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Sample records for core gut microbiome

  1. 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. PMID

  2. 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

  3. Marek's disease virus influences the core gut microbiome of the chicken during the early and late phases of viral replication.

    PubMed

    Perumbakkam, Sudeep; Hunt, Henry D; Cheng, Hans H

    2014-10-01

    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-derived samples from individual birds were used to estimate the influence of MDV infection on the gut microbiome of chicken. Our analysis shows that MDV infection alters the core gut flora in the total fecal samples relatively early after infection (2-7 days) and in the late phase of viral infection (28-35 days) in cecal samples, corresponding well with the life cycle of MDV. Principle component analyses of total fecal and cecal samples showed clustering at the early and late time points, respectively. The genus Lactobacillus was exclusively present in the infected samples in both total fecal and cecal bird samples. The community colonization of core gut flora was altered by viral infection, which manifested in the enrichment of several genera during the early and late phases of MDV replication. The results suggest a relationship between viral infection and microbial composition of the intestinal tract that may influence inflammation and immunosuppression of T and B cells in the host. PMID:25065611

  4. Gut Microbiome and Colorectal Adenomas

    PubMed Central

    Dulal, Santosh; Keku, Temitope O.

    2015-01-01

    The trillions of bacteria that naturally reside in the human gut collectively constitute the complex system known the gut microbiome, a vital player for the host’s homeostasis and health. However, there is mounting evidence that dysbiosis, a state of pathological imbalance in the gut microbiome is present in many disease states. In this review, we present recent insights concerning the gut microbiome’s contribution to the development of colorectal adenomas and the subsequent progression to colorectal cancer (CRC). In the United States alone, CRC is the second leading cause of cancer deaths. As a result, there is a high interest in identifying risk factors for adenomas, which are intermediate precursors to CRC. Recent research on CRC and the microbiome suggest that modulation of the gut bacterial composition and structure may be useful in preventing adenomas and CRC. We highlight the known risk factors for colorectal adenomas and the potential mechanisms by which microbial dysbiosis may contribute to the etiology of CRC. We also underscore novel findings from recent studies on the gut microbiota and colorectal adenomas along with current knowledge gaps. Understanding the microbiome may provide promising new directions towards novel diagnostic tools, biomarkers, and therapeutic interventions for CRC. PMID:24855012

  5. 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. PMID:27255389

  6. 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

  7. 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. PMID:26842811

  8. Diet, gut microbiome, and bone health.

    PubMed

    Weaver, Connie M

    2015-04-01

    Interactions between the environment, the gut microbiome, and host characteristics that influence bone health are beginning to be explored. This is the first area where functional benefits from diet-induced changes in the gut microbiome have been reported for healthy people. Several prebiotics that reach the lower intestine have resulted in an altered gut microbiome that is thought to enhance fermentation of the fibers to produce short-chain fatty acids. These changes are positively correlated with increases in fractional calcium absorption in adolescents and with increases in measures of bone density and strength in animal models. New methodologies are available to explore mechanisms and to refine intervention strategies. PMID:25616772

  9. Diet, Gut Microbiome, and Bone Health

    PubMed Central

    2016-01-01

    Interactions between the environment, the gut microbiome, and host characteristics that influence bone health are beginning to be explored. This is the first area where functional benefits from diet-induced changes in the gut microbiome have been reported for healthy people. Several prebiotics that reach the lower intestine have resulted in an altered gut microbiome that is thought to enhance fermentation of the fibers to produce short-chain fatty acids. These changes are positively correlated with increases in fractional calcium absorption in adolescents and with increases in measures of bone density and strength in animal models. New methodologies are available to explore mechanisms and to refine intervention strategies. PMID:25616772

  10. 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. PMID:26719306

  11. Human genetics shape the gut microbiome

    PubMed Central

    Goodrich, Julia K.; Waters, Jillian L.; Poole, Angela C.; Sutter, Jessica L.; Koren, Omry; Blekhman, Ran; Beaumont, Michelle; Van Treuren, William; Knight, Rob; Bell, Jordana T.; Spector, Timothy D.; Clark, Andrew G.; Ley, Ruth E.

    2014-01-01

    Summary Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across > 1,000 fecal samples obtained from the TwinsUK population, including 416 twin-pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a cooccurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germfree mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism. PMID:25417156

  12. 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

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

    DOE PAGESBeta

    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 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

  14. 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.

  15. 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. PMID:24118574

  16. 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. PMID:24957091

  17. 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

  18. 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. PMID:23251439

  19. The Gut Microbiome in the NOD Mouse.

    PubMed

    Peng, Jian; Hu, Youjia; Wong, F Susan; Wen, Li

    2016-01-01

    The microbiome (or microbiota) are an ecological community of commensal, symbiotic, and pathogenic microorganisms that outnumber the cells of the human body tenfold. These microorganisms are most abundant in the gut where they play an important role in health and disease. Alteration of the homeostasis of the gut microbiota can have beneficial or harmful consequences to health. There has recently been a major increase in studies on the association of the gut microbiome composition with disease phenotypes.The nonobese diabetic (NOD) mouse is an excellent mouse model to study spontaneous type 1 diabetes development. We, and others, have reported that gut bacteria are critical modulators for type 1 diabetes development in genetically susceptible NOD mice.Here we present our standard protocol for gut microbiome analysis in NOD mice that has been routinely implemented in our research laboratory. This incorporates the following steps: (1) Isolation of total DNA from gut bacteria from mouse fecal samples or intestinal contents; (2) bacterial DNA sequencing, and (3) basic data analysis. PMID:27032947

  20. Diet, the Gut Microbiome, and Epigenetics

    PubMed Central

    Hullar, Meredith A. J.; Fu, Benjamin C.

    2014-01-01

    Increasingly, the gut microbiome is implicated in the etiology of cancer, not only as an infectious agent, but also by altering exposure to dietary compounds that influence disease risk. While the composition and metabolism of the gut microbiome is influenced by diet, the gut microbiome can also modify dietary exposures in ways that are beneficial or detrimental to the human host. The colonic bacteria metabolize macronutrients, either as specialists or in consortia of bacteria, in a variety of diverse metabolic pathways. Microbial metabolites of diet can also be epigenetic activators of gene expression that may influence cancer risk in humans. Epigenetic involves heritable changes in gene expression via post translational and post transcriptional modifications. Microbial metabolites can influence epigenetics by altering the pool of compounds used for modification or by directly inhibiting enzymes involved in epigenetic pathways. Colonic epithelium is immediately exposed to these metabolites, although some metabolites are also found in systemic circulation. In this review, we discuss the role of the gut microbiome in dietary metabolism and how microbial metabolites may influence gene expression linked to colon cancer risk. PMID:24855003

  1. Gut microbiome and nonalcoholic fatty liver diseases.

    PubMed

    Zhu, Lixin; Baker, Robert D; Baker, Susan S

    2015-01-01

    We review recent findings and hypotheses on the roles of gut microbiome in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD). Microbial metabolites and cell components contribute to the development of hepatic steatosis and inflammation, key components of nonalcoholic steatohepatitis (NASH), the severe form of NAFLD. Altered gut microbiome can independently cause obesity, the most important risk factor for NAFLD. This capability is attributed to short-chain fatty acids (SCFAs), major gut microbial fermentation products. SCFAs account for a large portion of caloric intake of the host, and they enhance intestinal absorption by activating GLP-2 signaling. However, elevated SCFAs may be an adaptive measure to suppress colitis, which could be a higher priority than imbalanced calorie intake. The microbiome of NASH patients features an elevated capacity for alcohol production. The pathomechanisms for alcoholic steatohepatitis may apply to NASH. NAFLD/NASH is associated with elevated Gram-negative microbiome and endotoxemia. However, many NASH patients exhibited normal serum endotoxin indicating that endotoxemia is not required for the pathogenesis of NASH. These observations suggest that microbial intervention may benefit NAFLD/NASH patients. However, very limited effects were observed using traditional probiotic species. Novel probiotic therapy based on NAFLD/NASH specific microbial composition represents a promising future direction. PMID:25310763

  2. 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

  3. 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. PMID:26143242

  4. 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

  5. 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

  6. 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

  7. 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

  8. Gut microbiome-host interactions in health and disease

    PubMed Central

    2011-01-01

    The gut microbiome is the term given to describe the vast collection of symbiotic microorganisms in the human gastrointestinal system and their collective interacting genomes. Recent studies have suggested that the gut microbiome performs numerous important biochemical functions for the host, and disorders of the microbiome are associated with many and diverse human disease processes. Systems biology approaches based on next generation 'omics' technologies are now able to describe the gut microbiome at a detailed genetic and functional (transcriptomic, proteomic and metabolic) level, providing new insights into the importance of the gut microbiome in human health, and they are able to map microbiome variability between species, individuals and populations. This has established the importance of the gut microbiome in the disease pathogenesis for numerous systemic disease states, such as obesity and cardiovascular disease, and in intestinal conditions, such as inflammatory bowel disease. Thus, understanding microbiome activity is essential to the development of future personalized strategies of healthcare, as well as potentially providing new targets for drug development. Here, we review recent metagenomic and metabonomic approaches that have enabled advances in understanding gut microbiome activity in relation to human health, and gut microbial modulation for the treatment of disease. We also describe possible avenues of research in this rapidly growing field with respect to future personalized healthcare strategies. PMID:21392406

  9. Rapid changes in the gut microbiome during human evolution

    PubMed Central

    Moeller, Andrew H.; Li, Yingying; Mpoudi Ngole, Eitel; Ahuka-Mundeke, Steve; Lonsdorf, Elizabeth V.; Pusey, Anne E.; Peeters, Martine; Hahn, Beatrice H.; Ochman, Howard

    2014-01-01

    Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan. PMID:25368157

  10. 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. PMID:25368157

  11. 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.

