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Sample records for human gut flora

  1. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora.

    PubMed Central

    Mathan, V I; Wiederman, J; Dobkin, J F; Lindenbaum, J

    1989-01-01

    The inactivation of digoxin by conversion to reduced metabolites (digoxin reduction products, or DRP), a function of the anaerobic gut flora, was studied in normal volunteers from southern India and the United States. Digoxin was metabolised to DRP by 28 (13.7%) of 204 healthy south Indians in contrast to 67 (36.0%) of 186 New Yorkers (p less than 1 X 10(-6)). Only 1.0% of Indians compared with 14.0% of Americans excreted large amounts of metabolites (greater than 40% DRP) in the urine (p less than 1 X 10(-5)). Of 104 urban Indians, 23 (22.1%) were metabolisers, in contrast with five of 100 rural villagers (p less than 0.001). Within the urban group, digoxin metabolism correlated with education, frequency of animal protein intake, and most significantly, personal income. Organisms capable of reducing digoxin in vitro were found with similar frequencies in stool cultures from Indians and Americans. In the cultures of some subjects, DRP production was inhibited at lower dilutions but expressed at higher dilutions. We conclude that variations in drug metabolism between population groups may result from differences in the metabolic activity of the anaerobic gut flora probably mediated by environmentally determined factors. PMID:2759492

  2. [Multiple Sclerosis and Commensal Gut Flora].

    PubMed

    Yamamura, Takashi

    2016-06-01

    Although a symbiotic relationship between commensal gut microbiota and host is widely appreciated, recent works have indicated that normal gut flora functions to prevent inflammatory bowel diseases and obesity in the host, indicating a more mutualistic relationship. Dysbiosis of the commensal flora may lead to development of these disorders. Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS. PMID:27279159

  3. Resistant starch modifies gut microflora and microbial metabolism in human flora-associated rats inoculated with faeces from Italian and UK donors.

    PubMed

    Silvi, S; Rumney, C J; Cresci, A; Rowland, I R

    1999-03-01

    The effect of sucrose and resistant starch ('CrystaLean'--a retrograded, amylose starch) on human gut microflora and associated parameters was studied in human flora-associated (HFA) rats, colonized with microfloras from UK or Italian subjects, to determine whether such floras were affected differently by dietary carbohydrates. Consumption of the resistant starch diet resulted in significant changes in four of the seven main groups of bacteria enumerated. In both the UK and Italian flora-associated rats, numbers of lactobacilli and bifidobacteria were increased 10-100-fold, and there was a concomitant decrease in enterobacteria when compared with sucrose-fed rats. The induced changes in caecal microflora of both HFA rat groups were reflected in changes in bacterial enzyme activities and caecal ammonia concentration. Although it had little effect on caecal short-chain fatty acid concentration, CrystaLean markedly increased the proportion of n-butyric acid in both rat groups and was associated with a significant increase in cell proliferation in the proximal colon of the Italian flora-associated rats. CrystaLean appeared to play a protective role in the colon environment, lowering caecal ammonia concentration, caecal pH and beta-glucuronidase activity. PMID:10196757

  4. The gut flora as a forgotten organ

    PubMed Central

    O'Hara, Ann M; Shanahan, Fergus

    2006-01-01

    The intestinal microflora is a positive health asset that crucially influences the normal structural and functional development of the mucosal immune system. Mucosal immune responses to resident intestinal microflora require precise control and an immunosensory capacity for distinguishing commensal from pathogenic bacteria. In genetically susceptible individuals, some components of the flora can become a liability and contribute to the pathogenesis of various intestinal disorders, including inflammatory bowel diseases. It follows that manipulation of the flora to enhance the beneficial components represents a promising therapeutic strategy. The flora has a collective metabolic activity equal to a virtual organ within an organ, and the mechanisms underlying the conditioning influence of the bacteria on mucosal homeostasis and immune responses are beginning to be unravelled. An improved understanding of this hidden organ will reveal secrets that are relevant to human health and to several infectious, inflammatory and neoplastic disease processes. PMID:16819463

  5. Products formed during fermentation of the prebiotic inulin with human gut flora enhance expression of biotransformation genes in human primary colon cells.

    PubMed

    Sauer, Julia; Richter, Konrad Klaus; Pool-Zobel, Beatrice Louise

    2007-05-01

    Inulin-type fructans are fermented by gut bacteria to yield SCFA, including butyrate which is trophic for colonocytes and induces glutathione S-transferases (GST) that detoxify carcinogens. Since little is known on similar effects by complex fermentation samples, we studied related products in non-transformed human colonocytes. Inulin enriched with oligofructose (1:1, Synergy1) was fermented with human gut flora. SCFA were quantified and a SCFA mixture was prepared accordingly. Colonocytes were incubated (4-12 h) with the Synergy1 fermentation supernatant (SFS), faeces control, a mixture of the three major SCFA (each 0-15 %, v/v) or butyrate (0-50 mM). Metabolic activity was determined to assess trophic effects and cytotoxicity. Expression of ninety-six genes related to biotransformation was studied using cDNA macroarrays. Results on modulated GST were reassessed with real-time PCR and GST activity was measured. Fermentation of inulin resulted in 2-3-fold increases of SCFA. The samples were non-cytotoxic. SFS increased metabolic activity, pointing to trophic effects. The samples modulated gene expression with different response patterns. Key results were that GSTM2 (2.0-fold) and GSTM5 (2.2-fold) were enhanced by SFS, whereas the SCFA mixture reduced expression. The faeces control enhanced GSTA4 (2.0-fold), but reduced GSTM2 (0.2-fold) and GSTM5 (0.2-fold). Realtime qPCR confirmed the induction of GSTM2 and GSTM5 by SFS and of GSTA4 and GSTT2 by butyrate. Activity of GST was not modulated. High concentrations of fermentation products were well tolerated by primary colonocytes, pointing to trophic effects. The induction of GST by the SFS may protect the cells from carcinogenic compounds. PMID:17381985

  6. Both wheat (Triticum aestivum) bran arabinoxylans and gut flora-mediated fermentation products protect human colon cells from genotoxic activities of 4-hydroxynonenal and hydrogen peroxide.

    PubMed

    Glei, Michael; Hofmann, Thomas; Küster, Katrin; Hollmann, Jürgen; Lindhauer, Meinolf G; Pool-Zobel, Beatrice L

    2006-03-22

    Dietary fibers are fermented by the gut flora to yield short chain fatty acids (SCFAs), which inhibit the growth of tumor cells, induce glutathione S-transferases (GSTs), and protect cells from the genotoxic activity of 4-hydroxynonenal (HNE). Here, we investigated effects of wheat bran-derived arabinoxylans and fermentation products on these parameters of chemoprevention. Newly isolated water extractable (WeAx) and alkali extractable arabinoxylans (AeAx) were fermented under anaerobic conditions with human feces. Resulting fermentation supernatants (FSs) were analyzed for SCFAs and used to treat HT29 colon cancer cells. Cell growth, cytotoxicity, antigenotoxicity against hydrogen peroxide (H2O2) or HNE, and GST activity were determined. Nonfermented WeAx decreased H2O2-induced DNA damage by 64%, thus demonstrating chemoprotective properties by this nonfermented wheat bran fiber. The fermentation of WeAx and AeAx resulted in 3-fold increases of SCFA, but all FSs (including the control without arabinoxylans) inhibited the growth of the HT29 cells, reduced the genotoxicity of HNE, and enhanced the activity of GSTs (FS WeAx, 2-fold; FS AeAx, 1.7-fold; and control FS, 1.4-fold), which detoxify HNE. Thus, increases in SCFAs were not reflected by enhanced functional effects. The conclusion is that fermentation mixtures contain modulatory compounds that arise from the feces and might add to the effectiveness of SCFAs. PMID:16536580

  7. Human gut flora-fermented nondigestible fraction from cooked bean ( Phaseolus vulgaris L.) modifies protein expression associated with apoptosis, cell cycle arrest, and proliferation in human adenocarcinoma colon cancer cells.

    PubMed

    Campos-Vega, Rocio; García-Gasca, Teresa; Guevara-Gonzalez, Ramón; Ramos-Gomez, Minerva; Oomah, B Dave; Loarca-Piña, Guadalupe

    2012-12-26

    Metabolism of the nondigested fraction (NDF) from common bean ( Phaseolus vulgaris L.) by the human gut flora (hgf) produces short-chain fatty acids (SCFAs) that may benefit cancer by reducing colorectal tumor risks. This paper reports the effect of fermentation products (FP) by hgf (FP-hgf) from NDF of cooked beans on survival and protein expression associated with apoptosis, cell cycle arrest, and proliferation in human adenocarcinoma colon cancer cells. FP-hgf was the only inoculum eliciting butyrate production after 24 h of NDF fermentation using different bacterial sources. FP-hgf inhibited HT-29 cell growth and modulated protein expression associated with apoptosis, cell cycle arrest, and proliferation, as well as morphological changes linked to apoptosis evaluated by TUNEL and hematoxylin and eosin stains, confirming previous results on gene expression. The current results suggest that fermentation of NDF from common beans can elicit beneficial chemoprotective effects in colon cancer by modulating protein expression in HT-29 cells. PMID:23194196

  8. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

    PubMed Central

    Wang, Zeneng; Klipfell, Elizabeth; Bennett, Brian J.; Koeth, Robert; Levison, Bruce S.; DuGar, Brandon; Feldstein, Ariel E.; Britt, Earl B.; Fu, Xiaoming; Chung, Yoon-Mi; Wu, Yuping; Schauer, Phil; Smith, Jonathan D.; Allayee, Hooman; Tang, W. H. Wilson; DiDonato, Joseph A.; Lusis, Aldons J.; Hazen, Stanley L.

    2011-01-01

    Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease. PMID:21475195

  9. Healthy human gut phageome.

    PubMed

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health. PMID:27573828

  10. Modulating the gut flora alters amino acid metabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intestinal microbes consume and produce amino acids (AA). This may impact intestinal threonine (THR) metabolism necessary for adequate gut function. We hypothesized that modulating the gut flora results in an alteration of intestinal THR utilization and hence whole body AA metabolism. Neonatal pigs ...

  11. The Human Gut Microbiota.

    PubMed

    Harmsen, Hermie J M; de Goffau, Marcus C

    2016-01-01

    The microbiota in our gut performs many different essential functions that help us to stay healthy. These functions include vitamin production, regulation of lipid metabolism and short chain fatty acid production as fuel for epithelial cells and regulation of gene expression. There is a very numerous and diverse microbial community present in the gut, especially in the colon, with reported numbers of species that vary between 400 and 1500, for some those we even do not yet have culture representatives.A healthy gut microbiota is important for maintaining a healthy host. An aberrant microbiota can cause diseases of different nature and at different ages ranging from allergies at early age to IBD in young adults. This shows that our gut microbiota needs to be treated well to stay healthy. In this chapter we describe what we consider a healthy microbiota and discuss what the role of the microbiota is in various diseases. Research into these described dysbiosis conditions could lead to new strategies for treatment and/or management of our microbiota to improve health. PMID:27161353

  12. Malnutrition and Gut Flora Dysbiosis: Specific Therapies for Emerging Comorbidities in Heart Failure

    PubMed Central

    Pasini, Evasio; Aquilani, Roberto; Corsetti, Giovanni; Dioguardi, Francesco S.

    2015-01-01

    Chronic heart failure is a complicated multifactorial disease with wide-spread social-economic consequences. In spite of the recent development of new drugs and therapeutic strategies, CHF-related mortality and morbidity remain high. Recent evidence suggests that changes in organs such as skeletal muscle and gut flora may play an important and independent role in CHF prognosis. This paper illustrates these phenomena, proposing how to identify them and presenting current therapies which treat organs all too often underestimated but which have a fundamental role in worsening CHF. PMID:26491666

  13. Real-time analysis of gut flora in Entamoeba histolytica infected patients of Northern India

    PubMed Central

    2012-01-01

    Background Amebic dysentery is caused by the protozoan parasite Entamoeba histolytica and the ingestion of quadrinucleate cyst of E. histolytica from fecally contaminated food or water initiates infection. Excystation occurs in the lumen of small intestine, where motile and potentially invasive trophozoites germinate from cysts. The ability of trophozoites to interact and digest gut bacteria is apparently important for multiplication of the parasite and its pathogenicity; however the contribution of resident bacterial flora is not well understood. We quantified the population of Bacteroides, Bifidobacterium, Ruminococcus, Lactobacillus, Clostridium leptum subgroup, Clostridium coccoides subgroup, Eubacterium, Campylobacter, Methanobrevibacter smithii and Sulphur reducing bacteria using genus specific primers in healthy (N = 22) vs amebic patients (E. histolytica positive, N = 17) stool samples by Real-time PCR. Results Absolute quantification of Bacteroides (p = .001), Closrtridium coccoides subgroup (p = 0.002), Clostridium leptum subgroup (p = 0.0001), Lactobacillus (p = 0.037), Campylobacter (p = 0.0014) and Eubacterium (p = 0.038) show significant drop in their population however, significant increase in Bifdobacterium (p = 0.009) was observed where as the population of Ruminococcus (p = 0.33) remained unaltered in healthy vs amebic patients (E. histolytica positive). We also report high prevalence of nimE gene in stool samples of both healthy volunteers and amebic patients. No significant decrease in nimE gene copy number was observed before and after the treatment with antiamebic drug. Conclusions Our results show significant alteration in predominant gut bacteria in E. histolytica infected individuals. The frequent episodes of intestinal amoebic dysentery thus result in depletion of few predominant genera in gut that may lead to poor digestion and absorption of food in intestine. It further disturbs the homeostasis

  14. 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

  15. 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

  16. Naturally Occurring Culturable Aerobic Gut Flora of Adult Phlebotomus papatasi, Vector of Leishmania major in the Old World

    PubMed Central

    Mukhopadhyay, Jaba; Braig, Henk R.; Rowton, Edgar D.; Ghosh, Kashinath

    2012-01-01

    Background Cutaneous leishmaniasis is a neglected, vector-borne parasitic disease and is responsible for persistent, often disfiguring lesions and other associated complications. Leishmania, causing zoonotic cutaneous leishmaniasis (ZCL) in the Old World are mainly transmitted by the predominant sand fly vector, Phlebotomus papatasi. To date, there is no efficient control measure or vaccine available for this widespread insect-borne infectious disease. Methodology/Principal Findings A survey was carried out to study the abundance of different natural gut flora in P. papatasi, with the long-term goal of generating a paratransgenic sand fly that can potentially block the development of Leishmania in the sand fly gut, thereby preventing transmission of leishmania in endemic disease foci. Sand flies, in particular, P. papatasi were captured from different habitats of various parts of the world. Gut microbes were cultured and identified using 16S ribosomal DNA analysis and a phylogenetic tree was constructed. We found variation in the species and abundance of gut flora in flies collected from different habitats. However, a few Gram-positive, nonpathogenic bacteria including Bacillus flexus and B. pumilus were common in most of the sites examined. Conclusion/Significance Our results indicate that there is a wide range of variation of aerobic gut flora inhabiting sand fly guts, which possibly reflect the ecological condition of the habitat where the fly breeds. Also, some species of bacteria (B. pumilus, and B. flexus) were found from most of the habitats. Important from an applied perspective of dissemination, our results support a link between oviposition induction and adult gut flora. PMID:22629302

  17. An in vitro metabolic system of gut flora and the metabolism of ginsenoside Rg3 and cholic acid.

    PubMed

    Zhao, Chunyan; Sun, Runbin; Cao, Bei; Gu, Shenghua; Zhao, Jieyu; Liu, Linsheng; Wang, Xinwen; Zha, Weibin; Yu, Xiaoyi; Xiao, Wenjing; Mao, Yong; Ge, Chun; Ju, Jiaqi; Aa, Lixiang; Fei, Fei; Ding, Yi; Aa, Jiye; Wang, Guangji

    2014-06-01

    For orally administered drugs, the metabolism of a drug by the gut flora plays an important role in the bioavailability, activation and disposition of the drug in vivo. However, no in vitro system is currently available to evaluate the metabolism of a drug by the gut flora before the drug is absorbed into the body. This paper presents an in vitro metabolic system in an anaerobic environment that could be used to evaluate the metabolism of an endogenous compound, cholic acid, and a xenobiotic compound, ginsenoside Rg3. We showed that the proliferation of the anaerobic bacteria of the gut content of hamsters produced a similar composition of gut flora in a culture medium for yeast to that in vivo. Incubation of ginsenoside Rg3 and cholic acid in the anaerobic in vitro system efficiently produced the metabolites Rh2 and deoxycholic acid, respectively, similar to those seen in the gut content in vivo. In comparison with in vivo analysis, this anaerobic in vitro metabolic system is convenient, reproducible, economic and animal saving, and can easily be applied to assess the transformation and disposition of a drug before it enters into the circulatory system. PMID:23749587

  18. FLORA

    Energy Science and Technology Software Center (ESTSC)

    1985-04-01

    FLORA solves, in a 2D domain for the linearized stability of a long-thin (paraxial)axisymmetric equilibrium. This is of interest for determining the magnetohydrodynamic stability of a magnetic mirror plasma confinement system including finite-Larmor radius and rotation effects. An axisymmetric plasma equilibrium is specified by providing pressure profiles, the plasma mass density, the vacuum magnetic fields, and plasma electric potential as functions of (?).

  19. Ecological consequences of ingestion of Bacillus cereus on Bacillus thuringiensis infections and on the gut flora of a lepidopteran host.

    PubMed

    Raymond, Ben; Lijek, Rebeccah S; Griffiths, Robert I; Bonsall, Michael B

    2008-09-01

    The Bacillus cereus group comprises a diverse array of non-pathogenic bacteria as well as pathogens such as Bacillus thuringiensis. Their spores are found together in soil and leaves and are therefore likely to commonly interact within hosts. Mixed infections of pathogenic B. thuringiensis and non-pathogenic strains have been little studied, despite their potential impact on biological control and the evolutionary ecology of virulence. Antibiotic secreting strains of B. cereus have been shown to be able to synergize B. thuringiensis (Bt) infections. We explored the ecology of these mixed infections more broadly in the diamondback moth (DBM). We tested whether antibiotic-expressing B. cereus can synergize Bt infections initiated with spores, investigated whether ingestion of antibiotic-expressing B. cereus had any consequences for the larval gut flora and whether synergistic interactions with B. cereus increase Bt reproduction. Ingestion of high-antibiotic secreting B. cereus synergized infections of B. thuringiensis in diamondback moth larvae, but at a lower level than previously reported. Coinfection also increased slightly the number of Bt spores found in cadavers. Culture independent analysis of gut homogenates indicated that ingestion of an antibiotic-expressing strain of B. cereus reduced the abundance of the gut flora and led to gut communities being dominated bacteria with DGGE profiles very similar to pure B. cereus cultures. Ingestion of B. cereus, regardless of genotype, reduced densities of an enteric isolate of Enterobacter sp. These findings support the hypothesis that antibiotic secretion in the gut synergizes B. thuringiensis infections by reducing the abundance of the commensal gut flora and facilitating invasion by bacteria in the B. cereus group. PMID:18533180

  20. Antibiotic residues and drug resistance in human intestinal flora.

    PubMed Central

    Corpet, D E

    1987-01-01

    The effect of residual levels of ampicillin on the drug resistance of fecal flora was studied in human volunteers given 1.5 mg of ampicillin orally per day for 21 days. This treatment failed to have any significant reproducible effect on the number of resistant Escherichia coli in their feces. The effect of continuous administration of small doses of ampicillin, chlortetracycline, or streptomycin in the drinking water was studied in gnotobiotic mice inoculated with a human fecal flora. In this animal model, which is free of many interfering factors, an increase in the fecal concentration of resistant E. coli was observed when the mice were given 0.5 microgram of ampicillin or chlortetracycline per ml of water. This model is therefore a sensitive system for testing the effect of antimicrobial drugs on the resistance characteristics of the intestinal flora. PMID:3300533

  1. 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

  2. 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

  3. 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

  4. Alteration in Bacillus thuringiensis toxicity by curing gut flora: novel approach for mosquito resistance management.

    PubMed

    Patil, Chandrashekhar D; Borase, Hemant P; Salunke, Bipinchandra K; Patil, Satish V

    2013-09-01

    Mosquitoes are known for acquiring resistance against insecticides in many ways, namely target side mutation, enzyme modification, sequestration, quick elimination, etc. But, the role of microflora present in abundance in the larval midgut is less explored with respect to their role in insecticide resistance. During the course of their development, mosquitoes are continuously exposed to microbes and have naturally acquired midgut microbial flora. This midgut flora can modulate the mosquito's susceptibility to Bacillus thuringiensis (Bt) infection by degrading toxic Bt protein forms through an unknown mechanism. In this study, we show that microbe-free aseptic mosquito larvae displayed an increased susceptibility to Bt toxicity compared to larvae harboring natural microbial flora. Fourth instar larvae of Anopheles stephensi were treated separately with penicillin, streptomycin, erythromycin (100 μg/ml), and mixtures of all three antibiotics and then analyzed for Bt toxicity. We have also examined the influence of the mosquito's midgut microbial flora under microaerophilic condition on the Bt protein degradation through plate, broth, TLC, and UV-vis spectrophotometric assay. A better understanding of the roles of microbiota in preventing Bt toxicity to mosquitoes could potentially lead to the development of new sustainable mosquito control strategies. PMID:23820604

  5. 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

  6. The human gut virome: a multifaceted majority

    PubMed Central

    Ogilvie, Lesley A.; Jones, Brian V.

    2015-01-01

    Here, we outline our current understanding of the human gut virome, in particular the phage component of this ecosystem, highlighting progress, and challenges in viral discovery in this arena. We reveal how developments in high-throughput sequencing technologies and associated data analysis methodologies are helping to illuminate this abundant ‘biological dark matter.’ Current evidence suggests that the human gut virome is a highly individual but temporally stable collective, dominated by phages exhibiting a temperate lifestyle. This viral community also appears to encode a surprisingly rich functional repertoire that confers a range of attributes to their bacterial hosts, ranging from bacterial virulence and pathogenesis to maintaining host–microbiome stability and community resilience. Despite the significant advances in our understanding of the gut virome in recent years, it is clear that we remain in a period of discovery and revelation, as new methods and technologies begin to provide deeper understanding of the inherent ecological characteristics of this viral ecosystem. As our understanding increases, the nature of the multi-partite interactions occurring between host and microbiome will become clearer, helping us to more rationally define the concepts and principles that will underpin approaches to using human gut virome components for medical or biotechnological applications. PMID:26441861

  7. Peptidoglycan Recognition Proteins Protect Mice from Experimental Colitis by Promoting Normal Gut Flora and Preventing Induction of Interferon-γ

    PubMed Central

    Saha, Sukumar; Jing, Xuefang; Park, Shin Yong; Wang, Shiyong; Li, Xinna; Gupta, Dipika; Dziarski, Roman

    2010-01-01

    SUMMARY There are multiple mechanisms of maintaining tolerance in the gut that protect the intestine from excessive inflammatory response to intestinal microorganisms. We report here that all four mammalian Peptidoglycan Recognition Proteins (PGRPs or Pglyrps) protect the host from colitis induced by dextran sulfate sodium (DSS). Pglyrp1−/−, Pglyrp2−/−, Pglyrp3−/−, and Pglyrp4−/− mice are all more sensitive than wild type (WT) mice to DSS-induced colitis due to changes to more inflammatory gut microflora, higher production of interferon-γ and interferon-inducible genes, and increase in NK cells in the colon upon initial exposure to DSS, which leads to severe hyperplasia of the lamina propria, loss of epithelial cells, and ulceration in the colon. Thus in WT mice PGRPs protect the colon from early inflammatory response and loss of the barrier function of intestinal epithelium by promoting normal bacterial flora and by preventing damaging production of interferon-γ by NK cells in response to injury. PMID:20709292

  8. Commensal gut flora and brain autoimmunity: a love or hate affair?

    PubMed

    Berer, Kerstin; Krishnamoorthy, Gurumoorthy

    2012-05-01

    Multiple sclerosis (MS) and other chronic inflammatory autoimmune diseases represent major public health challenges in industrialised Western society. MS results from an autoimmune attack against myelin structures by self-reactive lymphocytes, which are normal components of the healthy immune repertoire. The nature of the triggers that convert the innocuous self-reactive lymphocytes into an autoaggressive phenotype is poorly understood. In the past, it was primarily suspected that pathogenic infections trigger MS. However, so far, none of the incriminated pathogenic microbes were firmly associated with the disease. A growing body of evidence in animal models of MS implicates the gut microbiota in the induction of central nervous system (CNS) autoimmunity. The mammalian gut harbors a diverse population of microbial organisms which are essential for our well being. There is an increasing understanding that the gut microbiota not only modulates the local immune functions but also affects the systemic immune system. We are only just beginning to understand the nature of the interactions of the gut microbiota with the host's immune system especially in the context of autoimmune diseases. This review will address the influence of intestinal microbiota on immune homeostasis and on the development of autoimmune responses at sites distal to the intestine with a particular emphasis placed on a discussion about CNS autoimmunity. PMID:22322994

  9. Rapid evolution of the human gut virome.

    PubMed

    Minot, Samuel; Bryson, Alexandra; Chehoud, Christel; Wu, Gary D; Lewis, James D; Bushman, Frederic D

    2013-07-23

    Humans are colonized by immense populations of viruses, which metagenomic analysis shows are mostly unique to each individual. To investigate the origin and evolution of the human gut virome, we analyzed the viral community of one adult individual over 2.5 y by extremely deep metagenomic sequencing (56 billion bases of purified viral sequence from 24 longitudinal fecal samples). After assembly, 478 well-determined contigs could be identified, which are inferred to correspond mostly to previously unstudied bacteriophage genomes. Fully 80% of these types persisted throughout the duration of the 2.5-y study, indicating long-term global stability. Mechanisms of base substitution, rates of accumulation, and the amount of variation varied among viral types. Temperate phages showed relatively lower mutation rates, consistent with replication by accurate bacterial DNA polymerases in the integrated prophage state. In contrast, Microviridae, which are lytic bacteriophages with single-stranded circular DNA genomes, showed high substitution rates (>10(-5) per nucleotide each day), so that sequence divergence over the 2.5-y period studied approached values sufficient to distinguish new viral species. Longitudinal changes also were associated with diversity-generating retroelements and virus-encoded Clustered Regularly Interspaced Short Palindromic Repeats arrays. We infer that the extreme interpersonal diversity of human gut viruses derives from two sources, persistence of a small portion of the global virome within the gut of each individual and rapid evolution of some long-term virome members. PMID:23836644

  10. Human Gut Microbiota: Repertoire and Variations

    PubMed Central

    Lagier, Jean-Christophe; Million, Matthieu; Hugon, Perrine; Armougom, Fabrice; Raoult, Didier

    2012-01-01

    The composition of human gut microbiota and their relationship with the host and, consequently, with human health and disease, presents several challenges to microbiologists. Originally dominated by culture-dependent methods for exploring this ecosystem, the advent of molecular tools has revolutionized our ability to investigate these relationships. However, many biases that have led to contradictory results have been identified. Microbial culturomics, a recent concept based on a use of several culture conditions with identification by MALDI-TOF followed by the genome sequencing of the new species cultured had allowed a complementarity with metagenomics. Culturomics allowed to isolate 31 new bacterial species, the largest human virus, the largest bacteria, and the largest Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes, giant viruses, Archaea, and Planctomycetes, have been neglected by the majority of studies. In addition, numerous factors, such as age, geographic provenance, dietary habits, antibiotics, or probiotics, can influence the composition of the microbiota. Finally, in addition to the countless biases associated with the study techniques, a considerable limitation to the interpretation of studies of human gut microbiota is associated with funding sources and transparency disclosures. In the future, studies independent of food industry funding and using complementary methods from a broad range of both culture-based and molecular tools will increase our knowledge of the repertoire of this complex ecosystem and host-microbiota mutualism. PMID:23130351

  11. Human gut microbiota: does diet matter?

    PubMed

    Maukonen, Johanna; Saarela, Maria

    2015-02-01

    The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated. PMID:25156389

  12. Assessing the Human Gut Microbiota in Metabolic Diseases

    PubMed Central

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-01-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens–derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology. PMID:24065795

  13. Impacts of gut bacteria on human health and diseases.

    PubMed

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  14. Impacts of Gut Bacteria on Human Health and Diseases

    PubMed Central

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  15. 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...

  16. Collective unconscious: how gut microbes shape human behavior.

    PubMed

    Dinan, Timothy G; Stilling, Roman M; Stanton, Catherine; Cryan, John F

    2015-04-01

    The human gut harbors a dynamic and complex microbial ecosystem, consisting of approximately 1 kg of bacteria in the average adult, approximately the weight of the human brain. The evolutionary formation of a complex gut microbiota in mammals has played an important role in enabling brain development and perhaps sophisticated social interaction. Genes within the human gut microbiota, termed the microbiome, significantly outnumber human genes in the body, and are capable of producing a myriad of neuroactive compounds. Gut microbes are part of the unconscious system regulating behavior. Recent investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management. In the absence of microbes, underlying neurochemistry is profoundly altered. Studies of gut microbes may play an important role in advancing understanding of disorders of cognitive functioning and social interaction, such as autism. PMID:25772005

  17. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-01-01

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. PMID:27517891

  18. Challenges of metabolomics in human gut microbiota research.

    PubMed

    Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

    2016-08-01

    The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. PMID:27012595

  19. Gut Inflammation and Immunity: What Is the Role of the Human Gut Virome?

    PubMed Central

    Focà, Alfredo; Quirino, Angela; Marascio, Nadia; Zicca, Emilia; Pavia, Grazia

    2015-01-01

    The human virome comprises viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect other organisms, including bacteriophages and plant viruses. The development of high-throughput sequencing techniques has shown that the human gut microbiome is a complex community in which the virome plays a crucial role into regulation of intestinal immunity and homeostasis. Nevertheless, the size of the human virome is still poorly understood. Indeed the enteric virome is in a continuous and dynamic equilibrium with other components of the gut microbiome and the gut immune system, an interaction that may influence the health and disease of the host. We review recent evidence on the viruses found in the gastrointestinal tract, discussing their interactions with the resident bacterial microbiota and the host immune system, in order to explore the potential impact of the virome on human health. PMID:25944980

  20. Obesity changes the human gut mycobiome

    PubMed Central

    Mar Rodríguez, M.; Pérez, Daniel; Javier Chaves, Felipe; Esteve, Eduardo; Marin-Garcia, Pablo; Xifra, Gemma; Vendrell, Joan; Jové, Mariona; Pamplona, Reinald; Ricart, Wifredo; Portero-Otin, Manuel; Chacón, Matilde R.; Fernández Real, José Manuel

    2015-01-01

    The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity. PMID:26455903

  1. Obesity changes the human gut mycobiome.

    PubMed

    Mar Rodríguez, M; Pérez, Daniel; Javier Chaves, Felipe; Esteve, Eduardo; Marin-Garcia, Pablo; Xifra, Gemma; Vendrell, Joan; Jové, Mariona; Pamplona, Reinald; Ricart, Wifredo; Portero-Otin, Manuel; Chacón, Matilde R; Fernández Real, José Manuel

    2015-01-01

    The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically "healthy" from "unhealthy" obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity. PMID:26455903

  2. Gene expression profiling gut microbiota in different races of humans.

    PubMed

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-01-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome. PMID:26975620

  3. Gene expression profiling gut microbiota in different races of humans

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-03-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome.

  4. Gene expression profiling gut microbiota in different races of humans

    PubMed Central

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-01-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome. PMID:26975620

  5. Detection of carboxylesterase and esterase activity in culturable gut bacterial flora isolated from diamondback moth, Plutella xylostella (Linnaeus), from India and its possible role in indoxacarb degradation.

    PubMed

    Ramya, Shanivarsanthe Leelesh; Venkatesan, Thiruvengadam; Srinivasa Murthy, Kottilingam; Jalali, Sushil Kumar; Verghese, Abraham

    2016-01-01

    Diamondback moth (DBM), Plutella xylostella (Linnaeus), is a notorious pest of brassica crops worldwide and is resistant to all groups of insecticides. The insect system harbors diverse groups of microbiota, which in turn helps in enzymatic degradation of xenobiotic-like insecticides. The present study aimed to determine the diversity of gut microflora in DBM, quantify esterase activity and elucidate their possible role in degradation of indoxacarb. We screened 11 geographic populations of DBM in India and analyzed them for bacterial diversity. The culturable gut bacterial flora underwent molecular characterization with 16S rRNA. We obtained 25 bacterial isolates from larvae (n=13) and adults (n=12) of DBM. In larval gut isolates, gammaproteobacteria was the most abundant (76%), followed by bacilli (15.4%). Molecular characterization placed adult gut bacterial strains into three major classes based on abundance: gammaproteobacteria (66%), bacilli (16.7%) and flavobacteria (16.7%). Esterase activity from 19 gut bacterial isolates ranged from 0.072 to 2.32μmol/min/mg protein. Esterase bands were observed in 15 bacterial strains and the banding pattern differed in Bacillus cereus - KC985225 and Pantoea agglomerans - KC985229. The bands were characterized as carboxylesterase with profenofos used as an inhibitor. Minimal media study showed that B. cereus degraded indoxacarb up to 20%, so it could use indoxacarb for metabolism and growth. Furthermore, esterase activity was greater with minimal media than control media: 1.87 versus 0.26μmol/min/mg protein. Apart from the insect esterases, bacterial carboxylesterase may aid in the degradation of insecticides in DBM. PMID:26991291

  6. Some Changes in Gut Bacterial Flora of Field-Grown Peridroma saucia (Lepidoptera: Noctuidae) When Brought into the Laboratory.

    PubMed

    Lighthart, B

    1988-07-01

    Removal of Peridroma saucia from the field to the laboratory caused little change in the quantity of facultative and aerobic bacteria in the gut but produced significant qualitative and quantitative changes in distinguishable groups of the family Enterobacteriaceae in the gut. PMID:16347703

  7. Some Changes in Gut Bacterial Flora of Field-Grown Peridroma saucia (Lepidoptera: Noctuidae) When Brought into the Laboratory

    PubMed Central

    Lighthart, Bruce

    1988-01-01

    Removal of Peridroma saucia from the field to the laboratory caused little change in the quantity of facultative and aerobic bacteria in the gut but produced significant qualitative and quantitative changes in distinguishable groups of the family Enterobacteriaceae in the gut. PMID:16347703

  8. Diversity, stability and resilience of the human gut microbiota

    PubMed Central

    Lozupone, Catherine A.; Stombaugh, Jesse I.; Gordon, Jeffrey I.; Jansson, Janet K.; Knight, Rob

    2013-01-01

    Preface The gut microbiota, the trillions of microbes inhabiting the human intestine, is a complex ecological community that through its collective metabolic activities and host interactions, influences both normal physiology and disease susceptibilities. Understanding factors underlying compositional and functional changes will aid in designing therapies that target the gut microbiota. This goal is formidable because of the immense diversity of the microbiota, interpersonal variation and temporal fluctuations in composition, especially during disease and early development. Here, we describe recent advances in understanding gut microbiota from an ecological perspective, and discuss how these insights might promote health by guiding therapeutic strategy development. PMID:22972295

  9. How informative is the mouse for human gut microbiota research?

    PubMed Central

    Nguyen, Thi Loan Anh; Vieira-Silva, Sara; Liston, Adrian; Raes, Jeroen

    2015-01-01

    The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research. PMID:25561744

  10. Human oral, gut, and plaque microbiota in patients with atherosclerosis

    PubMed Central

    Koren, Omry; Spor, Aymé; Felin, Jenny; Fåk, Frida; Stombaugh, Jesse; Tremaroli, Valentina; Behre, Carl Johan; Knight, Rob; Fagerberg, Björn; Ley, Ruth E.; Bäckhed, Fredrik

    2011-01-01

    Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis. PMID:20937873

  11. 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

  12. 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

  13. 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

  14. Country-specific antibiotic use practices impact the human gut resistome

    PubMed Central

    Forslund, Kristoffer; Sunagawa, Shinichi; Kultima, Jens Roat; Mende, Daniel R.; Arumugam, Manimozhiyan; Typas, Athanasios; Bork, Peer

    2013-01-01

    Despite increasing concerns over inappropriate use of antibiotics in medicine and food production, population-level resistance transfer into the human gut microbiota has not been demonstrated beyond individual case studies. To determine the “antibiotic resistance potential” for entire microbial communities, we employ metagenomic data and quantify the totality of known resistance genes in each community (its resistome) for 68 classes and subclasses of antibiotics. In 252 fecal metagenomes from three countries, we show that the most abundant resistance determinants are those for antibiotics also used in animals and for antibiotics that have been available longer. Resistance genes are also more abundant in samples from Spain, Italy, and France than from Denmark, the United States, or Japan. Where comparable country-level data on antibiotic use in both humans and animals are available, differences in these statistics match the observed resistance potential differences. The results are robust over time as the antibiotic resistance determinants of individuals persist in the human gut flora for at least a year. PMID:23568836

  15. 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

  16. 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

  17. 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

  18. Comparative Analysis of Korean Human Gut Microbiota by Barcoded Pyrosequencing

    PubMed Central

    Nam, Young-Do; Jung, Mi-Ja; Roh, Seong Woon; Kim, Min-Soo; Bae, Jin-Woo

    2011-01-01

    Human gut microbiota plays important roles in harvesting energy from the diet, stimulating the proliferation of the intestinal epithelium, developing the immune system, and regulating fat storage in the host. Characterization of gut microbiota, however, has been limited to western people and is not sufficiently extensive to fully describe microbial communities. In this study, we investigated the overall composition of the gut microbiota and its host specificity and temporal stability in 20 Koreans using 454-pyrosequencing with barcoded primers targeting the V1 to V3 region of the bacterial 16S rRNA gene. A total of 303,402 high quality reads covered each sample and 8,427 reads were analyzed on average. The results were compared with those of individuals from the USA, China and Japan. In general, microbial communities were dominated by five previously identified phyla: Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Proteobacteria. UPGMA cluster analysis showed that the species composition of gut microbiota was host-specific and stable over the duration of the test period, but the relative abundance of each member fluctuated. 43 core Korean gut microbiota were identified by comparison of sequences from each individual, of which 15 species level phylotypes were related to previously-reported butyrate-producing bacteria. UniFrac analysis revealed that human gut microbiota differed between countries: Korea, USA, Japan and China, but tended to vary less between individual Koreans, suggesting that gut microbial composition is related to internal and external characteristics of each country member such as host genetics and diet styles. PMID:21829445

  19. 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

  20. Shotgun metaproteomics of the human distal gut microbiota

    SciTech Connect

    VerBerkmoes, N.C.; Russell, A.L.; Shah, M.; Godzik, A.; Rosenquist, M.; Halfvarsson, J.; Lefsrud, M.G.; Apajalahti, J.; Tysk, C.; Hettich, R.L.; Jansson, Janet K.

