroidetes dominated the adult guts, with core taxa of Enterobacteriaceae and Flavobacteriaceae. At the adult stage, diet regime (sugar meal and blood meal) significantly affects the microbial structure. Intriguingly, blood meals drastically reduced the community diversity and favored enteric bacteria. Comparative genomic analysis revealed that the enriched enteric bacteria possess large genetic redox capacity of coping with oxidative and nitrosative stresses that are associated with the catabolism of blood meal, suggesting a beneficial role in maintaining gut redox homeostasis. Interestingly, gut community structure was similar in the adult stage between the field and laboratory mosquitoes, indicating that mosquito gut is a selective eco-environment for its microbiome. This comprehensive gut metatgenomic profile suggests a concerted symbiotic genetic association between gut inhabitants and host. PMID:21957459

  8. Modulating the human gut microbiome as an emerging therapeutic paradigm.

    PubMed

    Rajpal, Deepak K; Brown, James R

    2013-01-01

    The human body is actually a vast and changing ecosystem comprised of billions of microbial organisms, known collectively as the microbiome. Within the last few years, the study of the microbiome and its impact on human health has been a rapidly growing area of biomedical science. The gut intestinal tract microbiome has been a particular focus of research given its potential role in many inflammatory and metabolic diseases as well as drug metabolism. Although a nascent field, the potential for modulating the gut microbiome or human host interactions associated with these microbes offers new therapeutic strategies for many chronic diseases, in particular obesity, diabetes and inflammatory bowel diseases. Here we provide an overview of present knowledge about the gut microbiome, its putative role in metabolic diseases and the potential for microbiome focused treatments from the drug development perspective.

  9. 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.

  10. Development of the preterm infant gut microbiome: A research priority

    SciTech Connect

    Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; Ashmeade, Terri L.; Miller, Elizabeth; Gilbert, Jack A.

    2014-10-13

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.

  11. Development of the preterm infant gut microbiome: A research priority

    DOE PAGES

    Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; ...

    2014-10-13

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role ofmore » the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.« less

  12. Panorganismal gut microbiome-host metabolic crosstalk.

    PubMed

    Martin, Francois-Pierre J; Sprenger, Norbert; Yap, Ivan K S; Wang, Yulan; Bibiloni, Rodrigo; Rochat, Florence; Rezzi, Serge; Cherbut, Christine; Kochhar, Sunil; Lindon, John C; Holmes, Elaine; Nicholson, Jeremy K

    2009-04-01

    Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.

  13. Synthetic biology and the gut microbiome.

    PubMed

    Dou, Jennifer; Bennett, Matthew R

    2017-10-04

    The gut microbiome plays a crucial role in maintaining human health. Functions performed by gastrointestinal microbes range from regulating metabolism to modulating immune and nervous system development. Scientists have attempted to exploit this importance through the development of engineered probiotics that are capable of producing and delivering small molecule therapeutics within the gut. However, existing synthetic probiotics are simplistic and fail to replicate the complexity and adaptability of native homeostatic mechanisms. In this review, we discuss the ways in which the tools and approaches of synthetic biology have been applied to improve the efficacy of therapeutic probiotics, and the ways in which they might be applied in the future. Simple devices, such as a bistable switches and integrase memory arrays, have been successfully implemented in the mammalian gut, and models for targeted delivery in this environment have also been developed. In the future, it will be necessary to introduce concepts such as logic-gating and biocontainment mechanisms into synthetic probiotics, as well as to expand the collection of relevant biosensors. Ideally, this will bring us closer to a reality in which engineered therapeutic microbes will be able to accurately diagnose and effectively respond to a variety of disease states. This article is protected by copyright. All rights reserved.

  14. Correlations of Host Genetics and Gut Microbiome Composition

    PubMed Central

    Dąbrowska, Krystyna; Witkiewicz, Wojciech

    2016-01-01

    The human gut microbiome has a considerable impact on host health. The long list of microbiome-related health disorders raises the question of what in fact determines microbiome composition. In this review we sought to understand how the host itself impacts the structure of the gut microbiota population, specifically by correlations of host genetics and gut microbiome composition. Host genetic profile has been linked to differences in microbiome composition, thus suggesting that host genetics can shape the gut microbiome of the host. However, cause-consequence mechanisms behind these links are still unclear. A survey of the possible mechanisms allowing host genetics to shape microbiota composition in the gut demonstrated the major role of metabolic functions and the immune system. A considerable impact of other factors, such as diet, may outweigh the effects of host genetic background. More studies are necessary for good understanding of the relations between the host genetic profile, gut microbiome composition, and host health. According to the idea of personalized medicine, patient-tailored management of microbiota content remains a fascinating area for further inquiry. PMID:27625642

  15. Gut microbiome in chronic kidney disease: challenges and opportunities.

    PubMed

    Nallu, Anitha; Sharma, Shailendra; Ramezani, Ali; Muralidharan, Jagadeesan; Raj, Dominic

    2017-01-01

    More than 100 trillion microbial cells that reside in the human gut heavily influence nutrition, metabolism, and immune function of the host. Gut dysbiosis, seen commonly in patients with chronic kidney disease (CKD), results from qualitative and quantitative changes in host microbiome profile and disruption of gut barrier function. Alterations in gut microbiota and a myriad of host responses have been implicated in progression of CKD, increased cardiovascular risk, uremic toxicity, and inflammation. We present a discussion of dysbiosis, various uremic toxins produced from dysbiotic gut microbiome, and their roles in CKD progression and complications. We also review the gut microbiome in renal transplant, highlighting the role of commensal microbes in alteration of immune responses to transplantation, and conclude with therapeutic interventions that aim to restore intestinal dysbiosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Alterations of the human gut microbiome in multiple sclerosis

    PubMed Central

    Jangi, Sushrut; Gandhi, Roopali; Cox, Laura M.; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria Antonietta; Liu, Shirong; Glanz, Bonnie L.; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D.; Holden, James; Kivisäkk, Pia; Chitnis, Tanuja; De Jager, Philip L.; Quintana, Francisco J.; Gerber, Georg K.; Bry, Lynn; Weiner, Howard L.

    2016-01-01

    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. PMID:27352007

  17. The gut microbiome-an emerging complex trait.

    PubMed

    Benson, Andrew K

    2016-10-27

    As the first series of genetic analyses of gut microbiome composition in humans is now emerging, the results should be met with enthusiasm, but also with caution. Findings from the initial offerings demonstrate how population-scale approaches can provide deeper insights into host-microbiome interactions while at the same time illustrating that our understanding of the architecture of highly complex microbiome 'traits' is still rudimentary.

  18. Gut Microbiome and Kidney Disease in Pediatrics: Does Connection Exist?

    PubMed Central

    Vasylyeva, Tetyana L.; Singh, Ruchi

    2016-01-01

    Child development is a unique and continuous process that is impacted by genetics and environmental factors. Gut microbiome changes with development and depends on the stage of gut maturation, nutrition, and overall health. In spite of emerging data and active study in adults, the gut-renal axis in pediatrics has not been well considered and investigated. This review will focus on the current knowledge of gut microbiota impacts on kidney disease with extrapolation to the pediatric population. PMID:26973613

  19. Gut Microbiome and Kidney Disease in Pediatrics: Does Connection Exist?

    PubMed

    Vasylyeva, Tetyana L; Singh, Ruchi

    2016-01-01

    Child development is a unique and continuous process that is impacted by genetics and environmental factors. Gut microbiome changes with development and depends on the stage of gut maturation, nutrition, and overall health. In spite of emerging data and active study in adults, the gut-renal axis in pediatrics has not been well considered and investigated. This review will focus on the current knowledge of gut microbiota impacts on kidney disease with extrapolation to the pediatric population.

  20. Gut Microbiome: Westernization and the Disappearance of Intestinal Diversity.

    PubMed

    Segata, Nicola

    2015-07-20

    The environment shapes our intestinal microbiome. By contrasting the gut microbiomes of African hunter-gatherer and European subjects, a new study reveals that urbanization is associated with a loss of microbial organisms and genes. What will be the consequences of the lost biodiversity in the sanitized, western-diet world? Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Unexplored Archaeal Diversity in the Great Ape Gut Microbiome

    PubMed Central

    Moeller, Andrew H.; Goodman, Andrew L.; Ochman, Howard

    2017-01-01

    ABSTRACT Archaea are habitual residents of the human gut flora but are detected at substantially lower frequencies than bacteria. Previous studies have indicated that each human harbors very few archaeal species. However, the low diversity of human-associated archaea that has been detected could be due to the preponderance of bacteria in these communities, such that relatively few sequences are classified as Archaea even when microbiomes are sampled deeply. Moreover, the universal prokaryotic primer pair typically used to interrogate microbial diversity has low specificity to the archaeal domain, potentially leaving vast amounts of diversity unobserved. As a result, the prevalence, diversity, and distribution of archaea may be substantially underestimated. Here we evaluate archaeal diversity in gut microbiomes using an approach that targets virtually all known members of this domain. Comparing microbiomes across five great ape species allowed us to examine the dynamics of archaeal lineages over evolutionary time scales. These analyses revealed hundreds of gut-associated archaeal lineages, indicating that upwards of 90% of the archaeal diversity in the human and great ape gut microbiomes has been overlooked. Additionally, these results indicate a progressive reduction in archaeal diversity in the human lineage, paralleling the decline reported for bacteria. IMPORTANCE Our findings show that Archaea are a habitual and vital component of human and great ape gut microbiomes but are largely ignored on account of the failure of previous studies to realize their full diversity. Here we report unprecedented levels of archaeal diversity in great ape gut microbiomes, exceeding that detected by conventional 16S rRNA gene surveys. Paralleling what has been reported for bacteria, there is a vast reduction of archaeal diversity in humans. Our study demonstrates that archaeal diversity in the great ape gut microbiome greatly exceeds that reported previously and provides the basis

  2. Unexplored Archaeal Diversity in the Great Ape Gut Microbiome.

    PubMed

    Raymann, Kasie; Moeller, Andrew H; Goodman, Andrew L; Ochman, Howard

    2017-01-01

    Archaea are habitual residents of the human gut flora but are detected at substantially lower frequencies than bacteria. Previous studies have indicated that each human harbors very few archaeal species. However, the low diversity of human-associated archaea that has been detected could be due to the preponderance of bacteria in these communities, such that relatively few sequences are classified as Archaea even when microbiomes are sampled deeply. Moreover, the universal prokaryotic primer pair typically used to interrogate microbial diversity has low specificity to the archaeal domain, potentially leaving vast amounts of diversity unobserved. As a result, the prevalence, diversity, and distribution of archaea may be substantially underestimated. Here we evaluate archaeal diversity in gut microbiomes using an approach that targets virtually all known members of this domain. Comparing microbiomes across five great ape species allowed us to examine the dynamics of archaeal lineages over evolutionary time scales. These analyses revealed hundreds of gut-associated archaeal lineages, indicating that upwards of 90% of the archaeal diversity in the human and great ape gut microbiomes has been overlooked. Additionally, these results indicate a progressive reduction in archaeal diversity in the human lineage, paralleling the decline reported for bacteria. IMPORTANCE Our findings show that Archaea are a habitual and vital component of human and great ape gut microbiomes but are largely ignored on account of the failure of previous studies to realize their full diversity. Here we report unprecedented levels of archaeal diversity in great ape gut microbiomes, exceeding that detected by conventional 16S rRNA gene surveys. Paralleling what has been reported for bacteria, there is a vast reduction of archaeal diversity in humans. Our study demonstrates that archaeal diversity in the great ape gut microbiome greatly exceeds that reported previously and provides the basis for

  3. The human gut microbiome, a taxonomic conundrum.

    PubMed

    Sankar, Senthil Alias; Lagier, Jean-Christophe; Pontarotti, Pierre; Raoult, Didier; Fournier, Pierre-Edouard

    2015-06-01

    From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geographic origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested associations between specific gut microbiota compositions and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health.

  4. Social networks predict gut microbiome composition in wild baboons.

    PubMed

    Tung, Jenny; Barreiro, Luis B; Burns, Michael B; Grenier, Jean-Christophe; Lynch, Josh; Grieneisen, Laura E; Altmann, Jeanne; Alberts, Susan C; Blekhman, Ran; Archie, Elizabeth A

    2015-03-16

    Social relationships have profound effects on health in humans and other primates, but the mechanisms that explain this relationship are not well understood. Using shotgun metagenomic data from wild baboons, we found that social group membership and social network relationships predicted both the taxonomic structure of the gut microbiome and the structure of genes encoded by gut microbial species. Rates of interaction directly explained variation in the gut microbiome, even after controlling for diet, kinship, and shared environments. They therefore strongly implicate direct physical contact among social partners in the transmission of gut microbial species. We identified 51 socially structured taxa, which were significantly enriched for anaerobic and non-spore-forming lifestyles. Our results argue that social interactions are an important determinant of gut microbiome composition in natural animal populations-a relationship with important ramifications for understanding how social relationships influence health, as well as the evolution of group living.

  5. Marek’s Disease Virus influences the core gut microbiome of the chicken during the early and late phases of viral replication

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease (MD) is an important neoplastic disease of chickens caused by the Marek’s disease virus (MDV), an oncogenic alphaherpesvirus. In this study, dysbiosis induced by MDV on the core gut flora of chicken was assessed using next generation sequence (NGS) analysis. Total fecal and cecum-der...

  6. Application of metagenomics in the human gut microbiome

    PubMed Central

    Wang, Wei-Lin; Xu, Shao-Yan; Ren, Zhi-Gang; Tao, Liang; Jiang, Jian-Wen; Zheng, Shu-Sen

    2015-01-01

    There are more than 1000 microbial species living in the complex human intestine. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and is even regarded as an endocrine organ. However, traditional culture methods are very limited for identifying microbes. With the application of molecular biologic technology in the field of the intestinal microbiome, especially metagenomic sequencing of the next-generation sequencing technology, progress has been made in the study of the human intestinal microbiome. Metagenomics can be used to study intestinal microbiome diversity and dysbiosis, as well as its relationship to health and disease. Moreover, functional metagenomics can identify novel functional genes, microbial pathways, antibiotic resistance genes, functional dysbiosis of the intestinal microbiome, and determine interactions and co-evolution between microbiota and host, though there are still some limitations. Metatranscriptomics, metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome. This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects. The limitations of metagenomics to be overcome are also discussed. Metatranscriptomics, metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed. PMID:25624713

  7. Application of metagenomics in the human gut microbiome.

    PubMed

    Wang, Wei-Lin; Xu, Shao-Yan; Ren, Zhi-Gang; Tao, Liang; Jiang, Jian-Wen; Zheng, Shu-Sen

    2015-01-21

    There are more than 1000 microbial species living in the complex human intestine. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and is even regarded as an endocrine organ. However, traditional culture methods are very limited for identifying microbes. With the application of molecular biologic technology in the field of the intestinal microbiome, especially metagenomic sequencing of the next-generation sequencing technology, progress has been made in the study of the human intestinal microbiome. Metagenomics can be used to study intestinal microbiome diversity and dysbiosis, as well as its relationship to health and disease. Moreover, functional metagenomics can identify novel functional genes, microbial pathways, antibiotic resistance genes, functional dysbiosis of the intestinal microbiome, and determine interactions and co-evolution between microbiota and host, though there are still some limitations. Metatranscriptomics, metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome. This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects. The limitations of metagenomics to be overcome are also discussed. Metatranscriptomics, metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.

  8. Dynamics of the human gut microbiome in inflammatory bowel disease.

    PubMed

    Halfvarson, Jonas; Brislawn, Colin J; Lamendella, Regina; Vázquez-Baeza, Yoshiki; Walters, William A; Bramer, Lisa M; D'Amato, Mauro; Bonfiglio, Ferdinando; McDonald, Daniel; Gonzalez, Antonio; McClure, Erin E; Dunklebarger, Mitchell F; Knight, Rob; Jansson, Janet K

    2017-02-13

    Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.

  9. Human gut microbiome viewed across age and geography

    USDA-ARS?s Scientific Manuscript database

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

  10. The gut microbiome, probiotics, bile acids axis, and human health.

    PubMed

    Jones, Mitchell Lawrence; Tomaro-Duchesneau, Catherine; Prakash, Satya

    2014-06-01

    The human gut microbiome produces potent ligands to bile acid receptors, and probiotics could act as therapeutics of bile acid dysmetabolism. A recent study in Cell Reports demonstrates that probiotic VSL#3 affects bile acid deconjugation and excretion, as well as the gut-liver FXR-FGF15 axis.

  11. 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

  12. Metabolome of human gut microbiome is predictive of host dysbiosis

    SciTech Connect

    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 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.

  13. Metabolome of human gut microbiome is predictive of host dysbiosis

    SciTech Connect

    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. 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. 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.

  14. The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes.

    PubMed

    Rath, Christopher M; Dorrestein, Pieter C

    2012-04-01

    Microbial communities in the gut have been hypothesized to play key roles in the health of the host organism. Exploring the relationship between these populations and disease states has been a focus of the human microbiome project. However, the biological roles of the compounds produced by the gut bacteria are largely unknown. We hypothesize that these compounds act as metabolic exchange factors-mediating inter-species and intra-species interactions in the microbiome. This view is supported through this review of known bacterial metabolic exchange factors and evidence for uncharacterized metabolic exchange factors in the gut. The impact of model systems and technological developments in exploring this hypothesis are also discussed. Together, these investigations are revolutionizing our understanding of the gut microbiome-presenting the possibility of identifying new strategies for treating disease in the host.

  15. Mechanisms Linking the Gut Microbiome and Glucose Metabolism

    PubMed Central

    Kratz, Mario; Damman, Chris J.; Hullarg, Meredith

    2016-01-01

    Context: Type 2 diabetes mellitus is associated with gastrointestinal dysbiosis involving both compositional and functional changes in the gut microbiome. Changes in diet and supplementation with probiotics and prebiotics (ie, fermentable fibers) can induce favorable changes in gut bacterial species and improve glucose homeostasis. Objective: This paper will review the data supporting several potential mechanisms whereby gut dysbiosis contributes to metabolic dysfunction, including microbiota driven increases in systemic lipopolysaccharide concentrations, changes in bile acid metabolism, alterations in short chain fatty acid production, alterations in gut hormone secretion, and changes in circulating branched-chain amino acids. Methods: Data for this review were identified by searching English language references from PubMed and relevant articles. Conclusions: Understanding the mechanisms linking the gut microbiome to glucose metabolism, and the relevant compositional and functional characteristics of the gut microbiome, will help direct future research to develop more targeted approaches or novel compounds aimed at restoring a more healthy gut microbiome as a new approach to prevent and treat type 2 diabetes mellitus and related metabolic conditions. PMID:26938201

  16. Gut microbiome perturbations induced by bacterial infection affect arsenic biotransformation

    PubMed Central

    Lu, Kun; Cable, Peter Hans; Abo, Ryan Phillip; Ru, Hongyu; Graffam, Michelle E.; Schieper, Katherine Ann; Parry, Nicola M.A.; Levine, Stuart; Bodnar, Wanda M; Wishnok, John S.; Styblo, Miroslav; Swenberg, James A; Fox, James G.; Tannenbaum, Steven R.

    2014-01-01

    Exposure to arsenic affects large human populations worldwide, and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which are frequently associated with different patterns of arsenic metabolism. Several underlying mechanisms, such as genetic polymorphisms and epigenetics, have been proposed, as these factors closely impact the individuals' capacity to metabolize arsenic. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that perturbations of the gut microbial communities affect the spectrum of metabolized arsenic species and subsequent toxicological effects. In this study, we used an animal model with altered gut microbiome induced by bacterial infection, 16S rRNA gene sequencing and inductively coupled plasma mass spectrometry (ICP-MS)-based arsenic speciation to examine the effect of gut microbiome perturbations on the biotransformation of arsenic. Metagenomics sequencing revealed that bacterial infection significantly perturbed the gut microbiome composition in C57BL/6 mice, which in turn resulted in altered spectra of arsenic metabolites in urine, with inorganic arsenic species, methylated and thiolated arsenic being perturbed. These data clearly illustrated that gut microbiome phenotypes significantly affected arsenic metabolic reactions, including reduction, methylation and thiolation. These findings improve our understanding of how infectious diseases and environmental exposure interact, and may also provide novel insight regarding the gut microbiome composition as a new risk factor of individual susceptibility to environmental chemicals. PMID:24134150

  17. Gut microbiome and kidney disease: a bidirectional relationship.

    PubMed

    Al Khodor, Souhaila; Shatat, Ibrahim F

    2017-06-01

    Recent technological advances and efforts, including powerful metagenomic and metatranscriptomic analyses, have led to a tremendous growth in our understanding of microbial communities. Changes in microbial abundance or composition of human microbial communities impact human health or disease state. However, explorations into the mechanisms underlying host-microbe interactions in health and disease are still in their infancy. Although changes in the gut microbiota have been described in patients with kidney disease, the relationships between pathogenesis, mechanisms of disease progression, and the gut microbiome are still evolving. Here, we review changes in the host-microbiome symbiotic relationship in an attempt to explore the bidirectional relationship in which alterations in the microbiome affect kidney disease progression and how kidney disease may disrupt a balanced microbiome. We also discuss potential targeted interventions that may help re-establish this symbiosis and propose more effective ways to deploy traditional treatments in patients with kidney disease.

  18. Unraveling the processes shaping mammalian gut microbiomes over evolutionary time.

    PubMed

    Groussin, Mathieu; Mazel, Florent; Sanders, Jon G; Smillie, Chris S; Lavergne, Sébastien; Thuiller, Wilfried; Alm, Eric J

    2017-02-23

    Whether mammal-microbiome interactions are persistent and specific over evolutionary time is controversial. Here we show that host phylogeny and major dietary shifts have affected the distribution of different gut bacterial lineages and did so on vastly different bacterial phylogenetic resolutions. Diet mostly influences the acquisition of ancient and large microbial lineages. Conversely, correlation with host phylogeny is mostly seen among more recently diverged bacterial lineages, consistent with processes operating at similar timescales to host evolution. Considering microbiomes at appropriate phylogenetic scales allows us to model their evolution along the mammalian tree and to infer ancient diets from the predicted microbiomes of mammalian ancestors. Phylogenetic analyses support co-speciation as having a significant role in the evolution of mammalian gut microbiome compositions. Highly co-speciating bacterial genera are also associated with immune diseases in humans, laying a path for future studies that probe these co-speciating bacteria for signs of co-evolution.

  19. Unraveling the processes shaping mammalian gut microbiomes over evolutionary time

    PubMed Central

    Groussin, Mathieu; Mazel, Florent; Sanders, Jon G.; Smillie, Chris S.; Lavergne, Sébastien; Thuiller, Wilfried; Alm, Eric J.

    2017-01-01

    Whether mammal–microbiome interactions are persistent and specific over evolutionary time is controversial. Here we show that host phylogeny and major dietary shifts have affected the distribution of different gut bacterial lineages and did so on vastly different bacterial phylogenetic resolutions. Diet mostly influences the acquisition of ancient and large microbial lineages. Conversely, correlation with host phylogeny is mostly seen among more recently diverged bacterial lineages, consistent with processes operating at similar timescales to host evolution. Considering microbiomes at appropriate phylogenetic scales allows us to model their evolution along the mammalian tree and to infer ancient diets from the predicted microbiomes of mammalian ancestors. Phylogenetic analyses support co-speciation as having a significant role in the evolution of mammalian gut microbiome compositions. Highly co-speciating bacterial genera are also associated with immune diseases in humans, laying a path for future studies that probe these co-speciating bacteria for signs of co-evolution. PMID:28230052

  20. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis.

    PubMed

    Wen, Chengping; Zheng, Zhijun; Shao, Tiejuan; Liu, Lin; Xie, Zhijun; Le Chatelier, Emmanuelle; He, Zhixing; Zhong, Wendi; Fan, Yongsheng; Zhang, Linshuang; Li, Haichang; Wu, Chunyan; Hu, Changfeng; Xu, Qian; Zhou, Jia; Cai, Shunfeng; Wang, Dawei; Huang, Yun; Breban, Maxime; Qin, Nan; Ehrlich, Stanislav Dusko

    2017-07-27

    The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers. Alterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.

  1. Characterization of the human gut microbiome during travelers' diarrhea

    PubMed Central

    Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Campbell, Frederick; Wadsworth, W Duncan; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

    2015-01-01

    Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel. PMID:25695334

  2. Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases.

    PubMed

    Singh, Bhagirath; Qin, Nan; Reid, Gregor

    2015-01-01

    Extensive analysis of the complexity and diversity of microbiota using metagenomics in the gut and other body sites has provided evidence that dysbiosis occurs in many disease states. With the application of next generation sequencing technology this research is starting to uncover the impact of microbiota on metabolic, physiological and immunological pathways and elucidate the cellular and molecular mechanisms involved. To highlight these advances we have focused on autoimmunity and gut and liver related diseases and discuss the opportunities and challenges of translating microbiome research towards its application in humans. Towards this goal we discuss the application of fecal microbiome transplantation (FMT) for the treatment of multiple chronic gut associated inflammatory diseases such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). The potential role of human migration across continents and cultures leading to alteration in their microbiome and its implication in health and disease is also discussed.

  3. Gut mucosal microbiome across stages of colorectal carcinogenesis.

    PubMed

    Nakatsu, Geicho; Li, Xiangchun; Zhou, Haokui; Sheng, Jianqiu; Wong, Sunny Hei; Wu, William Ka Kai; Ng, Siew Chien; Tsoi, Ho; Dong, Yujuan; Zhang, Ning; He, Yuqi; Kang, Qian; Cao, Lei; Wang, Kunning; Zhang, Jingwan; Liang, Qiaoyi; Yu, Jun; Sung, Joseph J Y

    2015-10-30

    Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). Here we catalogue the microbial communities in human gut mucosae at different stages of colorectal tumorigenesis. We analyse the gut mucosal microbiome of 47 paired samples of adenoma and adenoma-adjacent mucosae, 52 paired samples of carcinoma and carcinoma-adjacent mucosae and 61 healthy controls. Probabilistic partitioning of relative abundance profiles reveals that a metacommunity predominated by members of the oral microbiome is primarily associated with CRC. Analysis of paired samples shows differences in community configurations between lesions and the adjacent mucosae. Correlations of bacterial taxa indicate early signs of dysbiosis in adenoma, and co-exclusive relationships are subsequently more common in cancer. We validate these alterations in CRC-associated microbiome by comparison with two previously published data sets. Our results suggest that a taxonomically defined microbial consortium is implicated in the development of CRC.

  4. Human gut microbiome viewed across age and geography.

    PubMed

    Yatsunenko, Tanya; Rey, Federico E; Manary, Mark J; Trehan, Indi; Dominguez-Bello, Maria Gloria; Contreras, Monica; Magris, Magda; Hidalgo, Glida; Baldassano, Robert N; Anokhin, Andrey P; Heath, Andrew C; Warner, Barbara; Reeder, Jens; Kuczynski, Justin; Caporaso, J Gregory; Lozupone, Catherine A; Lauber, Christian; Clemente, Jose Carlos; Knights, Dan; Knight, Rob; Gordon, Jeffrey I

    2012-05-09

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.

  5. The emerging medical ecology of the human gut microbiome.

    PubMed

    Pepper, John W; Rosenfeld, Simon

    2012-07-01

    It is increasingly clear that the human gut microbiome has great medical importance, and researchers are beginning to investigate its basic biology and to appreciate the challenges that it presents to medical science. Several striking new empirical results in this area are perplexing within the standard conceptual framework of biomedicine, and this highlights the need for new perspectives from ecology and from dynamical systems theory. Here, we discuss recent results concerning sources of individual variation, temporal variation within individuals, long-term changes after transient perturbations and individualized responses to perturbation within the human gut microbiome.

  6. Early-life gut microbiome composition and milk allergy resolution.

    PubMed

    Bunyavanich, Supinda; Shen, Nan; Grishin, Alexander; Wood, Robert; Burks, Wesley; Dawson, Peter; Jones, Stacie M; Leung, Donald Y M; Sampson, Hugh; Sicherer, Scott; Clemente, Jose C

    2016-10-01

    Gut microbiota may play a role in the natural history of cow's milk allergy. We sought to examine the association between early-life gut microbiota and the resolution of cow's milk allergy. We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η(2) = 0.43; ANOVA P = .034). Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Mosquito C-type lectins maintain gut microbiome homeostasis

    PubMed Central

    Pang, Xiaojing; Xiao, Xiaoping; Liu, Yang; Zhang, Rudian; Liu, Jianying; Liu, Qiyong; Wang, Penghua; Cheng, Gong

    2016-01-01

    The long-term evolutionary interaction between the host immune system and symbiotic bacteria determines their cooperative rather than antagonistic relationship. It is known that commensal bacteria have evolved a number of mechanisms to manipulate the mammalian host immune system and maintain homeostasis. However, the strategies employed by the microbiome to overcome host immune responses in invertebrates still remain to be understood. Here, we report that the gut microbiome in mosquitoes utilizes C-type lectins (mosGCTLs) to evade the bactericidal capacity of antimicrobial peptides (AMPs). Aedes aegypti mosGCTLs facilitate colonization by multiple bacterial strains. Furthermore, maintenance of the gut microbial flora relies on the expression of mosGCTLs in A. aegypti. Silencing the orthologues of mosGCTL in another major mosquito vector (Culex pipiens pallens) also impairs the survival of gut commensal bacteria. The gut microbiome stimulates the expression of mosGCTLs, which coat the bacterial surface and counteract AMP activity. Our study describes a mechanism by which the insect symbiotic microbiome offsets gut immunity to achieve homeostasis. PMID:27170846

  8. 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.

  9. Succession of microbial consortia in the developing infant gut microbiome.

    PubMed

    Koenig, Jeremy E; Spor, Aymé; Scalfone, Nicholas; Fricker, Ashwana D; Stombaugh, Jesse; Knight, Rob; Angenent, Largus T; Ley, Ruth E

    2011-03-15

    The colonization process of the infant gut microbiome has been called chaotic, but this view could reflect insufficient documentation of the factors affecting the microbiome. We performed a 2.5-y case study of the assembly of the human infant gut microbiome, to relate life events to microbiome composition and function. Sixty fecal samples were collected from a healthy infant along with a diary of diet and health status. Analysis of >300,000 16S rRNA genes indicated that the phylogenetic diversity of the microbiome increased gradually over time and that changes in community composition conformed to a smooth temporal gradient. In contrast, major taxonomic groups showed abrupt shifts in abundance corresponding to changes in diet or health. Community assembly was nonrandom: we observed discrete steps of bacterial succession punctuated by life events. Furthermore, analysis of ≈ 500,000 DNA metagenomic reads from 12 fecal samples revealed that the earliest microbiome was enriched in genes facilitating lactate utilization, and that functional genes involved in plant polysaccharide metabolism were present before the introduction of solid food, priming the infant gut for an adult diet. However, ingestion of table foods caused a sustained increase in the abundance of Bacteroidetes, elevated fecal short chain fatty acid levels, enrichment of genes associated with carbohydrate utilization, vitamin biosynthesis, and xenobiotic degradation, and a more stable community composition, all of which are characteristic of the adult microbiome. This study revealed that seemingly chaotic shifts in the microbiome are associated with life events; however, additional experiments ought to be conducted to assess how different infants respond to similar life events.

  10. Control of the gut microbiome by fecal microRNA

    PubMed Central

    Liu, Shirong; Weiner, Howard L.

    2016-01-01

    Since their discovery in the early 90s, microRNAs (miRNAs), small non-coding RNAs, have mainly been associated with posttranscriptional regulation of gene expression on a cell-autonomous level. Recent evidence has extended this role by adding inter-species communication to the manifold functional range. In our latest study [Liu S, et al., 2016, Cell Host & Microbe], we identified miRNAs in gut lumen and feces of both mice and humans. We found that intestinal epithelial cells (IEC) and Hopx+ cells were the two main sources of fecal miRNA. Deficiency of IEC-miRNA resulted in gut dysbiosis and WT fecal miRNA transplantation restored the gut microbiota. We investigated potential mechanisms for this effect and found that miRNAs were able to regulate the gut microbiome. By culturing bacteria with miRNAs, we found that host miRNAs were able to enter bacteria, specifically regulate bacterial gene transcripts and affect bacterial growth. Oral administration of synthetic miRNA mimics affected specific bacteria in the gut. Our findings describe a previously unknown pathway by which the gut microbiome is regulated by the host and raises the possibility that miRNAs may be used therapeutically to manipulate the microbiome for the treatment of disease. PMID:28357349

  11. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

    USDA-ARS?s Scientific Manuscript database

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin ...

  12. Metabolic modeling with Big Data and the gut microbiome.

    PubMed

    Sung, Jaeyun; Hale, Vanessa; Merkel, Annette C; Kim, Pan-Jun; Chia, Nicholas

    2016-09-01

    The recent advances in high-throughput omics technologies have enabled researchers to explore the intricacies of the human microbiome. On the clinical front, the gut microbial community has been the focus of many biomarker-discovery studies. While the recent deluge of high-throughput data in microbiome research has been vastly informative and groundbreaking, we have yet to capture the full potential of omics-based approaches. Realizing the promise of multi-omics data will require integration of disparate omics data, as well as a biologically relevant, mechanistic framework - or metabolic model - on which to overlay these data. Also, a new paradigm for metabolic model evaluation is necessary. Herein, we outline the need for multi-omics data integration, as well as the accompanying challenges. Furthermore, we present a framework for characterizing the ecology of the gut microbiome based on metabolic network modeling.

  13. High diversity and unique composition of gut microbiomes in pygmy (Kogia breviceps) and dwarf (K. sima) sperm whales.

    PubMed

    Erwin, Patrick M; Rhodes, Ryan G; Kiser, Kevin B; Keenan-Bateman, Tiffany F; McLellan, William A; Pabst, D Ann

    2017-08-03

    Mammals host diverse bacterial and archaeal symbiont communities (i.e. microbiomes) that play important roles in digestive and immune system functioning, yet cetacean microbiomes remain largely unexplored, in part due to sample collection difficulties. Here, fecal samples from stranded pygmy (Kogia breviceps) and dwarf (K. sima) sperm whales were used to characterize the gut microbiomes of two closely-related species with similar diets. 16S rRNA gene sequencing revealed diverse microbial communities in kogiid whales dominated by Firmicutes and Bacteroidetes. Core symbiont taxa were affiliated with phylogenetic lineages capable of fermentative metabolism and sulfate respiration, indicating potential symbiont contributions to energy acquisition during prey digestion. The diversity and phylum-level composition of kogiid microbiomes differed from those previously reported in toothed whales, which exhibited low diversity communities dominated by Proteobacteria and Actinobacteria. Community structure analyses revealed distinct gut microbiomes in K. breviceps and K. sima, driven by differential relative abundances of shared taxa, and unique microbiomes in kogiid hosts compared to other toothed and baleen whales, driven by differences in symbiont membership. These results provide insight into the diversity, composition and structure of kogiid gut microbiomes and indicate that host identity plays an important role in structuring cetacean microbiomes, even at fine-scale taxonomic levels.

  14. Understanding the role of gut microbiome in metabolic disease risk.

    PubMed

    Sanz, Yolanda; Olivares, Marta; Moya-Pérez, Ángela; Agostoni, Carlo

    2015-01-01

    The gut microbiota structure, dynamics, and function result from interactions with environmental and host factors, which jointly influence the communication between the gut and peripheral tissues, thereby contributing to health programming and disease risk. Incidence of both type-1 and type-2 diabetes has increased during the past decades, suggesting that there have been changes in the interactions between predisposing genetic and environmental factors. Animal studies show that gut microbiota and its genome (microbiome) influence alterations in energy balance (increased energy harvest) and immunity (inflammation and autoimmunity), leading to metabolic dysfunction (e.g., insulin resistance and deficiency). Thus, although they have different origins, both disorders are linked by the association of the gut microbiota with the immune-metabolic axis. Human studies have also revealed shifts in microbiome signatures in diseased subjects as compared with controls, and a few of them precede the development of these disorders. These studies contribute to pinpointing specific microbiome components and functions (e.g., butyrate-producing bacteria) that can protect against both disorders. These could exert protective roles by strengthening gut barrier function and regulating inflammation, as alterations in these are a pathophysiological feature of both disorders, constituting common targets for future preventive approaches.

  15. Social networks predict gut microbiome composition in wild baboons

    PubMed Central

    Tung, Jenny; Barreiro, Luis B; Burns, Michael B; Grenier, Jean-Christophe; Lynch, Josh; Grieneisen, Laura E; Altmann, Jeanne; Alberts, Susan C; Blekhman, Ran; Archie, Elizabeth A

    2015-01-01

    Social relationships have profound effects on health in humans and other primates, but the mechanisms that explain this relationship are not well understood. Using shotgun metagenomic data from wild baboons, we found that social group membership and social network relationships predicted both the taxonomic structure of the gut microbiome and the structure of genes encoded by gut microbial species. Rates of interaction directly explained variation in the gut microbiome, even after controlling for diet, kinship, and shared environments. They therefore strongly implicate direct physical contact among social partners in the transmission of gut microbial species. We identified 51 socially structured taxa, which were significantly enriched for anaerobic and non-spore-forming lifestyles. Our results argue that social interactions are an important determinant of gut microbiome composition in natural animal populations—a relationship with important ramifications for understanding how social relationships influence health, as well as the evolution of group living. DOI: http://dx.doi.org/10.7554/eLife.05224.001 PMID:25774601

  16. Insect gut microbiome - An unexploited reserve for biotechnological application

    PubMed Central

    Krishnan, Muthukalingan; Bharathiraja, Chinnapandi; Pandiarajan, Jeyaraj; Prasanna, Vimalanathan Arun; Rajendhran, Jeyaprakash; Gunasekaran, Paramasamy

    2014-01-01

    Metagenomics research has been developed over the past decade to elucidate the genomes of the uncultured microorganisms with an aim of understanding microbial ecology. On the other hand, it has also been provoked by the increasing biotechnological demands for novel enzymes, antibiotic and signal mimics. The gut microbiota of insects plays crucial roles in the growth, development and environmental adaptation to the host insects. Very recently, the insect microbiota and their genomes (microbiome), isolated from insects were recognized as a major genetic resources for bio-processing industry. Consequently, the exploitation of insect gut microbiome using metagenomic approaches will enable us to find novel biocatalysts and to develop innovative strategies for identifying smart molecules for biotechnological applications. In this review, we discuss the critical footstep in extraction and purification of metagenomic DNA from insect gut, construction of metagenomic libraries and screening procedure for novel gene identification. Recent innovations and potential applications in bioprocess industries are highlighted. PMID:25183073

  17. Insect gut microbiome - An unexploited reserve for biotechnological application.

    PubMed

    Krishnan, Muthukalingan; Bharathiraja, Chinnapandi; Pandiarajan, Jeyaraj; Prasanna, Vimalanathan Arun; Rajendhran, Jeyaprakash; Gunasekaran, Paramasamy

    2014-05-01

    Metagenomics research has been developed over the past decade to elucidate the genomes of the uncultured microorganisms with an aim of understanding microbial ecology. On the other hand, it has also been provoked by the increasing biotechnological demands for novel enzymes, antibiotic and signal mimics. The gut microbiota of insects plays crucial roles in the growth, development and environmental adaptation to the host insects. Very recently, the insect microbiota and their genomes (microbiome), isolated from insects were recognized as a major genetic resources for bio-processing industry. Consequently, the exploitation of insect gut microbiome using metagenomic approaches will enable us to find novel biocatalysts and to develop innovative strategies for identifying smart molecules for biotechnological applications. In this review, we discuss the critical footstep in extraction and purification of metagenomic DNA from insect gut, construction of metagenomic libraries and screening procedure for novel gene identification. Recent innovations and potential applications in bioprocess industries are highlighted.

  18. Gut microbiome composition is associated with temperament during early childhood

    PubMed Central

    Christian, Lisa M.; Galley, Jeffrey D.; Hade, Erinn M.; Schoppe-Sullivan, Sarah; Kamp-Dush, Claire; Bailey, Michael T.