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

    DOE PAGESBeta

    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 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

  13. Population-level analysis of gut microbiome variation.

    PubMed

    Falony, Gwen; Joossens, Marie; Vieira-Silva, Sara; Wang, Jun; Darzi, Youssef; Faust, Karoline; Kurilshikov, Alexander; Bonder, Marc Jan; Valles-Colomer, Mireia; Vandeputte, Doris; Tito, Raul Y; Chaffron, Samuel; Rymenans, Leen; Verspecht, Chloë; De Sutter, Lise; Lima-Mendez, Gipsi; D'hoe, Kevin; Jonckheere, Karl; Homola, Daniel; Garcia, Roberto; Tigchelaar, Ettje F; Eeckhaudt, Linda; Fu, Jingyuan; Henckaerts, Liesbet; Zhernakova, Alexandra; Wijmenga, Cisca; Raes, Jeroen

    2016-04-29

    Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design. PMID:27126039

  14. Correlations of Host Genetics and Gut Microbiome Composition.

    PubMed

    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. 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

  16. Alterations of the human gut microbiome in multiple sclerosis.

    PubMed

    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. 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

  18. Gut microbiome phenotypes driven by host genetics affect arsenic metabolism.

    PubMed

    Lu, Kun; Mahbub, Ridwan; Cable, Peter Hans; Ru, Hongyu; Parry, Nicola M A; Bodnar, Wanda M; Wishnok, John S; Styblo, Miroslav; Swenberg, James A; Fox, James G; Tannenbaum, Steven R

    2014-02-17

    Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism. PMID:24490651

  19. 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

  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? PMID:26196489

  1. 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. PMID:25624713

  2. Mining the human gut microbiome for novel stress resistance genes

    PubMed Central

    Culligan, Eamonn P.; Marchesi, Julian R.; Hill, Colin; Sleator, Roy D.

    2012-01-01

    With the rapid advances in sequencing technologies in recent years, the human genome is now considered incomplete without the complementing microbiome, which outnumbers human genes by a factor of one hundred. The human microbiome, and more specifically the gut microbiome, has received considerable attention and research efforts over the past decade. Many studies have identified and quantified “who is there?,” while others have determined some of their functional capacity, or “what are they doing?” In a recent study, we identified novel salt-tolerance loci from the human gut microbiome using combined functional metagenomic and bioinformatics based approaches. Herein, we discuss the identified loci, their role in salt-tolerance and their importance in the context of the gut environment. We also consider the utility and power of functional metagenomics for mining such environments for novel genes and proteins, as well as the implications and possible applications for future research. PMID:22688726

  3. Human gut microbiome viewed across age and geography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. The emerging relevance of the gut microbiome in cardiometabolic health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Host metabolic pathways and physiological responses are regulated by signals linking the host to the gut microbial community or microbiome. Here, we draw a spotlight on lipid and bile acid metabolism and inflammatory response as they pertain to cardiometabolic dysfunction. Gut microbial dysbiosis al...

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

    DOE PAGESBeta

    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

  6. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed

    Lu, Kun; Cable, Peter Hans; Abo, Ryan Phillip; Ru, Hongyu; Graffam, Michelle E; Schlieper, 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

    2013-12-16

    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 an altered gut microbiome induced by bacterial infection, 16S rRNA gene sequencing, and inductively coupled plasma mass spectrometry-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 and 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

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

    PubMed

    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

  10. 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

  11. Gut mucosal microbiome across stages of colorectal carcinogenesis

    PubMed Central

    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.

    2015-01-01

    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. PMID:26515465

  12. 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

    2012-06-14

    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. PMID:22699611

  13. 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. PMID:22537667

  14. Mosquito C-type lectins maintain gut microbiome homeostasis.

    PubMed

    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:27572642

  15. 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

  16. 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. PMID:20668239

  17. Human gut microbiome viewed across age and geography

    PubMed Central

    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.

    2012-01-01

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ between human populations when viewed from the perspective of component microbial lineages, encoded metabolic functions, stage of postnatal development, and environmental exposures, we characterized bacterial species present in fecal samples obtained from 531 individuals representing healthy Amerindians from the Amazonas of Venezuela, residents of rural Malawian communities, and inhabitants of USA metropolitan areas, as well as the gene content of 110 of their microbiomes. This cohort encompassed infants, children, teenagers and adults, parents and offspring, 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 representation of genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial species assemblages and functional gene repertoires were noted between individuals residing in the USA compared to the other two countries. These distinctive features are evident in early infancy as well as adulthood. In addition, the similarity of fecal microbiomes among family members extends across cultures. These findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of Westernization. PMID:22699611

  18. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  19. Sex-Specific Effects of Arsenic Exposure on the Trajectory and Function of the Gut Microbiome.

    PubMed

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

    2016-06-20

    The gut microbiome is deeply involved in numerous aspects of human health; however, it can be readily perturbed by environmental toxicants, such as arsenic. Meanwhile, the interaction among host, gut microbiome, and xenobiotics is a very complex dynamic process. Previously, we have demonstrated that gut microbiome phenotypes driven by host genetics and bacterial infection affect the responses to arsenic exposure. The role of host sex in shaping the gut microbiome raises the question whether sex plays a role in exposure-induced microbiome responses. To examine this, we used 16S rRNA sequencing and metagenomics sequencing to analyze the changes of the gut microbiome and its associated functional metagenome in both female and male C57/BL6 mice. Our results clearly demonstrated that arsenic exposure perturbed the trajectory and function of the gut microbiome in a sex-specific manner. PMID:27268458

  20. The Role of the Gut Microbiome on Chronic Kidney Disease.

    PubMed

    Sampaio-Maia, B; Simões-Silva, L; Pestana, M; Araujo, R; Soares-Silva, I J

    2016-01-01

    Chronic kidney disease (CKD) is estimated to affect nearly 500 million people worldwide and cardiovascular (CV) disease is a major cause of death in this population. However, therapeutic interventions targeting traditional CV risks are not effective at lowering the incidence of CV events or at delaying the progression of the disease in CKD patients. In recent years, disturbances of normal gut microbiome were recognized in the pathogenesis of diverse chronic diseases. Gut dysbiosis is being unraveled in CKD and pointed as a nontraditional risk factor for CV risk and CKD progression. The most often reported changes in gut microbiome in CKD are related to the lower levels of Bifidobacteriaceae and Lactobacillaceae and to higher levels of Enterobacteriaceae. Although metagenomics brought us an amplified vision on the microbial world that inhabits the human host, it still lacks the sensitivity to characterize the microbiome up to species level, not revealing alterations that occur within specific genus. Here, we review the current state-of-the-art concerning gut dysbiosis in CKD and its role in pathophysiological mechanisms in CKD, particularly in relation with CV risk. Also, the strategies towards prevention and treatment of gut dysbiosis in CKD progression will be discussed. PMID:27565581

  1. 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

  2. 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

  3. Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome.

    PubMed

    Pitt, Jonathan M; Vétizou, Marie; Waldschmitt, Nadine; Kroemer, Guido; Chamaillard, Mathias; Boneca, Ivo Gomperts; Zitvogel, Laurence

    2016-08-15

    The equilibrium linking the intestinal microbiota, the intestinal epithelium, and the host immune system establishes host health and homeostasis, with perturbations of this balance resulting in chronic inflammatory and autoimmune immunopathologies. The mutualistic symbiosis between gut microbiota and host immunity raises the possibility that dysbiosis of the intestinal content also influences the outcome of cancer immunotherapy. Here, we present our recent findings that specific gut-resident bacteria determine the immunotherapeutic responses associated with CTLA-4 checkpoint blockade. This new evidence hints that interindividual differences in the microbiome may account for the significant heterogeneity in therapeutic and immunopathologic responses to immune checkpoint therapies. We discuss how this new understanding could improve the therapeutic coverage of immune checkpoint inhibitors, and potentially limit their immune-mediated toxicity, through the use of adjunctive "oncomicrobiotics" that indirectly promote beneficial immune responses through optimizing the gut microbiome. Cancer Res; 76(16); 4602-7. ©2016 AACR. PMID:27474734

  4. Overgrowth of the indigenous gut microbiome and irritable bowel syndrome.

    PubMed

    Bye, William; Ishaq, Naveed; Bolin, Terry D; Duncombe, Vic M; Riordan, Stephen M

    2014-03-14

    Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable. Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years, leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders, including irritable bowel syndrome (IBS). Use of culture-independent molecular techniques already employed to characterise faecal and, to a lesser extent, colonic mucosal microbial populations in IBS, without reliance on insensitive, traditional microbiological culture techniques, has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder, at least that occurring proximally and within reach of sampling. Current data concerning culture-based and culture-independent analyses of the small intestinal microbiome in IBS are considered here. PMID:24627582