    2008-10-15

    The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

  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. Shotgun Metaproteomics of the Human Distal Gut Microbiota

    SciTech Connect

    Verberkmoes, Nathan C; Erickson, Alison L; Shah, Manesh B; Godzik, A; Rosenquist, M; Halfvarsson, J; Lefsrud, Mark G; Apajalahti, J.; Hettich, Robert {Bob} L; Jansson, J

    2009-01-01

    The human gut contains a dense, complex, and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about what genes were expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production, and carbohydrate metabolism compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

  3. From lifetime to evolution: timescales of human gut microbiota adaptation.

    PubMed

    Quercia, Sara; Candela, Marco; Giuliani, Cristina; Turroni, Silvia; Luiselli, Donata; Rampelli, Simone; Brigidi, Patrizia; Franceschi, Claudio; Bacalini, Maria Giulia; Garagnani, Paolo; Pirazzini, Chiara

    2014-01-01

    Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies. PMID:25408692

  4. From lifetime to evolution: timescales of human gut microbiota adaptation

    PubMed Central

    Quercia, Sara; Candela, Marco; Giuliani, Cristina; Turroni, Silvia; Luiselli, Donata; Rampelli, Simone; Brigidi, Patrizia; Franceschi, Claudio; Bacalini, Maria Giulia; Garagnani, Paolo; Pirazzini, Chiara

    2014-01-01

    Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies. PMID:25408692

  5. Antivirulence Activity of the Human Gut Metabolome

    PubMed Central

    Antunes, L. Caetano M.; McDonald, Julie A. K.; Schroeter, Kathleen; Carlucci, Christian; Ferreira, Rosana B. R.; Wang, Melody; Yurist-Doutsch, Sophie; Hira, Gill; Jacobson, Kevan; Davies, Julian; Allen-Vercoe, Emma

    2014-01-01

    ABSTRACT The mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor of Salmonella virulence, obliterating expression of the Salmonella pathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential. PMID:25073640

  6. In vitro fermentation of fructooligosaccharides with human gut bacteria.

    PubMed

    Mao, Bingyong; Li, Dongyao; Zhao, Jianxin; Liu, Xiaoming; Gu, Zhennan; Chen, Yong Q; Zhang, Hao; Chen, Wei

    2015-03-01

    Fructooligosaccharides (FOS) are one of the most studied prebiotics, selectively stimulating the growth of health-promoting bacteria in the host. However, there is increasing evidence that commensal gut bacteria, such as Bacteroides fragilis, Clostridium butyricum, Enterobacter cloacae, and even the pathogenic Escherichia coli BEN2908, are also able to metabolize FOS in vitro, and in some cases, FOS displayed adverse effects. Therefore, it is necessary to identify FOS-metabolizing species that are present in the gut. Unlike previous studies focusing on individual strains, this study used the traditional culture method combined with an alignment search on the gut bacteria database established from the Human Microbiome Project (HMP). The alignment results showed that homologous proteins for FOS transporters and glycosidases were distributed in 237 of the 453 strains of gut bacteria. La506 msmK encoding the ATP-binding protein and Aec45 fosGH1 encoding glycoside hydrolase were most widely distributed, in 155 and 55 strains, respectively. Seven of eight strains with both transporters and glycosidases were proven to be capable of metabolizing FOS, while five strains without either transporters or glycosidases were not. Fifteen species isolated from human feces and 11 species from the alignment search were identified to be FOS-metabolizing, of which Cronobacter sakazakii, Marvinbryantia formatexigens, Ruminococcus gnavus, and Weissella paramesenteroides are reported here for the first time. Thus, alignment search combined with the culture method is an effective method for obtaining a global view of the FOS-metabolizing bacteria in the gut and will be helpful in further investigating the relationship between FOS and human gut bacteria. PMID:25653214

  7. 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

  8. 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

  9. Gut Microbial Succession Follows Acute Secretory Diarrhea in Humans

    PubMed Central

    David, Lawrence A.; Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi

    2015-01-01

    ABSTRACT Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. PMID:25991682

  10. Role of the normal gut microbiota

    PubMed Central

    Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Reddy, D Nageshwar

    2015-01-01

    Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual’s life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool. PMID:26269668

  11. Role of the normal gut microbiota.

    PubMed

    Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

    2015-08-01

    Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool. PMID:26269668

  12. Human gut microbes use multiple transporters to distinguish vitamin B12 analogs and compete in the gut

    PubMed Central

    Degnan, Patrick H.; Barry, Natasha A.; Mok, Kenny C.; Taga, Michiko E.; Goodman, Andrew L.

    2014-01-01

    Summary Genomic and metagenomic sequencing efforts, including human microbiome projects, reveal that microbes often encode multiple systems that appear to accomplish the same task. Whether these predictions reflect actual functional redundancies is unclear. We report that the prominent human gut symbiont Bacteroides thetaiotaomicron employs three functional, homologous vitamin B12 transporters that in at least two cases confer a competitive advantage in the presence of distinct B12 analogs (corrinoids). In the mammalian gut, microbial fitness can be determined by the presence or absence of a single transporter. The total number of distinct corrinoid transporter families in the human gut microbiome likely exceeds those observed in B. thetaiotaomicron by an order of magnitude. These results demonstrate that human gut microbes use elaborate mechanisms to capture and differentiate corrinoids in vivo and that apparent redundancies observed in these genomes can instead reflect hidden specificities that determine whether a microbe will colonize its host. PMID:24439897

  13. Dysbiotic Events in Gut Microbiota: Impact on Human Health

    PubMed Central

    Schippa, Serena; Conte, Maria Pia

    2014-01-01

    The human body is colonized by a large number of microbes coexisting peacefully with their host. The most colonized site is the gastrointestinal tract (GIT). More than 70% of all the microbes in the human body are in the colon. The microorganism population is 10 times larger of the total number of our somatic and germ cells. Two bacterial phyla, accounting for more than 90% of the bacterial cells, dominate the healthy adult intestine: Firmicutes and Bacteroidetes. Considerable variability in the microbiota compositions between people is found when we look at the taxonomic level of species, and strains within species. It is possible to assert that the human microbiota could be compared to a fingerprint. The microbiota acts as a barrier from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis), has been linked to important human diseases such as inflammation related disorders. The present review summarizes our knowledge on the gut microbiota in a healthy context, and examines intestinal dysbiosis in inflammatory bowel disease (IBD) patients; the most frequently reported disease proven to be associated with changes in the gut microbiota. PMID:25514560

  14. Application of the Human Intestinal Tract Chip to the non-human primate gut microbiota.

    PubMed

    Bello González, T D J; van Passel, M W J; Tims, S; Fuentes, S; De Vos, W M; Smidt, H; Belzer, C

    2015-01-01

    The human intestinal microbiota is responsible for various health-related functions, and its diversity can be readily mapped with the 16S ribosomal RNA targeting Human Intestinal Tract (HIT) Chip. Here we characterise distal gut samples from chimpanzees, gorillas and marmosets, and compare them with human gut samples. Our results indicated applicability of the HITChip platform can be extended to chimpanzee and gorilla faecal samples for analysis of microbiota composition and enterotypes, but not to the evolutionary more distant marmosets. PMID:25519524

  15. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults

    PubMed Central

    Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

    2016-01-01

    Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants. PMID:26743949

  16. 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

  17. Gut Microbiota, Probiotics, and Human Health

    PubMed Central

    SUVOROV, Alexander

    2013-01-01

    The review is devoted to the problems of microbiota and the ways of it correction employing beneficial life bacteria- probiotics. It covers the issues related to the functioning of human microbiota and its importance for the health, individual variability of microbial content, functioning of the probiotics in the human organism and the history of probiotic studies with particular focus on the microbiological investigations in the USSR. The article discusses the safety issues related to probiotics and the problems with probiotic therapy, trying to explain the reasons for the side effects caused by probiotics. The necessity of personified selection of the probiotic strain or individual microbial therapy autoprobiotics is also discussed. PMID:24936366

  18. Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health.

    PubMed

    Mai, Volker; Draganov, Peter V

    2009-01-01

    The complex gut microbial flora harbored by individuals (microbiota) has long been proposed to contribute to intestinal health as well as disease. Pre- and probiotic products aimed at improving health by modifying microbiota composition have already become widely available and acceptance of these products appears to be on the rise. However, although required for the development of effective microbiota based interventions, our basic understanding of microbiota variation on a population level and its dynamics within individuals is still rudimentary. Powerful new parallel sequence technologies combined with other efficient molecular microbiota analysis methods now allow for comprehensive analysis of microbiota composition in large human populations. Recent findings in the field strongly suggest that microbiota contributes to the development of obesity, atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the ongoing National Institutes of Health Roadmap 'Human Microbiome Project' and similar projects in other parts of the world, a large coordinated effort is currently underway to study how microbiota can impact human health. Translating findings from these studies into effective interventions that can improve health, possibly personalized based on an individuals existing microbiota, will be the task for the next decade(s). PMID:19115471

  19. How glycan metabolism shapes the human gut microbiota

    PubMed Central

    Koropatkin, Nicole M.; Cameron, Elizabeth A.; Martens, Eric C.

    2014-01-01

    Preface Symbiotic microorganisms that reside in the human intestine are adept at foraging glycans and polysaccharides, including those in dietary plants (starch, hemicellulose, pectin), animal-derived cartilage and tissue (glycosaminoglycans and N-linked glycans), and endogenous glycans from host mucus (O-linked glycans). Fluctuations in the abundance of dietary and endogenous glycans, combined with the immense chemical variation among these molecules, create a dynamic and heterogeneous environment in which gut microorganisms proliferate. In this review, we describe how glycans shape the composition of the gut microbiota over various lengths of time, the mechanisms by which individual microorganisms degrade these glycans, and potential opportunities to intentionally influence this ecosystem for better health and nutrition. PMID:22491358

  20. Human gut microbes impact host serum metabolome and insulin sensitivity.

    PubMed

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn; Hyotylainen, Tuulia; Nielsen, Trine; Jensen, Benjamin A H; Forslund, Kristoffer; Hildebrand, Falk; Prifti, Edi; Falony, Gwen; Le Chatelier, Emmanuelle; Levenez, Florence; Doré, Joel; Mattila, Ismo; Plichta, Damian R; Pöhö, Päivi; Hellgren, Lars I; Arumugam, Manimozhiyan; Sunagawa, Shinichi; Vieira-Silva, Sara; Jørgensen, Torben; Holm, Jacob Bak; Trošt, Kajetan; Kristiansen, Karsten; Brix, Susanne; Raes, Jeroen; Wang, Jun; Hansen, Torben; Bork, Peer; Brunak, Søren; Oresic, Matej; Ehrlich, S Dusko; Pedersen, Oluf

    2016-07-21

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders. PMID:27409811

  1. Glucosinolate and Desulfo-glucosinolate Metabolism by a Selection of Human Gut Bacteria.

    PubMed

    Luang-In, Vijitra; Albaser, Abdulhadi Ali; Nueno-Palop, Carmen; Bennett, Mark H; Narbad, Arjan; Rossiter, John T

    2016-09-01

    Glucosinolate (GSL) hydrolysis is mediated by the enzyme myrosinase which together with specifier proteins can give rise to isothiocyanates (ITCs), thiocyanates, and nitriles (NITs) in cruciferous plants. However, little is known about the metabolism of GSLs by the human gut flora. The aim of the work was to investigate the metabolic fates of sinigrin (SNG), glucotropaeolin (GTP), gluconasturtiin (GNT), and their corresponding desulfo-GSLs (DS-GSLs). Three human gut bacterial strains, Enterococcus casseliflavus CP1, Lactobacillus agilis R16, and Escherichia coli VL8, were chosen for this study. GNT was metabolized to completion within 24 h to phenethyl ITC and phenethyl NIT (PNIT) by all bacteria, except for L. agilis R16 which produced only PNIT. At least 80 % of GTP and SNG were metabolized by all bacteria within 24 h to the corresponding ITCs and NITs. The pH of media over time gradually became acidic for both L. agilis R16 and E. coli VL8, while for E. casseliflavus CP1 the media became slightly alkaline with NIT and ITC production occurring between pH 3.0 and 7.5. ITC production peaked between 4 and 10 h in most cases and gradually declined while NIT production increased and remained relatively constant over time. The total percentage products accounted for 3-53 % of the initial GSL. NITs were produced from DS-GSLs suggesting an alternative metabolism via desulfation for the food based GSLs. The metal ion dependency for NIT production for GNT and its DS form was investigated where it was shown that Fe(2+) increased NIT production, while Mg(2+) stimulated the formation of ITC. PMID:27301252

  2. Evaluation of an Oral Subchronic Exposure of Deoxynivalenol on the Composition of Human Gut Microbiota in a Model of Human Microbiota-Associated Rats

    PubMed Central

    Saint-Cyr, Manuel J.; Perrin-Guyomard, Agnès; Houée, Paméla; Rolland, Jean-Guy; Laurentie, Michel

    2013-01-01

    Background Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is one of the most prevalent mycotoxins present in cereal crops worldwide. Due to its toxic properties, high stability and prevalence, the presence of DON in the food chain represents a health risk for both humans and animals. The gastrointestinal microbiota represents potentially the first target for these food contaminants. Thus, the effects of mycotoxins on the human gut microbiota is clearly an issue that needs to be addressed in further detail. Using a human microbiota-associated rat model, the aim of the present study was to evaluate the impact of a chronic exposure of DON on the composition of human gut microbiota. Methodology/Principal Findings Four groups of 5 germ free male rats each, housed in 4 sterile isolators, were inoculated with a different fresh human fecal flora. Rats were then fed daily by gavage with a solution of DON at 100 µg/kg bw for 4 weeks. Fecal samples were collected at day 0 before the beginning of the treatment; days 7, 16, 21, and 27 during the treatment; and 10 days after the end of the treatment at day 37. DON effect was assessed by real-time PCR quantification of dominant and subdominant bacterial groups in feces. Despite a different intestinal microbiota in each isolator, similar trends were generally observed. During oral DON exposure, a significant increase of 0.5 log10 was observed for the Bacteroides/Prevotella group during the first 3 weeks of administration. Concentration levels for Escherichia coli decreased at day 27. This significant decrease (0.9 log10 CFU/g) remained stable until the end of the experiment. Conclusions/Significance We have demonstrated an impact of oral DON exposure on the human gut microbiota composition. These findings can serve as a template for risk assessment studies of food contaminants on the human gut microbiota. PMID:24260424

  3. In vitro fermentation of lactulose by human gut bacteria.

    PubMed

    Mao, Bingyong; Li, Dongyao; Zhao, Jianxin; Liu, Xiaoming; Gu, Zhennan; Chen, Yong Q; Zhang, Hao; Chen, Wei

    2014-11-12

    Lactulose has been known as a prebiotic that can selectively stimulate the growth of beneficial bifidobacteria and lactobacilli. Recent studies have indicated that Streptococcus mutans, Clostridium perfringens, and Faecalibacterium prausnitzii are also able to utilize lactulose. However, the previous studies mainly focused on the utilization of lactulose by individual strains, and few studies were designed to identify the species that could utilize lactulose among gut microbiota. This study aimed to identify lactulose-metabolizing bacteria in the human gut, using in silico and traditional culture methods. The prediction results suggested that genes for the transporters and glycosidases of lactulose are well distributed in the genomes of 222 of 453 strains of gastrointestinal-tract bacteria. The screening assays identified 35 species with the ability to utilize lactulose, of which Cronobacter sakazakii, Enterococcus faecium, Klebsiella pneumoniae, and Pseudomonas putida were reported for the first time to be capable of utilizing lactulose. In addition, significant correlations between lactulose and galactooligosaccharide metabolism were found. Thus, more attention should be paid to bacteria besides bifidobacteria and lactobacilli to further investigate the relationship between functional oligosaccharides and gut bacteria. PMID:25340538

  4. Estimating Time Since Death from Postmortem Human Gut Microbial Communities.

    PubMed

    Hauther, Kathleen A; Cobaugh, Kelly L; Jantz, Lee Meadows; Sparer, Tim E; DeBruyn, Jennifer M

    2015-09-01

    Postmortem succession of human-associated microbial communities ("human microbiome") has been suggested as a possible method for estimating postmortem interval (PMI) for forensic analyses. Here we evaluate human gut bacterial populations to determine quantifiable, time-dependent changes postmortem. Gut microflora were repeatedly sampled from the proximal large intestine of 12 deceased human individuals as they decayed under environmental conditions. Three intestinal bacterial genera were quantified by quantitative PCR (qPCR) using group-specific primers targeting 16S rRNA genes. Bacteroides and Lactobacillus relative abundances declined exponentially with increasing PMI at rates of Nt=0.977e(-0.0144t) (r2=0.537, p<0.001) and Nt=0.019e(-0.0087t) (r2=0.396, p<0.001), respectively, where Nt is relative abundance at time (t) in cumulative degree hours. Bifidobacterium relative abundances did not change significantly: Nt=0.003e(-0.002t) (r2=0.033, p=0.284). Therefore, Bacteroides and Lactobacillus abundances could be used as quantitative indicators of PMI. PMID:26096156

  5. Superresolution Imaging Captures Carbohydrate Utilization Dynamics in Human Gut Symbionts

    PubMed Central

    Karunatilaka, Krishanthi S.; Cameron, Elizabeth A.; Martens, Eric C.; Koropatkin, Nicole M.

    2014-01-01

    ABSTRACT Gut microbes play a key role in human health and nutrition by catabolizing a wide variety of glycans via enzymatic activities that are not encoded in the human genome. The ability to recognize and process carbohydrates strongly influences the structure of the gut microbial community. While the effects of diet on the microbiota are well documented, little is known about the molecular processes driving metabolism. To provide mechanistic insight into carbohydrate catabolism in gut symbionts, we studied starch processing in real time in the model Bacteroides thetaiotaomicron starch utilization system (Sus) by single-molecule fluorescence. Although previous studies have explored Sus protein structure and function, the transient interactions, assembly, and collaboration of these outer membrane proteins have not yet been elucidated in live cells. Our live-cell superresolution imaging reveals that the polymeric starch substrate dynamically recruits Sus proteins, serving as an external scaffold for bacterial membrane assembly of the Sus complex, which may promote efficient capturing and degradation of starch. Furthermore, by simultaneously localizing multiple Sus outer membrane proteins on the B. thetaiotaomicron cell surface, we have characterized the dynamics and stoichiometry of starch-induced Sus complex assembly on the molecular scale. Finally, based on Sus protein knockout strains, we have discerned the mechanism of starch-induced Sus complex assembly in live anaerobic cells with nanometer-scale resolution. Our insights into the starch-induced outer membrane protein assembly central to this conserved nutrient uptake mechanism pave the way for the development of dietary or pharmaceutical therapies to control Bacteroidetes in the intestinal tract to enhance human health and treat disease. PMID:25389179

  6. Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats.

    PubMed

    Dostal, Alexandra; Lacroix, Christophe; Pham, Van T; Zimmermann, Michael B; Del'homme, Christophe; Bernalier-Donadille, Annick; Chassard, Christophe

    2014-06-28

    The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gut microbiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gut microbiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70 mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35 mg Fe/kg diet; (5) Fe-depleted diet followed by 70 mg Fe/kg diet. Faecal and caecal samples were analysed for gut microbiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gut microbiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35 mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut health. PMID:24555487

  7. 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

  8. 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

  9. Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

    PubMed

    Bryant, Charlotte; Mclaughlin, John

    2016-10-01

    The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. PMID:27133729

  10. Identifying genetic determinants needed to establish a human gut symbiont in its habitat

    PubMed Central

    Goodman, Andrew L.; McNulty, Nathan P.; Zhao, Yue; Leip, Douglas; Mitra, Robi D.; Lozupone, Catherine A.; Knight, Rob; Gordon, Jeffrey I.

    2010-01-01

    Summary The human gut microbiota is a metabolic organ whose cellular composition is determined by a dynamic process of selection and competition. To identify microbial genes required for establishment of human symbionts in the gut, we developed an approach (insertion-sequencing, or INSeq) based on a mutagenic transposon that allows capture of adjacent chromosomal DNA to define its genomic location. We used massively parallel sequencing to monitor the relative abundance of tens of thousands of transposon mutants of a saccharolytic human gut bacterium, Bacteroides thetaiotaomicron, as they established themselves in wild-type and immunodeficient gnotobiotic mice, in the presence or absence of other human gut commensals. In vivo selection transforms this population, revealing functions necessary for survival in the gut: we show how this selection is influenced by community composition and competition for nutrients (vitamin B12). INSeq provides a broadly applicable platform to explore microbial adaptation to the gut and other ecosystems. PMID:19748469

  11. Transformation of trollioside and isoquercetin by human intestinal flora in vitro.

    PubMed

    Yuan, Ming; Shi, Duo-Zhi; Wang, Teng-Yu; Zheng, Shi-Qi; Liu, Li-Jia; Sun, Zhen-Xiao; Wang, Ru-Feng; Ding, Yi

    2016-03-01

    The present study was designed to determine the intestinal bacterial metabolites of trollioside and isoquercetin and their antibacterial activities. A systematic in vitro biotransformation investigation on trollioside and isoquercetin, including metabolite identification, metabolic pathway deduction, and time course, was accomplished using a human intestinal bacterial model. The metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial activities of trollioside, isoquercetin, and their metabolites were evaluated using the broth microdilution method with berberine as a positive control, and their potency was measured as minimal inhibitory concentration (MIC). Our results indicated that trollioside and isoquercetin were metabolized by human intestinal flora through O-deglycosylation, yielding aglycones proglobeflowery acid and quercetin, respectively The antibacterial activities of both metabolites were more potent than that of their parent compounds. In conclusion, trollioside and isoquercetin are totally and rapidly transformed by human intestinal bacteria in vitro and the transformation favors the improvement of the antibacterial activities of the parent compounds. PMID:27025369

  12. 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

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

    SciTech Connect

    Larsen, Peter E.; Dai, Yang

    2015-09-14

    Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. The community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

  14. Human Colon-Derived Soluble Factors Modulate Gut Microbiota Composition

    PubMed Central

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O.; Fernández-Salazar, Luis; Garrote, Jose A.; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C.; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune – IL-15- and microbiota – LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  15. Human colon-derived soluble factors modulate gut microbiota composition.

    PubMed

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O; Fernández-Salazar, Luis; Garrote, Jose A; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  16. Gut Bifidobacteria Populations in Human Health and Aging.

    PubMed

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  17. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  18. Impact of experimental hookworm infection on the human gut microbiota.

    PubMed

    Cantacessi, Cinzia; Giacomin, Paul; Croese, John; Zakrzewski, Martha; Sotillo, Javier; McCann, Leisa; Nolan, Matthew J; Mitreva, Makedonka; Krause, Lutz; Loukas, Alex

    2014-11-01

    The interactions between gastrointestinal parasitic helminths and commensal bacteria are likely to play a pivotal role in the establishment of host-parasite cross-talk, ultimately shaping the development of the intestinal immune system. However, little information is available on the impact of infections by gastrointestinal helminths on the bacterial communities inhabiting the human gut. We used 16S rRNA gene amplification and pyrosequencing to characterize, for the first time to our knowledge, the differences in composition and relative abundance of fecal microbial communities in human subjects prior to and following experimental infection with the blood-feeding intestinal hookworm, Necator americanus. Our data show that, although hookworm infection leads to a minor increase in microbial species richness, no detectable effect is observed on community structure, diversity or relative abundance of individual bacterial species. PMID:24795483

  19. Impact of Experimental Hookworm Infection on the Human Gut Microbiota

    PubMed Central

    Cantacessi, Cinzia; Giacomin, Paul; Croese, John; Zakrzewski, Martha; Sotillo, Javier; McCann, Leisa; Nolan, Matthew J.; Mitreva, Makedonka; Krause, Lutz; Loukas, Alex

    2014-01-01

    The interactions between gastrointestinal parasitic helminths and commensal bacteria are likely to play a pivotal role in the establishment of host-parasite cross-talk, ultimately shaping the development of the intestinal immune system. However, little information is available on the impact of infections by gastrointestinal helminths on the bacterial communities inhabiting the human gut. We used 16S rRNA gene amplification and pyrosequencing to characterize, for the first time to our knowledge, the differences in composition and relative abundance of fecal microbial communities in human subjects prior to and following experimental infection with the blood-feeding intestinal hookworm, Necator americanus. Our data show that, although hookworm infection leads to a minor increase in microbial species richness, no detectable effect is observed on community structure, diversity or relative abundance of individual bacterial species. PMID:24795483

  20. Human gut microbiota and its relationship to health and disease.

    PubMed

    Wallace, Taylor C; Guarner, Francisco; Madsen, Karen; Cabana, Michael D; Gibson, Glenn; Hentges, Eric; Sanders, Mary Ellen

    2011-07-01

    Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics. PMID:21729093

  1. Genome-Wide Association Studies of the Human Gut Microbiota.

    PubMed

    Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  2. Genome-Wide Association Studies of the Human Gut Microbiota

    PubMed Central

    Davenport, Emily R.; Cusanovich, Darren A.; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10−7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  3. Antibacterial potential and genetic profile of Enterococcus faecium strains isolated from human normal flora.

    PubMed

    Karimaei, Samira; Sadeghi, Javad; Asadian, Mahla; Esghaei, Maryam; Pourshafie, Mohammad Reza; Talebi, Malihe

    2016-07-01

    Enterococci have a widespread attendance in the circumference and belongs to the enteric commensal microbiota. Most of them produce the antimicrobial compounds and have an inhibition effect on pathogenic microorganisms. The objective of this study was to characterize the enterococcal strains isolated from human normal flora and assess their antibacterial activity. Enterococcal isolates were obtained from the feces of eighteen healthy humans. All enterococcal species were identified by biochemical and species-specific polymerase chain reaction (PCR). These isolates were investigated further to examine their ability to inhibit growth of Salmonella typhi, Shigella flexneri and Escherichia coli by well diffusion assay. Furthermore, antibiotic susceptibility test was performed and genetic relatedness of all isolates was evaluated by Pulse Field Gel Electrophoresis (PFGE). In all, 432 isolates were obtained from fecal samples. All of the isolates identified as Enterococcus faecium by biochemical and molecular (PCR) methods. Using repetitive element palindromic (REP)-PCR method 54 patterns have been obtained and were selected for further evaluation. The results indicated that 66%, 38% and 24% of our isolates had antimicrobial effect against S. typhi, S flexneri and enteroaggregative Escherichia coli (EAEC), respectively. On the other hand, there was no significant inhibition effect against enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). All isolates were sensitive to vancomycin, teicoplanin, linezolid, ampicillin, chloramphenicol and gentamicin. On the other hand, the resistance rates for erythromycin, tetracycline and ciprofloxacin were 20%, 22%, and 1.8% respectively. In addition, the analysis of PFGE showed forty patterns with eight (40.7%) common types (CT) and thirty two (59.2%) single types (ST). Among eight common types, only one common type (CT5) had similar antimicrobial effect. These results suggested that enterococcal isolates obtained from

  4. Gut microbiota: next frontier in understanding human health and development of biotherapeutics

    PubMed Central

    Prakash, Satya; Rodes, Laetitia; Coussa-Charley, Michael; Tomaro-Duchesneau, Catherine

    2011-01-01

    The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required. PMID:21847343

  5. The influence of various factors on the human resident skin flora.

    PubMed

    Hartmann, A A

    1990-12-01

    Various factors, e.g. prolonged occlusion, skin disinfectants, systemic antimicrobials, can have an impact on the ecosystem of the normal human skin flora for a short time. These impacts are of clinical importance in the treatment of some skin diseases, where members of the normal human skin flora are involved in the pathogenesis of the disease, e.g. Propionibacterium acnes in acne vulgaris, Corynebacterium species in erythrasma, trichomycosis palmellina and pitted keratolysis, Pityrosporum orbiculare/ovale in Pityriasis versicolor, Pityrosporum folliculitis and others. Using the standardized forehead skin test, SFST, proposed by us, antibacterial short-term effects including the action degree profile, the action time profile, and the depth penetration profile of a topically applied antibacterial agent can be measured. Testing 60 v/v% isopropanol, 60 v/v% n-propanol, povidone iodine (aques solution), 3 w/v% salicylic acid in 50 v/v% isopropanol and 1 v/v% phenoli liquefacti in 50 v/v% isopropanol, salicylic acid showed equivalent reduction factors as 60 v/v% n-propanol immediately after the application. With the modified SFST, salicyclic acid tincture produced a 50-fold higher bacterial density reduction 12 hours after the fourth application and a 100-fold reduction 12 hours after the eighth application in comparison with 60 v/v% isopropanol. Salicylic acid, mainly used in dermatotherapy as a keratolytic agent, fulfills all these above mentioned requirements including a well antimicrobial efficacy. Since Salicyclic acid is also effective against yeast and dermatophytes, the substance has some advantages over other antimicrobials used in the dermatotherapy. PMID:2285575

  6. Evolutionary, ecological and biotechnological perspectives on plasmids resident in the human gut mobile metagenome

    PubMed Central

    Ogilvie, Lesley A.; Firouzmand, Sepinoud; Jones, Brian V.

    2012-01-01

    Numerous mobile genetic elements (MGE) are associated with the human gut microbiota and collectively referred to as the gut mobile metagenome. The role of this flexible gene pool in development and functioning of the gut microbial community remains largely unexplored, yet recent evidence suggests that at least some MGE comprising this fraction of the gut microbiome reflect the co-evolution of host and microbe in the gastro-intestinal tract. In conjunction, the high level of novel gene content typical of MGE coupled with their predicted high diversity, suggests that the mobile metagenome constitutes an immense and largely unexplored gene-space likely to encode many novel activities with potential biotechnological or pharmaceutical value, as well as being important to the development and functioning of the gut microbiota. Of the various types of MGE that comprise the gut mobile metagenome, plasmids are of particular importance since these elements are often capable of autonomous transfer between disparate bacterial species, and are known to encode accessory functions that increase bacterial fitness in a given environment facilitating bacterial adaptation. In this article current knowledge regarding plasmids resident in the human gut mobile metagenome is reviewed, and available strategies to access and characterize this portion of the gut microbiome are described. The relative merits of these methods and their present as well as prospective impact on our understanding of the human gut microbiota is discussed. PMID:22126801

  7. Consumption of Human Milk Oligosaccharides by Gut-related Microbes

    PubMed Central

    Marcobal, Angela; Barboza, Mariana; Froehlich, John W.; Block, David E.; German, J. Bruce; Lebrilla, Carlito B.; Mills, David A.

    2010-01-01

    Human milk contains large amounts of complex oligosaccharides that putatively modulate the intestinal microbiota of breast-fed infants by acting as decoy binding sites for pathogens and as prebiotics for enrichment of beneficial bacteria. Several bifidobacterial species have been shown to grow well on human milk oligosaccharides. However, little data exists on other bacterial species. In this work we examined 16 bacterial strains belonging to 10 different genera for growth on human milk oligosaccharides. For this propose, we used a chemically-defined medium, ZMB1, which allows vigorous growth of a number gut–related microorganisms in a fashion similar to complex media. Interestingly, Bifidobacterium longum subsp. infantis, Bacteroides fragilis and Bacteroides vulgatus strains were able to metabolize milk oligosaccharides with high efficiency, while Enterococcus, Streptococcus, Veillonella, Eubacterium, Clostridium, and Escherichia coli strains grew less well or not at all. Mass spectrometry-based glycoprofiling of the oligosaccharide consumption behavior revealed a specific preference for fucosylated oligosaccharides by Bifidobacterium longum subsp. infantis and Bacteroides vulgatus. This work expands the current knowledge of human milk oligosaccharides consumption by gut microbes, revealing bacteroides as avid consumer of this substrate. These results provide insight on how human milk oligosaccharides shape the infant intestinal microbiota. PMID:20394371

  8. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

    PubMed

    Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2016-01-01

    The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being. PMID:27416027

  9. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment

    PubMed Central

    Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2016-01-01

    The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being. PMID:27416027

  10. 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

  11. Fusobacterium nucleatum, inflammation, and immunity: the fire within human gut.

    PubMed

    Bashir, Arif; Miskeen, Abid Yousuf; Hazari, Younis Mohammad; Asrafuzzaman, Syed; Fazili, Khalid Majid

    2016-03-01

    Fusobacterium nucleatum is an identified proinflammatory autochthonous bacterium implicated in human colorectal cancer. It is also abundantly found in patients suffering from chronic gut inflammation (inflammatory bowel disease), consequently contributing to the pathogenesis of colorectal cancer. Majority of the studies have reported that colorectal tumors/colorectal adenocarcinomas are highly enriched with F. nucleatum compared to noninvolved adjacent colonic tissue. During the course of multistep development of colorectal cancer, tumors have evolved many mechanisms to resist the antitumor immune response. One of such favorite ploy is providing access to pathogenic bacteria, especially F. nucleatum in the colorectal tumor microenvironment, wherein both (colorectal tumors and F. nucleatum) exert profound effect on each other, consequently attracting tumor-permissive myeloid-derived suppressor cells, suppressing cytotoxic CD8+ T cells and inhibiting NK cell-mediated cancer cell killing. In this review, we have primarily focused on how this bug modulates the immune response, consequently rendering the antitumor immune cells inactive. PMID:26718210

  12. Human symbionts inject and neutralize antibacterial toxins to persist in the gut.

    PubMed

    Wexler, Aaron G; Bao, Yiqiao; Whitney, John C; Bobay, Louis-Marie; Xavier, Joao B; Schofield, Whitman B; Barry, Natasha A; Russell, Alistair B; Tran, Bao Q; Goo, Young Ah; Goodlett, David R; Ochman, Howard; Mougous, Joseph D; Goodman, Andrew L

    2016-03-29

    The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes--one of two major phyla in the gut--also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation. PMID:26957597

  13. Complex Glycan Catabolism by the Human Gut Microbiota: The Bacteroidetes Sus-like Paradigm*

    PubMed Central

    Martens, Eric C.; Koropatkin, Nicole M.; Smith, Thomas J.; Gordon, Jeffrey I.

    2009-01-01

    Trillions of microbes inhabit the distal gut of adult humans. They have evolved to compete efficiently for nutrients, including a wide array of chemically diverse, complex glycans present in our diets, secreted by our intestinal mucosa, and displayed on the surfaces of other gut microbes. Here, we review how members of the Bacteroidetes, one of two dominant gut-associated bacterial phyla, process complex glycans using a series of similarly patterned, cell envelope-associated multiprotein systems. These systems provide insights into how gut, as well as terrestrial and aquatic, Bacteroidetes survive in highly competitive ecosystems. PMID:19553672

  14. [Why could gut microbiota become a medication?].