    2014-01-01

    Background Understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans. Methods We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27 months of age. It was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics. Results Among both boys and girls, greater Surgency/Extraversion was associated greater phylogenetic diversity. In addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the Shannon Diversity index (SDI), beta diversity, and differences in abundances of Dialister, Rikenellaceae, Ruminococcaceae, and Parabacteroides. In girls only, higher Effortful Control was associated with a lower SDI score and differences in both beta diversity and Rikenellaceae were observed in relation to Fear. Some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome. Conclusions Differences in gut microbiome composition, including alpha diversity, beta diversity, and abundances of specific bacterial species, were observed in association with temperament in toddlers. This study was cross-sectional and observational and, therefore, does not permit determination of the causal direction of effects. However, if bidirectional brain-gut relationships are present in humans in early life, this may represent an opportunity for intervention relevant to physical as well as mental health disorders. PMID:25449582

  19. Gut microbiome composition is associated with temperament during early childhood.

    PubMed

    Christian, Lisa M; Galley, Jeffrey D; Hade, Erinn M; Schoppe-Sullivan, Sarah; Kamp Dush, Claire; Bailey, Michael T

    2015-03-01

    Understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. As such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans. We used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27months of age. It was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics. Among both boys and girls, greater Surgency/Extraversion was associated greater phylogenetic diversity. In addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the Shannon Diversity index (SDI), beta diversity, and differences in abundances of Dialister, Rikenellaceae, Ruminococcaceae, and Parabacteroides. In girls only, higher Effortful Control was associated with a lower SDI score and differences in both beta diversity and Rikenellaceae were observed in relation to Fear. Some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome. Differences in gut microbiome composition, including alpha diversity, beta diversity, and abundances of specific bacterial species, were observed in association with temperament in toddlers. This study was cross-sectional and observational and, therefore, does not permit determination of the causal direction of effects. However, if bidirectional brain-gut relationships are present in humans in early life, this may represent an opportunity for intervention relevant to physical as well as mental health disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. SIV-INDUCED INSTABILITY OF THE CHIMPANZEE GUT MICROBIOME

    PubMed Central

    Moeller, Andrew H.; Shilts, Meghan; Li, Yingying; Rudicell, Rebecca S.; Lonsdorf, Elizabeth V.; Pusey, Anne E.; Wilson, Michael L.; Hahn, Beatrice H.; Ochman, Howard

    2013-01-01

    Summary Simian immunodeficiency virus of chimpanzees (SIVcpz) is the ancestor of human immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS) in humans. Like HIV-1-infected humans, SIVcpz-infected chimpanzees can either remain asymptomatic for prolonged periods or develop AIDS-like symptoms. Because SIVcpz/HIV-1 may disrupt regulation of the gut microbiome and because it has not been possible to sample individual humans pre- and post- infection, we investigated the influence of infection on gut communities through long-term monitoring of chimpanzees from Gombe National Park, Tanzania. SIVcpz infection accelerated the rate of change in gut microbiota composition within individuals for periods of years after the initial infection and led to gut communities marked by high frequencies of pathogen-containing bacterial genera absent from SIVcpz-negative individuals. Our results indicate that immune function maintains temporally stable gut communities that are lost when individuals become infected with SIVcpz. PMID:24034619

  1. SIV-induced instability of the chimpanzee gut microbiome.

    PubMed

    Moeller, Andrew H; Shilts, Meghan; Li, Yingying; Rudicell, Rebecca S; Lonsdorf, Elizabeth V; Pusey, Anne E; Wilson, Michael L; Hahn, Beatrice H; Ochman, Howard

    2013-09-11

    Simian immunodeficiency virus of chimpanzees (SIVcpz) is the ancestor of human immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS) in humans. Like HIV-1-infected humans, SIVcpz-infected chimpanzees can develop AIDS-like symptoms. Because SIVcpz/HIV-1 may disrupt regulation of the gut microbiome and because it has not been possible to sample individual humans pre- and postinfection, we investigated the influence of infection on gut communities through long-term monitoring of chimpanzees from Gombe National Park, Tanzania. SIVcpz infection accelerated the rate of change in gut microbiota composition within individuals for periods of years after the initial infection and led to gut communities marked by high frequencies of pathogen-containing bacterial genera absent from SIVcpz-negative individuals. Our results indicate that immune function maintains temporally stable gut communities that are lost when individuals become infected with SIVcpz.

  2. Antibiotic resistance potential of the healthy preterm infant gut microbiome

    PubMed Central

    Shaw, Alexander G.; Sim, Kathleen; Wooldridge, David J.; Li, Ming-Shi; Gharbia, Saheer; Misra, Raju; Kroll, John Simon

    2017-01-01

    Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities. PMID:28149696

  3. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor.

    PubMed

    Smith, Michelle I; Yatsunenko, Tanya; Manary, Mark J; Trehan, Indi; Mkakosya, Rajhab; Cheng, Jiye; Kau, Andrew L; Rich, Stephen S; Concannon, Patrick; Mychaleckyj, Josyf C; Liu, Jie; Houpt, Eric; Li, Jia V; Holmes, Elaine; Nicholson, Jeremy; Knights, Dan; Ursell, Luke K; Knight, Rob; Gordon, Jeffrey I

    2013-02-01

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.

  4. Intrinsic association between diet and the gut microbiome: current evidence

    PubMed Central

    Winglee, Kathryn; Fodor, Anthony A

    2017-01-01

    The gut microbiome performs many crucial functions for the human host, but the molecular mechanisms by which host, microbe and diet interact to mediate health and disease are only starting to be revealed. Here we review the literature on how changes in the diet affect the microbiome. A number of studies have shown that within a geographic region, different diets (such as vegan vs. omnivore) are associated with differences in a modest number of taxa but do not reliably produce radical differences within the gut microbial community. In contrast, studies that look across continents consistently find profoundly different microbial communities between Westernized and traditional populations, although it remains unclear to what extent diet or other differences in lifestyle drive these distinct microbial community structures. Furthermore, studies that place subjects on controlled short term experimental diets have found the resulting alterations to the gut microbial community to generally be small in scope, with changes that do not overcome initial individual differences in microbial community structure. These results emphasize that the human gut microbial community is relatively stable over time. In contrast, short term changes in diet can cause large changes in metabolite profiles, including metabolites processed by the gut microbial community. These results suggest that commensal gut microbes have a great deal of genetic plasticity and can activate different metabolic pathways independent of changes to microbial community composition. Thus, future studies of the how diet impacts host health via the microbiome may wish to focus on functional assays such as transcriptomics and metabolomics, in addition to 16S rRNA and whole-genome metagenome shotgun analyses of DNA. Taken together, the literature is most consistent with a model in which the composition of the adult gut microbial community undergoes modest compositional changes in response to altered diet but can

  5. The gut microbiome and diet in psychiatry: focus on depression.

    PubMed

    Dash, Sarah; Clarke, Gerard; Berk, Michael; Jacka, Felice N

    2015-01-01

    With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. A rapidly emerging field of research suggests that the microbiome-gut-brain axis is of substantial relevance to mood and behaviour. Similarly, unhealthy diet has recently emerged as a significant correlate of and risk factor for depression. This review provides evidence for the gut microbiota as a key factor mediating the link between diet and depressive illness. The development of new technologies is affording a better understanding of how diet influences gut microbiota composition and activity and how this may, in turn, influence depressive illness. New interventions are also suggesting the possible utility of pre and probiotic formulations and fermented food in influencing mental health. Although in its early stages, the emerging field of research focused on the human microbiome suggests an important role for the gut microbiota in influencing brain development, behaviour and mood in humans. The recognition that the gut microbiota interacts bidirectionally with other environmental risk factors, such as diet and stress, suggests promise in the development of interventions targeting the gut microbiota for the prevention and treatment of common mental health disorders.

  6. Practical considerations for large-scale gut microbiome studies.

    PubMed

    Vandeputte, Doris; Tito, Raul Y; Vanleeuwen, Rianne; Falony, Gwen; Raes, Jeroen

    2017-08-01

    First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and characterisation of the multiple influencing factors and their relative contribution. In order to guide future research projects and standardisation efforts, we here review currently applied collection and preservation methods for gut microbiome research. We discuss aspects such as sample quality, applicable omics techniques, user experience and time and cost efficiency. In addition, we evaluate the protocols of a large-scale microbiome cohort initiative, the Flemish Gut Flora Project, to give an idea of perspectives, and pitfalls of large-scale faecal sampling studies. Although cryopreservation can be regarded as the gold standard, freezing protocols generally require more resources due to cold chain management. However, here we show that much can be gained from an optimised transport chain and sample aliquoting before freezing. Other protocols can be useful as long as they preserve the microbial signature of a sample such that relevant conclusions can be drawn regarding the research question, and the obtained data are stable and reproducible over time. © FEMS 2017.

  7. Stabilization of the murine gut microbiome following weaning.

    PubMed

    Schloss, Patrick D; Schubert, Alyxandria M; Zackular, Joseph P; Iverson, Kathryn D; Young, Vincent B; Petrosino, Joseph F

    2012-01-01

    Ecologists hypothesize that community structure and stability affect productivity, sensitivity to invasion and extinction, and resilience and resistance to perturbations. Viewed in the context of the gut microbiome, the stability of the gut community is important for understanding the effects of antibiotics, diet change and other perturbations on host health and colonization resistance. Here we describe the dynamics of a self-contained community, the murine gut microbiome. Using 16S rRNA gene sequencing of fecal samples collected daily from individual mice, we characterized the community membership and structure to determine whether there were significant changes in the gut community during the first year of life. Based on analysis of molecular variance, we observed two community states. The first was observed in the 10 days following weaning and the second was observed by 15 days following weaning. Interestingly, these two states had the same bacterial populations, but those populations had different relative abundances in the two states. By calculating the root mean squared distances between samples collected in the early and late states for each mouse, we observed that the late state was more stable than the early state. This increase in stability was not correlated with increased taxonomic richness, taxonomic diversity, or phylogenetic diversity. In the absence of an experimentally induced perturbation, the second community state was relatively constant through 364 days post weaning. These results suggest a high degree of stability in the microbiome once the community reached the second state.

  8. The gut microbiome: scourge, sentinel or spectator?

    PubMed Central

    Korecka, Agata; Arulampalam, Velmurugesan

    2012-01-01

    The gut microbiota consists of trillions of prokaryotes that reside in the intestinal mucosa. This long-established commensalism indicates that these microbes are an integral part of the eukaryotic host. Recent research findings have implicated the dynamics of microbial function in setting thresholds for many physiological parameters. Conversely, it has been convincingly argued that dysbiosis, representing microbial imbalance, may be an important underlying factor that contributes to a variety of diseases, inside and outside the gut. This review discusses the latest findings, including enterotype classification, changes brought on by dysbiosis, gut inflammation, and metabolic mediators in an attempt to underscore the importance of the gut microbiota for human health. A cautiously optimistic idea is taking hold, invoking the gut microbiota as a medium to track, target and treat a plethora of diseases. PMID:22368769

  9. Brain Gut Microbiome Interactions and Functional Bowel Disorders

    PubMed Central

    Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

    2014-01-01

    Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

  10. Community characteristics of the gut microbiomes of competitive cyclists.

    PubMed

    Petersen, Lauren M; Bautista, Eddy J; Nguyen, Hoan; Hanson, Blake M; Chen, Lei; Lek, Sai H; Sodergren, Erica; Weinstock, George M

    2017-08-10

    Changes in diet and exercise can alter the gut microbiome of humans and mice; however, few studies to date have assessed the microbiomes of highly fit athletes. In this pilot study, we used metagenomic whole genome shotgun (mWGS) and metatranscriptomic (RNA-Seq) sequencing to show what organisms are both present and active in the gut microbiomes of both professional and amateur level competitive cyclists and to determine if any significant differences exist between these two groups. Using mWGS sequencing data, we showed that the gut microbiomes of 33 cyclists split into three taxonomic clusters, characterized by either high Prevotella, high Bacteroides or a mix of many genera including Bacteroides, Prevotella, Eubacterium, Ruminococcus, and Akkermansia. While no significant correlations could be found between taxonomic cluster and being either a professional or amateur level cyclist, high abundance of the genus Prevotella (≥2.5%) was significantly correlated with time reported exercising during an average week. Increased abundance of Prevotella was correlated with a number of amino acid and carbohydrate metabolism pathways, including branched chain amino acid metabolism. Further analysis of the metatranscriptome revealed significant taxonomic differences when compared to the metagenome. There was increased abundance of Methanobrevibacter smithii transcripts in a number of professional cyclists in comparison to amateur cyclists and this archaeon had upregulation of genes involved in the production of methane. Furthermore, when methane metabolism was upregulated, there was similar upregulation of energy and carbohydrate metabolism pathways. These results provide a framework for common constituents of the gut community in individuals who follow an exercise-rich lifestyle. These data also suggest how certain organisms such as M. smithii may beneficially influence the metabolic efficiency of the gut community in professional cyclists due to synergistic metabolic cross

  11. Structure and function of the healthy pre-adolescent pediatric gut microbiome

    USDA-ARS?s Scientific Manuscript database

    The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limite...

  12. A bacterial filter protects and structures the gut microbiome of an insect

    PubMed Central

    Lanan, Michele Caroline; Rodrigues, Pedro Augusto Pos; Agellon, Al; Jansma, Patricia; Wheeler, Diana Esther

    2016-01-01

    Associations with symbionts within the gut lumen of hosts are particularly prone to disruption due to the constant influx of ingested food and non-symbiotic microbes, yet we know little about how partner fidelity is maintained. Here we describe for the first time the existence of a gut morphological filter capable of protecting an animal gut microbiome from disruption. The proventriculus, a valve located between the crop and midgut of insects, functions as a micro-pore filter in the Sonoran Desert turtle ant (Cephalotes rohweri), blocking the entry of bacteria and particles ⩾0.2 μm into the midgut and hindgut while allowing passage of dissolved nutrients. Initial establishment of symbiotic gut bacteria occurs within the first few hours after pupation via oral–rectal trophallaxis, before the proventricular filter develops. Cephalotes ants are remarkable for having maintained a consistent core gut microbiome over evolutionary time and this partner fidelity is likely enabled by the proventricular filtering mechanism. In addition, the structure and function of the cephalotine proventriculus offers a new perspective on organismal resistance to pathogenic microbes, structuring of gut microbial communities, and development and maintenance of host–microbe fidelity both during the animal life cycle and over evolutionary time. PMID:26872040

  13. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome.

    PubMed

    Zarrinpar, Amir; Chaix, Amandine; Yooseph, Shibu; Panda, Satchidananda

    2014-12-02

    The gut microbiome and daily feeding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiome's contribution to host metabolism.

  14. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors

    PubMed Central

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A.

    2016-01-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns. PMID:27698614

  15. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

    PubMed

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

    2016-09-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  16. Nutrition and the gut microbiome in the elderly.

    PubMed

    Salazar, Nuria; Valdés-Varela, Lorena; González, Sonia; Gueimonde, Miguel; de Los Reyes-Gavilán, Clara G

    2016-11-03

    The gut microbiota is the assembly of microorganisms living in our intestine and their genomes are known as the microbiome. The correct composition and functionality of this microbiome is essential for maintaining a "healthy status." Aging is related to changes in the gut microbiota which are frequently associated with physiological modifications of the gastrointestinal tract, as well as, to changes in dietary patterns, together with a concomitant decline in cognitive and immune function, all together contributing to frailty. Therefore, nutritional strategies directed at restoring the microbiota in the elderly have to be addressed from a global perspective, considering not only the microbiota but also other extra-intestinal targets of action. The present review aims at summarizing the current knowledge on intestinal microbiota alterations and other functions impaired in the elderly and to analyze tools for implementing nutritional strategies, through the use of probiotics, prebiotics or specific nutrients in order to counterbalance such alterations.

  17. Overweight and the feline gut microbiome - a pilot study.

    PubMed

    Kieler, I N; Mølbak, L; Hansen, L L; Hermann-Bank, M L; Bjornvad, C R

    2016-06-01

    Compared with lean humans, the gut microbiota is altered in the obese. Whether these changes are due to an obesogenic diet, and whether the microbiota contributes to adiposity is currently discussed. In the cat population, where obesity is also prevalent, gut microbiome changes associated with obesity have not been studied. Consequently, the aim of this study was to compare the gut microbiota of lean cats, with that of overweight and obese cats. Seventy-seven rescue-shelter cats housed for ≥3 consecutive days were included in the study. Faecal samples were obtained by rectal swab and, when available, by a paired litter box sample. Body condition was assessed using a 9-point scoring system. DNA was extracted, and the 16S rRNA gene was amplified with a high-throughput quantitative real-time PCR chip. Overweight and obese cats had a significantly different gut microbiota compared to lean cats (p < 0.05), but this finding could not be linked to differences in specific bacterial groups. The rectal samples obtained higher DNA concentration than litter box samples (p < 0.0001). In conclusion, overweight and obese cats seem to have an altered gut microbiome as compared to lean cats. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  18. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

    PubMed Central

    Smith, Michelle I.; Yatsunenko, Tanya; Manary, Mark J.; Trehan, Indi; Mkakosya, Rajhab; Cheng, Jiye; Kau, Andrew L.; Rich, Stephen S.; Concannon, Patrick; Mychaleckyj, Josyf C.; Liu, Jie; Houpt, Eric; Li, Jia V.; Holmes, Elaine; Nicholson, Jeremy; Knights, Dan; Ursell, Luke K.; Knight, Rob; Gordon, Jeffrey I.

    2013-01-01

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well-nourished, while 43% became discordant and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor microbiomes that regressed when RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor. PMID:23363771

  19. Obesity and the gut microbiome: Striving for causality

    PubMed Central

    Harley, Isaac T.W.; Karp, Christopher L.

    2012-01-01

    The gut microbiome has been proposed to play a causal role in obesity. Here, we review the historical context for this hypothesis, highlight recent key findings, and critically discuss issues central to further progress in the field, including the central epistemological problem for the field: how to define causality in the relationship between microbiota and obesity phenotypes. Definition of such will be critical for the field to move forward. PMID:24024115

  20. Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder.

    PubMed

    Vuong, Helen E; Hsiao, Elaine Y

    2017-03-01

    Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that affects one in 45 children in the United States, with a similarly striking prevalence in countries around the world. However, mechanisms underlying its etiology and manifestations remain poorly understood. Although ASD is diagnosed based on the presence and severity of impaired social communication and repetitive behavior, immune dysregulation and gastrointestinal issues are common comorbidities. The microbiome is an integral part of human physiology; recent studies show that changes in the gut microbiota can modulate gastrointestinal physiology, immune function, and even behavior. Links between particular bacteria from the indigenous gut microbiota and phenotypes relevant to ASD raise the important question of whether microbial dysbiosis plays a role in the development or presentation of ASD symptoms. Here we review reports of microbial dysbiosis in ASD. We further discuss potential effects of the microbiota on ASD-associated symptoms, drawing on signaling mechanisms for reciprocal interactions among the microbiota, immunity, gut function, and behavior. In addition, we discuss recent findings supporting a role for the microbiome as an interface between environmental and genetic risk factors that are associated with ASD. These studies highlight the integration of pathways across multiple body systems that together can impact brain and behavior and suggest that changes in the microbiome may contribute to symptoms of neurodevelopmental disease. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Whole gut microbiome composition of damselfish and cardinalfish before and after reef settlement

    PubMed Central

    Parris, Darren J.; Brooker, Rohan M.; Morgan, Michael A.; Dixson, Danielle L.

    2016-01-01

    The Pomacentridae (damselfish) and Apogonidae (cardinalfish) are among the most common fish families on coral reefs and in the aquarium trade. Members of both families undergo a pelagic larvae phase prior to settlement on the reef, where adults play key roles in benthic habitat structuring and trophic interactions. Fish-associated microbial communities (microbiomes) significantly influence fish health and ecology, yet little is known of how microbiomes change with life stage. We quantified the taxonomic (16S rRNA gene) composition of whole gut microbiomes from ten species of damselfish and two species of cardinalfish from Lizard Island, Australia, focusing specifically on comparisons between pelagic larvae prior to settlement on the reef versus post-settlement juvenile and adult individuals. On average, microbiome phylogenetic diversity increased from pre- to post-settlement, and was unrelated to the microbial composition in the surrounding water column. However, this trend varied among species, suggesting stochasticity in fish microbiome assembly. Pre-settlement fish were enriched with bacteria of the Endozoicomonaceae, Shewanellaceae, and Fusobacteriaceae, whereas settled fish harbored higher abundances of Vibrionaceae and Pasteurellaceae. Several individual operational taxonomic units, including ones related to Vibrio harveyi, Shewanella sp., and uncultured Endozoicomonas bacteria, were shared between both pre and post-settlement stages and may be of central importance in the intestinal niche across development. Richness of the core microbiome shared among pre-settlement fish was comparable to that of settled individuals, suggesting that changes in diversity with adulthood are due to the acquisition or loss of host-specific microbes. These results identify a key transition in microbiome structure across host life stage, suggesting changes in the functional contribution of microbiomes over development in two ecologically dominant reef fish families. PMID:27635360

  2. Whole gut microbiome composition of damselfish and cardinalfish before and after reef settlement.

    PubMed

    Parris, Darren J; Brooker, Rohan M; Morgan, Michael A; Dixson, Danielle L; Stewart, Frank J

    2016-01-01

    The Pomacentridae (damselfish) and Apogonidae (cardinalfish) are among the most common fish families on coral reefs and in the aquarium trade. Members of both families undergo a pelagic larvae phase prior to settlement on the reef, where adults play key roles in benthic habitat structuring and trophic interactions. Fish-associated microbial communities (microbiomes) significantly influence fish health and ecology, yet little is known of how microbiomes change with life stage. We quantified the taxonomic (16S rRNA gene) composition of whole gut microbiomes from ten species of damselfish and two species of cardinalfish from Lizard Island, Australia, focusing specifically on comparisons between pelagic larvae prior to settlement on the reef versus post-settlement juvenile and adult individuals. On average, microbiome phylogenetic diversity increased from pre- to post-settlement, and was unrelated to the microbial composition in the surrounding water column. However, this trend varied among species, suggesting stochasticity in fish microbiome assembly. Pre-settlement fish were enriched with bacteria of the Endozoicomonaceae, Shewanellaceae, and Fusobacteriaceae, whereas settled fish harbored higher abundances of Vibrionaceae and Pasteurellaceae. Several individual operational taxonomic units, including ones related to Vibrio harveyi, Shewanella sp., and uncultured Endozoicomonas bacteria, were shared between both pre and post-settlement stages and may be of central importance in the intestinal niche across development. Richness of the core microbiome shared among pre-settlement fish was comparable to that of settled individuals, suggesting that changes in diversity with adulthood are due to the acquisition or loss of host-specific microbes. These results identify a key transition in microbiome structure across host life stage, suggesting changes in the functional contribution of microbiomes over development in two ecologically dominant reef fish families.

  3. Opportunities and challenges for gut microbiome studies in the Indian population

    PubMed Central

    2013-01-01

    The gut microbiome is a complex ecosystem that affects the development, immunological responses and nutritional status of the host. Efforts are being made to unravel the complex interaction between the gut microbiome and host to have a greater understanding about its role in human health. Colonization of the gut by microbes begins at birth, but the succession and composition of the microbial community depends on a number of factors including, but not limited to, the age, diet, genetic composition, gender, geographic location, and health status of an individual. Therefore, inclusion of diverse human subjects in the study of the gut microbiome is indispensable. However, conducting such studies in India presents unique opportunities and challenges. The vast diversity in human genetic composition, dietary habits, and geographic distribution that exists in the Indian population adds to the complexity in understanding the gut microbiome. Gut microbiome-related studies from other parts of the world have reported a possible association of diseases such as obesity and diabetes with the human gut microbiome. In contrast, an in-depth assessment of risk factors associated with altered gut microbiome in such diseases in the Indian population is lacking. Studies including the Indian population may give insights into the association of the gut microbiome with various factors and diseases that may not be possible from studies on western populations. This review briefly discusses the significance of the gut microbiome on human health and the present status of gut microbiome studies in the Indian population. In addition, this review will highlight the unique opportunities and challenges for gut microbiome studies in the Indian population. PMID:24451035

  4. Gut Microbiome and Obesity: A Plausible Explanation for Obesity

    PubMed Central

    Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A.

    2015-01-01

    Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host’s adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity. PMID:26029487

  5. Gut Microbiome and Obesity: A Plausible Explanation for Obesity.

    PubMed

    Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A

    2015-06-01

    Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host's adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity.

  6. Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases.

    PubMed

    Ghaisas, Shivani; Maher, Joshua; Kanthasamy, Anumantha

    2016-02-01

    The gut microbiome comprises the collective genome of the trillions of microorganisms residing in our gastrointestinal ecosystem. The interaction between the host and its gut microbiome is a complex relationship whose manipulation could prove critical to preventing or treating not only various gut disorders, like irritable bowel syndrome (IBS) and ulcerative colitis (UC), but also central nervous system (CNS) disorders, such as Alzheimer's and Parkinson's diseases. The purpose of this review is to summarize what is known about the gut microbiome, how it is connected to the development of disease and to identify the bacterial and biochemical targets that should be the focus of future research. Understanding the mechanisms behind the activity and proliferation of the gut microbiome will provide us new insights that may pave the way for novel therapeutic strategies.

  7. Gut microbiome in health and disease: linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases

    PubMed Central

    Ghaisas, Shivani; Maher, Joshua; Kanthasamy, Anumantha

    2015-01-01

    The gut microbiome comprises the collective genome of the trillions of microorganisms residing in our gastrointestinal ecosystem. The interaction between the host and its gut microbiome is a complex relationship whose manipulation could prove critical to preventing or treating not only various gut disorders, like irritable bowel syndrome (IBS) and ulcerative colitis (UC), but also central nervous system (CNS) disorders, such as Alzheimer’s and Parkinson’s diseases. The purpose of this review is to summarize what is known about the gut microbiome, how it is connected to the development of disease and to identify the bacterial and biochemical targets that should be the focus of future research. Understanding the mechanisms behind the activity and proliferation of the gut microbiome will provide us new insights that may pave the way for novel therapeutic strategies. PMID:26627987

  8. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

    PubMed

    O'Mahony, S M; Clarke, G; Borre, Y E; Dinan, T G; Cryan, J F

    2015-01-15

    The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders.

  9. Diet rapidly and reproducibly alters the human gut microbiome

    PubMed Central

    David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Ling, Alisha V.; Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.; Biddinger, Sudha B.; Dutton, Rachel J.; Turnbaugh, Peter J.

    2013-01-01

    Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut1–5, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease6. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. PMID:24336217

  10. Subsistence strategies in traditional societies distinguish gut microbiomes.

    PubMed

    Obregon-Tito, Alexandra J; Tito, Raul Y; Metcalf, Jessica; Sankaranarayanan, Krithivasan; Clemente, Jose C; Ursell, Luke K; Zech Xu, Zhenjiang; Van Treuren, Will; Knight, Rob; Gaffney, Patrick M; Spicer, Paul; Lawson, Paul; Marin-Reyes, Luis; Trujillo-Villarroel, Omar; Foster, Morris; Guija-Poma, Emilio; Troncoso-Corzo, Luzmila; Warinner, Christina; Ozga, Andrew T; Lewis, Cecil M

    2015-03-25

    Recent studies suggest that gut microbiomes of urban-industrialized societies are different from those of traditional peoples. Here we examine the relationship between lifeways and gut microbiota through taxonomic and functional potential characterization of faecal samples from hunter-gatherer and traditional agriculturalist communities in Peru and an urban-industrialized community from the US. We find that in addition to taxonomic and metabolic differences between urban and traditional lifestyles, hunter-gatherers form a distinct sub-group among traditional peoples. As observed in previous studies, we find that Treponema are characteristic of traditional gut microbiomes. Moreover, through genome reconstruction (2.2-2.5 MB, coverage depth × 26-513) and functional potential characterization, we discover these Treponema are diverse, fall outside of pathogenic clades and are similar to Treponema succinifaciens, a known carbohydrate metabolizer in swine. Gut Treponema are found in non-human primates and all traditional peoples studied to date, suggesting they are symbionts lost in urban-industrialized societies.

  11. Subsistence strategies in traditional societies distinguish gut microbiomes

    PubMed Central

    Obregon-Tito, Alexandra J.; Tito, Raul Y.; Metcalf, Jessica; Sankaranarayanan, Krithivasan; Clemente, Jose C.; Ursell, Luke K.; Zech Xu, Zhenjiang; Van Treuren, Will; Knight, Rob; Gaffney, Patrick M.; Spicer, Paul; Lawson, Paul; Marin-Reyes, Luis; Trujillo-Villarroel, Omar; Foster, Morris; Guija-Poma, Emilio; Troncoso-Corzo, Luzmila; Warinner, Christina; Ozga, Andrew T.; Lewis, Cecil M.

    2015-01-01

    Recent studies suggest that gut microbiomes of urban-industrialized societies are different from those of traditional peoples. Here we examine the relationship between lifeways and gut microbiota through taxonomic and functional potential characterization of faecal samples from hunter-gatherer and traditional agriculturalist communities in Peru and an urban-industrialized community from the US. We find that in addition to taxonomic and metabolic differences between urban and traditional lifestyles, hunter-gatherers form a distinct sub-group among traditional peoples. As observed in previous studies, we find that Treponema are characteristic of traditional gut microbiomes. Moreover, through genome reconstruction (2.2–2.5 MB, coverage depth × 26–513) and functional potential characterization, we discover these Treponema are diverse, fall outside of pathogenic clades and are similar to Treponema succinifaciens, a known carbohydrate metabolizer in swine. Gut Treponema are found in non-human primates and all traditional peoples studied to date, suggesting they are symbionts lost in urban-industrialized societies. PMID:25807110

  12. Antibiotic perturbation of the preterm infant gut microbiome and resistome.

    PubMed

    Gasparrini, Andrew J; Crofts, Terence S; Gibson, Molly K; Tarr, Phillip I; Warner, Barbara B; Dantas, Gautam

    2016-09-02

    The gut microbiota plays important roles in nutrient absorption, immune system development, and pathogen colonization resistance. Perturbations early in life may be detrimental to host health in the short and the long-term. Antibiotics are among the many factors that influence the development of the microbiota. Because antibiotics are heavily administered during the first critical years of gut microbiota development, it is important to understand the effects of these interventions. Infants, particularly those born prematurely, represent an interesting population because they receive early and often extensive antibiotic therapy in the first months after birth. Gibson et al. recently demonstrated that antibiotic therapy in preterm infants can dramatically affect the gut microbiome. While meropenem, ticarcillin-clavulanate, and cefotaxime treatments were associated with decreased species richness, gentamicin and vancomycin had variable effects on species richness. Interestingly, the direction of species richness response could be predicted based on the abundance of 2 species and 2 genes in the microbiome prior to gentamicin or vancomycin treatment. Nonetheless, all antibiotic treatments enriched the presence of resistance genes and multidrug resistant organisms. Treatment with different antibiotics further resulted in unique population shifts of abundant organisms and selection for different sets of resistance genes. In this addendum, we provide an extended discussion of these recent findings, and outline important future directions for elucidating the interplay between antibiotics and preterm infant gut microbiota development.

  13. Diet rapidly and reproducibly alters the human gut microbiome.

    PubMed

    David, Lawrence A; Maurice, Corinne F; Carmody, Rachel N; Gootenberg, David B; Button, Julie E; Wolfe, Benjamin E; Ling, Alisha V; Devlin, A Sloan; Varma, Yug; Fischbach, Michael A; Biddinger, Sudha B; Dutton, Rachel J; Turnbaugh, Peter J

    2014-01-23

    Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

  14. 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.

  15. The gut microbiome of healthy Japanese and its microbial and functional uniqueness

    PubMed Central

    Nishijima, Suguru; Suda, Wataru; Oshima, Kenshiro; Kim, Seok-Won; Hirose, Yuu; Morita, Hidetoshi; Hattori, Masahira

    2016-01-01

    The human gut microbiome has profound influences on the host's health largely through its interference with various intestinal functions. As recent studies have suggested diversity in the human gut microbiome among human populations, it will be interesting to analyse how gut microbiome is correlated with geographical, cultural, and traditional differences. The Japanese people are known to have several characteristic features such as eating a variety of traditional foods and exhibiting a low BMI and long life span. In this study, we analysed gut microbiomes of the Japanese by comparing the metagenomic data obtained from 106 Japanese individuals with those from 11 other nations. We found that the composition of the Japanese gut microbiome showed more abundant in the phylum Actinobacteria, in particular in the genus Bifidobacterium, than other nations. Regarding the microbial functions, those of carbohydrate metabolism were overrepresented with a concurrent decrease in those for replication and repair, and cell motility. The remarkable low prevalence of genes for methanogenesis with a significant depletion of the archaeon Methanobrevibacter smithii and enrichment of acetogenesis genes in the Japanese gut microbiome compared with others suggested a difference in the hydrogen metabolism pathway in the gut between them. It thus seems that the gut microbiome of the Japanese is considerably different from those of other populations, which cannot be simply explained by diet alone. We postulate possible existence of hitherto unknown factors contributing to the population-level diversity in human gut microbiomes. PMID:26951067

  16. The gut microbiome of healthy Japanese and its microbial and functional uniqueness.

    PubMed

    Nishijima, Suguru; Suda, Wataru; Oshima, Kenshiro; Kim, Seok-Won; Hirose, Yuu; Morita, Hidetoshi; Hattori, Masahira

    2016-04-01

    The human gut microbiome has profound influences on the host's health largely through its interference with various intestinal functions. As recent studies have suggested diversity in the human gut microbiome among human populations, it will be interesting to analyse how gut microbiome is correlated with geographical, cultural, and traditional differences. The Japanese people are known to have several characteristic features such as eating a variety of traditional foods and exhibiting a low BMI and long life span. In this study, we analysed gut microbiomes of the Japanese by comparing the metagenomic data obtained from 106 Japanese individuals with those from 11 other nations. We found that the composition of the Japanese gut microbiome showed more abundant in the phylum Actinobacteria, in particular in the genus Bifidobacterium, than other nations. Regarding the microbial functions, those of carbohydrate metabolism were overrepresented with a concurrent decrease in those for replication and repair, and cell motility. The remarkable low prevalence of genes for methanogenesis with a significant depletion of the archaeon Methanobrevibacter smithii and enrichment of acetogenesis genes in the Japanese gut microbiome compared with others suggested a difference in the hydrogen metabolism pathway in the gut between them. It thus seems that the gut microbiome of the Japanese is considerably different from those of other populations, which cannot be simply explained by diet alone. We postulate possible existence of hitherto unknown factors contributing to the population-level diversity in human gut microbiomes.

  17. Gut microbiome development along the colorectal adenoma-carcinoma sequence.

    PubMed

    Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

    2015-03-11

    Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

  18. Circadian Rhythm and the Gut Microbiome.

    PubMed

    Voigt, R M; Forsyth, C B; Green, S J; Engen, P A; Keshavarzian, A

    2016-01-01

    Circadian rhythms are 24-h patterns regulating behavior, organs, and cells in living organisms. These rhythms align biological functions with regular and predictable environmental patterns to optimize function and health. Disruption of these rhythms can be detrimental resulting in metabolic syndrome, cancer, or cardiovascular disease, just to name a few. It is now becoming clear that the intestinal microbiome is also regulated by circadian rhythms via intrinsic circadian clocks as well as via the host organism. Microbiota rhythms are regulated by diet and time of feeding which can alter both microbial community structure and metabolic activity which can significantly impact host immune and metabolic function. In this review, we will cover how host circadian rhythms are generated and maintained, how host circadian rhythms can be disrupted, as well as the consequences of circadian rhythm disruption. We will further highlight the newly emerging literature indicating the importance of circadian rhythms of the intestinal microbiota. © 2016 Elsevier Inc. All rights reserved.

  19. Divergence across diet, time and populations rules out parallel evolution in the gut microbiomes of Trinidadian guppies

    PubMed Central

    Sullam, Karen E; Rubin, Benjamin ER; Dalton, Christopher M; Kilham, Susan S; Flecker, Alexander S; Russell, Jacob A

    2015-01-01

    Diverse microbial consortia profoundly influence animal biology, necessitating an understanding of microbiome variation in studies of animal adaptation. Yet, little is known about such variability among fish, in spite of their importance in aquatic ecosystems. The Trinidadian guppy, Poecilia reticulata, is an intriguing candidate to test microbiome-related hypotheses on the drivers and consequences of animal adaptation, given the recent parallel origins of a similar ecotype across streams. To assess the relationships between the microbiome and host adaptation, we used 16S rRNA amplicon sequencing to characterize gut bacteria of two guppy ecotypes with known divergence in diet, life history, physiology and morphology collected from low-predation (LP) and high-predation (HP) habitats in four Trinidadian streams. Guts were populated by several recurring, core bacteria that are related to other fish associates and rarely detected in the environment. Although gut communities of lab-reared guppies differed from those in the wild, microbiome divergence between ecotypes from the same stream was evident under identical rearing conditions, suggesting host genetic divergence can affect associations with gut bacteria. In the field, gut communities varied over time, across streams and between ecotypes in a stream-specific manner. This latter finding, along with PICRUSt predictions of metagenome function, argues against strong parallelism of the gut microbiome in association with LP ecotype evolution. Thus, bacteria cannot be invoked in facilitating the heightened reliance of LP guppies on lower-quality diets. We argue that the macroevolutionary microbiome convergence seen across animals with similar diets may be a signature of secondary microbial shifts arising some time after host-driven adaptation. PMID:25575311

  20. Proteobacteria explain significant functional variability in the human gut microbiome.

    PubMed

    Bradley, Patrick H; Pollard, Katherine S

    2017-03-23

    While human gut microbiomes vary significantly in taxonomic composition, biological pathway abundance is surprisingly invariable across hosts. We hypothesized that healthy microbiomes appear functionally redundant due to factors that obscure differences in gene abundance between individuals. To account for these biases, we developed a powerful test of gene variability called CCoDA, which is applicable to shotgun metagenomes from any environment and can integrate data from multiple studies. Our analysis of healthy human fecal metagenomes from three separate cohorts revealed thousands of genes whose abundance differs significantly and consistently between people, including glycolytic enzymes, lipopolysaccharide biosynthetic genes, and secretion systems. Even housekeeping pathways contain a mix of variable and invariable genes, though most highly conserved genes are significantly invariable. Variable genes tend to be associated with Proteobacteria, as opposed to taxa used to define enterotypes or the dominant phyla Bacteroidetes and Firmicutes. These results establish limits on functional redundancy and predict specific genes and taxa that may explain physiological differences between gut microbiomes.

  1. The gut microbiome and degradation enzyme activity of wild freshwater fishes influenced by their trophic levels

    PubMed Central

    Liu, Han; Guo, Xianwu; Gooneratne, Ravi; Lai, Ruifang; Zeng, Cong; Zhan, Fanbin; Wang, Weimin

    2016-01-01

    Vertebrate gut microbiome often underpins the metabolic capability and provides many beneficial effects on their hosts. However, little was known about how host trophic level influences fish gut microbiota and metabolic activity. In this study, more than 985,000 quality-filtered sequences from 24 16S rRNA libraries were obtained and the results revealed distinct compositions and diversities of gut microbiota in four trophic categories. PCoA test showed that gut bacterial communities of carnivorous and herbivorous fishes formed distinctly different clusters in PCoA space. Although fish in different trophic levels shared a large size of OTUs comprising a core microbiota community, at the genus level a strong distinction existed. Cellulose-degrading bacteria Clostridium, Citrobacter and Leptotrichia were dominant in the herbivorous, while Cetobacterium and protease-producing bacteria Halomonas were dominant in the carnivorous. PICRUSt predictions of metagenome function revealed that fishes in different trophic levels affected the metabolic capacity of their gut microbiota. Moreover, cellulase and amylase activities in herbivorous fishes were significantly higher than in the carnivorous, while trypsin activity in the carnivorous was much higher than in the herbivorous. These results indicated that host trophic level influenced the structure and composition of gut microbiota, metabolic capacity and gut content enzyme activity. PMID:27072196

  2. Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses.

    PubMed

    Tözün, Nurdan; Vardareli, Eser

    Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virus-related chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.

  3. 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.

  4. Gut microbiome and dietary patterns in different Saudi populations and monkeys

    PubMed Central

    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

    2016-01-01

    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. PMID:27578328

  5. The human gut microbiome impacts health and disease.

    PubMed

    Ehrlich, Stanislav Dusko

    2016-01-01

    The human gut microbiome can now be characterized in unprecedented detail by an approach based on high-throughput sequencing of total stool DNA, that we name quantitative metagenomics. Central to the approach is a catalog that lists all the genes of intestinal microbes that are known - 9.9 millions, identified by the analysis of 1267 stool samples. Beyond the gene list, genetic units that carry them begun to be known; many of these correspond to bacterial species that were never isolated and cultured yet. Quantitative metagenomics allows developing powerful algorithms to diagnose a disease, monitor patients and identify individuals at risk to progress towards a disease. This lays ground for developing new approaches to better restore and even preserve the health by modulation of the altered microbiome, which contributes to promote or aggravate a disease.

  6. Towards predictive models of the human gut microbiome

    PubMed Central

    2014-01-01

    The intestinal microbiota is an ecosystem susceptible to external perturbations such as dietary changes and antibiotic therapies. Mathematical models of microbial communities could be of great value in the rational design of microbiota-tailoring diets and therapies. Here, we discuss how advances in another field, engineering of microbial communities for wastewater treatment bioreactors, could inspire development of mechanistic mathematical models of the gut microbiota. We review the current state-of-the-art in bioreactor modeling and current efforts in modeling the intestinal microbiota. Mathematical modeling could benefit greatly from the deluge of data emerging from metagenomic studies, but data-driven approaches such as network inference that aim to predict microbiome dynamics without explicit mechanistic knowledge seem better suited to model these data. Finally, we discuss how the integration of microbiome shotgun sequencing and metabolic modeling approaches such as flux balance analysis may fulfill the promise of a mechanistic model of the intestinal microbiota. PMID:24727124

  7. Connections between the human gut microbiome and gestational diabetes mellitus.

    PubMed

    Kuang, Ya-Shu; Lu, Jin-Hua; Li, Sheng-Hui; Li, Jun-Hua; Yuan, Ming-Yang; He, Jian-Rong; Chen, Nian-Nian; Xiao, Wan-Qing; Shen, Song-Ying; Qiu, Lan; Wu, Ying-Fang; Hu, Cui-Yue; Wu, Yan-Yan; Li, Wei-Dong; Chen, Qiao-Zhu; Deng, Hong-Wen; Papasian, Christopher J; Xia, Hui-Min; Qiu, Xiu

    2017-08-01

    The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM. © The Author 2017. Published by Oxford University Press.

  8. Gut microbiome, gut function, and probiotics: Implications for health.

    PubMed

    Hajela, Neerja; Ramakrishna, B S; Nair, G Balakrish; Abraham, Philip; Gopalan, Sarath; Ganguly, Nirmal K

    2015-03-01

    New insights from a rapidly developing field of research have ushered in a new era of understanding of the complexity of host-microbe interactions within the human body. The paradigm shift from culturing to metagenomics has provided an insight into the complex diversity of the microbial species that we harbor, revealing the fact that we are in fact more microbes than human cells. The largest consortium of these microbes resides in the gut and is called the gut microbiota. This new science has expanded the ability to document shifts in microbial populations to an unparalleled degree. It is now understood that signals from the microbiota provide trophic, nutritional, metabolic, and protective effects for the development and maintenance of the host digestive, immune, and neuroendocrine system. Evidence linking changes in the gut microbiota to gastrointestinal and extraintestinal disorders like irritable bowel syndrome, inflammatory bowel disease, obesity, diabetes, and celiac disease have begun to emerge recently. Probiotics act through diverse mechanisms positively affecting the composition and/or function of the commensal microbiota and alter host immunological responses. Well-controlled intervention trials, systematic reviews, and meta-analysis provide convincing evidence for the benefit of probiotics in prevention and treatment of gastrointestinal as well as extraintestinal disorders.