  5. 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. PMID:25183073

  6. The biogeography of the atlantic salmon (Salmo salar) gut microbiome.

    PubMed

    Llewellyn, Martin S; McGinnity, Philip; Dionne, Melanie; Letourneau, Justine; Thonier, Florian; Carvalho, Gary R; Creer, Simon; Derome, Nicolas

    2016-05-01

    Although understood in many vertebrate systems, the natural diversity of host-associated microbiota has been little studied in teleosts. For migratory fishes, successful exploitation of multiple habitats may affect and be affected by the composition of the intestinal microbiome. We collected 96 Salmo salar from across the Atlantic encompassing both freshwater and marine phases. Dramatic differences between environmental and gut bacterial communities were observed. Furthermore, community composition was not significantly impacted by geography. Instead life-cycle stage strongly defined both the diversity and identity of microbial assemblages in the gut, with evidence for community destabilisation in migratory phases. Mycoplasmataceae phylotypes were abundantly recovered in all life-cycle stages. Patterns of Mycoplasmataceae phylotype recruitment to the intestinal microbial community among sites and life-cycle stages support a dual role for deterministic and stochastic processes in defining the composition of the S. salar gut microbiome. PMID:26517698

  7. 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

  8. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Stabilization of the murine gut microbiome following weaning

    PubMed Central

    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. PMID:22688727

  11. 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

  12. 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

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

    PubMed

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

    2016-08-01

    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

  14. Part 1: The Human Gut Microbiome in Health and Disease

    PubMed Central

    Bull, Matthew J.; Plummer, Nigel T.

    2014-01-01

    The bacterial cells harbored within the human gastrointestinal tract (GIT) outnumber the host’s cells by a factor of 10 and the genes encoded by the bacteria resident within the GIT outnumber their host’s genes by more than 100 times. These human digestive-tract associated microbes are referred to as the gut microbiome. The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physiology, and immune function. Imbalance of the normal gut microbiota have been linked with gastrointestinal conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and wider systemic manifestations of disease such as obesity, type 2 diabetes, and atopy. In the first part of this review, we evaluate our evolving knowledge of the development, complexity, and functionality of the healthy gut microbiota, and the ways in which the microbial community is perturbed in dysbiotic disease states; the second part of this review covers the role of interventions that have been shown to modulate and stabilize the gut microbiota and also to restore it to its healthy composition from the dysbiotic states seen in IBS, IBD, obesity, type 2 diabetes, and atopy. PMID:26770121

  15. 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. PMID:26452635

  16. The human neonatal gut microbiome: a brief review.

    PubMed

    Gritz, Emily C; Bhandari, Vineet

    2015-01-01

    The field of genomics has expanded into subspecialties such as metagenomics over the course of the last decade and a half. The development of massively parallel sequencing capabilities has allowed for increasingly detailed study of the genome of the human microbiome, the microbial super organ that resides symbiotically within the mucosal tissues and integumentary system of the human host. The gut microbiome, and particularly the study of its origins in neonates, has become subtopics of great interest within the field of genomics. This brief review seeks to summarize recent literature regarding the origins and establishment of the neonatal gut microbiome, beginning in utero, and how it is affected by neonatal nutritional status (breastfed versus formula fed) and gestational age (term versus preterm). We also explore the role of dysbiosis, a perturbation within the fragile ecosystem of the microbiome, and its role in the origin of select pathologic states, specifically, obesity and necrotizing enterocolitis (NEC) in preterm infants. We discuss the evidence supporting enteral pre- and pro-biotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of NEC in premature infants. Finally, we review directions to consider for further research to promote human health within this field. PMID:25798435

  17. 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

  18. The Human Neonatal Gut Microbiome: A Brief Review

    PubMed Central

    Gritz, Emily C.; Bhandari, Vineet

    2015-01-01

    The field of genomics has expanded into subspecialties such as metagenomics over the course of the last decade and a half. The development of massively parallel sequencing capabilities has allowed for increasingly detailed study of the genome of the human microbiome, the microbial super organ that resides symbiotically within the mucosal tissues and integumentary system of the human host. The gut microbiome, and particularly the study of its origins in neonates, has become subtopics of great interest within the field of genomics. This brief review seeks to summarize recent literature regarding the origins and establishment of the neonatal gut microbiome, beginning in utero, and how it is affected by neonatal nutritional status (breastfed versus formula fed) and gestational age (term versus preterm). We also explore the role of dysbiosis, a perturbation within the fragile ecosystem of the microbiome, and its role in the origin of select pathologic states, specifically, obesity and necrotizing enterocolitis (NEC) in preterm infants. We discuss the evidence supporting enteral pre- and pro-biotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of NEC in premature infants. Finally, we review directions to consider for further research to promote human health within this field. PMID:25798435

  19. 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.

  20. 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

  1. 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

  2. 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. PMID:26627987

  3. 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. PMID:25078296

  4. 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

  5. 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

  6. 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. PMID:24336217

  7. 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

    2015-01-01

    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

  8. 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 genusBifidobacterium, 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 archaeonMethanobrevibacter smithiiand 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

  9. 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

  10. Caspase deficiency alters the murine gut microbiome

    PubMed Central

    Brinkman, B M; Hildebrand, F; Kubica, M; Goosens, D; Del Favero, J; Declercq, W; Raes, J; Vandenabeele, P

    2011-01-01

    Caspases are aspartate-specific cysteine proteases that have an essential role in apoptosis and inflammation, and contribute to the maintenance of homeostasis in the intestine. These facts, together with the knowledge that caspases are implicated in host-microbe crosstalk, prompted us to investigate the effect of caspase (Casp)1, -3 and -7 deficiency on the composition of the murine gut microbiota. We observed significant changes in the abundance of the Firmicutes and Bacteroidetes phyla, in particular the Lachnospiraceae, Porphyromonodaceae and Prevotellacea families, when comparing Casp-1, -7 and -3 knockout mice with wild-type mice. Our data point toward an intricate relationship between these caspases and the composition of the murine gut microflora. PMID:22012254

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

    PubMed

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

    2015-07-01

    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

  12. Complexities of Gut Microbiome Dysbiosis in the Context of HIV Infection and Antiretroviral Therapy.

    PubMed

    Li, S X; Armstrong, Ajs; Neff, C P; Shaffer, M; Lozupone, C A; Palmer, B E

    2016-06-01

    Human immunodeficiency virus (HIV) infection is associated with an altered gut microbiome that is not consistently restored with effective antiretroviral therapy (ART). Interpretation of the specific microbiome changes observed during HIV infection is complicated by factors like population, sample type, and ART-each of which may have dramatic effects on gut bacteria. Understanding how these factors shape the microbiome during HIV infection (which we refer to as the HIV-associated microbiome) is critical for defining its role in HIV disease, and for developing therapies that restore gut health during infection. PMID:26940481

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

    PubMed

    Angelakis, Emmanouil; Yasir, Muhammad; Bachar, Dipankar; Azhar, Esam I; Lagier, Jean-Christophe; Bibi, Fehmida; Jiman-Fatani, Asif A; Alawi, Maha; Bakarman, Marwan A; Robert, Catherine; Raoult, Didier

    2016-01-01

    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

  14. 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

  15. 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

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

    PubMed

    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

  17. 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. PMID:27236827

  18. 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

  19. 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. PMID:25917520

  20. 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

  1. Gut Microbiome of Coexisting BaAka Pygmies and Bantu Reflects Gradients of Traditional Subsistence Patterns.

    PubMed

    Gomez, Andres; Petrzelkova, Klara J; Burns, Michael B; Yeoman, Carl J; Amato, Katherine R; Vlckova, Klara; Modry, David; Todd, Angelique; Jost Robinson, Carolyn A; Remis, Melissa J; Torralba, Manolito G; Morton, Elise; Umaña, Juan D; Carbonero, Franck; Gaskins, H Rex; Nelson, Karen E; Wilson, Brenda A; Stumpf, Rebecca M; White, Bryan A; Leigh, Steven R; Blekhman, Ran

    2016-03-01

    To understand how the gut microbiome is impacted by human adaptation to varying environments, we explored gut bacterial communities in the BaAka rainforest hunter-gatherers and their agriculturalist Bantu neighbors in the Central African Republic. Although the microbiome of both groups is compositionally similar, hunter-gatherers harbor increased abundance of Prevotellaceae, Treponema, and Clostridiaceae, while the Bantu gut microbiome is dominated by Firmicutes. Comparisons with US Americans reveal microbiome differences between Africans and westerners but show western-like features in the Bantu, including an increased abundance of predictive carbohydrate and xenobiotic metabolic pathways. In contrast, the hunter-gatherer gut shows increased abundance of predicted virulence, amino acid, and vitamin metabolism functions, as well as dominance of lipid and amino-acid-derived metabolites, as determined through metabolomics. Our results demonstrate gradients of traditional subsistence patterns in two neighboring African groups and highlight the adaptability of the microbiome in response to host ecology. PMID:26923597

  2. Exercise Attenuates PCB-Induced Changes in the Mouse Gut Microbiome

    PubMed Central

    Choi, Jeong June; Eum, Sung Yong; Rampersaud, Evadnie; Daunert, Sylvia; Abreu, Maria T.