    PubMed

    Bourlioux, P; Megerlin, F; Corthier, G; Gobert, J-G; Butel, M-J

    2014-09-01

    The gut microbiota (or gut flora) is a set of bacteria living in symbiosis with the host. Strictly associated with the intestinal tract and interacting with it, the gut microbiota is not a tissue nor an organ, but a supra-organism. A disruption of dialogue between bacteria and human cells is a risk factor or a possible cause of various diseases. The restoration of this dialogue, thanks to the transfer of the gut microbiota of a healthy individual to a patient whose balance of gut flora has been broken, is a new therapeutic approach. If its exact effect still eludes scientific understanding, its clinical benefit is well established for an indication, and is recently being tested for many others. The proven contribution of gut microbiota in the human physiological balance calls for intensifying research throughout the world about the state of knowledge and technologies, as well as on the legal and ethical dimension of fecal microbiota transfer. This didactic paper updates the questions in relation with this therapeutic act. PMID:25220228

  15. 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

  16. Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.

    PubMed Central

    Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

    1981-01-01

    Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners. PMID:7240404

  17. 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

  18. 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

  19. [The gut microbiota in sickness and health].

    PubMed

    Lankelma, Jacqueline M; Nieuwdorp, Max; de Vos, Willem M; Wiersinga, W Joost

    2014-01-01

    The human gut microbiota, formerly known as 'gut flora', may be regarded as an external organ with many physiological functions in metabolism, development of the immune system and defense against pathogens. The adult gut microbiota consist of 1013-1014 micro-organisms. The aggregate genome of these, known as the microbiome, is 100 times larger than the human genome. The gut microbiotica may be involved in the pathogenesis of a range of syndromes, such as inflammatory bowel disease, obesity, diabetes mellitus and atopic disorders. It should be noted that until now most of the studies conducted have been association studies, without proof of causality. This increasing insight has led to identification of new therapeutic strategies, which are currently being investigated in clinical studies. Although the implications of this knowledge for individual patients have yet to become clear, various interventions are conceivable, such as supplementation of nutritional elements, prebiotics or probiotics and feces transplantation. PMID:24780568

  20. Effect of Raw-Milk Cheese Consumption on the Enterococcal Flora of Human Feces

    PubMed Central

    Gelsomino, Roberto; Vancanneyt, Marc; Cogan, Timothy M.; Swings, Jean

    2003-01-01

    Enterococci are one of the major facultative anaerobic bacterial groups that reside in the human gastrointestinal tract. In the present study, the composition of the enterococcal fecal flora in three healthy humans was analyzed before, during, and after the daily consumption of ∼125 g of a raw-milk Cheddar-type cheese containing 3.2 × 104 enterococci/g of cheese. Enterococcal counts ranged between 1.4 × 102 and 2.5 × 108 CFU/g of feces and differed from subject to subject and from week to week. The cheese contained mainly Enterococcus casseliflavus and a small population of Enterococcus faecalis. Clonal relationships were determined by pulsed-field gel electrophoresis. Before and after consumption of the cheese, samples from humans contained mainly Enterococcus faecium, with some of the clones being resident. During consumption of the cheese, one particular transient clone of E. faecalis, clone Fs2, which was present in small numbers in the cheese, largely dominated the feces. Two clones of E. casseliflavus from the cheese were also found in the feces of one of the subjects during cheese consumption. These results suggest that a clone need not be present in a food in high numbers to establish itself in the intestine. PMID:12514010

  1. Human symbionts inject and neutralize antibacterial toxins to persist in the gut

    PubMed Central

    Wexler, Aaron G.; Bao, Yiqiao; Whitney, John C.; Bobay, Louis-Marie; Xavier, Joao B.; Schofield, Whitman B.; Barry, Natasha A.; Russell, Alistair B.; Tran, Bao Q.; Goo, Young Ah; Goodlett, David R.; Ochman, Howard; Mougous, Joseph D.; Goodman, Andrew L.

    2016-01-01

    The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes—one of two major phyla in the gut—also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation. PMID:26957597

  2. The Active Human Gut Microbiota Differs from the Total Microbiota

    PubMed Central

    Peris-Bondia, Francesc; Latorre, Amparo; Artacho, Alejandro; Moya, Andrés; D'Auria, Giuseppe

    2011-01-01

    The human gut microbiota is considered one of the most fascinating reservoirs of microbial diversity hosting between 400 to 1000 bacterial species distributed among nine phyla with Firmicutes, Bacteroidetes and Actinobacteria representing around of the diversity. One of the most intriguing issues relates to understanding which microbial groups are active players in the maintenance of the microbiota homeostasis. Here, we describe the diversity of active microbial fractions compared with the whole community from raw human fecal samples. We studied four healthy volunteers by 16S rDNA gene pyrosequencing. The fractions were obtained by cell sorting based on bacterial RNA concentration. Bacterial families were observed to appear or disappear on applying a cell sorting method in which flow cytometry was used to evaluate the active cells by pyronin-Y staining of RNA. This method was able to detect active bacteria, indicating that the active players differed from that observed in raw fecal material. Generally, observations showed that in the active fractions, the number of reads related to Bacteroidetes decreased whereas several families from Clostridiales (Firmicutes) were more highly represented. Moreover, a huge number of families appeared as part of the active fraction when cell sorting was applied, indicating reads that are simply statistically hidden by the total reads. PMID:21829462

  3. 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

  4. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.

    PubMed

    Forslund, Kristoffer; Hildebrand, Falk; Nielsen, Trine; Falony, Gwen; Le Chatelier, Emmanuelle; Sunagawa, Shinichi; Prifti, Edi; Vieira-Silva, Sara; Gudmundsdottir, Valborg; Krogh Pedersen, Helle; Arumugam, Manimozhiyan; Kristiansen, Karsten; Voigt, Anita Yvonne; Vestergaard, Henrik; Hercog, Rajna; Igor Costea, Paul; Kultima, Jens Roat; Li, Junhua; Jørgensen, Torben; Levenez, Florence; Dore, Joël; Nielsen, H Bjørn; Brunak, Søren; Raes, Jeroen; Hansen, Torben; Wang, Jun; Ehrlich, S Dusko; Bork, Peer; Pedersen, Oluf

    2015-12-10

    In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication. PMID:26633628

  5. Effect of dextransucrase cellobiose acceptor products on the growth of human gut bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The selective fermentation by human gut bacteria of gluco-oligosaccharides obtained from the reaction between the glucosyl group of sucrose and cellobiose, catalyzed by dextransucrases from Leuconostoc mesenteroides, has been evaluated. Oligosaccharides were fractionated according to their molecula...

  6. Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation.

    PubMed

    Newburg, David S; He, Yingying

    2015-12-01

    Glycans of the intestinal mucosa and oligosaccharides of human milk influence the early colonization of the infant gut and establishment of mucosal homeostasis, and differences in colonization of the gut influence the ontogeny of glycans on the surface of the intestinal mucosa, proinflammatory signaling, homeostasis, and resilience to insult. This interkingdom reciprocal interaction is typical of a mutualistic symbiotic relationship. The period in which the infant gut most needs protection from hypersensitive inflammation overlaps with the recommended period of exclusive nursing; electively substituting artificial formula that lacks human milk protective glycans seems ill advised, especially for premature infants. PMID:26457857

  7. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    DOE PAGESBeta

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs.more » disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.« less

  8. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    SciTech Connect

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs. disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.

  9. Human gut microbiota community structures in urban and rural populations in Russia

    PubMed Central

    Tyakht, Alexander V.; Kostryukova, Elena S.; Popenko, Anna S.; Belenikin, Maxim S.; Pavlenko, Alexander V.; Larin, Andrey K.; Karpova, Irina Y.; Selezneva, Oksana V.; Semashko, Tatyana A.; Ospanova, Elena A.; Babenko, Vladislav V.; Maev, Igor V.; Cheremushkin, Sergey V.; Kucheryavyy, Yuriy A.; Shcherbakov, Petr L.; Grinevich, Vladimir B.; Efimov, Oleg I.; Sas, Evgenii I.; Abdulkhakov, Rustam A.; Abdulkhakov, Sayar R.; Lyalyukova, Elena A.; Livzan, Maria A.; Vlassov, Valentin V.; Sagdeev, Renad Z.; Tsukanov, Vladislav V.; Osipenko, Marina F.; Kozlova, Irina V.; Tkachev, Alexander V.; Sergienko, Valery I.; Alexeev, Dmitry G.; Govorun, Vadim M.

    2013-01-01

    The microbial community of the human gut has a crucial role in sustaining host homeostasis. High-throughput DNA sequencing has delineated the structural and functional configurations of gut metagenomes in world populations. The microbiota of the Russian population is of particular interest to researchers, because Russia encompasses a uniquely wide range of environmental conditions and ethnogeographical cohorts. Here we conduct a shotgun metagenomic analysis of gut microbiota samples from 96 healthy Russian adult subjects, which reveals novel microbial community structures. The communities from several rural regions display similarities within each region and are dominated by the bacterial taxa associated with the healthy gut. Functional analysis shows that the metabolic pathways exhibiting differential abundance in the novel types are primarily associated with the trade-off between the Bacteroidetes and Firmicutes phyla. The specific signatures of the Russian gut microbiota are likely linked to the host diet, cultural habits and socioeconomic status. PMID:24036685

  10. 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

  11. 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

  12. 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

  13. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism.

    PubMed

    Morrison, Douglas J; Preston, Tom

    2016-05-01

    The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems. PMID:26963409

  14. Biodiversity of Active and Inactive Bacteria in the Gut Flora of Wood-Feeding Huhu Beetle Larvae (Prionoplus reticularis)▿†

    PubMed Central

    Reid, Nicola M.; Addison, Sarah L.; Macdonald, Lucy J.; Lloyd-Jones, Gareth

    2011-01-01

    Huhu grubs (Prionoplus reticularis) are wood-feeding beetle larvae endemic to New Zealand and belonging to the family Cerambycidae. Compared to the wood-feeding lower termites, very little is known about the diversity and activity of microorganisms associated with xylophagous cerambycid larvae. To address this, we used pyrosequencing to evaluate the diversity of metabolically active and inactive bacteria in the huhu larval gut. Our estimate, that the gut harbors at least 1,800 phylotypes, is based on 33,420 sequences amplified from genomic DNA and reverse-transcribed RNA. Analysis of genomic DNA- and RNA-derived data sets revealed that 71% of all phylotypes (representing 95% of all sequences) were metabolically active. Rare phylotypes contributed considerably to the richness of the community and were also largely metabolically active, indicating their participation in digestive processes in the gut. The dominant families in the active community (RNA data set) included Acidobacteriaceae (24.3%), Xanthomonadaceae (16.7%), Acetobacteraceae (15.8%), Burkholderiaceae (8.7%), and Enterobacteriaceae (4.1%). The most abundant phylotype comprised 14% of the active community and affiliated with Dyella ginsengisoli (Gammaproteobacteria), suggesting that a Dyella-related organism is a likely symbiont. This study provides new information on the diversity and activity of gut-associated microorganisms that are essential for the digestion of the nutritionally poor diet consumed by wood-feeding larvae. Many huhu gut phylotypes affiliated with insect symbionts or with bacteria present in acidic environments or associated with fungi. PMID:21841025

  15. Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune-deficient mice.

    PubMed

    Hurez, Vincent; Dao, Vinh; Liu, Aijie; Pandeswara, Srilakshmi; Gelfond, Jonathan; Sun, Lishi; Bergman, Molly; Orihuela, Carlos J; Galvan, Veronica; Padrón, Álvaro; Drerup, Justin; Liu, Yang; Hasty, Paul; Sharp, Zelton Dave; Curiel, Tyler J

    2015-12-01

    The mammalian (mechanistic) target of rapamycin (mTOR) regulates critical immune processes that remain incompletely defined. Interest in mTOR inhibitor drugs is heightened by recent demonstrations that the mTOR inhibitor rapamycin extends lifespan and healthspan in mice. Rapamycin or related analogues (rapalogues) also mitigate age-related debilities including increasing antigen-specific immunity, improving vaccine responses in elderly humans, and treating cancers and autoimmunity, suggesting important new clinical applications. Nonetheless, immune toxicity concerns for long-term mTOR inhibition, particularly immunosuppression, persist. Although mTOR is pivotal to fundamental, important immune pathways, little is reported on immune effects of mTOR inhibition in lifespan or healthspan extension, or with chronic mTOR inhibitor use. We comprehensively analyzed immune effects of rapamycin as used in lifespan extension studies. Gene expression profiling found many and novel changes in genes affecting differentiation, function, homeostasis, exhaustion, cell death, and inflammation in distinct T- and B-lymphocyte and myeloid cell subpopulations. Immune functions relevant to aging and inflammation, and to cancer and infections, and innate lymphoid cell effects were validated in vitro and in vivo. Rapamycin markedly prolonged lifespan and healthspan in cancer- and infection-prone mice supporting disease mitigation as a mechanism for mTOR suppression-mediated longevity extension. It modestly altered gut metagenomes, and some metagenomic effects were linked to immune outcomes. Our data show novel mTOR inhibitor immune effects meriting further studies in relation to longevity and healthspan extension. PMID:26315673

  16. 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

  17. 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

  18. 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

  19. Comparative evaluation of establishing a human gut microbial community within rodent models

    PubMed Central

    Wos-Oxley, Melissa L.; Bleich, André; Oxley, Andrew P.A.; Kahl, Silke; Janus, Lydia M.; Smoczek, Anna; Nahrstedt, Hannes; Pils, Marina C.; Taudien, Stefan; Platzer, Matthias; Hedrich, Hans-Jürgen; Medina, Eva; Pieper, Dietmar H.

    2012-01-01

    The structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of different diseases. Establishing a defined human gut microbial community within inbred rodent models provides a means to study microbial-related pathologies, however, an in-depth comparison of the established human gut microbiota in the different models is lacking. We compared the efficiency of establishing the bacterial component of a defined human microbial community within germ-free (GF) rats, GF mice and antibiotic-treated specific pathogen-free mice. Remarkable differences were observed between the different rodent models. While the majority of abundant human-donor bacterial phylotypes were established in the GF rats, only a subset was present in the GF mice. Despite the fact that members of the phylum Bacteriodetes were well established in all rodent models, mice enriched for phylotypes related to species of Bacteroides. In contrary to the efficiency of Clostridiales to populate the GF rat in relative proportions to that of the human-donor, members of Clostridia cluster IV only poorly colonize the mouse gut. Thus, the genetic background of the different recipient rodent systems (that is, rats and mice) strongly influences the nature of the populating human gut microbiota, determining each model’s biological suitability. PMID:22572831

  20. 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

  1. The human gut mycobiome: pitfalls and potentials--a mycologist's perspective.

    PubMed

    Suhr, Mallory J; Hallen-Adams, Heather E

    2015-01-01

    We have entered the Age of the Microbiome, with new studies appearing constantly and whole journals devoted to the human microbiome. While bacteria outnumber other gut microbes by orders of magnitude, eukaryotes are consistently found in the human gut and are represented primarily by the fungi. Compiling 36 studies 1917-2015 we found at least 267 distinct fungal taxa have been reported from the human gut, and seemingly every new study includes one or more fungi not previously described from this niche. This diversity, while impressive, is illusory. If we examine gut fungi, we will quickly observe a division between a small number of commonly detected species (Candida yeasts, Saccharomyces and yeasts in the Dipodascaceae, and Malassezia species) and a long tail of taxa that have been reported only once. Furthermore, an investigation into the ecology of these rare species reveals that many of them are incapable of colonization or long-term persistence in the gut. This paper examines what we know and have yet to learn about the fungal component of the gut microbiome, or "mycobiome", and an overview of methods. We address the potential of the field while introducing some caveats and argue for the necessity of including mycologists in mycobiome studies. PMID:26354806

  2. Gut microbiota and its pathophysiology in disease paradigms.

    PubMed

    Festi, Davide; Schiumerini, Ramona; Birtolo, Chiara; Marzi, Luca; Montrone, Lucia; Scaioli, Eleonora; Di Biase, Anna Rita; Colecchia, Antonio

    2011-01-01

    The gut flora carries out important functions for human health, although most of them are still unknown, and an alteration of any of them, due to a condition of dysbiosis, can lead to relevant pathological implications. Commensal bacteria in the gut are essential for the preservation of the integrity of the mucosal barrier function and an alteration in the anatomic functional integrity of this barrier has been implicated in the pathophysiologic process of different diseases. The gut microflora plays a role in modulating the intestinal immune system; in fact, it is essential for the maturation of gut-associated lymphatic tissue, the secretion of IgA and the production of antimicrobial peptides. The enteric flora represents a potent bioreactor which controls several metabolic functions, even if most of them are still unknown. The main metabolic functions are represented by the fermentation of indigestible food substances into simple sugars, absorbable nutrients, and short-chain fatty acids. Furthermore, the gut microbiota exerts important trophic and developmental functions on the intestinal mucosa. This overview focuses briefly on the physiological role of the gut microbiota in maintaining a healthy state and the potential role played by disturbances of both the function and composition of the gut microbiota in determining important pathological conditions, such as irritable bowel syndrome, inflammatory bowel disease, metabolic syndrome, obesity, and cancer. PMID:22179206

  3. Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis

    PubMed Central

    Duranti, Sabrina; Milani, Christian; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Ferrario, Chiara; Mangifesta, Marta; Viappiani, Alice; Sánchez, Borja; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2016-01-01

    Bifidobacteria are members of the human gut microbiota, being numerically dominant in the colon of infants, while also being prevalent in the large intestine of adults. In this study, we determined and analyzed the pan-genome of Bifidobacterium adolescentis, which is one of many bacteria found in the human adult gut microbiota. In silico analysis of the genome sequences of eighteen B. adolescentis strains isolated from various environments, such as human milk, human feces and bovine rumen, revealed a high level of genetic variability, resulting in an open pan-genome. Compared to other bifidobacterial taxa such as Bifidobacterium bifidum and Bifidobacterium breve, the more extensive B. adolescentis pan-genome supports the hypothesis that the genetic arsenal of this taxon expanded so as to become more adaptable to the variable and changing ecological niche of the gut. These increased genetic capabilities are particularly evident for genes required for dietary glycan-breakdown. PMID:27035119

  4. Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis.

    PubMed

    Duranti, Sabrina; Milani, Christian; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Ferrario, Chiara; Mangifesta, Marta; Viappiani, Alice; Sánchez, Borja; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2016-01-01

    Bifidobacteria are members of the human gut microbiota, being numerically dominant in the colon of infants, while also being prevalent in the large intestine of adults. In this study, we determined and analyzed the pan-genome of Bifidobacterium adolescentis, which is one of many bacteria found in the human adult gut microbiota. In silico analysis of the genome sequences of eighteen B. adolescentis strains isolated from various environments, such as human milk, human feces and bovine rumen, revealed a high level of genetic variability, resulting in an open pan-genome. Compared to other bifidobacterial taxa such as Bifidobacterium bifidum and Bifidobacterium breve, the more extensive B. adolescentis pan-genome supports the hypothesis that the genetic arsenal of this taxon expanded so as to become more adaptable to the variable and changing ecological niche of the gut. These increased genetic capabilities are particularly evident for genes required for dietary glycan-breakdown. PMID:27035119

  5. The Gut Microbiota and Immune System Relationship in Human Graft-versus-Host Disease

    PubMed Central

    Laterza, Lucrezia; Rizzatti, Gianenrico; Gaetani, Eleonora; Chiusolo, Patrizia; Gasbarrini, Antonio

    2016-01-01

    Gut microbiota has gained increasing interest in the pathogenesis of immune-related diseases. In this context, graft-versus-host disease is a condition characterized by an immune response which frequently complicates and limits the outcomes of hematopoietic stem cell transplantations. Past studies, carried mostly in animals, already supported a relationship between gut microbiota and graft-versus-host disease. However, the possible mechanisms underlying this connection remain elusory. Moreover, strategies to prevent graft-versus-host disease are of great interest as well as the potential role of gut microbiota modulation. We reviewed the role of gut microbiota in the development of immune system and its involvement in the graft-versus-host disease, focusing on data available on humans. PMID:27158438

  6. 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

  7. Mucosal Glycan Foraging Enhances Fitness and Transmission of a Saccharolytic Human Gut Bacterial Symbiont

    PubMed Central

    Martens, Eric C.; Chiang, Herbert C.; Gordon, Jeffrey I.

    2008-01-01

    Summary The distal human gut is a microbial bioreactor that digests complex carbohydrates. The strategies evolved by gut microbes to sense and process diverse glycans have important implications for the assembly and operations of this ecosystem. The human gut bacterium Bacteroides thetaiotaomicron forages on host and dietary glycans. Its ability to target these substrates resides in 88 polysaccharide utilization loci (PULs), encompassing 18% of its genome. In this report, whole-genome transcriptional profiling and genetic tests are used to define the mechanisms underlying host glycan foraging in vivo and in vitro. PULs that target all major classes of host glycans were identified. Mucin O-glycans are the principal substrate foraged in vivo. Simultaneous deletion of five ECF-σ transcription factors that activate mucin O-glycan utilization produces defects in bacterial persistence in the gut and in mother-to-offspring transmission. Thus, PUL-mediated glycan catabolism is an important factor in gut colonization and likely impacts gut ecology. PMID:18996345

  8. 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

  9. 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

  10. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The architecture of the human distal gut microbiota (microbiota) is sculpted by the complex carbohydrates delivered in the diet. Yeasts, which are among the earliest domesticated microorganisms and have been a component of the human diet for at least 7000 years, possess an elaborate cell wall alpha-...

  11. 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

  12. 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

  13. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides.

    PubMed

    Wu, Meng; McNulty, Nathan P; Rodionov, Dmitry A; Khoroshkin, Matvei S; Griffin, Nicholas W; Cheng, Jiye; Latreille, Phil; Kerstetter, Randall A; Terrapon, Nicolas; Henrissat, Bernard; Osterman, Andrei L; Gordon, Jeffrey I

    2015-10-01

    Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness. PMID:26430127

  14. 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

  15. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides

    PubMed Central

    Wu, Meng; McNulty, Nathan P.; Rodionov, Dmitry A.; Khoroshkin, Matvei S.; Griffin, Nicholas W.; Cheng, Jiye; Latreille, Phil; Kerstetter, Randall A.; Terrapon, Nicolas; Henrissat, Bernard; Osterman, Andrei L.; Gordon, Jeffrey I.

    2015-01-01

    Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in ordered sequence. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability and resilience, and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness. PMID:26430127

  16. Human Milk Glycomics and Gut Microbial Genomics in Infant Feces Show a Correlation between Human Milk Oligosaccharides and Gut Microbiota: A Proof-of-Concept Study

    PubMed Central

    2015-01-01

    Human milk oligosaccharides (HMOs) play a key role in shaping and maintaining a healthy infant gut microbiota. This article demonstrates the potential of combining recent advances in glycomics and genomics to correlate abundances of fecal microbes and fecal HMOs. Serial fecal specimens from two healthy breast-fed infants were analyzed by bacterial DNA sequencing to characterize the microbiota and by mass spectrometry to determine abundances of specific HMOs that passed through the intestinal tract without being consumed by the luminal bacteria. In both infants, the fecal bacterial population shifted from non-HMO-consuming microbes to HMO-consuming bacteria during the first few weeks of life. An initial rise in fecal HMOs corresponded with bacterial populations composed primarily of non-HMO-consuming Enterobacteriaceae and Staphylococcaeae. This was followed by decreases in fecal HMOs as the proportion of HMO-consuming Bacteroidaceae and Bifidobacteriaceae increased. Analysis of HMO structures with isomer differentiation revealed that HMO consumption is highly structure-specific, with unique isomers being consumed and others passing through the gut unaltered. These results represent a proof-of-concept and are consistent with the highly selective, prebiotic effect of HMOs in shaping the gut microbiota in the first weeks of life. The analysis of selective fecal bacterial substrates as a measure of alterations in the gut microbiota may be a potential marker of dysbiosis. PMID:25300177

  17. Probiotics and virulent human rotavirus modulate the transplanted human gut microbiota in gnotobiotic pigs

    PubMed Central

    2014-01-01

    We generated a neonatal pig model with human infant gut microbiota (HGM) to study the effect of a probiotic on the composition of the transplanted microbiota following rotavirus vaccination and challenge. All the HGM-transplanted pigs received two doses of an oral attenuated rotavirus vaccine. The gut microbiota of vaccinated pigs were investigated for effects of Lactobacillus rhamnosus GG (LGG) supplement and homotypic virulent human rotavirus (HRV) challenge. High-throughput sequencing of V4 region of 16S rRNA genes demonstrated that HGM-transplanted pigs carried microbiota similar to that of the C-section delivered baby. Firmicutes and Proteobacteria represented over 98% of total bacteria in the human donor and the recipient pigs. HRV challenge caused a phylum-level shift from Firmicutes to Proteobacteria. LGG supplement prevented the changes in microbial communities caused by HRV challenge. In particular, members of Enterococcus in LGG-supplemented pigs were kept at the baseline level, while they were enriched in HRV challenged pigs. Taken together, our results suggested that HGM pigs are valuable for testing the microbiota’s response to probiotic interventions for treating infantile HRV infection. PMID:25349634

  18. Fate, activity, and impact of ingested bacteria within the human gut microbiota.

    PubMed

    Derrien, Muriel; van Hylckama Vlieg, Johan E T

    2015-06-01

    The human gut contains a highly diverse microbial community that is essentially an open ecosystem, despite being deeply embedded within the human body. Food-associated fermentative bacteria, including probiotics, are major sources of ingested bacteria that may temporarily complement resident microbial communities, thus forming part of our transient microbiome. Here, we review data on the fate and activity of ingested bacteria and, in particular, lactobacilli and bifidobacteria in the gastrointestinal (GI) tract and their impact on the composition and metabolism of the gut microbiome with a focus on data from clinical studies. In addition, we discuss the mechanisms involved and the potential impact on the host's health. PMID:25840765

  19. Bifidobacterium bifidum as an example of a specialized human gut commensal

    PubMed Central

    Turroni, Francesca; Duranti, Sabrina; Bottacini, Francesca; Guglielmetti, Simone; Van Sinderen, Douwe; Ventura, Marco

    2014-01-01

    Bifidobacteria are considered dominant and for this reason key members of the human gut microbiota, particularly during the first one to two years following birth. A substantial proportion of the bifidobacterial population in the intestine of infants belong to the Bifidobacterium bifidum taxon, whose members have been shown to display remarkable physiological and genetic features involving adhesion to epithelia, as well as utilization of host-derived glycans. Here, we reviewed the current knowledge on the genetic features and associated adaptations of B. bifidum to the human gut. PMID:25191315

  20. 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

  1. 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

  2. The Yin and Yang of Bacterial Resilience in the Human Gut Microbiota

    PubMed Central

    Gibson, Molly K.; Pesesky, Mitchell W.; Dantas, Gautam

    2014-01-01

    The human gut is home to trillions of microbes that form a symbiotic relationship with the human host. During health, the intestinal microbiota provides many benefits to the host and is generally resistant to colonization by new species; however, disruption of this complex community can lead to pathogen invasion, inflammation, and disease. Restoration and maintenance of a healthy gut microbiota composition requires effective therapies to reduce and prevent colonization of harmful bacteria (pathogens) while simultaneously promoting growth of beneficial bacteria (probiotics). Here we review the mechanisms by which the host modulates the gut community composition during health and disease, and discuss prospects for antibiotic and probiotic therapy for restoration of a healthy intestinal community following disruption. PMID:24911583

  3. Starch Catabolism by a Prominent Human Gut Symbiont Is Directed by the Recognition of Amylose Helices

    SciTech Connect

    Koropatkin, Nicole M.; Martens, Eric C.; Gordon, Jeffrey I.; Smith, Thomas J.

    2009-01-12

    The human gut microbiota performs functions that are not encoded in our Homo sapiens genome, including the processing of otherwise undigestible dietary polysaccharides. Defining the structures of proteins involved in the import and degradation of specific glycans by saccharolytic bacteria complements genomic analysis of the nutrient-processing capabilities of gut communities. Here, we describe the atomic structure of one such protein, SusD, required for starch binding and utilization by Bacteroides thetaiotaomicron, a prominent adaptive forager of glycans in the distal human gut microbiota. The binding pocket of this unique {alpha}-helical protein contains an arc of aromatic residues that complements the natural helical structure of starch and imposes this conformation on bound maltoheptaose. Furthermore, SusD binds cyclic oligosaccharides with higher affinity than linear forms. The structures of several SusD/oligosaccharide complexes reveal an inherent ligand recognition plasticity dominated by the three-dimensional conformation of the oligosaccharides rather than specific interactions with the composite sugars.

  4. Prebiotics as gut microflora management tools.

    PubMed

    Gibson, Glenn R

    2008-07-01

    Functional foods is an often-used term applied to dietary ingredients that serve to improve consumer health. Over the last few decades, these foods have gained in popularity with sales continuing to increase rapidly. Recent scientific, and some lay, reports have shown the popularity of both probiotics and prebiotics. These serve to elicit changes in the gut microbiota composition that increase populations of purported beneficial gut bacterial genera, for example, lactobacilli or bifidobacteria. Probiotics use live microbial feed additions, whereas prebiotics target indigenous flora components. As gastrointestinal disorders are prevalent in terms of human health, both probiotics and prebiotics serve an important role in the prophylactic management of various acute and chronic gut derived conditions. Examples include protection from gastroenteritis and some inflammatory conditions. PMID:18542038

  5. Nitrogen fixation and nifH diversity in human gut microbiota.

    PubMed

    Igai, Katsura; Itakura, Manabu; Nishijima, Suguru; Tsurumaru, Hirohito; Suda, Wataru; Tsutaya, Takumi; Tomitsuka, Eriko; Tadokoro, Kiyoshi; Baba, Jun; Odani, Shingo; Natsuhara, Kazumi; Morita, Ayako; Yoneda, Minoru; Greenhill, Andrew R; Horwood, Paul F; Inoue, Jun-Ichi; Ohkuma, Moriya; Hongoh, Yuichi; Yamamoto, Taro; Siba, Peter M; Hattori, Masahira; Minamisawa, Kiwamu; Umezaki, Masahiro

    2016-01-01

    It has been hypothesized that nitrogen fixation occurs in the human gut. However, whether the gut microbiota truly has this potential remains unclear. We investigated the nitrogen-fixing activity and diversity of the nitrogenase reductase (NifH) genes in the faecal microbiota of humans, focusing on Papua New Guinean and Japanese individuals with low to high habitual nitrogen intake. A (15)N2 incorporation assay showed significant enrichment of (15)N in all faecal samples, irrespective of the host nitrogen intake, which was also supported by an acetylene reduction assay. The fixed nitrogen corresponded to 0.01% of the standard nitrogen requirement for humans, although our data implied that the contribution in the gut in vivo might be higher than this value. The nifH genes recovered in cloning and metagenomic analyses were classified in two clusters: one comprising sequences almost identical to Klebsiella sequences and the other related to sequences of Clostridiales members. These results are consistent with an analysis of databases of faecal metagenomes from other human populations. Collectively, the human gut microbiota has a potential for nitrogen fixation, which may be attributable to Klebsiella and Clostridiales strains, although no evidence was found that the nitrogen-fixing activity substantially contributes to the host nitrogen balance. PMID:27554344

  6. Contribution of diet to the composition of the human gut microbiota

    PubMed Central

    Graf, Daniela; Di Cagno, Raffaella; Fåk, Frida; Flint, Harry J.; Nyman, Margareta; Saarela, Maria; Watzl, Bernhard

    2015-01-01

    In the human gut, millions of bacteria contribute to the microbiota, whose composition is specific for every individual. Although we are just at the very beginning of understanding the microbiota concept, we already know that the composition of the microbiota has a profound impact on human health. A key factor in determining gut microbiota composition is diet. Preliminary evidence suggests that dietary patterns are associated with distinct combinations of bacteria in the intestine, also called enterotypes. Western diets result in significantly different microbiota compositions than traditional diets. It is currently unknown which food constituents specifically promote growth and functionality of beneficial bacteria in the intestine. The aim of this review is to summarize the recently published evidence from human in vivo studies on the gut microbiota-modulating effects of diet. It includes sections on dietary patterns (e.g. Western diet), whole foods, food constituents, as wells as food-associated microbes and their influence on the composition of human gut microbiota. The conclusions highlight the problems faced by scientists in this fast-developing field of research, and the need for high-quality, large-scale human dietary intervention studies. PMID:25656825

  7. Nitrogen fixation and nifH diversity in human gut microbiota

    PubMed Central

    Igai, Katsura; Itakura, Manabu; Nishijima, Suguru; Tsurumaru, Hirohito; Suda, Wataru; Tsutaya, Takumi; Tomitsuka, Eriko; Tadokoro, Kiyoshi; Baba, Jun; Odani, Shingo; Natsuhara, Kazumi; Morita, Ayako; Yoneda, Minoru; Greenhill, Andrew R.; Horwood, Paul F.; Inoue, Jun-ichi; Ohkuma, Moriya; Hongoh, Yuichi; Yamamoto, Taro; Siba, Peter M.; Hattori, Masahira; Minamisawa, Kiwamu; Umezaki, Masahiro

    2016-01-01

    It has been hypothesized that nitrogen fixation occurs in the human gut. However, whether the gut microbiota truly has this potential remains unclear. We investigated the nitrogen-fixing activity and diversity of the nitrogenase reductase (NifH) genes in the faecal microbiota of humans, focusing on Papua New Guinean and Japanese individuals with low to high habitual nitrogen intake. A 15N2 incorporation assay showed significant enrichment of 15N in all faecal samples, irrespective of the host nitrogen intake, which was also supported by an acetylene reduction assay. The fixed nitrogen corresponded to 0.01% of the standard nitrogen requirement for humans, although our data implied that the contribution in the gut in vivo might be higher than this value. The nifH genes recovered in cloning and metagenomic analyses were classified in two clusters: one comprising sequences almost identical to Klebsiella sequences and the other related to sequences of Clostridiales members. These results are consistent with an analysis of databases of faecal metagenomes from other human populations. Collectively, the human gut microbiota has a potential for nitrogen fixation, which may be attributable to Klebsiella and Clostridiales strains, although no evidence was found that the nitrogen-fixing activity substantially contributes to the host nitrogen balance. PMID:27554344

  8. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

    SciTech Connect

    Mahowald, Michael; Rey, Frederico E.; Seedorf, Henning; Turnbaugh, Peter J.; Fulton, Robert S.; Wollam, Aye; Shah, Neha; Wang, Chunyan; Magrini, Vincent; Wilson, Richard K.; Cantarel, Brandi L.; Coutinho, Pedro M; Henrissat, Bernard; Crock, Lara W.; Verberkmoes, Nathan C; Hettich, Robert {Bob} L; Erickson, Alison L; Gordon, Jeffrey

    2009-01-01

    The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial microbial and microbial host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.

  9. Gut Microbiota: Impact of probiotics, prebiotics, synbiotics, pharmabiotics and postbiotics on human health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multidisciplinary approaches enabled a better understanding of the connection between human gut microbes and health. This knowledge is rapidly changing how we think about probiotics and related –biotics (prebiotics, synbiotics, pharmabiotics and postbiotics). Functional –omics approaches are very im...

  10. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

  11. In vitro fermentation patterns of rice bran components by human gut microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice bran is a rich source of bioactive components that can promote gastrointestinal health. However, bran is removed during polishing. Among those, feruloylated arabinoxylan oligosaccharides (FAXO) and rice bran polyphenolics (RBPP) are hypothesized to have positive impacts on human gut microbiota ...

  12. The long-term stability of the human gut microbiota

    PubMed Central

    Faith, Jeremiah J.; Guruge, Janaki L.; Charbonneau, Mark; Subramanian, Sathish; Seedorf, Henning; Goodman, Andrew L.; Clemente, Jose C.; Knight, Rob; Heath, Andrew C.; Leibel, Rudolph L.; Rosenbaum, Michael; Gordon, Jeffrey I.