  9. Seasonal variation in nutrient utilization shapes gut microbiome structure and function in wild giant pandas.

    PubMed

    Wu, Qi; Wang, Xiao; Ding, Yun; Hu, Yibo; Nie, Yonggang; Wei, Wei; Ma, Shuai; Yan, Li; Zhu, Lifeng; Wei, Fuwen

    2017-09-13

    Wild giant pandas use different parts of bamboo (shoots, leaves and stems) and different bamboo species at different times of the year. Their usage of bamboo can be classified temporally into a distinct leaf stage, shoot stage and transition stage. An association between this usage pattern and variation in the giant panda gut microbiome remains unknown. Here, we found associations using a gut metagenomic approach and nutritional analyses whereby diversity of the gut microbial community in the leaf and shoot stages was significantly different. Functional metagenomic analysis showed that in the leaf stage, bacteria species over-represented genes involved in raw fibre utilization and cell cycle control. Thus, raw fibre utilization by the gut microbiome was guaranteed during the nutrient-deficient leaf stage by reinforcing gut microbiome robustness. During the protein-abundant shoot stage, the functional capacity of the gut microbiome expanded to include prokaryotic secretion and signal transduction activity, suggesting active interactions between the gut microbiome and host. These results illustrate that seasonal nutrient variation in wild giant pandas substantially influences gut microbiome composition and function. Nutritional interactions between gut microbiomes and hosts appear to be complex and further work is needed. © 2017 The Author(s).

  10. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions

    PubMed Central

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2016-01-01

    Background: 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. Objectives: We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. Methods: 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. Results: 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. Conclusions: 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

  11. Gut microbiome and chronic prostatitis/chronic pelvic pain syndrome

    PubMed Central

    Arora, Hans C.; Eng, Charis

    2017-01-01

    Analysis of the human microbiome continues to reveal new and previously unrealized associations between microbial dysbiosis and disease. Novel approaches to bacterial identification using culture-independent methods allow practitioners to discern the presence of alterations in the taxa and diversity of the microbiome and identify correlations with disease processes. While some of these diseases that have been extensively studied are well-defined in their etiology and treatment methods (colorectal cancer), others have provided much more significant challenges in both diagnosis and treatment. One such condition, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), has several etiological and potentiating contributions from infection, inflammation, central nervous system (CNS) changes, stress, and central sensitization—all factors that play important roles in the crosstalk between the human body and its microbiome. No singular cause of CP/CPPS has been identified and it is most likely a syndrome with multifactorial causes. This heterogeneity and ambiguity are sources of significant frustration for patients and providers alike. Despite multiple attempts, treatment of chronic prostatitis with monotherapy has seen limited success, which is thought to be due to its heterogeneous nature. Phenotypic approaches to both classify the disease and direct treatment for CP/CPPS have proven beneficial in these patients, but questions still remain regarding etiology. Newer microbiome research has found correlations between symptom scores and disease severity and the degree of dysbiosis in urine and gut (stool) microbiomes in these patients as compared to un-afflicted controls. These findings present potential new diagnostic and therapeutic targets in CP/CPPS patients. PMID:28217695

  12. Gut microbiome and chronic prostatitis/chronic pelvic pain syndrome.

    PubMed

    Arora, Hans C; Eng, Charis; Shoskes, Daniel A

    2017-01-01

    Analysis of the human microbiome continues to reveal new and previously unrealized associations between microbial dysbiosis and disease. Novel approaches to bacterial identification using culture-independent methods allow practitioners to discern the presence of alterations in the taxa and diversity of the microbiome and identify correlations with disease processes. While some of these diseases that have been extensively studied are well-defined in their etiology and treatment methods (colorectal cancer), others have provided much more significant challenges in both diagnosis and treatment. One such condition, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), has several etiological and potentiating contributions from infection, inflammation, central nervous system (CNS) changes, stress, and central sensitization-all factors that play important roles in the crosstalk between the human body and its microbiome. No singular cause of CP/CPPS has been identified and it is most likely a syndrome with multifactorial causes. This heterogeneity and ambiguity are sources of significant frustration for patients and providers alike. Despite multiple attempts, treatment of chronic prostatitis with monotherapy has seen limited success, which is thought to be due to its heterogeneous nature. Phenotypic approaches to both classify the disease and direct treatment for CP/CPPS have proven beneficial in these patients, but questions still remain regarding etiology. Newer microbiome research has found correlations between symptom scores and disease severity and the degree of dysbiosis in urine and gut (stool) microbiomes in these patients as compared to un-afflicted controls. These findings present potential new diagnostic and therapeutic targets in CP/CPPS patients.

  13. Alcoholic liver disease: The gut microbiome and liver crosstalk

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

  14. Dysbiotic gut microbiome: A key element of Crohn's disease.

    PubMed

    Øyri, Styrk Furnes; Műzes, Györgyi; Sipos, Ferenc

    2015-12-01

    Since the first publication on "regional ileitis", the relevance of this chronic inflammatory disease condition termed finally as Crohn's disease is continuously increasing. Although we are beginning to comprehend certain aspects of its pathogenesis, many facets remain unexplored. Host's gut microbiota is involved in a wide range of physiological and pathological processes including immune system development, and pathogen regulation. Further, the microbiome is thought to play a key role in Crohn's disease. The presence of Crohn's-associated variants of NOD2 and ATG16L genes appears to be associated not only with alterations of mucosal barrier functions, and bacterial killing, but the gut microbiota, as well, reflecting a potential relationship between the host's genotype and intestinal dysbiosis, involved in disease etiology. This review aims to characterize some exciting new aspect of Crohn's disease pathology, focusing mainly on the role of intestinal microbes, and their interplay with the immune system of the host.

  15. Alcoholic liver disease: the gut microbiome and liver cross talk.

    PubMed

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  16. Diet, the gut microbiome and the metabolome in IBD.

    PubMed

    Wu, Gary D

    2014-01-01

    The human gut contains a vast number of microorganisms known collectively as the gut microbiota. Despite its importance in maintaining the health of the host, growing evidence suggests the gut microbiota may also be an important factor in the pathogenesis of various diseases, a number of which have shown a rapid increase in incidence over the past few decades. In some of these diseases, such as inflammatory bowel disease (IBD), the microbiota is dysbiotic with an abnormal community structure and decrease in diversity. If the dysbiotic microbiota plays a role in disease pathogenesis, interventions that modify its composition to make it more similar to the microbiota observed in health, might be a strategy to treat certain disease processes. Indeed, the high-level efficacy of fecal microbiota transplantation in the treatment of refractory Clostridia difficile infection supports this notion as proof-of-principle. The composition of the microbiota can be influenced by many factors including age, genetics, host environment, and diet. With respect to the later, diet has an impact upon both the composition and function of the microbiota. There are epidemiologic data associating diet with the development of IBD as well as evidence that diet can influence both the form and function of the microbiome in a manner that impacts upon the development of intestinal inflammation. Based on this evidence, studies are now underway to examine the effect of defined formula diets, an effective therapeutic modality in Crohn's disease, on both the gut microbiome and its metabolome as a therapeutic probe with the hope of better defining the 'healthy' diet in patients with IBD.

  17. Early Life Experience and Gut Microbiome: the Brain-Gut-Microbiota Signaling System

    PubMed Central

    Cong, Xiaomei; Henderson, Wendy A.; Graf, Joerg; McGrath, Jacqueline M.

    2015-01-01

    Background Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuro-immune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short and long term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. Purpose The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. Conclusions The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking; leading potentially to changes in practice and targeted interventions. PMID:26240939

  18. Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

    PubMed

    Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

    2015-10-01

    Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.

  19. Genetic Determinants of the Gut Microbiome in UK Twins.

    PubMed

    Goodrich, Julia K; Davenport, Emily R; Beaumont, Michelle; Jackson, Matthew A; Knight, Rob; Ober, Carole; Spector, Tim D; Bell, Jordana T; Clark, Andrew G; Ley, Ruth E

    2016-05-11

    Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism, and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene locus and identify an association between the host gene ALDH1L1 and the bacteria SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet-sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Irritable bowel syndrome: a microbiome-gut-brain axis disorder?

    PubMed

    Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-10-21

    Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.

  1. Two dynamic regimes in the human gut microbiome

    PubMed Central

    Smillie, Chris S.; Alm, Eric J.

    2017-01-01

    The gut microbiome is a dynamic system that changes with host development, health, behavior, diet, and microbe-microbe interactions. Prior work on gut microbial time series has largely focused on autoregressive models (e.g. Lotka-Volterra). However, we show that most of the variance in microbial time series is non-autoregressive. In addition, we show how community state-clustering is flawed when it comes to characterizing within-host dynamics and that more continuous methods are required. Most organisms exhibited stable, mean-reverting behavior suggestive of fixed carrying capacities and abundant taxa were largely shared across individuals. This mean-reverting behavior allowed us to apply sparse vector autoregression (sVAR)—a multivariate method developed for econometrics—to model the autoregressive component of gut community dynamics. We find a strong phylogenetic signal in the non-autoregressive co-variance from our sVAR model residuals, which suggests niche filtering. We show how changes in diet are also non-autoregressive and that Operational Taxonomic Units strongly correlated with dietary variables have much less of an autoregressive component to their variance, which suggests that diet is a major driver of microbial dynamics. Autoregressive variance appears to be driven by multi-day recovery from frequent facultative anaerobe blooms, which may be driven by fluctuations in luminal redox. Overall, we identify two dynamic regimes within the human gut microbiota: one likely driven by external environmental fluctuations, and the other by internal processes. PMID:28222117

  2. Gut microbiome interactions with drug metabolism, efficacy, and toxicity.

    PubMed

    Wilson, Ian D; Nicholson, Jeremy K

    2017-01-01

    The gut microbiota has both direct and indirect effects on drug and xenobiotic metabolisms, and this can have consequences for both efficacy and toxicity. Indeed, microbiome-driven drug metabolism is essential for the activation of certain prodrugs, for example, azo drugs such as prontosil and neoprontosil resulting in the release of sulfanilamide. In addition to providing a major source of reductive metabolizing capability, the gut microbiota provides a suite of additional reactions including acetylation, deacylation, decarboxylation, dehydroxylation, demethylation, dehalogenation, and importantly, in the context of certain types of drug-related toxicity, conjugates hydrolysis reactions. In addition to direct effects, the gut microbiota can affect drug metabolism and toxicity indirectly via, for example, the modulation of host drug metabolism and disposition and competition of bacterial-derived metabolites for xenobiotic metabolism pathways. Also, of course, the therapeutic drugs themselves can have effects, both intended and unwanted, which can impact the health and composition of the gut microbiota with unforeseen consequences. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Two dynamic regimes in the human gut microbiome.

    PubMed

    Gibbons, Sean M; Kearney, Sean M; Smillie, Chris S; Alm, Eric J

    2017-02-01

    The gut microbiome is a dynamic system that changes with host development, health, behavior, diet, and microbe-microbe interactions. Prior work on gut microbial time series has largely focused on autoregressive models (e.g. Lotka-Volterra). However, we show that most of the variance in microbial time series is non-autoregressive. In addition, we show how community state-clustering is flawed when it comes to characterizing within-host dynamics and that more continuous methods are required. Most organisms exhibited stable, mean-reverting behavior suggestive of fixed carrying capacities and abundant taxa were largely shared across individuals. This mean-reverting behavior allowed us to apply sparse vector autoregression (sVAR)-a multivariate method developed for econometrics-to model the autoregressive component of gut community dynamics. We find a strong phylogenetic signal in the non-autoregressive co-variance from our sVAR model residuals, which suggests niche filtering. We show how changes in diet are also non-autoregressive and that Operational Taxonomic Units strongly correlated with dietary variables have much less of an autoregressive component to their variance, which suggests that diet is a major driver of microbial dynamics. Autoregressive variance appears to be driven by multi-day recovery from frequent facultative anaerobe blooms, which may be driven by fluctuations in luminal redox. Overall, we identify two dynamic regimes within the human gut microbiota: one likely driven by external environmental fluctuations, and the other by internal processes.

  4. Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

    PubMed Central

    Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-01-01

    Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. PMID:25339800

  5. Richness of human gut microbiome correlates with metabolic markers.

    PubMed

    Le Chatelier, Emmanuelle; Nielsen, Trine; Qin, Junjie; Prifti, Edi; Hildebrand, Falk; Falony, Gwen; Almeida, Mathieu; Arumugam, Manimozhiyan; Batto, Jean-Michel; Kennedy, Sean; Leonard, Pierre; Li, Junhua; Burgdorf, Kristoffer; Grarup, Niels; Jørgensen, Torben; Brandslund, Ivan; Nielsen, Henrik Bjørn; Juncker, Agnieszka S; Bertalan, Marcelo; Levenez, Florence; Pons, Nicolas; Rasmussen, Simon; Sunagawa, Shinichi; Tap, Julien; Tims, Sebastian; Zoetendal, Erwin G; Brunak, Søren; Clément, Karine; Doré, Joël; Kleerebezem, Michiel; Kristiansen, Karsten; Renault, Pierre; Sicheritz-Ponten, Thomas; de Vos, Willem M; Zucker, Jean-Daniel; Raes, Jeroen; Hansen, Torben; Bork, Peer; Wang, Jun; Ehrlich, S Dusko; Pedersen, Oluf

    2013-08-29

    We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.

  6. The Gut Microbiome and Its Role in Obesity

    PubMed Central

    Davis, Cindy D.

    2016-01-01

    The human body is host to a vast number of microbes, including bacterial, fungal and protozoal microoganisms, which together constitute our microbiota. Evidence is emerging that the intestinal microbiome is intrinsically linked with overall health, including obesity risk. Obesity and obesity-related metabolic disorders are characterized by specific alterations in the composition and function of the human gut microbiome. Mechanistic studies have indicated that the gastrointestinal microbiota can influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Moreover, its composition is not fixed and can be influenced by several dietary components. This fact raises the attractive possibility that manipulating the gut microbiota could facilitate weight loss or prevent obesity in humans. Emerging as possible strategies for obesity prevention and/or treatment are targeting the microbiota, in order to restore or modulate its composition through the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics), or both (synbiotics), or even fecal transplants. PMID:27795585

  7. Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.

    PubMed

    Gao, Bei; Chi, Liang; Mahbub, Ridwan; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-03-16

    Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development, and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multiomics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing, and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress, and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.

  8. Metabolic Modeling of Common Escherichia coli Strains in Human Gut Microbiome

    PubMed Central

    Huang, Jingfei

    2014-01-01

    The recent high-throughput sequencing has enabled the composition of Escherichia coli strains in the human microbial community to be profiled en masse. However, there are two challenges to address: (1) exploring the genetic differences between E. coli strains in human gut and (2) dynamic responses of E. coli to diverse stress conditions. As a result, we investigated the E. coli strains in human gut microbiome using deep sequencing data and reconstructed genome-wide metabolic networks for the three most common E. coli strains, including E. coli HS, UTI89, and CFT073. The metabolic models show obvious strain-specific characteristics, both in network contents and in behaviors. We predicted optimal biomass production for three models on four different carbon sources (acetate, ethanol, glucose, and succinate) and found that these stress-associated genes were involved in host-microbial interactions and increased in human obesity. Besides, it shows that the growth rates are similar among the models, but the flux distributions are different, even in E. coli core reactions. The correlations between human diabetes-associated metabolic reactions in the E. coli models were also predicted. The study provides a systems perspective on E. coli strains in human gut microbiome and will be helpful in integrating diverse data sources in the following study. PMID:25126572

  9. The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome

    PubMed Central

    Kelley, Scott T.; Skarra, Danalea V.; Rivera, Alissa J.; Thackray, Varykina G.

    2016-01-01

    Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet. PMID:26731268

  10. The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome.

    PubMed

    Kelley, Scott T; Skarra, Danalea V; Rivera, Alissa J; Thackray, Varykina G

    2016-01-01

    Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet.

  11. Structure, and culture of the gut microbiome of the Mormon cricket Anabrus simplex

    USDA-ARS?s Scientific Manuscript database

    The gut microbiome of insects plays an important role in their ecology and evolution, participating in nutrient acquisition, immunity, and behavior. Microbial community structure within the gut is heavily influenced by differences among gut regions in morphology and physiology, which determine the n...

  12. From next-generation sequencing to systematic modeling of the gut microbiome

    PubMed Central

    Ji, Boyang; Nielsen, Jens

    2015-01-01

    Changes in the human gut microbiome are associated with altered human metabolism and health, yet the mechanisms of interactions between microbial species and human metabolism have not been clearly elucidated. Next-generation sequencing has revolutionized the human gut microbiome research, but most current applications concentrate on studying the microbial diversity of communities and have at best provided associations between specific gut bacteria and human health. However, little is known about the inner metabolic mechanisms in the gut ecosystem. Here we review recent progress in modeling the metabolic interactions of gut microbiome, with special focus on the utilization of metabolic modeling to infer host–microbe interactions and microbial species interactions. The systematic modeling of metabolic interactions could provide a predictive understanding of gut microbiome, and pave the way to synthetic microbiota design and personalized-microbiome medicine and healthcare. Finally, we discuss the integration of metabolic modeling and gut microbiome engineering, which offer a new way to explore metabolic interactions across members of the gut microbiota. PMID:26157455

  13. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: More than a gut feeling

    PubMed Central

    Severance, Emily G.; Yolken, Robert H.; Eaton, William W.

    2014-01-01

    Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. PMID:25034760

  14. Sex, Body Mass Index, and Dietary Fiber Intake Influence the Human Gut Microbiome

    PubMed Central

    Dominianni, Christine; Sinha, Rashmi; Goedert, James J.; Pei, Zhiheng; Yang, Liying; Hayes, Richard B.; Ahn, Jiyoung

    2015-01-01

    Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention. PMID:25874569

  15. Sex, body mass index, and dietary fiber intake influence the human gut microbiome.

    PubMed

    Dominianni, Christine; Sinha, Rashmi; Goedert, James J; Pei, Zhiheng; Yang, Liying; Hayes, Richard B; Ahn, Jiyoung

    2015-01-01

    Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention.

  16. The Gut Microbiome, Obesity, and Weight Control in Women's Reproductive Health.

    PubMed

    Greathouse, K Leigh; Faucher, Mary Ann; Hastings-Tolsma, Marie

    2017-08-01

    The microbes residing in the human gut, referred to as the microbiome, are intricately linked to energy homeostasis and subsequently obesity. Integral to the origins of obesity, the microbiome is believed to affect not only health of the human gut but also overall health. This microbiome-obesity association is mediated through the process of energy extraction, metabolism, and cross talk between the brain and the gut microbiome. Host exposures, including diet, that potentially modify genetic predisposition to obesity and affect weight management are reviewed. The higher prevalence of obesity among women and recent evidence linking obesity during pregnancy with offspring health make this topic particularly relevant. Current limitations in microbiome research to address obesity and future advances in this field are described. Applications of this science with respect to applied nursing and overall health care in general are included, with emphasis on the reproductive health of women and their offspring.

  17. Manganese-induced sex-specific gut microbiome perturbations in C57BL/6 mice.

    PubMed

    Chi, Liang; Gao, Bei; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-09-15

    Overexposure to manganese (Mn) leads to toxic effects, such as promoting the development of Parkinson's-like neurological disorders. The gut microbiome is deeply involved in immune development, host metabolism, and xenobiotics biotransformation, and significantly influences central nervous system (CNS) via the gut-brain axis, i.e. the biochemical signaling between the gastrointestinal tract and the CNS. However, it remains unclear whether Mn can affect the gut microbiome and its metabolic functions, particularly those linked to neurotoxicity. In addition, sex-specific effects of Mn have been reported, with no mechanism being identified yet. Recently, we have shown that the gut microbiome is largely different between males and females, raising the possibility that differential gut microbiome responses may contribute to sex-selective toxicity of Mn. Here, we applied high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics to explore how Mn(2+) exposure affects the gut microbiome and its metabolism in C57BL/6 mice. Mn(2+) exposure perturbed the gut bacterial compositions, functional genes and fecal metabolomes in a highly sex-specific manner. In particular, bacterial genes and/or key metabolites of neurotransmitter synthesis and pro-inflammatory mediators are significantly altered by Mn(2+) exposure, which can potentially affect chemical signaling of gut-brain interactions. Likewise, functional genes involved in iron homeostasis, flagellar motility, quorum sensing, and Mn transportation/oxidation are also widely changed by Mn(2+) exposure. Taken together, this study has demonstrated that Mn(2+) exposure perturbs the gut microbiome and its metabolic functions, which highlights the potential role of the gut microbiome in Mn(2+) toxicity, particularly its sex-specific toxic effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Rapidly expanding knowledge on the role of the gut microbiome in health and disease.

    PubMed

    Cénit, M C; Matzaraki, V; Tigchelaar, E F; Zhernakova, A

    2014-10-01

    The human gut is colonized by a wide diversity of micro-organisms, which are now known to play a key role in the human host by regulating metabolic functions and immune homeostasis. Many studies have indicated that the genomes of our gut microbiota, known as the gut microbiome or our "other genome" could play an important role in immune-related, complex diseases, and growing evidence supports a causal role for gut microbiota in regulating predisposition to diseases. A comprehensive analysis of the human gut microbiome is thus important to unravel the exact mechanisms by which the gut microbiota are involved in health and disease. Recent advances in next-generation sequencing technology, along with the development of metagenomics and bioinformatics tools, have provided opportunities to characterize the microbial communities. Furthermore, studies using germ-free animals have shed light on how the gut microbiota are involved in autoimmunity. In this review we describe the different approaches used to characterize the human microbiome, review current knowledge about the gut microbiome, and discuss the role of gut microbiota in immune homeostasis and autoimmunity. Finally, we indicate how this knowledge could be used to improve human health by manipulating the gut microbiota. This article is part of a Special Issue entitled: From Genome to Function. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition.

    PubMed

    Deehan, Edward C; Walter, Jens

    2016-05-01

    Increasing evidence indicates that modern lifestyle, and specifically a Western diet, has led to a substantial depletion of the human gut microbiome. This loss is implicated in the rampant increase of chronic diseases, providing an incentive to fundamentally transform human nutrition towards being more holistic and microbiome-focused. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine.

    PubMed

    Khalsa, Jag; Duffy, Linda C; Riscuta, Gabriela; Starke-Reed, Pamela; Hubbard, Van S

    2017-03-01

    Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular-based high-throughput technologies are providing novel insight about host-gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in-depth studies of the liver-microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost-effective precision therapies.

  1. “I Am I and My Bacterial Circumstances”: Linking Gut Microbiome, Neurodevelopment, and Depression

    PubMed Central

    Lima-Ojeda, Juan M.; Rupprecht, Rainer; Baghai, Thomas C.

    2017-01-01

    Recently, there has been renewed interest in the role played by microbiome in both human health and human disease. A correct equilibrium between the human host and their microorganisms is important for an appropriate physiological function. Extensive research has shown that microbes that inhabit the gastrointestinal tract—or gut microbiota—are involved not only in both nutritive and digestive activities but also in immunological processes. Moreover, the gut microbiome influences both central nervous system and energy homeostasis. An altered gut microbiome has been associated with the pathophysiology of different diseases, including neuropsychiatric disorders. Apparently, both environmental—diet, exposition to antibiotics, and infections—and host-genetic factors have a strong influence on gut microbiome, modulating the risk for neuropsychiatric illness. Also, early life disruption of the microbiome–gut–brain (MGB) axis has been associated with an increased risk of developing depression later in life, suggesting a link between gut microbiome, neurodevelopment, and depression. This review aims to contribute to this growing area of research by exploring the role played by the gut microbiome in neurodevelopment and in the etiology of the depressive syndrome, including nutritional, immunological, and energy homeostasis approaches. PMID:28878696

  2. The malleable gut microbiome of juvenile rainbow trout (Oncorhynchus mykiss): Diet-dependent shifts of bacterial community structures.

    PubMed

    Michl, Stéphanie Céline; Ratten, Jenni-Marie; Beyer, Matt; Hasler, Mario; LaRoche, Julie; Schulz, Carsten

    2017-01-01

    Plant-derived protein sources are the most relevant substitutes for fishmeal in aquafeeds. Nevertheless, the effects of plant based diets on the intestinal microbiome especially of juvenile Rainbow trout (Oncorhynchus mykiss) are yet to be fully investigated. The present study demonstrates, based on 16S rDNA bacterial community profiling, that the intestinal microbiome of juvenile Rainbow trout is strongly affected by dietary plant protein inclusion levels. After first feeding of juveniles with either 0%, 50% or 97% of total dietary protein content derived from plants, statistically significant differences of the bacterial gut community for the three diet-types were detected, both at phylum and order level. The microbiome of juvenile fish consisted mainly of the phyla Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria and Actinobacteria, and thus fits the salmonid core microbiome suggested in previous studies. Dietary plant proteins significantly enhanced the relative abundance of the orders Lactobacillales, Bacillales and Pseudomonadales. Animal proteins in contrast significantly promoted Bacteroidales, Clostridiales, Vibrionales, Fusobacteriales and Alteromonadales. The overall alpha diversity significantly decreased with increasing plant protein inclusion levels and with age of experimental animals. In order to investigate permanent effects of the first feeding diet-type on the early development of the microbiome, a diet change was included in the study after 54 days, but no such effects could be detected. Instead, the microbiome of juvenile trout fry was highly dependent on the actual diet fed at the time of sampling.

  3. Structure and function of the healthy pre-adolescent pediatric gut microbiome.

    PubMed

    Hollister, Emily B; Riehle, Kevin; Luna, Ruth Ann; Weidler, Erica M; Rubio-Gonzales, Michelle; Mistretta, Toni-Ann; Raza, Sabeen; Doddapaneni, Harsha V; Metcalf, Ginger A; Muzny, Donna M; Gibbs, Richard A; Petrosino, Joseph F; Shulman, Robert J; Versalovic, James

    2015-08-26

    The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limited. Using 16S rRNA gene and shotgun metagenomic sequencing, we characterized the structure, function, and variation of the healthy pediatric gut microbiome in a cohort of school-aged, pre-adolescent children (ages 7-12 years). We compared the healthy pediatric gut microbiome with that of healthy adults previously recruited from the same region (Houston, TX, USA). Although healthy children and adults harbored similar numbers of taxa and functional genes, their composition and functional potential differed significantly. Children were enriched in Bifidobacterium spp., Faecalibacterium spp., and members of the Lachnospiraceae, while adults harbored greater abundances of Bacteroides spp. From a functional perspective, significant differences were detected with respect to the relative abundances of genes involved in vitamin synthesis, amino acid degradation, oxidative phosphorylation, and triggering mucosal inflammation. Children's gut communities were enriched in functions which may support ongoing development, while adult communities were enriched in functions associated with inflammation, obesity, and increased risk of adiposity. Previous studies suggest that the human gut microbiome is relatively stable and adult-like after the first 1 to 3 years of life. Our results suggest that the healthy pediatric gut microbiome harbors compositional and functional qualities that differ from those of healthy adults and that the gut microbiome may undergo a more prolonged development than previously suspected.

  4. Alterations of the human gut microbiome in liver cirrhosis.

    PubMed

    Qin, Nan; Yang, Fengling; Li, Ang; Prifti, Edi; Chen, Yanfei; Shao, Li; Guo, Jing; Le Chatelier, Emmanuelle; Yao, Jian; Wu, Lingjiao; Zhou, Jiawei; Ni, Shujun; Liu, Lin; Pons, Nicolas; Batto, Jean Michel; Kennedy, Sean P; Leonard, Pierre; Yuan, Chunhui; Ding, Wenchao; Chen, Yuanting; Hu, Xinjun; Zheng, Beiwen; Qian, Guirong; Xu, Wei; Ehrlich, S Dusko; Zheng, Shusen; Li, Lanjuan

    2014-09-04

    Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

  5. The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders.

    PubMed

    Malan-Muller, Stefanie; Valles-Colomer, Mireia; Raes, Jeroen; Lowry, Christopher A; Seedat, Soraya; Hemmings, Sian M J

    2017-08-02

    Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.

  6. Gut Microbiome and the Development of Food Allergy and Allergic Disease.

    PubMed

    Prince, Benjamin T; Mandel, Mark J; Nadeau, Kari; Singh, Anne Marie

    2015-12-01

    The impact of gut microbiome on human development, nutritional needs, and disease has become evident with advances in the ability to study these complex communities of microorganisms, and there is growing appreciation for the role of the microbiome in immune regulation. Several studies have examined associations between changes in the commensal microbiota and the development of asthma, allergic rhinitis, and asthma, but far less have evaluated the impact of the microbiome on the development of food allergy. This article reviews the human gastrointestinal microbiome, focusing on the theory and evidence for its role in the development of IgE-mediated food allergy and other allergic diseases.

  7. Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

    PubMed Central

    Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; Scott, Jarrod J.; Emerson, David; McCarthy, James J.; Girguis, Peter R.

    2015-01-01

    Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut. PMID:26393325

  8. Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores.

    PubMed

    Sanders, Jon G; Beichman, Annabel C; Roman, Joe; Scott, Jarrod J; Emerson, David; McCarthy, James J; Girguis, Peter R

    2015-09-22

    Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.

  9. Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

    SciTech Connect

    Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; Scott, Jarrod J.; Emerson, David; McCarthy, James J.; Girguis, Peter R.

    2015-09-22

    Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.

  10. Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

    DOE PAGES

    Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; ...

    2015-09-22

    Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism andmore » essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.« less

  11. Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine

    USDA-ARS?s Scientific Manuscript database

    Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. Gut microbiota, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease...

  12. Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations

    PubMed Central

    Shashkova, Tatiana; Popenko, Anna; Tyakht, Alexander; Peskov, Kirill; Kosinsky, Yuri; Bogolubsky, Lev; Raigorodskii, Andrei; Ischenko, Dmitry; Alexeev, Dmitry; Govorun, Vadim

    2016-01-01

    Background Intestinal microbiota plays an important role in the human health. It is involved in the digestion and protects the host against external pathogens. Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. Methodology/Principal Findings In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. Bacterial species are known to mutate and acquire resistance to the antibiotics. The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. Conclusion/Significance The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. The recovery of sensitive strains is explained by fitness cost of the resistance. The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms

  13. Evidence of cellulose metabolism by the giant panda gut microbiome.

    PubMed

    Zhu, Lifeng; Wu, Qi; Dai, Jiayin; Zhang, Shanning; Wei, Fuwen

    2011-10-25

    The giant panda genome codes for all necessary enzymes associated with a carnivorous digestive system but lacks genes for enzymes needed to digest cellulose, the principal component of their bamboo diet. It has been posited that this iconic species must therefore possess microbial symbionts capable of metabolizing cellulose, but these symbionts have remained undetected. Here we examined 5,522 prokaryotic ribosomal RNA gene sequences in wild and captive giant panda fecal samples. We found lower species richness of the panda microbiome than of mammalian microbiomes for herbivores and nonherbivorous carnivores. We detected 13 operational taxonomic units closely related to Clostridium groups I and XIVa, both of which contain taxa known to digest cellulose. Seven of these 13 operational taxonomic units were unique to pandas compared with other mammals. Metagenomic analysis using ~37-Mbp contig sequences from gut microbes recovered putative genes coding two cellulose-digesting enzymes and one hemicellulose-digesting enzyme, cellulase, β-glucosidase, and xylan 1,4-β-xylosidase, in Clostridium group I. Comparing glycoside hydrolase profiles of pandas with those of herbivores and omnivores, we found a moderate abundance of oligosaccharide-degrading enzymes for pandas (36%), close to that for humans (37%), and the lowest abundance of cellulases and endohemicellulases (2%), which may reflect low digestibility of cellulose and hemicellulose in the panda's unique bamboo diet. The presence of putative cellulose-digesting microbes, in combination with adaptations related to feeding, physiology, and morphology, show that giant pandas have evolved a number of traits to overcome the anatomical and physiological challenge of digesting a diet high in fibrous matter.

  14. Role of oral and gut microbiome in nitric oxide-mediated colon motility.

    PubMed

    Walker, Miriam Y; Pratap, Siddharth; Southerland, Janet H; Farmer-Dixon, Cherae M; Lakshmyya, Kesavalu; Gangula, Pandu R

    2017-06-07

    Periodontal disease (PD), a severe form of gum disease, is among the most prevalent chronic infection in humans and is associated with complex microbial synergistic dysbiosis in the subgingival cavity. The immune system of the body interacts with the microbes as the plaque extends and propagates below the gingival sulcus. Once bacteria reach the gingival sulcus, it can enter the blood stream and affect various areas of the human body. The polymicrobial nature of periodontal disease, if left untreated, promotes chronic inflammation, not only within the oral cavity, but also throughout the human body. Alterations seen in the concentrations of healthy gut microbiota may lead to systemic alterations, such as gut motility disorders, high blood pressure, and atherosclerosis. Although gut microbiome has been shown to play a vital role in intestinal motility functions, the role of oral bacteria in this setting remains to be investigated. It is unclear whether oral microbial DNA is present in the large intestine and, if so, whether it alters the gut microbiome. In addition, polybacterial infection induced PD reduced nitric oxide (NO) synthesis and antioxidant enzymes in rodent colon. In this review, we will discuss the interactions between oral and gut microbiome, specifics of how the oral microbiome may modulate the activities of the gut microbiome, and possible ramifications of these alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. New Frontiers in Fibers: Innovative and Emerging Research on the Gut Microbiome and Bone Health.

    PubMed

    Wallace, Taylor C; Marzorati, Massimo; Spence, Lisa; Weaver, Connie M; Williamson, Patricia S

    2017-01-01

    The complex interactions between the diet, gut microbiome, and host characteristics that provide a functional benefit to the host are an area of great interest and current exploration in the nutrition and health science community. New technologies are available to assess mechanisms that may explain these functional benefits to the host. One emerging functional benefit from changes in the gut microbiome is increased calcium absorption, increased calcium retention, and improved indices of bone health. Prebiotic fibers enhance microbial fermentation in the gut, providing an ecological advantage to specific nonpathogenic bacteria that have the ability to modify an individual's metabolic potential. Fermentation of fibers also leads to increased production of short-chain fatty acids. These changes have been positively correlated with increased calcium absorption in humans and increased bone density and strength in animal models. Dietary fibers may offer an additional means to enhance calcium absorption with the possibility of stimulating the gut microbiome to ultimately influence bone health. This hot topic perspectives piece reviews innovative technologies that can be used to assess the impact of prebiotic fibers on the gastrointestinal tract (GIT) as well as the potential mechanisms that may explain their health effects on bone. Validated in vitro models used to measure alterations in the gut microbiome, as well as animal and clinical studies assessing the role of prebiotic fibers on calcium absorption and bone indices through alternations in the gut microbiome, are presented.

  16. Inside Out: HIV, the Gut Microbiome, and the Mucosal Immune System.

    PubMed

    Liu, Jay; Williams, Brett; Frank, Daniel; Dillon, Stephanie M; Wilson, Cara C; Landay, Alan L

    2017-01-15

    The components of the human gut microbiome have been found to influence a broad array of pathologic conditions ranging from heart disease to diabetes and even to cancer. HIV infection upsets the delicate balance in the normal host-microbe interaction both through alterations in the taxonomic composition of gut microbial communities as well as through disruption of the normal host response mechanisms. In this article we review the current methods of gut microbiome analysis and the resulting data regarding how HIV infection might change the balance of commensal bacteria in the gut. Additionally, we cover the various effects gut microbes have on host immune homeostasis and the preliminary but intriguing data on how HIV disrupts those mechanisms. Finally, we briefly describe some of the important biomolecules produced by gut microbiota and the role that they may play in maintaining host immune homeostasis with and without HIV infection.

  17. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

    PubMed

    Bäckhed, Fredrik; Roswall, Josefine; Peng, Yangqing; Feng, Qiang; Jia, Huijue; Kovatcheva-Datchary, Petia; Li, Yin; Xia, Yan; Xie, Hailiang; Zhong, Huanzi; Khan, Muhammad Tanweer; Zhang, Jianfeng; Li, Junhua; Xiao, Liang; Al-Aama, Jumana; Zhang, Dongya; Lee, Ying Shiuan; Kotowska, Dorota; Colding, Camilla; Tremaroli, Valentina; Yin, Ye; Bergman, Stefan; Xu, Xun; Madsen, Lise; Kristiansen, Karsten; Dahlgren, Jovanna; Wang, Jun; Jun, Wang

    2015-05-13

    The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.

  18. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders.

    PubMed

    Kelly, John R; Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard; Hyland, Niall P

    2015-01-01

    The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.

  19. Mining gut microbiome oligopeptides by functional metaproteome display

    PubMed Central

    Zantow, Jonas; Just, Sarah; Lagkouvardos, Ilias; Kisling, Sigrid; Dübel, Stefan; Lepage, Patricia; Clavel, Thomas; Hust, Michael

    2016-01-01

    Pathogen infections, autoimmune diseases, and chronic inflammatory disorders are associated with systemic antibody responses from the host immune system. Disease-specific antibodies can be important serum biomarkers, but the identification of antigens associated with specific immune reactions is challenging, in particular if complex communities of microorganisms are involved in the disease progression. Despite promising new diagnostic opportunities, the discovery of these serological markers becomes more difficult with increasing complexity of microbial communities. In the present work, we used a metagenomic M13 phage display approach to select immunogenic oligopeptides from the gut microbiome of transgenic mice suffering from chronic ileitis. We constructed three individual metaproteome phage display libraries with a library size of approximately 107 clones each. Using serum antibodies, we selected and validated three oligopeptides that induced specific antibody responses in the mouse model. This proof-of-concept study provides the first successful application of functional metaproteome display for the study of protein-protein interactions and the discovery of potential disease biomarkers. PMID:27703179

  20. Mining gut microbiome oligopeptides by functional metaproteome display.

    PubMed

    Zantow, Jonas; Just, Sarah; Lagkouvardos, Ilias; Kisling, Sigrid; Dübel, Stefan; Lepage, Patricia; Clavel, Thomas; Hust, Michael

    2016-10-05

    Pathogen infections, autoimmune diseases, and chronic inflammatory disorders are associated with systemic antibody responses from the host immune system. Disease-specific antibodies can be important serum biomarkers, but the identification of antigens associated with specific immune reactions is challenging, in particular if complex communities of microorganisms are involved in the disease progression. Despite promising new diagnostic opportunities, the discovery of these serological markers becomes more difficult with increasing complexity of microbial communities. In the present work, we used a metagenomic M13 phage display approach to select immunogenic oligopeptides from the gut microbiome of transgenic mice suffering from chronic ileitis. We constructed three individual metaproteome phage display libraries with a library size of approximately 10(7) clones each. Using serum antibodies, we selected and validated three oligopeptides that induced specific antibody responses in the mouse model. This proof-of-concept study provides the first successful application of functional metaproteome display for the study of protein-protein interactions and the discovery of potential disease biomarkers.

  1. Gut Microbiome and Behavior: Focus on Neuroimmune Interactions.

    PubMed

    Foster, J A

    2016-01-01

    As neuroscientists, psychologists, and psychiatrists are starting to appreciate the importance of the gut microbiota to mental health, it is critical to determine the mechanisms of microbiota to brain communication and thereby provide a better understanding of the aspects that may be modifiable with proper intervention in individuals with mental illness. Microbiota-brain communication is emerging as an important factor in brain development and function. Further, immune dysfunction is clearly established to play a role in mental illness. Investigators in the field have established expertise in studying the microbiota, the immune system, brain, and behavior and are poised to contribute significant novel findings to our understanding of microbiota-immune-brain communication in mental illness. This chapter provides a review of the literature related to the influence of microbiota-immune-brain communication to behavior. This research has a clear translational relevance for mental health, contributing to extant findings that indicate a role for the microbiome in brain development and behavior. © 2016 Elsevier Inc. All rights reserved.

  2. The Gut Commensal Microbiome of Drosophila melanogaster Is Modified by the Endosymbiont Wolbachia

    PubMed Central

    Fast, Eva M.; Guo, Rong; Vaisman, Natalie; Ortiz, Luis; Bybee, Joanna; Slatko, Barton E.

    2017-01-01

    ABSTRACT Endosymbiotic Wolbachia bacteria and the gut microbiome have independently been shown to affect several aspects of insect biology, including reproduction, development, life span, stem cell activity, and resistance to human pathogens, in insect vectors. This work shows that Wolbachia bacteria, which reside mainly in the fly germline, affect the microbial species present in the fly gut in a lab-reared strain. Drosophila melanogaster hosts two main genera of commensal bacteria—Acetobacter and Lactobacillus. Wolbachia-infected flies have significantly reduced titers of Acetobacter. Sampling of the microbiome of axenic flies fed with equal proportions of both bacteria shows that the presence of Wolbachia bacteria is a significant determinant of the composition of the microbiome throughout fly development. However, this effect is host genotype dependent. To investigate the mechanism of microbiome modulation, the effect of Wolbachia bacteria on Imd and reactive oxygen species pathways, the main regulators of immune response in the fly gut, was measured. The presence of Wolbachia bacteria does not induce significant changes in the expression of the genes for the effector molecules in either pathway. Furthermore, microbiome modulation is not due to direct interaction between Wolbachia bacteria and gut microbes. Confocal analysis shows that Wolbachia bacteria are absent from the gut lumen. These results indicate that the mechanistic basis of the modulation of composition of the microbiome by Wolbachia bacteria is more complex than a direct bacterial interaction or the effect of Wolbachia bacteria on fly immunity. The findings reported here highlight the importance of considering the composition of the gut microbiome and host genetic background during Wolbachia-induced phenotypic studies and when formulating microbe-based disease vector control strategies. IMPORTANCE Wolbachia bacteria are intracellular bacteria present in the microbiome of a large fraction of

  3. Gut microbiome and the risk factors in central nervous system autoimmunity.

    PubMed

    Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-11-17

    Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process.