    2013-01-01

    Background: The gut microbiome, a dynamic bacterial community that interacts with the host, is integral to human health because it regulates energy metabolism and immune functions. The gut microbiome may also play a role in risks from environmental toxicants. Objectives: We investigated the effects of polychlorinated biphenyls (PCBs) and exercise on the composition and structure of the gut microbiome in mice. Methods: After mice exercised voluntarily for 5 weeks, they were treated by oral gavage with a mixture of environmentally relevant PCB congeners (PCB153, PCB138, and PCB180; total PCB dose, 150 µmol/kg) for 2 days. We then assessed the microbiome by determination of 16S rRNA using microarray analysis. Results: Oral exposure to PCBs significantly altered the abundance of the gut microbiome in mice primarily by decreasing the levels of Proteobacteria. The activity level of the mice correlated with a substantial shift in abundance, biodiversity, and composition of the microbiome. Importantly, exercise attenuated PCB-induced changes in the gut microbiome. Conclusions: Our results show that oral exposure to PCBs can induce substantial changes in the gut microbiome, which may then influence their systemic toxicity. These changes can be attenuated by behavioral factors, such as voluntary exercise. PMID:23632211

  3. 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. PMID:27173935

  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. 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. PMID:25339800

  6. Early diet impacts infant rhesus gut microbiome, immunity, and metabolism.

    PubMed

    O'Sullivan, Aifric; He, Xuan; McNiven, Elizabeth M S; Haggarty, Neill W; Lönnerdal, Bo; Slupsky, Carolyn M

    2013-06-01

    Epidemiological research has indicated a relationship between infant formula feeding and increased risk of chronic diseases later in life including obesity, type-2 diabetes, and cardiovascular disease. The present study used an infant rhesus monkey model to compare the comprehensive metabolic implications of formula- and breast-feeding practices using NMR spectroscopy to characterize metabolite fingerprints from urine and serum, in combination with anthropometric measurements, fecal microbial profiling, and cytokine measurements. Here we show that formula-fed infants are larger than their breast-fed counterparts and have a different gut microbiome that includes higher levels of bacteria from the Ruminococcus genus and lower levels of bacteria from the Lactobacillus genus. In addition, formula-fed infants have higher serum insulin coupled with higher amino acid levels, while amino acid degradation products were higher in breast-fed infants. Increases in serum and urine galactose and urine galactitol were observed in the second month of life in formula-fed infants, along with higher levels of TNFα, IFN-γ, IL-1β, IL-4, and other cytokines and growth factors at week 4. These results demonstrate that metabolic and gut microbiome development of formula-fed infants is different from breast-fed infants and that the choice of infant feeding may hold future health consequences. PMID:23651394

  7. 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. PMID:26731268

  8. 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

  9. 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

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

    PubMed

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

    2016-09-01

    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

  11. 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

  12. 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

  13. The interplay of the gut microbiome, bile acids, and volatile organic compounds.

    PubMed

    Sagar, Nidhi M; Cree, Ian A; Covington, James A; Arasaradnam, Ramesh P

    2015-01-01

    Background. There has been an increasing interest in the use of volatile organic compounds (VOCs) as potential surrogate markers of gut dysbiosis in gastrointestinal disease. Gut dysbiosis occurs when pathological imbalances in gut bacterial colonies precipitate disease and has been linked to the dysmetabolism of bile acids (BA) in the gut. BA metabolites as a result of microbial transformations act as signaling molecules and have demonstrated regulation of intestinal homeostasis through the TGR5 and FXR receptors by inhibiting inflammation, preventing pathogen invasion, and maintaining cell integrity. The presence of VOC footprints is the resultant effect to gut microbiome substrate fermentation. Aim. To review the role of the gut microbiome and bile acid signaling in intestinal homeostasis and the resultant use of VOCs as potential noninvasive surrogate biomarkers in gut dysbiosis. Methods. A systematic search on PubMed and Medline databases was performed to identify articles relevant to gut dysbiosis, BA metabolism, and VOCs. Conclusions. The host and presence of the gut microbiome appear to regulate the BA pool size. A dysbiotic gut microbiome results in disrupted intestinal homeostasis, which may be reflected by VOCs, differentiating those who are healthy and those with disease. PMID:25821460

  14. Reshaping the gut microbiome with bacterial transplantation and antibiotic intake

    PubMed Central

    Manichanh, Chaysavanh; Reeder, Jens; Gibert, Prudence; Varela, Encarna; Llopis, Marta; Antolin, Maria; Guigo, Roderic; Knight, Rob; Guarner, Francisco

    2010-01-01

    The intestinal microbiota consists of over 1000 species, which play key roles in gut physiology and homeostasis. Imbalances in the composition of this bacterial community can lead to transient intestinal dysfunctions and chronic disease states. Understanding how to manipulate this ecosystem is thus essential for treating many disorders. In this study, we took advantage of recently developed tools for deep sequencing and phylogenetic clustering to examine the long-term effects of exogenous microbiota transplantation combined with and without an antibiotic pretreatment. In our rat model, deep sequencing revealed an intestinal bacterial diversity exceeding that of the human gut by a factor of two to three. The transplantation produced a marked increase in the microbial diversity of the recipients, which stemmed from both capture of new phylotypes and increase in abundance of others. However, when transplantation was performed after antibiotic intake, the resulting state simply combined the reshaping effects of the individual treatments (including the reduced diversity from antibiotic treatment alone). Therefore, lowering the recipient bacterial load by antibiotic intake prior to transplantation did not increase establishment of the donor phylotypes, although some dominant lineages still transferred successfully. Remarkably, all of these effects were observed after 1 mo of treatment and persisted after 3 mo. Overall, our results indicate that the indigenous gut microbial composition is more plastic that previously anticipated. However, since antibiotic pretreatment counterintuitively interferes with the establishment of an exogenous community, such plasticity is likely conditioned more by the altered microbiome gut homeostasis caused by antibiotics than by the primary bacterial loss. PMID:20736229

  15. Gastroenvironmental distress: metaphorical antecedents of the gut microbiome.

    PubMed

    Ahuja, Nitin K; Ahuja, Amisha

    2016-06-01

    The human gut has been viewed for centuries as a potential mediator of systemic disease. The theory of autointoxication, which found its clearest articulation in the late nineteenth and early twentieth centuries, focused on altered bowel habits as the cause of widespread physical decay and advocated for the pursuit of health through regular defecation. More recently, under the banner of the microbiome, research on commensal bacteria makes a similar case for associations between alimentary dynamics and illness manifestations far outside the gastrointestinal tract. Surface distinctions between these two conceptual frameworks are apparently antipodal, the former championing emptiness and sterility, the latter abundance and restoration. Within both models, however, persists a common anxiety about the detrimental effects of civilisation on the body in relation to the natural world. As scientific understanding of the microbiome continues to mature, acknowledging the historical and moral parameters of its borrowed ecological idiom may facilitate critical distinctions between what is true and what feels like it should be. PMID:26856356

  16. 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. PMID:27079516

  17. Sex differences in the gut microbiome-brain axis across the lifespan.

    PubMed

    Jašarević, Eldin; Morrison, Kathleen E; Bale, Tracy L

    2016-02-19

    In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome-brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan. PMID:26833840

  18. Brain-gut microbiome interactions and functional bowel disorders.

    PubMed

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

    2014-05-01

    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 role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut-brain interactions. PMID:24583088

  19. 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. PMID:26456445

  20. 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

  1. 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

    2015-01-01

    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

  2. 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.

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

    DOE PAGESBeta

    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 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

  4. Pyrosequencing reveals the predominance of Pseudomonadaceae in gut microbiome of a Gall Midge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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. PMID:22006317

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

    PubMed Central

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

    2011-01-01

    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. PMID:22006317

  7. 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

  8. 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. PMID:25974306

  9. 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

  10. 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. PMID:25286403

  11. 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

  12. Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target.