    2013-01-01

    A low-error 16S rRNA amplicon sequencing method (LEA-Seq) plus whole genome sequencing of >500 cultured isolates were used to characterize bacterial strain composition in the fecal microbiota of 37 USA adults sampled for up to five years. Microbiota stability follows a power law function which, when extrapolated, suggests that most strains in an individual are residents for decades. Shared strains were recovered from family members, but not from unrelated individuals. Sampling individuals for up to 32 weeks while consuming a monotonous liquid diet indicated that changes in weight are more predictive of changes in strain composition than sampling interval. This combination of stability and responsiveness to physiologic change confirms the potential of the gut microbiota as a diagnostic tool and therapeutic target. PMID:23828941

  13. 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

  14. Chronic arthritis induced in rats by cell wall fragments of Eubacterium species from the human intestinal flora.

    PubMed Central

    Severijnen, A J; van Kleef, R; Hazenberg, M P; van de Merwe, J P

    1990-01-01

    To investigate arthritis-inducing properties of Eubacterium species, which are major residents of the human intestinal flora, cell wall fragments (CWF) of several Eubacterium strains were prepared and tested in an animal model. After a single intraperitoneal injection in the rat, CWF of E. aerofaciens, E. contortum, and E. lentum induced a chronic polyarthritis. E. limosum and E. tortuosum CWF induced an acute self-limiting joint inflammation, whereas E. rectale CWF failed to do so. The rhamnose contents of the isolated CWF were not related to their arthritis-inducing properties. Paradoxically, the sensitivity of CWF to lysozyme digestion, which is regarded as a parameter for the clearance of CWF in tissues, appeared to be positively correlated with the ability of Eubacterium CWF to induce chronic joint inflammation. Our findings show the diversity in arthritis-inducing properties among different species of the anaerobic genus Eubacterium and underline the importance of the anaerobic intestinal flora in the induction of joint inflammation. Images PMID:2298490

  15. The Effect of Pomegranate (Punica granatum L.) Byproducts and Ellagitannins on the Growth of Human Gut Bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The consumption of pomegranate products leads to a significant accumulation of ellagitannins in the large intestines, where they interact with complex gut microflora. This study investigated the effect of pomegranate tannin constituents on the growth of various species of human gut bacteria. Our r...

  16. 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

  17. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota

    PubMed Central

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Safadi, Dima El; Certad, Gabriela; Delhaes, Laurence; Pereira, Bruno; Nourrisson, Céline; Poirier, Philippe; Wawrzyniak, Ivan; Delbac, Frédéric; Morelle, Christelle; Bastien, Patrick; Lachaud, Laurence; Bellanger, Anne-Pauline; Botterel, Françoise; Candolfi, Ermanno; Desoubeaux, Guillaume; Morio, Florent; Pomares, Christelle; Rabodonirina, Meja; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-01-01

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract. PMID:27147260

  18. Coordinate Regulation of Glycan Degradation and Polysaccharide Capsule Biosynthesis by a Prominent Human Gut Symbiont*

    PubMed Central

    Martens, Eric C.; Roth, Robyn; Heuser, John E.; Gordon, Jeffrey I.

    2009-01-01

    Bacteria in the distal human gut have evolved diverse abilities to metabolize complex glycans, including the capacity to degrade these compounds as nutrients and to assemble their component sugars into new polymers such as extracellular capsules. The human gut bacterium Bacteroides thetaiotaomicron is well endowed with the ability to metabolize both host- and diet-derived glycans. Its genome contains 88 different polysaccharide utilization loci (PULs) for complex glycan catabolism and eight different gene clusters for capsular polysaccharide biosynthesis. Here, we investigate one of the prominent mechanisms by which this gut symbiont regulates many PULs involved in host mucin O-glycan degradation; namely, transcriptional regulation via the concerted interactions of cell-envelope-localized TonB-dependent transporters, extra-cytoplasmic function σ factors and anti-σ factors, which participate together in a regulatory pathway termed trans-envelope signaling. Unexpectedly, we found that several different trans-envelope signaling switches involved in PUL-mediated O-glycan degradation also modulate capsular polysaccharide synthesis. A novel regulatory pathway, which is dependent on expression of O-glycan-targeting outer membrane proteins, governs this coordinated regulation of glycan catabolism and capsule synthesis. This latter finding provides a new link in the dynamic interplay between complex glycan metabolism, microbial physiology, and host responses that occurs during colonization of the gut. PMID:19403529

  19. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota.

    PubMed

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-01-01

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract. PMID:27147260

  20. 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.

  1. 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

  2. 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

  3. Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts

    PubMed Central

    Chiang, Herbert; Pudlo, Nicholas A.; Wu, Meng; McNulty, Nathan P.; Abbott, D. Wade; Henrissat, Bernard; Gilbert, Harry J.; Bolam, David N.; Gordon, Jeffrey I.

    2011-01-01

    Symbiotic bacteria inhabiting the human gut have evolved under intense pressure to utilize complex carbohydrates, primarily plant cell wall glycans in our diets. These polysaccharides are not digested by human enzymes, but are processed to absorbable short chain fatty acids by gut bacteria. The Bacteroidetes, one of two dominant bacterial phyla in the adult gut, possess broad glycan-degrading abilities. These species use a series of membrane protein complexes, termed Sus-like systems, for catabolism of many complex carbohydrates. However, the role of these systems in degrading the chemically diverse repertoire of plant cell wall glycans remains unknown. Here we show that two closely related human gut Bacteroides, B. thetaiotaomicron and B. ovatus, are capable of utilizing nearly all of the major plant and host glycans, including rhamnogalacturonan II, a highly complex polymer thought to be recalcitrant to microbial degradation. Transcriptional profiling and gene inactivation experiments revealed the identity and specificity of the polysaccharide utilization loci (PULs) that encode individual Sus-like systems that target various plant polysaccharides. Comparative genomic analysis indicated that B. ovatus possesses several unique PULs that enable degradation of hemicellulosic polysaccharides, a phenotype absent from B. thetaiotaomicron. In contrast, the B. thetaiotaomicron genome has been shaped by increased numbers of PULs involved in metabolism of host mucin O-glycans, a phenotype that is undetectable in B. ovatus. Binding studies of the purified sensor domains of PUL-associated hybrid two-component systems in conjunction with transcriptional analyses demonstrate that complex oligosaccharides provide the regulatory cues that induce PUL activation and that each PUL is highly specific for a defined cell wall polymer. These results provide a view of how these species have diverged into different carbohydrate niches by evolving genes that target unique suites of

  4. Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?

    PubMed Central

    Mosca, Alexis; Leclerc, Marion; Hugot, Jean P.

    2016-01-01

    Most of the Human diseases affecting westernized countries are associated with dysbiosis and loss of microbial diversity in the gut microbiota. The Western way of life, with a wide use of antibiotics and other environmental triggers, may reduce the number of bacterial predators leading to a decrease in microbial diversity of the Human gut. We argue that this phenomenon is similar to the process of ecosystem impoverishment in macro ecology where human activity decreases ecological niches, the size of predator populations, and finally the biodiversity. Such pauperization is fundamental since it reverses the evolution processes, drives life backward into diminished complexity, stability, and adaptability. A simple therapeutic approach could thus be to reintroduce bacterial predators and restore a bacterial diversity of the host microbiota. PMID:27065999

  5. 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.

  6. Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

    PubMed Central

    El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P

    1996-01-01

    BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2

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

    PubMed

    Deng, Ping; Swanson, Kelly S

    2015-01-01

    High-throughput DNA sequencing techniques allow for the identification and characterisation of microbes and their genes (microbiome). Using these new techniques, microbial populations in several niches of the human body, including the oral and nasal cavities, skin, urogenital tract and gastrointestinal tract, have been described recently. Very little data on the microbiome of companion animals exist, and most of the data have been derived from the analysis of the faeces of healthy laboratory animals. High-throughput assays provide opportunities to study the complex and dense populations of the gut microbiota, including bacteria, archaea, fungi, protozoa and viruses. Our laboratory and others have recently described the predominant microbial taxa and genes of healthy dogs and cats and how these respond to dietary interventions. In general, faecal microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) and functional capacity (e.g. major functional groups related to carbohydrate, protein, DNA and vitamin metabolism; virulence factors; and cell wall and capsule) of the canine and feline gut are similar to those of the human gut. Initial sequencing projects have provided a glimpse of the microbial super-organism that exists within the canine and feline gut, but leaves much to be explored and discovered. As DNA provides information only about potential functions, studies that focus on the microbial transcriptome, metabolite profiles, and how microbiome changes affect host physiology and health are clearly required. Future studies must determine how diet composition, antibiotics and other drug therapies, breed and disease affect or are affected by the gut microbiome and how this information may be used to improve diets, identify disease biomarkers and develop targeted disease therapies. PMID:25414978

  8. The chemical interactome space between the human host and the genetically defined gut metabotypes

    PubMed Central

    Jacobsen, Ulrik Plesner; Nielsen, Henrik Bjørn; Hildebrand, Falk; Raes, Jeroen; Sicheritz-Ponten, Thomas; Kouskoumvekaki, Irene; Panagiotou, Gianni

    2013-01-01

    The bacteria that colonize the gastrointestinal tracts of mammals represent a highly selected microbiome that has a profound influence on human physiology by shaping the host's metabolic and immune system activity. Despite the recent advances on the biological principles that underlie microbial symbiosis in the gut of mammals, mechanistic understanding of the contributions of the gut microbiome and how variations in the metabotypes are linked to the host health are obscure. Here, we mapped the entire metabolic potential of the gut microbiome based solely on metagenomics sequencing data derived from fecal samples of 124 Europeans (healthy, obese and with inflammatory bowel disease). Interestingly, three distinct clusters of individuals with high, medium and low metabolic potential were observed. By illustrating these results in the context of bacterial population, we concluded that the abundance of the Prevotella genera is a key factor indicating a low metabolic potential. These metagenome-based metabolic signatures were used to study the interaction networks between bacteria-specific metabolites and human proteins. We found that thirty-three such metabolites interact with disease-relevant protein complexes several of which are highly expressed in cells and tissues involved in the signaling and shaping of the adaptive immune system and associated with squamous cell carcinoma and bladder cancer. From this set of metabolites, eighteen are present in DrugBank providing evidence that we carry a natural pharmacy in our guts. Furthermore, we established connections between the systemic effects of non-antibiotic drugs and the gut microbiome of relevance to drug side effects and health-care solutions. PMID:23178670

  9. MALINA: a web service for visual analytics of human gut microbiota whole-genome metagenomic reads

    PubMed Central

    2012-01-01

    MALINA is a web service for bioinformatic analysis of whole-genome metagenomic data obtained from human gut microbiota sequencing. As input data, it accepts metagenomic reads of various sequencing technologies, including long reads (such as Sanger and 454 sequencing) and next-generation (including SOLiD and Illumina). It is the first metagenomic web service that is capable of processing SOLiD color-space reads, to authors’ knowledge. The web service allows phylogenetic and functional profiling of metagenomic samples using coverage depth resulting from the alignment of the reads to the catalogue of reference sequences which are built into the pipeline and contain prevalent microbial genomes and genes of human gut microbiota. The obtained metagenomic composition vectors are processed by the statistical analysis and visualization module containing methods for clustering, dimension reduction and group comparison. Additionally, the MALINA database includes vectors of bacterial and functional composition for human gut microbiota samples from a large number of existing studies allowing their comparative analysis together with user samples, namely datasets from Russian Metagenome project, MetaHIT and Human Microbiome Project (downloaded from http://hmpdacc.org). MALINA is made freely available on the web at http://malina.metagenome.ru. The website is implemented in JavaScript (using Ext JS), Microsoft .NET Framework, MS SQL, Python, with all major browsers supported. PMID:23216677

  10. Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions

    PubMed Central

    Upadhyaya, Bijaya; McCormack, Lacey; Fardin-Kia, Ali Reza; Juenemann, Robert; Nichenametla, Sailendra; Clapper, Jeffrey; Specker, Bonny; Dey, Moul

    2016-01-01

    Dietary modulation of the gut microbiota impacts human health. Here we investigated the hitherto unknown effects of resistant starch type 4 (RS4) enriched diet on gut microbiota composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions in twenty individuals with signs of metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin, and proinflammatory markers in the blood as well as waist circumference and % body fat were lower post intervention in the RS4 group compared with the control group. 16S-rRNA gene sequencing revealed a differential abundance of 71 bacterial operational taxonomic units, including the enrichment of three Bacteroides species and one each of Parabacteroides, Oscillospira, Blautia, Ruminococcus, Eubacterium, and Christensenella species in the RS4 group. Gas chromatography–mass spectrometry revealed higher faecal SCFAs, including butyrate, propionate, valerate, isovalerate, and hexanoate after RS4-intake. Bivariate analyses showed RS4-specific associations of the gut microbiota with the host metabolic functions and SCFA levels. Here we show that dietary RS4 induced changes in the gut microbiota are linked to its biological activity in individuals with signs of MetS. These findings have potential implications for dietary guidelines in metabolic health management. PMID:27356770

  11. Variation of glucoraphanin metabolism in vivo and ex vivo by human gut bacteria

    PubMed Central

    Li, Fei; Hullar, Meredith AJ; Beresford, Shirley AA; Lampe, Johanna W

    2011-01-01

    Glucosinolates, phytochemicals found in cruciferous vegetables, are metabolized to bioactive isothiocyanates (ITC) by certain bacteria in the human gut. Substantial individual variation in urinary ITC excretion has been observed in previous cruciferous-vegetable feeding studies. We hypothesized that individual differences in gut microbial community contribute to the observed variation in glucosinolate metabolism, i.e., gut microbiota composition between high- and low-ITC excreters differ. We recruited 23 healthy individuals and fed them a standardized meal containing 200 g cooked broccoli. 24-h urinary ITC excretion was measured after the meal. Study participants with the highest (n=5) and the lowest (n=5) ITC excretion provided fecal samples for ex vivo bacterial cultivation with 50 μM glucoraphanin, the major glucosinolate found in broccoli. When grown ex vivo, fecal bacteria from the selected high ITC excreters were able to degrade more glucoraphanin than those from the low excreters (P=0.05). However, bacterial fingerprints of fecal and ex vivo culture microbiota revealed no statistically significant differences between the high and low ITC excreters in terminal restriction fragment length polymorphism analysis of the bacterial 16S rRNA gene. In conclusion, glucosinolate degradation by fecal bacteria ex vivo may be associated with in vivo bacterial glucosinolate metabolism capacity but no direct link to specific bacterial species could be established, possibly due to the complexity and functional redundancy of the gut microbiota. PMID:21342607

  12. Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions.

    PubMed

    Upadhyaya, Bijaya; McCormack, Lacey; Fardin-Kia, Ali Reza; Juenemann, Robert; Nichenametla, Sailendra; Clapper, Jeffrey; Specker, Bonny; Dey, Moul

    2016-01-01

    Dietary modulation of the gut microbiota impacts human health. Here we investigated the hitherto unknown effects of resistant starch type 4 (RS4) enriched diet on gut microbiota composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions in twenty individuals with signs of metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin, and proinflammatory markers in the blood as well as waist circumference and % body fat were lower post intervention in the RS4 group compared with the control group. 16S-rRNA gene sequencing revealed a differential abundance of 71 bacterial operational taxonomic units, including the enrichment of three Bacteroides species and one each of Parabacteroides, Oscillospira, Blautia, Ruminococcus, Eubacterium, and Christensenella species in the RS4 group. Gas chromatography-mass spectrometry revealed higher faecal SCFAs, including butyrate, propionate, valerate, isovalerate, and hexanoate after RS4-intake. Bivariate analyses showed RS4-specific associations of the gut microbiota with the host metabolic functions and SCFA levels. Here we show that dietary RS4 induced changes in the gut microbiota are linked to its biological activity in individuals with signs of MetS. These findings have potential implications for dietary guidelines in metabolic health management. PMID:27356770

  13. Dissecting the in Vivo Metabolic Potential of Two Human Gut Acetogens*

    PubMed Central

    Rey, Federico E.; Faith, Jeremiah J.; Bain, James; Muehlbauer, Michael J.; Stevens, Robert D.; Newgard, Christopher B.; Gordon, Jeffrey I.

    2010-01-01

    Fermenting microbial communities generate hydrogen; its removal through the production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs (microbial RNA-Seq) and, together with mass spectrometry of metabolites, showed that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD+/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest. PMID:20444704

  14. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    PubMed

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  15. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

    PubMed Central

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  16. Romboutsia timonensis, a new species isolated from human gut.

    PubMed

    Ricaboni, D; Mailhe, M; Khelaifia, S; Raoult, D; Million, M

    2016-07-01

    The exploration of the human microbiome was recently revolutionized by microbial culturomics and taxonogenomics. Thanks to this approach, we report here the main characteristics of Romboutsia timonensis strain Marseille-P326, a new bacterium isolated from the right human colon by colonoscopy in a 63-year-old French man with severe anaemia with melaena. PMID:27200178

  17. Effects of resistant starch type III polymorphs on human colon microbiota and short chain fatty acids in human gut models.

    PubMed

    Lesmes, Uri; Beards, Emma J; Gibson, Glenn R; Tuohy, Kieran M; Shimoni, Eyal

    2008-07-01

    This study probed the possible effects of type III resistant starch (RS) crystalline polymorphism on RS fermentability by human gut microbiota and the short chain fatty acids production in vitro. Human fecal pH-controlled batch cultures showed RS induces an ecological shift in the colonic microbiota with polymorph B inducing Bifidobacterium spp. and polymorph A inducing Atopobium spp. Interestingly, polymorph B also induced higher butyrate production to levels of 0.79 mM. In addition, human gut simulation demonstrated that polymorph B promotes the growth of bifidobacteria in the proximal part of the colon and double their relative proportion in the microbiota in the distal colon. These findings suggest that RS polymorph B may promote large bowel health. While the findings are limited by study constraints, they do raise the possibility of using different thermal processing to delineate differences in the prebiotic capabilities of RS, especially its butryrogenicity in the human colon. PMID:18543927

  18. Direct Analysis of Genes Encoding 16S rRNA from Complex Communities Reveals Many Novel Molecular Species within the Human Gut

    PubMed Central

    Suau, Antonia; Bonnet, Régis; Sutren, Malène; Godon, Jean-Jacques; Gibson, Glenn R.; Collins, Matthew D.; Doré, Joel

    1999-01-01

    The human intestinal tract harbors a complex microbial ecosystem which plays a key role in nutrition and health. Although this microbiota has been studied in great detail by culture techniques, microscopic counts on human feces suggest that 60 to 80% of the observable bacteria cannot be cultivated. Using comparative analysis of cloned 16S rRNA gene (rDNA) sequences, we have investigated the bacterial diversity (both cultivated and noncultivated bacteria) within an adult-male fecal sample. The 284 clones obtained from 10-cycle PCR were classified into 82 molecular species (at least 98% similarity). Three phylogenetic groups contained 95% of the clones: the Bacteroides group, the Clostridium coccoides group, and the Clostridium leptum subgroup. The remaining clones were distributed among a variety of phylogenetic clusters. Only 24% of the molecular species recovered corresponded to described organisms (those whose sequences were available in public databases), and all of these were established members of the dominant human fecal flora (e.g., Bacteroides thetaiotaomicron, Fusobacterium prausnitzii, and Eubacterium rectale). However, the majority of generated rDNA sequences (76%) did not correspond to known organisms and clearly derived from hitherto unknown species within this human gut microflora. PMID:10543789

  19. The effects of gut microbiota on CNS function in humans

    PubMed Central

    Tillisch, Kirsten

    2014-01-01

    The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. Preclinical models suggest a role for the microbiota in broad aspects of human health, including mood, cognition, and chronic pain. Early human studies suggest that altering the microbiota with beneficial bacteria, or probiotics, can lead to changes in brain function, as well as subjective reports of mood. As the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat disease. PMID:24838095

  20. The effects of gut microbiota on CNS function in humans.

    PubMed

    Tillisch, Kirsten

    2014-01-01

    The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. Preclinical models suggest a role for the microbiota in broad aspects of human health, including mood, cognition, and chronic pain. Early human studies suggest that altering the microbiota with beneficial bacteria, or probiotics, can lead to changes in brain function, as well as subjective reports of mood. As the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat disease. PMID:24838095

  1. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

    PubMed

    Saad, M J A; Santos, A; Prada, P O

    2016-07-01

    Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. PMID:27252163

  2. 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

  3. Archaea and the human gut: new beginning of an old story.

    PubMed

    Gaci, Nadia; Borrel, Guillaume; Tottey, William; O'Toole, Paul William; Brugère, Jean-François

    2014-11-21

    Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales, Methanobrevibacter smithii and Methanosphaera stadtmanae. During the last decade, diversity of archaea encountered in the human gastrointestinal tract (GIT) has been extended by sequence identification and culturing of new strains. Here we provide an updated census of the archaeal diversity associated with the human GIT and their possible role in the gut physiology and health. We particularly focus on the still poorly characterized 7th order of methanogens, the Methanomassiliicoccales, associated to aged population. While also largely distributed in non-GIT environments, our actual knowledge on this novel order of methanogens has been mainly revealed through GIT inhabitants. They enlarge the number of final electron acceptors of the gut metabolites to mono- di- and trimethylamine. Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. This therefore supports interest on these methanogenic species and its use as archaebiotics, a term coined from the notion of archaea-derived probiotics. PMID:25473158

  4. Genome signature-based dissection of human gut metagenomes to extract subliminal viral sequences

    PubMed Central

    Ogilvie, Lesley A.; Bowler, Lucas D.; Caplin, Jonathan; Dedi, Cinzia; Diston, David; Cheek, Elizabeth; Taylor, Huw; Ebdon, James E.; Jones, Brian V.

    2013-01-01

    Bacterial viruses (bacteriophages) have a key role in shaping the development and functional outputs of host microbiomes. Although metagenomic approaches have greatly expanded our understanding of the prokaryotic virosphere, additional tools are required for the phage-oriented dissection of metagenomic data sets, and host-range affiliation of recovered sequences. Here we demonstrate the application of a genome signature-based approach to interrogate conventional whole-community metagenomes and access subliminal, phylogenetically targeted, phage sequences present within. We describe a portion of the biological dark matter extant in the human gut virome, and bring to light a population of potentially gut-specific Bacteroidales-like phage, poorly represented in existing virus like particle-derived viral metagenomes. These predominantly temperate phage were shown to encode functions of direct relevance to human health in the form of antibiotic resistance genes, and provided evidence for the existence of putative ‘viral-enterotypes’ among this fraction of the human gut virome. PMID:24036533

  5. Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale

    PubMed Central

    Cockburn, Darrell W.; Orlovsky, Nicole I.; Foley, Matthew H.; Kwiatkowski, Kurt J.; Bahr, Constance M.; Maynard, Mallory; Demeler, Borries; Koropatkin, Nicole M.

    2015-01-01

    Summary Eubacterium rectale is a prominent human gut symbiont yet little is known about the molecular strategies this bacterium has developed to acquire nutrients within the competitive gut ecosystem. Starch is one of the most abundant glycans in the human diet, and E. rectale increases in vivo when the host consumes a diet rich in resistant starch, although it is not a primary degrader of this glycan. Here we present the results of a quantitative proteomics study in which we identify two glycoside hydrolase 13 family enzymes, and three ABC transporter solute-binding proteins that are abundant during growth on starch and, we hypothesize, work together at the cell surface to degrade starch and capture the released maltooligosaccharides. EUR_21100 is a multidomain cell wall anchored amylase that preferentially targets starch polysaccharides, liberating maltotetraose, while the membrane associated maltogenic amylase EUR_01860 breaks down maltooligosaccharides longer than maltotriose. The three solute-binding proteins display a range of glycan-binding specificities that ensure the capture of glucose through maltoheptaose and some α1,6-branched glycans. Taken together, we describe a pathway for starch utilization by E. rectale DSM 17629 that may be conserved among other starch-degrading Clostridium cluster XIVa organisms in the human gut. PMID:25388295

  6. Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization*

    PubMed Central

    Kreisman, Lori S. C.; Cobb, Brian A.

    2011-01-01

    The carbohydrate antigen (glycoantigen) PSA from an intestinal commensal bacteria is able to down-regulate inflammatory bowel disease in model mice, suggesting that stimulation with PSA results in regulatory T cell (Treg) generation. However, mechanisms of how peripheral human T cells respond and home in response to commensal antigens are still not understood. Here, we demonstrate that a single exposure to PSA induces differentiation of human peripheral CD4+ T cells into type-Tr1 Tregs. This is in contrast to mouse models where PSA induced the production of Foxp3+ iTregs. The human PSA-induced Tr1 cells are profoundly anergic and exhibit nonspecific bystander suppression mediated by IL-10 secretion. Most surprisingly, glycoantigen exposure provoked expression of gut homing receptors on their surface. These findings reveal a mechanism for immune homeostasis in the gut whereby exposure to commensal glycoantigens provides the requisite information to responding T cells for proper tissue localization (gut) and function (anti-inflammatory/regulatory). PMID:21228275

  7. Two new xylanases with different substrate specificities from the human gut bacterium Bacteroides intestinalis DSM 17393.

    PubMed

    Hong, Pei-Ying; Iakiviak, Michael; Dodd, Dylan; Zhang, Meiling; Mackie, Roderick I; Cann, Isaac

    2014-04-01

    Xylan is an abundant plant cell wall polysaccharide and is a dominant component of dietary fiber. Bacteria in the distal human gastrointestinal tract produce xylanase enzymes to initiate the degradation of this complex heteropolymer. These xylanases typically derive from glycoside hydrolase (GH) families 10 and 11; however, analysis of the genome sequence of the xylan-degrading human gut bacterium Bacteroides intestinalis DSM 17393 revealed the presence of two putative GH8 xylanases. In the current study, we demonstrate that the two genes encode enzymes that differ in activity. The xyn8A gene encodes an endoxylanase (Xyn8A), and rex8A encodes a reducing-end xylose-releasing exo-oligoxylanase (Rex8A). Xyn8A hydrolyzed both xylopentaose (X5) and xylohexaose (X6) to a mixture of xylobiose (X2) and xylotriose (X3), while Rex8A hydrolyzed X3 through X6 to a mixture of xylose (X1) and X2. Moreover, rex8A is located downstream of a GH3 gene (xyl3A) that was demonstrated to exhibit β-xylosidase activity and would be able to further hydrolyze X2 to X1. Mutational analyses of putative active site residues of both Xyn8A and Rex8A confirm their importance in catalysis by these enzymes. Recent genome sequences of gut bacteria reveal an increase in GH8 Rex enzymes, especially among the Bacteroidetes, indicating that these genes contribute to xylan utilization in the human gut. PMID:24463968

  8. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    SciTech Connect

    Xiong, Weili; Richard J. Giannone; Morowitz, Michael J.; Banfield, Jillian F.; Robert L. Hettich

    2014-10-28

    The early-life microbiota establishment in the human infant gut is highly variable and plays a crucial role in host nutrients and immunity maturation. While high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the construction of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on Double Filtering (DF) to enhance microbial protein characterization in complex fecal samples from healthy premature infants. We improved the overall depth of infant gut proteome measurement, with an increase in the number of identified low abundance proteins, and observed greater than twofold improvement in metrics for microbial protein identifications and quantifications with a relatively high rank correlation to control. We further showed the substantial enhancement of this approach for extensively interpreting microbial functional categories between infants by affording more detailed and confident identified categories. This approach provided an avenue for in-depth measurement in the microbial component of infant fecal samples and thus comprehensive characterization of infant gut microbiome functionality.

  9. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    DOE PAGESBeta

    Xiong, Weili; Richard J. Giannone; Morowitz, Michael J.; Banfield, Jillian F.; Robert L. Hettich

    2014-10-28

    The early-life microbiota establishment in the human infant gut is highly variable and plays a crucial role in host nutrients and immunity maturation. While high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the construction of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on Double Filtering (DF) to enhance microbial protein characterization in complex fecal samples from healthy premature infants. We improved the overall depth of infant gut proteome measurement, withmore » an increase in the number of identified low abundance proteins, and observed greater than twofold improvement in metrics for microbial protein identifications and quantifications with a relatively high rank correlation to control. We further showed the substantial enhancement of this approach for extensively interpreting microbial functional categories between infants by affording more detailed and confident identified categories. This approach provided an avenue for in-depth measurement in the microbial component of infant fecal samples and thus comprehensive characterization of infant gut microbiome functionality.« less

  10. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

    PubMed Central

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A.; Joachimiak, Andrzej

    2015-01-01

    Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR–DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides. PMID:26438537

  11. Archaea and the human gut: New beginning of an old story

    PubMed Central

    Gaci, Nadia; Borrel, Guillaume; Tottey, William; O’Toole, Paul William; Brugère, Jean-François

    2014-01-01

    Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales, Methanobrevibacter smithii and Methanosphaera stadtmanae. During the last decade, diversity of archaea encountered in the human gastrointestinal tract (GIT) has been extended by sequence identification and culturing of new strains. Here we provide an updated census of the archaeal diversity associated with the human GIT and their possible role in the gut physiology and health. We particularly focus on the still poorly characterized 7th order of methanogens, the Methanomassiliicoccales, associated to aged population. While also largely distributed in non-GIT environments, our actual knowledge on this novel order of methanogens has been mainly revealed through GIT inhabitants. They enlarge the number of final electron acceptors of the gut metabolites to mono- di- and trimethylamine. Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. This therefore supports interest on these methanogenic species and its use as archaebiotics, a term coined from the notion of archaea-derived probiotics. PMID:25473158

  12. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection

    PubMed Central

    Hsiao, Ansel; Shamsir Ahmed, A.M.; Subramanian, Sathish; Griffin, Nicholas W.; Drewry, Lisa L.; Petri, William A.; Haque, Rashidul; Ahmed, Tahmeed; Gordon, Jeffrey I.

    2015-01-01

    Given the global burden of diarrheal diseases1, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. We have conducted a detailed time-series metagenomic study of fecal microbiota collected during the acute diarrheal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease2. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children3. To define underlying mechanisms, we introduced into gnotobiotic mice an artificial community that was composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children3. One of the species, Ruminococcus obeum, exhibited consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, established that R. obeum restricts V. cholerae colonization, that R. obeum luxS [autoinducer-2 (AI-2) synthase] expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants disclosed that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other

  13. Innate Immune Responses of Human Neonatal Cells to Bacteria from the Normal Gastrointestinal Flora

    PubMed Central

    Karlsson, Helen; Hessle, Christina; Rudin, Anna

    2002-01-01

    The hygiene hypothesis postulates that the prevalence of allergy has increased due to decreased microbial stimulation early in life, leading to delayed maturation of the immune system. The aim of this study was to examine the cytokine pattern produced from cord blood mononuclear cells relative to adult cells after stimulation with bacterial strains from the normal flora. Mononuclear cells from cord and adult blood samples were stimulated with the following bacteria: Bifidobacterium adolescentis, Enterococcus faecalis, Lactobacillus plantarum, Streptococcus mitis, Corynebacterium minutissimum, Clostridium perfringens, Bacteroides vulgatus, Escherichia coli, Pseudomonas aeruginosa, Veillonella parvula, and Neisseria sicca. The levels of interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-α), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay. The TNF-α production was also analyzed after blocking CD14, Toll-like receptor 2 (TLR-2), and TLR-4 prior to stimulation with bacteria. The levels of IL-12 and TNF-α were similar in cord and adult cells. Gram-positive bacteria induced considerably higher levels of IL-12 and TNF-α than gram-negative bacteria in both cord and adult cells. The levels of IL-6 were significantly higher in newborns than in adults, whereas the levels of IL-10 were similar in newborns and adults. Gram-negative and gram-positive bacteria induced similar levels of IL-6 and IL-10 in cord cells. L. plantarum bound or signaled through CD14, TLR-2, and TLR-4, whereas E. coli acted mainly through CD14 and TLR-4. These results indicate that the innate immune response in newborns to commensal bacteria is strong and also suggest that different bacterial strains may have differential effects on the maturation of the immune system of infants. PMID:12438343

  14. Innate immune responses of human neonatal cells to bacteria from the normal gastrointestinal flora.

    PubMed

    Karlsson, Helen; Hessle, Christina; Rudin, Anna

    2002-12-01

    The hygiene hypothesis postulates that the prevalence of allergy has increased due to decreased microbial stimulation early in life, leading to delayed maturation of the immune system. The aim of this study was to examine the cytokine pattern produced from cord blood mononuclear cells relative to adult cells after stimulation with bacterial strains from the normal flora. Mononuclear cells from cord and adult blood samples were stimulated with the following bacteria: Bifidobacterium adolescentis, Enterococcus faecalis, Lactobacillus plantarum, Streptococcus mitis, Corynebacterium minutissimum, Clostridium perfringens, Bacteroides vulgatus, Escherichia coli, Pseudomonas aeruginosa, Veillonella parvula, and Neisseria sicca. The levels of interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay. The TNF-alpha production was also analyzed after blocking CD14, Toll-like receptor 2 (TLR-2), and TLR-4 prior to stimulation with bacteria. The levels of IL-12 and TNF-alpha were similar in cord and adult cells. Gram-positive bacteria induced considerably higher levels of IL-12 and TNF-alpha than gram-negative bacteria in both cord and adult cells. The levels of IL-6 were significantly higher in newborns than in adults, whereas the levels of IL-10 were similar in newborns and adults. Gram-negative and gram-positive bacteria induced similar levels of IL-6 and IL-10 in cord cells. L. plantarum bound or signaled through CD14, TLR-2, and TLR-4, whereas E. coli acted mainly through CD14 and TLR-4. These results indicate that the innate immune response in newborns to commensal bacteria is strong and also suggest that different bacterial strains may have differential effects on the maturation of the immune system of infants. PMID:12438343

  15. Microbes in the gut: a digestable account of host-symbiont interactions.

    PubMed

    Pai, Rekha; Kang, Gagandeep

    2008-11-01

    The human bowel is host to a diverse group of bacteria with over 500 different bacterial species contributing to this diversity. Until recently these bacteria were regarded as residents without any specific functions. The last two decades have seen a radical change in our understanding of the interactions between the gut flora and their eukaryotic hosts and there is a growing appreciation of the spectrum of functions performed by these symbionts. Intestinal bacteria are recognized for their role in nutrient absorption, mucosal barrier function, angiogenesis, morphogenesis and postnatal maturation of intestinal cell lineages, intestinal motility and more importantly maturation of gut associated lymphoid tissue (GALT). Although gut flora are implicated in certain pathological disorders, their remarkable contributions to health and homeostasis of the host need to be recognized and understood. PMID:19179677

  16. Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer.