  4. Gut microbiome and the risk factors in central nervous system autoimmunity

    PubMed Central

    Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-01-01

    Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary system in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector immune sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process. PMID:25286403

  5. [Gut microbiome and major depressive disorder : The other side of ourselves].

    PubMed

    Manook, A; Hiergeist, A; Rupprecht, R; Baghai, T C

    2016-11-01

    Microbiological ecology and its ambition to describe the complete genome of complex living communities as a whole, have given us powerful tools to characterize the human gut microbiome on a genetic and, hence, taxonomic and abundance level; for a decade now, they have become sufficiently inexpensive, fast and feasible. Thus, opportunities arose to have a fresh and closer look at the microbiota-gut-brain-axis and its impact on human health; this axis comprises a complex multisystemic network of multidirectional interactions between brain and gut including influences beyond one generation. Gnotobiotic animal models have become essential for specific research targets. Combining gut microbiome analysis with observations on the hypothalamus-pituitary-adrenal axis and various aspects of inflammation helped to gain first insights into the role of the microbiota-gut-brain-axis in depressive disorders. Therapeutic endeavors with psychobiotics have not yet shown their value in clinical studies.

  6. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

    PubMed Central

    Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

    2015-01-01

    The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

  7. Fermentation potential of the gut microbiome: implications for energy homeostasis and weight management.

    PubMed

    Arora, Tulika; Sharma, Rajkumar

    2011-02-01

    Energy homeostasis is regulated by twin factors, energy intake and energy expenditure. Obesity arises when these two factors are out of balance. Recently, the microflora residing in the human gut has been found to be one of the influential factors disturbing energy balance. Recent interest in this field has led to use of the term "gut microbiome" to describe the genomes of trillions of microbes residing in the gut. Metagenomic studies have shown that the human gut microbiome facilitates fermentation of indigestible carbohydrates to short-chain fatty acids that provide excess energy to the body, thus contributing to the obese phenotype. Alteration in the ratio of Bacteroidetes and Firmicutes drives a change in fermentation patterns that could explain weight gain. Therefore, changes in the gut microbiome (induced by antibiotics or dietary supplements) may be helpful in curbing the obesity pandemic. This review provides information on the expansive role the gut microbiome is believed to play in obesity and other related metabolic disorders. © 2011 International Life Sciences Institute.

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

    PubMed

    Lerner, Aaron; Neidhöfer, Sandra; Matthias, Torsten

    2017-10-12

    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

  9. "WHAT'S BUGGING THE GUT IN OCD?" A REVIEW OF THE GUT MICROBIOME IN OBSESSIVE-COMPULSIVE DISORDER.

    PubMed

    Turna, Jasmine; Grosman Kaplan, Keren; Anglin, Rebecca; Van Ameringen, Michael

    2016-03-01

    The gut microbiome has become a topic of major interest as of late, with a new focus specifically on psychiatric disorders. Recent studies have revealed that variations in the composition of the gut microbiota may influence anxiety and mood and vice versa. Keeping the concept of this bidirectional "microbiota-gut-brain" axis in mind, this review aims to shed light on how these findings may also be implicated in obsessive-compulsive disorder (OCD); potentially outlining a novel etiological pathway of interest for future research in the field.

  10. Gut Microbiome Diversity among Cheyenne and Arapaho Individuals from Western Oklahoma.

    PubMed

    Sankaranarayanan, Krithivasan; Ozga, Andrew T; Warinner, Christina; Tito, Raul Y; Obregon-Tito, Alexandra J; Xu, Jiawu; Gaffney, Patrick M; Jervis, Lori L; Cox, Derrell; Stephens, Lancer; Foster, Morris; Tallbull, Gloria; Spicer, Paul; Lewis, Cecil M

    2015-12-21

    Existing studies characterizing gut microbiome variation in the United States suffer from population ascertainment biases, with individuals of American Indian ancestry being among the most underrepresented. Here, we describe the first gut microbiome diversity study of an American Indian community. We partnered with the Cheyenne and Arapaho (C&A), federally recognized American Indian tribes in Oklahoma, and compared gut microbiome diversity and metabolic function of C&A participants to individuals of non-native ancestry in Oklahoma (NNIs). While the C&A and NNI participants share microbiome features common to industrialized populations, the C&A participants had taxonomic profiles characterized by a reduced abundance of the anti-inflammatory bacterial genus Faecalibacterium, along with a fecal metabolite profile similar to dysbiotic states described for metabolic disorders. American Indians are known to be at elevated risk for metabolic disorders. While many aspects of this health disparity remain poorly understood, our results support the need to further study the microbiome as a contributing factor. As the field of microbiome research transitions to therapeutic interventions, it raises concerns that the continued exclusion and lack of participation of American Indian communities in these studies will further exacerbate health disparities. To increase momentum in fostering these much needed partnerships, it is essential that the scientific community actively engage in and recruit these vulnerable populations in basic research through a strategy that promotes mutual trust and understanding, as outlined in this study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Maternal Obesity Is Associated with Alterations in the Gut Microbiome in Toddlers

    PubMed Central

    Galley, Jeffrey D.; Bailey, Michael; Kamp Dush, Claire; Schoppe-Sullivan, Sarah; Christian, Lisa M.

    2014-01-01

    Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully delineated. A novel possible pathway linking maternal and child weight is the transmission of obesogenic microbes from mother to child. The current study examined whether maternal obesity was associated with differences in the composition of the gut microbiome in children in early life. Fecal samples from children 18–27 months of age (n = 77) were analyzed by pyro-tag 16S sequencing. Significant effects of maternal obesity on the composition of the gut microbiome of offspring were observed among dyads of higher socioeconomic status (SES). In the higher SES group (n = 47), children of obese (BMI≥30) versus non-obese mothers clustered on a principle coordinate analysis (PCoA) and exhibited greater homogeneity in the composition of their gut microbiomes as well as greater alpha diversity as indicated by the Shannon Diversity Index, and measures of richness and evenness. Also in the higher SES group, children born to obese versus non-obese mothers had differences in abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp. Prior studies have linked some of these bacterial groups to differences in weight and diet. This study provides novel evidence that maternal obesity is associated with differences in the gut microbiome in children in early life, particularly among those of higher SES. Among obese adults, the relative contribution of genetic versus behavioral factors may differ based on SES. Consequently, the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. Continued research is needed to examine this question as well as the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course. PMID:25409177

  12. Maternal obesity is associated with alterations in the gut microbiome in toddlers.

    PubMed

    Galley, Jeffrey D; Bailey, Michael; Kamp Dush, Claire; Schoppe-Sullivan, Sarah; Christian, Lisa M

    2014-01-01

    Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully delineated. A novel possible pathway linking maternal and child weight is the transmission of obesogenic microbes from mother to child. The current study examined whether maternal obesity was associated with differences in the composition of the gut microbiome in children in early life. Fecal samples from children 18-27 months of age (n = 77) were analyzed by pyro-tag 16S sequencing. Significant effects of maternal obesity on the composition of the gut microbiome of offspring were observed among dyads of higher socioeconomic status (SES). In the higher SES group (n = 47), children of obese (BMI≥30) versus non-obese mothers clustered on a principle coordinate analysis (PCoA) and exhibited greater homogeneity in the composition of their gut microbiomes as well as greater alpha diversity as indicated by the Shannon Diversity Index, and measures of richness and evenness. Also in the higher SES group, children born to obese versus non-obese mothers had differences in abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp. Prior studies have linked some of these bacterial groups to differences in weight and diet. This study provides novel evidence that maternal obesity is associated with differences in the gut microbiome in children in early life, particularly among those of higher SES. Among obese adults, the relative contribution of genetic versus behavioral factors may differ based on SES. Consequently, the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. Continued research is needed to examine this question as well as the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course.

  13. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.

    PubMed

    Conley, Melissa N; Wong, Carmen P; Duyck, Kyle M; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

  14. 11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet

    PubMed Central

    Johnson, Jethro S; Opiyo, Monica N; Thomson, Marian; Gharbi, Karim; Seckl, Jonathan R; Heger, Andreas

    2016-01-01

    The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched ‘Western’ diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae. Our results demonstrate that (i) genetic effects on host–microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency. PMID:27885053

  15. 11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet.

    PubMed

    Johnson, Jethro S; Opiyo, Monica N; Thomson, Marian; Gharbi, Karim; Seckl, Jonathan R; Heger, Andreas; Chapman, Karen E

    2017-02-01

    The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched 'Western' diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae Our results demonstrate that (i) genetic effects on host-microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency. © 2017 The authors.

  16. Early life dynamics of the human gut virome and bacterial microbiome in infants

    PubMed Central

    Lim, Efrem S.; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K.; Droit, Lindsay; Ndao, I. Malick; Warner, Barbara B.; Tarr, Phillip I.; Wang, David; Holtz, Lori R.

    2016-01-01

    The early years of life are important for immune development and influences health in adulthood. While it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or, virome), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome are more similar between co-twins than between non-related infants. From birth to two years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra predator-prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophage with age. PMID:26366711

  17. Early life dynamics of the human gut virome and bacterial microbiome in infants.

    PubMed

    Lim, Efrem S; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K; Droit, Lindsay; Ndao, I Malick; Warner, Barbara B; Tarr, Phillip I; Wang, David; Holtz, Lori R

    2015-10-01

    The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age.

  18. Arsenic Exposure Perturbs the Gut Microbiome and Its Metabolic Profile in Mice: An Integrated Metagenomics and Metabolomics Analysis

    PubMed Central

    Abo, Ryan Phillip; Schlieper, Katherine Ann; Graffam, Michelle E.; Levine, Stuart; Wishnok, John S.; Swenberg, James A.; Tannenbaum, Steven R.; Fox, James G.

    2014-01-01

    Background: The human intestine is host to an enormously complex, diverse, and vast microbial community—the gut microbiota. The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development, epithelial homeostasis, and so forth. However, the composition and diversity of the gut microbiome can be readily affected by external factors, which raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration, or dysbiosis. Arsenic exposure affects large human populations worldwide and has been linked to a number of diseases, including cancer, diabetes, and cardiovascular disorders. Objectives: We investigated the impact of arsenic exposure on the gut microbiome composition and its metabolic profiles. Methods: We used an integrated approach combining 16S rRNA gene sequencing and mass spectrometry–based metabolomics profiling to examine the functional impact of arsenic exposure on the gut microbiome. Results: 16S rRNA gene sequencing revealed that arsenic significantly perturbed the gut microbiome composition in C57BL/6 mice after exposure to 10 ppm arsenic for 4 weeks in drinking water. Moreover, metabolomics profiling revealed a concurrent effect, with a number of gut microflora–related metabolites being perturbed in multiple biological matrices. Conclusions: Arsenic exposure not only alters the gut microbiome community at the abundance level but also substantially disturbs its metabolic profiles at the function level. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism by which arsenic exposure leads to or exacerbates human diseases. Citation: Lu K, Abo RP, Schlieper KA, Graffam ME, Levine S, Wishnok JS, Swenberg JA, Tannenbaum SR, Fox JG. 2014. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis. Environ Health

  19. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis.

    PubMed

    Lu, Kun; Abo, Ryan Phillip; Schlieper, Katherine Ann; Graffam, Michelle E; Levine, Stuart; Wishnok, John S; Swenberg, James A; Tannenbaum, Steven R; Fox, James G

    2014-03-01

    The human intestine is host to an enormously complex, diverse, and vast microbial community-the gut microbiota. The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development, epithelial homeostasis, and so forth. However, the composition and diversity of the gut microbiome can be readily affected by external factors, which raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration, or dysbiosis. Arsenic exposure affects large human populations worldwide and has been linked to a number of diseases, including cancer, diabetes, and cardiovascular disorders. We investigated the impact of arsenic exposure on the gut microbiome composition and its metabolic profiles. We used an integrated approach combining 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling to examine the functional impact of arsenic exposure on the gut microbiome. 16S rRNA gene sequencing revealed that arsenic significantly perturbed the gut microbiome composition in C57BL/6 mice after exposure to 10 ppm arsenic for 4 weeks in drinking water. Moreover, metabolomics profiling revealed a concurrent effect, with a number of gut microflora-related metabolites being perturbed in multiple biological matrices. Arsenic exposure not only alters the gut microbiome community at the abundance level but also substantially disturbs its metabolic profiles at the function level. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism by which arsenic exposure leads to or exacerbates human diseases. Lu K, Abo RP, Schlieper KA, Graffam ME, Levine S, Wishnok JS, Swenberg JA, Tannenbaum SR, Fox JG. 2014. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis. Environ Health Perspect 122:284-291; http://dx.doi.org/10.1289/ehp.1307429.

  20. An integrated catalog of reference genes in the human gut microbiome.

    PubMed

    Li, Junhua; Jia, Huijue; Cai, Xianghang; Zhong, Huanzi; Feng, Qiang; Sunagawa, Shinichi; Arumugam, Manimozhiyan; Kultima, Jens Roat; Prifti, Edi; Nielsen, Trine; Juncker, Agnieszka Sierakowska; Manichanh, Chaysavanh; Chen, Bing; Zhang, Wenwei; Levenez, Florence; Wang, Juan; Xu, Xun; Xiao, Liang; Liang, Suisha; Zhang, Dongya; Zhang, Zhaoxi; Chen, Weineng; Zhao, Hailong; Al-Aama, Jumana Yousuf; Edris, Sherif; Yang, Huanming; Wang, Jian; Hansen, Torben; Nielsen, Henrik Bjørn; Brunak, Søren; Kristiansen, Karsten; Guarner, Francisco; Pedersen, Oluf; Doré, Joel; Ehrlich, S Dusko; Bork, Peer; Wang, Jun

    2014-08-01

    Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease.

  1. Xenobiotics shape the physiology and gene expression of the active human gut microbiome

    PubMed Central

    Maurice, Corinne Ferrier; Haiser, Henry Joseph; Turnbaugh, Peter James

    2012-01-01

    SUMMARY The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider inter-individual variations in the active human gut microbiome. PMID:23332745

  2. Development of the honey bee gut microbiome throughout the queen-rearing process.

    PubMed

    Tarpy, David R; Mattila, Heather R; Newton, Irene L G

    2015-05-01

    The European honey bee (Apis mellifera) is used extensively to produce hive products and for crop pollination, but pervasive concerns about colony health and population decline have sparked an interest in the microbial communities that are associated with these important insects. Currently, only the microbiome of workers has been characterized, while little to nothing is known about the bacterial communities that are associated with queens, even though their health and proper function are central to colony productivity. Here, we provide a large-scale analysis of the gut microbiome of honey bee queens during their developmental trajectory and through the multiple colonies that host them as part of modern queen-rearing practices. We found that queen microbiomes underwent a dramatic shift in size and composition as they aged and encountered different worker populations and colony environments. Queen microbiomes were dominated by enteric bacteria in early life but were comprised primarily of alphaproteobacteria at maturity. Furthermore, queen gut microbiomes did not reflect those of the workers who tended them and, indeed, they lacked many of the bacteria that are considered vital to workers. While worker gut microbiotas were consistent across the unrelated colony populations sampled, the microbiotas of the related queens were highly variable. Bacterial communities in mature queen guts were similar in size to those of mature workers and were characterized by dominant and specific alphaproteobacterial strains known to be associated with worker hypopharyngeal glands. Our results suggest a model in which queen guts are colonized by bacteria from workers' glands, in contrast to routes of maternal inoculation for other animal microbiomes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Mucin glycan foraging in the human gut microbiome

    PubMed Central

    Tailford, Louise E.; Crost, Emmanuelle H.; Kavanaugh, Devon; Juge, Nathalie

    2015-01-01

    The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health. PMID:25852737

  4. Taxonomic and predicted metabolic profiles of the human gut microbiome in pre-Columbian mummies.

    PubMed

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E; Toranzos, Gary A; Marota, Isolina; Cano, Raul J

    2016-11-01

    Characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. We characterized the gut microbiome of two pre-Columbian Andean mummies dating to the 10-15th centuries using 16S rRNA gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century AD pre-Columbian Andean mummy. Our previous study showed that the Clostridiales represented the majority of the bacterial communities in the mummified gut remains, but that other microbial communities were also preserved during the process of natural mummification, as shown with the metagenomics analyses. The gut microbiome of the other two mummies were mainly comprised by Clostridiales or Bacillales, as demonstrated with 16S rRNA gene amplicon sequencing, many of which are facultative anaerobes, possibly consistent with the process of natural mummification requiring low oxygen levels. Metagenome analyses showed the presence of other microbial groups that were positively or negatively correlated with specific metabolic profiles. The presence of sequences similar to both Trypanosoma cruzi and Leishmania donovani could suggest that these pathogens were prevalent in pre-Columbian individuals. Taxonomic and functional profiling of mummified human gut remains will aid in the understanding of the microbial ecology of the process of natural mummification.

  5. Food: a new form of personalised (gut microbiome) medicine for chronic diseases?

    PubMed

    Pallister, Tess; Spector, Tim D

    2016-09-01

    Filling in the knowledge gaps between what we eat and the diseases we develop may lie in our guts, literally. The human large intestine houses the largest reservoir of microorganisms in or on the human body. With a 100-fold greater gene count than humans, the gut microbiome has huge potential to place a large metabolic burden (or advantage) on its host. The number of diverse gut microbial species is diminished in nearly all modern chronic conditions studied. The 'Western diet', rich in animal protein, fats and artificial additives, and lacking in fibre, beneficial microbes, plant phytochemicals, vitamins and minerals, is thought to drive these conditions by encouraging gut dysbiosis. Evidence from recent dietary intervention studies suggest adopting a plant-based, minimally processed high-fibre diet may rapidly reverse the effects of meat-based diets on the gut microbiome. However, recent work has shown that individual diet responses may be complicated by host genetics and the wide variation in the gut microbiome. Now that we measure genes and microbes more accurately, we are embarking on an exciting era of using both food and microbes as potential therapies.

  6. Deciphering interactions between the gut microbiota and the immune system via microbial cultivation and minimal microbiomes.

    PubMed

    Clavel, Thomas; Gomes-Neto, João Carlos; Lagkouvardos, Ilias; Ramer-Tait, Amanda E

    2017-09-01

    The community of microorganisms in the mammalian gastrointestinal tract, referred to as the gut microbiota, influences host physiology and immunity. The last decade of microbiome research has provided significant advancements for the field and highlighted the importance of gut microbes to states of both health and disease. Novel molecular techniques have unraveled the tremendous diversity of intestinal symbionts that potentially influence the host, many proof-of-concept studies have demonstrated causative roles of gut microbial communities in various pathologies, and microbiome-based approaches are beginning to be implemented in the clinic for diagnostic purposes or for personalized treatments. However, several challenges for the field remain: purely descriptive reports outnumbering mechanistic studies and slow translation of experimental results obtained in animal models into the clinics. Moreover, there is a dearth of knowledge regarding how gut microbes, including novel species that have yet to be identified, impact host immune responses. The sheer complexity of the gut microbial ecosystem makes it difficult, in part, to fully understand the microbiota-host networks that regulate immunity. In the present manuscript, we review key findings on the interactions between gut microbiota members and the immune system. Because culturing microbes allows performing functional studies, we have emphasized the impact of specific taxa or communities thereof. We also highlight underlying molecular mechanisms and discuss opportunities to implement minimal microbiome-based strategies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The gut microbiome composition associates with bipolar disorder and illness severity.

    PubMed

    Evans, Simon J; Bassis, Christine M; Hein, Robert; Assari, Shervin; Flowers, Stephanie A; Kelly, Marisa B; Young, Vince B; Ellingrod, Vicky E; McInnis, Melvin G

    2017-04-01

    The gut microbiome is emerging as an important factor in regulating mental health yet it remains unclear what the target should be for psychiatric treatment. We aimed to elucidate the complement of the gut-microbiome community for individuals with bipolar disorder relative to controls; and test for relationships with burden of disease measures. We compared the stool microbiome from individuals with bipolar disorder (n = 115) and control subjects (n = 64) using 16S ribosomal RNA (rRNA) gene sequence analysis. Analysis of molecular variance (AMOVA) revealed global community case-control differences (AMOVA p = 0.047). Operational Taxonomical Unit (OTU) level analysis revealed significantly decreased fractional representation (p < 0.001) of Faecalibacterium after adjustment for age, sex, BMI and false discovery rate (FDR) correction at the p < 0.05 level. Within individuals with bipolar disorder, the fractional representation of Faecalibacterium associated with better self-reported health outcomes based on the Short Form Health Survey (SF12); the Patient Health Questionnaire (PHQ9); the Pittsburg Sleep Quality Index (PSQI); the Generalized Anxiety Disorder scale (GAD7); and the Altman Mania Rating Scale (ASRM), independent of covariates. This study provides the first detailed analysis of the gut microbiome relationships with multiple psychiatric domains from a bipolar population. The data support the hypothesis that targeting the microbiome may be an effective treatment paradigm for bipolar disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. The initial state of the human gut microbiome determines its reshaping by antibiotics.

    PubMed

    Raymond, Frédéric; Ouameur, Amin A; Déraspe, Maxime; Iqbal, Naeem; Gingras, Hélène; Dridi, Bédis; Leprohon, Philippe; Plante, Pier-Luc; Giroux, Richard; Bérubé, Ève; Frenette, Johanne; Boudreau, Dominique K; Simard, Jean-Luc; Chabot, Isabelle; Domingo, Marc-Christian; Trottier, Sylvie; Boissinot, Maurice; Huletsky, Ann; Roy, Paul H; Ouellette, Marc; Bergeron, Michel G; Corbeil, Jacques

    2016-03-01

    Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments.

  9. The initial state of the human gut microbiome determines its reshaping by antibiotics

    PubMed Central

    Raymond, Frédéric; Ouameur, Amin A; Déraspe, Maxime; Iqbal, Naeem; Gingras, Hélène; Dridi, Bédis; Leprohon, Philippe; Plante, Pier-Luc; Giroux, Richard; Bérubé, Ève; Frenette, Johanne; Boudreau, Dominique K; Simard, Jean-Luc; Chabot, Isabelle; Domingo, Marc-Christian; Trottier, Sylvie; Boissinot, Maurice; Huletsky, Ann; Roy, Paul H; Ouellette, Marc; Bergeron, Michel G; Corbeil, Jacques

    2016-01-01

    Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments. PMID:26359913

  10. Microbiome as mediator: Do systemic infections start in the gut?

    PubMed

    Latorre, Melissa; Krishnareddy, Suneeta; Freedberg, Daniel E

    2015-10-07

    The intestinal microbiome is emerging as a crucial mediator between external insults and systemic infections. New research suggests that our intestinal microorganisms contribute to critical illness and the development of non-gastrointestinal infectious diseases. Common pathways include a loss of fecal intestinal bacterial diversity and a disproportionate increase in toxogenic bacterial species. Therapeutic interventions targeting the microbiome - primarily probiotics - have yielded limited results to date. However, knowledge in this area is rapidly expanding and microbiome-based therapy such as short-chain fatty acids may eventually become a standard strategy for preventing systemic infections in the context of critical illness.

  11. Microbiome as mediator: Do systemic infections start in the gut?

    PubMed Central

    Latorre, Melissa; Krishnareddy, Suneeta; Freedberg, Daniel E

    2015-01-01

    The intestinal microbiome is emerging as a crucial mediator between external insults and systemic infections. New research suggests that our intestinal microorganisms contribute to critical illness and the development of non-gastrointestinal infectious diseases. Common pathways include a loss of fecal intestinal bacterial diversity and a disproportionate increase in toxogenic bacterial species. Therapeutic interventions targeting the microbiome - primarily probiotics - have yielded limited results to date. However, knowledge in this area is rapidly expanding and microbiome-based therapy such as short-chain fatty acids may eventually become a standard strategy for preventing systemic infections in the context of critical illness. PMID:26457009

  12. Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease.

    PubMed

    Cabrera-Perez, Javier; Badovinac, Vladimir P; Griffith, Thomas S

    2017-01-01

    Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis.

  13. Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease

    PubMed Central

    Cabrera-Perez, Javier; Badovinac, Vladimir P

    2016-01-01

    Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis. PMID:27633573

  14. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome.

    PubMed

    Fujimura, Kei E; Lynch, Susan V

    2015-05-13

    Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature.

  15. Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome

    PubMed Central

    Fujimura, Kei E.; Lynch, Susan V.

    2015-01-01

    Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are amongst the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut and environmental microbiomes in asthma and allergic disease development, manifestation and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature. PMID:25974301

  16. Spatial structure of the Mormon cricket gut microbiome and its predicted contribution to nutrition and immune function

    USDA-ARS?s Scientific Manuscript database

    The gut microbiome of insects plays an important role in their ecology and evolution, participating in nutrient acquisition, immunity, and behavior. Microbial community structure within the gut is heavily influenced by differences among gut regions in morphology and physiology, which determine the n...

  17. Gut microbiome in ADHD and its relation to neural reward anticipation.

    PubMed

    Aarts, Esther; Ederveen, Thomas H A; Naaijen, Jilly; Zwiers, Marcel P; Boekhorst, Jos; Timmerman, Harro M; Smeekens, Sanne P; Netea, Mihai G; Buitelaar, Jan K; Franke, Barbara; van Hijum, Sacha A F T; Arias Vasquez, Alejandro

    2017-01-01

    Microorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing. We used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis. For the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age. Our results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses

  18. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

    PubMed Central

    Fu, Jingyuan; Bonder, Marc Jan; Cenit, María Carmen; Tigchelaar, Ettje F.; Maatman, Astrid; Dekens, Jackie A.M.; Brandsma, Eelke; Marczynska, Joanna; Imhann, Floris; Weersma, Rinse K.; Franke, Lude; Poon, Tiffany W.; Xavier, Ramnik J.; Gevers, Dirk; Hofker, Marten H.; Wijmenga, Cisca; Zhernakova, Alexandra

    2015-01-01

    Rationale: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host–microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. Objectives: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins. PMID:26358192

  19. Alterations in the gut microbiome of children with severe ulcerative colitis

    PubMed Central

    Michail, Sonia; Durbin, Matthew; Turner, Dan; Griffiths, Anne M; Mack, David R.; Hyams, Jeffrey; Leleiko, Neal; Kenche, Harshavardhan; Stolfi, Adrienne; Wine, Eytan

    2011-01-01

    Background Although the role of microbes in disease pathogenesis is well established, data describing the variability of the vast microbiome in children diagnosed with ulcerative colitis (UC) are lacking. This study characterizes the gut microbiome in hospitalized children with severe UC and determines the relationship between microbiota and response to steroid therapy. Methods Fecal samples were collected from 26 healthy controls and 27 children hospitalized with severe UC as part of a prospective multi-center study. DNA extraction, PCR amplification of bacterial 16S rRNA, and microarray hybridization were performed. Results were analyzed in Genespring GX 11.0 comparing healthy controls to children with UC, and steroid responsive (n=17) to non-responsive patients (n=10). Results Bacterial signal strength and distribution showed differences between UC and healthy controls (adjusted p<0.05) for Phylum, Class, Order, Family, Genus, and Phylospecies levels with reduction in Clostridia and an increase in Gamma-proteobacteria. The number of microbial phylospecies was reduced in UC (266±69) vs. controls (758±3, p<0.001), as was the Shannon diversity index (6.1±0.23 vs. 6.49±0.04, respectively; p<0.0001). Steroids non-responders harbored less phylospecies than responders (142±49 vs. 338±62, p=0.013). Conclusions Richness, evenness, and biodiversity of the gut microbiome were remarkably reduced in children with UC, compared to healthy controls. Children who did not respond to steroids harbored a microbiome that was even less rich than steroid responders. This study is the first to characterize the gut microbiome in a large cohort of pediatric patients with severe ulcerative colitis and describes changes in the gut microbiome as a potential prognostic feature. PMID:22170749

  20. Gut Microbiome and the Development of Food Allergy and Allergic Disease

    PubMed Central

    Prince, Benjamin T.; Mandel, Mark J.; Nadeau, Kari; Singh, Anne Marie

    2015-01-01

    The prevalence of food allergy and other allergic diseases continues to rise within the industrialized world, yet the cause of this epidemic remains elusive. Environmental factors such as microbial exposures have more recently been implicated as one possible driving factor behind the increasing burden of allergic disease. The impact of gut microbiome on human development, nutritional needs, and disease has become evident with advances in our ability to study these complex communities of microorganisms, and there is a growing appreciation for the role of the microbiome in immune regulation. Several studies have examined associations between changes in the commensal microbiota and the development of asthma, allergic rhinitis, and asthma, but far less have evaluated the impact of the microbiome on the development of food allergy. In this article we review the human gastrointestinal microbiome, focusing on the theory and evidence for its role in the development of IgE-mediated food allergy and other allergic diseases. PMID:26456445

  1. Improved Glucose Homeostasis in Obese Mice Treated With Resveratrol Is Associated With Alterations in the Gut Microbiome.

    PubMed

    Sung, Miranda M; Kim, Ty T; Denou, Emmanuel; Soltys, Carrie-Lynn M; Hamza, Shereen M; Byrne, Nikole J; Masson, Grant; Park, Heekuk; Wishart, David S; Madsen, Karen L; Schertzer, Jonathan D; Dyck, Jason R B

    2017-02-01

    Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol. © 2017 by the American Diabetes Association.

  2. Metabolic tinkering by the gut microbiome: Implications for brain development and function.

    PubMed

    Selkrig, Joel; Wong, Peiyan; Zhang, Xiaodong; Pettersson, Sven

    2014-01-01

    Brain development is an energy demanding process that relies heavily upon diet derived nutrients. Gut microbiota enhance the host's ability to extract otherwise inaccessible energy from the diet via fermentation of complex oligosaccharides in the colon. This nutrient yield is estimated to contribute up to 10% of the host's daily caloric requirement in humans and fluctuates in response to environmental variations. Research over the past decade has demonstrated a surprising role for the gut microbiome in normal brain development and function. In this review we postulate that perturbations in the gut microbial-derived nutrient supply, driven by environmental variation, profoundly impacts upon normal brain development and function.

  3. Modeling the Context-Dependent Associations between the Gut Microbiome, Its Environment, and Host Health.

    PubMed

    Sharpton, Thomas J; Gaulke, Christopher A

    2015-09-08

    Changes in the gut microbiome are often associated with disease. One of the major goals in microbiome research is determining which components of this complex system are responsible for the observed differences in health state. Most studies apply a reductionist approach, wherein individual organisms are evaluated independently of the surrounding context of the microbiome. While such methods have yielded valuable insights into the microbiome, they fail to identify patterns that may be obscured by contextual variation. A recent report by Schubert et al. [A. M. Schubert, H. Sinani, and P. D. Schloss, mBio 6(4):e00974-15, 2015, doi: 10.1128/mBio.00974-15] communicates an alternative approach to the study of the microbiome's association with host health. By coupling a multifactored experimental design with regression modeling, the authors are able to profile context-dependent changes in the microbiome and predict health status. This work underscores the value of incorporating model-based procedures into the investigation of the microbiome and illustrates the potential clinical transformations that may arise through their use.

  4. The Gut Microbiome, Energy Homeostasis, and Implications for Hypertension.

    PubMed

    Riedl, Ruth A; Atkinson, Samantha N; Burnett, Colin M L; Grobe, Justin L; Kirby, John R

    2017-04-01

    The influence of gut bacteria upon host physiology is increasingly recognized, but mechanistic links are lacking. Diseases of energetic imbalance such as obesity and diabetes represent major risk factors for cardiovascular diseases such as hypertension. Thus, here, we review current mechanistic contributions of the gut microbiota to host energetics. Gut bacteria generate a multitude of small molecules which can signal to host tissues within and beyond the gastrointestinal tract to influence host physiology, and gut bacteria can also influence host digestive efficiency by altering the bioavailability of polysaccharides, yet the quantitative energetic effects of these processes remain unclear. Recently, our team has demonstrated that gut bacteria constitute a major anaerobic thermogenic biomass, which can quantitatively account for obesity. Quantitative understanding of the mechanisms by which gut bacteria influence energy homeostasis may ultimately inform the relationship between gut bacteria and cardiovascular dysfunction.

  5. Gut to Brain Dysbiosis: Mechanisms Linking Western Diet Consumption, the Microbiome, and Cognitive Impairment

    PubMed Central

    Noble, Emily E.; Hsu, Ted M.; Kanoski, Scott E.

    2017-01-01

    Consumption of a Western Diet (WD) that is high in saturated fat and added sugars negatively impacts cognitive function, particularly mnemonic processes that rely on the integrity of the hippocampus. Emerging evidence suggests that the gut microbiome influences cognitive function via the gut-brain axis, and that WD factors significantly alter the proportions of commensal bacteria in the gastrointestinal tract. Here we review mechanisms through which consuming a WD negatively impacts neurocognitive function, with a particular focus on recent evidence linking the gut microbiome with dietary- and metabolic-associated hippocampal impairment. We highlight evidence linking gut bacteria to altered intestinal permeability and blood brain barrier integrity, thus making the brain more vulnerable to the influx of deleterious substances from the circulation. WD consumption also increases production of endotoxin by commensal bacteria, which may promote neuroinflammation and cognitive dysfunction. Recent findings also show that diet-induced alterations in gut microbiota impair peripheral insulin sensitivity, which is associated with hippocampal neuronal derrangements and associated mnemonic deficits. In some cases treatment with specific probiotics or prebiotics can prevent or reverse some of the deleterious impact of WD consumption on neuropsychological outcomes, indicating that targeting the microbiome may be a successful strategy for combating dietary- and metabolic-associated cognitive impairment. PMID:28194099

  6. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

    PubMed Central

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan ET; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-01-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet−/− Rag2−/− mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  7. Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis

    PubMed Central

    Liu, Wenjun; Zhang, Jiachao; Wu, Chunyan; Cai, Shunfeng; Huang, Weiqiang; Chen, Jing; XI, Xiaoxia; Liang, Zebin; Hou, Qiangchuan; Zhou, Bing; Qin, Nan; Zhang, Heping

    2016-01-01

    The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian’s gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment. PMID:27708392

  8. Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis.

    PubMed

    Liu, Wenjun; Zhang, Jiachao; Wu, Chunyan; Cai, Shunfeng; Huang, Weiqiang; Chen, Jing; Xi, Xiaoxia; Liang, Zebin; Hou, Qiangchuan; Zhou, Bing; Qin, Nan; Zhang, Heping

    2016-10-06

    The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian's gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment.

  9. Edible Plants and Their Influence on the Gut Microbiome and Acne

    PubMed Central

    Clark, Ashley K.; Haas, Kelly N.; Sivamani, Raja K.

    2017-01-01

    Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development. PMID:28513546

  10. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome.

    PubMed

    Snijders, Antoine M; Langley, Sasha A; Kim, Young-Mo; Brislawn, Colin J; Noecker, Cecilia; Zink, Erika M; Fansler, Sarah J; Casey, Cameron P; Miller, Darla R; Huang, Yurong; Karpen, Gary H; Celniker, Susan E; Brown, James B; Borenstein, Elhanan; Jansson, Janet K; Metz, Thomas O; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease(1), we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut. We used the genetically diverse Collaborative Cross mouse system(2) to discover that early life history impacts the microbiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  11. Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

    PubMed

    Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

    2017-04-14

    The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p<0.05) and beta (p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (p<0.001), Dorea (p<0.01), and Coprococcus (p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress.

  12. Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice.

    PubMed

    Bian, Xiaoming; Chi, Liang; Gao, Bei; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-01-01

    Sucralose is the most widely used artificial sweetener, and its health effects have been highly debated over the years. In particular, previous studies have shown that sucralose consumption can alter the gut microbiota. The gut microbiome plays a key role in processes related to host health, such as food digestion and fermentation, immune cell development, and enteric nervous system regulation. Inflammation is one of the most common effects associated with gut microbiome dysbiosis, which has been linked to a series of human diseases, such as diabetes and obesity. The aim of this study was to investigate the structural and functional effects of sucralose on the gut microbiota and associated inflammation in the host. In this study, C57BL/6 male mice received sucralose in their drinking water for 6 months. The difference in gut microbiota composition and metabolites between control and sucralose-treated mice was determined using 16S rRNA gene sequencing, functional gene enrichment analysis and metabolomics. Inflammatory gene expression in tissues was analyzed by RT-PCR. Alterations in bacterial genera showed that sucralose affects the gut microbiota and its developmental dynamics. Enrichment of bacterial pro-inflammatory genes and disruption in fecal metabolites suggest that 6-month sucralose consumption at the human acceptable daily intake (ADI) may increase the risk of developing tissue inflammation by disrupting the gut microbiota, which is supported by elevated pro-inflammatory gene expression in the liver of sucralose-treated mice. Our results highlight the role of sucralose-gut microbiome interaction in regulating host health-related processes, particularly chronic inflammation.

  13. Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome.

    PubMed

    Hoffman, Jared D; Parikh, Ishita; Green, Stefan J; Chlipala, George; Mohney, Robert P; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M S; Lin, Ai-Ling

    2017-01-01

    Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the

  14. Effects of Host Phylogeny and Habitats on Gut Microbiomes of Oriental River Prawn (Macrobrachium nipponense).

    PubMed

    Tzeng, Tzong-Der; Pao, Yueh-Yang; Chen, Po-Cheng; Weng, Francis Cheng-Hsuan; Jean, Wen Dar; Wang, Daryi

    2015-01-01

    The gut microbial community is one of the richest and most complex ecosystems on earth, and the intestinal microbes play an important role in host development and health. Next generation sequencing approaches, which rapidly produce millions of short reads that enable the investigation on a culture independent basis, are now popular for exploring microbial community. Currently, the gut microbiome in fresh water shrimp is unexplored. To explore gut microbiomes of the oriental river prawn (Macrobrachium nipponense) and investigate the effects of host genetics and habitats on the microbial composition, 454 pyrosequencing based on the 16S rRNA gene were performed. We collected six groups of samples, including M. nipponense shrimp from two populations, rivers and lakes, and one sister species (M. asperulum) as an out group. We found that Proteobacteria is the major phylum in oriental river prawn, followed by Firmicutes and Actinobacteria. Compositional analysis showed microbial divergence between the two shrimp species is higher than that between the two populations of one shrimp species collected from river and lake. Hierarchical clustering also showed that host genetics had a greater impact on the divergence of gut microbiome than host habitats. This finding was also congruent with the functional prediction from the metagenomic data implying that the two shrimp species still shared the same type of biological functions, reflecting a similar metabolic profile in their gut environments. In conclusion, this study provides the first investigation of the gut microbiome of fresh water shrimp, and supports the hypothesis of host species-specific signatures of bacterial community composition.

  15. Effects of Host Phylogeny and Habitats on Gut Microbiomes of Oriental River Prawn (Macrobrachium nipponense)

    PubMed Central

    Chen, Po-Cheng; Weng, Francis Cheng-Hsuan; Jean, Wen Dar; Wang, Daryi

    2015-01-01

    The gut microbial community is one of the richest and most complex ecosystems on earth, and the intestinal microbes play an important role in host development and health. Next generation sequencing approaches, which rapidly produce millions of short reads that enable the investigation on a culture independent basis, are now popular for exploring microbial community. Currently, the gut microbiome in fresh water shrimp is unexplored. To explore gut microbiomes of the oriental river prawn (Macrobrachium nipponense) and investigate the effects of host genetics and habitats on the microbial composition, 454 pyrosequencing based on the 16S rRNA gene were performed. We collected six groups of samples, including M. nipponense shrimp from two populations, rivers and lakes, and one sister species (M. asperulum) as an out group. We found that Proteobacteria is the major phylum in oriental river prawn, followed by Firmicutes and Actinobacteria. Compositional analysis showed microbial divergence between the two shrimp species is higher than that between the two populations of one shrimp species collected from river and lake. Hierarchical clustering also showed that host genetics had a greater impact on the divergence of gut microbiome than host habitats. This finding was also congruent with the functional prediction from the metagenomic data implying that the two shrimp species still shared the same type of biological functions, reflecting a similar metabolic profile in their gut environments. In conclusion, this study provides the first investigation of the gut microbiome of fresh water shrimp, and supports the hypothesis of host species-specific signatures of bacterial community composition. PMID:26168244

  16. 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...

  17. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances.

    PubMed

    Francino, M P

    2015-01-01

    The human microbiome is overly exposed to antibiotics, due, not only to their medical use, but also to their utilization in farm animals and crops. Microbiome composition can be rapidly altered by exposure to antibiotics, with potential immediate effects on health, for instance through the selection of resistant opportunistic pathogens that can cause acute disease. Microbiome alterations induced by antibiotics can also indirectly affect health in the long-term. The mutualistic microbes in the human body interact with many physiological processes, and participate in the regulation of immune and metabolic homeostasis. Therefore, antibiotic exposure can alter many basic physiological equilibria, promoting long-term disease. In addition, excessive antibiotic use fosters bacterial resistance, and the overly exposed human microbiome has become a significant reservoir of resistance genes, contributing to the increasing difficulty in controlling bacterial infections. Here, the complex relationships between antibiotics and the human microbiome are reviewed, with focus on the intestinal microbiota, addressing (1) the effects of antibiotic use on the composition and function of the gut microbiota, (2) the impact of antibiotic-induced microbiota alterations on immunity, metabolism, and health, and (3) the role of the gut microbiota as a reservoir of antibiotic resistances.