    PubMed

    Ramezani, Ali; Massy, Ziad A; Meijers, Björn; Evenepoel, Pieter; Vanholder, Raymond; Raj, Dominic S

    2016-03-01

    Also known as the "second human genome," the gut microbiome plays important roles in both the maintenance of health and the pathogenesis of disease. The symbiotic relationship between host and microbiome is disturbed due to the proliferation of dysbiotic bacteria in patients with chronic kidney disease (CKD). Fermentation of protein and amino acids by gut bacteria generates excess amounts of potentially toxic compounds such as ammonia, amines, thiols, phenols, and indoles, but the generation of short-chain fatty acids is reduced. Impaired intestinal barrier function in patients with CKD permits translocation of gut-derived uremic toxins into the systemic circulation, contributing to the progression of CKD, cardiovascular disease, insulin resistance, and protein-energy wasting. The field of microbiome research is still nascent, but is evolving rapidly. Establishing symbiosis to treat uremic syndrome is a novel concept, but if proved effective, it will have a significant impact on the management of patients with CKD. PMID:26590448

  13. "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. PMID:26629974

  14. 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. PMID:26671671

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

    PubMed Central

    Conley, Melissa N.; Wong, Carmen P.; Duyck, Kyle M.; Hord, Norman; Ho, Emily

    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

  16. 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

  17. Connections Between the Gut Microbiome and Metabolic Hormones in Early Pregnancy in Overweight and Obese Women.

    PubMed

    Gomez-Arango, Luisa F; Barrett, Helen L; McIntyre, H David; Callaway, Leonie K; Morrison, Mark; Dekker Nitert, Marloes

    2016-08-01

    Overweight and obese women are at a higher risk for gestational diabetes mellitus. The gut microbiome could modulate metabolic health and may affect insulin resistance and lipid metabolism. The aim of this study was to reveal relationships between gut microbiome composition and circulating metabolic hormones in overweight and obese pregnant women at 16 weeks' gestation. Fecal microbiota profiles from overweight (n = 29) and obese (n = 41) pregnant women were assessed by 16S rRNA sequencing. Fasting metabolic hormone (insulin, C-peptide, glucagon, incretin, and adipokine) concentrations were measured using multiplex ELISA. Metabolic hormone levels as well as microbiome profiles differed between overweight and obese women. Furthermore, changes in some metabolic hormone levels were correlated with alterations in the relative abundance of specific microbes. Adipokine levels were strongly correlated with Ruminococcaceae and Lachnospiraceae, which are dominant families in energy metabolism. Insulin was positively correlated with the genus Collinsella. Gastrointestinal polypeptide was positively correlated with the genus Coprococcus but negatively with family Ruminococcaceae This study shows novel relationships between gut microbiome composition and the metabolic hormonal environment in overweight and obese pregnant women at 16 weeks' gestation. These results suggest that manipulation of the gut microbiome composition may influence pregnancy metabolism. PMID:27217482

  18. 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

  19. 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. PMID:26366711

  20. Microbial endocrinology: host-bacteria communication within the gut microbiome.

    PubMed

    Sandrini, Sara; Aldriwesh, Marwh; Alruways, Mashael; Freestone, Primrose

    2015-05-01

    The human body is home to trillions of micro-organisms, which are increasingly being shown to have significant effects on a variety of disease states. Evidence exists that a bidirectional communication is taking place between us and our microbiome co-habitants, and that this dialogue is capable of influencing our health in a variety of ways. This review considers how host hormonal signals shape the microbiome, and what in return the microbiome residents may be signalling to their hosts. PMID:25792117

  1. 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. PMID:24997786

  2. The human gut microbiome and its dysfunctions through the meta-omics prism.

    PubMed

    Mondot, Stanislas; Lepage, Patricia

    2016-05-01

    The microorganisms inhabiting the human gut are abundant (10(14) cells) and diverse (approximately 500 species per individual). It is now acknowledged that the microbiota has coevolved with its host to achieve a symbiotic relationship, leading to physiological homeostasis. The gut microbiota ensures vital functions, such as food digestibility, maturation of the host immune system, and protection against pathogens. Over the last few decades, the gut microbiota has also been associated with numerous diseases, such as inflammatory bowel disease, irritable bowel syndrome, obesity, and metabolic diseases. In most of these pathologies, a microbial dysbiosis has been found, indicating shifts in the taxonomic composition of the gut microbiota and changes in its functionality. Our understanding of the influence of the gut microbiota on human health is still growing. Working with microorganisms residing in the gut is challenging since most of them are anaerobic and a vast majority (approximately 75%) are uncultivable to date. Recently, a wide range of new approaches (meta-omics) has been developed to bypass the uncultivability and reveal the intricate mechanisms that sustain gut microbial homeostasis. After a brief description of these approaches (metagenomics, metatranscriptomics, metaproteomics, and metabolomics), this review will discuss the importance of considering the gut microbiome as a structured ecosystem and the use of meta-omics to decipher dysfunctions of the gut microbiome in diseases. PMID:26945826

  3. 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

  4. 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. PMID:25724964

  5. Development of the Honey Bee Gut Microbiome throughout the Queen-Rearing Process

    PubMed Central

    Tarpy, David R.; Mattila, Heather R.

    2015-01-01

    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. PMID:25724964

  6. 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. PMID:27609798

  7. 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. PMID:27559027

  8. 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

  9. Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

    PubMed

    Boursier, Jerome; Diehl, Anna Mae

    2016-05-01

    Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice. Gut microbiota adds complexity to the pathophysiology of nonalcoholic fatty liver disease but represents an opportunity to discover new therapeutic targets. PMID:27063268

  10. Mucin glycan foraging in the human gut microbiome.

    PubMed

    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

  11. 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

  12. Investigating the Overlooked Genomes That Impact Animal Health: The Gut Microbiome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mucosal surfaces of humans and animals are colonized by a diverse microbiota that contributes significantly to host health. The gut microbiome influences animal health through assuring nutritional uptake and metabolism, developing and mediating innate immunity, and modulating virulence and abun...

  13. 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

  14. 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

  15. Emerging Concepts on the Gut Microbiome and Multiple Sclerosis.

    PubMed

    Glenn, Justin D; Mowry, Ellen M

    2016-06-01

    Microbiota of the human body perform fundamental tasks that contribute to normal development, health, and homeostasis and are intimately associated with numerous organ systems, including the gut. Microbes begin gut inhabitance immediately following birth and promote proper gut epithelial construction and function, metabolism and nutrition, and immune system development. Inappropriate immune recognition of self-tissue can lead to autoimmune disease, including conditions such as multiple sclerosis (MS), in which the immune system recognizes and attacks central nervous system tissue. Preclinical studies have demonstrated a requirement of gut microbiota for neuroinflammatory autoimmune disease in animal models, and a growing number of clinical investigations are finding associations between MS status and the composition of the gut microbiota. In this review, we examine current undertakings into better understanding the role of gut bacteria and their phages in MS development, review associations of the gut microbiota makeup and MS, and discuss potential mechanisms by which the gut microbiota may be manipulated for therapeutic benefit. PMID:27145057

  16. 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

  17. 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. PMID:24685620

  18. 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

  19. The Human Gut Microbiome and Body Metabolism: Implications for Obesity and Diabetes

    PubMed Central

    Devaraj, Sridevi; Hemarajata, Peera; Versalovic, James

    2014-01-01

    BACKGROUND Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders. CONTENT Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways. CONCLUSION Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes. PMID:23401286

  20. Effects of chlorpyrifos on the gut microbiome and urine metabolome in mouse (Mus musculus).

    PubMed

    Zhao, Yanping; Zhang, Yan; Wang, Guoxiang; Han, Ruiming; Xie, Xianchuan

    2016-06-01

    In this study, the toxic effects of clorpyrifos (CPF) on the gut microbiome and related urine metabolome in mouse (Mus musculus) were investigated. Mice were exposed to a daily dose of 1 mg kg(-1) bodyweight of CPF for 30 d. As a result, CPF significantly altered the gut microbiota composition in terms of the relative abundance of key microbes. Meanwhile, CPF exposure induced the alterations of urine metabolites related to the metabolism of amino acids, energy, short-chain fatty acids (SCFAs), phenyl derivatives and bile acids. High correlations were observed between perturbed gut microbiome and altered metabolic profiles. These perturbations finally resulted in intestinal inflammation and abnormal intestinal permeability, which were also confirm by the histologic changes in colon and remarkable increase of lipopolysaccharide (LPS) and diamine oxidase (DAO) in the serum of CPF-treated mice. Our findings will provide a new perspective to reveal the mechanism of CPF toxicity. PMID:27018521

  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

    2015-08-01

    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. PMID:26244934

  2. 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. PMID:26168244

  3. 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

  4. 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

  5. The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome

    PubMed Central

    Omenetti, Sara; Pizarro, Theresa T.

    2015-01-01

    T-helper 17 (Th17) and T-regulatory (Treg) cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect the host from pathogenic microorganisms and to restrain excessive effector T-cell responses, respectively. Despite their differing functional properties, Th17 cells and Tregs share similar developmental requirements. In fact, the fate of antigen-naïve T-cells to either Th17 or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6, and all-trans retinoic acid. Importantly, the intestinal microbiome also provides immunostimulatory signals, which can activate innate and downstream adaptive immune responses. Specific components of the gut microbiome have been implicated in the production of proinflammatory cytokines by innate immune cells, such as IL-6, IL-23, IL-1β, and the subsequent generation and expansion of Th17 cells. Similarly, commensal bacteria and their metabolites can also promote the generation of intestinal Tregs that can actively induce mucosal tolerance. As such, dysbiosis of the gut microbiome may not solely represent a consequence of gut inflammation, but rather shape the Treg/Th17 commitment and influence susceptibility to inflammatory bowel disease. In this review, we discuss Treg and Th17 cell plasticity, its dynamic regulation by the microbiome, and highlight its impact on intestinal homeostasis and disease. PMID:26734006

  6. 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. PMID:27093431

  7. 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

  8. High Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity

    PubMed Central

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

    2009-01-01

    Background The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here we used the phenotype of RELMβ Knockout (KO) mice to assess the influence of these factors. Methods and Results Both wild-type and RELMβ KO mice were lean on a standard chow diet, but upon switching to a high fat diet, wild-type mice became obese while RELMβ 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 (i.e. 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 RELMβ genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content due to a high fat diet, including an increase in transporters and two-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. Conclusions 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. PMID:19706296