    PubMed

    Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tsubo, Takahisa; Suga, Shogo; Inai, Makoto; Aoki, Yuichi; Takahashi, Seiji; Tsutsumi, Eri; Suwa, Yoshihide; Morita, Hidetoshi; Kinoshita, Kenji; Totsuka, Yukari; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Toru

    2016-01-01

    Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic. However, the effects of chronic ethanol consumption on the human gut microbiome are poorly understood, and the role of gut microbes in the proposed AcH-mediated pathogenesis of ER-CRC remains to be elaborated. Here we analyse and compare the gut microbiota structures of non-alcoholics and alcoholics. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes (e.g., Bacteroides and Ruminococcus) and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The AcH productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. The faecal phenotype of the alcoholics could be rationalised based on their gut microbiota structures and the ability of gut bacteria to accumulate AcH from ethanol. PMID:27295340

  17. Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer

    PubMed Central

    Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tsubo, Takahisa; Suga, Shogo; Inai, Makoto; Aoki, Yuichi; Takahashi, Seiji; Tsutsumi, Eri; Suwa, Yoshihide; Morita, Hidetoshi; Kinoshita, Kenji; Totsuka, Yukari; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Toru

    2016-01-01

    Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic. However, the effects of chronic ethanol consumption on the human gut microbiome are poorly understood, and the role of gut microbes in the proposed AcH-mediated pathogenesis of ER-CRC remains to be elaborated. Here we analyse and compare the gut microbiota structures of non-alcoholics and alcoholics. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes (e.g., Bacteroides and Ruminococcus) and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The AcH productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. The faecal phenotype of the alcoholics could be rationalised based on their gut microbiota structures and the ability of gut bacteria to accumulate AcH from ethanol. PMID:27295340

  18. Broad-spectrum antibacterial activity of carbon nanotubes to human gut bacteria.

    PubMed

    Chen, Hanqing; Wang, Bing; Gao, Di; Guan, Ming; Zheng, Lingna; Ouyang, Hong; Chai, Zhifang; Zhao, Yuliang; Feng, Weiyue

    2013-08-26

    Carbon nanotubes (CNTs) hold promise in manufacturing, environmental, and biomedical applications, as well as food and agricultural industries. Previous observations have shown that CNTs have antimicrobial activity; however, the impact of CNTs to human gut microbes has not been investigated. Here, the antibacterial activity of CNTs against the microbes commonly encountered in the human digestion system--L. acidophilus, B. adolescentis, E. coli, E. faecalis, and S. aureus--are evaluated. The bacteria studied include pathogenic and non-pathogenic, gram-positive and negative, and both sphere and rod strains. In this study, CNTs, including single-walled CNTs (SWCNTs, 1-3 μm), short and long multi-walled CNTs (s-MWCNTs: 0.5-2 μm; l-MWCNTs: >50 μm), and functionalized multi-walled CNTs (hydroxyl- and carboxyl-modification, 0.5-2 μm), all have broad-spectrum antibacterial effects. Notably, CNTs may selectively lyse the walls and membranes of human gut microbes, depending on not only the length and surface functional groups of CNTs, but also the shapes of the bacteria. The mechanism of antibacterial activity is associated with their diameter-dependent piercing and length-dependent wrapping on the lysis of microbial walls and membranes, inducing release of intracellular components DNA and RNA and allowing a loss of bacterial membrane potential, demonstrating complete destruction of bacteria. Thin and rigid SWCNT show more effective wall/membrane piercing on spherical bacteria than MWCNTs. Long MWCNT may wrap around gut bacteria, increasing the area making contact with the bacterial wall. This work suggests that CNTs may be broad-spectrum and efficient antibacterial agents in the gut, and selective application of CNTs could reduce the potential hazard to probiotic bacteria. PMID:23463684

  19. Higher-Level Production of Volatile Fatty Acids In Vitro by Chicken Gut Microbiotas than by Human Gut Microbiotas as Determined by Functional Analyses

    PubMed Central

    Lei, Fang; Yin, Yeshi; Wang, Yuezhu; Deng, Bo; Yu, Hongwei David; Li, Lanjuan; Xiang, Charlie; Wang, Shengyue

    2012-01-01

    The aim of this study was to determine the relationship between the composition and function of gut microbiota. Here, we compared the bacterial compositions and fermentation metabolites of human and chicken gut microbiotas. Results generated by quantitative PCR (qPCR) and 454 pyrosequencing of the 16S rRNA gene V3 region showed the compositions of human and chicken microbiotas to be markedly different, with chicken cecal microbiotas displaying more diversity than human fecal microbiotas. The nutrient requirements of each microbiota growing under batch and chemostat conditions were analyzed. The results showed that chicken cecal microbiotas required simple sugars and peptides to maintain balanced growth in vitro but that human fecal microbiotas preferred polysaccharides and proteins. Chicken microbiotas also produced higher concentrations of volatile fatty acids than did human microbiotas. Our data suggest that the availability of different fermentable substrates in the chicken cecum, which exist due to the unique anatomical structure of the cecum, may provide an environment favorable to the nourishment of microbiotas suited to the production of the higher-energy metabolites required by the bird. Therefore, gut structure, nutrition, immunity, and life-style all contribute to the selection of an exclusive bacterial community that produces types of metabolites beneficial to the host. PMID:22685152

  20. Role of the gut microbiota in defining human health

    PubMed Central

    Fujimura, Kei E; Slusher, Nicole A; Cabana, Michael D; Lynch, Susan V

    2010-01-01

    The human superorganism is a conglomerate of mammalian and microbial cells, with the latter estimated to outnumber the former by ten to one and the microbial genetic repertoire (microbiome) to be approximately 100-times greater than that of the human host. Given the ability of the immune response to rapidly counter infectious agents, it is striking that such a large density of microbes can exist in a state of synergy within the human host. This is particularly true of the distal gastrointestinal (GI) tract, which houses up to 1000 distinct bacterial species and an estimated excess of 1 × 1014 microorganisms. An ever-increasing body of evidence implicates the GI microbiota in defining states of health and disease. Here, we review the literature in adult and pediatric GI microbiome studies, the emerging links between microbial community structure, function, infection and disease, and the approaches to manipulate this crucial ecosystem to improve host health. PMID:20377338

  1. Ecological Interactions of Bacteria in the Human Gut

    NASA Astrophysics Data System (ADS)

    Falony, Gwen; de Vuyst, Luc

    The colon or large intestine is one of the most important organs of the human body (Macfarlane and Cummings, 1991). Moreover, its inhabitants, the colon microbiota, are the key elements of the human digestive ecosystem. The vast complexity of the human large-intestinal microbiota has inspired researchers to consider it as an organ itself, located inside the colon and acquired postnatally (Bäckhed et al., 2005; Zocco et al., 2007). From a physiologist's point of view, this image of the colon microbiota is relevant: like an organ, it is composed of different cell lineages that communicate with both one another and the host; it consumes, stores, and redistributes energy; it mediates physiologically important chemical transformations; and it is able to maintain and repair itself through self-replication (Bäckhed et al., 2005). As a microbial organ, the human colon community does not only broaden the digestive abilities of the host (Gill et al., 2006), but also influences body processes far beyond digestion (Roberfroid, 2005b; Turnbaugh et al., 2007).

  2. Comparative (Meta)genomic Analysis and Ecological Profiling of Human Gut-Specific Bacteriophage φB124-14

    PubMed Central

    Ogilvie, Lesley A.; Caplin, Jonathan; Dedi, Cinzia; Diston, David; Cheek, Elizabeth; Bowler, Lucas; Taylor, Huw; Ebdon, James; Jones, Brian V.

    2012-01-01

    Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape

  3. Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

    PubMed Central

    Crost, Emmanuelle H.; Tailford, Louise E.; Le Gall, Gwenaelle; Fons, Michel; Henrissat, Bernard; Juge, Nathalie

    2013-01-01

    Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease. PMID:24204617

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

    PubMed Central

    Ridlon, Jason M.; Bajaj, Jasmohan S.

    2015-01-01

    The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an “endocrine organ” with potential to alter host physiology, perhaps to their own favor. We propose the term “sterolbiome” to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed. PMID:26579434

  5. 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

  6. Changes of the human gut microbiome induced by a fermented milk product

    PubMed Central

    Veiga, Patrick; Pons, Nicolas; Agrawal, Anurag; Oozeer, Raish; Guyonnet, Denis; Brazeilles, Rémi; Faurie, Jean-Michel; van Hylckama Vlieg, Johan E. T.; Houghton, Lesley A.; Whorwell, Peter J.; Ehrlich, S. Dusko; Kennedy, Sean P.

    2014-01-01

    The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects. PMID:25209713

  7. Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

    PubMed Central

    Vincent, Caroline; Manges, Amee R.

    2015-01-01

    Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material. PMID:27025623

  8. Diversified mcr-1-Harbouring Plasmid Reservoirs Confer Resistance to Colistin in Human Gut Microbiota

    PubMed Central

    Ye, Huiyan; Li, Yihui; Li, Zhencui; Gao, Rongsui; Zhang, Han; Wen, Ronghui; Gao, George F.; Hu, Qinghua

    2016-01-01

    ABSTRACT Colistin is an ultimate line of refuge against multidrug-resistant Gram-negative pathogens. Very recently, the emergence of plasmid-mediated mcr-1 colistin resistance has become a great challenge to global public health, raising the possibility that dissemination of the mcr-1 gene is underestimated and diversified. Here, we report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients. Structural and functional analyses determined that the colistin resistance is conferred purely by the single mcr-1 gene. Genetic and sequence mapping revealed that mcr-1-harbouring plasmid reservoirs are present in diversity. Together, the data represent the first evidence of diversity in mcr-1-harbouring plasmid reservoirs of human gut microbiota. PMID:27048797

  9. Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora.

    PubMed

    Gloster, Tracey M; Turkenburg, Johan P; Potts, Jennifer R; Henrissat, Bernard; Davies, Gideon J

    2008-10-20

    Enzymatic cleavage of the glycosidic bond yields products in which the anomeric configuration is either retained or inverted. Each mechanism reflects the dispositions of the enzyme functional groups; a facet of which is essentially conserved in 113 glycoside hydrolase (GH) families. We show that family GH97 has diverged significantly, as it contains both inverting and retaining alpha-glycosidases. This reflects evolution of the active center; a glutamate acts as a general base in inverting members, exemplified by Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a, whereas an aspartate likely acts as a nucleophile in retaining members. The structure of BtGH97a and its complexes with inhibitors, coupled to kinetic analysis of active-site variants, reveals an unusual calcium ion dependence. 1H NMR analysis shows an inversion mechanism for BtGH97a, whereas another GH97 enzyme from B. thetaiotaomicron, BtGH97b, functions as a retaining alpha-galactosidase. PMID:18848471

  10. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes.

    PubMed

    Larsbrink, Johan; Rogers, Theresa E; Hemsworth, Glyn R; McKee, Lauren S; Tauzin, Alexandra S; Spadiut, Oliver; Klinter, Stefan; Pudlo, Nicholas A; Urs, Karthik; Koropatkin, Nicole M; Creagh, A Louise; Haynes, Charles A; Kelly, Amelia G; Cederholm, Stefan Nilsson; Davies, Gideon J; Martens, Eric C; Brumer, Harry

    2014-02-27

    A well-balanced human diet includes a significant intake of non-starch polysaccharides, collectively termed 'dietary fibre', from the cell walls of diverse fruits and vegetables. Owing to the paucity of alimentary enzymes encoded by the human genome, our ability to derive energy from dietary fibre depends on the saccharification and fermentation of complex carbohydrates by the massive microbial community residing in our distal gut. The xyloglucans (XyGs) are a ubiquitous family of highly branched plant cell wall polysaccharides whose mechanism(s) of degradation in the human gut and consequent importance in nutrition have been unclear. Here we demonstrate that a single, complex gene locus in Bacteroides ovatus confers XyG catabolism in this common colonic symbiont. Through targeted gene disruption, biochemical analysis of all predicted glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional structural determination of the vanguard endo-xyloglucanase, we reveal the molecular mechanisms through which XyGs are hydrolysed to component monosaccharides for further metabolism. We also observe that orthologous XyG utilization loci (XyGULs) serve as genetic markers of XyG catabolism in Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes. Our findings reveal that the metabolism of even highly abundant components of dietary fibre may be mediated by niche species, which has immediate fundamental and practical implications for gut symbiont population ecology in the context of human diet, nutrition and health. PMID:24463512

  11. Metaproteomics Reveals Functional Shifts in Microbial and Human Proteins During Infant Gut Colonization Case

    DOE PAGESBeta

    Young, Jacque C.; Pan, Chongle; Adams, Rachel M.; Brooks, Brandon; Banfield, Jillian F.; Morowitz, Michael J.; Robert L. Hettich

    2015-01-01

    The microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity and functions increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data indicating three distinct colonization phases. Overall microbial community functions were established relatively early in development andmore » remained stable. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Moreover, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. Our study provides the first snapshot of coordinated human and microbial protein expression in the infant gut during early development.« less

  12. Metaproteomics reveals functional shifts in microbial and human proteins during a preterm infant gut colonization case.

    PubMed

    Young, Jacque C; Pan, Chongle; Adams, Rachel M; Brooks, Brandon; Banfield, Jillian F; Morowitz, Michael J; Hettich, Robert L

    2015-10-01

    Microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. To this end, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data. More specifically, the function of the microbial community initially involved biomass growth, protein production, and lipid metabolism, and then switched to more complex metabolic functions, such as carbohydrate metabolism, once the community stabilized and matured. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Likewise, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. This study provides the first snapshot of coordinated human and microbial protein expression in a preterm infant's gut during early development. PMID:26077811

  13. In Vitro Method To Assess Soil Arsenic Metabolism by Human Gut Microbiota: Arsenic Speciation and Distribution.

    PubMed

    Yin, Naiyi; Zhang, Zhennan; Cai, Xiaolin; Du, Huili; Sun, Guoxin; Cui, Yanshan

    2015-09-01

    Arsenic (As) speciation and distribution are two important factors in assessing human health risk from As-contaminated soil. In this study, we used the combination of physiologically based extraction test (PBET) and Simulator of Human Intestinal Microbial Ecosystem (SHIME) to determine soil As metabolism by human gut microbiota. The results showed that the percentage of soil arsenate [As(V)] transformation reached 22.1-38.2%, while that of arsenite [As(III)] attained 66.5-92.0%; 30.1-56.4% of As(V) transformed was attached to the soil solid phase. In comparison to sequential extraction results, almost all amorphous Fe/Al-oxide-bound As was liberated in the colon phase. An X-ray absorption near-edge structure (XANES) showed that the As(III) percentage in the soil solid phase reached 16.6-26.9% and reached 73.4% (soil 1) in the colon phase. Additionally, plenty of As(III) and different extents of methylation were also observed in colon extraction solution. As bioaccessibility in the colon phase was 1.8-2.8 times that in the small intestinal phase. Our results indicated that human gut microbiota increased As bioaccessibility, and large amounts of As(III) were adsorbed onto the soil solid phase as a result of microbial reduction. Determining As speciation and distribution in extraction solution and soil solid phases will allow for an accurate assessment of the risk to human health upon soil As exposure. PMID:26248026

  14. Metaproteomics Reveals Functional Shifts in Microbial and Human Proteins During Infant Gut Colonization Case

    SciTech Connect

    Young, Jacque C.; Pan, Chongle; Adams, Rachel M.; Brooks, Brandon; Banfield, Jillian F.; Morowitz, Michael J.; Robert L. Hettich

    2015-01-01

    The microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity and functions increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data indicating three distinct colonization phases. Overall microbial community functions were established relatively early in development and remained stable. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Moreover, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. Our study provides the first snapshot of coordinated human and microbial protein expression in the infant gut during early development.

  15. Reversing Gut Damage in HIV Infection: Using Non-Human Primate Models to Instruct Clinical Research

    PubMed Central

    Ponte, Rosalie; Mehraj, Vikram; Ghali, Peter; Couëdel-Courteille, Anne; Cheynier, Rémi; Routy, Jean-Pierre

    2016-01-01

    Antiretroviral therapy (ART) has led to dramatic improvements in the lives of HIV-infected persons. However, residual immune activation, which persists despite ART, is associated with increased risk of non-AIDS morbidities. Accumulating evidence shows that disruption of the gut mucosal epithelium during SIV/HIV infections allows translocation of microbial products into the circulation, triggering immune activation. This disruption is due to immune, structural and microbial alterations. In this review, we highlighted the key findings of gut mucosa studies of SIV-infected macaques and HIV-infected humans that have revealed virus-induced changes of intestinal CD4, CD8 T cells, innate lymphoid cells, myeloid cells, and of the local cytokine/chemokine network in addition to epithelial injuries. We review the interplay between the host immune response and the intestinal microbiota, which also impacts disease progression. Collectively, these studies have instructed clinical research on early ART initiation, modifiers of microbiota composition, and recombinant cytokines for restoring gut barrier integrity. PMID:26981570

  16. The impact of diet and lifestyle on gut microbiota and human health.

    PubMed

    Conlon, Michael A; Bird, Anthony R

    2015-01-01

    There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented. PMID:25545101

  17. The Impact of Diet and Lifestyle on Gut Microbiota and Human Health

    PubMed Central

    Conlon, Michael A.; Bird, Anthony R.

    2014-01-01

    There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented. PMID:25545101

  18. Long-Term Green Tea Supplementation Does Not Change the Human Gut Microbiota

    PubMed Central

    Janssens, Pilou L. H. R.; Penders, John; Hursel, Rick; Budding, Andries E.; Savelkoul, Paul H. M.; Westerterp-Plantenga, Margriet S.

    2016-01-01

    Background Green tea catechins may play a role in body weight regulation through interactions with the gut microbiota. Aim We examined whether green tea supplementation for 12 weeks induces changes in composition of the human gut microbiota. Methods 58 Caucasian men and women were included in a randomized, placebo-controlled design. For 12 weeks, subjects consumed either green tea (>0.56 g/d epigallocatechin-gallate + 0.28 ∼ 0.45 g/d caffeine) or placebo capsules. Fecal samples were collected twice (baseline, vs. week 12) for analyses of total bacterial profiles by means of IS-profiling, a 16S-23S interspacer region-based profiling method. Results No significant changes between baseline and week 12 in subjects receiving green tea or placebo capsules, and no significant interactions between treatment (green tea or placebo) and time (baseline and week 12) were observed for body composition. Analysis of the fecal samples in subjects receiving green tea and placebo showed similar bacterial diversity and community structures, indicating there were no significant changes in bacterial diversity between baseline and week 12 in subjects receiving green tea capsules or in subjects receiving placebo capsules. No significant interactions were observed between treatment (green tea or placebo) and time (baseline and week 12) for the gut microbial diversity. Although, there were no significant differences between normal weight and overweight subjects in response to green tea, we did observe a reduced bacterial alpha diversity in overweight as compared to normal weight subjects (p = 0.002). Conclusion Green tea supplementation for 12 weeks did not have a significant effect on composition of the gut microbiota. Trial Registration ClinicalTrials.gov NCT01556321 PMID:27054321

  19. Pantoea intestinalis sp. nov., isolated from the human gut.

    PubMed

    Prakash, Om; Nimonkar, Yogesh; Vaishampayan, Ankita; Mishra, Mrinal; Kumbhare, Shreyas; Josef, Neetha; Shouche, Yogesh S

    2015-10-01

    A novel bacterial strain, 29Y89BT, was isolated from a faecal sample of a healthy human subject. Cells were Gram-stain-negative, motile, non-spore-forming and rod-shaped. Strain 29Y89BT formed cream-coloured colonies 2 mm in diameter on trypticase soy agar and showed optimum growth at 35 °C. Strain 29Y89BT showed highest 16S rRNA gene sequence similarity to Pantoea gaviniae A18/07T (98.4 %) followed by Pantoea calida 1400/07T (97.2 %). Multi-locus sequence analysis using atpD (ATP synthase β subunit), gyrB (DNA gyrase), infB (initiation translation factor 2) and rpoB (RNA polymerase β subunit) genes also supported the result of 16S rRNA gene sequence based phylogeny. Strain 29Y89BT showed 62 and 40.7 % DNA-DNA relatedness with P. calida DSM 22759T and P. gaviniae DSM 22758T. Strain 29Y89BT contained C17  : 0 cyclo, C19  : 0 cyclo ω8c, C16 : 0, C14 : 0 and C12 : 0 as predominant fatty acids. In addition, strain 29Y89BT showed physiological and phenotypic differences from its closest relatives P. gaviniae DSM 22758T and P. calida DSM 22759T. The polar lipid profile mainly comprised phospholipids. The DNA G+C content was 59.1 mol%. Thus, based on the findings of the current study, strain 29Y89BT showed clear delineations from its closest relatives P. gaviniae DSM 22758T and P. calida DSM 22759T, and is thus considered to represent a novel species of the genus Pantoea, for which the name Pantoea intestinalis sp. nov. is proposed. The type strain is 29Y89BT ( = DSM 28113T = MCC 2554T). PMID:26297006

  20. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    PubMed Central

    2015-01-01

    The establishment of early life microbiota in the human infant gut is highly variable and plays a crucial role in host nutrient availability/uptake and maturation of immunity. Although high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the acquisition of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on double filtering (DF) the raw samples, a method that fractionates microbial from human cells to enhance microbial protein identification and characterization in complex fecal samples from healthy premature infants. This method dramatically improved the overall depth of infant gut proteome measurement, with an increase in the number of identified low-abundance proteins and a greater than 2-fold improvement in microbial protein identification and quantification. This enhancement of proteome measurement depth enabled a more extensive microbiome comparison between infants by not only increasing the confidence of identified microbial functional categories but also revealing previously undetected categories. PMID:25350865

  1. 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

  2. In vitro fermentation of alginate and its derivatives by human gut microbiota.

    PubMed

    Li, Miaomiao; Li, Guangsheng; Shang, Qingsen; Chen, Xiuxia; Liu, Wei; Pi, Xiong'e; Zhu, Liying; Yin, Yeshi; Yu, Guangli; Wang, Xin

    2016-06-01

    Alginate (Alg) has a long history as a food ingredient in East Asia. However, the human gut microbes responsible for the degradation of alginate and its derivatives have not been fully understood yet. Here, we report that alginate and the low molecular polymer derivatives of mannuronic acid oligosaccharides (MO) and guluronic acid oligosaccharides (GO) can be completely degraded and utilized at various rates by fecal microbiota obtained from six Chinese individuals. However, the derivative of propylene glycol alginate sodium sulfate (PSS) was not hydrolyzed. The bacteria having a pronounced ability to degrade Alg, MO and GO were isolated from human fecal samples and were identified as Bacteroides ovatus, Bacteroides xylanisolvens, and Bacteroides thetaiotaomicron. Alg, MO and GO can increase the production level of short chain fatty acids (SCFA), but GO generates the highest level of SCFA. Our data suggest that alginate and its derivatives could be degraded by specific bacteria in the human gut, providing the basis for the impacts of alginate and its derivates as special food additives on human health. PMID:26891629

  3. The human gut virome: inter-individual variation and dynamic response to diet.

    PubMed

    Minot, Samuel; Sinha, Rohini; Chen, Jun; Li, Hongzhe; Keilbaugh, Sue A; Wu, Gary D; Lewis, James D; Bushman, Frederic D

    2011-10-01

    Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human "virome") in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from human subjects on a controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175 contigs, many identifiable as complete or partial bacteriophage genomes. Contigs were rich in viral functions required in lytic and lysogenic growth, as well as unexpected functions such as viral CRISPR arrays and genes for antibiotic resistance. The largest source of variance among virome samples was interpersonal variation. Parallel deep-sequencing analysis of bacterial populations showed covaration of the virome with the larger microbiome. The dietary intervention was associated with a change in the virome community to a new state, in which individuals on the same diet converged. Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet. PMID:21880779

  4. Dining in with Trillions of Fascinating Friends: Exploring Our Human Gut Microbiome in Health and Disease

    PubMed Central

    Gordon, J.I.

    2011-01-01

    Our genetic landscape is a summation of the genes embedded in our human genome and in the genomes of our microbial symbionts (the microbiome). Similarly, our metabolic features (metabotypes) are an amalgamation of human and microbial traits. Therefore, understanding of the range of human genetic and metabolic diversity means that we must characterize our microbiomes, which contain at least several hundred-fold more genes than our human genome, as well as the factors that influence the properties of our microbial communities (microbiota). The results should provide an additional perspective about contemporary human biology as we assess how our changing lifestyles, cultural norms, socioeconomic status, and biosphere are influencing our microbial ecology and health status. I will discuss the results of our group's ongoing metagenomic studies of the interrelationships between diet and the structure and dynamic operations of the human gut microbiome. We believe that understanding these interrelationships is important for advancing our appreciation of the nutritional value of food ingredients, for creating new nutritional guidelines for humans at various stages of their lifespan, and for developing new ways to deliberately manipulate the properties of the gut microbiota to prevent or treat various diseases. We have developed a translational medicine pipeline that involves metagenomic analyses of the gut microbial communities of adult mono- and dizygotic twins living in the USA who are lean, or concordant or discordant for obesity, and twins aged 0–3 years living in developing countries who develop normally, or who become malnourished and are treated with a ready-to-use therapeutic food (RUTF). Intact fecal communities from these individuals, or ‘personal’ culture collections that capture the majority of bacterial diversity in their microbiota, are then transplanted into germ-free mice, which are fed the diets of the human donors, or systematically manipulated

  5. 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

  6. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

    DOE PAGESBeta

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A.; Joachimiak, Andrzej

    2015-10-04

    We report that carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specificmore » DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR–DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Furthermore, our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.« less

  7. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

    SciTech Connect

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A.; Joachimiak, Andrzej

    2015-10-04

    We report that carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR–DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Furthermore, our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.

  8. Direct sequencing of human gut virome fractions obtained by flow cytometry.

    PubMed

    Džunková, Mária; D'Auria, Giuseppe; Moya, Andrés

    2015-01-01

    The sequence assembly of the human gut virome encounters several difficulties. A high proportion of human and bacterial matches is detected in purified viral samples. Viral DNA extraction results in a low DNA concentration, which does not reach the minimal limit required for sequencing library preparation. Therefore, the viromes are usually enriched by whole genome amplification (WGA), which is, however, prone to the development of chimeras and amplification bias. In addition, as there is a very wide diversity of gut viral species, very extensive sequencing efforts must be made for the assembling of whole viral genomes. We present an approach to improve human gut virome assembly by employing a more precise preparation of a viral sample before sequencing. Particles present in a virome previously filtered through 0.2 μm pores were further divided into groups in accordance with their size and DNA content by fluorescence activated cell sorting (FACS). One selected viral fraction was sequenced excluding the WGA step, so that unbiased sequences with high reliability were obtained. The DNA extracted from the 314 viral particles of the selected fraction was assembled into 34 contigs longer than 1,000 bp. This represents an increase to the number of assembled long contigs per sequenced Gb in comparison with other studies where non-fractioned viromes are sequenced. Seven of these contigs contained open reading frames (ORFs) with explicit matches to proteins related to bacteriophages. The remaining contigs also possessed uncharacterized ORFs with bacteriophage-related domains. When the particles that are present in the filtered viromes are sorted into smaller groups by FACS, large pieces of viral genomes can be recovered easily. This approach has several advantages over the conventional sequencing of non-fractioned viromes: non-viral contamination is reduced and the sequencing efforts required for viral assembly are minimized. PMID:26441889

  9. Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

    PubMed Central

    Reyes, Alejandro; Wu, Meng; McNulty, Nathan P.; Rohwer, Forest L.; Gordon, Jeffrey I.

    2013-01-01

    Bacterial viruses (phages) are the most abundant biological group on Earth and are more genetically diverse than their bacterial prey/hosts. To characterize their role as agents shaping gut microbial community structure, adult germ-free mice were colonized with a consortium of 15 sequenced human bacterial symbionts, 13 of which harbored one or more predicted prophages. One member, Bacteroides cellulosilyticus WH2, was represented by a library of isogenic transposon mutants that covered 90% of its genes. Once assembled, the community was subjected to a staged phage attack with a pool of live or heat-killed virus-like particles (VLPs) purified from the fecal microbiota of five healthy humans. Shotgun sequencing of DNA from the input pooled VLP preparation plus shotgun sequencing of gut microbiota samples and purified fecal VLPs from the gnotobiotic mice revealed a reproducible nonsimultaneous pattern of attack extending over a 25-d period that involved five phages, none described previously. This system allowed us to (i) correlate increases in specific phages present in the pooled VLPs with reductions in the representation of particular bacterial taxa, (ii) provide evidence that phage resistance occurred because of ecological or epigenetic factors, (iii) track the origin of each of the five phages among the five human donors plus the extent of their genome variation between and within recipient mice, and (iv) establish the dramatic in vivo fitness advantage that a locus within a B. cellulosilyticus prophage confers upon its host. Together, these results provide a defined community-wide view of phage–bacterial host dynamics in the gut. PMID:24259713

  10. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression.

    PubMed

    Fisher, Charles K; Mehta, Pankaj

    2014-01-01

    Human associated microbial communities exert tremendous influence over human health and disease. With modern metagenomic sequencing methods it is now possible to follow the relative abundance of microbes in a community over time. These microbial communities exhibit rich ecological dynamics and an important goal of microbial ecology is to infer the ecological interactions between species directly from sequence data. Any algorithm for inferring ecological interactions must overcome three major obstacles: 1) a correlation between the abundances of two species does not imply that those species are interacting, 2) the sum constraint on the relative abundances obtained from metagenomic studies makes it difficult to infer the parameters in timeseries models, and 3) errors due to experimental uncertainty, or mis-assignment of sequencing reads into operational taxonomic units, bias inferences of species interactions due to a statistical problem called "errors-in-variables". Here we introduce an approach, Learning Interactions from MIcrobial Time Series (LIMITS), that overcomes these obstacles. LIMITS uses sparse linear regression with boostrap aggregation to infer a discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on synthetic data and showed that it could reliably infer the topology of the inter-species ecological interactions. We then used LIMITS to characterize the species interactions in the gut microbiomes of two individuals and found that the interaction networks varied significantly between individuals. Furthermore, we found that the interaction networks of the two individuals are dominated by distinct "keystone species", Bacteroides fragilis and Bacteroided stercosis, that have a disproportionate influence on the structure of the gut microbiome even though they are only found in moderate abundance. Based on our results, we hypothesize that the abundances of certain keystone species may be responsible for individuality in the human gut

  11. Gnotobiotic mouse model of phage-bacterial host dynamics in the human gut.

    PubMed

    Reyes, Alejandro; Wu, Meng; McNulty, Nathan P; Rohwer, Forest L; Gordon, Jeffrey I

    2013-12-10

    Bacterial viruses (phages) are the most abundant biological group on Earth and are more genetically diverse than their bacterial prey/hosts. To characterize their role as agents shaping gut microbial community structure, adult germ-free mice were colonized with a consortium of 15 sequenced human bacterial symbionts, 13 of which harbored one or more predicted prophages. One member, Bacteroides cellulosilyticus WH2, was represented by a library of isogenic transposon mutants that covered 90% of its genes. Once assembled, the community was subjected to a staged phage attack with a pool of live or heat-killed virus-like particles (VLPs) purified from the fecal microbiota of five healthy humans. Shotgun sequencing of DNA from the input pooled VLP preparation plus shotgun sequencing of gut microbiota samples and purified fecal VLPs from the gnotobiotic mice revealed a reproducible nonsimultaneous pattern of attack extending over a 25-d period that involved five phages, none described previously. This system allowed us to (i) correlate increases in specific phages present in the pooled VLPs with reductions in the representation of particular bacterial taxa, (ii) provide evidence that phage resistance occurred because of ecological or epigenetic factors, (iii) track the origin of each of the five phages among the five human donors plus the extent of their genome variation between and within recipient mice, and (iv) establish the dramatic in vivo fitness advantage that a locus within a B. cellulosilyticus prophage confers upon its host. Together, these results provide a defined community-wide view of phage-bacterial host dynamics in the gut. PMID:24259713

  12. Direct sequencing of human gut virome fractions obtained by flow cytometry

    PubMed Central

    Džunková, Mária; D’Auria, Giuseppe; Moya, Andrés

    2015-01-01

    The sequence assembly of the human gut virome encounters several difficulties. A high proportion of human and bacterial matches is detected in purified viral samples. Viral DNA extraction results in a low DNA concentration, which does not reach the minimal limit required for sequencing library preparation. Therefore, the viromes are usually enriched by whole genome amplification (WGA), which is, however, prone to the development of chimeras and amplification bias. In addition, as there is a very wide diversity of gut viral species, very extensive sequencing efforts must be made for the assembling of whole viral genomes. We present an approach to improve human gut virome assembly by employing a more precise preparation of a viral sample before sequencing. Particles present in a virome previously filtered through 0.2 μm pores were further divided into groups in accordance with their size and DNA content by fluorescence activated cell sorting (FACS). One selected viral fraction was sequenced excluding the WGA step, so that unbiased sequences with high reliability were obtained. The DNA extracted from the 314 viral particles of the selected fraction was assembled into 34 contigs longer than 1,000 bp. This represents an increase to the number of assembled long contigs per sequenced Gb in comparison with other studies where non-fractioned viromes are sequenced. Seven of these contigs contained open reading frames (ORFs) with explicit matches to proteins related to bacteriophages. The remaining contigs also possessed uncharacterized ORFs with bacteriophage-related domains. When the particles that are present in the filtered viromes are sorted into smaller groups by FACS, large pieces of viral genomes can be recovered easily. This approach has several advantages over the conventional sequencing of non-fractioned viromes: non-viral contamination is reduced and the sequencing efforts required for viral assembly are minimized. PMID:26441889

  13. Characterization and Detection of a Widely Distributed Gene Cluster That Predicts Anaerobic Choline Utilization by Human Gut Bacteria

    PubMed Central

    Martínez-del Campo, Ana; Bodea, Smaranda; Hamer, Hilary A.; Marks, Jonathan A.; Haiser, Henry J.; Turnbaugh, Peter J.

    2015-01-01

    ABSTRACT Elucidation of the molecular mechanisms underlying the human gut microbiota’s effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective. PMID:25873372

  14. Functional Metabolic Map of Faecalibacterium prausnitzii, a Beneficial Human Gut Microbe

    PubMed Central

    Heinken, Almut; Khan, M. Tanweer; Paglia, Giuseppe; Rodionov, Dmitry A.; Harmsen, Hermie J. M.

    2014-01-01

    The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism. PMID:25002542

  15. Detecting human impacts on the flora, fauna, and summer monsoon of Pleistocene Australia

    NASA Astrophysics Data System (ADS)

    Miller, G. H.; Magee, J. W.; Fogel, M. L.; Gagan, M. K.

    2006-08-01

    All of Australia's largest mammalian vertebrates became extinct 50 to 45 ka (thousand years ago), shortly after human colonization. Between 60 and 40 ka Australian climate was similar to present and not changing rapidly. Consequently, attention has turned toward plausible human mechanisms for the extinction, with proponents for over-hunting, ecosystem change, and introduced disease. To differentiate between these options we utilize isotopic tracers of diet preserved in eggshells of two large, flightless birds to track the status of ecosystems before and after human colonization. δ13C preserved in their eggshells monitor a bird's dietary intake in the weeks to months before egg-laying. More than 500 dated eggshells from central Australia of the Australian emu (Dromaius novaehollandiae), an opportunistic, dominantly herbivorous feeder, provide a continuous 140 kyr dietary δ 13C reconstruction. More than 350 dated eggshells from the same region of the heavier, extinct, giant bird Genyornis newtoni define its dietary intake from 140 ka until its extinction about 50 ka. Additional dietary records for both species were developed from two distant regions. Dromaius eggshell dietary δ13C reveals an unprecedented reduction in the bird's food resources about 50 ka, coeval in all three regions, suggesting conversion at that time of a tree/shrub savannah with occasionally rich grasslands to the modern desert scrub. We speculate that ecosystem collapse across the arid and semi-arid zones is a consequence of systematic burning by early humans. Genyornis diet everywhere is more restricted than in co-existing Dromaius, implying a more specialized feeding strategy. These data suggest that generalist feeders, such as Dromaius, were able to adapt to a changed vegetation regime, whereas more specialized feeders, such as Genyornis, became extinct. The altered vegetation may have also impacted Australian climate. Changes in the strength of climate feedbacks linked to vegetation and

  16. Detecting human impacts on the flora, fauna, and summer monsoon of Pleistocene Australia

    NASA Astrophysics Data System (ADS)

    Miller, G. H.; Magee, J. W.; Fogel, M. L.; Gagan, M. K.

    2007-08-01

    The moisture balance across northern and central Australia is dominated by changes in the strength of the Australian Summer Monsoon. Lake-level records that record changes in monsoon strength on orbital timescales are most consistent with a Northern Hemisphere insolation control on monsoon strength, a result consistent with recent modeling studies. A weak Holocene monsoon relative to monsoon strength 65-60 ka, despite stronger forcing, suggests a changed monsoon regime after 60 ka. Shortly after 60 ka humans colonized Australia and all of Australia's largest mammals became extinct. Between 60 and 40 ka Australian climate was similar to present and not changing rapidly. Consequently, attention has turned toward plausible human mechanisms for the extinction, with proponents for over-hunting, ecosystem change, and introduced disease. To differentiate between these options we utilize isotopic tracers of diet preserved in eggshells of two large, flightless birds to track the status of ecosystems before and after human colonization. More than 800 dated eggshells of the Australian emu (Dromaius novaehollandiae), an opportunistic, dominantly herbivorous feeder, provide a 140-kyr dietary reconstruction that reveals unprecedented reduction in the bird's food resources about 50 ka, coeval in three distant regions. These data suggest a tree/shrub savannah with occasionally rich grasslands was converted abruptly to the modern desert scrub. The diet of the heavier, extinct Genyornis newtoni, derived from >550 dated eggshells, was more restricted than in co-existing Dromaius, implying a more specialized feeding strategy. We suggest that generalist feeders, such as Dromaius, were able to adapt to a changed vegetation regime, whereas more specialized feeders, such as Genyornis, became extinct. We speculate that ecosystem collapse across arid and semi-arid zones was a consequence of systematic burning by early humans. We also suggest that altered climate feedbacks linked to changes

  17. 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

  18. Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans

    PubMed Central

    Pudlo, Nicholas A.; Urs, Karthik; Kumar, Supriya Suresh; German, J. Bruce; Mills, David A.