  18. A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter.

    PubMed

    Finucane, Mariel M; Sharpton, Thomas J; Laurent, Timothy J; Pollard, Katherine S

    2014-01-01

    Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic target. However, human and animal-model studies have yielded conflicting results about the precise nature of associations between microbiome composition and obesity. In this paper, we use publicly available data from the Human Microbiome Project (HMP) and MetaHIT, both surveys of healthy adults that include obese individuals, plus two smaller studies that specifically examined lean versus obese adults. We find that inter-study variability in the taxonomic composition of stool microbiomes far exceeds differences between lean and obese individuals within studies. Our analyses further reveal a high degree of variability in stool microbiome composition and diversity across individuals. While we confirm the previously published small, but statistically significant, differences in phylum-level taxonomic composition between lean and obese individuals in several cohorts, we find no association between BMI and taxonomic composition of stool microbiomes in the larger HMP and MetaHIT datasets. We explore a range of different statistical techniques and show that this result is robust to the choice of methodology. Differences between studies are likely due to a combination of technical and clinical factors. We conclude that there is no simple taxonomic signature of obesity in the microbiota of the human gut.

  19. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances

    PubMed Central

    Francino, M. P.

    2016-01-01

    The human microbiome is overly exposed to antibiotics, due, not only to their medical use, but also to their utilization in farm animals and crops. Microbiome composition can be rapidly altered by exposure to antibiotics, with potential immediate effects on health, for instance through the selection of resistant opportunistic pathogens that can cause acute disease. Microbiome alterations induced by antibiotics can also indirectly affect health in the long-term. The mutualistic microbes in the human body interact with many physiological processes, and participate in the regulation of immune and metabolic homeostasis. Therefore, antibiotic exposure can alter many basic physiological equilibria, promoting long-term disease. In addition, excessive antibiotic use fosters bacterial resistance, and the overly exposed human microbiome has become a significant reservoir of resistance genes, contributing to the increasing difficulty in controlling bacterial infections. Here, the complex relationships between antibiotics and the human microbiome are reviewed, with focus on the intestinal microbiota, addressing (1) the effects of antibiotic use on the composition and function of the gut microbiota, (2) the impact of antibiotic-induced microbiota alterations on immunity, metabolism, and health, and (3) the role of the gut microbiota as a reservoir of antibiotic resistances. PMID:26793178

  20. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster

    PubMed Central

    Krogsdam, Anne; Orth-Höller, Dorothea; Trajanoski, Zlatko; Lusser, Alexandra

    2016-01-01

    The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster. PMID:27093431

  1. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster.

    PubMed

    Sebald, Johanna; Willi, Michaela; Schoberleitner, Ines; Krogsdam, Anne; Orth-Höller, Dorothea; Trajanoski, Zlatko; Lusser, Alexandra

    2016-01-01

    The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster.

  2. High-fat diet determines the composition of the murine gut microbiome independently of obesity.

    PubMed

    Hildebrandt, Marie A; Hoffmann, Christian; Sherrill-Mix, Scott A; Keilbaugh, Sue A; Hamady, Micah; Chen, Ying-Yu; Knight, Rob; Ahima, Rexford S; Bushman, Frederic; Wu, Gary D

    2009-11-01

    The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMbeta knockout (KO) mice to assess the influence of these factors. Both wild-type and RELMbeta KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMbeta KO mice remained comparatively lean. To investigate the influence of diet, genotype, and obesity on microbiome composition, we used deep sequencing to characterize 25,790 16S rDNA sequences from uncultured bacterial communities from both genotypes on both diets. We found large alterations associated with switching to the high-fat diet, including a decrease in Bacteroidetes and an increase in both Firmicutes and Proteobacteria. This was seen for both genotypes (ie, in the presence and absence of obesity), indicating that the high-fat diet itself, and not the obese state, mainly accounted for the observed changes in the gut microbiota. The RELMbeta genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content because of a high-fat diet, including an increase in transporters and 2-component sensor responders as well as a general decrease in metabolic genes. Unexpectedly, we found a substantial amount of murine DNA in our samples that increased in proportion on a high-fat diet. These results demonstrate the importance of diet as a determinant of gut microbiome composition and suggest the need to control for dietary variation when evaluating the composition of the human gut microbiome.

  3. Does our gut microbiome predict cardiovascular risk? A review of the evidence from metabolomics.

    PubMed

    Griffin, Julian L; Wang, Xinzhu; Stanley, Elizabeth

    2015-02-01

    Millions of microbes are found in the human gut, and are collectively referred as the gut microbiota. Recent studies have estimated that the microbiota genome contains 100-fold more genes than the host genome. These microbiota contribute to digestion by processing energy substrates unutilized by the host, with about half of the total genome of the gut microbiota being related to central carbon and amino acid metabolism as well as the biosynthesis of secondary metabolites. Therefore, the gut microbiome and its interaction with the host influences many aspects of health and disease, including the composition of biofluids such as urine and blood plasma. Metabolomics is uniquely suited to capture these functional host-microbe interactions. This review aims at providing an overview of recent metabolomics evidence of gut microbiota-host metabolic interactions with a specific focus on cardiovascular disease and related aspects of the metabolic syndrome. Furthermore, the emphasis is given on the complexities of translating these metabolite signatures as potential clinical biomarkers, as the composition and activity of gut microbiome change with many factors, particularly with diet, with special reference to trimethylamine-oxide.

  4. Does Our Gut Microbiome Predict Cardiovascular Risk? A Review of the Evidence from Metabolomics

    PubMed Central

    Griffin, Julian L.; Wang, Xinzhu; Stanley, Elizabeth

    2014-01-01

    Millions of microbes are found in the human gut, and are collectively referred as the gut microbiota. Recent studies have estimated that the microbiota genome contains 100-fold more genes than the host genome. These microbiota contribute to digestion by processing energy substrates unutilized by the host, with about half of the total genome of the gut microbiota being related to central carbon and amino acid metabolism as well as the biosynthesis of secondary metabolites. Therefore, the gut microbiome and its interaction with the host influences many aspects of health and disease, including influencing the composition of biofluids such as urine and blood plasma. Metabolomics is uniquely suited to capture these functional host-microbe interactions. This review aims at providing an overview of recent metabolomics evidence of gut microbiota-host metabolic interactions with a specific focus on cardiovascular disease and related aspects of the metabolic syndrome. Furthermore, the emphasis is given on the complexities of translating these metabolite signatures as potential clinical biomarkers, as the composition and activity of gut microbiome change with many factors, particularly with diet with special reference to trimethylamine-oxide. PMID:25691688

  5. The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management.

    PubMed

    Flowers, Stephanie A; Ellingrod, Vicki L

    2015-10-01

    The gut microbiome is composed of ~10(13) -10(14) microbial cells and viruses that exist in a symbiotic bidirectional communicative relationship with the host. Bacterial functions in the gut have an important role in healthy host metabolic function, and dysbiosis can contribute to the pathology of many medical conditions. Alterations in the relationship between gut microbiota and host have gained some attention in mental health because new evidence supports the association of gut bacteria to cognitive and emotional processes. Of interest, illnesses such as major depressive disorder are disproportionately prevalent in patients with gastrointestinal illnesses such as inflammatory bowel disease, which pathologically has been strongly linked to microbiome function. Not only is the microbiome associated with the disease itself, but it may also influence the effectiveness or adverse effects associated with pharmacologic agents used to treat these disorders. This field of study may also provide new insights on how dietary agents may help manage mental illness both directly as well as though their influence on the therapeutic and adverse effects of psychotropic agents. © 2015 Pharmacotherapy Publications, Inc.

  6. 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

  7. 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

  8. The Gut Microbiome, Kidney Disease, and Targeted Interventions

    PubMed Central

    Ramezani, Ali

    2014-01-01

    The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms. PMID:24231662

  9. The gut microbiome, kidney disease, and targeted interventions.

    PubMed

    Ramezani, Ali; Raj, Dominic S

    2014-04-01

    The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms.

  10. Development and Validation of a Microarray for the Investigation of the CAZymes Encoded by the Human Gut Microbiome

    PubMed Central

    Leroy, Quentin; Vialettes, Bernard; Million, Matthieu; Raoult, Didier; Henrissat, Bernard

    2013-01-01

    Distal gut bacteria play a pivotal role in the digestion of dietary polysaccharides by producing a large number of carbohydrate-active enzymes (CAZymes) that the host otherwise does not produce. We report here the design of a custom microarray that we used to spot non-redundant DNA probes for more than 6,500 genes encoding glycoside hydrolases and lyases selected from 174 reference genomes from distal gut bacteria. The custom microarray was tested and validated by the hybridization of bacterial DNA extracted from the stool samples of lean, obese and anorexic individuals. Our results suggest that a microarray-based study can detect genes from low-abundance bacteria better than metagenomic-based studies. A striking example was the finding that a gene encoding a GH6-family cellulase was present in all subjects examined, whereas metagenomic studies have consistently failed to detect this gene in both human and animal gut microbiomes. In addition, an examination of eight stool samples allowed the identification of a corresponding CAZome core containing 46 families of glycoside hydrolases and polysaccharide lyases, which suggests the functional stability of the gut microbiota despite large taxonomical variations between individuals. PMID:24391873

  11. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

    PubMed

    Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

  12. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

    PubMed Central

    Xu, Wanli; Janton, Susan; Henderson, Wendy A.; Matson, Adam; McGrath, Jacqueline M.; Maas, Kendra; Graf, Joerg

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

  13. 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.

  14. Intersections Between Microbiome and Heart Failure: Revisiting the Gut Hypothesis.

    PubMed

    Nagatomo, Yuji; Tang, W H Wilson

    2015-12-01

    Microbes play an important role in human health and disease. In the setting of heart failure (HF), substantial hemodynamic changes, such as hypoperfusion and congestion in the intestines, can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota. These changes can disrupt the barrier function of the intestines and exacerbate systemic inflammation via microbial or endotoxin translocation into systemic circulation. Furthermore, cardiorenal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine N-oxide (TMAO) has emerged as a key mediator that provides a mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF. Potential intervention strategies which may target this microbiota-driven pathology include dietary modification, prebiotics/probiotics, and selective binders of microbial enzymes or molecules, but further investigations into their safety and efficacy are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The intestinal microbiome and the leaky gut as therapeutic targets in alcoholic liver disease.

    PubMed

    Hartmann, Phillipp; Chen, Wei-Chung; Schnabl, Bernd

    2012-01-01

    Alcoholic liver disease (ALD) encompasses hepatic steatosis, which may progress to alcoholic hepatitis, fibrosis, and cirrhosis. It remains a leading cause of morbidity and mortality in the US and worldwide. The severity of liver disease correlates with plasma levels of bacterial products in patients, and experimental ALD depends on the level of gut derived bacterial products in rodents. Since intestinal decontamination and deficiency of bacterial product receptors or their downstream signaling molecules protect from alcohol-induced liver disease, bacterial translocation (BT), qualitative, and quantitative changes of the enteric microbiome are considered as being of fundamental importance in the pathogenesis of ALD. Recent enhancements in diagnostic technologies provide a better insight into these shifts. This review highlights vital events in ALD such as BT, the importance of Toll-like receptor (TLR) signaling, intestinal bacterial overgrowth (IBO), and changes in the intestinal microbiome. Furthermore, a treatment trial section of patients reviews possible future options of therapy for ALD modifying the enteric microbiome.

  16. Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties.

    PubMed

    Guss, Jason D; Horsfield, Michael W; Fontenele, Fernanda F; Sandoval, Taylor N; Luna, Marysol; Apoorva, Fnu; Lima, Svetlana F; Bicalho, Rodrigo C; Singh, Ankur; Ley, Ruth E; van der Meulen, Marjolein Ch; Goldring, Steven R; Hernandez, Christopher J

    2017-02-27

    Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll-like receptor 5-deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross-sectional geometry, implicating impaired bone tissue material properties. Small differences in whole-bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole-bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.

  17. Role of the Gut Microbiome in Obesity and Diabetes Mellitus.

    PubMed

    Barlow, Gillian M; Yu, Allen; Mathur, Ruchi

    2015-12-01

    Type 2 diabetes mellitus (T2DM) and obesity represent two of the biggest global health challenges of this century and are associated with significant comorbidities and healthcare costs. Although multiple factors undoubtedly contribute to the development and progression of DM and obesity, research over the last decade has demonstrated that the microbes that colonize the human gut may play key contributory roles. Gut microbes are now known to codevelop with the human host and are strongly influenced by mode of birth and early diet and nutrition, as well as environmental and other factors including antibiotic exposure. Gut microbes contribute to human health through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses, gut permeability, and bile acid modification. Numerous studies have suggested that disruptions in the relative proportions of gut microbial populations may contribute to weight gain and insulin resistance, including alterations in Gammaproteobacteria and Verrucomicrobia and the ratios of Firmicutes to Bacteroidetes in weight gain and possible alterations in butyrate-producing bacteria such as Faecalibacterium prausnitzii in DM. In addition, it has been shown that the methanogenic Archaea may contribute to altered metabolism and weight gain in the host. However, the majority of studies are performed with stool or colonic samples and may not be representative of the metabolically active small intestine. Studies predominantly in rodent models are beginning to elucidate the mechanisms by which gut microbes contribute to DM and obesity, but much remains to be learned before we can begin to approach targeted treatments.

  18. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans.

    PubMed

    Muegge, Brian D; Kuczynski, Justin; Knights, Dan; Clemente, Jose C; González, Antonio; Fontana, Luigi; Henrissat, Bernard; Knight, Rob; Gordon, Jeffrey I

    2011-05-20

    Coevolution of mammals and their gut microbiota has profoundly affected their radiation into myriad habitats. We used shotgun sequencing of microbial community DNA and targeted sequencing of bacterial 16S ribosomal RNA genes to gain an understanding of how microbial communities adapt to extremes of diet. We sampled fecal DNA from 33 mammalian species and 18 humans who kept detailed diet records, and we found that the adaptation of the microbiota to diet is similar across different mammalian lineages. Functional repertoires of microbiome genes, such as those encoding carbohydrate-active enzymes and proteases, can be predicted from bacterial species assemblages. These results illustrate the value of characterizing vertebrate gut microbiomes to understand host evolutionary histories at a supraorganismal level.

  19. Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome.

    PubMed

    Casero, David; Gill, Kirandeep; Sridharan, Vijayalakshmi; Koturbash, Igor; Nelson, Gregory; Hauer-Jensen, Martin; Boerma, Marjan; Braun, Jonathan; Cheema, Amrita K

    2017-08-18

    Space travel is associated with continuous low dose rate exposure to high linear energy transfer (LET) radiation. Pathophysiological manifestations after low dose radiation exposure are strongly influenced by non-cytocidal radiation effects, including changes in the microbiome and host gene expression. Although the importance of the gut microbiome in the maintenance of human health is well established, little is known about the role of radiation in altering the microbiome during deep-space travel. Using a mouse model for exposure to high LET radiation, we observed substantial changes in the composition and functional potential of the gut microbiome. These were accompanied by changes in the abundance of multiple metabolites, which were related to the enzymatic activity of the predicted metagenome by means of metabolic network modeling. There was a complex dynamic in microbial and metabolic composition at different radiation doses, suggestive of transient, dose-dependent interactions between microbial ecology and signals from the host's cellular damage repair processes. The observed radiation-induced changes in microbiota diversity and composition were analyzed at the functional level. A constitutive change in activity was found for several pathways dominated by microbiome-specific enzymatic reactions like carbohydrate digestion and absorption and lipopolysaccharide biosynthesis, while the activity in other radiation-responsive pathways like phosphatidylinositol signaling could be linked to dose-dependent changes in the abundance of specific taxa. The implication of microbiome-mediated pathophysiology after low dose ionizing radiation may be an unappreciated biologic hazard of space travel and deserves experimental validation. This study provides a conceptual and analytical basis of further investigations to increase our understanding of the chronic effects of space radiation on human health, and points to potential new targets for intervention in adverse radiation

  20. Altered microbiomes in bovine digital dermatitis lesions, and the gut as a pathogen reservoir.

    PubMed

    Zinicola, Martin; Lima, Fabio; Lima, Svetlana; Machado, Vinicius; Gomez, Marilia; Döpfer, Dörte; Guard, Charles; Bicalho, Rodrigo

    2015-01-01

    Bovine digital dermatitis (DD) is the most important infectious disease associated with lameness in cattle worldwide. Since the disease was first described in 1974, a series of Treponema species concurrent with other microbes have been identified in DD lesions, suggesting a polymicrobial etiology. However, the pathogenesis of DD and the source of the causative microbes remain unclear. Here we characterized the microbiomes of healthy skin and skin lesions in dairy cows affected with different stages of DD and investigated the gut microbiome as a potential reservoir for microbes associated with this disease. Discriminant analysis revealed that the microbiomes of healthy skin, active DD lesions (ulcerative and chronic ulcerative) and inactive DD lesions (healing and chronic proliferative) are completely distinct. Treponema denticola, Treponema maltophilum, Treponema medium, Treponema putidum, Treponema phagedenis and Treponema paraluiscuniculi were all found to be present in greater relative abundance in active DD lesions when compared with healthy skin and inactive DD lesions, and these same Treponema species were nearly ubiquitously present in rumen and fecal microbiomes. The relative abundance of Candidatus Amoebophilus asiaticus, a bacterium not previously reported in DD lesions, was increased in both active and inactive lesions when compared with healthy skin. In conclusion, our data support the concept that DD is a polymicrobial disease, with active DD lesions having a markedly distinct microbiome dominated by T. denticola, T. maltophilum, T. medium, T. putidum, T. phagedenis and T. paraluiscuniculi. Furthermore, these Treponema species are nearly ubiquitously found in rumen and fecal microbiomes, suggesting that the gut is an important reservoir of microbes involved in DD pathogenesis. Additionally, the bacterium Candidatus Amoebophilus asiaticus was highly abundant in active and inactive DD lesions.

  1. The Infant Gut Microbiome: Evidence for Obesity Risk and Dietary Intervention

    PubMed Central

    Koleva, Petya T.; Bridgman, Sarah L.; Kozyrskyj, Anita L.

    2015-01-01

    Increasing globally, particularly in children, obesity is a serious public health issue and risk factor for overweight and metabolic disease in later life. Both in experimental animal and human studies, advances in gene sequencing technologies have yielded intriguing possibilities for the role of the gut microbiome in later development of overweight status. Before translating study findings into practice, we must first reconcile inconsistencies between animal experimentation, and human adult and infant studies. Recent evidence for associations with gut microbiota and infant weight gain or child weight status, implicate Bacteroides and Lactobacillus species. Dietary manipulation with human milk and pre/probiotic formulations holds promise for preventing obesity. PMID:25835047

  2. Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways.

    PubMed

    Hagland, Hanne R; Søreide, Kjetil

    2015-01-28

    The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity.

  3. The Gut Microbiome, Its Metabolome, and Their Relationship to Health and Disease.

    PubMed

    Wu, Gary D

    2016-01-01

    Despite its importance in maintaining the health of the host, growing evidence suggests that gut microbiota may also be an important factor in the pathogenesis of various diseases. The composition of the microbiota can be influenced by many factors, including age, genetics, host environment, and diet. There are epidemiologic data associating diet with the development of inflammatory bowel disease as well as evidence that diet can influence both the form and the function of the microbiome. Based on this evidence, studies are now underway to examine the effect of defined formula diets, an effective therapeutic modality in Crohn's disease, on both the gut microbiome and its metabolome as a therapeutic probe. Diet has an impact upon both the composition and the function of the microbiota in part through small-molecule production that may influence the development of both immune-mediated and metabolic diseases. By comparing dietary intake, the gut microbiota, and the plasma metabolome in omnivores versus vegans, we provide evidence that the production of certain bacterial metabolites is constrained by the composition of the gut microbiota. In total, these results demonstrate the potential promise of dietary manipulation of the gut microbiota and its metabolome as a modality to both maintain health and treat disease.

  4. Infection with diverse immune-modulating poxviruses elicits different compositional shifts in the mouse gut microbiome

    PubMed Central

    Hernáez, Bruno; Rastrojo, Alberto; Alcamí, Antonio

    2017-01-01

    It is often not possible to demonstrate causality within the context of gut microbiota dysbiosis-linked diseases. Thus, we need a better understanding of the mechanisms whereby an altered host immunophysiology shapes its resident microbiota. In this regard, immune-modulating poxvirus strains and mutants could differentially alter gut mucosal immunity in the context of a natural immune response, providing a controlled natural in vivo setting to deepen our understanding of the immune determinants of microbiome composition. This study represents a proof-of-concept that the use of an existing collection of different immune-modulating poxviruses may represent an innovative tool in gut microbiome research. To this end, 16S rRNA amplicon sequencing and RNAseq transcriptome profiling were employed as proxies for microbiota composition and gut immunophysiological status in the analysis of caecal samples from control mice and mice infected with various poxvirus types. Our results show that different poxvirus species and mutants elicit different shifts in the mice mucosa-associated microbiota and, in some instances, significant concomitant shifts in gut transcriptome profiles, thus providing an initial validation to the proposed model. PMID:28282449

  5. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.

    PubMed

    Zheng, P; Zeng, B; Zhou, C; Liu, M; Fang, Z; Xu, X; Zeng, L; Chen, J; Fan, S; Du, X; Zhang, X; Yang, D; Yang, Y; Meng, H; Li, W; Melgiri, N D; Licinio, J; Wei, H; Xie, P

    2016-06-01

    Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.

  6. Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity

    PubMed Central

    Levin, Albert M.; Sitarik, Alexandra R.; Havstad, Suzanne L.; Fujimura, Kei E.; Wegienka, Ganesa; Cassidy-Bushrow, Andrea E.; Kim, Haejin; Zoratti, Edward M.; Lukacs, Nicholas W.; Boushey, Homer A.; Ownby, Dennis R.; Lynch, Susan V.; Johnson, Christine C.

    2016-01-01

    The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race-ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease. PMID:27558272

  7. Enrichment of the Lung Microbiome with Gut Bacteria in Sepsis and the Acute Respiratory Distress Syndrome

    PubMed Central

    Dickson, Robert P.; Singer, Benjamin H.; Newstead, Michael W.; Falkowski, Nicole R.; Erb-Downward, John R.; Standiford, Theodore J.; Huffnagle, Gary B.

    2016-01-01

    SUMMARY Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here we report culture-independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecologic analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut-specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture, and correlated with the intensity of systemic inflammation. Alveolar TNF-α, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases. PMID:27670109

  8. Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.

    PubMed

    Kreznar, Julia H; Keller, Mark P; Traeger, Lindsay L; Rabaglia, Mary E; Schueler, Kathryn L; Stapleton, Donald S; Zhao, Wen; Vivas, Eugenio I; Yandell, Brian S; Broman, Aimee Teo; Hagenbuch, Bruno; Attie, Alan D; Rey, Federico E

    2017-02-14

    Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion.

  9. The Gut Microbiome of Wild Lemurs: A Comparison of Sympatric Lemur catta and Propithecus verreauxi.

    PubMed

    Fogel, Andrew T

    2015-01-01

    Mammalian gut microbes are invaluable to the host's metabolism, but few researchers have examined gut microbial dynamics under natural conditions in wild mammals. This study aims to help fill this knowledge gap with a survey of the natural variation of the gut microbiome in 2 wild lemur species, Lemur catta and Propithecus verreauxi. The wild L. catta were also compared to a captive population to discern the effect of habitat within a species. Gut microbial DNA was extracted from fecal samples collected in Madagascar and the Vienna Zoo and sequenced. The wild and captive L. catta had distinct microbial communities, likely due to differences in diet and development between their populations. The wild L. catta and P. verreauxi also had distinct gut microbiomes, due to a change in microbial abundance, not composition. Within each lemur species, there was abundant variation between individuals and from the dry to the wet season. The intraspecific and temporal microbial variation requires more investigation, with changes in diet a likely contributor.

  10. Defining the core Arabidopsis thaliana root microbiome

    PubMed Central

    Gehring, Jase; Malfatti, Stephanie; Tremblay, Julien; Engelbrektson, Anna; Kunin, Victor; del Rio, Tijana Glavina; Edgar, Robert C.; Eickhorst, Thilo; Ley, Ruth E.; Hugenholtz, Philip; Tringe, Susannah Green; Dangl, Jeffery L.

    2014-01-01

    Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing therhizosphere(immediately surroundingthe root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation1-3. Colonization of the root occurs despite a sophisticated plant immune system4,5, suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plantmicrobe interactions derived from complex soil communities. PMID:22859206

  11. The Gut Microbiome of the Vector Lutzomyia longipalpis Is Essential for Survival of Leishmania infantum

    PubMed Central

    Kelly, Patrick H.; Bahr, Sarah M.; Serafim, Tiago D.; Ajami, Nadim J.; Petrosino, Joseph F.; Meneses, Claudio; Kirby, John R.; Valenzuela, Jesus G.; Kamhawi, Shaden

    2017-01-01

    ABSTRACT The vector-borne disease leishmaniasis, caused by Leishmania species protozoa, is transmitted to humans by phlebotomine sand flies. Development of Leishmania to infective metacyclic promastigotes in the insect gut, a process termed metacyclogenesis, is an essential prerequisite for transmission. Based on the hypothesis that vector gut microbiota influence the development of virulent parasites, we sequenced midgut microbiomes in the sand fly Lutzomyia longipalpis with or without Leishmania infantum infection. Sucrose-fed sand flies contained a highly diverse, stable midgut microbiome. Blood feeding caused a decrease in microbial richness that eventually recovered. However, bacterial richness progressively decreased in L. infantum-infected sand flies. Acetobacteraceae spp. became dominant and numbers of Pseudomonadaceae spp. diminished coordinately as the parasite underwent metacyclogenesis and parasite numbers increased. Importantly, antibiotic-mediated perturbation of the midgut microbiome rendered sand flies unable to support parasite growth and metacyclogenesis. Together, these data suggest that the sand fly midgut microbiome is a critical factor for Leishmania growth and differentiation to its infective state prior to disease transmission. PMID:28096483

  12. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome.

    PubMed

    Rogers, M A M; Aronoff, D M

    2016-02-01

    The composition of the gut microbiome with the use of non-steroidal anti-inflammatory drugs (NSAIDs) has not been fully characterized. Drug use within the past 30 days was ascertained in 155 adults, and stool specimens were submitted for analysis. Area under the receiver operating characteristic curve (AUC) was calculated in logit models to distinguish the relative abundance of operational taxonomic units (OTUs) by medication class. The type of medication had a greater influence on the gut microbiome than the number of medications. NSAIDs were particularly associated with distinct microbial populations. Four OTUs (Prevotella species, Bacteroides species, family Ruminococcaceae, and Barnesiella species) discriminated aspirin users from those using no medication (AUC = 0.96; 95% CI 0.84-1.00). The microbiome profile of celecoxib users was similar to that of ibuprofen users, with both showing enrichment of Acidaminococcaceae and Enterobacteriaceae. Bacteria from families Propionibacteriaceae, Pseudomonadaceae, Puniceicoccaceae and Rikenellaceae were more abundant in ibuprofen users than in controls or naproxen users. Bacteroides species and Erysipelotrichaceae species discriminated individuals using NSAIDs plus proton-pump inhibitors from those using NSAIDs alone (AUC = 0.96; 95% CI 0.87-1.00). Bacteroides species and a bacterium of family Ruminococcaceae discriminated individuals using NSAIDs in combination with antidepressants and laxatives from those using NSAIDs alone (AUC = 0.98; 95% CI 0.93-1.00). In conclusion, bacteria in the gastrointestinal tract reflect the combinations of medications that people ingest. The bacterial composition of the gut varied with the type of NSAID ingested.

  13. Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases.

    PubMed

    Paul, Bidisha; Barnes, Stephen; Demark-Wahnefried, Wendy; Morrow, Casey; Salvador, Carolina; Skibola, Christine; Tollefsbol, Trygve O

    2015-01-01

    Epigenetic modulation of gene activity occurs in response to non-genetic factors such as body weight status, physical activity, dietary factors, and environmental toxins. In addition, each of these factors is thought to affect and be affected by the gut microbiome. A primary mechanism that links these various factors together in mediating control of gene expression is the production of metabolites that serve as critical cofactors and allosteric regulators of epigenetic processes. Here, we review the involvement of the gut microbiota and its interactions with dietary factors, many of which have known cellular bioactivity, focusing on particular epigenetic processes affected and the influence they have on human health and disease, particularly cancer and response to treatment. Advances in DNA sequencing have expanded the capacity for studying the microbiome. Combining this with rapidly improving techniques to measure the metabolome provides opportunities to understand complex relationships that may underlie the development and progression of cancer as well as treatment-related sequelae. Given broad reaching and fundamental biology, both at the cellular and organismal levels, we propose that interactive research programs, which utilize a wide range of mutually informative experimental model systems-each one optimally suited for answering particular questions-provide the best path forward for breaking ground on new knowledge and ultimately understanding the epigenetic significance of the gut microbiome and its response to dietary factors in cancer prevention and therapy.

  14. Gut microbiota and obesity: lessons from the microbiome.

    PubMed

    Cani, Patrice D

    2013-07-01

    The distal gut harbours microbial communities that outnumber our own eukaryotic cells. The contribution of the gut microbiota to the development of several diseases (e.g. obesity, type 2 diabetes, steatosis, cardiovascular diseases and inflammatory bowel diseases) is becoming clear, although the causality remains to be proven in humans. Global changes in the gut microbiota have been observed by a number of culture-dependent and culture-independent methods, and while the latter have mostly included 16S ribosomal RNA gene analyses, more recent studies have utilized DNA sequencing of whole-microbial communities. Altogether, these high-throughput methods have facilitated the identification of novel candidate bacteria and, most importantly, metabolic functions that might be associated with obesity and type 2 diabetes. This review discusses the association between specific taxa and obesity, together with the techniques that are used to characterize the gut microbiota in the context of obesity and type 2 diabetes. Recent results are discussed in the framework of the interactions between gut microbiota and host metabolism.

  15. Gut microbiome of the Hadza hunter-gatherers

    PubMed Central

    Schnorr, Stephanie L.; Candela, Marco; Rampelli, Simone; Centanni, Manuela; Consolandi, Clarissa; Basaglia, Giulia; Turroni, Silvia; Biagi, Elena; Peano, Clelia; Severgnini, Marco; Fiori, Jessica; Gotti, Roberto; De Bellis, Gianluca; Luiselli, Donata; Brigidi, Patrizia; Mabulla, Audax; Marlowe, Frank; Henry, Amanda G.; Crittenden, Alyssa N.

    2014-01-01

    Human gut microbiota directly influences health and provides an extra means of adaptive potential to different lifestyles. To explore variation in gut microbiota and to understand how these bacteria may have co-evolved with humans, here we investigate the phylogenetic diversity and metabolite production of the gut microbiota from a community of human hunter-gatherers, the Hadza of Tanzania. We show that the Hadza have higher levels of microbial richness and biodiversity than Italian urban controls. Further comparisons with two rural farming African groups illustrate other features unique to Hadza that can be linked to a foraging lifestyle. These include absence of Bifidobacterium and differences in microbial composition between the sexes that probably reflect sexual division of labour. Furthermore, enrichment in Prevotella, Treponema and unclassified Bacteroidetes, as well as a peculiar arrangement of Clostridiales taxa, may enhance the Hadza’s ability to digest and extract valuable nutrition from fibrous plant foods. PMID:24736369

  16. Gut microbiome of the Hadza hunter-gatherers.

    PubMed

    Schnorr, Stephanie L; Candela, Marco; Rampelli, Simone; Centanni, Manuela; Consolandi, Clarissa; Basaglia, Giulia; Turroni, Silvia; Biagi, Elena; Peano, Clelia; Severgnini, Marco; Fiori, Jessica; Gotti, Roberto; De Bellis, Gianluca; Luiselli, Donata; Brigidi, Patrizia; Mabulla, Audax; Marlowe, Frank; Henry, Amanda G; Crittenden, Alyssa N

    2014-04-15

    Human gut microbiota directly influences health and provides an extra means of adaptive potential to different lifestyles. To explore variation in gut microbiota and to understand how these bacteria may have co-evolved with humans, here we investigate the phylogenetic diversity and metabolite production of the gut microbiota from a community of human hunter-gatherers, the Hadza of Tanzania. We show that the Hadza have higher levels of microbial richness and biodiversity than Italian urban controls. Further comparisons with two rural farming African groups illustrate other features unique to Hadza that can be linked to a foraging lifestyle. These include absence of Bifidobacterium and differences in microbial composition between the sexes that probably reflect sexual division of labour. Furthermore, enrichment in Prevotella, Treponema and unclassified Bacteroidetes, as well as a peculiar arrangement of Clostridiales taxa, may enhance the Hadza's ability to digest and extract valuable nutrition from fibrous plant foods.

  17. Immune Disorders and Its Correlation with Gut Microbiome

    PubMed Central

    Hwang, Ji-Sun; Im, Chang-Rok

    2012-01-01

    Allergic disorders such as atopic dermatitis and asthma are common hyper-immune disorders in industrialized countries. Along with genetic association, environmental factors and gut microbiota have been suggested as major triggering factors for the development of atopic dermatitis. Numerous studies support the association of hygiene hypothesis in allergic immune disorders that a lack of early childhood exposure to diverse microorganism increases susceptibility to allergic diseases. Among the symbiotic microorganisms (e.g. gut flora or probiotics), probiotics confer health benefits through multiple action mechanisms including modification of immune response in gut associated lymphoid tissue (GALT). Although many human clinical trials and mouse studies demonstrated the beneficial effects of probiotics in diverse immune disorders, this effect is strain specific and needs to apply specific probiotics for specific allergic diseases. Herein, we briefly review the diverse functions and regulation mechanisms of probiotics in diverse disorders. PMID:23091436

  18. Functional Changes in the Gut Microbiome Contribute to Transforming Growth Factor β-Deficient Colon Cancer.

    PubMed

    Daniel, Scott G; Ball, Corbie L; Besselsen, David G; Doetschman, Tom; Hurwitz, Bonnie L

    2017-01-01

    Colorectal cancer (CRC) is one of the most treatable cancers, with a 5-year survival rate of ~64%, yet over 50,000 deaths occur yearly in the United States. In 15% of cases, deficiency in mismatch repair leads to null mutations in transforming growth factor β (TGF-β) type II receptor, yet genotype alone is not responsible for tumorigenesis. Previous work in mice shows that disruptions in TGF-β signaling combined with Helicobacter hepaticus cause tumorigenesis, indicating a synergistic effect between genotype and microbial environment. Here, we examine functional shifts in the gut microbiome in CRC using integrated -omics approaches to untangle the role of host genotype, inflammation, and microbial ecology. We profile the gut microbiome of 40 mice with/without deficiency in TGF-β signaling from a Smad3 (mothers against decapentaplegic homolog-3) knockout and with/without inoculation with H. hepaticus. Clear functional differences in the microbiome tied to specific bacterial species emerge from four pathways related to human colon cancer: lipopolysaccharide (LPS) production, polyamine synthesis, butyrate metabolism, and oxidative phosphorylation (OXPHOS). Specifically, an increase in Mucispirillum schaedleri drives LPS production, which is associated with an inflammatory response. We observe a commensurate decrease in butyrate production from Lachnospiraceae bacterium A4, which could promote tumor formation. H. hepaticus causes an increase in OXPHOS that may increase DNA-damaging free radicals. Finally, multiple bacterial species increase polyamines that are associated with colon cancer, implicating not just diet but also the microbiome in polyamine levels. These insights into cross talk between the microbiome, host genotype, and inflammation could promote the development of diagnostics and therapies for CRC. IMPORTANCE Most research on the gut microbiome in colon cancer focuses on taxonomic changes at the genus level using 16S rRNA gene sequencing. Here, we

  19. The nutrition-gut microbiome-physiology axis and allergic diseases.

    PubMed

    McKenzie, Craig; Tan, Jian; Macia, Laurence; Mackay, Charles R

    2017-07-01

    Dietary and bacterial metabolites influence immune responses. This raises the question whether the increased incidence of allergies, asthma, some autoimmune diseases, cardiovascular disease, and others might relate to intake of unhealthy foods, and the decreased intake of dietary fiber. In recent years, new knowledge on the molecular mechanisms underpinning a 'diet-gut microbiota-physiology axis' has emerged to substantiate this idea. Fiber is fermented to short chain fatty acids (SCFAs), particularly acetate, butyrate, and propionate. These metabolites bind 'metabolite-sensing' G-protein-coupled receptors such as GPR43, GPR41, and GPR109A. These receptors play fundamental roles in the promotion of gut homeostasis and the regulation of inflammatory responses. For instance, these receptors and their metabolites influence Treg biology, epithelial integrity, gut homeostasis, DC biology, and IgA antibody responses. The SCFAs also influence gene transcription in many cells and tissues, through their inhibition of histone deacetylase expression or function. Contained in this mix is the gut microbiome, as commensal bacteria in the gut have the necessary enzymes to digest dietary fiber to SCFAs, and dysbiosis in the gut may affect the production of SCFAs and their distribution to tissues throughout the body. SCFAs can epigenetically modify DNA, and so may be one mechanism to account for diseases with a 'developmental origin', whereby in utero or post-natal exposure to environmental factors (such as nutrition of the mother) may account for disease later in life. If the nutrition-gut microbiome-physiology axis does underpin at least some of the Western lifestyle influence on asthma and allergies, then there is tremendous scope to correct this with healthy foodstuffs, probiotics, and prebiotics. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Brain gut microbiome interactions and functional bowel disorders

    USDA-ARS?s Scientific Manuscript database

    Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined r...

  1. Posttraumatic Stress Disorder: Does the Gut Microbiome Hold the Key?

    PubMed Central

    Leclercq, Sophie; Forsythe, Paul

    2016-01-01

    Gut bacteria strongly influence our metabolic, endocrine, immune, and both peripheral and central nervous systems. Microbiota do this directly and indirectly through their components, shed and secreted, ranging from fermented and digested dietary and host products to functionally active neurotransmitters including serotonin, dopamine, and γ-aminobutyric acid. Depression has been associated with enhanced levels of proinflammatory biomarkers and abnormal responses to stress. Posttraumatic stress disorder (PTSD) appears to be marked in addition by low cortisol responses, and these factors seem to predict and predispose individuals to develop PTSD after a traumatic event. Dysregulation of the immune system and of the hypothalamic-pituitary-adrenal axis observed in PTSD may reflect prior trauma exposure, especially early in life. Early life, including the prenatal period, is a critical time in rodents, and may well be for humans, for the functional and structural development of the immune and nervous systems. These, in turn, are likely shaped and programmed by gut and possibly other bacteria. Recent experimental and clinical data converge on the hypothesis that imbalanced gut microbiota in early life may have long-lasting immune and other physiologic effects that make individuals more susceptible to develop PTSD after a traumatic event and contribute to the disorder. This suggests that it may be possible to target abnormalities in these systems by manipulation of certain gut bacterial communities directly through supplementation or indirectly by dietary and other novel approaches. PMID:27254412

  2. On Growth and Form of the Zebrafish Gut Microbiome

    NASA Astrophysics Data System (ADS)

    Jemielita, Matthew; Taormina, Michael; Rolig, Annah; Burns, Adam; Hampton, Jennifer; Guillemin, Karen; Parthasarathy, Raghuveer

    2014-03-01

    The vertebrate gut is home to a diverse microbial community whose composition has a strong influence on the development and health of the host organism. Researchers can identify the members of the microbiota, yet little is known about the spatial and temporal dynamics of these microbial communities, including the mechanisms guiding their nucleation, growth, and interactions. We address these issues using the larval zebrafish (Danio rerio) as a model organism, which are raised microbe-free and then inoculated with controlled compositions of fluorophore-expressing bacteria. Live imaging using light sheet fluorescence microscopy enables visualization of the gut's entire microbial population over the first 24 hours of colonization. Image analysis allows us to quantify microbial populations that range from a few individuals to tens of thousands of microbes, and analyze the structure and growth kinetics of gut bacterial communities. We find that genetically-identical microbes can show surprisingly different growth rates and colonization abilities depending on their order of arrival. This demonstrates that knowing only the constituents of the gut community is insufficient to determine their dynamics; rather, the history of colonization matters.

  3. Gut Microbiome Standardization in Control and Experimental Mice.

    PubMed

    McCoy, Kathy D; Geuking, Markus B; Ronchi, Francesca

    2017-04-03

    Mouse models are used extensively to study human health and to investigate the mechanisms underlying human disease. In the past, most animal studies were performed without taking into consideration the impact of the microbiota. However, the microbiota that colonizes all body surfaces, including the gastrointestinal tract, respiratory tract, genitourinary tract, and skin, heavily impacts nearly every aspect of host physiology. When performing studies utilizing mouse models it is critical to understand that the microbiome is heavily impacted by environmental factors, including (but not limited to) food, bedding, caging, and temperature. In addition, stochastic changes in the microbiota can occur over time that also play a role in shaping microbial composition. These factors lead to massive variability in the composition of the microbiota between animal facilities and research institutions, and even within a single facility. Lack of experimental reproducibility between research groups has highlighted the necessity for rigorously controlled experimental designs in order to standardize the microbiota between control and experimental animals. Well controlled experiments are mandatory in order to reduce variability and allow correct interpretation of experimental results, not just of host-microbiome studies but of all mouse models of human disease. The protocols presented are aimed to design experiments that control the microbiota composition between different genetic strains of experimental mice within an animal unit. © 2017 by John Wiley & Sons, Inc.