  9. 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

  10. Strain-level dissection of the contribution of the gut microbiome to human metabolic disease.

    PubMed

    Zhang, Chenhong; Zhao, Liping

    2016-01-01

    The gut microbiota has been linked with metabolic diseases in humans, but demonstration of causality remains a challenge. The gut microbiota, as a complex microbial ecosystem, consists of hundreds of individual bacterial species, each of which contains many strains with high genetic diversity. Recent advances in genomic and metabolomic technologies are facilitating strain-level dissection of the contribution of the gut microbiome to metabolic diseases. Interventional studies and correlation analysis between variations in the microbiome and metabolome, captured by longitudinal sampling, can lead to the identification of specific bacterial strains that may contribute to human metabolic diseases via the production of bioactive metabolites. For example, high-quality draft genomes of prevalent gut bacterial strains can be assembled directly from metagenomic datasets using a canopy-based algorithm. Specific metabolites associated with a disease phenotype can be identified by nuclear magnetic resonance-based metabolomics of urine and other samples. Such multi-omics approaches can be employed to identify specific gut bacterial genomes that are not only correlated with detected metabolites but also encode the genes required for producing the precursors of those metabolites in the gut. Here, we argue that if a causative role can be demonstrated in follow-up mechanistic studies--for example, using gnotobiotic models--such functional strains have the potential to become biomarkers for diagnostics and targets for therapeutics. PMID:27098841

  11. 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. PMID:25691688

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

    PubMed

    Lee, Heetae; Ko, GwangPyo

    2016-01-01

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

  13. Species-function relationships shape ecological properties of the human gut microbiome.

    PubMed

    Vieira-Silva, Sara; Falony, Gwen; Darzi, Youssef; Lima-Mendez, Gipsi; Garcia Yunta, Roberto; Okuda, Shujiro; Vandeputte, Doris; Valles-Colomer, Mireia; Hildebrand, Falk; Chaffron, Samuel; Raes, Jeroen

    2016-01-01

    Despite recent progress, the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated. Here, using a manually curated metabolic module framework for (meta-)genomic data analysis, we studied species-function relationships in gut microbial genomes and microbiomes. Half of gut-associated species were found to be generalists regarding overall substrate preference, but we observed significant genus-level metabolic diversification linked to bacterial life strategies. Within each genus, metabolic consistency varied significantly, being low in Firmicutes genera and higher in Bacteroides. Differentiation of fermentable substrate degradation potential contributed to metagenomic functional repertoire variation between individuals, with different enterotypes showing distinct saccharolytic/proteolytic/lipolytic profiles. Finally, we found that module-derived functional redundancy was reduced in the low-richness Bacteroides enterotype, potentially indicating a decreased resilience to perturbation, in line with its frequent association to dysbiosis. These results provide insights into the complex structure of gut microbiome-encoded metabolic properties and emphasize the importance of functional and ecological assessment of gut microbiome variation in clinical studies. PMID:27573110

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

    PubMed Central

    Lee, Heetae; Ko, GwangPyo

    2016-01-01

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

  15. 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. PMID:26497477

  16. Subchronic Exposure of Mice to Cadmium Perturbs Their Hepatic Energy Metabolism and Gut Microbiome.

    PubMed

    Zhang, Songbin; Jin, Yuanxiang; Zeng, Zhaoyang; Liu, Zhenzhen; Fu, Zhengwei

    2015-10-19

    Cadmium (Cd) is an environmental pollutant known to cause liver damage; however, the mechanisms of its hepatotoxicity remain poorly understood. In this study, the effects of subchronic exposure in mice to low doses of Cd on energy metabolism and the gut microbiome were evaluated. The exposure of mice to 10 mg/L Cd supplied in drinking water for 10 weeks increased hepatic triacylglycerol (TG), serum free fatty acid (FFA), and TG levels. The mRNA levels of several key genes involved in both de novo FFA synthesis and transport pathways and in TG synthesis in the liver also increased significantly in the Cd-treated mice, indicating that alterations of these genes may be a possible mechanism to explain subchronic Cd exposure induced hepatic toxicity at a molecular level. As for the gut microbiome, at the phylum level, the amounts of Firmicutes and γ-proteobacteria decreased significantly in the feces after 4 weeks of Cd exposure, and the quantity of Firmicutes decreased significantly in the cecum contents after 10 weeks of Cd exposure. In addition, 16S rRNA gene sequencing further revealed that Cd exposure significantly perturbed the gut microflora structure and richness at family and genus levels. The alteration of gut microbiome composition might result in an increase in serum lipopolysaccharide (LPS) and induce hepatic inflammation, which may indirectly cause perturbations of energy homeostasis after Cd exposure. Taken together, the present study indicated that subchronic Cd exposure caused the dysregulation of energy metabolism and changed the gut microbiome composition in mice. PMID:26352046

  17. 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

  18. 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. PMID:24231662

  19. 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

  20. 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

  1. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity.

    PubMed

    Zhernakova, Alexandra; Kurilshikov, Alexander; Bonder, Marc Jan; Tigchelaar, Ettje F; Schirmer, Melanie; Vatanen, Tommi; Mujagic, Zlatan; Vila, Arnau Vich; Falony, Gwen; Vieira-Silva, Sara; Wang, Jun; Imhann, Floris; Brandsma, Eelke; Jankipersadsing, Soesma A; Joossens, Marie; Cenit, Maria Carmen; Deelen, Patrick; Swertz, Morris A; Weersma, Rinse K; Feskens, Edith J M; Netea, Mihai G; Gevers, Dirk; Jonkers, Daisy; Franke, Lude; Aulchenko, Yurii S; Huttenhower, Curtis; Raes, Jeroen; Hofker, Marten H; Xavier, Ramnik J; Wijmenga, Cisca; Fu, Jingyuan

    2016-04-29

    Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions. PMID:27126040

  2. The obese gut microbiome across the epidemiologic transition.

    PubMed

    Dugas, Lara R; Fuller, Miles; Gilbert, Jack; Layden, Brian T

    2016-01-01

    The obesity epidemic has emerged over the past few decades and is thought to be a result of both genetic and environmental factors. A newly identified factor, the gut microbiota, which is a bacterial ecosystem residing within the gastrointestinal tract of humans, has now been implicated in the obesity epidemic. Importantly, this bacterial community is impacted by external environmental factors through a variety of undefined mechanisms. We focus this review on how the external environment may impact the gut microbiota by considering, the host's geographic location 'human geography', and behavioral factors (diet and physical activity). Moreover, we explore the relationship between the gut microbiota and obesity with these external factors. And finally, we highlight here how an epidemiologic model can be utilized to elucidate causal relationships between the gut microbiota and external environment independently and collectively, and how this will help further define this important new factor in the obesity epidemic. PMID:26759600

  3. Infant-feeding practices and American Indian infants' gut microbiome: Rationale of the pilot study.

    PubMed

    Zamor-Kapoor, Anna; Sinclair, Ka'imi

    2016-03-01

    This study aims to examine the relationship between infant-feeding practices and American Indian infants' gut microbiome--laying the foundation of a research program aimed at identifying potential aetiologies of childhood obesity in this population. Previous studies have emphasised the high prevalence of obesity in American Indian infants, but its underlying causes remain unclear. We received funding from the University of Washington to examine attitudes towards breastfeeding and formula feeding in American Indian mothers, their dietary and physical activity habits and the yield, quality and diversity of their infants' gut microbiome. Our study combines the strengths of qualitative and quantitative data with DNA sequencing. Results will be used to propose a larger study aimed at clarifying aetiologies of childhood obesity in this population and to identify prevention strategies. This protocol describes the theoretical basis of the study, rationale for the target population, study design, participant recruitment and data analysis plan. PMID:27188076

  4. 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

  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. PMID:27067014

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

    PubMed

    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. 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. PMID:26764479

  8. 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

  9. 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. PMID:26452391

  10. Functional Cloning and Characterization of Antibiotic Resistance Genes from the Chicken Gut Microbiome

    PubMed Central

    Zhou, Wei; Wang, Ying

    2012-01-01

    Culture-independent sampling in conjunction with a functional cloning approach identified diverse antibiotic resistance genes for different classes of antibiotics in gut microbiomes from both conventionally raised and free-range chickens. Many of the genes are phylogenetically distant from known resistance genes. Two unique genes that conferred ampicillin and spectinomycin resistance were also functional in Campylobacter, a distant relative of the Escherichia coli host used to generate the genomic libraries. PMID:22286984

  11. Digesting the emerging role for the gut microbiome in central nervous system demyelination.

    PubMed

    Joscelyn, Jennifer; Kasper, Lloyd H

    2014-10-01

    The fields of microbiology, immunology, neurology and nutrition are rapidly converging, as advanced sequencing and genomics-based methodologies have enabled the mapping out of the microbial diversity of humans for the first time. Bugs, guts, brains and behavior were once believed to be separate domains of clinical practice and research; however, recent observations in our understanding of the microbiome indicate that the boundaries between domains are becoming permeable. This permeability is multidirectional: Biological systems are operating simultaneously in a vastly complex and interconnected web. Understanding the microbiome-gut-brain axis will entail fleshing out the mechanisms by which transduction across each domain occurs, allowing us ultimately to appreciate the role of commensal organisms in shaping and modulating host immunity. This article will highlight animal and human research to date, as well as highlight directions for future research. We speculate that the gut microbiome is potentially the premier environmental risk factor mediating inflammatory central nervous system demyelination, in particular multiple sclerosis. PMID:25070675

  12. Immune disorders and its correlation with gut microbiome.

    PubMed

    Hwang, Ji-Sun; Im, Chang-Rok; Im, Sin-Hyeog

    2012-08-01

    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

  13. 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

    2014-01-01

    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

  14. 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

  15. 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

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

    PubMed

    Leclercq, Sophie; Forsythe, Paul; Bienenstock, John

    2016-04-01

    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

  17. Brain gut microbiome interactions and functional bowel disorders

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. 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.