    2015-01-01

    ABSTRACT Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. PMID:26556271

  19. Molecular Studies Neglect Apparently Gram-Negative Populations in the Human Gut Microbiota

    PubMed Central

    Hugon, Perrine; Lagier, Jean-Christophe; Robert, Catherine; Lepolard, Catherine; Papazian, Laurent; Musso, Didier; Vialettes, Bernard

    2013-01-01

    Studying the relationships between gut microbiota, human health, and diseases is a major challenge that generates contradictory results. Most studies draw conclusions about the gut repertoire using a single biased metagenomics approach. We analyzed 16 different stool samples collected from healthy subjects who were from different areas, had metabolic disorders, were immunocompromised, or were treated with antibiotics at the time of the stool collection. The analyses performed included Gram staining, flow cytometry, transmission electron microscopy (TEM), quantitative real-time PCR (qPCR) of the Bacteroidetes and Firmicutes phyla, and pyrosequencing of the 16S rRNA gene amplicons targeting the V6 region. We quantified 1010 prokaryotes per gram of feces, which is less than was previously described. The Mann-Whitney test revealed that Gram-negative proportions of the prokaryotes obtained by Gram staining, TEM, and pyrosequencing differed according to the analysis used, with Gram-negative prokaryotes yielding median percentages of 70.6%, 31.0%, and 16.4%, respectively. A comparison of TEM and pyrosequencing analyses highlighted a difference of 14.6% in the identification of Gram-negative prokaryotes, and a Spearman test showed a tendency toward correlation, albeit not significant, in the Gram-negative/Gram-positive prokaryote ratio (ρ = 0.3282, P = 0.2146). In contrast, when comparing the qPCR and pyrosequencing results, a significant correlation was found for the Bacteroidetes/Firmicutes ratio (ρ = 0.6057, P = 0.0130). Our study showed that the entire diversity of the human gut microbiota remains unknown because different techniques generate extremely different results. We found that to assess the overall composition of bacterial communities, multiple techniques must be combined. The biases that exist for each technique may be useful in exploring the major discrepancies in molecular studies. PMID:23885002

  20. Metabolic niche of a prominent sulfate-reducing human gut bacterium

    PubMed Central

    Rey, Federico E.; Gonzalez, Mark D.; Cheng, Jiye; Ahern, Philip P.; Gordon, Jeffrey I.

    2013-01-01

    Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage’s substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it. PMID:23898195

  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. The diatom flora of Lake Kinneret (Israel) - Paleolimnological evidence for Holocene climate change and human impact in the southeastern Mediterranean

    NASA Astrophysics Data System (ADS)

    Vossel, Hannah; Reed, Jane M.; Litt, Thomas

    2015-04-01

    The Mediterranean basin is a region of highly complex topography and climatic variability, such that our understanding of the past environmental variability is still limited. Diatoms (single-celled siliceous algae, Bacillariophyceae) are abundant, diverse and sensitive to a wide range of environmental parameters. They are often well preserved in lake sediment records, and have well-recognised potential to generate high-quality paleolimnological data. Diatoms remain one of the least-exploited proxies in Mediterranean palaeoclimate research. Here, we present results of diatom analysis of an 18 m sediment core from Lake Kinneret (Israel) as part of a multi-proxy study of Holocene climate change and human impact in the Levant (http://www.sfb806.uni-koeln.de). Results are compared with other proxy data including pollen, and with output data from regional climate modelling, to strengthen interpretation of environmental change in the southeastern Mediterranean. The results show remarkable shifts in the diatom flora over the last ca. 8,000 years. Preliminary investigations show that 98% of the diatom taxa can be classified as oligohalobous-indifferent and as alkaliphilous, as is typical of freshwater, alkaline lakes of open hydrology in limestone, karst-dominated catchments. Changes in the diatom data over time can be interpreted mainly in terms of productivity shifts, with a clear trend from oligotrophic at the base to hypereutrophic in the modern lake. The eutrophication trend accelerates after ca. 3,000 cal. yrs. BP, indicating the influence of increased human activity in the catchment, identified previously by analysis of the vegetational history (Schiebel, 2013). The analysis of the composition of the diatom flora also provides some evidence for lake-level fluctuations, as a proxy for shifts in moisture availability. Low lake-level stands are characterized by low diatom concentration and increased relative abundance of littoral taxa. High lake-level stands are marked

  3. The Gut Bacteria-Driven Obesity Development.

    PubMed

    Compare, Debora; Rocco, Alba; Sanduzzi Zamparelli, Marco; Nardone, Gerardo

    2016-01-01

    It is now well established that a healthy gut flora is largely responsible for the overall health of the host, while a perturbation in gut microbial communities can contribute to disease susceptibility. Obesity is a complex process involving genetic and environmental factors with an epidemiological burden that makes it a major public health issue. Studies of germ-free or gnotobiotic mice provided evidence that the diversity, as well as the presence and relative proportion of different microbes in the gut play active roles in energy homeostasis. Similarly, human studies showed that both the diversity of the microbiota and the Bacteroidetes/Firmicutes ratio are decreased in obese individuals. The 'obese microbiota' seems to be able to increase dietary energy harvest and favor weight gain and fat deposition. Although research in this field has just started and many of the available data are still conflicting, the results are providing exciting perspectives, and gut microbiota manipulation has already become a new target for both prevention and treatment of obesity. PMID:27028448

  4. Composition of the gut microbiota modulates the severity of malaria.

    PubMed

    Villarino, Nicolas F; LeCleir, Gary R; Denny, Joshua E; Dearth, Stephen P; Harding, Christopher L; Sloan, Sarah S; Gribble, Jennifer L; Campagna, Shawn R; Wilhelm, Steven W; Schmidt, Nathan W

    2016-02-23

    Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden. PMID:26858424

  5. Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

    PubMed Central

    Tailford, Louise E.; Owen, C. David; Walshaw, John; Crost, Emmanuelle H.; Hardy-Goddard, Jemma; Le Gall, Gwenaelle; de Vos, Willem M.; Taylor, Garry L.; Juge, Nathalie

    2015-01-01

    The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of >90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal α2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease. PMID:26154892

  6. Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

    NASA Astrophysics Data System (ADS)

    Tailford, Louise E.; Owen, C. David; Walshaw, John; Crost, Emmanuelle H.; Hardy-Goddard, Jemma; Le Gall, Gwenaelle; de Vos, Willem M.; Taylor, Garry L.; Juge, Nathalie

    2015-07-01

    The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of >90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal α2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.

  7. Effect of Tulathromycin on Colonization Resistance, Antimicrobial Resistance, and Virulence of Human Gut Microbiota in Chemostats

    PubMed Central

    Hao, Haihong; Zhou, Shengxi; Cheng, Guyue; Dai, Menghong; Wang, Xu; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2016-01-01

    To evaluate microbiological safety of tulathromycin on human intestinal bacteria, tulathromycin (0, 0.1, 1, 10, and 100 μg/mL) was added into Chemostats. Before and after drug exposure, we monitored (1) population, SCFA products, antimicrobial resistance, and colonization resistance of gut microbiota, and (2) the antimicrobial resistance genes, transferability, virulent genes, pathogenicity of Enterococus faecalis. Results showed that low level of tulathromycin did not exhibit microbiological hazard on resistance selection and colonization resistance. However, high level of tulathromycin (10 and 100 μg/mL) may disturb colonization resistance of human gut microbiota and select antimicrobial resistant E. faecalis. Most of the selected resistant E. faecalis carried resistant gene of ermB, transferable element of Tn1545 and three virulence genes (esp, cylA, and ace). One of them (E. faecalis 143) was confirmed to have higher horizontal transfer risk and higher pathogenicity. The calculated no observable adverse effect concentration (NOAEC) and microbiological acceptable daily intake (mADI) in our study was 1 μg/mL and 14.66 μg/kg.bw/day, respectively. PMID:27092131

  8. Exploring gut microbes in human health and disease: Pushing the envelope

    PubMed Central

    Sun, Jun; Chang, Eugene B.

    2014-01-01

    Humans have coevolved with their microbes over thousands of years, but this relationship, is now being dramatically affected by shifts in the collective human microbiome resulting from changes in the environment and societal norms. Resulting perturbations of intestinal host-microbe interactions can lead to miscues and altered host responses that increase the risk of pathogenic processes and promote “western” disorders such as inflammatory bowel diseases, cancers, obesity, diabetes, autism, and asthma. Given the current challenges and limitations in gene therapy, approaches that can reshape the gut microbiome represent a reasonable strategy for restoring the balance between host and microbes. In this review and commentary, we highlight recent progress in our understanding of the intestinal microbiome in the context of health and diseases, focusing on mechanistic concepts that underlie the complex relationships between host and microbes. Despite these gains, many challenges lie ahead that make it difficult to close the gap between the basic sciences and clinical application. We will discuss the potential therapeutic strategies that can be used to manipulate the gut microbiota, recognizing that the promise of pharmabiotics (“bugs to drugs”) is unlikely to be completely fulfilled without a greater understanding of enteric microbiota and its impact on mammalian physiology. By leveraging the knowledge gained through these studies, we will be prepared to enter the era of personalized medicine where clinical inventions can be custom-tailored to individual patients to achieve better outcomes. PMID:25642449

  9. Comparative Genome Analysis of Megasphaera sp. Reveals Niche Specialization and Its Potential Role in the Human Gut

    PubMed Central

    Lanjekar, Vikram; Ranade, Dilip; Shouche, Yogesh S.

    2013-01-01

    With increasing number of novel bacteria being isolated from the human gut ecosystem, there is a greater need to study their role in the gut ecosystem and their effect on the host health. In the present study, we carried out in silico genome-wide analysis of two novel Megasphaera sp. isolates NM10 (DSM25563) and BL7 (DSM25562), isolated from feces of two healthy individuals and validated the key features by in vitro studies. The analysis revealed the general metabolic potential, adaptive features and the potential effects of these isolates on the host. The comparative genome analysis of the two human gut isolates NM10 and BL7 with ruminal isolate Megasphaera elsdenii (DSM20460) highlighted the differential adaptive features for their survival in human gut. The key findings include features like bile resistance, presence of various sensory and regulatory systems, stress response systems, membrane transporters and resistance to antibiotics. Comparison of the “glycobiome” based on the genomes of the ruminal isolate with the human gut isolates NM10 and BL revealed the presence of diverse and unique sets of Carbohydrate-Active enzymes (CAZymes) amongst these isolates, with a higher collection of CAZymes in the human gut isolates. This could be attributed to the difference in host diet and thereby the environment, consequently suggesting host specific adaptation in these isolates. In silico analysis of metabolic potential predicted the ability of these isolates to produce important metabolites like short chain fatty acids (butyrate, acetate, formate, and caproate), vitamins and essential amino acids, which was further validated by in vitro experiments. The ability of these isolates to produce important metabolites advocates for a potential healthy influence on the host. Further in vivo studies including transcriptomic and proteomic analysis will be required for better understanding the role and impact of these Megasphaera sp. isolates NM10 and BL7 on the human host

  10. Bacterial species involved in the conversion of dietary flavonoids in the human gut.

    PubMed

    Braune, Annett; Blaut, Michael

    2016-05-01

    The gut microbiota plays a crucial role in the conversion of dietary flavonoids and thereby affects their health-promoting effects in the human host. The identification of the bacteria involved in intestinal flavonoid conversion has gained increasing interest. This review summarizes available information on the so far identified human intestinal flavonoid-converting bacterial species and strains as well as their enzymes catalyzing the underlying reactions. The majority of described species involved in flavonoid transformation are capable of carrying out the O-deglycosylation of flavonoids. Other bacteria cleave the less common flavonoid-C-glucosides and/or further degrade the aglycones of flavonols, flavanonols, flavones, flavanones, dihydrochalcones, isoflavones and monomeric flavan-3-ols. To increase the currently limited knowledge in this field, identification of flavonoid-converting bacteria should be continued using culture-dependent screening or isolation procedures and molecular approaches based on sequence information of the involved enzymes. PMID:26963713

  11. [The effect of new broad-spectrum cephamycin, cefotetan administered intravenously on human fecal flora (author's transl)].

    PubMed

    Nakaya, R; Chida, T; Shibaoka, H; Sagara, H

    1982-03-01

    The changes in the fecal flora and their correlation with the fecal drug concentrations were studied, employing 4 volunteers (healthy adult males) to whom 1 g of cefotetan was intravenously administered daily for 6 days. 1. In all of the subjects, the total counts of fecal organisms were slightly decreased 1 day after administration of cefotetan, then showed gradual increase, and recovered to the normal level on 8 days after the withdrawal of the drug. 2. Cefotetan caused drastic suppression of normal aerobic and anaerobic flora during the administration period, except streptococci that remained unchanged at all. The bacterial groups suppressed were bacteroidaceae, eubacteria, bifidobacteria, peptococcaceae, lactobacilli, enterobacteriaceae, lecithinase-positive clostridia, and staphylococci. Yeasts were found to increase during the administration period. 3. The changes in flora well correlated with the fecal level of the drug concentrations. This is in accordance with the in vitro antibacterial activity of the drug. 4. A period of more than 15 days was required after the withdrawal of cefotetan to recover the normal fecal flora. 5. Loss of body weight and diarrhoea were not observed in any of the subjects. PMID:6954292

  12. Antioxidants Keep the Potentially Probiotic but Highly Oxygen-Sensitive Human Gut Bacterium Faecalibacterium prausnitzii Alive at Ambient Air

    PubMed Central

    Khan, M. Tanweer; van Dijl, Jan Maarten; Harmsen, Hermie J. M.

    2014-01-01

    The beneficial human gut microbe Faecalibacterium prausnitzii is a ‘probiotic of the future’ since it produces high amounts of butyrate and anti-inflammatory compounds. However, this bacterium is highly oxygen-senstive, making it notoriously difficult to cultivate and preserve. This has so far precluded its clinical application in the treatment of patients with inflammatory bowel diseases. The present studies were therefore aimed at developing a strategy to keep F. prausnitzii alive at ambient air. Our previous research showed that F. prausnitzii can survive in moderately oxygenized environments like the gut mucosa by transfer of electrons to oxygen. For this purpose, the bacterium exploits extracellular antioxidants, such as riboflavin and cysteine, that are abundantly present in the gut. We therefore tested to what extent these antioxidants can sustain the viability of F. prausnitzii at ambient air. The present results show that cysteine can facilitate the survival of F. prausnitzii upon exposure to air, and that this effect is significantly enhanced the by addition of riboflavin and the cryoprotectant inulin. The highly oxygen-sensitive gut bacterium F. prausnitzii can be kept alive at ambient air for 24 h when formulated with the antioxidants cysteine and riboflavin plus the cryoprotectant inulin. Improved formulations were obtained by addition of the bulking agents corn starch and wheat bran. Our present findings pave the way towards the biomedical exploitation of F. prausnitzii in redox-based therapeutics for treatment of dysbiosis-related inflammatory disorders of the human gut. PMID:24798051

  13. Time course production of urolithins from ellagic acid by human gut microbiota.

    PubMed

    García-Villalba, Rocío; Beltrán, David; Espín, Juan Carlos; Selma, María Victoria; Tomás-Barberán, Francisco A

    2013-09-18

    Ellagic acid (EA) is converted to urolithins by gut microbiota. Urolithins have beneficial biological effects in humans, but differences in urolithin production capacity among individuals have been shown. Therefore, the identification of the urolithin production pathways and the microorganisms implicated is of high interest. EA was incubated with gut microbiota from two volunteers able to produce urolithins but with different in vivo urolithin profiles (urolithin A and isourolithin A producers). The metabolic capabilities observed in vivo were retained in vitro. Both individuals showed a much higher abundance of Clostridium leptum group of Firmicutes phylum than Bacteroides / Prevotella . EA was either dissolved in DMSO or suspended in water. DMSO increased EA solubility but decreased urolithin production rate due to a delay in growth of some microbial groups, principally, Clostridium coccoides . This allowed the detection of catabolic intermediates [urolithins M-5, M-6, M-7, C, and 2,3,8,10-tetrahydroxy urolithin (urolithin E)]. Bacteria from C. coccoides group (or genera co-occurring in vivo with this group) seem to be involved in production of different urolithins. PMID:23984796

  14. In vitro utilization of gold and green kiwifruit oligosaccharides by human gut microbial populations.

    PubMed

    Parkar, Shanthi G; Rosendale, Doug; Paturi, Gunaranjan; Herath, Thanuja D; Stoklosinski, Halina; Phipps, Janet E; Hedderley, Duncan; Ansell, Juliet

    2012-09-01

    We examined the effects of whole kiwifruit on gut microbiota using an in vitro batch model of gastric-ileal digestion and colonic fermentation. Faecal fermentations of gold and green kiwifruit, inulin and water (control) digests were performed for up to 48 h. As compared to the control, gold and green kiwifruit increased Bifidobacterium spp. by 0.9 and 0.8 log(10) cfu/ml, respectively (P < 0.001), and the Bacteroides-Prevotella-Porphyromonas group by 0.4 and 0.5 log(10) cfu/ml, respectively. Inulin only had a bifidogenic effect (+0.4 log(10) cfu/ml). This was accompanied with increases in microbial glycosidases, especially those with substrate specificities relating to the breakdown of kiwifruit oligosaccharides, and with increased generation of short chain fatty acids. The microbial metabolic activity was sustained for up to 48 h, which we attribute to the complexity of the carbohydrate substrate provided by whole kiwifruit. Kiwifruit fermenta supernatant was also separately shown to affect the in vitro proliferation of Bifidobacterium longum, and its adhesion to Caco-2 intestinal epithelial cells. Collectively, these data suggest that whole kiwifruit may modulate human gut microbial composition and metabolism to produce metabolites conducive to increased bifidobacteria-host association. PMID:22576129

  15. Insights from genomes of representatives of the human gut commensal Bifidobacterium bifidum.

    PubMed

    Duranti, Sabrina; Milani, Christian; Lugli, Gabriele Andrea; Turroni, Francesca; Mancabelli, Leonardo; Sanchez, Borja; Ferrario, Chiara; Viappiani, Alice; Mangifesta, Marta; Mancino, Walter; Gueimonde, Miguel; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2015-07-01

    Bifidobacteria are bacterial gut commensals of mammals, birds and social insects that are perceived to influence the metabolism/physiology of their host. In this context, members of the Bifidobacterium bifidum species are believed to significantly contribute to the overall microbiota of the human gut at infant stage. However, the molecular reasons for their adaptation to this environment are poorly understood. In this study, we analysed the pan-genome of B. bifidum species by decoding genomes of 15 B. bifidum strains, which highlighted the existence of a conserved gene uniquely present in this bifidobacterial taxon, underscoring a nutrient acquisition strategy that targets host-derived glycans, such as those present in mucin. Growth experiments and corresponding transcriptomic analyses confirmed the in silico data and supported these intriguing and unique host glycan-specific saccharolytic features. The ubiquity of the genetic features of B. bifidum for the breakdown of host glycans was confirmed by interrogating metagenomic datasets, thereby supporting the notion that metabolic access to host-derived glycans is a potent evolutionary force that has shaped B. bifidum genomes and consequently the ecology of the infant intestinal microbiota. PMID:25523018

  16. Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species

    PubMed Central

    Perez-Muñoz, Maria Elisa; Joglekar, Payal; Shen, Yi-Ji; Chang, Kuan Y.; Peterson, Daniel A.

    2015-01-01

    Host T cell reactivity toward gut bacterial epitopes has been recognized as part of disease pathogenesis. However, the specificity of T cells that recognize this vast number of epitopes has not yet been well described. After colonizing a C57BL/6J germ-free mouse with the human gut symbiotic bacteria Bacteroides thetaiotaomicron, we isolated a T cell that recognized these bacteria in vitro. Using this T cell, we mapped the first known non-carbohydrate T cell epitope within the phylum Bacteroidetes. The T cell also reacted to two other additional Bacteroides species. We identified the peptide that stimulated the T cell by using a genetic approach. Genomic data from the epitope-positive and epitope-negative bacteria explain the cross-reactivity of the T cell to multiple species. This epitope degeneracy should shape our understanding of the T cell repertoire stimulated by the complex microbiome residing in the gastrointestinal tract in both healthy and disease states. PMID:26637014

  17. The Sus operon: a model system for starch uptake by the human gut Bacteroidetes.

    PubMed

    Foley, Matthew H; Cockburn, Darrell W; Koropatkin, Nicole M

    2016-07-01

    Resident bacteria in the densely populated human intestinal tract must efficiently compete for carbohydrate nutrition. The Bacteroidetes, a dominant bacterial phylum in the mammalian gut, encode a plethora of discrete polysaccharide utilization loci (PULs) that are selectively activated to facilitate glycan capture at the cell surface. The most well-studied PUL-encoded glycan-uptake system is the starch utilization system (Sus) of Bacteroides thetaiotaomicron. The Sus includes the requisite proteins for binding and degrading starch at the surface of the cell preceding oligosaccharide transport across the outer membrane for further depolymerization to glucose in the periplasm. All mammalian gut Bacteroidetes possess analogous Sus-like systems that target numerous diverse glycans. In this review, we discuss what is known about the eight Sus proteins of B. thetaiotaomicron that define the Sus-like paradigm of nutrient acquisition that is exclusive to the Gram-negative Bacteroidetes. We emphasize the well-characterized outer membrane proteins SusDEF and the α-amylase SusG, each of which have unique structural features that allow them to interact with starch on the cell surface. Despite the apparent redundancy in starch-binding sites among these proteins, each has a distinct role during starch catabolism. Additionally, we consider what is known about how these proteins dynamically interact and cooperate in the membrane and propose a model for the formation of the Sus outer membrane complex. PMID:27137179

  18. Transcriptional interactions suggest niche segregation among microorganisms in the human gut.

    PubMed

    Plichta, Damian Rafal; Juncker, Agnieszka Sierakowska; Bertalan, Marcelo; Rettedal, Elizabeth; Gautier, Laurent; Varela, Encarna; Manichanh, Chaysavanh; Fouqueray, Charlène; Levenez, Florence; Nielsen, Trine; Doré, Joël; Machado, Ana Manuel Dantas; de Evgrafov, Mari Cristina Rodriguez; Hansen, Torben; Jørgensen, Torben; Bork, Peer; Guarner, Francisco; Pedersen, Oluf; Sommer, Morten O A; Ehrlich, S Dusko; Sicheritz-Pontén, Thomas; Brunak, Søren; Nielsen, H Bjørn

    2016-01-01

    The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species(1). Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species(2,3). To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level. PMID:27564131

  19. Progress and Challenges in Developing Metabolic Footprints from Diet in Human Gut Microbial Cometabolism12

    PubMed Central

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-01-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  20. Progress and challenges in developing metabolic footprints from diet in human gut microbial cometabolism.

    PubMed

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-05-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  1. The Gut Microbiota in Immune-Mediated Inflammatory Diseases

    PubMed Central

    Forbes, Jessica D.; Van Domselaar, Gary; Bernstein, Charles N.

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  2. The Gut Microbiota in Immune-Mediated Inflammatory Diseases.

    PubMed

    Forbes, Jessica D; Van Domselaar, Gary; Bernstein, Charles N

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  3. Gut microbiota and obesity.

    PubMed

    Gérard, Philippe

    2016-01-01

    The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity. PMID:26459447

  4. Gut microbiota and hepatic encephalopathy.

    PubMed

    Dhiman, Radha K

    2013-06-01

    There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE. PMID:23463489

  5. Non-invasive assessment of barrier integrity and function of the human gut

    PubMed Central

    Grootjans, Joep; Thuijls, Geertje; Verdam, Froukje; Derikx, Joep PM; Lenaerts, Kaatje; Buurman, Wim A

    2010-01-01

    Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease, and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion, including trauma and major surgery. Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease. A variety of tests have been developed to assess intestinal epithelial cell damage, intestinal tight junction status and consequences of intestinal barrier integrity loss, i.e. increased intestinal permeability. This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function. PMID:21160852

  6. Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts

    PubMed Central

    Lozupone, Catherine; Faust, Karoline; Raes, Jeroen; Faith, Jeremiah J.; Frank, Daniel N.; Zaneveld, Jesse; Gordon, Jeffrey I.; Knight, Rob

    2012-01-01

    We lack a deep understanding of genetic and metabolic attributes specializing in microbial consortia for initial and subsequent waves of colonization of our body habitats. Here we show that phylogenetically interspersed bacteria in Clostridium cluster XIVa, an abundant group of bacteria in the adult human gut also known as the Clostridium coccoides or Eubacterium rectale group, contains species that have evolved distribution patterns consistent with either early successional or stable gut communities. The species that specialize to the infant gut are more likely to associate with systemic infections and can reach high abundances in individuals with Inflammatory Bowel Disease (IBD), indicating that a subset of the microbiota that have adapted to pioneer/opportunistic lifestyles may do well in both early development and with disease. We identified genes likely selected during adaptation to pioneer/opportunistic lifestyles as those for which early succession association and not phylogenetic relationships explain genomic abundance. These genes reveal potential mechanisms by which opportunistic gut bacteria tolerate osmotic and oxidative stress and potentially important aspects of their metabolism. These genes may not only be biomarkers of properties associated with adaptation to early succession and disturbance, but also leads for developing therapies aimed at promoting reestablishment of stable gut communities following physiologic or pathologic disturbances. PMID:22665442

  7. Ranking the impact of human health disorders on gut metabolism: systemic lupus erythematosus and obesity as study cases.

    PubMed

    Rojo, David; Hevia, Arancha; Bargiela, Rafael; López, Patricia; Cuervo, Adriana; González, Sonia; Suárez, Ana; Sánchez, Borja; Martínez-Martínez, Mónica; Milani, Christian; Ventura, Marco; Barbas, Coral; Moya, Andrés; Suárez, Antonio; Margolles, Abelardo; Ferrer, Manuel

    2015-01-01

    Multiple factors have been shown to alter intestinal microbial diversity. It remains to be seen, however, how multiple collective pressures impact the activity in the gut environment and which, if any, is positioned as a dominant driving factor determining the final metabolic outcomes. Here, we describe the results of a metabolome-wide scan of gut microbiota in 18 subjects with systemic lupus erythematosus (SLE) and 17 healthy control subjects and demonstrate a statistically significant difference (p < 0.05) between the two groups. Healthy controls could be categorized (p < 0.05) based on their body mass index (BMI), whereas individuals with SLE could not. We discuss the prevalence of SLE compared with BMI as the dominant factor that regulates gastrointestinal microbial metabolism and provide plausible explanatory causes. Our results uncover novel perspectives with clinical relevance for human biology. In particular, we rank the importance of various pathophysiologies for gut homeostasis. PMID:25655524

  8. Role of Glycoside Phosphorylases in Mannose Foraging by Human Gut Bacteria*

    PubMed Central

    Ladevèze, Simon; Tarquis, Laurence; Cecchini, Davide A.; Bercovici, Juliette; André, Isabelle; Topham, Christopher M.; Morel, Sandrine; Laville, Elisabeth; Monsan, Pierre; Lombard, Vincent; Henrissat, Bernard; Potocki-Véronèse, Gabrielle

    2013-01-01

    To metabolize both dietary fiber constituent carbohydrates and host glycans lining the intestinal epithelium, gut bacteria produce a wide range of carbohydrate-active enzymes, of which glycoside hydrolases are the main components. In this study, we describe the ability of phosphorylases to participate in the breakdown of human N-glycans, from an analysis of the substrate specificity of UhgbMP, a mannoside phosphorylase of the GH130 protein family discovered by functional metagenomics. UhgbMP is found to phosphorolyze β-d-Manp-1,4-β-d-GlcpNAc-1,4-d-GlcpNAc and is also a highly efficient enzyme to catalyze the synthesis of this precious N-glycan core oligosaccharide by reverse phosphorolysis. Analysis of sequence conservation within family GH130, mapped on a three-dimensional model of UhgbMP and supported by site-directed mutagenesis results, revealed two GH130 subfamilies and allowed the identification of key residues responsible for catalysis and substrate specificity. The analysis of the genomic context of 65 known GH130 sequences belonging to human gut bacteria indicates that the enzymes of the GH130_1 subfamily would be involved in mannan catabolism, whereas the enzymes belonging to the GH130_2 subfamily would rather work in synergy with glycoside hydrolases of the GH92 and GH18 families in the breakdown of N-glycans. The use of GH130 inhibitors as therapeutic agents or functional foods could thus be considered as an innovative strategy to inhibit N-glycan degradation, with the ultimate goal of protecting, or restoring, the epithelial barrier. PMID:24043624

  9. Risungbinella massiliensis sp. nov., a new member of Thermoactinomycetaceae isolated from human gut.

    PubMed

    Dubourg, Grégory; Lagier, Jean-Christophe; Robert, Catherine; Armstrong, Nicholas; Couderc, Carine; Fournier, Pierre-Edouard; Raoult, Didier

    2016-06-01

    A novel filamentous bacterium, designated GD1(T), was isolated from the gut microbiota of a 38-year-old male who suffered from a Coxiella burnetii vascular for which he received multiple a broad-spectrum antibiotic cocktail at the time of the stool collection. The strain was isolated as a part of culturomics study by cultivation on 5 % sheep blood agar in aerobic condition at 28 °C, after 14 days of incubation. Strain GD1(T) shows 16S rRNA gene sequence similarities of 98.01 % to the type strain of Risungbinella pyongyangensis. We describe here the features of this bacterium, together with the complete genome sequence and annotation. The G+C content of the genomic DNA was determined to be 40.1 mol %. The major fatty acids of strain GD1(T) were identified as iso-C15:0, iso-C17:0, anteiso-C15:0, iso-C14:0 and C16:0. The 3,440,191 bp long genome contains 3540 protein-coding and 67 RNA genes, including three rRNA genes. Strain GD1(T) (= DSM 46691 = CSUR P1082) sp. nov. is here classified as the type strain of a new species, Risungbinella massiliensis, within the family Thermoactinomycetaceae. To date, strain GD1(T) is the first member of the family Thermoactinomycetaceae isolated from human gut and the fourth from a human specimen. PMID:26984352

  10. CKD impairs barrier function and alters microbial flora of the intestine: a major link to inflammation and uremic toxicity

    PubMed Central

    Vaziri, Nosratola D.

    2013-01-01

    Purpose of review Chronic kidney disease (CKD) is associated with oxidative stress and inflammation which contribute to progression of kidney disease and its numerous complications. Until recently, little attention had been paid to the role of the intestine and its microbial flora in the pathogenesis of CKD-associated inflammation. This article is intended to provide an over view of the impact of uremia on the structure and function of the gut and its microbial flora and their potential link to the associated systemic inflammation. Recent findings Recent studies conducted in the author’s laboratories have demonstrated marked disintegration of the colonic epithelial barrier structure and significant alteration of the colonic bacterial flora in humans and animals with advanced CKD. The observed disruption of the intestinal epithelial barrier complex can play an important part in the development of systemic inflammation by enabling influx of endotoxin and other noxious luminal contents into the systemic circulation. Similarly via disruption of the normal symbiotic relationship and production, absorption and retention of noxious products, alteration of the microbial flora can contribute to systemic inflammation and uremic toxicity. In fact recent studies have documented the role of colonic bacteria as the primary source of several well known pro-inflammatory/pro-oxidant uremic toxins as well as many as-yet unidentified retained compounds. Summary CKD results in disruption of the intestinal barrier structure and marked alteration of its microbial flora –events that play a major role in the pathogenesis of inflammation and uremic toxicity. PMID:23010760

  11. Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health.

    PubMed

    Wasielewski, Helen; Alcock, Joe; Aktipis, Athena

    2016-05-01

    Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health. PMID:27270755

  12. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans

    PubMed Central

    Fernandes, J; Su, W; Rahat-Rozenbloom, S; Wolever, T M S; Comelli, E M

    2014-01-01

    Background/Objectives: High dietary fibre intakes may protect against obesity by influencing colonic fermentation and the colonic microbiota. Though, recent studies suggest that increased colonic fermentation contributes to adiposity. Diet influences the composition of the gut microbiota. Previous research has not evaluated dietary intakes, body mass index (BMI), faecal microbiota and short chain fatty acid (SCFA) in the same cohort. Our objectives were to compare dietary intakes, faecal SCFA concentrations and gut microbial profiles in healthy lean (LN, BMI⩽25) and overweight or obese (OWOB, BMI>25) participants. Design: We collected demographic information, 3-day diet records, physical activity questionnaires and breath and faecal samples from 94 participants of whom 52 were LN and 42 OWOB. Results: Dietary intakes and physical activity levels did not differ significantly between groups. OWOB participants had higher faecal acetate (P=0.05), propionate (P=0.03), butyrate (P=0.05), valerate (P=0.03) and total short chain fatty acid (SCFA; P=0.02) concentrations than LN. No significant differences in Firmicutes to Bacteroides/Prevotella (F:B) ratio was observed between groups. However, in the entire cohort, Bacteroides/Prevotella counts were negatively correlated with faecal total SCFA (r=−0.32, P=0.002) and F:B ratio was positively correlated with faecal total SCFA (r=0.42, P<0.0001). Principal component analysis identified distinct gut microbiota and SCFA–F:B ratio components, which together accounted for 59% of the variation. F:B ratio loaded with the SCFA and not with the microbiota suggesting that SCFA and F:B ratio vary together and may be interrelated. Conclusions: The results support the hypothesis that colonic fermentation patterns may be altered, leading to different faecal SCFA concentrations in OWOB compared with LN humans. More in-depth studies looking at the metabolic fate of SCFA produced in LN and OWOB participants are needed in order to

  13. Metagenome of the gut of a malnourished child

    PubMed Central

    2011-01-01

    Background Malnutrition, a major health problem, affects a significant proportion of preschool children in developing countries. The devastating consequences of malnutrition include diarrhoea, malabsorption, increased intestinal permeability, suboptimal immune response, etc. Nutritional interventions and dietary solutions have not been effective for treatment of malnutrition till date. Metagenomic procedures allow one to access the complex cross-talk between the gut and its microbial flora and understand how a different community composition affects various states of human health. In this study, a metagenomic approach was employed for analysing the differences between gut microbial communities obtained from a malnourished and an apparently healthy child. Results Our results indicate that the malnourished child gut has an abundance of enteric pathogens which are known to cause intestinal inflammation resulting in malabsorption of nutrients. We also identified a few functional sub-systems from these pathogens, which probably impact the overall metabolic capabilities of the malnourished child gut. Conclusion The present study comprehensively characterizes the microbial community resident in the gut of a malnourished child. This study has attempted to extend the understanding of the basis of malnutrition beyond nutrition deprivation. PMID:21599906

  14. Characterization of functional properties of Enterococcus faecium strains isolated from human gut.

    PubMed

    İspirli, Hümeyra; Demirbaş, Fatmanur; Dertli, Enes

    2015-11-01

    The aim of this work was to characterize the functional properties of Enterococcus faecium strains identified after isolation from human faeces. Of these isolates, strain R13 showed the best resistance to low pH, bile salts, and survival in the simulated in vitro digestion assay, and demonstrated an important level of adhesion to hexadecane as a potential probiotic candidate. Analysis of the antibiotic resistance of E. faecium strains indicated that in general these isolates were sensitive to the tested antibiotics and no strain appeared to be resistant to vancomycin. Examination of the virulence determinants for E. faecium strains demonstrated that all strains contained the virulence genes common in gut- and food-originated enterococci, and strain R13 harboured the lowest number of virulence genes. Additionally, no strain contained the genes related to cytolysin metabolism and showed hemolytic activity. The antimicrobial role of E. faecium strains was tested against several pathogens, in which different levels of inhibitory effects were observed, and strain R13 was inhibitory to all tested pathogens. PCR screening of genes encoding enterocin A and B indicated the presence of these genes in E. faecium strains. Preliminary characterization of bacteriocins revealed that their activity was lost after proteolytic enzyme treatments, but no alteration in antimicrobial activity was observed at different pHs (3.5 to 9.5) and after heat treatments. In conclusion, this study revealed the functional characteristics of E. faecium R13 as a gut isolate, and this strain could be developed as a new probiotic after further tests. PMID:26485327

  15. The Rebirth of Culture in Microbiology through the Example of Culturomics To Study Human Gut Microbiota

    PubMed Central

    Lagier, Jean-Christophe; Hugon, Perrine; Khelaifia, Saber; Fournier, Pierre-Edouard; La Scola, Bernard

    2015-01-01

    SUMMARY Bacterial culture was the first method used to describe the human microbiota, but this method is considered outdated by many researchers. Metagenomics studies have since been applied to clinical microbiology; however, a “dark matter” of prokaryotes, which corresponds to a hole in our knowledge and includes minority bacterial populations, is not elucidated by these studies. By replicating the natural environment, environmental microbiologists were the first to reduce the “great plate count anomaly,” which corresponds to the difference between microscopic and culture counts. The revolution in bacterial identification also allowed rapid progress. 16S rRNA bacterial identification allowed the accurate identification of new species. Mass spectrometry allowed the high-throughput identification of rare species and the detection of new species. By using these methods and by increasing the number of culture conditions, culturomics allowed the extension of the known human gut repertoire to levels equivalent to those of pyrosequencing. Finally, taxonogenomics strategies became an emerging method for describing new species, associating the genome sequence of the bacteria systematically. We provide a comprehensive review on these topics, demonstrating that both empirical and hypothesis-driven approaches will enable a rapid increase in the identification of the human prokaryote repertoire. PMID:25567229

  16. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut.