  4. Defining the Core Microbiome in Corals' Microbial Soup.

    PubMed

    Hernandez-Agreda, Alejandra; Gates, Ruth D; Ainsworth, Tracy D

    2017-02-01

    Corals are considered one of the most complex microbial biospheres studied to date, hosting thousands of bacterial phylotypes in species-specific associations. There are, however, substantial knowledge gaps and challenges in understanding the functional significance of bacterial communities and bacterial symbioses of corals. The ubiquitous nature of some bacterial interactions has only recently been investigated and an accurate differentiation between the healthy (symbiotic) and unhealthy (dysbiotic) microbial state has not yet been determined. Here we review the complexity of the coral holobiont, coral microbiome diversity, and recently proposed bacterial symbioses of corals. We provide insight into coupling the core microbiome framework with community ecology principals, and draw on the theoretical insights from other complex systems, to build a framework to aid in deciphering ecologically significant microbes within a corals' microbial soup.

  5. Bisphenol A alters gut microbiome: Comparative metagenomics analysis.

    PubMed

    Lai, Keng-Po; Chung, Yan-Tung; Li, Rong; Wan, Hin-Ting; Wong, Chris Kong-Chu

    2016-11-01

    Mounting evidence has shown that an alteration of the gut microbiota is associated with diet, and plays an important role in animal health and metabolic diseases. However, little is known about the influence of environmental contaminants on the gut microbial community. Bisphenol A (BPA), which is widely used for manufacturing plastic products, has recently been classified as an environmental obesogen. Although many studies have demonstrated the metabolic-disrupting effects of BPA on liver and pancreatic functions, the possible effects of this synthetic compound on the metabolic diversity of the intestinal microbiota is unknown. Using 16S rRNA gene sequencing analysis on caecum samples of CD-1 mice, the present study aimed to test the hypothesis that dietary BPA intake may influence the gut microbiota composition and functions, an important attributing factor to development of the metabolic syndrome. A high-fat diet (HFD) and high-sucrose diet (HSD) were included as the positive controls for comparing the changes in the intestinal microbial profiles. Our results demonstrated a significant reduction of species diversity in the gut microbiota of BPA-fed mice. Alpha and beta diversity analyses showed that dietary BPA intake led to a similar gut microbial community structure as that induced by HFD and HSD in mice. In addition, comparative analysis of the microbial communities revealed that both BPA and a HFD favored the growth of Proteobacteria, a microbial marker of dysbiosis. Consistently, growth induction of the family Helicobacteraceae and reduction of the Firmicutes and Clostridia populations were observed in the mice fed BPA or a HFD. Collectively, our study highlighted that the effects of dietary BPA intake on the shift of microbial community structure were similar to those of a HFD and HSD, and revealed microbial markers for the development of diseases associated with an unstable microbiota.

  6. Adaptation of gut microbiome to different dietary nonstarch polysaccharide fractions in a porcine model.

    PubMed

    Tian, Gang; Wu, Xiying; Chen, Daiwen; Yu, Bing; He, Jun

    2017-10-01

    Dietary fibers, consisting of nonstarch polysaccharides (NSPs) were found to modulate the gut microbiota. However, little is known about the role of a separated fiber fraction. Here, we describe a response in gut microbiome to different fiber fractions using a porcine model. Ileal and cecal digesta were collected from pigs fed with fiber-free diet (FFD) or diet containing 5% cellulose (CEL), xylan (XYL) or β-glucan (GLU). We observed an elevated 16S rRNA gene copies in ileum and cecum digesta after NSP ingestion. Interestingly, we found that cecum digesta contained higher bacterial diversity than ileum digesta. Moreover, NSPs had no significant influence on overall diversity, but acutely altered the abundance of specific bacteria. Importantly, NSPs decreased the abundance of phylum Firmicutes, but increased the phylum Proteobacteria in ileal samples. Among the NSP-treated groups, pigs on CEL-containing diet had exclusively higher abundance of Lactobacillus spp. in the ileum. Whereas, the GLU-treated samples had more Clostridium spp. This study not only indicated how the gut microbiome adapts to the three major NSP fractions, but the results also contribute to our understanding of the role of dietary fibers in modulating gut microbiota and health. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis.

    PubMed

    Lv, Long-Xian; Fang, Dai-Qiong; Shi, Ding; Chen, De-Ying; Yan, Ren; Zhu, Yi-Xin; Chen, Yan-Fei; Shao, Li; Guo, Fei-Fei; Wu, Wen-Rui; Li, Ang; Shi, Hai-Yan; Jiang, Xia-Wei; Jiang, Hui-Yong; Xiao, Yong-Hong; Zheng, Shu-Sen; Li, Lan-Juan

    2016-07-01

    We selected 42 early-stage primary biliary cirrhosis (PBC) patients and 30 healthy controls (HC). Metagenomic sequencing of the 16S rRNA gene was used to characterize the fecal microbiome. UPLC-MS/MS assaying of small molecules was used to characterize the metabolomes of the serum, urine and feces. Liquid chip assaying of serum cytokines was used to characterize the immune profiles. The gut of PBC patients were depleted of some potentially beneficial bacteria, such as Acidobacteria, Lachnobacterium sp., Bacteroides eggerthii and Ruminococcus bromii, but were enriched in some bacterial taxa containing opportunistic pathogens, such as γ-Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis and Paraprevotella clara. Several altered gut bacterial taxa exhibited potential interactions with PBC through their associations with altered metabolism, immunity and liver function indicators, such as those of Klebsiella with IL-2A and Neisseriaceae with urinary indoleacrylate. Many gut bacteria, such as some members of Bacteroides, were altered in their associations with the immunity and metabolism of PBC patients, although their relative abundances were unchanged. Consequently, the gut microbiome is altered and may be critical for the onset or development of PBC by interacting with metabolism and immunity. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  8. Metabolomics view on gut microbiome modulation by polyphenol-rich foods.

    PubMed

    Moco, Sofia; Martin, François-Pierre J; Rezzi, Serge

    2012-10-05

    Health is influenced by genetic, lifestyle, and diet determinants; therefore, nutrition plays an essential role in health management. Still, the substantiation of nutritional health benefits is challenged by the intrinsic macro- and micronutrient complexity of foods and individual responses. Evidence of healthy effects of food requires new strategies not only to stratify populations according to their metabolic requirements but also to predict and measure individual responses to dietary intakes. The influence of the gut microbiome and its interaction with the host is pivotal to understand nutrition and metabolism. Thus, the modulation of the gut microbiome composition by alteration of food habits has potentialities in health improvement or even disease prevention. Dietary polyphenols are naturally occurring constituents in vegetables and fruits, including coffee and cocoa. They are commonly associated to health benefits, although mechanistic evidence in vivo is not yet fully understood. Polyphenols are extensively metabolized by gut bacteria into a complex series of end-products that support a significant effect on the functional ecology of symbiotic partners that can affect the host physiology. This review reports recent nutritional metabolomics inspections of gut microbiota-host metabolic interactions with a particular focus on the cometabolism of cocoa and coffee polyphenols.

  9. Xenobiotics shape the physiology and gene expression of the active human gut microbiome.

    PubMed

    Maurice, Corinne Ferrier; Haiser, Henry Joseph; Turnbaugh, Peter James

    2013-01-17

    The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider interindividual variations in the active human gut microbiome. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. The Cirrhosis Dysbiosis Ratio defines Changes in the Gut Microbiome Associated with Cirrhosis and its Complications

    PubMed Central

    Bajaj, Jasmohan S; Heuman, Douglas M; Hylemon, Phillip B; Sanyal, Arun J; White, Melanie B; Monteith, Pamela; Noble, Nicole A; Unser, Ariel B; Daita, Kalyani; Fisher, Andmorgan R; Sikaroodi, Masoumeh; Gillevet, Patrick M

    2014-01-01

    Background & Aims The gut microbiome is altered in cirrhosis; however its evolution with disease progression is partly understood. We aimed to study changes in microbiome over cirrhosis severity, its stability over time and its longitudinal alterations with decompensation. Methods Controls and age-matched cirrhotics (compensated/decompensated/hospitalized) were included. Their stool microbiota was quantified using multi-tagged pyrosequencing. Ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio(CDR); a low number indicating dysbiosis. Firstly, microbiome was compared between controls and cirrhotic sub-groups. Second, for stability assessment, stool collected twice within 6 months in compensated outpatients was analyzed. Thirdly, changes after decompensation were assessed using (a) longitudinal comparison in patients before/after hepatic encephalopathy development (HE), (b) longitudinal cohort of hospitalized infected cirrhotics MELD-matched to uninfected cirrhotics followed for 30 days. Results 244 subjects [219 cirrhotics (121 compensated outpatients,54 decompensated outpatients,44 inpatients) and 25 age-matched controls)] were included. CDR was highest in controls(2.05) than compensated(0.89), decompensated(0.66) and inpatients(0.32,p<0.0001) and negatively correlated with endotoxin. Microbiota and CDR remained unchanged in stable outpatient cirrhotics (0.91 vs. 0.86, p=0.45). In patients studied before/after HE development, dysbiosis occurred post-HE(CDR:1.2 to 0.42, p=0.03). In the longitudinal matched-cohort, microbiota were significantly different between infected/uninfected cirrhotics at baseline and a low CDR was associated with death and organ failures within 30 days. Conclusions Progressive changes in the gut microbiome accompany cirrhosis and become more severe in the setting of decompensation. The cirrhosis dysbiosis ratio may be a useful quantitative index to describe microbiome alterations accompanying

  11. Honey Bee Gut Microbiome Is Altered by In-Hive Pesticide Exposures

    PubMed Central

    Kakumanu, Madhavi L.; Reeves, Alison M.; Anderson, Troy D.; Rodrigues, Richard R.; Williams, Mark A.

    2016-01-01

    Honey bees (Apis mellifera) are the primary pollinators of major horticultural crops. Over the last few decades, a substantial decline in honey bees and their colonies have been reported. While a plethora of factors could contribute to the putative decline, pathogens, and pesticides are common concerns that draw attention. In addition to potential direct effects on honey bees, indirect pesticide effects could include alteration of essential gut microbial communities and symbionts that are important to honey bee health (e.g., immune system). The primary objective of this study was to determine the microbiome associated with honey bees exposed to commonly used in-hive pesticides: coumaphos, tau-fluvalinate, and chlorothalonil. Treatments were replicated at three independent locations near Blacksburg Virginia, and included a no-pesticide amended control at each location. The microbiome was characterized through pyrosequencing of V2–V3 regions of the bacterial 16S rRNA gene and fungal ITS region. Pesticide exposure significantly affected the structure of bacterial but not fungal communities. The bee bacteriome, similar to other studies, was dominated by sequences derived from Bacilli, Actinobacteria, α-, β-, γ-proteobacteria. The fungal community sequences were dominated by Ascomycetes and Basidiomycetes. The Multi-response permutation procedures (MRPP) and subsequent Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that chlorothalonil caused significant change to the structure and functional potential of the honey bee gut bacterial community relative to control. Putative genes for oxidative phosphorylation, for example, increased while sugar metabolism and peptidase potential declined in the microbiome of chlorothalonil exposed bees. The results of this field-based study suggest the potential for pesticide induced changes to the honey bee gut microbiome that warrant further investigation. PMID:27579024

  12. Honey Bee Gut Microbiome Is Altered by In-Hive Pesticide Exposures.

    PubMed

    Kakumanu, Madhavi L; Reeves, Alison M; Anderson, Troy D; Rodrigues, Richard R; Williams, Mark A

    2016-01-01

    Honey bees (Apis mellifera) are the primary pollinators of major horticultural crops. Over the last few decades, a substantial decline in honey bees and their colonies have been reported. While a plethora of factors could contribute to the putative decline, pathogens, and pesticides are common concerns that draw attention. In addition to potential direct effects on honey bees, indirect pesticide effects could include alteration of essential gut microbial communities and symbionts that are important to honey bee health (e.g., immune system). The primary objective of this study was to determine the microbiome associated with honey bees exposed to commonly used in-hive pesticides: coumaphos, tau-fluvalinate, and chlorothalonil. Treatments were replicated at three independent locations near Blacksburg Virginia, and included a no-pesticide amended control at each location. The microbiome was characterized through pyrosequencing of V2-V3 regions of the bacterial 16S rRNA gene and fungal ITS region. Pesticide exposure significantly affected the structure of bacterial but not fungal communities. The bee bacteriome, similar to other studies, was dominated by sequences derived from Bacilli, Actinobacteria, α-, β-, γ-proteobacteria. The fungal community sequences were dominated by Ascomycetes and Basidiomycetes. The Multi-response permutation procedures (MRPP) and subsequent Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that chlorothalonil caused significant change to the structure and functional potential of the honey bee gut bacterial community relative to control. Putative genes for oxidative phosphorylation, for example, increased while sugar metabolism and peptidase potential declined in the microbiome of chlorothalonil exposed bees. The results of this field-based study suggest the potential for pesticide induced changes to the honey bee gut microbiome that warrant further investigation.

  13. Analyses of the stability and core taxonomic memberships of the human microbiome.

    PubMed

    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.

  14. Gut microbiome composition and metabolomic profiles of wild western lowland gorillas (Gorilla gorilla gorilla) reflect host ecology.

    PubMed

    Gomez, Andres; Petrzelkova, Klara; Yeoman, Carl J; Vlckova, Klara; Mrázek, Jakub; Koppova, Ingrid; Carbonero, Franck; Ulanov, Alexander; Modry, David; Todd, Angelique; Torralba, Manolito; Nelson, Karen E; Gaskins, H Rex; Wilson, Brenda; Stumpf, Rebecca M; White, Bryan A; Leigh, Steven R

    2015-05-01

    The metabolic activities of gut microbes significantly influence host physiology; thus, characterizing the forces that modulate this micro-ecosystem is key to understanding mammalian biology and fitness. To investigate the gut microbiome of wild primates and determine how these microbial communities respond to the host's external environment, we characterized faecal bacterial communities and, for the first time, gut metabolomes of four wild lowland gorilla groups in the Dzanga-Sangha Protected Areas, Central African Republic. Results show that geographical range may be an important modulator of the gut microbiomes and metabolomes of these gorilla groups. Distinctions seemed to relate to feeding behaviour, implying energy harvest through increased fruit consumption or fermentation of highly fibrous foods. These observations were supported by differential abundance of metabolites and bacterial taxa associated with the metabolism of cellulose, phenolics, organic acids, simple sugars, lipids and sterols between gorillas occupying different geographical ranges. Additionally, the gut microbiomes of a gorilla group under increased anthropogenic pressure could always be distinguished from that of all other groups. By characterizing the interplay between environment, behaviour, diet and symbiotic gut microbes, we present an alternative perspective on primate ecology and on the forces that shape the gut microbiomes of wild primates from an evolutionary context. © 2015 John Wiley & Sons Ltd.

  15. Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome.

    PubMed

    Pannaraj, Pia S; Li, Fan; Cerini, Chiara; Bender, Jeffrey M; Yang, Shangxin; Rollie, Adrienne; Adisetiyo, Helty; Zabih, Sara; Lincez, Pamela J; Bittinger, Kyle; Bailey, Aubrey; Bushman, Frederic D; Sleasman, John W; Aldrovandi, Grace M

    2017-07-01

    Establishment of the infant microbiome has lifelong implications on health and immunity. Gut microbiota of breastfed compared with nonbreastfed individuals differ during infancy as well as into adulthood. Breast milk contains a diverse population of bacteria, but little is known about the vertical transfer of bacteria from mother to infant by breastfeeding. To determine the association between the maternal breast milk and areolar skin and infant gut bacterial communities. In a prospective, longitudinal study, bacterial composition was identified with sequencing of the 16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of 107 healthy mother-infant pairs. The study was conducted in Los Angeles, California, and St Petersburg, Florida, between January 1, 2010, and February 28, 2015. Amount and duration of daily breastfeeding and timing of solid food introduction. Bacterial composition in maternal breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal RNA gene. In the 107 healthy mother and infant pairs (median age at the time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the infants were male. Bacterial communities were distinct in milk, areolar skin, and stool, differing in both composition and diversity. The infant gut microbial communities were more closely related to an infant's mother's milk and skin compared with a random mother (mean difference in Bray-Curtis distances, 0.012 and 0.014, respectively; P < .001 for both). Source tracking analysis was used to estimate the contribution of the breast milk and areolar skin microbiomes to the infant gut microbiome. During the first 30 days of life, infants who breastfed to obtain 75% or more of their daily milk intake received a mean (SD) of 27.7% (15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin. Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition changes were associated with the

  16. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

    SciTech Connect

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo; Brislawn, Colin J.; Noecker, Cecilia; Zink, Erika M.; Fansler, Sarah J.; Casey, Cameron P.; Miller, Darla R.; Huang, Yurong; Karpen, Gary H.; Celniker, Susan E.; Brown, James B.; Borenstein, Elhanan; Jansson, Janet K.; Metz, Thomas O.; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  17. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention.

    PubMed

    Liu, Ruixin; Hong, Jie; Xu, Xiaoqiang; Feng, Qiang; Zhang, Dongya; Gu, Yanyun; Shi, Juan; Zhao, Shaoqian; Liu, Wen; Wang, Xiaokai; Xia, Huihua; Liu, Zhipeng; Cui, Bin; Liang, Peiwen; Xi, Liuqing; Jin, Jiabin; Ying, Xiayang; Wang, Xiaolin; Zhao, Xinjie; Li, Wanyu; Jia, Huijue; Lan, Zhou; Li, Fengyu; Wang, Rui; Sun, Yingkai; Yang, Minglan; Shen, Yuxin; Jie, Zhuye; Li, Junhua; Chen, Xiaomin; Zhong, Huanzi; Xie, Hailiang; Zhang, Yifei; Gu, Weiqiong; Deng, Xiaxing; Shen, Baiyong; Xu, Xun; Yang, Huanming; Xu, Guowang; Bi, Yufang; Lai, Shenghan; Wang, Jian; Qi, Lu; Madsen, Lise; Wang, Jiqiu; Ning, Guang; Kristiansen, Karsten; Wang, Weiqing

    2017-07-01

    Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

  18. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

    SciTech Connect

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo; Brislawn, Colin J.; Noecker, Cecilia; Zink, Erika M.; Fansler, Sarah J.; Casey, Cameron P.; Miller, Darla R.; Huang, Yurong; Karpen, Gary H.; Celniker, Susan E.; Brown, James B.; Borenstein, Elhanan; Jansson, Janet K.; Metz, Thomas O.; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  19. The mouse gut microbiome revisited: From complex diversity to model ecosystems.

    PubMed

    Clavel, Thomas; Lagkouvardos, Ilias; Blaut, Michael; Stecher, Bärbel

    2016-08-01

    Laboratory mice are the most commonly used animal model in translational medical research. In recent years, the impact of the gut microbiota (i.e. communities of microorganisms in the intestine) on host physiology and the onset of diseases, including metabolic and neuronal disorders, cancers, gastrointestinal infections and chronic inflammation, became a focal point of interest. There is abundant evidence that mouse phenotypes in disease models vary greatly between animal facilities or commercial providers, and that this variation is associated with differences in the microbiota. Hence, there is a clear discrepancy between the widespread use of mouse models in research and the patchwork knowledge on the mouse gut microbiome. In the present manuscript, we summarize data pertaining to the diversity and functions of the mouse gut microbiota, review existing work on gnotobiotic mouse models, and discuss challenges and opportunities for current and future research in the field.

  20. Human nutrition, the gut microbiome and the immune system.

    PubMed

    Kau, Andrew L; Ahern, Philip P; Griffin, Nicholas W; Goodman, Andrew L; Gordon, Jeffrey I

    2011-06-15

    Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.

  1. Probiotics: Interaction with gut microbiome and antiobesity potential.

    PubMed

    Arora, Tulika; Singh, Satvinder; Sharma, Raj Kumar

    2013-04-01

    Obesity is a metabolic disorder afflicting people globally. There has been a pivotal advancement in the understanding of the intestinal microbiota composition and its implication in extraintestinal (metabolic) diseases. Therefore, any agent modulating gut microbiota may produce an influential effect in preventing the pathogenesis of disease. Probiotics are live microbes that, when administered in adequate amounts, have been shown to confer health benefits to the host. Over the years, probiotics have been a part of the human diet in the form of different fermented foods consumed around the world. Their influence on different physiologic functions in the host is increasingly being documented. The antiobesity potential of probiotics is also gaining wide attention because of increasing evidence of the role of gut microbiota in energy homeostasis and fat accumulation. Probiotics have also been shown to interact with the resident bacterial members already present in the gut by altering their properties, which may also affect the metabolic pathways involved in the regulation of fat metabolism. The underlying pathways governing the antiobesity effects of probiotics remain unclear. However, it is hoped that the evidence presented and discussed in this review will encourage and thus drive more extensive research in this field.

  2. From complex gut communities to minimal microbiomes via cultivation.

    PubMed

    Clavel, Thomas; Lagkouvardos, Ilias; Stecher, Bärbel

    2017-06-15

    The mammalian gut microbiota is dominated by populations of bacteria, mostly strict anaerobes. Because these bacteria can influence the health of their host, it is important to investigate their diversity and functions, which can be done via culture-based or molecular approaches. In recent years, microbiologists have very often preferred the use of molecular techniques, as they do not limit the analysis to the fraction of communities that can be grown in the laboratory. In reality, cultivation and molecular methods are complementary, and we are now witnessing a period of unification. Obtaining strains that can be grown in vitro is currently indispensable for the description of novel diversity and eventually the improvement of taxonomic and sequence databases. Moreover, cultivation allows using host-specific minimal consortia of microbes that are helpful for detailed and standardized studies of gut microbial communities and microbe-host interactions. Molecular techniques are helpful because they can provide insights into strain-level diversity and the functional potential of organisms. Furthermore, genomic and metagenomic data allow inferring growth conditions for uncultured bacteria and also enable detailed genetic studies. In the present manuscript, we highlight recent work on culture-based investigation of mammalian gut bacteria and microbe-host interactions and give our opinions on challenges and perspectives in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Changes in the Gut Microbiome of the Sea Lamprey during Metamorphosis

    PubMed Central

    Tetlock, Amanda; Yost, Christopher K.; Stavrinides, John

    2012-01-01

    Vertebrate metamorphosis is often marked by dramatic morphological and physiological changes of the alimentary tract, along with major shifts in diet following development from larva to adult. Little is known about how these developmental changes impact the gut microbiome of the host organism. The metamorphosis of the sea lamprey (Petromyzon marinus) from a sedentary filter-feeding larva to a free-swimming sanguivorous parasite is characterized by major physiological and morphological changes to all organ systems. The transformation of the alimentary canal includes closure of the larval esophagus and the physical isolation of the pharynx from the remainder of the gut, which results in a nonfeeding period that can last up to 8 months. To determine how the gut microbiome is affected by metamorphosis, the microbial communities of feeding and nonfeeding larval and parasitic sea lamprey were surveyed using both culture-dependent and -independent methods. Our results show that the gut of the filter-feeding larva contains a greater diversity of bacteria than that of the blood-feeding parasite, with the parasite gut being dominated by Aeromonas and, to a lesser extent, Citrobacter and Shewanella. Phylogenetic analysis of the culturable Aeromonas from both the larval and parasitic gut revealed that at least five distinct species were represented. Phenotypic characterization of these isolates revealed that over half were capable of sheep red blood cell hemolysis, but all were capable of trout red blood cell hemolysis. This suggests that the enrichment of Aeromonas that accompanies metamorphosis is likely related to the sanguivorous lifestyle of the parasitic sea lamprey. PMID:22923392

  4. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

    PubMed Central

    Liu, Zuheng; Liu, Hai-Yue; Zhou, Haobin; Zhan, Qiong; Lai, Wenyan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2017-01-01

    Physical exercise is commonly regarded as protective against cardiovascular disease (CVD). Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI). Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma) that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD. PMID:28919891

  5. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice.

    PubMed

    Liu, Zuheng; Liu, Hai-Yue; Zhou, Haobin; Zhan, Qiong; Lai, Wenyan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2017-01-01

    Physical exercise is commonly regarded as protective against cardiovascular disease (CVD). Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI). Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma) that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

  6. Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

    PubMed Central

    Yap, Theresa Wan-Chen; Gan, Han-Ming; Lee, Yin-Peng; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Francois, Fritz; Perez-Perez, Guillermo I.; Loke, Mun-Fai; Goh, Khean-Lee; Vadivelu, Jamuna

    2016-01-01

    Background Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. Methods As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. Results We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. Conclusions Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen

  7. Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults.

    PubMed

    Yap, Theresa Wan-Chen; Gan, Han-Ming; Lee, Yin-Peng; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Francois, Fritz; Perez-Perez, Guillermo I; Loke, Mun-Fai; Goh, Khean-Lee; Vadivelu, Jamuna

    2016-01-01

    Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of

  8. Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India.

    PubMed

    Kedia, Saurabh; Rampal, Ritika; Paul, Jaishree; Ahuja, Vineet

    2016-07-01

    The disease profile in the Indian population provides a unique opportunity for studying the host microbiome interaction in both infectious (amebiasis) and autoimmune diseases like inflammatory bowel disease (IBD) from a similar environment and genetic background. Analysis of fecal samples from untreated amebic liver abscess (ALA) patients, Entamoeba histolytica (Eh)-negative and -positive asymptomatic individuals, and pus samples from naive ALA patients revealed a significant reduction in Lactobacillus in asymptomatic individuals (Eh +ve) and ALA patients. Two anaerobic genera, namely Bacteroides and Peptostreptococcus, were detected in naive ALA pus samples. Analysis of fecal samples from amoebic colitis patients showed a significant decline in population of Bacteroides, Clostridium coccoides and leptum subgroup, Lactobacillus, Campylobacter, and Eubacterium, whereas a significant increase in Bifidobacterium was observed. Mucosa-associated bacterial flora analysis from IBD patients and healthy controls revealed a significant difference in concentration of bacteria among predominating and subdominating genera between ulcerative colitis (UC), Crohn's disease (CD) patients, and controls. In contrast to the mucosal studies, we found a significant increase in lactobacilli population in fecal samples of active UC patients. Another study revealed a significant decrease of Clostridium coccoides and leptum clusters in fecal samples of active UC patients along with decreased concentrations of fecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate. We therefore found similar perturbations in gut microbiome in both infectious and autoimmune diseases, indicating inflammation to be the major driver for changes in gut microbiome.

  9. Characterization of the Gut Microbiome Using 16S or Shotgun Metagenomics

    PubMed Central

    Jovel, Juan; Patterson, Jordan; Wang, Weiwei; Hotte, Naomi; O'Keefe, Sandra; Mitchel, Troy; Perry, Troy; Kao, Dina; Mason, Andrew L.; Madsen, Karen L.; Wong, Gane K.-S.

    2016-01-01

    The advent of next generation sequencing (NGS) has enabled investigations of the gut microbiome with unprecedented resolution and throughput. This has stimulated the development of sophisticated bioinformatics tools to analyze the massive amounts of data generated. Researchers therefore need a clear understanding of the key concepts required for the design, execution and interpretation of NGS experiments on microbiomes. We conducted a literature review and used our own data to determine which approaches work best. The two main approaches for analyzing the microbiome, 16S ribosomal RNA (rRNA) gene amplicons and shotgun metagenomics, are illustrated with analyses of libraries designed to highlight their strengths and weaknesses. Several methods for taxonomic classification of bacterial sequences are discussed. We present simulations to assess the number of sequences that are required to perform reliable appraisals of bacterial community structure. To the extent that fluctuations in the diversity of gut bacterial populations correlate with health and disease, we emphasize various techniques for the analysis of bacterial communities within samples (α-diversity) and between samples (β-diversity). Finally, we demonstrate techniques to infer the metabolic capabilities of a bacteria community from these 16S and shotgun data. PMID:27148170

  10. 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

  11. Sex-specific modulation of the gut microbiome and behavior in Siberian hamsters.

    PubMed

    Sylvia, Kristyn E; Jewell, Cathleen P; Rendon, Nikki M; St John, Emma A; Demas, Gregory E

    2017-02-01

    The gut microbiome is a diverse, host-specific, and symbiotic bacterial environment that is critical for mammalian survival and exerts a surprising yet powerful influence on brain and behavior. Gut dysbiosis has been linked to a wide range of physical and psychological disorders, including autism spectrum disorders and anxiety, as well as autoimmune and inflammatory disorders. A wealth of information on the effects of dysbiosis on anxiety and depression has been reported in laboratory model systems (e.g., germ-free mice); however, the effects of microbiome disruption on social behaviors (e.g., aggression) of non-model species that may be particularly important in understanding many aspects of physiology and behavior have yet to be fully explored. Here we assessed the sex-specific effects of a broad-spectrum antibiotic on the gut microbiome and its effects on social behaviors in male and female Siberian hamsters (Phodopus sungorus). In Experiment 1, we administered a broad-spectrum antibiotic on a short-term basis and found that antibiotic treatment altered the microbial communities in the gut in male and female hamsters. In Experiment 2, we tested the effects of single versus repeated antibiotic treatment (including a recovery phase) on behavior, and found that two, but not one, treatments caused marked decreases in aggressive behavior, but not other social behaviors, in males; aggression returned to normal levels following recovery. Antibiotic-treated females, in contrast, showed decreased aggression after a single treatment, with all other social behaviors unaffected. Unlike males, female aggression did not return to normal during either recovery period. The present findings demonstrate that modest antibiotic treatment results in marked disruption of the gut microbiome in hamsters, akin to research done in other rodent species and humans. Further, we show that treatment with a broad-spectrum antibiotic, which has dysbiotic effects, also has robust, sex

  12. Relationship between Obesity, Gut Microbiome and Hepatocellular Carcinoma Development.

    PubMed

    Hara, Eiji

    2015-01-01

    During the past several decades, the percentage of excess bodyweight and obese adults and children has increased dramatically, and is becoming one of the most serious public health problems worldwide. Extensive epidemiological studies have revealed that there is a strong link between obesity and some common cancers. However, the exact molecular mechanisms linking obesity and cancer are not fully understood yet. Recently, we have reported that dietary or genetic obesity provokes alterations of gut microbiota profile, thereby increasing the levels of deoxycholic acid (DCA), a secondary bile acid produced solely by the 7α-dehydroxylation of primary bile acids carried out by gut bacteria. The enterohepatic circulation of DCA provokes DNA damage and consequent cellular senescence in hepatic stellate cells (HSCs) which, in turn, secrete various inflammatory and tumor-promoting factors in the liver, thus facilitating hepatocellular carcinoma (HCC) development in mice. Interestingly, signs of senescence-associated secretory phenotypes were also observed in the HSCs in the area of HCC arising in patients with nonalcoholic steatohepatitis, implying that a similar pathway is likely to contribute to at least certain aspects of obesity-associated HCC development in humans as well. In this review, I will provide an overview of our recent work and discuss the next steps, focusing on the potential clinical implications of our findings. 2015 S. Karger AG, Basel.

  13. Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design

    PubMed Central

    Laukens, Debby; Brinkman, Brigitta M.; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

    2015-01-01

    Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host–microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. PMID:26323480

  14. Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design.

    PubMed

    Laukens, Debby; Brinkman, Brigitta M; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

    2016-01-01

    Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host-microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. © FEMS 2015.

  15. Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice

    PubMed Central

    Howe, Adina; Ringus, Daina L; Williams, Ryan J; Choo, Zi-Ning; Greenwald, Stephanie M; Owens, Sarah M; Coleman, Maureen L; Meyer, Folker; Chang, Eugene B

    2016-01-01

    To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showed significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. The contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health. PMID:26473721

  16. Gut microbiome as a clinical tool in gastrointestinal disease management: are we there yet?

    PubMed

    Quigley, Eamonn M M

    2017-05-01

    Spurred on by ever-evolving developments in analytical methodology, the microbiome, and the gut microbiome in particular, has become the hot topic in biomedical research. Ingenious experiments in animal models have revealed the extent to which the gut microbiota sustains health and how its disruption might contribute to disease pathogenesis. Not surprisingly, associations between the microbiota and disease states in humans have been the subject of considerable interest and many links proposed. However, with rare exceptions, the incrimination of an altered microbiota in disease pathogenesis seems premature at this time given our incomplete understanding of the composition of the gut microbiota in health and the effect of many confounding factors in the interpretation of supposedly abnormal microbial signatures. Future studies must account for these variables and the bidirectionality of host-microorganism interactions in health and disease. In this Perspectives, the status of microbiota signatures in the clinical arena (for facilitating diagnosis or refining prognosis) will be critically assessed and guidance toward future progress provided.

  17. Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice

    DOE PAGES

    Howe, Adina; Ringus, Daina L.; Williams, Ryan J.; ...

    2015-10-16

    To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showedmore » significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. Finally, the contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health.« less

  18. Functional profiling of the gut microbiome in disease-associated inflammation

    PubMed Central

    2013-01-01

    The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation. PMID:23906180

  19. Composition of the Cockroach Gut Microbiome in the Presence of Parasitic Nematodes

    PubMed Central

    Vicente, Cláudia S. L.; Ozawa, Sota; Hasegawa, Koichi

    2016-01-01

    Cockroaches are parasitized by thelastomatid nematodes, which live in an obligate manner in their hindgut and interact with the resident microbial community. In the present study, a composition analysis was performed on the gut microbiome of Periplaneta fuliginosa and P. americana to investigate natural and artificial infection by thelastomatid nematodes. Nine libraries of the 16S rRNA gene V3–V4 region were prepared for pyrosequencing. We examined the complete gut microbiome (fore-, mid-, and hindgut) of lab-reared P. fuliginosa naturally infected with the parasitic nematode Leidynema appendiculatum and those that were nematode-free, and complemented our study by characterizing the hindgut microbial communities of lab-reared P. americana naturally infected with Hammerschmidtiella diesingi and Thelastoma bulhoesi, artificially infected with L. appendiculatum, and those that were nematode-free. Our results revealed that the fore- and midgut of naturally infected and nematode-free P. fuliginosa have close microbial communities, which is in contrast with hindgut communities; the hindgut communities of both cockroaches exhibit higher microbial diversities in the presence of their natural parasites and marked differences were observed in the abundance of the most representative taxa, namely Firmicutes, Proteobacteria, and Bacteroidetes. Our results have provided basic information and encourage further studies on multitrophic interactions in the cockroach gut as well as the thelastomatid nematodes that play a role in this environment. PMID:27524304

  20. Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice

    SciTech Connect

    Howe, Adina; Ringus, Daina L.; Williams, Ryan J.; Choo, Zi -Ning; Greenwald, Stephanie M.; Owens, Sarah M.; Coleman, Maureen L.; Meyer, Folker; Chang, Eugene B.

    2015-10-16

    To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showed significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. Finally, the contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health.

  1. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome.

    PubMed

    Shoaie, Saeed; Ghaffari, Pouyan; Kovatcheva-Datchary, Petia; Mardinoglu, Adil; Sen, Partho; Pujos-Guillot, Estelle; de Wouters, Tomas; Juste, Catherine; Rizkalla, Salwa; Chilloux, Julien; Hoyles, Lesley; Nicholson, Jeremy K; Dore, Joel; Dumas, Marc E; Clement, Karine; Bäckhed, Fredrik; Nielsen, Jens

    2015-08-04

    The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Alterations of the Murine Gut Microbiome with Age and Allergic Airway Disease.

    PubMed

    Vital, Marius; Harkema, Jack R; Rizzo, Mike; Tiedje, James; Brandenberger, Christina

    2015-01-01

    The gut microbiota plays an important role in the development of asthma. With advanced age the microbiome and the immune system are changing and, currently, little is known about how these two factors contribute to the development of allergic asthma in the elderly. In this study we investigated the associations between the intestinal microbiome and allergic airway disease in young and old mice that were sensitized and challenged with house dust mite (HDM). After challenge, the animals were sacrificed, blood serum was collected for cytokine analysis, and the lungs were processed for histopathology. Fecal pellets were excised from the colon and subjected to 16S rRNA analysis. The microbial community structure changed with age and allergy development, where alterations in fecal communities from young to old mice resembled those after HDM challenge. Allergic mice had induced serum levels of IL-17A and old mice developed a greater allergic airway response compared to young mice. This study demonstrates that the intestinal bacterial community structure differs with age, possibly contributing to the exaggerated pulmonary inflammatory response in old mice. Furthermore, our results show that the composition of the gut microbiota changes with pulmonary allergy, indicating bidirectional gut-lung communications.

  3. Novel {alpha}-glucosidase from human gut microbiome : substrate specificities and their switch.

    SciTech Connect

    Tan, K.; Tesar, C.; Wilton, R.; Keigher, L.; Babnigg, G.; Joachimiak, A.; Biosciences Division

    2010-01-01

    The human intestine harbors a large number of microbes forming a complex microbial community that greatly affects the physiology and pathology of the host. In the human gut microbiome, the enrichment in certain protein gene families appears to be widespread. They include enzymes involved in carbohydrate metabolism such as glucoside hydrolases of dietary polysaccharides and glycoconjugates. We report the crystal structures (wild type, 2 mutants, and a mutant/substrate complex) and the enzymatic activity of a recombinant {alpha}-glucosidase from human gut bacterium Ruminococcus obeum. The first ever protein structures from this bacterium reveal a structural homologue to human intestinal maltase-glucoamylase with a highly conserved catalytic domain and reduced auxiliary domains. The {alpha}-glucosidase, a member of GH31 family, shows substrate preference for {alpha}(1-6) over {alpha}(1-4) glycosidic linkages and produces glucose from isomaltose as well as maltose. The preference can be switched by a single mutation at its active site, suggestive of widespread adaptation to utilization of a variety of polysaccharides by intestinal micro-organisms as energy resources. Novel {alpha}-glucosidase from human gut microbiome: substrate specificities and their switch.

  4. Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients.

    PubMed

    Galloway-Peña, Jessica R; Smith, Daniel P; Sahasrabhojane, Pranoti; Wadsworth, W Duncan; Fellman, Bryan M; Ajami, Nadim J; Shpall, Elizabeth J; Daver, Naval; Guindani, Michele; Petrosino, Joseph F; Kontoyiannis, Dimitrios P; Shelburne, Samuel A

    2017-02-28

    temporal variability of both oral microbial diversity (P = 0.03) and community structure (P = 0.002). These data quantify the longitudinal variability of the oral and gut microbiota in AML patients, show that increased variability was correlated with adverse clinical outcomes, and offer the possibility of using stabilizing taxa as a method of focused microbiome repletion. Furthermore, these results support the importance of longitudinal microbiome sampling and analyses, rather than one time measurements, in research and future clinical practice.

  5. Social Influences on Prevotella and the Gut Microbiome of Young Monkeys.

    PubMed

    Amaral, Wellington Z; Lubach, Gabriele R; Proctor, Alexandra; Lyte, Mark; Phillips, Gregory J; Coe, Christopher L

    2017-10-01

    Our aim was to evaluate the bacterial profiles of young monkeys as they were weaned into peer groups with a particular focus on Prevotella, an important taxon in both human and nonhuman primates. The weaning of infants and increased social contact with peers is a developmental stage that is likely to affect the gut microbiome. Gut bacteria were assessed in 63 rhesus monkeys living in social groups comprised of 4 to 7 individuals. Two groups were assessed prospectively on day 1 and 2 weeks after rehousing away from the mother and group formation. Ten additional groups were assessed at 2 weeks after group establishment. Fecal genomic DNA was extracted and 16S ribosomal RNA sequenced by Illumina MiSeq (5 social groups) and 454-amplicon pyrosequencing (7 social groups). Combining weaned infants into small social groups led to a microbial convergence by 2 weeks (p < .001). Diversity analyses indicated more similar community structure within peer groups than across groups (p < .01). Prevotella was the predominant taxon, and its abundance differed markedly across individuals. Indices of richness, microbial profiles, and less abundant taxa were all associated with the Prevotella levels. Functional Kyoto Encyclopedia of Genes and Genomes analyses suggested corresponding shifts in metabolic pathways. The formation of small groups of young rhesus monkeys was associated with significant shifts in the gut microbiota. The profiles were closely associated with the abundance of Prevotella, a predominant taxon in the rhesus monkey gut. Changes in the structure of the gut microbiome are likely to induce differences in metabolic and physiologic functioning.

  6. Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships.

    PubMed

    Lyte, Mark; Fodor, Anthony A; Chapman, Clinton D; Martin, Gary G; Perez-Chanona, Ernesto; Jobin, Christian; Dess, Nancy K

    2016-06-01

    The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.

  7. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden.

    PubMed

    Baxter, Nielson T; Zackular, Joseph P; Chen, Grace Y; Schloss, Patrick D

    2014-01-01

    A growing body of evidence indicates that the gut microbiome plays a role in the development of colorectal cancer (CRC). Patients with CRC harbor gut microbiomes that are structurally distinct from those of healthy individuals; however, without the ability to track individuals during disease progression, it has not been possible to observe changes in the microbiome over the course of tumorigenesis. Mouse models have demonstrated that these changes can further promote colonic tumorigenesis. However, these models have relied upon mouse-adapted bacterial populations and so it remains unclear which human-adapted bacterial populations are responsible for modulating tumorigenesis. We transplanted fecal microbiota from three CRC patients and three healthy individuals into germ-free mice, resulting in six structurally distinct microbial communities. Subjecting these mice to a chemically induced model of CRC resulted in different levels of tumorigenesis between mice. Differences in the number of tumors were strongly associated with the baseline microbiome structure in mice, but not with the cancer status of the human donors. Partitioning of baseline communities into enterotypes by Dirichlet multinomial mixture modeling resulted in three enterotypes that corresponded with tumor burden. The taxa most strongly positively correlated with increased tumor burden were members of the Bacteroides, Parabacteroides, Alistipes, and Akkermansia, all of which are Gram-negative. Members of the Gram-positive Clostridiales, including multiple members of Clostridium Group XIVa, were strongly negatively correlated with tumors. Analysis of the inferred metagenome of each community revealed a negative correlation between tumor count and the potential for butyrate production, and a positive correlation between tumor count and the capacity for host glycan degradation. Despite harboring distinct gut communities, all mice underwent conserved structural changes over the course of the model. The

  8. Marked alterations in the distal gut microbiome linked to diet-induced obesity

    PubMed Central

    Turnbaugh, Peter J.; Backhed, Fredrik; Fulton, Lucinda; Gordon, Jeffrey I.