  19. 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. PMID:27243236

  20. The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

    PubMed

    O'Callaghan, T F; Ross, R P; Stanton, C; Clarke, G

    2016-07-01

    The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety. PMID:27345323

  1. Lateral gene transfer of an ABC transporter complex between major constituents of the human gut microbiome

    PubMed Central

    2012-01-01

    Background Several links have been established between the human gut microbiome and conditions such as obesity and inflammatory bowel syndrome. This highlights the importance of understanding what properties of the gut microbiome can affect the health of the human host. Studies have been undertaken to determine the species composition of this microbiome and infer functional profiles associated with such host properties. However, lateral gene transfer (LGT) between community members may result in misleading taxonomic attributions for the recipient organisms, thus making species-function links difficult to establish. Results We identified a peptides/nickel transport complex whose components differed in abundance based upon levels of host obesity, and assigned the encoded proteins to members of the microbial community. Each protein was assigned to several distinct taxonomic groups, with moderate levels of agreement observed among different proteins in the complex. Phylogenetic trees of these proteins produced clusters that differed greatly from taxonomic attributions and indicated that habitat-directed LGT of this complex is likely to have occurred, though not always between the same partners. Conclusions These findings demonstrate that certain membrane transport systems may be an important factor within an obese-associated gut microbiome and that such complexes may be acquired several times by different strains of the same species. Additionally, an example of individual proteins from different organisms being transferred into one operon was observed, potentially demonstrating a functional complex despite the donors of the subunits being taxonomically disparate. Our results also highlight the potential impact of habitat-directed LGT on the resident microbiota. PMID:23116195

  2. 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

  3. 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. PMID:27579024

  4. 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. PMID:25846719

  5. 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. PMID:26995267

  6. Functional metagenomics to mine the human gut microbiome for dietary fiber catabolic enzymes.

    PubMed

    Tasse, Lena; Bercovici, Juliette; Pizzut-Serin, Sandra; Robe, Patrick; Tap, Julien; Klopp, Christophe; Cantarel, Brandi L; Coutinho, Pedro M; Henrissat, Bernard; Leclerc, Marion; Doré, Joël; Monsan, Pierre; Remaud-Simeon, Magali; Potocki-Veronese, Gabrielle

    2010-11-01

    The human gut microbiome is a complex ecosystem composed mainly of uncultured bacteria. It plays an essential role in the catabolism of dietary fibers, the part of plant material in our diet that is not metabolized in the upper digestive tract, because the human genome does not encode adequate carbohydrate active enzymes (CAZymes). We describe a multi-step functionally based approach to guide the in-depth pyrosequencing of specific regions of the human gut metagenome encoding the CAZymes involved in dietary fiber breakdown. High-throughput functional screens were first applied to a library covering 5.4 × 10(9) bp of metagenomic DNA, allowing the isolation of 310 clones showing beta-glucanase, hemicellulase, galactanase, amylase, or pectinase activities. Based on the results of refined secondary screens, sequencing efforts were reduced to 0.84 Mb of nonredundant metagenomic DNA, corresponding to 26 clones that were particularly efficient for the degradation of raw plant polysaccharides. Seventy-three CAZymes from 35 different families were discovered. This corresponds to a fivefold target-gene enrichment compared to random sequencing of the human gut metagenome. Thirty-three of these CAZy encoding genes are highly homologous to prevalent genes found in the gut microbiome of at least 20 individuals for whose metagenomic data are available. Moreover, 18 multigenic clusters encoding complementary enzyme activities for plant cell wall degradation were also identified. Gene taxonomic assignment is consistent with horizontal gene transfer events in dominant gut species and provides new insights into the human gut functional trophic chain. PMID:20841432

  7. 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

  8. Functional metagenomics to mine the human gut microbiome for dietary fiber catabolic enzymes

    PubMed Central

    Tasse, Lena; Bercovici, Juliette; Pizzut-Serin, Sandra; Robe, Patrick; Tap, Julien; Klopp, Christophe; Cantarel, Brandi L.; Coutinho, Pedro M.; Henrissat, Bernard; Leclerc, Marion; Doré, Joël; Monsan, Pierre; Remaud-Simeon, Magali; Potocki-Veronese, Gabrielle

    2010-01-01

    The human gut microbiome is a complex ecosystem composed mainly of uncultured bacteria. It plays an essential role in the catabolism of dietary fibers, the part of plant material in our diet that is not metabolized in the upper digestive tract, because the human genome does not encode adequate carbohydrate active enzymes (CAZymes). We describe a multi-step functionally based approach to guide the in-depth pyrosequencing of specific regions of the human gut metagenome encoding the CAZymes involved in dietary fiber breakdown. High-throughput functional screens were first applied to a library covering 5.4 × 109 bp of metagenomic DNA, allowing the isolation of 310 clones showing beta-glucanase, hemicellulase, galactanase, amylase, or pectinase activities. Based on the results of refined secondary screens, sequencing efforts were reduced to 0.84 Mb of nonredundant metagenomic DNA, corresponding to 26 clones that were particularly efficient for the degradation of raw plant polysaccharides. Seventy-three CAZymes from 35 different families were discovered. This corresponds to a fivefold target-gene enrichment compared to random sequencing of the human gut metagenome. Thirty-three of these CAZy encoding genes are highly homologous to prevalent genes found in the gut microbiome of at least 20 individuals for whose metagenomic data are available. Moreover, 18 multigenic clusters encoding complementary enzyme activities for plant cell wall degradation were also identified. Gene taxonomic assignment is consistent with horizontal gene transfer events in dominant gut species and provides new insights into the human gut functional trophic chain. PMID:20841432

  9. The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice

    PubMed Central

    Turnbaugh, Peter J.; Ridaura, Vanessa K.; Faith, Jeremiah J.; Rey, Federico E.; Knight, Rob; Gordon, Jeffrey I.

    2010-01-01

    Diet and nutritional status are among the most important, modifiable determinants of human health. The nutritional value of food is influenced in part by a person’s gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelationships between diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent, metagenomic analysis of the temporal, spatial and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized, and reproduced much of the bacterial diversity of the donor’s microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat/high-sugar “Western” diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community, but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle “clinical trials” that test the effects of environmental and genetic factors on the gut microbiota and host physiology. PMID:20368178

  10. The Gut Microbiome in Intestinal Fibrosis: Environmental Protector or Provocateur?

    PubMed Central

    Rieder, Florian

    2013-01-01

    In individuals with inflammatory bowel diseases, intestinal fibrosis is a serious clinical complication with no specific therapies. Patients develop bowel fistulae and strictures that usually require surgery and often reoccur. The main driver of gut fibrogenesis is believed to be chronic inflammation, which leads to mesenchymal cell recruitment and activation. Recent findings suggest that the environment—in particular the microbiome—plays a critical role in this process. PMID:23785034

  11. Metagenomic Analysis of the Human Distal Gut Microbiome

    PubMed Central

    Gill, Steven R.; Pop, Mihai; DeBoy, Robert T.; Eckburg, Paul B.; Turnbaugh, Peter J.; Samuel, Buck S.; Gordon, Jeffrey I.; Relman, David A.; Fraser-Liggett, Claire M.; Nelson, Karen E.

    2011-01-01

    The human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome (“microbiome”) contains at least 100 times as many genes as our own genome. We analyzed ~78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction–amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-d-erythritol 4-phosphate pathway–mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes. PMID:16741115

  12. 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

  13. 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

  14. 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. PMID:26994772

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

    PubMed

    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

  16. 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

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

    PubMed

    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

    2016-05-01

    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

  18. Alterations of the Murine Gut Microbiome with Age and Allergic Airway Disease

    PubMed Central

    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. PMID:26090504

  19. 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. PMID:26090504

  20. 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.

  1. 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

  2. Gut microbiome composition is linked to whole grain-induced immunological improvements

    PubMed Central

    Martínez, Inés; Lattimer, James M; Hubach, Kelcie L; Case, Jennifer A; Yang, Junyi; Weber, Casey G; Louk, Julie A; Rose, Devin J; Kyureghian, Gayaneh; Peterson, Daniel A; Haub, Mark D; Walter, Jens

    2013-01-01

    The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans. PMID:23038174

  3. 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

    2015-08-01

    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. PMID:25982560

  4. 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. PMID:26482265

  5. Plasmid metagenomics reveals multiple antibiotic resistance gene classes among the gut microbiomes of hospitalised patients.