    PubMed

    Pereira, Dora I A; Gibson, Glenn R

    2002-09-01

    The objective of this study was to evaluate the effect of human gut-derived lactic acid bacteria and bifidobacteria on cholesterol levels in vitro. Continuous cultures inoculated with fecal material from healthy human volunteers with media supplemented with cholesterol and bile acids were used to enrich for potential cholesterol assimilators among the indigenous bacterial populations. Seven potential probiotics were found: Lactobacillus fermentum strains F53 and KC5b, Bifidobacterium infantis ATCC 15697, Streptococcus bovis ATCC 43143, Enterococcus durans DSM 20633, Enterococcus gallinarum, and Enterococcus faecalis. A comparative evaluation regarding the in vitro cholesterol reduction abilities of these strains along with commercial probiotics was undertaken. The degree of acid and bile tolerance of strains was also evaluated. The human isolate L. fermentum KC5b was able to maintain viability for 2 h at pH 2 and to grow in a medium with 4,000 mg of bile acids per liter. This strain was also able to remove a maximum of 14.8 mg of cholesterol per g (dry weight) of cells from the culture medium and therefore was regarded as a candidate probiotic. PMID:12200334

  17. Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome.

    PubMed

    Soverini, Matteo; Rampelli, Simone; Turroni, Silvia; Schnorr, Stephanie L; Quercia, Sara; Castagnetti, Andrea; Biagi, Elena; Brigidi, Patrizia; Candela, Marco

    2016-01-01

    Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies. PMID:27462302

  18. Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome

    PubMed Central

    Soverini, Matteo; Rampelli, Simone; Turroni, Silvia; Schnorr, Stephanie L.; Quercia, Sara; Castagnetti, Andrea; Biagi, Elena; Brigidi, Patrizia; Candela, Marco

    2016-01-01

    Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe–host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies. PMID:27462302

  19. Bifidobacteria and Their Role as Members of the Human Gut Microbiota.

    PubMed

    O'Callaghan, Amy; van Sinderen, Douwe

    2016-01-01

    Members of the genus Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are believed to exert positive health benefits on their host. Due to their purported health-promoting properties, bifidobacteria have been incorporated into many functional foods as active ingredients. Bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract, such as the human oral cavity, the insect gut and sewage. To be able to survive in these particular ecological niches, bifidobacteria must possess specific adaptations to be competitive. Determination of genome sequences has revealed genetic attributes that may explain bifidobacterial ecological fitness, such as metabolic abilities, evasion of the host adaptive immune system and colonization of the host through specific appendages. However, genetic modification is crucial toward fully elucidating the mechanisms by which bifidobacteria exert their adaptive abilities and beneficial properties. In this review we provide an up to date summary of the general features of bifidobacteria, whilst paying particular attention to the metabolic abilities of this species. We also describe methods that have allowed successful genetic manipulation of bifidobacteria. PMID:27379055

  20. A human volunteer study to assess the impact of confectionery sweeteners on the gut microbiota composition.

    PubMed

    Beards, Emma; Tuohy, Kieran; Gibson, Glenn

    2010-09-01

    Sweeteners are being sourced to lower the energetic value of confectionery including chocolates. Some, especially non-digestible carbohydrates, may possess other benefits for human health upon their fermentation by the colonic microbiota. The present study assessed non-digestible carbohydrate sweeteners, selected for use in low-energy chocolates, for their ability to beneficially modulate faecal bacterial profiles in human volunteers. Forty volunteers consumed a test chocolate (low-energy or experimental chocolate) containing 22.8 g of maltitol (MTL), MTL and polydextrose (PDX), or MTL and resistant starch for fourteen consecutive days. The dose of the test chocolates was doubled every 2 weeks over a 6-week period. Numbers of faecal bifidobacteria significantly increased with all the three test treatments. Chocolate containing the PDX blend also significantly increased faecal lactobacilli (P = 0.00 001) after the 6 weeks. The PDX blend also showed significant increases in faecal propionate and butyrate (P = 0.002 and 0.006, respectively). All the test chocolates were well tolerated with no significant change in bowel habit or intestinal symptoms even at a daily dose of 45.6 g of non-digestible carbohydrate sweetener. This is of importance not only for giving manufacturers a sugar replacement that can reduce energetic content, but also for providing a well-tolerated means of delivering high levels of non-digestible carbohydrates into the colon, bringing about improvements in the biomarkers of gut health. PMID:20370946

  1. Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

    PubMed Central

    Powell, J J; Ainley, C C; Harvey, R S; Mason, I M; Kendall, M D; Sankey, E A; Dhillon, A P; Thompson, R P

    1996-01-01

    Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:8675092

  2. Suggested alternative starch utilization system from the human gut bacterium Bacteroides thetaiotaomicron.

    PubMed

    Chaudet, Marcia M; Rose, David R

    2016-06-01

    The human digestive system is host to a highly populated ecosystem of bacterial species that significantly contributes to our assimilation of dietary carbohydrates. Bacteroides thetaiotaomicron is a member of this ecosystem, and participates largely in the role of the gut microbiome by breaking down dietary complex carbohydrates. This process of acquiring glycans from the colon lumen is predicted to rely on the mechanisms of proteins that are part of a classified system known as polysaccharide utilization loci (PUL). These loci are responsible for binding substrates at the cell outer membrane, internalizing them, and then hydrolyzing them within the periplasm into simple sugars. Here we report our investigation into specific components of a PUL, and suggest an alternative starch utilization system in B. thetaiotaomicron. Our analysis of an outer membrane binding protein, a SusD homolog, highlights its contribution to this PUL by acquiring starch-based sugars from the colon lumen. Through our structural characterization of two Family GH31 α-glucosidases, we reveal the flexibility of this bacterium with respect to utilizing a range of starch-derived glycans with an emphasis on branched substrates. With these results we demonstrate the predicted function of a gene locus that is capable of contributing to starch hydrolysis in the human colon. PMID:27093479

  3. Effect of oligosaccharides on the adhesion of gut bacteria to human HT-29 cells.

    PubMed

    Altamimi, M; Abdelhay, O; Rastall, R A

    2016-06-01

    The influence of five oligosaccharides (cellobiose, stachyose, raffinose, lactulose and chito-oligosaccharides) on the adhesion of eight gut bacteria (Bifidobacterium bifidum ATCC 29521, Bacteroides thetaiotaomicron ATCC 29148D-5, Clostridium leptum ATCC 29065, Blautia coccoides ATCC 29236, Faecalibacterium prausnitzii ATCC 27766, Bacteroides fragilis ATCC 23745, Clostridium difficile ATCC 43255 and Lactobacillus casei ATCC 393) to mucous secreting and non-mucous secreting HT-29 human epithelial cells, was investigated. In pure culture, the bacteria showed variations in their ability to adhere to epithelial cells. The effect of oligosaccharides diminished adhesion and the presence of mucus played a major factor in adhesion, likely due to high adhesiveness to mucins present in the native human mucus layer covering the whole cell surface. However, clostridia displayed almost the same level of adhesion either with or without mucus being present. Bl. coccoides adhesion was decreased by stachyose and cellobiose in non-mucus-secreting cells in pure culture, while in mixed faecal culture cellobiose displayed the highest antiadhesive activity with an overall average of 65% inhibition amongst tested oligomers and lactulose displayed the lowest with an average of 47.4%. Bifidobacteria, Bacteroides, lactobacilli and clostridia were inhibited within the following ranges 47-78%, 32-65%, 11.7-58% and 64-85% respectively. This means that clostridia were the most strongly influenced members of the microflora amongst the bacterial groups tested in mixed culture. In conclusion, introducing oligosaccharides which are candidate prebiotics into pure or mixed cultures has affected bacterial adhesion. PMID:27018325

  4. Holding a grudge: persisting anti-phage CRISPR immunity in multiple human gut microbiomes.

    PubMed

    Mick, Eran; Stern, Adi; Sorek, Rotem

    2013-05-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) system of bacteria and archaea constitutes a mechanism of acquired adaptive immunity against phages, which is based on genome-encoded markers of previously infecting phage sequences ("spacers"). As a repository of phage sequences, these spacers make the system particularly suitable for elucidating phage-bacteria interactions in metagenomic studies. Recent metagenomic analyses of CRISPRs associated with the human microbiome intriguingly revealed conserved "memory spacers" shared by bacteria in multiple unrelated, geographically separated individuals. Here, we discuss possible avenues for explaining this phenomenon by integrating insights from CRISPR biology and phage-bacteria ecology, with a special focus on the human gut. We further explore the growing body of evidence for the role of CRISPR/Cas in regulating the interplay between bacteria and lysogenic phages, which may be intimately related to the presence of memory spacers and sheds new light on the multifaceted biological and ecological modes of action of CRISPR/Cas. PMID:23439321

  5. Bifidobacteria and Their Role as Members of the Human Gut Microbiota

    PubMed Central

    O'Callaghan, Amy; van Sinderen, Douwe

    2016-01-01

    Members of the genus Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are believed to exert positive health benefits on their host. Due to their purported health-promoting properties, bifidobacteria have been incorporated into many functional foods as active ingredients. Bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract, such as the human oral cavity, the insect gut and sewage. To be able to survive in these particular ecological niches, bifidobacteria must possess specific adaptations to be competitive. Determination of genome sequences has revealed genetic attributes that may explain bifidobacterial ecological fitness, such as metabolic abilities, evasion of the host adaptive immune system and colonization of the host through specific appendages. However, genetic modification is crucial toward fully elucidating the mechanisms by which bifidobacteria exert their adaptive abilities and beneficial properties. In this review we provide an up to date summary of the general features of bifidobacteria, whilst paying particular attention to the metabolic abilities of this species. We also describe methods that have allowed successful genetic manipulation of bifidobacteria. PMID:27379055

  6. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip

    PubMed Central

    Kim, Hyun Jung; Li, Hu; Collins, James J.; Ingber, Donald E.

    2016-01-01

    A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. PMID:26668389

  7. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip.

    PubMed

    Kim, Hyun Jung; Li, Hu; Collins, James J; Ingber, Donald E

    2016-01-01

    A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. PMID:26668389

  8. Host-derived glycans serve as selected nutrients for the gut microbe: human milk oligosaccharides and bifidobacteria.

    PubMed

    Katayama, Takane

    2016-04-01

    Lactation is a common feeding strategy of eutherian mammals, but its functions go beyond feeding the neonates. Ever since Tissier isolated bifidobacteria from the stool of breast-fed infants, human milk has been postulated to contain compounds that selectively stimulate the growth of bifidobacteria in intestines. However, until relatively recently, there have been no reports to link human milk compound(s) with bifidobacterial physiology. Over the past decade, successive studies have demonstrated that infant-gut-associated bifidobacteria are equipped with genetic and enzymatic toolsets dedicated to assimilation of host-derived glycans, especially human milk oligosaccharides (HMOs). Among gut microbes, the presence of enzymes required for degrading HMOs with type-1 chains is essentially limited to infant-gut-associated bifidobacteria, suggesting HMOs serve as selected nutrients for the bacteria. In this study, I shortly discuss the research on bifidobacteria and HMOs from a historical perspective and summarize the roles of bifidobacterial enzymes in the assimilation of HMOs with type-1 chains. Based on this overview, I suggest the co-evolution between bifidobacteria and human beings mediated by HMOs. PMID:26838671

  9. 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

  10. Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.

    PubMed

    Peters, Sheila Annie; Jones, Christopher R; Ungell, Anna-Lena; Hatley, Oliver J D

    2016-06-01

    Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. The primary objective of this review is to summarize the current knowledge in the quantitative prediction of gut-wall metabolism. As well as discussing the successes of current models for intestinal metabolism, the challenges in the establishment of good preclinical models are highlighted, including species differences in the isoforms; regional abundances and activities of drug metabolizing enzymes; the interplay of enzyme-transporter proteins; and lack of knowledge on enzyme abundances and availability of empirical scaling factors. Due to its broad specificity and high abundance in the intestine, CYP3A is the enzyme that is frequently implicated in human gut metabolism and is therefore the major focus of this review. A strategy to assess the impact of gut wall metabolism on oral bioavailability during drug discovery and early development phases is presented. Current gaps in the mechanistic understanding and the prediction of gut metabolism are highlighted, with suggestions on how they can be overcome in the future. PMID:26895020

  11. Gut Microbiota: A Modulator of Brain Plasticity and Cognitive Function in Ageing

    PubMed Central

    Leung, Katherine; Thuret, Sandrine

    2015-01-01

    Gut microbiota have recently been a topic of great interest in the field of microbiology, particularly their role in normal physiology and its influence on human health in disease. A large body of research has supported the presence of a pathway of communication between the gut and the brain, modulated by gut microbiota, giving rise to the term “microbiota-gut-brain” axis. It is now thought that, through this pathway, microbiota can affect behaviour and modulate brain plasticity and cognitive function in ageing. This review summarizes the evidence supporting the existence of such a connection and possible mechanisms of action whereby microbiota can influence the function of the central nervous system. Since normalisation of gut flora has been shown to prevent changes in behaviour, we further postulate on possible therapeutic targets to intervene with cognitive decline in ageing. The research poses various limitations, for example uncertainty about how this data translates to broad human populations. Nonetheless, the microbiota-gut-brain axis is an exciting field worthy of further investigation, particularly with regards to its implications on the ageing population. PMID:27417803

  12. Genomic Analysis of the Human Gut Microbiome Suggests Novel Enzymes Involved in Quinone Biosynthesis.

    PubMed

    Ravcheev, Dmitry A; Thiele, Ines

    2016-01-01

    Ubiquinone and menaquinone are membrane lipid-soluble carriers of electrons that are essential for cellular respiration. Eukaryotic cells can synthesize ubiquinone but not menaquinone, whereas prokaryotes can synthesize both quinones. So far, most of the human gut microbiome (HGM) studies have been based on metagenomic analysis. Here, we applied an analysis of individual HGM genomes to the identification of ubiquinone and menaquinone biosynthetic pathways. In our opinion, the shift from metagenomics to analysis of individual genomes is a pivotal milestone in investigation of bacterial communities, including the HGM. The key results of this study are as follows. (i) The distribution of the canonical pathways in the HGM genomes was consistent with previous reports and with the distribution of the quinone-dependent reductases for electron acceptors. (ii) The comparative genomics analysis identified four alternative forms of the previously known enzymes for quinone biosynthesis. (iii) Genes for the previously unknown part of the futalosine pathway were identified, and the corresponding biochemical reactions were proposed. We discuss the remaining gaps in the menaquinone and ubiquinone pathways in some of the microbes, which indicate the existence of further alternate genes or routes. Together, these findings provide further insight into the biosynthesis of quinones in bacteria and the physiology of the HGM. PMID:26904004

  13. 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

  14. Genomic Analysis of the Human Gut Microbiome Suggests Novel Enzymes Involved in Quinone Biosynthesis

    PubMed Central

    Ravcheev, Dmitry A.; Thiele, Ines

    2016-01-01

    Ubiquinone and menaquinone are membrane lipid-soluble carriers of electrons that are essential for cellular respiration. Eukaryotic cells can synthesize ubiquinone but not menaquinone, whereas prokaryotes can synthesize both quinones. So far, most of the human gut microbiome (HGM) studies have been based on metagenomic analysis. Here, we applied an analysis of individual HGM genomes to the identification of ubiquinone and menaquinone biosynthetic pathways. In our opinion, the shift from metagenomics to analysis of individual genomes is a pivotal milestone in investigation of bacterial communities, including the HGM. The key results of this study are as follows. (i) The distribution of the canonical pathways in the HGM genomes was consistent with previous reports and with the distribution of the quinone-dependent reductases for electron acceptors. (ii) The comparative genomics analysis identified four alternative forms of the previously known enzymes for quinone biosynthesis. (iii) Genes for the previously unknown part of the futalosine pathway were identified, and the corresponding biochemical reactions were proposed. We discuss the remaining gaps in the menaquinone and ubiquinone pathways in some of the microbes, which indicate the existence of further alternate genes or routes. Together, these findings provide further insight into the biosynthesis of quinones in bacteria and the physiology of the HGM. PMID:26904004

  15. Mining the human gut microbiota for effector strains that shape the immune system

    PubMed Central

    Ahern, Philip P.; Faith, Jeremiah J.; Gordon, Jeffrey I.

    2014-01-01

    Summary The gut microbiota co-develops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community-immune system co-regulation, and in order to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally-arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually-housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed. PMID:24950201

  16. Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron

    PubMed Central

    Saraf, Aakanksha; Martens, Eric C.; Dijkhuizen, Lubbert

    2015-01-01

    Probiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal species Bacteroides thetaiotaomicron efficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probiotic Lactobacillus reuteri strain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers. B. thetaiotaomicron metabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism in B. thetaiotaomicron and suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir for B. thetaiotaomicron nutrient acquisition in the gastrointestinal tract. PMID:25841008

  17. Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron.

    PubMed

    Lammerts van Bueren, Alicia; Saraf, Aakanksha; Martens, Eric C; Dijkhuizen, Lubbert

    2015-06-15

    Probiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal species Bacteroides thetaiotaomicron efficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probiotic Lactobacillus reuteri strain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers. B. thetaiotaomicron metabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism in B. thetaiotaomicron and suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir for B. thetaiotaomicron nutrient acquisition in the gastrointestinal tract. PMID:25841008

  18. "Lachnoclostridium bouchesdurhonense," a new bacterial species isolated from human gut microbiota.

    PubMed

    Amadou, T; Hosny, M; La Scola, B; Cassir, N

    2016-09-01

    We report the main characteristics of "Lachnoclostridium bouchesdurhonense" strain AT5(T) (=CSUR P2181), a new bacterial species isolated from the gut microbiota of an obese patient from Marseille. PMID:27493758

  19. 'Lachnoclostridium massiliosenegalense', a new bacterial species isolated from the human gut microbiota.

    PubMed

    Tidjani Alou, M; Lagier, J-C; La Scola, B; Cassir, N

    2016-11-01

    We report the main characteristics of 'Lachnoclostridium massiliosenegalense' strain mt23(T) (=CSUR P299 =DSM 102084), a new bacterial species isolated from the gut microbiota of a healthy young girl from Senegal. PMID:27595004

  20. Arsenic Metabolism by Human Gut Microbiota upon in Vitro Digestion of Contaminated Soils

    EPA Science Inventory

    Speciation analysis is essential when evaluating risks from, arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. Howeve...

  1. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species.

    PubMed

    Chatzidaki-Livanis, Maria; Geva-Zatorsky, Naama; Comstock, Laurie E

    2016-03-29

    Type VI secretion systems (T6SSs) are multiprotein complexes best studied in Gram-negative pathogens where they have been shown to inhibit or kill prokaryotic or eukaryotic cells and are often important for virulence. We recently showed that T6SS loci are also widespread in symbiotic human gut bacteria of the order Bacteroidales, and that these T6SS loci segregate into three distinct genetic architectures (GA). GA1 and GA2 loci are present on conserved integrative conjugative elements (ICE) and are transferred and shared among diverse human gut Bacteroidales species. GA3 loci are not contained on conserved ICE and are confined toBacteroides fragilis Unlike GA1 and GA2 T6SS loci, most GA3 loci do not encode identifiable effector and immunity proteins. Here, we studied GA3 T6SSs and show that they antagonize most human gut Bacteroidales strains analyzed, except forB. fragilisstrains with the same T6SS locus. A combination of mutation analyses,trans-protection analyses, and in vitro competition assays, allowed us to identify novel effector and immunity proteins of GA3 loci. These proteins are not orthologous to known proteins, do not contain identified motifs, and most have numerous predicted transmembrane domains. Because the genes encoding effector and immunity proteins are contained in two variable regions of GA3 loci, GA3 T6SSs of the speciesB. fragilisare likely the source of numerous novel effector and immunity proteins. Importantly, we show that the GA3 T6SS of strain 638R is functional in the mammalian gut and provides a competitive advantage to this organism. PMID:26951680

  2. [Metabolic therapy at the edge between human hosts and gut microbes].

    PubMed

    Blasco-Baque, V; Serino, M; Burcelin, R

    2013-01-01

    Personalized medicine is becoming day-after-day more urgent taking into account the great diversity characterizing patients affected by a given pathology, especially metabolic diseases. In fact, antidiabetic/obesity treatments have shown a reduced or no effect at all in some patients, representing a major challenge physicians have to face worldwide. Therefore, efforts have to be put to identify individual factors affecting our susceptibility towards a given medication. In that regard, gut microbiota may stand for the missing piece of the metabolic puzzle regulating host response, since its role in the induction of metabolic diseases has now been achieved. In fact, we firstly provided a bacterial explanation for the low-grade chronic inflammation featuring metabolic diseases, by showing the lipopolysaccharide as a trigger and risk factor of such pathologies. However, despite similar lineages of microbes characterize the gut of people, important differences still remain, which may be responsible for opposite effect of treatments such as pre- or probiotics, whose efficacy seems to be governed by the own gut microbiota of subjects. We have recently shown that gut microbiota is associated to the inclination to resist or not high-fat diet-induced type 2 diabetes in mice. In addition, the direct targeting of gut microbes by dietary fibers reversed the observed metabolic phenotype. These results, together with the literature, strongly suggest gut microbiota as a new target for the development of personalized metabolic therapy. PMID:23348854

  3. Molecular Dissection of Xyloglucan Recognition in a Prominent Human Gut Symbiont

    PubMed Central

    Tauzin, Alexandra S.; Kwiatkowski, Kurt J.; Orlovsky, Nicole I.; Smith, Christopher J.; Creagh, A. Louise; Haynes, Charles A.; Wawrzak, Zdzislaw

    2016-01-01

    ABSTRACT Polysaccharide utilization loci (PUL) within the genomes of resident human gut Bacteroidetes are central to the metabolism of the otherwise indigestible complex carbohydrates known as “dietary fiber.” However, functional characterization of PUL lags significantly behind sequencing efforts, which limits physiological understanding of the human-bacterial symbiosis. In particular, the molecular basis of complex polysaccharide recognition, an essential prerequisite to hydrolysis by cell surface glycosidases and subsequent metabolism, is generally poorly understood. Here, we present the biochemical, structural, and reverse genetic characterization of two unique cell surface glycan-binding proteins (SGBPs) encoded by a xyloglucan utilization locus (XyGUL) from Bacteroides ovatus, which are integral to growth on this key dietary vegetable polysaccharide. Biochemical analysis reveals that these outer membrane-anchored proteins are in fact exquisitely specific for the highly branched xyloglucan (XyG) polysaccharide. The crystal structure of SGBP-A, a SusD homolog, with a bound XyG tetradecasaccharide reveals an extended carbohydrate-binding platform that primarily relies on recognition of the β-glucan backbone. The unique, tetra-modular structure of SGBP-B is comprised of tandem Ig-like folds, with XyG binding mediated at the distal C-terminal domain. Despite displaying similar affinities for XyG, reverse-genetic analysis reveals that SGBP-B is only required for the efficient capture of smaller oligosaccharides, whereas the presence of SGBP-A is more critical than its carbohydrate-binding ability for growth on XyG. Together, these data demonstrate that SGBP-A and SGBP-B play complementary, specialized roles in carbohydrate capture by B. ovatus and elaborate a model of how vegetable xyloglucans are accessed by the Bacteroidetes. PMID:27118585

  4. Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction.

    PubMed

    Skosnik, Patrick D; Cortes-Briones, Jose A

    2016-08-01

    Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." PMID:27372861

  5. The Dynamics of the Human Infant Gut Microbiome in Development and in Progression towards Type 1 Diabetes

    PubMed Central

    Kostic, Aleksandar D.; Gevers, Dirk; Siljander, Heli; Vatanen, Tommi; Hyötyläinen, Tuulia; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Pöhö, Päivi; Mattila, Ismo; Lähdesmäki, Harri; Franzosa, Eric A.; Vaarala, Outi; de Goffau, Marcus; Harmsen, Hermie; Ilonen, Jorma; Virtanen, Suvi M.; Clish, Clary B.; Orešič, Matej; Huttenhower, Curtis; Knip, Mikael

    2015-01-01

    SUMMARY Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time-window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from non-progressors. PMID:25662751

  6. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes.

    PubMed

    Kostic, Aleksandar D; Gevers, Dirk; Siljander, Heli; Vatanen, Tommi; Hyötyläinen, Tuulia; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Pöhö, Päivi; Mattila, Ismo; Lähdesmäki, Harri; Franzosa, Eric A; Vaarala, Outi; de Goffau, Marcus; Harmsen, Hermie; Ilonen, Jorma; Virtanen, Suvi M; Clish, Clary B; Orešič, Matej; Huttenhower, Curtis; Knip, Mikael; Xavier, Ramnik J

    2015-02-11

    Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors. PMID:25662751

  7. The effect of pomegranate (Punica granatum L.) byproducts and ellagitannins on the growth of human gut bacteria.

    PubMed

    Bialonska, Dobroslawa; Kasimsetty, Sashi G; Schrader, Kevin K; Ferreira, Daneel

    2009-09-23

    The consumption of pomegranate products leads to a significant accumulation of ellagitannins in the large intestines, where they interact with complex gut microflora. This study investigated the effect of pomegranate tannin constituents on the growth of various species of human gut bacteria. Our results showed that pomegranate byproducts and punicalagins inhibited the growth of pathogenic clostridia and Staphyloccocus aureus. Probiotic lactobacilli and bifidobacteria were generally not affected by ellagitannins, while relatively small growth inhibition by ellagic acid likely resulted from decreasing media quality due to the formation of tannin-protein complexes. The effect of pomegranate ellagitannins on bifidobacteria was species- and tannin-dependent. The growth of Bifidobacterium animalis ssp. lactis was slightly inhibited by punicalagins, punicalins, and ellagic acid. POMx supplementation significantly enhanced the growth of Bifidobacterium breve and Bifidobacterium infantis. PMID:19705832

  8. The Extended Nutrigenomics – Understanding the Interplay between the Genomes of Food, Gut Microbes, and Human Host

    PubMed Central

    Kussmann, Martin; Van Bladeren, Peter J.

    2011-01-01

    Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well as specific bioactives, with those genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex ecosystem in the intestine with profound impact on host metabolism. It is being studied at genomic and, more recently, also at proteomic and metabonomic level. Humans are being characterized at the level of genetic pre-disposition and inter-individual variability in terms of (i) response to nutritional interventions and direction of health trajectories; (ii) epigenetic, metabolic programming at certain life stages with health consequences later in life and even for subsequent generations; and (iii) acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level. Modern nutrition science explores health-related aspects of bioactive food components, thereby promoting health, preventing, or delaying the onset of disease, optimizing performance and assessing benefits and risks in individuals and subpopulations. Personalized nutrition means adapting food to individual needs, depending on the human host’s life stage, -style, and -situation. Traditionally, nutrigenomics and nutri(epi)genetics are seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, namely the food, the gut microbial and the human host’s genome, and calls for an “extended nutrigenomics” approach in order to build the future tools for personalized nutrition, health maintenance, and disease prevention. We discuss examples of these genomes

  9. Correlation network analysis reveals relationships between diet-induced changes in human gut microbiota and metabolic health

    PubMed Central

    Kelder, T; Stroeve, J H M; Bijlsma, S; Radonjic, M; Roeselers, G

    2014-01-01

    Background: Recent evidence suggests that the gut microbiota plays an important role in human metabolism and energy homeostasis and is therefore a relevant factor in the assessment of metabolic health and flexibility. Understanding of these host–microbiome interactions aids the design of nutritional strategies that act via modulation of the microbiota. Nevertheless, relating gut microbiota composition to host health states remains challenging because of the sheer complexity of these ecosystems and the large degrees of interindividual variation in human microbiota composition. Methods: We assessed fecal microbiota composition and host response patterns of metabolic and inflammatory markers in 10 apparently healthy men subjected to a high-fat high-caloric diet (HFHC, 1300 kcal/day extra) for 4 weeks. DNA was isolated from stool and barcoded 16S rRNA gene amplicons were sequenced. Metabolic health parameters, including anthropomorphic and blood parameters, where determined at t=0 and t=4 weeks. Results: A correlation network approach revealed diet-induced changes in Bacteroides levels related to changes in carbohydrate oxidation rates, whereas the change in Firmicutes correlates with changes in fat oxidation. These results were confirmed by multivariate models. We identified correlations between microbial diversity indices and several inflammation-related host parameters that suggest a relation between diet-induced changes in gut microbiota diversity and inflammatory processes. Conclusions: This approach allowed us to identify significant correlations between abundances of microbial taxa and diet-induced shifts in several metabolic health parameters. Constructed correlation networks provide an overview of these relations, revealing groups of correlations that are of particular interest for explaining host health aspects through changes in the gut microbiota. PMID:24979151

  10. Prebiotic Potential of a Maize-Based Soluble Fibre and Impact of Dose on the Human Gut Microbiota

    PubMed Central

    Costabile, Adele; Deaville, Eddie R.; Morales, Agustin Martin; Gibson, Glenn R.

    2016-01-01

    Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12g and 18g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention. PMID:26731113

  11. Prebiotic Potential of a Maize-Based Soluble Fibre and Impact of Dose on the Human Gut Microbiota.

    PubMed

    Costabile, Adele; Deaville, Eddie R; Morales, Agustin Martin; Gibson, Glenn R

    2016-01-01

    Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12 g and 18 g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention. PMID:26731113

  12. The gut is the epicentre of antibiotic resistance

    PubMed Central

    2012-01-01

    The gut contains very large numbers of bacteria. Changes in the composition of the gut flora, due in particular to antibiotics, can happen silently, leading to the selection of highly resistant bacteria and Candida species. These resistant organisms may remain for months in the gut of the carrier without causing any symptoms or translocate through the gut epithelium, induce healthcare-associated infections, undergo cross-transmission to other individuals, and cause limited outbreaks. Techniques are available to prevent, detect, and treat the carriage of resistant organisms in the gut. However, evidence on these techniques is scant, the only exception being selective digestive decontamination (SDD), which has been extensively studied in neutropenic and ICU patients. After the destruction of resistant colonizing bacteria, which has been successfully obtained in several studies, the gut could be re-colonized with normal faecal flora or probiotics. Studies are warranted to evaluate this concept. PMID:23181506

  13. Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut.

    PubMed

    Selma, María V; Tomás-Barberán, Francisco A; Beltrán, David; García-Villalba, Rocio; Espín, Juan C

    2014-07-01

    Urolithins are dibenzopyranone metabolites that exert anti-inflammatory activity in vivo and are produced by the gut microbiota from the dietary polyphenols ellagic acid (EA) and ellagitannins. However, the bacteria involved in this process remain unknown. We report here a novel bacterium, strain CEBAS 1/15P(T), capable of metabolizing EA to urolithins, that was isolated from healthy human faeces and characterized by determining phenotypic, biochemical and molecular methods. The strain was related to Gordonibacter pamelaeae 7-10-1-b(T), the type and only reported strain of the only species of the genus Gordonibacter, with about 97% 16S rRNA gene sequence similarity; they were both obligately anaerobic, non-spore-forming, Gram-stain-positive, short-rods/coccobacilli and metabolized only small numbers of carbon sources. L-Fucose, D-fructose, turanose, D-galacturonic acid and α-ketobutyric acid were metabolized by strain CEBAS 1/15P(T), while G. pamelaeae was negative for metabolism of these compounds. The whole-cell fatty acids consisted predominantly of saturated fatty acids (70%); strain CEBAS 1/15P(T) differed significantly from G. pamelaeae in the major fatty acid, which was C18 : 1ω9c, while anteiso-C15 : 0 was the major component for G. pamelaeae. The presence of a number of different fatty acid peaks, especially C19 : 0 cyclo and C18 : 1ω6c, was also indicative of distinct species. Six glycolipids (GL1-6) were recognized, while, in G. pamelaeae, only four glycolipids were described. On the basis of these data, the novel species Gordonibacter urolithinfaciens sp. nov. is described, with strain CEBAS 1/15P(T) ( = DSM 27213(T) = CCUG 64261(T)) as the type strain. PMID:24744017

  14. The Complex Exogenous RNA Spectra in Human Plasma: An Interface with Human Gut Biota?

    PubMed Central

    Wang, Kai; Li, Hong; Yuan, Yue; Etheridge, Alton; Zhou, Yong; Huang, David; Wilmes, Paul; Galas, David

    2012-01-01

    Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health. PMID:23251414

  15. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences

    PubMed Central

    Wagner Mackenzie, Brett; Waite, David W.; Taylor, Michael W.

    2015-01-01

    The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates. PMID:25741335

  16. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.

    PubMed

    Wagner Mackenzie, Brett; Waite, David W; Taylor, Michael W

    2015-01-01

    The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates. PMID:25741335

  17. Going viral: next generation sequencing applied to human gut phage populations

    PubMed Central

    Reyes, Alejandro; Semenkovich, Nicholas P.; Whiteson, Katrine; Rohwer, Forest; Gordon, Jeffrey I.

    2013-01-01

    Over the past decade researchers have begun to characterize viral diversity using metagenomic methods. These studies have shown that viruses, the majority of which infect bacteria (bacteriophages), are likely the most genetically diverse components of the biosphere. Here we briefly review the incipient rise of a phage biology renaissance catalyzed by recent advances in next generation sequencing. We explore how work characterizing phage diversity and their lifestyles in the gut is changing our view of ourselves as supra-organisms. Finally, we discuss how a new appreciation of phage dynamics may yield new applications for phage therapies designed to manipulate the structure and functions of our gut microbiomes. PMID:22864264

  18. Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool.

    PubMed

    Gorzelak, Monika A; Gill, Sandeep K; Tasnim, Nishat; Ahmadi-Vand, Zahra; Jay, Michael; Gibson, Deanna L

    2015-01-01

    Gut microbiome community analysis is used to understand many diseases like inflammatory bowel disease, obesity, and diabetes. Sampling methods are an important consideration for human microbiome research, yet are not emphasized in many studies. In this study, we demonstrate that the preparation, handling, and storage of human faeces are critical processes that alter the outcomes of downstream DNA-based bacterial community analyses via qPCR. We found that stool subsampling resulted in large variability of gut microbiome data due to different microenvironments harbouring various taxa within an individual stool. However, we reduced intra-sample variability by homogenizing the entire stool sample in liquid nitrogen and subsampling from the resulting crushed powder prior to DNA extraction. We experimentally determined that the bacterial taxa varied with room temperature storage beyond 15 minutes and beyond three days storage in a domestic frost-free freezer. While freeze thawing only had an effect on bacterial taxa abundance beyond four cycles, the use of samples stored in RNAlater should be avoided as overall DNA yields were reduced as well as the detection of bacterial taxa. Overall we provide solutions for processing and storing human stool samples that reduce variability of microbiome data. We recommend that stool is frozen within 15 minutes of being defecated, stored in a domestic frost-free freezer for less than three days, and homogenized prior to DNA extraction. Adoption of these simple protocols will have a significant and positive impact on future human microbiome research. PMID:26252519

  19. Arsenic Metabolism by Human Gut Microbiota upon In Vitro Digestion of Contaminated Soils

    EPA Science Inventory

    Background: Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with ...

  20. Impact of the gut microbiota on rodent models of human disease

    PubMed Central

    Hansen, Axel Kornerup; Friis Hansen, Camilla Hartmann; Krych, Lukasz; Nielsen, Dennis Sandris

    2014-01-01

    Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 1014 organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gut microbiota. Correlation studies may for some diseases show correlation between gut microbiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation. PMID:25548471

  1. 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

  2. Christensenella timonensis, a new bacterial species isolated from the human gut.

    PubMed

    Ndongo, S; Dubourg, G; Khelaifia, S; Fournier, P-E; Raoult, D

    2016-09-01

    We propose a new species, Christensenella timonensis, strain Marseille-P2437(T) (CSUR P2437(T)), which was isolated from gut microbiota of a 66-year-old patient as a part of culturomics study. C. timonensis represents the second species isolated within the Christensenella genus. PMID:27408737

  3. Vegetable microbiomes: is there a connection among opportunistic infections, human health and our ‘gut feeling'?

    PubMed Central

    Berg, Gabriele; Erlacher, Armin; Smalla, Kornelia; Krause, Robert

    2014-01-01

    The highly diverse microbiomes of vegetables are reservoirs for opportunistic and emerging pathogens. In recent years, an increased consumption, larger scale production and more efficient distribution of vegetables together with an increased number of immunocompromised individuals resulted in an enhanced number of documented outbreaks of human infections associated with the consumption of vegetables. Here we discuss the occurrence of potential pathogens in vegetable microbiomes, the impact of farming and processing practices, and plant and human health issues. Based on these results, we discuss the question if vegetables can serve as a source of infection for immunocompromised individuals as well as possible solutions to avoid outbreaks. Moreover, the potentially positive aspects of the vegetables microbiome for the gut microbiota and human health are presented. PMID:25186140

  4. Bacillus rubiinfantis sp. nov. strain mt2T, a new bacterial species isolated from human gut

    PubMed Central

    Tidjiani Alou, M.; Rathored, J.; Khelaifia, S.; Michelle, C.; Brah, S.; Diallo, B.A.; Raoult, D.; Lagier, J.-C.