    2013-01-01

    SUMMARY We have investigated the inter-relationship between diet, gut microbial ecology and energy balance using a mouse model of obesity produced by consumption of a prototypic Western diet. Diet-induced obesity (DIO) produced a bloom in a single uncultured clade within the Mollicutes class of the Firmicutes, which became the dominant lineage within the distal gut microbiota. This bloom was diminished by subsequent dietary manipulations that limit weight gain and reduce adiposity. Transplantation of the microbiota from mice with DIO to lean germ-free recipients produced a significantly greater increase in adiposity than transplants from lean donors. Metagenomic sequencing of the gut microbiome, biochemical assays, plus sequencing and in silico metabolic reconstructions of a related human gut-associated Mollicute (E.dolichum), revealed features that may provide a competitive advantage for members of the bloom in the Western diet nutrient milieu, including genes involved in import and metabolism of simple sugars. Our study illustrates how combining comparative metagenomics with gnotobiotic mouse models and specific dietary manipulations can disclose the niches of previously uncharacterized members of the gut microbiota. PMID:18407065

  9. Identifying Keystone Species in the Human Gut Microbiome from Metagenomic Timeseries Using Sparse Linear Regression

    PubMed Central

    Fisher, Charles K.; Mehta, Pankaj

    2014-01-01

    Human associated microbial communities exert tremendous influence over human health and disease. With modern metagenomic sequencing methods it is now possible to follow the relative abundance of microbes in a community over time. These microbial communities exhibit rich ecological dynamics and an important goal of microbial ecology is to infer the ecological interactions between species directly from sequence data. Any algorithm for inferring ecological interactions must overcome three major obstacles: 1) a correlation between the abundances of two species does not imply that those species are interacting, 2) the sum constraint on the relative abundances obtained from metagenomic studies makes it difficult to infer the parameters in timeseries models, and 3) errors due to experimental uncertainty, or mis-assignment of sequencing reads into operational taxonomic units, bias inferences of species interactions due to a statistical problem called “errors-in-variables”. Here we introduce an approach, Learning Interactions from MIcrobial Time Series (LIMITS), that overcomes these obstacles. LIMITS uses sparse linear regression with boostrap aggregation to infer a discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on synthetic data and showed that it could reliably infer the topology of the inter-species ecological interactions. We then used LIMITS to characterize the species interactions in the gut microbiomes of two individuals and found that the interaction networks varied significantly between individuals. Furthermore, we found that the interaction networks of the two individuals are dominated by distinct “keystone species”, Bacteroides fragilis and Bacteroided stercosis, that have a disproportionate influence on the structure of the gut microbiome even though they are only found in moderate abundance. Based on our results, we hypothesize that the abundances of certain keystone species may be responsible for individuality in the human

  10. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression.

    PubMed

    Fisher, Charles K; Mehta, Pankaj

    2014-01-01

    Human associated microbial communities exert tremendous influence over human health and disease. With modern metagenomic sequencing methods it is now possible to follow the relative abundance of microbes in a community over time. These microbial communities exhibit rich ecological dynamics and an important goal of microbial ecology is to infer the ecological interactions between species directly from sequence data. Any algorithm for inferring ecological interactions must overcome three major obstacles: 1) a correlation between the abundances of two species does not imply that those species are interacting, 2) the sum constraint on the relative abundances obtained from metagenomic studies makes it difficult to infer the parameters in timeseries models, and 3) errors due to experimental uncertainty, or mis-assignment of sequencing reads into operational taxonomic units, bias inferences of species interactions due to a statistical problem called "errors-in-variables". Here we introduce an approach, Learning Interactions from MIcrobial Time Series (LIMITS), that overcomes these obstacles. LIMITS uses sparse linear regression with boostrap aggregation to infer a discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on synthetic data and showed that it could reliably infer the topology of the inter-species ecological interactions. We then used LIMITS to characterize the species interactions in the gut microbiomes of two individuals and found that the interaction networks varied significantly between individuals. Furthermore, we found that the interaction networks of the two individuals are dominated by distinct "keystone species", Bacteroides fragilis and Bacteroided stercosis, that have a disproportionate influence on the structure of the gut microbiome even though they are only found in moderate abundance. Based on our results, we hypothesize that the abundances of certain keystone species may be responsible for individuality in the human gut

  11. Characterization of Gut Microbiome Dynamics in Developing Pekin Ducks and Impact of Management System.

    PubMed

    Best, Aaron A; Porter, Amanda L; Fraley, Susan M; Fraley, Gregory S

    2016-01-01

    Little to no research has been conducted on the gut microbiome of the Pekin duck, yet over 24.5 million ducks are raised for human consumption each year in the United States alone. Knowledge of the microbiome could lead to an understanding of the effects of growing conditions such as the use of prebiotics, probiotics, and enzymes in feeding practices, the use of antibiotics, and the sources of pathogenic bacteria in diseased ducks. In order to characterize changes in the caecal microbiome that occur as ducks develop through a typical industry grow-out period, a 16S rRNA community analysis of caecal contents collected over a 6-week period was conducted using a next generation sequencing approach. Transitions in the composition of the caecal microbiome occurred throughout the lifespan, with a large shift during days 4 through 10 posthatch. Two major phyla of bacteria were found to be present within the caeca of aviary raised ducks, with the relative abundance of each phylum varying by age of the duck. Proteobacteria is dominant for the first 3 days of age, and Firmicutes increases and dominates beginning at day 4. Barn raised ducks contained a significant population of Bacteroidetes in addition to Proteobacteria and Firmicutes at later developmental time points, though this phylum was absent in aviary raised ducks. Genera containing pathogens of anseriformes most often found in industry settings were either absent or found as normal parts of the caecal microbial populations. The high level differences in phylum abundance highlight the importance of well-designed sampling strategies for microbiome based studies. Results showed clear distinctions between Pekin Duck caecal contents and those of Broiler Chickens and Turkey in a qualitative comparison. These data provide a reference point for studies of the Pekin Duck through industry grow-out ages, provide a foundation for understanding the types of bacteria that promote health, and may lead to improved methods to

  12. New frontiers in nanotoxicology: Gut microbiota/microbiome-mediated effects of engineered nanomaterials.

    PubMed

    Pietroiusti, Antonio; Magrini, Andrea; Campagnolo, Luisa

    2016-05-15

    It has been recently recognized that the gut microbiota, the community of organisms living within the gastrointestinal tract is an integral part of the human body, and that its genoma (the microbiome) interacts with the genes expressed by the cells of the host organism. Several important physiological functions require the cooperation of microbiota/microbiome, whose alterations play an important role in several human diseases. On this basis, it is probable that microbiota/microbiome may in part be involved in many biological effects of engineered nanomaterials (ENMs). There are still few reports on the possible toxicological effects of ENMs on microbiota/microbiome, and on their possible clinical consequences. Available data suggest that several ENMs, including carbon nanotubes (CNTs), titanium dioxide, cerium dioxide, zinc oxide, nanosilica and nanosilver may affect the microbiota and that clinical disorders such as colitis, obesity and immunological dysfunctions might follow. On the other hand, other ENMs such as iron nanoparticles may show advantages over traditional iron-based supplemental treatment because they do not interfere with the microbiota/microbiome, and some ENM-based therapeutic interventions might be employed for treating intestinal infections, while sparing the microbiota. The final section of the review is focused on the possible future developments of the research in this field: new in vitro and in vivo models, possible biomarkers and new pathophysiological pathways are proposed and discussed, as well as the possibility that metabolic changes following ENMs/microbiota interactions might be exploited as a fingerprint of ENM exposure. The potential toxicological relevance of physico-chemical modifications of ENMs induced by the microbiota is also highlighted. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Neuroblastoma causes alterations of the intestinal microbiome, gut hormones, inflammatory cytokines, and bile acid composition.

    PubMed

    Castellani, Christoph; Singer, Georg; Kaiser, Margarita; Kaiser, Thomas; Huang, Jianfeng; Sperl, Daniela; Kashofer, Karl; Fauler, Guenter; Guertl-Lackner, Barbara; Höfler, Gerald; Till, Holger

    2017-08-01

    To assess the effect of neuroblastoma (NB) on the intestinal microbiome, metabolism, and inflammatory parameters in a murine model. Athymic Hsd:Fox1nu mice received subperitoneal implantation of human NB cells (MHH-NB11) (tumor group, TG) or culture medium (sham group). Following 10 weeks of tumor growth, all animals were sacrificed to collect total white adipose tissue (WAT). Luminex assays were performed for gut hormone and inflammation marker analysis. Bile acids were measured by high-performance liquid chromatography-mass spectrometry in feces and serum. The microbiome of the ileal content was determined by 16S rDNA next-generation sequencing. At 10 weeks, tumors masses in the TG reached a mean weight of 1.10 g (interquartile range 3.45 g) associated with a significant reduction in WAT. Furthermore, in the TG, there was a marked reduction in leptin and an increase in glucagon-like peptide 1 serum levels. Moreover, the TG mice displayed a pro-inflammatory profile, with significant increases in monocyte chemotactic protein 1, tumor necrosis factor alpha, and interleukin-10. Lithocholic acid, deoxycholic acid, and ursodeoxycholic acid were significantly decreased in the stool of TG mice. Significant alterations of the intestinal microbiome were found in the ileal contents of the TG. The present study provides a first glimpse that human NB in a murine model induces tumor cachexia associated with alterations in metabolic and inflammatory parameters, as well as changes in the intestinal microbiota. Since the intestinal microbiome is known to contribute to the host's ability to harvest energy, a favorable modulation of the intestinal microbiome in tumor patients could potentially represent a novel therapeutic target to prevent tumor-associated cachexia. © 2017 Wiley Periodicals, Inc.

  14. Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health.

    PubMed

    Malmuthuge, Nilusha; Guan, Le Luo

    2017-07-01

    Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed. An increasing number of studies are exploring the microbial composition of the gut, the mucosal immune system, and early dietary interventions to improve the health of dairy calves, revealing possibilities for effectively reducing the susceptibility of calves to enteric infections while promoting growth. Still, comprehensive understanding of the effect of dietary interventions on gut microbiota-one of the key aspects of gut health-is lacking. Such knowledge may provide in-depth understanding of the mechanisms behind functional changes in response to dietary interventions. Understanding of host-microbial interactions with dietary interventions and the role of the gut microbiota during pathogenesis at the site of infection in early life is vital for designing effective tools and techniques to improve calf gut health. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice.

    PubMed

    Bian, Xiaoming; Chi, Liang; Gao, Bei; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-01-01

    Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.

  16. Genomics and metagenomics of trimethylamine-utilizing Archaea in the human gut microbiome.

    PubMed

    Borrel, Guillaume; McCann, Angela; Deane, Jennifer; Neto, Marta C; Lynch, Denise B; Brugère, Jean-François; O'Toole, Paul W

    2017-09-01

    The biological significance of Archaea in the human gut microbiota is largely unclear. We recently reported genomic and biochemical analyses of the Methanomassiliicoccales, a novel order of methanogenic Archaea dwelling in soil and the animal digestive tract. We now show that these Methanomassiliicoccales are present in published microbiome data sets from eight countries. They are represented by five Operational Taxonomic Units present in at least four cohorts and phylogenetically distributed into two clades. Genes for utilizing trimethylamine (TMA), a bacterial precursor to an atherosclerogenic human metabolite, were present in four of the six novel Methanomassiliicoccales genomes assembled from ELDERMET metagenomes. In addition to increased microbiota TMA production capacity in long-term residential care subjects, abundance of TMA-utilizing Methanomassiliicoccales correlated positively with bacterial gene count for TMA production and negatively with fecal TMA concentrations. The two large Methanomassiliicoccales clades have opposite correlations with host health status in the ELDERMET cohort and putative distinct genomic signatures for gut adaptation.

  17. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection.

    PubMed

    Theriot, Casey M; Koenigsknecht, Mark J; Carlson, Paul E; Hatton, Gabrielle E; Nelson, Adam M; Li, Bo; Huffnagle, Gary B; Z Li, Jun; Young, Vincent B

    2014-01-01

    Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.

  18. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    PubMed Central

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  19. Recovery of the gut microbiome following fecal microbiota transplantation.

    PubMed

    Seekatz, Anna M; Aas, Johannes; Gessert, Charles E; Rubin, Timothy A; Saman, Daniel M; Bakken, Johan S; Young, Vincent B

    2014-06-17

    Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection. Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for

  20. Longitudinal Prediction of the Infant Gut Microbiome with Dynamic Bayesian Networks

    PubMed Central

    McGeachie, Michael J.; Sordillo, Joanne E.; Gibson, Travis; Weinstock, George M.; Liu, Yang-Yu; Gold, Diane R.; Weiss, Scott T.; Litonjua, Augusto

    2016-01-01

    Sequencing of the 16S rRNA gene allows comprehensive assessment of bacterial community composition from human body sites. Previously published and publicly accessible data on 58 preterm infants in the Neonatal Intensive Care Unit who underwent frequent stool collection was used. We constructed Dynamic Bayesian Networks from the data and analyzed predictive performance and network characteristics. We constructed a DBN model of the infant gut microbial ecosystem, which explicitly captured specific relationships and general trends in the data: increasing amounts of Clostridia, residual amounts of Bacilli, and increasing amounts of Gammaproteobacteria that then give way to Clostridia. Prediction performance of DBNs with fewer edges were overall more accurate, although less so on harder-to-predict subjects (p = 0.045). DBNs provided quantitative likelihood estimates for rare abruptions events. Iterative prediction was less accurate (p < 0.001), but showed remarkable insensitivity to initial conditions and predicted convergence to a mix of Clostridia, Gammaproteobacteria, and Bacilli. DBNs were able to identify important relationships between microbiome taxa and predict future changes in microbiome composition from measured or synthetic initial conditions. DBNs also provided likelihood estimates for sudden, dramatic shifts in microbiome composition, which may be useful in guiding further analysis of those samples. PMID:26853461

  1. 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.

  2. The early infant gut microbiome varies in association with a maternal high-fat diet.

    PubMed

    Chu, Derrick M; Antony, Kathleen M; Ma, Jun; Prince, Amanda L; Showalter, Lori; Moller, Michelle; Aagaard, Kjersti M

    2016-08-09

    Emerging evidence suggests that the in utero environment is not sterile as once presumed. Work in the mouse demonstrated transmission of commensal bacteria from mother to fetus during gestation, though it is unclear what modulates this process. We have previously shown in the nonhuman primate that, independent of obesity, a maternal high-fat diet during gestation and lactation persistently shapes the juvenile gut microbiome. We therefore sought to interrogate in a population-based human longitudinal cohort whether a maternal high-fat diet similarly alters the neonatal and infant gut microbiome in early life. A representative cohort was prospectively enrolled either in the early third trimester or intrapartum (n = 163), with a subset consented to longitudinal sampling through the postpartum interval (n = 81). Multiple body site samples, including stool and meconium, were collected from neonates at delivery and by 6 weeks of age. A rapid dietary questionnaire was administered to estimate intake of fat, added sugars, and fiber over the past month (National Health and Examination Survey). DNA was extracted from each infant meconium/stool sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis. On average, the maternal dietary intake of fat ranged from 14.0 to 55.2 %, with an average intake of 33.1 % (σ = 6.1 %). Mothers whose diets significantly differed from the mean (±1 standard deviation) were separated into two distinct groups, a control group (n = 13, μ = 24.4 %) and a high-fat group (n = 13, μ = 43.1 %). Principal coordinate analysis revealed that the microbiome of the neonatal stool at birth (meconium) clustered differently by virtue of maternal gestational diet (PERMANOVA p = 0.001). LEfSe feature selection identified several taxa that discriminated the groups, with a notable relative depletion of Bacteroides in the neonates exposed to a maternal high-fat gestational diet (Student's t-test, p < 0

  3. Feeding Systems and the Gut Microbiome: Gut-Brain Interactions With Relevance to Psychiatric Conditions.

    PubMed

    Mason, Brittany L

    2017-06-08

    Physical and mental health is dependent on the environment, and feeding is a prime example of this environmental exchange. While the hypothalamus controls both feeding behavior and the stress response, the integration of the neural control centers and the peripheral gut allows for disruption in the gastrointestinal systems and dysfunctional communication to the brain. The purpose of this review is to familiarize clinicians with the physiology controlling feeding behavior and its implications for psychiatric conditions, such as anorexia nervosa and depression. Growing understanding of how integrated bacterial life is in the body has shown that gut bacteria regulate basic physiologic processes and are implicated in various disease states and contribute to regulation of mood. Responses to stress have effects on feeding behavior and mood and the regulation of the stress response by the gut microbiota could contribute to the dysfunction seen in patients with psychiatric illnesses. Gut microbiota may contribute to dysfunction in psychiatric illnesses. New opportunities to modulate existing gut microbiota using probiotics could be novel targets for clinical interventions. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  4. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

    PubMed

    Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J

    2016-06-01

    The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota

  5. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition

    PubMed Central

    Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J

    2016-01-01

    The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota–inflammasome–brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota

  6. Gut microbiomes of free-ranging and captive Namibian cheetahs: Diversity, putative functions and occurrence of potential pathogens.

    PubMed

    Wasimuddin; Menke, Sebastian; Melzheimer, Jörg; Thalwitzer, Susanne; Heinrich, Sonja; Wachter, Bettina; Sommer, Simone

    2017-08-07

    Although the significance of the gut microbiome for host health is well acknowledged, the impact of host traits and environmental factors on the interindividual variation of gut microbiomes of wildlife species is not well understood. Such information is essential; however, as changes in the composition of these microbial communities beyond the natural range might cause dysbiosis leading to increased susceptibility to infections. We examined the potential influence of sex, age, genetic relatedness, spatial tactics and the environment on the natural range of the gut microbiome diversity in free-ranging Namibian cheetahs (Acinonyx jubatus). We further explored the impact of an altered diet and frequent contact with roaming dogs and cats on the occurrence of potential bacterial pathogens by comparing free-ranging and captive individuals living under the same climatic conditions. Abundance patterns of particular bacterial genera differed between the sexes, and bacterial diversity and richness were higher in older (>3.5 years) than in younger individuals. In contrast, male spatial tactics, which probably influence host exposure to environmental bacteria, had no discernible effect on the gut microbiome. The profound resemblance of the gut microbiome of kin in contrast to nonkin suggests a predominant role of genetics in shaping bacterial community characteristics and functional similarities. We also detected various Operational Taxonomic Units (OTUs) assigned to potential pathogenic bacteria known to cause diseases in humans and wildlife species, such as Helicobacter spp., and Clostridium perfringens. Captive individuals did not differ in their microbial alpha diversity but exhibited higher abundances of OTUs related to potential pathogenic bacteria and shifts in disease-associated functional pathways. Our study emphasizes the need to integrate ecological, genetic and pathogenic aspects to improve our comprehension of the main drivers of natural variation and shifts in

  7. Application of a hierarchical enzyme classification method reveals the role of gut microbiome in human metabolism

    PubMed Central

    2015-01-01

    Background Enzymes are known as the molecular machines that drive the metabolism of an organism; hence identification of the full enzyme complement of an organism is essential to build the metabolic blueprint of that species as well as to understand the interplay of multiple species in an ecosystem. Experimental characterization of the enzymatic reactions of all enzymes in a genome is a tedious and expensive task. The problem is more pronounced in the metagenomic samples where even the species are not adequately cultured or characterized. Enzymes encoded by the gut microbiota play an essential role in the host metabolism; thus, warranting the need to accurately identify and annotate the full enzyme complements of species in the genomic and metagenomic projects. To fulfill this need, we develop and apply a method called ECemble, an ensemble approach to identify enzymes and enzyme classes and study the human gut metabolic pathways. Results ECemble method uses an ensemble of machine-learning methods to accurately model and predict enzymes from protein sequences and also identifies the enzyme classes and subclasses at the finest resolution. A tenfold cross-validation result shows accuracy between 97 and 99% at different levels in the hierarchy of enzyme classification, which is superior to comparable methods. We applied ECemble to predict the entire complements of enzymes from ten sequenced proteomes including the human proteome. We also applied this method to predict enzymes encoded by the human gut microbiome from gut metagenomic samples, and to study the role played by the microbe-derived enzymes in the human metabolism. After mapping the known and predicted enzymes to canonical human pathways, we identified 48 pathways that have at least one bacteria-encoded enzyme, which demonstrates the complementary role of gut microbiome in human gut metabolism. These pathways are primarily involved in metabolizing dietary nutrients such as carbohydrates, amino acids, lipids

  8. Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models

    PubMed Central

    Rajpal, Deepak K.; Klein, Jean-Louis; Mayhew, David; Boucheron, Joyce; Spivak, Aaron T.; Kumar, Vinod; Ingraham, Karen; Paulik, Mark; Chen, Lihong; Van Horn, Stephanie; Thomas, Elizabeth; Sathe, Ganesh; Livi, George P.; Holmes, David J.; Brown, James R.

    2015-01-01

    The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases. PMID:26709835

  9. Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models.

    PubMed

    Rajpal, Deepak K; Klein, Jean-Louis; Mayhew, David; Boucheron, Joyce; Spivak, Aaron T; Kumar, Vinod; Ingraham, Karen; Paulik, Mark; Chen, Lihong; Van Horn, Stephanie; Thomas, Elizabeth; Sathe, Ganesh; Livi, George P; Holmes, David J; Brown, James R

    2015-01-01

    The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases.

  10. The New Era of Treatment for Obesity and Metabolic Disorders: Evidence and Expectations for Gut Microbiome Transplantation.

    PubMed

    Jayasinghe, Thilini N; Chiavaroli, Valentina; Holland, David J; Cutfield, Wayne S; O'Sullivan, Justin M

    2016-01-01

    Key Points: The microbiome has been implicated in the development of obesity. Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications. Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an "endocrine" organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.

  11. Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses.

    PubMed

    Bartley, Jenna M; Zhou, Xin; Kuchel, George A; Weinstock, George M; Haynes, Laura

    2017-01-01

    Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection to explore the impact of flu infection, aging, and caloric restriction on the gut microbiome. Young, middle-aged, and aged caloric restricted (CR) and ad lib fed (AL) mice were examined after a sublethal flu infection. All mice lost 10-20% body weight and, as expected for these early time points, losses were similar at different ages and between diet groups. Cytokine and chemokine levels were also similar with the notable exception of IL-1α, which rose more than fivefold in aged AL mouse serum, while it remained unchanged in aged CR serum. Fecal microbiome phyla abundance profiles were similar in young, middle-aged, and aged AL mice at baseline and at 4 days post flu infection, while increases in Proteobacteria were evident at 7 days post flu infection in all three age groups. CR mice, compared to AL mice in each age group, had increased abundance of Proteobacteria and Verrucomicrobia at all time points. Interestingly, principal coordinate analysis determined that diet exerts a greater effect on the microbiome than age or flu infection. Percentage body weight loss correlated with the relative abundance of Proteobacteria regardless of age, suggesting flu pathogenicity is related to Proteobacteria abundance. Further, several microbial Operational Taxonomic Units from the Bacteroidetes phyla correlated with serum chemokine/cytokines regardless of both diet and age suggesting an interplay between flu-induced systemic inflammation and gut microbiota. These exploratory studies

  12. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives.

    PubMed

    Gloux, Karine; Anba-Mondoloni, Jamila

    2016-01-01

    Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn's disease.

  13. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn’s Disease Patients and Unaffected First-Degree Relatives

    PubMed Central

    Gloux, Karine; Anba-Mondoloni, Jamila

    2016-01-01

    Crohn’s disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn’s disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn’s disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn’s disease. PMID:26824357

  14. Environmental Particulate Matter Induces Murine Intestinal Inflammatory Responses and Alters the Gut Microbiome

    PubMed Central

    Kish, Lisa; Hotte, Naomi; Kaplan, Gilaad G.; Vincent, Renaud; Tso, Robert; Gänzle, Michael; Rioux, Kevin P.; Thiesen, Aducio; Barkema, Herman W.; Wine, Eytan; Madsen, Karen L.

    2013-01-01

    Background Particulate matter (PM) is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions. Methods Wild-type 129/SvEv mice were gavaged with Ottawa urban PM10 (EHC-93) for 7–14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM10 for measurement of proliferation. Long-term effects of exposure (35 days) on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10−/−) mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum. Results Short-term treatment of wild-type mice with PM10 altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10−/− mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10−/− mice had increased disease as evidenced by enhanced histological damage. Conclusions Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine. PMID:23638009

  15. Natural history of the infant gut microbiome and impact of antibiotic treatments on strain-level diversity and stability

    PubMed Central

    Yassour, Moran; Vatanen, Tommi; Siljander, Heli; Hämäläinen, Anu-Maaria; Härkönen, Taina; Ryhänen, Samppa J; Franzosa, Eric A; Vlamakis, Hera; Huttenhower, Curtis; Gevers, Dirk; Lander, Eric S; Knip, Mikael; Xavier, Ramnik J

    2016-01-01

    The gut microbiome plays a key role in human health. This community is dynamic during the first three years of life, before stabilizing to an adult-like state. However, relatively little is known about the impact of environmental factors on the developing human gut microbiome. Here we report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, approximately half of whom received multiple courses of antibiotics during the first three years of life. While the gut microbiome of most vaginally born children was dominated by Bacteroides species, we found that all four children born by Cesarean section and approximately 20% of vaginally born children lacked Bacteroides in the first six to eighteen months. Our longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed us to detect strain-level variation as well as the abundance of antibiotic resistance (AR) genes. The microbiota of antibiotic-treated children was less diverse at the level of both species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. AR genes carried on microbial chromosomes showed a strong peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes on mobile elements persisted longer after the end of antibiotic therapy. Our results highlight the value of dense longitudinal studies with high-resolution strain profiles in studying the establishment and response to perturbation of the infant gut microbiome. PMID:27306663

  16. Spatial Structure of the Mormon Cricket Gut Microbiome and its Predicted Contribution to Nutrition and Immune Function

    PubMed Central

    Smith, Chad C.; Srygley, Robert B.; Healy, Frank; Swaminath, Karthikeyan; Mueller, Ulrich G.

    2017-01-01

    The gut microbiome of insects plays an important role in their ecology and evolution, participating in nutrient acquisition, immunity, and behavior. Microbial community structure within the gut is heavily influenced by differences among gut regions in morphology and physiology, which determine the niches available for microbes to colonize. We present a high-resolution analysis of the structure of the gut microbiome in the Mormon cricket Anabrus simplex, an insect known for its periodic outbreaks in the western United States and nutrition-dependent mating system. The Mormon cricket microbiome was dominated by 11 taxa from the Lactobacillaceae, Enterobacteriaceae, and Streptococcaceae. While most of these were represented in all gut regions, there were marked differences in their relative abundance, with lactic-acid bacteria (Lactobacillaceae) more common in the foregut and midgut and enteric (Enterobacteriaceae) bacteria more common in the hindgut. Differences in community structure were driven by variation in the relative prevalence of three groups: a Lactobacillus in the foregut, Pediococcus lactic-acid bacteria in the midgut, and Pantoea agglomerans, an enteric bacterium, in the hindgut. These taxa have been shown to have beneficial effects on their hosts in insects and other animals by improving nutrition, increasing resistance to pathogens, and modulating social behavior. Using PICRUSt to predict gene content from our 16S rRNA sequences, we found enzymes that participate in carbohydrate metabolism and pathogen defense in other orthopterans. These were predominately represented in the hindgut and midgut, the most important sites for nutrition and pathogen defense. Phylogenetic analysis of 16S rRNA sequences from cultured isolates indicated low levels of divergence from sequences derived from plants and other insects, suggesting that these bacteria are likely to be exchanged between Mormon crickets and the environment. Our study shows strong spatial variation in

  17. Spatial Structure of the Mormon Cricket Gut Microbiome and its Predicted Contribution to Nutrition and Immune Function.

    PubMed

    Smith, Chad C; Srygley, Robert B; Healy, Frank; Swaminath, Karthikeyan; Mueller, Ulrich G

    2017-01-01

    The gut microbiome of insects plays an important role in their ecology and evolution, participating in nutrient acquisition, immunity, and behavior. Microbial community structure within the gut is heavily influenced by differences among gut regions in morphology and physiology, which determine the niches available for microbes to colonize. We present a high-resolution analysis of the structure of the gut microbiome in the Mormon cricket Anabrus simplex, an insect known for its periodic outbreaks in the western United States and nutrition-dependent mating system. The Mormon cricket microbiome was dominated by 11 taxa from the Lactobacillaceae, Enterobacteriaceae, and Streptococcaceae. While most of these were represented in all gut regions, there were marked differences in their relative abundance, with lactic-acid bacteria (Lactobacillaceae) more common in the foregut and midgut and enteric (Enterobacteriaceae) bacteria more common in the hindgut. Differences in community structure were driven by variation in the relative prevalence of three groups: a Lactobacillus in the foregut, Pediococcus lactic-acid bacteria in the midgut, and Pantoea agglomerans, an enteric bacterium, in the hindgut. These taxa have been shown to have beneficial effects on their hosts in insects and other animals by improving nutrition, increasing resistance to pathogens, and modulating social behavior. Using PICRUSt to predict gene content from our 16S rRNA sequences, we found enzymes that participate in carbohydrate metabolism and pathogen defense in other orthopterans. These were predominately represented in the hindgut and midgut, the most important sites for nutrition and pathogen defense. Phylogenetic analysis of 16S rRNA sequences from cultured isolates indicated low levels of divergence from sequences derived from plants and other insects, suggesting that these bacteria are likely to be exchanged between Mormon crickets and the environment. Our study shows strong spatial variation in

  18. Relationships between diet-related changes in the gut microbiome and cognitive flexibility.

    PubMed

    Magnusson, K R; Hauck, L; Jeffrey, B M; Elias, V; Humphrey, A; Nath, R; Perrone, A; Bermudez, L E

    2015-08-06

    Western diets are high in fat and sucrose and can influence behavior and gut microbiota. There is growing evidence that altering the microbiome can influence the brain and behavior. This study was designed to determine whether diet-induced changes in the gut microbiota could contribute to alterations in anxiety, memory or cognitive flexibility. Two-month-old, male C57BL/6 mice were randomly assigned high-fat (42% fat, 43% carbohydrate (CHO), high-sucrose (12% fat, 70% CHO (primarily sucrose) or normal chow (13% kcal fat, 62% CHO) diets. Fecal microbiome analysis, step-down latency, novel object and novel location tasks were performed prior to and 2weeks after diet change. Water maze testing for long- and short-term memory and cognitive flexibility was conducted during weeks 5-6 post-diet change. Some similarities in alterations in the microbiome were seen in both the high-fat and high-sucrose diets (e.g., increased Clostridiales), as compared to the normal diet, but the percentage decreases in Bacteroidales were greater in the high-sucrose diet mice. Lactobacillales was only significantly increased in the high-sucrose diet group and Erysipelotrichales was only significantly affected by the high-fat diet. The high-sucrose diet group was significantly impaired in early development of a spatial bias for long-term memory, short-term memory and reversal training, compared to mice on normal diet. An increased focus on the former platform position was seen in both high-sucrose and high-fat groups during the reversal probe trials. There was no significant effect of diet on step-down, exploration or novel recognitions. Higher percentages of Clostridiales and lower expression of Bacteroidales in high-energy diets were related to the poorer cognitive flexibility in the reversal trials. These results suggest that changes in the microbiome may contribute to cognitive changes associated with eating a Western diet. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights

  19. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    DOE PAGES

    Xiong, Weili; Richard J. Giannone; Morowitz, Michael J.; ...

    2014-10-28

    The early-life microbiota establishment in the human infant gut is highly variable and plays a crucial role in host nutrients and immunity maturation. While high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the construction of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on Double Filtering (DF) to enhance microbial protein characterization in complex fecal samples from healthy premature infants. We improved the overall depth of infant gut proteome measurement, withmore » an increase in the number of identified low abundance proteins, and observed greater than twofold improvement in metrics for microbial protein identifications and quantifications with a relatively high rank correlation to control. We further showed the substantial enhancement of this approach for extensively interpreting microbial functional categories between infants by affording more detailed and confident identified categories. This approach provided an avenue for in-depth measurement in the microbial component of infant fecal samples and thus comprehensive characterization of infant gut microbiome functionality.« less

  20. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics

    PubMed Central

    Ridlon, Jason M.; Bajaj, Jasmohan S.

    2015-01-01

    The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an “endocrine organ” with potential to alter host physiology, perhaps to their own favor. We propose the term “sterolbiome” to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed. PMID:26579434

  1. Gut Microbiome Composition in Young Nicaraguan Children during Diarrhea Episodes and Recovery

    PubMed Central

    Becker-Dreps, Sylvia; Allali, Imane; Monteagudo, Andrea; Vilchez, Samuel; Hudgens, Michael G.; Rogawski, Elizabeth T.; Carroll, Ian M.; Zambrana, Luis Enrique; Espinoza, Felix; Andrea Azcarate-Peril, M.

    2015-01-01

    Understanding how the gut microbiota is affected by diarrhea episodes may help explain alterations in intestinal function among children in low-income settings. This study examined the composition of the gut microbiome of Nicaraguan children both during diarrhea episodes and while free of diarrhea for at least 2 months. Relative abundances of bacterial taxa, phylogenetic diversity, and species richness were determined by 16S amplicon sequencing and compared between paired diarrhea and recovery samples. A total of 66 stools were provided by 25 children enrolled in a 1-year cohort study of diarrhea etiologies. Children in our cohort had a mean age of 21.9 months; 64% were breast-fed, and 10% had received an antibiotic during the diarrhea episode. Overall, phylogenetic diversity and species richness did not differ significantly between diarrhea and recovery stools. However, of children who had a bacterial enteropathogen detected in any diarrhea stool, none experienced an increase in phylogenetic diversity in recovery, whereas of those in whom no bacterial enteropathogens were detected in their diarrhea stool(s), 59% experienced an increase in phylogenetic diversity in recovery (P = 0.008). This preliminary study suggests that recovery of the gut microbiota after a diarrhea episode may take longer time than previously thought and may be pathogen specific. PMID:26350452

  2. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    SciTech Connect

    Xiong, Weili; Richard J. Giannone; Morowitz, Michael J.; Banfield, Jillian F.; Robert L. Hettich

    2014-10-28

    The early-life microbiota establishment in the human infant gut is highly variable and plays a crucial role in host nutrients and immunity maturation. While high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the construction of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on Double Filtering (DF) to enhance microbial protein characterization in complex fecal samples from healthy premature infants. We improved the overall depth of infant gut proteome measurement, with an increase in the number of identified low abundance proteins, and observed greater than twofold improvement in metrics for microbial protein identifications and quantifications with a relatively high rank correlation to control. We further showed the substantial enhancement of this approach for extensively interpreting microbial functional categories between infants by affording more detailed and confident identified categories. This approach provided an avenue for in-depth measurement in the microbial component of infant fecal samples and thus comprehensive characterization of infant gut microbiome functionality.

  3. Role of the Gut Microbiome in Modulating Arthritis Progression in Mice

    PubMed Central

    Liu, Xiaofei; Zeng, Benhua; Zhang, Juan; Li, Wenxia; Mou, Fangxiang; Wang, Heng; Zou, Qinghua; Zhong, Bing; Wu, Like; Wei, Hong; Fang, Yongfei

    2016-01-01

    Genetics alone cannot explain most cases of rheumatoid arthritis (RA). Thus, investigating environmental factors such as the gut microbiota may provide new insights into the initiation and progression of RA. In this study, we performed 16S rRNA sequencing to characterise the gut microbiota of DBA1 mice that did or did not develop arthritis after induction with collagen. We found that divergence in the distribution of microbiota after induction was pronounced and significant. Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset. With disease development, the abundance of OTUs affiliated with the families Bacteroidaceae, Lachnospiraceae, and S24-7 increased significantly in CIA-susceptible mice. Notably, germ-free mice conventionalized with the microbiota from CIA-susceptible mice showed a higher frequency of arthritis induction than those conventionalized with the microbiota from CIA-resistant mice. Consistently, the concentration of the cytokine interleukin-17 in serum and the proportions of CD8+T cells and Th17 lymphocytes in the spleen were significantly higher in the former group, whereas the abundances of dendritic cells, B cells, and Treg cells in the spleen were significantly lower. Our results suggest that the gut microbiome influences arthritis susceptibility. PMID:27481047

  4. Modulation of Gut Microbiome Composition and Function in Experimental Colitis Treated with Sulfasalazine

    PubMed Central

    Zheng, Haihui; Chen, Mingyi; Li, Yuan; Wang, Yuanyuan; Wei, Lin; Liao, Ziqiong; Wang, Mengxia; Ma, Fangli; Liao, Qiongfeng; Xie, Zhiyong

    2017-01-01

    Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of Mycoplasma was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD. PMID:28936203

  5. Modulation of Gut Microbiome Composition and Function in Experimental Colitis Treated with Sulfasalazine.

    PubMed

    Zheng, Haihui; Chen, Mingyi; Li, Yuan; Wang, Yuanyuan; Wei, Lin; Liao, Ziqiong; Wang, Mengxia; Ma, Fangli; Liao, Qiongfeng; Xie, Zhiyong

    2017-01-01

    Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of Mycoplasma was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD.

  6. Dining in with Trillions of Fascinating Friends: Exploring Our Human Gut Microbiome in Health and Disease

    PubMed Central

    Gordon, J.I.

    2011-01-01

    Our genetic landscape is a summation of the genes embedded in our human genome and in the genomes of our microbial symbionts (the microbiome). Similarly, our metabolic features (metabotypes) are an amalgamation of human and microbial traits. Therefore, understanding of the range of human genetic and metabolic diversity means that we must characterize our microbiomes, which contain at least several hundred-fold more genes than our human genome, as well as the factors that influence the properties of our microbial communities (microbiota). The results should provide an additional perspective about contemporary human biology as we assess how our changing lifestyles, cultural norms, socioeconomic status, and biosphere are influencing our microbial ecology and health status. I will discuss the results of our group's ongoing metagenomic studies of the interrelationships between diet and the structure and dynamic operations of the human gut microbiome. We believe that understanding these interrelationships is important for advancing our appreciation of the nutritional value of food ingredients, for creating new nutritional guidelines for humans at various stages of their lifespan, and for developing new ways to deliberately manipulate the properties of the gut microbiota to prevent or treat various diseases. We have developed a translational medicine pipeline that involves metagenomic analyses of the gut microbial communities of adult mono- and dizygotic twins living in the USA who are lean, or concordant or discordant for obesity, and twins aged 0–3 years living in developing countries who develop normally, or who become malnourished and are treated with a ready-to-use therapeutic food (RUTF). Intact fecal communities from these individuals, or ‘personal’ culture collections that capture the majority of bacterial diversity in their microbiota, are then transplanted into germ-free mice, which are fed the diets of the human donors, or systematically manipulated

  7. Characterization of Gut Microbiome Dynamics in Developing Pekin Ducks and Impact of Management System

    PubMed Central

    Best, Aaron A.; Porter, Amanda L.; Fraley, Susan M.; Fraley, Gregory S.

    2017-01-01

    Little to no research has been conducted on the gut microbiome of the Pekin duck, yet over 24.5 million ducks are raised for human consumption each year in the United States alone. Knowledge of the microbiome could lead to an understanding of the effects of growing conditions such as the use of prebiotics, probiotics, and enzymes in feeding practices, the use of antibiotics, and the sources of pathogenic bacteria in diseased ducks. In order to characterize changes in the caecal microbiome that occur as ducks develop through a typical industry grow-out period, a 16S rRNA community analysis of caecal contents collected over a 6-week period was conducted using a next generation sequencing approach. Transitions in the composition of the caecal microbiome occurred throughout the lifespan, with a large shift during days 4 through 10 posthatch. Two major phyla of bacteria were found to be present within the caeca of aviary raised ducks, with the relative abundance of each phylum varying by age of the duck. Proteobacteria is dominant for the first 3 days of age, and Firmicutes increases and dominates beginning at day 4. Barn raised ducks contained a significant population of Bacteroidetes in addition to Proteobacteria and Firmicutes at later developmental time points, though this phylum was absent in aviary raised ducks. Genera containing pathogens of anseriformes most often found in industry settings were either absent or found as normal parts of the caecal microbial populations. The high level differences in phylum abundance highlight the importance of well-designed sampling strategies for microbiome based studies. Results showed clear distinctions between Pekin Duck caecal contents and those of Broiler Chickens and Turkey in a qualitative comparison. These data provide a reference point for studies of the Pekin Duck through industry grow-out ages, provide a foundation for understanding the types of bacteria that promote health, and may lead to improved methods to

  8. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection

    PubMed Central

    Antharam, Vijay C.; McEwen, Daniel C.; Garrett, Timothy J.; Dossey, Aaron T.; Li, Eric C.; Kozlov, Andrew N.; Mesbah, Zhubene; Wang, Gary P.