    PubMed

    Jitwasinkul, Tossawan; Suriyaphol, Prapat; Tangphatsornruang, Sithichoke; Hansen, Martin Asser; Hansen, Lars Hestbjerg; Sørensen, Søren Johannes; Permpikul, Chairat; Rongrungruang, Yong; Tribuddharat, Chanwit

    2016-09-01

    Antibiotic resistance genes are rapidly spread between pathogens and the normal flora, with plasmids playing an important role in their circulation. This study aimed to investigate antibiotic resistance plasmids in the gut microbiome of hospitalised patients. Stool samples were collected from seven inpatients at Siriraj Hospital (Bangkok, Thailand) and were compared with a sample from a healthy volunteer. Plasmids from the gut microbiomes extracted from the stool samples were subjected to high-throughput DNA sequencing (GS Junior). Newbler-assembled DNA reads were categorised into known and unknown sequences (using >80% alignment length as the cut-off), and ResFinder was used to classify the antibiotic resistance gene pools. Plasmid replicon modules were used for plasmid typing. Forty-six genes conferring resistance to several classes of antibiotics were identified in the stool samples. Several antibiotic resistance genes were shared by the patients; interestingly, most were reported previously in food animals and healthy humans. Four antibiotic resistance genes were found in the healthy subject. One gene (aph3-III) was identified in the patients and the healthy subject and was related to that in cattle. Uncommon genes of hospital origin such as blaTEM-124-like and fosA, which confer resistance to extended-spectrum β-lactams and fosfomycin, respectively, were identified. The resistance genes did not match the patients' drug treatments. In conclusion, several plasmid types were identified in the gut microbiome; however, it was difficult to link these to the antibiotic resistance genes identified. That the antibiotic resistance genes came from hospital and community environments is worrying. PMID:27530840

  6. 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

  7. Genomics of schizophrenia: time to consider the gut microbiome?

    PubMed

    Dinan, T G; Borre, Y E; Cryan, J F

    2014-12-01

    Research into the genomics of schizophrenia promises much, but so far is resplendent with failures to replicate, and has yielded little of therapeutic potential. Within our bodies resides a dynamic population of gut microbes forming a symbiotic superorganism comprising a myriad of bacteria of approximately 10(14) cells, containing 100 times the number of genes of the human genome and weighing approximately the same as the human brain. Recent preclinical investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management. We are pivotally dependent on the neuroactive substances produced by such bacteria. The biological diversity of this ecosystem is established in the initial months of life and is highly impacted upon by environmental factors. To date, this vast quantity of DNA has been largely ignored in schizophrenia research. Perhaps it is time to reconsider this omission. PMID:25288135

  8. About the gut microbiome as a pharmacological target in atherosclerosis.

    PubMed

    Witjes, Julia J; van Raalte, Daniel H; Nieuwdorp, Max

    2015-09-15

    The contribution of intestinal bacterial strains (gut microbiota) in the development of cardiometabolic disease is increasingly recognized as potential diagnostic and pharmacological target. Changes in the intestinal bacterial composition and subsequent altered diversity has been associated with presence of chronic low-grade inflammation of mesenteric visceral adipose tissue, a known feature of malign obesity which can eventually lead to insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. In this regard, both fecal transplantation studies as well as multiethnic prospective cohorts can help to identify the causally involved driving intestinal bacterial strains in human cardiometabolism. Ultimately, it is expected that novel diagnostic markers as well as therapeutics (pharmabiotics and vaccine strategies) can be developed. PMID:26096558

  9. 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. PMID:26723910

  10. 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. PMID:27306663

  11. 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

  12. The gut microbiome in human immunodeficiency virus infection.

    PubMed

    Zilberman-Schapira, Gili; Zmora, Niv; Itav, Shlomik; Bashiardes, Stavros; Elinav, Hila; Elinav, Eran

    2016-01-01

    HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of 'multi-factorial' disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations. PMID:27256449

  13. The microbiome-gut-brain axis: from bowel to behavior.

    PubMed

    Cryan, J F; O'Mahony, S M

    2011-03-01

    The ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as an exciting concept in health and disease. The enteric microbiota interacts with the host to form essential relationships that govern homeostasis. Despite the unique enteric bacterial fingerprint of each individual, there appears to be a certain balance that confers health benefits. It is, therefore, reasonable to note that a decrease in the desirable gastrointestinal bacteria will lead to deterioration in gastrointestinal, neuroendocrine or immune relationships and ultimately disease. Therefore, studies focusing on the impact of enteric microbiota on the host and in particular on the central nervous system are essential to our understanding of the influence of this system. Recent studies published in this Journal demonstrate that germ-free mice display alterations in stress-responsivity, central neurochemistry and behavior indicative of a reduction in anxiety in comparison to conventional mice. Such data offer the enticing proposition that specific modulation of the enteric microbiota may be a useful strategy for stress-related disorders and for modulating the co-morbid aspects of gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease. PMID:21303428

  14. The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents

    PubMed Central

    Bengtsson-Palme, Johan; Angelin, Martin; Huss, Mikael; Kjellqvist, Sanela; Kristiansson, Erik; Palmgren, Helena; Larsson, D. G. Joakim

    2015-01-01

    Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics. PMID:26259788

  15. Longitudinal Prediction of the Infant Gut Microbiome with Dynamic Bayesian Networks.

    PubMed

    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

  16. 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

  17. Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation

    PubMed Central

    Earley, Zachary M.; Akhtar, Suhail; Green, Stefan J.; Naqib, Ankur; Khan, Omair; Cannon, Abigail R.; Hammer, Adam M.; Morris, Niya L.; Li, Xiaoling; Eberhardt, Joshua M.; Gamelli, Richard L; Kennedy, Richard H.; Choudhry, Mashkoor A.

    2015-01-01

    Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host. PMID:26154283

  18. Alterations of the gut microbiome and metabolome in alcoholic liver disease

    PubMed Central

    Zhong, Wei; Zhou, Zhanxiang

    2014-01-01

    Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic relationship with the host. Alterations of gut microbiome by alcohol consumption are referred to bacterial overgrowth, release of bacteria-derived products, and/or changed microbiota equilibrium. Alcohol consumption also perturbs the function of gastrointestinal mucosa and elicits a pathophysiological condition. These adverse effects caused by alcohol may ultimately result in a broad change of gastrointestinal luminal metabolites such as bile acids, short chain fatty acids, and branched chain amino acids. Gut microbiota alterations, metabolic changes produced in a dysbiotic intestinal environment, and the host factors are all critical contributors to the development and progression of alcoholic liver disease. This review summarizes recent findings of how alcohol-induced alterations of gut microbiota and metabolome, and discusses the mechanistic link between gastrointestinal dyshomeostasis and alcoholic liver injury. PMID:25400995

  19. 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

  20. 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

  1. 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

  2. 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. PMID:26709835

  3. 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

  4. 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. PMID:26925392

  5. 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

  6. 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

  7. Bespoke microbiome therapy to manage plant diseases

    PubMed Central

    Gopal, Murali; Gupta, Alka; Thomas, George V.

    2013-01-01

    Information gathered with advanced nucleotide sequencing technologies, small molecule detection systems and computational biology is revealing that a community of microbes and their genes, now termed “the microbiome,” located in gut and rhizosphere, is responsible for maintaining the health of human beings and plants, respectively. Within the complete microbiome a “core-microbiome” exists that plays the pivotal role in well being of humans and plants. Recent studies in medicine have shown that an artificial mixture of bacteria representing the core gut microbiome of healthy person when transferred into gut of diseased person results in re-establishment of normal microflora in the latter leading to alleviation from diseased condition. In agriculture, though not exactly in similar manner as in medicine, success in plant disease management has been achieved through transfer of microbiome by mixing disease suppressive soils with disease conducive soils. A study more similar to artificial gut microbiome transfer in medical field has been recently reported in agriculture, in which transfer of microbiome via soil solutions (filtered and unfiltered) has shown ability to alleviate drought stress in Arabidopsis thaliana. However, the exact practice of transferring artificially cultivated core-microbiome as in medicine has not thus far been attempted in plant disease management. Nonetheless, as the gut and rhizosphere microbiome are known to share many common traits, there exists a good scope for accomplishing similar studies in agriculture. Based upon the information drawn from all recent works in microbiome studies of gut and rhizosphere, we propose that tailor-made core-microbiome transfer therapy can be a success in agriculture too and it could become a viable strategy for management of plant diseases in future. PMID:24348466

  8. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics.

    PubMed

    Ridlon, Jason M; Bajaj, Jasmohan S

    2015-03-01

    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

  9. Gut Microbiome Composition in Young Nicaraguan Children During Diarrhea Episodes and Recovery.

    PubMed

    Becker-Dreps, Sylvia; Allali, Imane; Monteagudo, Andrea; Vilchez, Samuel; Hudgens, Michael G; Rogawski, Elizabeth T; Carroll, Ian M; Zambrana, Luis Enrique; Espinoza, Felix; Azcarate-Peril, M Andrea

    2015-12-01

    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

  10. 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