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism. PMID:26871580

  9. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    PubMed

    Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  10. Pyrosequencing Reveals the Predominance of Pseudomonadaceae in Gut Microbiome of a Gall Midge

    PubMed Central

    Bansal, Raman; Hulbert, Scot H.; Reese, John C.; Whitworth, Robert J.; Stuart, Jeffrey J.; Chen, Ming-Shun

    2014-01-01

    Gut microbes are known to play various roles in insects such as digestion of inaccessible nutrients, synthesis of deficient amino acids, and interaction with ecological environments, including host plants. Here, we analyzed the gut microbiome in Hessian fly, a serious pest of wheat. A total of 3,654 high quality sequences of the V3 hypervariable region of the 16S rRNA gene were obtained through 454-pyrosequencing. From these sequences, 311 operational taxonomic units (OTUs) were obtained at the ≥97% similarity cutoff. In the gut of 1st instar, otu01, a member of Pseudomonas, was predominant, representing 90.2% of total sequences. otu13, an unidentified genus in the Pseudomonadaceae family, represented 1.9% of total sequences. The remaining OTUs were each less than 1%. In the gut of the 2nd instar, otu01 and otu13 decreased to 85.5% and 1.5%, respectively. otu04, a member of Buttiauxella, represented 9.7% of total sequences. The remaining OTUs were each less than 1%. In the gut of the 3rd instar, otu01 and otu13 further decreased to 29.0% and 0%, respectively. otu06, otu08, and otu16, also three members of the Pseudomonadaceae family were 13.2%, 8.6%, and 2.3%, respectively. In addition, otu04 and otu14, two members of the Enterobacteriaceae family, were 4.7% and 2.5%; otu18 and otu20, two members of the Xanthomonadaceae family, were 1.3% and 1.2%, respectively; otu12, a member of Achromobacter, was 4.2%; otu19, a member of Undibacterium, was 1.4%; and otu9, otu10, and otu15, members of various families, were 6.1%, 6.3%, and 1.9%, respectively. The investigation into dynamics of Pseudomonas, the most abundant genera, revealed that its population level was at peak in freshly hatched or 1 day larvae as well as in later developmental stages, thus suggesting a prominent role for this bacterium in Hessian fly development and in its interaction with host plants. This study is the first comprehensive survey on bacteria associated with the gut of a gall midge, and

  11. Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool

    PubMed Central

    Gorzelak, Monika A.; Gill, Sandeep K.; Tasnim, Nishat; Ahmadi-Vand, Zahra; Jay, Michael; Gibson, Deanna L.

    2015-01-01

    Gut microbiome community analysis is used to understand many diseases like inflammatory bowel disease, obesity, and diabetes. Sampling methods are an important consideration for human microbiome research, yet are not emphasized in many studies. In this study, we demonstrate that the preparation, handling, and storage of human faeces are critical processes that alter the outcomes of downstream DNA-based bacterial community analyses via qPCR. We found that stool subsampling resulted in large variability of gut microbiome data due to different microenvironments harbouring various taxa within an individual stool. However, we reduced intra-sample variability by homogenizing the entire stool sample in liquid nitrogen and subsampling from the resulting crushed powder prior to DNA extraction. We experimentally determined that the bacterial taxa varied with room temperature storage beyond 15 minutes and beyond three days storage in a domestic frost-free freezer. While freeze thawing only had an effect on bacterial taxa abundance beyond four cycles, the use of samples stored in RNAlater should be avoided as overall DNA yields were reduced as well as the detection of bacterial taxa. Overall we provide solutions for processing and storing human stool samples that reduce variability of microbiome data. We recommend that stool is frozen within 15 minutes of being defecated, stored in a domestic frost-free freezer for less than three days, and homogenized prior to DNA extraction. Adoption of these simple protocols will have a significant and positive impact on future human microbiome research. PMID:26252519

  12. Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool.

    PubMed

    Gorzelak, Monika A; Gill, Sandeep K; Tasnim, Nishat; Ahmadi-Vand, Zahra; Jay, Michael; Gibson, Deanna L

    2015-01-01

    Gut microbiome community analysis is used to understand many diseases like inflammatory bowel disease, obesity, and diabetes. Sampling methods are an important consideration for human microbiome research, yet are not emphasized in many studies. In this study, we demonstrate that the preparation, handling, and storage of human faeces are critical processes that alter the outcomes of downstream DNA-based bacterial community analyses via qPCR. We found that stool subsampling resulted in large variability of gut microbiome data due to different microenvironments harbouring various taxa within an individual stool. However, we reduced intra-sample variability by homogenizing the entire stool sample in liquid nitrogen and subsampling from the resulting crushed powder prior to DNA extraction. We experimentally determined that the bacterial taxa varied with room temperature storage beyond 15 minutes and beyond three days storage in a domestic frost-free freezer. While freeze thawing only had an effect on bacterial taxa abundance beyond four cycles, the use of samples stored in RNAlater should be avoided as overall DNA yields were reduced as well as the detection of bacterial taxa. Overall we provide solutions for processing and storing human stool samples that reduce variability of microbiome data. We recommend that stool is frozen within 15 minutes of being defecated, stored in a domestic frost-free freezer for less than three days, and homogenized prior to DNA extraction. Adoption of these simple protocols will have a significant and positive impact on future human microbiome research.

  13. Gut microbiome analysis in neuromyelitis optica reveals overabundance of Clostridium perfringens

    PubMed Central

    Cree, Bruce A. C.; Spencer, Collin M.; Varrin‐Doyer, Michel; Baranzini, Sergio E.

    2016-01-01

    T cells from neuromyelitis optica (NMO) patients, which recognize the immunodominant epitope of aquaporin‐4, exhibit Th17 polarization and cross‐react with a homologous sequence of a Clostridium perfringens adenosine triphosphate‐binding cassette transporter. Therefore, this commensal microbe might participate in NMO pathogenesis. We examined the gut microbiome by PhyloChip G3 from 16 NMO patients, 16 healthy controls (HC), and 16 multiple sclerosis patients. A significant difference in the abundance of several microbial communities was observed between NMO and HC (Adonis test, p = 0.001). Strikingly, C. perfringens was overrepresented in NMO (p = 5.24 × 10−8). These observations support a potential role for C. perfringens in NMO pathogenesis. Ann Neurol 2016;80:443–447 PMID:27398819

  14. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder.

    PubMed

    Heintz-Buschart, Anna; Pandey, Urvashi; Wicke, Tamara; Sixel-Döring, Friederike; Janzen, Annette; Sittig-Wiegand, Elisabeth; Trenkwalder, Claudia; Oertel, Wolfgang H; Mollenhauer, Brit; Wilmes, Paul

    2017-08-26

    Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement

  15. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

    PubMed Central

    MacFabe, Derrick F.

    2012-01-01

    Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental

  16. Further analysis reveals new gut microbiome markers of type 2 diabetes mellitus.

    PubMed

    Wang, Xiaokai; Xu, Xiaoqiang; Xia, Yan

    2017-03-01

    In recent years, metagenome-wide association studies have revealed potential relationships between intestinal microbiomes and the pathogenesis of type 2 diabetes mellitus (T2DM). However, considering the increase in volume of gene catalogues and algorithms, an updated analysis would be expected to confirm previous discoveries and provide new knowledge. We therefore constructed new profiles after mapping the recent catalogue of reference genes in the human gut microbiome to reanalyze samples from T2DM cases and controls in the Chinese population. We identified different compositions between Chinese controls and T2DM patients at the species and genus levels, especially in the case of butyrate-producing bacteria, Haemophilus, and Lactobacillus. An effective metagenomic linkage group random forest model was built to differentiate controls from T2DM cases in different cohorts. Functional markers from the Kyoto Encyclopedia of Genes and Genomes database were identified using new annotations. We also report 16 virulence factor markers and 22 antibiotic resistance markers associated with T2DM.

  17. Gut Microbiome of an 11th Century A.D. Pre-Columbian Andean Mummy

    PubMed Central

    Santiago-Rodriguez, Tasha M.; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E.; Toranzos, Gary A.; Marota, Isolina; Cano, Raul J.

    2015-01-01

    The process of natural mummification is a rare and unique process from which little is known about the resulting microbial community structure. In the present study, we characterized the microbiome of paleofeces, and ascending, transverse and descending colon of an 11th century A.D. pre-Columbian Andean mummy by 16S rRNA gene high-throughput sequencing and metagenomics. Firmicutes were the most abundant bacterial group, with Clostridium spp. comprising up to 96.2% of the mummified gut, while Turicibacter spp. represented 89.2% of the bacteria identified in the paleofeces. Microbiome profile of the paleofeces was unique when compared to previously characterized coprolites that did not undergo natural mummification. We identified DNA sequences homologous to Clostridium botulinum, Trypanosoma cruzi and human papillomaviruses (HPVs). Unexpectedly, putative antibiotic-resistance genes including beta-lactamases, penicillin-binding proteins, resistance to fosfomycin, chloramphenicol, aminoglycosides, macrolides, sulfa, quinolones, tetracycline and vancomycin, and multi-drug transporters, were also identified. The presence of putative antibiotic-resistance genes suggests that resistance may not necessarily be associated with a selective pressure of antibiotics or contact with European cultures. Identification of pathogens and antibiotic-resistance genes in ancient human specimens will aid in the understanding of the evolution of pathogens as a way to treat and prevent diseases caused by bacteria, microbial eukaryotes and viruses. PMID:26422376

  18. Gut Microbiome of an 11th Century A.D. Pre-Columbian Andean Mummy.

    PubMed

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E; Toranzos, Gary A; Marota, Isolina; Cano, Raul J

    2015-01-01

    The process of natural mummification is a rare and unique process from which little is known about the resulting microbial community structure. In the present study, we characterized the microbiome of paleofeces, and ascending, transverse and descending colon of an 11th century A.D. pre-Columbian Andean mummy by 16S rRNA gene high-throughput sequencing and metagenomics. Firmicutes were the most abundant bacterial group, with Clostridium spp. comprising up to 96.2% of the mummified gut, while Turicibacter spp. represented 89.2% of the bacteria identified in the paleofeces. Microbiome profile of the paleofeces was unique when compared to previously characterized coprolites that did not undergo natural mummification. We identified DNA sequences homologous to Clostridium botulinum, Trypanosoma cruzi and human papillomaviruses (HPVs). Unexpectedly, putative antibiotic-resistance genes including beta-lactamases, penicillin-binding proteins, resistance to fosfomycin, chloramphenicol, aminoglycosides, macrolides, sulfa, quinolones, tetracycline and vancomycin, and multi-drug transporters, were also identified. The presence of putative antibiotic-resistance genes suggests that resistance may not necessarily be associated with a selective pressure of antibiotics or contact with European cultures. Identification of pathogens and antibiotic-resistance genes in ancient human specimens will aid in the understanding of the evolution of pathogens as a way to treat and prevent diseases caused by bacteria, microbial eukaryotes and viruses.

  19. Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development

    PubMed Central

    Bhinder, Ganive; Allaire, Joannie M.; Garcia, Cyrielle; Lau, Jennifer T.; Chan, Justin M.; Ryz, Natasha R.; Bosman, Else S.; Graef, Franziska A.; Crowley, Shauna M.; Celiberto, Larissa S.; Berkmann, Julia C.; Dyer, Roger A.; Jacobson, Kevan; Surette, Michael G.; Innis, Sheila M.; Vallance, Bruce A.

    2017-01-01

    Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition. Here we tested the effects of MFGM supplementation on intestinal development and the microbiome as well as its potential to protect against Clostridium difficile induced colitis. The pup-in-a-cup model was used to deliver either control or MFGM supplemented formula to rats from 5 to 15 days of age; with mother’s milk (MM) reared animals used as controls. While CTL formula yielded significant deficits in intestinal development as compared to MM littermates, addition of MFGM to formula restored intestinal growth, Paneth and goblet cell numbers, and tight junction protein patterns to that of MM pups. Moreover, the gut microbiota of MFGM and MM pups displayed greater similarities than CTL, and proved protective against C. difficile toxin induced inflammation. Our study thus demonstrates that addition of MFGM to formula promotes development of the intestinal epithelium and microbiome and protects against inflammation. PMID:28349941

  20. Extensive strain-level copy-number variation across human gut microbiome species.

    PubMed

    Greenblum, Sharon; Carr, Rogan; Borenstein, Elhanan

    2015-02-12

    Within each bacterial species, different strains may vary in the set of genes they encode or in the copy number of these genes. Yet, taxonomic characterization of the human microbiota is often limited to the species level or to previously sequenced strains, and accordingly, the prevalence of intra-species variation, its functional role, and its relation to host health remain unclear. Here, we present a comprehensive large-scale analysis of intra-species copy-number variation in the gut microbiome, introducing a rigorous computational pipeline for detecting such variation directly from shotgun metagenomic data. We uncover a large set of variable genes in numerous species and demonstrate that this variation has significant functional and clinically relevant implications. We additionally infer intra-species compositional profiles, identifying population structure shifts and the presence of yet uncharacterized variants. Our results highlight the complex relationship between microbiome composition and functional capacity, linking metagenome-level compositional shifts to strain-level variation. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Metagenomic Identification of a Novel Salt Tolerance Gene from the Human Gut Microbiome Which Encodes a Membrane Protein with Homology to a brp/blh-Family β-Carotene 15,15′-Monooxygenase

    PubMed Central

    Culligan, Eamonn P.; Sleator, Roy D.; Marchesi, Julian R.; Hill, Colin

    2014-01-01

    The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane. PMID:25058308

  2. Food matters: how the microbiome and gut-brain interaction might impact the development and course of anorexia nervosa.

    PubMed

    Herpertz-Dahlmann, Beate; Seitz, Jochen; Baines, John

    2017-01-31

    Anorexia nervosa (AN) is one of the most common chronic illnesses in female adolescents and exhibits the highest mortality risk of all psychiatric disorders. Evidence for the effectiveness of psychotherapeutic or psychopharmacological interventions is weak. Mounting data indicate that the gut microbiome interacts with the central nervous system and the immune system by neuroendocrine, neurotransmitter, neurotrophic and neuroinflammatory afferent and efferent pathways. There is growing evidence that the gut microbiota influences weight regulation and psychopathology, such as anxiety and depression. This article reviews how the gut-brain interaction may impact the development and course of AN. A "leaky gut", characterized by antigens traversing the intestinal wall, was demonstrated in an animal model of AN, and could underlie the low-grade inflammation and increased risk of autoimmune diseases found in AN. Moreover, starvation has a substantial impact on the gut microbiome, and diets used for re-nutrition based on animal products may support the growth of bacteria capable of triggering inflammation. As there is currently no empirically derived agreement on therapeutic re-nourishment in AN, this review discusses how consideration of gut-brain interactions may be important for treatment regarding the determination of target weight, rapidity of weight gain, refeeding methods and composition of the diet which might all be of importance to improve long-term outcome of one of the most chronic psychiatric disorders of adolescence.

  3. Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice.

    PubMed

    Ruan, Jhen-Wei; Statt, Sarah; Huang, Chih-Ting; Tsai, Yi-Ting; Kuo, Cheng-Chin; Chan, Hong-Lin; Liao, Yu-Chieh; Tan, Tse-Hua; Kao, Cheng-Yuan

    2016-11-28

    The gut microbiota plays profound roles in host metabolism and the inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6-deficient mice harbour unique gut microbiota with resistance to diet-induced-obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model, we found that faecal/gut microbiota derived from dusp6-deficient mice significantly increased energy expenditure and reduced weight gain in recipient wild-type mice fed on a high-fat diet. On analysis of the intestinal transcriptome of dusp6-deficient mice, we found that dusp6 deficiency mainly induced biological processes involved in metabolism and the extracellular matrix, particularly the peroxisome proliferator-activated receptor gamma (Pparγ) pathway and tight-junction genes. Furthermore, dusp6-deficient mice have a high-fat-diet-specific transcriptomic response to reverse the expression of genes associated with intestinal barrier functions and mucosal immunity involved in microbiome homeostasis. This study demonstrates that dusp6 deficiency is a strong genetic factor shaping gut microbiota, and that it confers obesity protection by ameliorating the gut microbiota response to diet-mediated stress.

  4. Evidence for a core gut microbiota in the zebrafish

    PubMed Central

    Roeselers, Guus; Mittge, Erika K; Stephens, W Zac; Parichy, David M; Cavanaugh, Colleen M; Guillemin, Karen; Rawls, John F

    2011-01-01

    Experimental analysis of gut microbial communities and their interactions with vertebrate hosts is conducted predominantly in domesticated animals that have been maintained in laboratory facilities for many generations. These animal models are useful for studying coevolved relationships between host and microbiota only if the microbial communities that occur in animals in lab facilities are representative of those that occur in nature. We performed 16S rRNA gene sequence-based comparisons of gut bacterial communities in zebrafish collected recently from their natural habitat and those reared for generations in lab facilities in different geographic locations. Patterns of gut microbiota structure in domesticated zebrafish varied across different lab facilities in correlation with historical connections between those facilities. However, gut microbiota membership in domesticated and recently caught zebrafish was strikingly similar, with a shared core gut microbiota. The zebrafish intestinal habitat therefore selects for specific bacterial taxa despite radical differences in host provenance and domestication status. PMID:21472014

  5. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability.

    PubMed

    Yassour, Moran; Vatanen, Tommi; Siljander, Heli; Hämäläinen, Anu-Maaria; Härkönen, Taina; Ryhänen, Samppa J; Franzosa, Eric A; Vlamakis, Hera; Huttenhower, Curtis; Gevers, Dirk; Lander, Eric S; Knip, Mikael; Xavier, Ramnik J

    2016-06-15

    The gut microbial community is dynamic during the first 3 years of life, before stabilizing to an adult-like state. However, little is known about the impact of environmental factors on the developing human gut microbiome. We report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, about half of whom received multiple courses of antibiotics during the first 3 years of life. Whereas the gut microbiome of most children born by vaginal delivery was dominated by Bacteroides species, the four children born by cesarean section and about 20% of vaginally born children lacked Bacteroides in the first 6 to 18 months of life. Longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed detection of strain-level variation as well as the abundance of antibiotic resistance genes. The microbiota of antibiotic-treated children was less diverse in terms of both bacterial species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. Antibiotic resistance genes carried on microbial chromosomes showed a peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes carried on mobile elements persisted longer after antibiotic therapy ended. Our results highlight the value of high-density longitudinal sampling studies with high-resolution strain profiling for studying the establishment and response to perturbation of the infant gut microbiome. Copyright © 2016, American Association for the Advancement of Science.

  6. The effect of gut microbiome on tolerance to morphine mediated antinociception in mice

    PubMed Central

    Kang, Minho; Mischel, Ryan A.; Bhave, Sukhada; Komla, Essie; Cho, Alvin; Huang, Charity; Dewey, William L.; Akbarali, Hamid I.

    2017-01-01

    There is growing appreciation for the importance of gastrointestinal microbiota in many physiological and pathophysiological processes. While morphine and other narcotics are the most widely prescribed therapy for moderate to severe pain clinically, they have been noted to alter microbial composition and promote bacterial translocation to other tissues. Here we examined the pharmacodynamic properties of chronic morphine in mice following bacterial depletion with oral gavage of an antibiotic cocktail (ABX). ABX significantly reduced gut bacteria and prevented chronic morphine induced increases in gut permeability, colonic mucosal destruction, and colonic IL-1β expression. In addition, ABX prevented the development of antinociceptive tolerance to chronic morphine in both the tail-immersion and acetic acid stretch assays. Morphine tolerance was also reduced by oral vancomycin that has 0% bioavailability. These findings were recapitulated in primary afferent neurons isolated from dorsal root ganglia (DRG) innervating the lower gastrointestinal tract, wherein in-vivo administration of ABX prevented tolerance to morphine-induced hypoexcitability. Finally, though ABX repeatedly demonstrated an ability to prevent tolerance, we show that it did not alter susceptibility to precipitation of withdrawal by naloxone. Collectively, these finding indicate that the gastrointestinal microbiome is an important modulator of physiological responses induced by chronic morphine administration. PMID:28211545

  7. Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.

    PubMed

    Livanos, Alexandra E; Greiner, Thomas U; Vangay, Pajau; Pathmasiri, Wimal; Stewart, Delisha; McRitchie, Susan; Li, Huilin; Chung, Jennifer; Sohn, Jiho; Kim, Sara; Gao, Zhan; Barber, Cecily; Kim, Joanne; Ng, Sandy; Rogers, Arlin B; Sumner, Susan; Zhang, Xue-Song; Cadwell, Ken; Knights, Dan; Alekseyenko, Alexander; Bäckhed, Fredrik; Blaser, Martin J

    2016-08-22

    The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.

  8. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    PubMed Central

    2015-01-01

    The establishment of early life microbiota in the human infant gut is highly variable and plays a crucial role in host nutrient availability/uptake and maturation of immunity. Although high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the acquisition of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on double filtering (DF) the raw samples, a method that fractionates microbial from human cells to enhance microbial protein identification and characterization in complex fecal samples from healthy premature infants. This method dramatically improved the overall depth of infant gut proteome measurement, with an increase in the number of identified low-abundance proteins and a greater than 2-fold improvement in microbial protein identification and quantification. This enhancement of proteome measurement depth enabled a more extensive microbiome comparison between infants by not only increasing the confidence of identified microbial functional categories but also revealing previously undetected categories. PMID:25350865

  9. Host remodeling of the gut microbiome and metabolic changes during pregnancy

    PubMed Central

    Koren, Omry; Goodrich, Julia K.; Cullender, Tyler C.; Spor, Aymé; Laitinen, Kirsi; Bäckhed, Helene Kling; Gonzalez, Antonio; Werner, Jeffrey J.; Angenent, Largus T.; Knight, Rob; Bäckhed, Fredrik; Isolauri, Erika; Salminen, Seppo; Ley, Ruth E.

    2012-01-01

    SUMMARY Many of the immune and metabolic changes occurring during normal pregnancy also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic syndrome in non-pregnant hosts: To explore their role in pregnancy, here we characterized fecal bacteria of 91 pregnant women of varying pre-pregnancy BMIs and gestational diabetes status, and their infants. Similarities between infant-mother microbiotas increased with children’s age, and the infant microbiota was unaffected by mother health status. Gut microbiota changed dramatically from first (T1) to third (T3) trimesters, with vast expansion of diversity between mothers, an overall increase in Proteobacteria and Actinobacteria, and reduced richness. T3 stool showed strongest signs of inflammation and energy loss, however microbiome gene repertoires were constant between trimesters. When transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1. Our findings indicate that host-microbial interactions impacting host metabolism can occur, and may be beneficial, in pregnancy. PMID:22863002

  10. The effect of gut microbiome on tolerance to morphine mediated antinociception in mice.

    PubMed

    Kang, Minho; Mischel, Ryan A; Bhave, Sukhada; Komla, Essie; Cho, Alvin; Huang, Charity; Dewey, William L; Akbarali, Hamid I

    2017-02-17

    There is growing appreciation for the importance of gastrointestinal microbiota in many physiological and pathophysiological processes. While morphine and other narcotics are the most widely prescribed therapy for moderate to severe pain clinically, they have been noted to alter microbial composition and promote bacterial translocation to other tissues. Here we examined the pharmacodynamic properties of chronic morphine in mice following bacterial depletion with oral gavage of an antibiotic cocktail (ABX). ABX significantly reduced gut bacteria and prevented chronic morphine induced increases in gut permeability, colonic mucosal destruction, and colonic IL-1β expression. In addition, ABX prevented the development of antinociceptive tolerance to chronic morphine in both the tail-immersion and acetic acid stretch assays. Morphine tolerance was also reduced by oral vancomycin that has 0% bioavailability. These findings were recapitulated in primary afferent neurons isolated from dorsal root ganglia (DRG) innervating the lower gastrointestinal tract, wherein in-vivo administration of ABX prevented tolerance to morphine-induced hypoexcitability. Finally, though ABX repeatedly demonstrated an ability to prevent tolerance, we show that it did not alter susceptibility to precipitation of withdrawal by naloxone. Collectively, these finding indicate that the gastrointestinal microbiome is an important modulator of physiological responses induced by chronic morphine administration.

  11. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile.

    PubMed

    Peterfreund, Gregory L; Vandivier, Lee E; Sinha, Rohini; Marozsan, Andre J; Olson, William C; Zhu, Jun; Bushman, Frederic D

    2012-01-01

    Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb) to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.

  12. Vegetable microbiomes: is there a connection among opportunistic infections, human health and our ‘gut feeling'?

    PubMed Central

    Berg, Gabriele; Erlacher, Armin; Smalla, Kornelia; Krause, Robert

    2014-01-01

    The highly diverse microbiomes of vegetables are reservoirs for opportunistic and emerging pathogens. In recent years, an increased consumption, larger scale production and more efficient distribution of vegetables together with an increased number of immunocompromised individuals resulted in an enhanced number of documented outbreaks of human infections associated with the consumption of vegetables. Here we discuss the occurrence of potential pathogens in vegetable microbiomes, the impact of farming and processing practices, and plant and human health issues. Based on these results, we discuss the question if vegetables can serve as a source of infection for immunocompromised individuals as well as possible solutions to avoid outbreaks. Moreover, the potentially positive aspects of the vegetables microbiome for the gut microbiota and human health are presented. PMID:25186140

  13. Early childhood gut microbiomes show strong geographic differences among subjects at high risk for type 1 diabetes.

    PubMed

    Kemppainen, Kaisa M; Ardissone, Alexandria N; Davis-Richardson, Austin G; Fagen, Jennie R; Gano, Kelsey A; León-Novelo, Luis G; Vehik, Kendra; Casella, George; Simell, Olli; Ziegler, Anette G; Rewers, Marian J; Lernmark, Åke; Hagopian, William; She, Jin-Xiong; Krischer, Jeffrey P; Akolkar, Beena; Schatz, Desmond A; Atkinson, Mark A; Triplett, Eric W

    2015-02-01

    Gut microbiome dysbiosis is associated with numerous diseases, including type 1 diabetes. This pilot study determines how geographical location affects the microbiome of infants at high risk for type 1 diabetes in a population of homogenous HLA class II genotypes. High-throughput 16S rRNA sequencing was performed on stool samples collected from 90 high-risk, nonautoimmune infants participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study in the U.S., Germany, Sweden, and Finland. Study site-specific patterns of gut colonization share characteristics across continents. Finland and Colorado have a significantly lower bacterial diversity, while Sweden and Washington state are dominated by Bifidobacterium in early life. Bacterial community diversity over time is significantly different by geographical location. The microbiome of high-risk infants is associated with geographical location. Future studies aiming to identify the microbiome disease phenotype need to carefully consider the geographical origin of subjects. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. Conditional postnatal deletion of the neonatal murine hepatic circadian gene, Npas2, alters the gut microbiome following restricted feeding.

    PubMed

    O'Neil, Derek S; Stewart, Christopher J; Chu, Derrick M; Goodspeed, Danielle M; Gonzalez-Rodriguez, Pablo J; Shope, Cynthia D; Aagaard, Kjersti M

    2017-08-01

    We have recently shown in both non-human primates and in rodents that fetal and neonatal hepatic expression of the circadian transcription factor, Npas2, is modulated by a high fat maternal diet and plays a critical role in establishing life-long metabolic homeostasis. Similarly, we and others have also established the importance of the maternal and early postnatal diet on establishment of the early gut microbiome. We hypothesized that altered circadian gene expression solely in the neonatal liver would result in gut microbiome dysbiosis, especially with diet-induced metabolic stress (ie, restricted feeding). Using a murine model in which we conditionally knock out Npas2 in the neonatal liver, we aimed to determine the role of the circadian machinery in gut dysbiosis with restricted feeding. We collected fecal samples from liver Npas2 conditional knockout (n = 11) and wild-type (n = 13) reproductive-aged mice before (study day 0) and after the restricted feeding study (study day 17). Extracted DNA was sequenced using the MiSeq Illumina platform using primers specific for the V4 region of the 16S ribosomal DNA gene. The resulting sequences were quality filtered, aligned, and assigned taxonomy. Principal coordinate analysis was performed on unweighted and weighted UniFrac distances between samples with a permutation analysis of variance to assess clustering significance between groups. Microbial taxa that significantly differ between groups of interest was determined using linear discriminate analysis effect size and randomForrest. Principal coordinate analysis performed on weighted UniFrac distances between male conditional knockout and wild-type cohorts revealed that the gut microbiome of the mice did not differ by genotype at the start of the restricted feeding study but did differ by virtue of genotype at the end of the study (P = .001). Moreover, these differences could be at least partially attributed to restricted feeding-associated alterations in relative

  15. A metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome

    PubMed Central

    Gloux, Karine; Berteau, Olivier; El oumami, Hanane; Béguet, Fabienne; Leclerc, Marion; Doré, Joël

    2011-01-01

    In the human gastrointestinal tract, bacterial β-D-glucuronidases (BG; E.C. 3.2.1.31) are involved both in xenobiotic metabolism and in some of the beneficial effects of dietary compounds. Despite their biological significance, investigations are hampered by the fact that only a few BGs have so far been studied. A functional metagenomic approach was therefore performed on intestinal metagenomic libraries using chromogenic glucuronides as probes. Using this strategy, 19 positive metagenomic clones were identified but only one exhibited strong β-D-glucuronidase activity when subcloned into an expression vector. The cloned gene encoded a β-D-glucuronidase (called H11G11-BG) that had distant amino acid sequence homologies and an additional C terminus domain compared with known β-D-glucuronidases. Fifteen homologs were identified in public bacterial genome databases (38–57% identity with H11G11-BG) in the Firmicutes phylum. The genomes identified derived from strains from Ruminococcaceae, Lachnospiraceae, and Clostridiaceae. The genetic context diversity, with closely related symporters and gene duplication, argued for functional diversity and contribution to adaptive mechanisms. In contrast to the previously known β-D-glucuronidases, this previously undescribed type was present in the published microbiome of each healthy adult/child investigated (n = 11) and was specific to the human gut ecosystem. In conclusion, our functional metagenomic approach revealed a class of BGs that may be part of a functional core specifically evolved to adapt to the human gut environment with major health implications. We propose consensus motifs for this unique Firmicutes β-D-glucuronidase subfamily and for the glycosyl hydrolase family 2. PMID:20615998

  16. A metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome.

    PubMed

    Gloux, Karine; Berteau, Olivier; El Oumami, Hanane; Béguet, Fabienne; Leclerc, Marion; Doré, Joël

    2011-03-15

    In the human gastrointestinal tract, bacterial β-D-glucuronidases (BG; E.C. 3.2.1.31) are involved both in xenobiotic metabolism and in some of the beneficial effects of dietary compounds. Despite their biological significance, investigations are hampered by the fact that only a few BGs have so far been studied. A functional metagenomic approach was therefore performed on intestinal metagenomic libraries using chromogenic glucuronides as probes. Using this strategy, 19 positive metagenomic clones were identified but only one exhibited strong β-D-glucuronidase activity when subcloned into an expression vector. The cloned gene encoded a β-D-glucuronidase (called H11G11-BG) that had distant amino acid sequence homologies and an additional C terminus domain compared with known β-D-glucuronidases. Fifteen homologs were identified in public bacterial genome databases (38-57% identity with H11G11-BG) in the Firmicutes phylum. The genomes identified derived from strains from Ruminococcaceae, Lachnospiraceae, and Clostridiaceae. The genetic context diversity, with closely related symporters and gene duplication, argued for functional diversity and contribution to adaptive mechanisms. In contrast to the previously known β-D-glucuronidases, this previously undescribed type was present in the published microbiome of each healthy adult/child investigated (n = 11) and was specific to the human gut ecosystem. In conclusion, our functional metagenomic approach revealed a class of BGs that may be part of a functional core specifically evolved to adapt to the human gut environment with major health implications. We propose consensus motifs for this unique Firmicutes β-D-glucuronidase subfamily and for the glycosyl hydrolase family 2.

  17. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure.

    PubMed

    Bahra, Sarah M; Weidemann, Benjamin J; Castro, Ana N; Walsh, John W; deLeon, Orlando; Burnett, Colin M L; Pearson, Nicole A; Murry, Daryl J; Grobe, Justin L; Kirby, John R

    2015-11-01

    Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism.

  18. The Dynamics of the Human Infant Gut Microbiome in Development and in Progression towards Type 1 Diabetes

    PubMed Central

    Kostic, Aleksandar D.; Gevers, Dirk; Siljander, Heli; Vatanen, Tommi; Hyötyläinen, Tuulia; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Pöhö, Päivi; Mattila, Ismo; Lähdesmäki, Harri; Franzosa, Eric A.; Vaarala, Outi; de Goffau, Marcus; Harmsen, Hermie; Ilonen, Jorma; Virtanen, Suvi M.; Clish, Clary B.; Orešič, Matej; Huttenhower, Curtis; Knip, Mikael

    2015-01-01

    SUMMARY Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time-window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from non-progressors. PMID:25662751

  19. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure

    PubMed Central

    Bahr, Sarah M.; Weidemann, Benjamin J.; Castro, Ana N.; Walsh, John W.; deLeon, Orlando; Burnett, Colin M.L.; Pearson, Nicole A.; Murry, Daryl J.; Grobe, Justin L.; Kirby, John R.

    2015-01-01

    Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism. PMID:26870798

  20. How do agricultural practices impact microbiomes? A case study of antibiotic effects on the swine gut microbiome

    USDA-ARS?s Scientific Manuscript database

    The swine gastrointestinal tract is a rich environment containing up to 1000 different species of commensal bacteria. This collection of gut bacteria, or gut microbiota, confers benefits to the host under normal conditions. Disturbance of the gut microbiota is one collateral effect of in-feed anti...

  1. Profound perturbation induced by triclosan exposure in mouse gut microbiome: a less resilient microbial community with elevated antibiotic and metal resistomes.

    PubMed

    Gao, Bei; Tu, Pengcheng; Bian, Xiaoming; Chi, Liang; Ru, Hongyu; Lu, Kun

    2017-06-12

    Environmental chemical-induced perturbations of gut microbiome are associated with a series of adverse health outcomes. The effects of triclosan on human health have been controversial in recent years. The purpose of this study is to investigate the functional impact of triclosan on the mouse gut microbiome and the link between triclosan exposure and resistomes in gut bacteria. We combined 16S rRNA gene sequencing and shotgun metagenomics sequencing to examine the compositional and functional impact of triclosan exposure on the gut microbiota of C57BL/6 mice. 16S rRNA sequencing results revealed that 13-week triclosan exposure in drinking water induced significant perturbations in mouse gut bacterial assemblages with distinct trajectories compared to controls. Metagenomics sequencing results indicated a remarkable enrichment of gut bacterial genes related to triclosan resistance, stress response, antibiotic resistance and heavy metal resistance. Triclosan exposure has a profound impact on the mouse gut microbiome by inducing perturbations at both compositional and functional levels. To our best knowledge, this is the first evidence regarding the functional alterations of gut microbiome induced by triclosan exposure, which may provide novel mechanistic insights into triclosan exposure and associated diseases.

  2. Evolutionary conservation of a core root microbiome across plant phyla along a tropical soil chronosequence.

    PubMed

    Yeoh, Yun Kit; Dennis, Paul G; Paungfoo-Lonhienne, Chanyarat; Weber, Lui; Brackin, Richard; Ragan, Mark A; Schmidt, Susanne; Hugenholtz, Philip

    2017-08-09

    Culture-independent molecular surveys of plant root microbiomes indicate that soil type generally has a stronger influence on microbial communities than host phylogeny. However, these studies have mostly focussed on model plants and crops. Here, we examine the root microbiomes of multiple plant phyla including lycopods, ferns, gymnosperms, and angiosperms across a soil chronosequence using 16S rRNA gene amplicon profiling. We confirm that soil type is the primary determinant of root-associated bacterial community composition, but also observe a significant correlation with plant phylogeny. A total of 47 bacterial genera are associated with roots relative to bulk soil microbial communities, including well-recognized plant-associated genera such as Bradyrhizobium, Rhizobium, and Burkholderia, and major uncharacterized lineages such as WPS-2, Ellin329, and FW68. We suggest that these taxa collectively constitute an evolutionarily conserved core root microbiome at this site. This lends support to the inference that a core root microbiome has evolved with terrestrial plants over their 400 million year history.Yeoh et al. study root microbiomes of different plant phyla across a tropical soil chronosequence. They confirm that soil type is the primary determinant of root-associated bacterial communities, but also observe a clear correlation with plant phylogeny and define a core root microbiome at this site.

  3. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease

    PubMed Central

    Greenblum, Sharon; Turnbaugh, Peter J.; Borenstein, Elhanan

    2012-01-01

    The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic “inputs.” These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health. PMID:22184244

  4. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.

    PubMed

    Greenblum, Sharon; Turnbaugh, Peter J; Borenstein, Elhanan

    2012-01-10

    The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.

  5. Impact of dietary deviation on disease progression and gut microbiome composition in lupus-prone SNF1 mice.

    PubMed

    Johnson, B M; Gaudreau, M-C; Al-Gadban, M M; Gudi, R; Vasu, C

    2015-08-01

    Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we have examined the impact of drinking water pH on immune response, disease incidence and gut microbiome in a spontaneous mouse model of SLE. Our results show that (SWR × NZB) F1 (SNF1 ) mice that were given acidic pH water (AW) developed nephritis at a slower pace compared to those on neutral pH water (NW). Immunological analyses revealed that the NW-recipient mice carry relatively higher levels of circulating autoantibodies against nuclear antigen (nAg) as well as plasma cells. Importantly, 16S rRNA gene-targeted sequencing revealed that the composition of gut microbiome is significantly different between NW and AW groups of mice. In addition, analysis of cytokine and transcription factor expression revealed that immune response in the gut mucosa of NW recipient mice is dominated by T helper type 17 (Th17) and Th9-associated factors. Segmented filamentous bacteria (SFB) promote a Th17 response and autoimmunity in mouse models of arthritis and multiple sclerosis. Interestingly, however, not only was SFB colonization unaffected by the pH of drinking water, but also SFB failed to cause a profound increase in Th17 response and had no significant effect on lupus incidence. Overall, these observations show that simple dietary deviations such as the pH of drinking water can influence lupus incidence and affect the composition of gut microbiome.

  6. Impact of dietary deviation on disease progression and gut microbiome composition in lupus-prone SNF1 mice

    PubMed Central

    Johnson, B M; Gaudreau, M-C; Al-Gadban, M M; Gudi, R; Vasu, C

    2015-01-01

    Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we have examined the impact of drinking water pH on immune response, disease incidence and gut microbiome in a spontaneous mouse model of SLE. Our results show that (SWR × NZB) F1 (SNF1) mice that were given acidic pH water (AW) developed nephritis at a slower pace compared to those on neutral pH water (NW). Immunological analyses revealed that the NW-recipient mice carry relatively higher levels of circulating autoantibodies against nuclear antigen (nAg) as well as plasma cells. Importantly, 16S rRNA gene-targeted sequencing revealed that the composition of gut microbiome is significantly different between NW and AW groups of mice. In addition, analysis of cytokine and transcription factor expression revealed that immune response in the gut mucosa of NW recipient mice is dominated by T helper type 17 (Th17) and Th9-associated factors. Segmented filamentous bacteria (SFB) promote a Th17 response and autoimmunity in mouse models of arthritis and multiple sclerosis. Interestingly, however, not only was SFB colonization unaffected by the pH of drinking water, but also SFB failed to cause a profound increase in Th17 response and had no significant effect on lupus incidence. Overall, these observations show that simple dietary deviations such as the pH of drinking water can influence lupus incidence and affect the composition of gut microbiome. PMID:25703185

  7. Destabilization of the Gut Microbiome Marks the End-Stage of Simian Immunodeficiency Virus Infection in Wild Chimpanzees

    PubMed Central

    BARBIAN, HANNAH J.; LI, YINGYING; RAMIREZ, MIGUEL; KLASE, ZACHARY; LIPENDE, IDDI; MJUNGU, DEUS; MOELLER, ANDREW H.; WILSON, MICHAEL L.; PUSEY, ANNE E.; LONSDORF, ELIZABETH V.; BUSHMAN, FREDERIC D.; HAHN, BEATRICE H.

    2016-01-01

    Enteric dysbiosis is a characteristic feature of progressive human immunodeficiency virus type 1 (HIV-1) infection but has not been observed in simian immunodeficiency virus (SIVmac)-infected macaques, including in animals with end-stage disease. This has raised questions concerning the mechanisms underlying the HIV-1 associated enteropathy, with factors other than virus infection, such as lifestyle and antibiotic use, implicated as playing possible causal roles. Simian immunodeficiency virus of chimpanzees (SIVcpz) is also associated with increased mortality in wild-living communities, and like HIV-1 and SIVmac, can cause CD4+ T cell depletion and immunodeficiency in infected individuals. Given the central role of the intestinal microbiome in mammalian health, we asked whether gut microbial constituents could be identified that are indicative of SIVcpz status and/or disease progression. Here, we characterized the gut microbiome of SIVcpz-infected and -uninfected chimpanzees in Gombe National Park, Tanzania. Subjecting a small number of fecal samples (N = 9) to metagenomic (shotgun) sequencing, we found bacteria of the family Prevotellaceae to be enriched in SIVcpz-infected chimpanzees. However, 16S rRNA gene sequencing of a larger number of samples (N = 123) failed to show significant differences in both the composition and diversity (alpha and beta) of gut bacterial communities between infected (N = 24) and uninfected (N = 26) chimpanzees. Similarly, chimpanzee stool-associated circular virus (Chi-SCV) and chimpanzee adenovirus (ChAdV) identified by metagenomic sequencing were neither more prevalent nor more abundant in SIVcpz-infected individuals. However, fecal samples collected from SIVcpz-infected chimpanzees within 5 months before their AIDS-related death exhibited significant compositional changes in their gut bacteriome. These data indicate that SIVcpz-infected chimpanzees retain a stable gut microbiome throughout much of their natural infection course

  8. Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling.

    PubMed

    Pallister, T; Jackson, M A; Martin, T C; Glastonbury, C A; Jennings, A; Beaumont, M; Mohney, R P; Small, K S; MacGregor, A; Steves, C J; Cassidy, A; Spector, T D; Menni, C; Valdes, A M

    2017-07-01

    Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The m