    2015-01-01

    Bacillus rubiinfantis sp. nov. strain mt2T is the type strain of B. rubiinfantis sp. nov., isolated from the fecal flora of a child with kwashiorkor in Niger. It is Gram-positive facultative anaerobic rod belonging to the Bacillaceae family. We describe the features of this organism alongside the complete genome sequence and annotation. The 4 311 083 bp long genome (one chromosome but no plasmid) contains 4028 protein-coding gene and 121 RNA genes including nine rRNA genes. PMID:27076912

  5. Bacillus niameyensis sp. nov., a new bacterial species isolated from human gut

    PubMed Central

    Tidjani Alou, M.; Rathored, J.; Traore, S.I.; Khelaifia, S.; Michelle, C.; Brah, S.; Diallo, B.A.; Raoult, D.; Lagier, J.-C.

    2015-01-01

    Bacillus niameyensis sp. nov. strain SIT3T (= CSUR P1266 = DSM 29725) is the type strain of B. niameyensis sp. nov. This Gram-positive strain was isolated from the digestive flora of a child with kwashiorkor and is a facultative anaerobic rod and a member of the Bacillaceae family. This organism is hereby described alongside its complete genome sequence and annotation. The 4  286  116 bp long genome (one chromosome but no plasmid) contains 4130 protein-coding and 66 RNA genes including five rRNA genes. PMID:27076913

  6. Impact of demographics on human gut microbial diversity in a US Midwest population

    PubMed Central

    Chen, Jun; Ryu, Euijung; Hathcock, Matthew; Ballman, Karla; Chia, Nicholas; Olson, Janet E

    2016-01-01

    The clinical utility of microbiome biomarkers depends on the reliable and reproducible nature of comparative results. Underappreciation of the variation associated with common demographic, health, and behavioral factors may confound associations of interest and generate false positives. Here, we present the Midwestern Reference Panel (MWRP), a resource for comparative gut microbiome studies conducted in the Midwestern United States. We analyzed the relationships between demographic and health behavior-related factors and the microbiota in this cohort, and estimated their effect sizes. Most variables investigated were associated with the gut microbiota. Specifically, body mass index (BMI), race, sex, and alcohol use were significantly associated with microbial β-diversity (P < 0.05, unweighted UniFrac). BMI, race and alcohol use were also significantly associated with microbial α-diversity (P < 0.05, species richness). Tobacco use showed a trend toward association with the microbiota (P < 0.1, unweighted UniFrac). The effect sizes of the associations, as quantified by adjusted R2 values based on unweighted UniFrac distances, were small (< 1% for all variables), indicating that these factors explain only a small percentage of overall microbiota variability. Nevertheless, the significant associations between these variables and the gut microbiota suggest that they could still be potential confounders in comparative studies and that controlling for these variables in study design, which is the main objective of the MWRP, is important for increasing reproducibility in comparative microbiome studies. PMID:26839739

  7. Suppression of inflammation by helminths: a role for the gut microbiota?

    PubMed Central

    Giacomin, Paul; Croese, John; Krause, Lutz; Loukas, Alex; Cantacessi, Cinzia

    2015-01-01

    Multiple recent investigations have highlighted the promise of helminth-based therapies for the treatment of inflammatory disorders of the intestinal tract of humans, including inflammatory bowel disease and coeliac disease. However, the mechanisms by which helminths regulate immune responses, leading to the amelioration of symptoms of chronic inflammation are unknown. Given the pivotal roles of the intestinal microbiota in the pathogenesis of these disorders, it has been hypothesized that helminth-induced modifications of the gut commensal flora may be responsible for the therapeutic properties of gastrointestinal parasites. In this article, we review recent progress in the elucidation of host–parasite–microbiota interactions in both animal models of chronic inflammation and humans, and provide a working hypothesis of the role of the gut microbiota in helminth-induced suppression of inflammation. PMID:26150662

  8. Prevention and treatment of hepatic encephalopathy: focusing on gut microbiota.

    PubMed

    Garcovich, Matteo; Zocco, Maria Assunta; Roccarina, Davide; Ponziani, Francesca Romana; Gasbarrini, Antonio

    2012-12-14

    The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation. PMID:23239905

  9. Prebiotic inulin: Useful dietary adjuncts to manipulate the livestock gut microflora

    PubMed Central

    Samanta, A.K.; Jayapal, Natasha; Senani, S.; Kolte, A.P.; Sridhar, Manpal

    2013-01-01

    In recent years, there has been a growing appreciation on the relevance of gastrointestinal microflora in both ruminants and non-ruminants owing to revelation of their role in several physiological functions including digestion, nutrient utilization, pathogen exclusion, gastrointestinal development, immunity system, gut gene expression and quality of animal products. The ban imposed on the use of antibiotics and hormones in feed has compelled animal researchers in finding an alternative which could overcome the issues of conventional feed additives. Though the concept of prebiotic was evolved keeping in mind the gastrointestinal flora of human beings, presently animal researchers are exploring the efficiency of prebiotic (inulin) for modulating the gut ecosystem of both ruminants and non-ruminants. It was revealed that prebiotic inulin is found to exhibit desirable changes in the gut of non-ruminants like poultry, swine, rabbit etc for augmenting gut health and improvement of product quality. Similarly, in ruminants the prebiotic reduces rumen ammonia nitrogen, methane production, increase microbial protein synthesis and live weight gains in calves. Unlike other feed additives, prebiotic exhibits its effect in multipronged ways for overall increase in the performances of the animals. In coming days, it is expected that prebiotics could be the part of diets in both ruminants and non-ruminants for enabling modulation of gut microflora vis a vis animals productivity in ecological ways. PMID:24159277

  10. big bang gene modulates gut immune tolerance in Drosophila.

    PubMed

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

    2013-02-19

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases. PMID:23378635

  11. Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

    PubMed Central

    Schjørring, Susanne; Krogfelt, Karen A.

    2011-01-01

    We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes. The increased use of fermented food products and probiotics, as food supplements and health promoting products containing massive amounts of bacteria acting as either donors and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic resistance gene transfer occurring in the gut. PMID:21318188

  12. Phlogistic properties of peptidoglycan-polysaccharide polymers from cell walls of pathogenic and normal-flora bacteria which colonize humans.

    PubMed Central

    Schwab, J H

    1993-01-01

    PG-PS polymers which can induce experimental chronic inflammation in joints and other tissues can be isolated from the cell walls of human pathogens, such as group A streptococci, as well as from certain indigenous bacterial species which colonize the human intestinal tract. The structural and biological properties that are required for cell wall fragments to express this remarkable activity are still not well defined, but polymer size, resistance to tissue enzymes, and capacity to sustain activation of complement, macrophages, neutrophils, and T cells are properties associated with the most active preparations. There is increasing evidence that PG-PS structures with arthropathogenic activity occur in the human intestinal lumen and that these polymers can be translocated systemically. These observations support the concept that PG-PS, derived from a variety of bacterial species, can be part of the etiology of rheumatoid arthritis and other chronic inflammatory diseases. Since the PG component provides a common element to which all individuals are exposed, it follows that susceptibility is related to efficiency of disposal of bacterial cell wall debris, as well as to cytokine networks and immune cell function (51). PMID:8406849

  13. High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity.

    PubMed

    Yang, Xingdong; Twitchell, Erica; Li, Guohua; Wen, Ke; Weiss, Mariah; Kocher, Jacob; Lei, Shaohua; Ramesh, Ashwin; Ryan, Elizabeth P; Yuan, Lijuan

    2015-01-01

    Previously, we showed that rice bran (RB) was able to reduce human rotavirus (HRV) diarrhea in gnotobiotic pigs. Here, we investigated its effect on the growth of diarrhea-reducing probiotic Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle (EcN), and the resulting effects on HRV diarrhea, gut epithelial health, permeability and innate immune responses during virulent HRV challenge. On 3, 5, and 7 days of age pigs were inoculated with 2 × 10(4) colony-forming-units LGG+EcN to initiate colonization. Daily RB supplementation (replacing 10% calorie intake) was started at 5 days of age and continued until euthanasia. A subset of pigs in each group was challenged orally with 10(5) focus-forming-units of virulent HRV at 33 days of age. RB completely prevented HRV diarrhea in LGG+EcN colonized pigs. RB significantly promoted the growth of both probiotic strains in the gut (~5 logs) and increased the body-weight-gain at 4-5 weeks of age compared to non-RB group. After HRV challenge, RB-fed pigs had significantly lower ileal mitotic index and villus width, and significantly increased intestinal IFN-γ and total IgA levels compared to non-RB group. Therefore, RB plus LGG+EcN colonization may represent a highly effective therapeutic approach against HRV and potentially a variety of other diarrhea-inducing enteric pathogens. PMID:26459937

  14. High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity

    PubMed Central

    Yang, Xingdong; Twitchell, Erica; Li, Guohua; Wen, Ke; Weiss, Mariah; Kocher, Jacob; Lei, Shaohua; Ramesh, Ashwin; Ryan, Elizabeth P.; Yuan, Lijuan

    2015-01-01

    Previously, we showed that rice bran (RB) was able to reduce human rotavirus (HRV) diarrhea in gnotobiotic pigs. Here, we investigated its effect on the growth of diarrhea-reducing probiotic Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle (EcN), and the resulting effects on HRV diarrhea, gut epithelial health, permeability and innate immune responses during virulent HRV challenge. On 3, 5, and 7 days of age pigs were inoculated with 2 × 104 colony-forming-units LGG+EcN to initiate colonization. Daily RB supplementation (replacing 10% calorie intake) was started at 5 days of age and continued until euthanasia. A subset of pigs in each group was challenged orally with 105 focus-forming-units of virulent HRV at 33 days of age. RB completely prevented HRV diarrhea in LGG+EcN colonized pigs. RB significantly promoted the growth of both probiotic strains in the gut (~5 logs) and increased the body-weight-gain at 4–5 weeks of age compared to non-RB group. After HRV challenge, RB-fed pigs had significantly lower ileal mitotic index and villus width, and significantly increased intestinal IFN-γ and total IgA levels compared to non-RB group. Therefore, RB plus LGG+EcN colonization may represent a highly effective therapeutic approach against HRV and potentially a variety of other diarrhea-inducing enteric pathogens. PMID:26459937

  15. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

    PubMed Central

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-01

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID:26819512

  16. Complete Genome Sequence of Clostridium septicum Strain CSUR P1044, Isolated from the Human Gut Microbiota.

    PubMed

    Benamar, Samia; Cassir, Nadim; Caputo, Aurélia; Cadoret, Frédéric; La Scola, Bernard

    2016-01-01

    Clostridium septicum is one of the first pathogenic anaerobes to be identified. Here, we announce the genome draft sequence of C. septicum strain CSUR P1044 isolated from the gut of a healthy adult. Its chromosome genome consists of 3.2 Mbp with a plasmid of 32 Kbp. C. septicum strain CSUR P1044 has a G+C content of 27.5%, and is composed of 3,125 protein-coding genes together with 103 RNA genes, including 22 rRNA genes. PMID:27609912

  17. Massilibacterium senegalense gen. nov., sp. nov., a new bacterial genus isolated from the human gut

    PubMed Central

    Tidjani Alou, M.; Rathored, J.; Lagier, J.-C.; Khelaifia, S.; Labas, N.; Sokhna, C.; Diallo, A.; Raoult, D.; Dubourg, G.

    2016-01-01

    Massilibacterium senegalense gen. nov., sp. nov., strain mt8T, is the type strain of Massilibacterium gen. nov., a new genus within the Bacillaceae family. This Gram-negative facultative anaerobic rod was isolated from the gut microbiota of a severely malnourished boy. Its phenotypic description is hereby presented with a complete annotation of its genome sequence. This genome is 5 697 950 bp long and contains 5615 protein-coding genes and 178 RNA genes, among which are 40 rRNA genes. PMID:26933503

  18. Bacterial flora as a cause or treatment of chronic diarrhea.

    PubMed

    Scaldaferri, Franco; Pizzoferrato, Marco; Pecere, Silvia; Forte, Fabrizio; Gasbarrini, Antonio

    2012-09-01

    Intestinal microflora can be considered an organ of the body. It has several functions in the human gut, mostly metabolic and immunologic, and constantly interacts with the intestinal mucosa in a delicate equilibrium. Chronic diarrhea is associated with an alteration of gut microbiota when a pathogen invades the gut and also in several conditions associated with intestinal mucosal damage or bowel dysfunction, as in inflammatory bowel disease, irritable bowel syndrome, or small bowel bacterial overgrowth. This article discusses the basis of gut microbiota modulation. Evidence for the efficacy of gut microbiota modulation in chronic conditions is also discussed. PMID:22917165

  19. Obesity and the gut microbiota.

    PubMed

    Flint, Harry J

    2011-11-01

    Gut microorganisms have the potential to influence weight gain and fat deposition through a variety of mechanisms. One factor is the ability of microorganisms in the large intestine to release energy by fermenting otherwise indigestible components of the diet ("energy harvest"). This energy becomes available to the host indirectly through the absorption of microbially produced short-chain fatty acids. Energy recovery from fiber will be largely determined by dietary intake and gut transit, but can also depend on the makeup of the gut microbiota. The species composition of the gut microbiota changes with diet composition, as has been shown in studies with obese individuals after reduced carbohydrate weight loss diets, or diets containing different nondigestible carbohydrates. There is conflicting evidence, however, on the extent to which gut microbiota composition differs between obese and nonobese humans. In contrast, there is increasing evidence to suggest that gut microorganisms and their metabolic products can influence gut hormones, inflammation, and gut motility. Any changes in gut microbiota composition that influence energy expenditure, satiety, and food intake have the potential to alter weight gain and weight loss, but a better understanding of the impact of different members of the gut microbial community upon host physiology is needed to establish these relationships. PMID:21992951

  20. Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes

    PubMed Central

    Zhang, Meiling; Chekan, Jonathan R.; Dodd, Dylan; Hong, Pei-Ying; Radlinski, Lauren; Revindran, Vanessa; Nair, Satish K.; Mackie, Roderick I.; Cann, Isaac

    2014-01-01

    Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose-configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 Å), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 Å), and the CBM from its homolog in the Prevotella bryantii B14 Xyn10C (1.68 Å) reveal an unanticipated mode for ligand binding. A minimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health. PMID:25136124

  1. 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

  2. Superantigen properties of a human sialoprotein involved in gut-associated immunity.

    PubMed Central

    Silverman, G J; Roben, P; Bouvet, J P; Sasano, M

    1995-01-01

    Protein Fv (pFv) is a recently described 175-kD gut-associated sialoprotein with a potent capacity for augmentation of antibody-dependent immune functions. To investigate the molecular basis for Fab-mediated binding of pFv, we evaluated a panel of 52 monoclonal IgM and found that approximately 40% bound pFv. Whereas the majority (> or = 75%) of V H3 and V H6 IgM strongly bound pFv, only a small minority (< 20%) of IgM from other V H families bound pFv, and these antibodies had weaker binding interactions. Inhibition studies suggested that all binding occurred at the same (or overlapping) site(s) on pFv. Surface plasmon resonance studies demonstrated binding affinity constants up to 6.7 x 10(8) M-1 for pFv. Biopanning of IgM and IgG Fab phage-display libraries with pFv preferentially selected for V H3 and V H6 antibodies, but also obtained certain V H4 IgM. V H sequence analyses of 36 pFv-binding antibodies revealed that binding did not correlate with CDR sequence, JH, or L chain usage. However, there was preferential selection of pFv binders with V H CDR3 of small size. These studies demonstrate that a protein which enhances immune defense in the gut has structural and functional properties similar to known superantigens. PMID:7615813

  3. Enrichment or depletion? The impact of stool pretreatment on metaproteomic characterization of the human gut microbiota.

    PubMed

    Tanca, Alessandro; Palomba, Antonio; Pisanu, Salvatore; Addis, Maria Filippa; Uzzau, Sergio

    2015-10-01

    To date, most metaproteomic studies of the gut microbiota employ stool sample pretreatment methods to enrich for microbial components. However, a specific investigation aimed at assessing if, how, and to what extent this may impact on the final taxonomic and functional results is still lacking. Here, stool replicates were either pretreated by differential centrifugation (DC) or not centrifuged. Protein extracts were then processed by filter-aided sample preparation, single-run LC, and high-resolution MS, and the metaproteomic data were compared by spectral counting. DC led to a higher number of identifications, a significantly richer microbial diversity, as well as to reduced information on the nonmicrobial components (host and food) when compared to not centrifuged. Nevertheless, dramatic differences in the relative abundance of several gut microbial taxa were also observed, including a significant change in the Firmicutes/Bacteroidetes ratio. Furthermore, some important microbial functional categories, including cell surface enzymes, membrane-associated proteins, extracellular proteins, and flagella, were significantly reduced after DC. In conclusion, this work underlines that a critical evaluation is needed when selecting the appropriate stool sample processing protocol in the context of a metaproteomic study, depending on the specific target to which the research is aimed. All MS data have been deposited in the ProteomeXchange with identifier PXD001573 (http://proteomecentral.proteomexchange.org/dataset/PXD001573). PMID:25677681

  4. 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

  5. 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

  6. The host and the flora.

    PubMed

    Nuding, S; Antoni, L; Stange, E F

    2013-01-01

    To prevent bacterial overgrowth, colonization of the epithelium and subsequent translocation, the gastrointestinal tract maintains an effective mucosal barrier. Besides mucus the most important components of this protective system are epithelial antimicrobial peptides such as defensins, the cathelicidin LL-37, lysozyme, phospholipase A, and proteins with additional antimicrobial properties such as ubiquicidin, ribosomal proteins or histones. Commensal species may tolerate intestinal antimicrobial peptides, for example Bacteroides ssp. or Parabacteroides ssp. as major species in the human colon were highly resistant to the constitutive defensin HBD-1 and only susceptible to the inducible defensin HBD-3. Reduction of disulfide bonds is an important mechanism activating HBD-1. As several studies show, alterations in the expression of antimicrobial peptides directly influence the composition of the intestinal flora. Correspondingly, an increased production of defensins or inhibition of the processing of mouse defensins to their active form led to a quantitative shift of luminal and mucosal bacterial species. On the other hand, microorganisms also modulate the synthesis of host defensins by induction or inhibition of specific peptides. Lactobacilli, the probiotic strain Escherichia coli Nissle and Salmonella enteritica stimulate HBD-2 expression, whereas Shigella flexneri downregulates the synthesis of HBD-1, HBD-3 and LL-37. Thus, the proper balance between the luminal flora and the mucosa is a permanently dynamic, sensitive and host-specific relationship. PMID:24246976

  7. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  8. New medium for isolating propionibacteria and its application to assay of normal flora of human facial skin.

    PubMed Central

    Kishishita, M; Ushijima, T; Ozaki, Y; Ito, Y

    1980-01-01

    The conditions for isolation and cultivation of Propionibacterium acnes and related propionibacteria were studied in detail. Triton X-100 added to the diluent inhibited the growth of propionibacteria in concentrations of 0.05 to 0.1%. However, such was not the case with Tween 80; rather, growth of the bacteria was further enhanced by this agent. Consequently, Tween 80 was considered to be a suitable surfactant for addition to the diluent for isolation of propionibacteria. A new medium for isolating propionibacteria from human skin was developed. Comparative studies with colonies of P. acnes, Propionibacterium granulosum, and Staphylococcus epidermidis showed morphological differences among the colonies; thus, the medium was very useful for differentiating and identifying species of the microbes. The new medium was used for studies on the distribution of propionibacteria on the foreheads of 30 Japanese volunteers. Among 447 strains of P. acnes and 86 strains of P. granulosum isolated from the volunteers, all strains of the former were positive for indole, nitrate, milk, and gelatin hydrolysis, whereas all strains of the latter were negative for all of the tests. Images PMID:7470244

  9. Modulation of gut microbiota downregulates the development of food allergy in infancy.

    PubMed

    Tsabouri, S; Priftis, K N; Chaliasos, N; Siamopoulou, A

    2014-01-01

    In humans, microbial colonisation of the intestine begins just after birth. However, development of the normal flora is a gradual process, which is initially determined by factors such as genetic aspects, the maternal-foetal interaction, place and mode of delivery, early feedings strategies, and the use of antibiotics. Current knowledge on the significance and impact of the gut microflora on the development of the gut immune system indicates that a close relationship between allergic sensitisation and the development of the intestinal microflora may occur in infancy. Intestinal micro-organisms could downregulate the allergic inflammation by counterbalancing type 2 T-helper cell responses and by enhancing allergen exclusion through an immunological response. PMID:23827644

  10. The development of bacterial flora of premature neonates.

    PubMed Central

    Rotimi, V. O.; Olowe, S. A.; Ahmed, I.

    1985-01-01

    The sequential acquisition of bacterial flora by premature neonates was studied during a 10 month period. Mean gestational age of the babies was 29.01 weeks and the mean birth weight was 1.728 kg. Escherichia coli and group B streptococci (GBS) colonized the umbilicus of 7 and 6 babies respectively, out of 23 studied, on the first day of life. E. coli and staphylococci were the predominant flora on the 6th day and they colonized 12 and 13 respectively. The oral flora was predominantly Gram-positive cocci, mainly Streptococcus salivarius which was isolated from 17 out of 22 babies on the 6th day, viridans streptococci were isolated from 14 babies, Staphylococcus albus from 16 babies and group D streptococci from 11 babies. Candida spp. also colonized the oral cavities of 17 out of 22 babies on the 6th day. At the end of the first week of life, the faecal flora was predominantly anaerobic represented by Bifidobacterium spp., Bacteroides spp. and Clostridium spp. The commonest facultative faecal flora were E. coli, which was isolated from all the babies, and Strept. faecalis isolated from 20 babies. Early gut colonization by GBS, Bacteroides spp. and Clostridium spp. was noticed in more babies delivered vaginally than by caesarean section where colonization by these bacteria was relatively delayed. The use of prophylactic penicillin plus gentamicin in the special neonatal unit probably prevented systemic spread of any of the potential opportunistic pathogens during the study. PMID:3891849

  11. The gut microbiota, obesity and insulin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

  12. Immunological functions of the gut in relation to nutritional state and mode of delivery of nutrients.

    PubMed Central

    Ferguson, A

    1994-01-01

    Gut immunology encompasses the need for local cellular immunity and prevention of systemic immune reactions to dietary antigens. The relation between these factors and nutritional state or the presence of luminal nutrients in the enterally fed and parenterally fed is poorly defined. Most studies suggest that acquisition of lymphoid characteristics is independent of luminal nutrition and its responsiveness is related more to bacterial challenge. Protein malnutrition may impair immune responsiveness by moderating the generalised inflammatory response, rather than through reduced T cell function and IgA synthesis. Predisposition to the development of gut hypersensitivity can be induced in animals by longterm feeding with elemental diets. The efficient absorption of these diets reduces the caecal microflora burden and together with changed gastric acid secretion and small bowel motility, may affect the composition of the gut flora. Changed luminal nutrition, enhanced tissue damage and inappropriately increased mucosal T cell function may thus be related. The clinical effectiveness, however, of elemental diets in treatment of unresponsive coeliac disease is reassuring. To investigate intestinal immunity in humans, an approach based on whole gut lavage has been developed. Data from this non-invasive human technique will prove to be a useful means of assessing the effects of nutritional rehabilitation on mucosal immunity. PMID:8125382

  13. Impact of increasing fruit and vegetables and flavonoid intake on the human gut microbiota.

    PubMed

    Klinder, Annett; Shen, Qing; Heppel, Susanne; Lovegrove, Julie A; Rowland, Ian; Tuohy, Kieran M

    2016-04-01

    Epidemiological studies have shown protective effects of fruits and vegetables (F&V) in lowering the risk of developing cardiovascular diseases (CVD) and cancers. Plant-derived dietary fibre (non-digestible polysaccharides) and/or flavonoids may mediate the observed protective effects particularly through their interaction with the gut microbiota. The aim of this study was to assess the impact of fruit and vegetable (F&V) intake on gut microbiota, with an emphasis on the role of flavonoids, and further to explore relationships between microbiota and factors associated with CVD risk. In the study, a parallel design with 3 study groups, participants in the two intervention groups representing high-flavonoid (HF) and low flavonoid (LF) intakes were asked to increase their daily F&V intake by 2, 4 and 6 portions for a duration of 6 weeks each, while a third (control) group continued with their habitual diet. Faecal samples were collected at baseline and after each dose from 122 subjects. Faecal bacteria enumeration was performed by fluorescence in situ hybridisation (FISH). Correlations of dietary components, flavonoid intake and markers of CVD with bacterial numbers were also performed. A significant dose X treatment interaction was only found for Clostidium leptum-Ruminococcus bromii/flavefaciens with a significant increase after intake of 6 additional portions in the LF group. Correlation analysis of the data from all 122 subjects independent from dietary intervention indicated an inhibitory role of F&V intake, flavonoid content and sugars against the growth of potentially pathogenic clostridia. Additionally, we observed associations between certain bacterial populations and CVD risk factors including plasma TNF-α, plasma lipids and BMI/waist circumference. PMID:26757793

  14. The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism.

    PubMed

    Selma, María V; Romo-Vaquero, María; García-Villalba, Rocío; González-Sarrías, Antonio; Tomás-Barberán, Francisco A; Espín, Juan C

    2016-04-20

    We recently identified three metabotypes (0, A and B) that depend on the metabolic profile of urolithins produced from polyphenol ellagic acid (EA). The gut microbiota and Gordonibacter spp. recently were identified as species able to produce urolithins. A higher percentage of metabotype B was found in patients with metabolic syndrome or colorectal cancer in comparison with healthy individuals. The aim of the present study was to analyse differences in EA metabolism between healthy overweight-obese and normoweight individuals and evaluate the role of gut microbial composition including Gordonibacter. Although the three metabotypes were confirmed in both groups, metabotype B prevailed in overweight-obese (31%) versus normoweight (20%) individuals while metabotype A was higher in normoweight (70%) than the overweight-obese group (57%). This suggests that weight gain favours the growth of bacteria capable of producing urolithin B and/or isourolithin A with respect to urolithin A-producing bacteria. Gordonibacter spp. levels were not significantly different between normoweight and overweight-obese groups but higher Gordonibacter levels were found in metabotype A individuals than in those with metabotype B. Other bacterial species have been reported to show a much closer relationship to obesity and dysbiosis than Gordonibacter. However, Gordonibacter levels are negatively correlated with metabotype B, which prevails in metabolic syndrome and colorectal cancer. This is the first report that links overweight and obesity with an alteration in the catabolism of EA, and where the correlation of Gordonibacter to this alteration is shown. Future investigation of Gordonibacter and urolithin metabotypes as potential biomarkers or therapeutic targets of obesity-related diseases is warranted. PMID:26597167

  15. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    PubMed

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. PMID:26617077

  16. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut

    PubMed Central

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

  17. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut.

    PubMed

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

  18. Study of the Aminoglycoside Subsistence Phenotype of Bacteria Residing in the Gut of Humans and Zoo Animals

    PubMed Central

    Bello González, Teresita de J.; Zuidema, Tina; Bor, Gerrit; Smidt, Hauke; van Passel, Mark W. J.

    2016-01-01

    Recent studies indicate that next to antibiotic resistance, bacteria are able to subsist on antibiotics as a carbon source. Here we evaluated the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics. Nine gut isolates of Escherichia coli and Cellulosimicrobium sp. displayed increases in colony forming units (CFU) during incubations in minimal medium with only antibiotics added, i.e., the antibiotic subsistence phenotype. Furthermore, laboratory strains of E. coli and Pseudomonas putida equipped with the aminoglycoside 3′ phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides. In order to address which endogenous genes could be involved in these subsistence phenotypes, the broad-range glycosyl-hydrolase inhibiting iminosugar deoxynojirimycin (DNJ) was used. Addition of DNJ to minimal medium containing glucose showed initial growth retardation of resistant E. coli, which was rapidly recovered to normal growth. In contrast, addition of DNJ to minimal medium containing kanamycin arrested resistant E. coli growth, suggesting that glycosyl-hydrolases were involved in the subsistence phenotype. However, antibiotic degradation experiments showed no reduction in kanamycin, even though the number of CFUs increased. Although antibiotic subsistence phenotypes are readily observed in bacterial species, and are even found in susceptible laboratory strains carrying standard resistance genes, we conclude there is a discrepancy between the observed antibiotic subsistence phenotype and actual antibiotic degradation. Based on these results we can hypothesize that aminoglycoside modifying enzymes might first inactivate the antibiotic (i.e., by acetylation of amino groups, modification of hydroxyl groups by adenylation and phosphorylation respectively), before the subsequent action of catabolic enzymes. Even though we do not dispute that antibiotics could be used as a single carbon source, our observations

  19. Anticancer Drugs from Marine Flora: An Overview

    PubMed Central

    Sithranga Boopathy, N.; Kathiresan, K.

    2010-01-01

    Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease. PMID:21461373

  20. Biochemical characterisation of the neuraminidase pool of the human gut symbiont Akkermansia muciniphila.

    PubMed

    Huang, Kun; Wang, Mao M; Kulinich, Anna; Yao, Hong L; Ma, Hong Y; Martínez, Juana E R; Duan, Xu C; Chen, Huan; Cai, Zhi P; Flitsch, Sabine L; Liu, Li; Voglmeir, Josef

    2015-10-13

    Since the isolation and identification of Akkermansia muciniphila one decade ago, much attention has been drawn to this gut bacterium due to its role in obesity and type 2 diabetes. This report describes the discovery and biochemical characterisation of all four putative neuraminidases annotated in the A. muciniphila genome. Recombinantly expressed candidate genes, which were designated Am0705, Am0707, Am1757 and Am2085, were shown to cover complementary pH ranges between 4.0 and 9.5. Temperature optima of the enzymes lay between 37 and 42 °C. All four enzymes were strongly inhibited by Cu(2+) and Zn(2+), and loss of activity after the addition of EDTA suggests that all neuraminidases, with the exception of Am0707, require divalent metal ions for their catalytic function. Chemoenzymatically synthesised α2,3- and α2,6-linked indoyl-sialosides were utilised to determine the regioselectivity and substrate promiscuity of the neuraminidases towards C5-modifications of sialic acids with N-acetyl-, N-glycolyl-, N-propionyl-, or hydroxyl-groups. The combination of simple purification procedures and good activities of some of the characterised neuraminidases makes them potentially interesting as tools in bioanalytical or industrial applications. PMID:26340137

  1. Influence of H7N9 virus infection and associated treatment on human gut microbiota

    PubMed Central

    Qin, Nan; Zheng, Beiwen; Yao, Jian; Guo, Lihua; Zuo, Jian; Wu, Lingjiao; Zhou, Jiawei; Liu, Lin; Guo, Jing; Ni, Shujun; Li, Ang; Zhu, Yixin; Liang, Weifeng; Xiao, Yonghong; Ehrlich, S. Dusko; Li, Lanjuan

    2015-01-01

    Between March and June, 2013, forty H7N9 patients were hospitalized in our hospital. Next-generation sequencing technologies have been used to sequence the fecal DNA samples of the patient, the within sample diversity analysis, enterotyping, functional gene and metagenomic species analysis have been carried on both the patients and healthy controls. The influence of associated treatment in H7N9 infected patients is dramatic and was firstly revealed in species level due to deep sequencing technology. We found that most of the MetaGenomic Species (MGS) enriched in the control samples were Roseburia inulinivorans DSM 16841, butyrate producing bacterium SS3/4 and most of MGS enriched in the H7N9 patients were Clostridium sp. 7 2 43FAA and Enterococcus faecium. It was concluded that H7N9 viral infection and antibiotic administration have a significant effect on the microbiota community with decreased diversity and overgrowth of the bacteria such as Escherichia coli and Enterococcus faecium. Enterotype analysis showed that the communities were unstable. Treatment including antivirals, probiotics and antibiotics helps to improve the microbiota diversity and the abundance of beneficial bacteria in the gut. PMID:26490635

  2. Recent advances in the role of probiotics in human inflammation and gut health.

    PubMed

    Rupa, Prithy; Mine, Yoshinori

    2012-08-29

    The gastrointestinal (GI) tract provides residence to an astounding number of bacterial species, which have profound effects on host biology, function, physiology, and immune response. Discovery of "symbiosis factors" from symbionts that facilitate the peaceful coexistence of microbiota and the host immune system are of interest. Symbionts synthesize immunomodulatory molecules that guide maturation of the immune system and have pivotal roles in many biological processes; however, individuals differ in the makeup of their GI microbiota, which is influenced by many external and internal factors such as diet, antibiotic use, and host genetics, which in turn influences health and disease outcomes. Various endogenous, genetic, and environmental factors influence GI development including species composition and health status of neonates, resulting in interactions that occur between the bacteria and the host. Mechanisms of probiotics involved in homeostasis of a balanced immune system have been inconclusive. The probable mechanism of action may be postulated as direct competition between pathogenic bacteria in the gut and/or immune modulation. This review focuses on probiotics in health and disease prevention, especially the biological importance of intestinal regulation of inflammatory processes that may be beneficial in a multitude of disorders both inside and outside the GI tract. PMID:22897745

  3. Human gut dendritic cells drive aberrant gut-specific t-cell responses in ulcerative colitis, characterized by increased IL-4 production and loss of IL-22 and IFNγ.

    PubMed

    Mann, Elizabeth R; Bernardo, David; Ng, Siew C; Rigby, Rachael J; Al-Hassi, Hafid O; Landy, Jon; Peake, Simon T C; Spranger, Henning; English, Nicholas R; Thomas, Linda V; Stagg, Andrew J; Knight, Stella C; Hart, Ailsa L

    2014-12-01

    : The pathogenesis of inflammatory bowel disease is incompletely understood but results from a dysregulated intestinal immune response to the luminal microbiota. CD4 T cells mediate tissue injury in the inflammatory bowel disease-associated immune response. Dendritic cells (DC) generate primary T-cell responses and mediate intestinal immune tolerance to prevent overt inflammation in response to the gut microbiota. However, most information regarding function of intestinal DC has come from mouse models, and information in humans is scarce. We show here that intestinal DC subsets are skewed in ulcerative colitis (UC) in humans, with a loss of CD103 lymph-node homing DC; this intestinal DC subset preferentially generates regulatory T cells in mice. We show infiltrates of DC negative for myeloid marker CD11c, with enhanced expression of Toll-like receptors for bacterial recognition. After mixed leukocyte reaction, DC from the inflamed UC colon had an enhanced ability to generate gut-specific CD4 T cells with enhanced production of interleukin-4 but a loss of interferon γ and interleukin-22 production. Conditioning intestinal DC with probiotic strain Lactobacillus casei Shirota in UC partially restored their normal function indicated by reduced Toll-like receptor 2/4 expression and restoration of their ability to imprint homing molecules on T cells and to generate interleukin-22 production by stimulated T cells. This study suggests that T-cell dysfunction in UC is driven by DC. T-cell responses can be manipulated indirectly through effects of bacterial conditioning on gut DC with implications for immunomodulatory effects of the commensal microbiota in vivo. Manipulation of DC to allow generation of DC-specific therapy may be beneficial in inflammatory bowel disease. PMID:25397892

  4. Evaluation of the effect of blackcurrant products on gut microbiota and on markers of risk for colon cancer in humans.

    PubMed

    Molan, Abdul-Lateef; Liu, Zhuojian; Plimmer, Gabriel

    2014-03-01

    The purpose of this study was to determine in healthy humans whether First Leaf (FL; composed of blackcurrant extract powder, lactoferrin and lutein) and Cassis Anthomix 30 (CAM30; blackcurrant extract powder) can positively modify the colonic microbiota by enhancing the growth of the beneficial bacteria and inactivating the toxic bacterial enzymes which are known to be involved in colonic carcinogenesis. Thirty healthy adult male and female volunteers were recruited for this study. Fluorescent in situ hybridization was carried out to analyse the populations of fecal microbiota. Consumption of FL and CAM30 led to significant increases (P < 0.0001) in the population sizes of lactobacilli and bifidobacteria whereas the population sizes of Clostridium spp. and Bacteroides spp were decreased significantly (P < 0.0001). In addition, feeding of FL and CAM30 decreases the activity of β-glucuronidase (bacterial enzyme which is considered to be one of the enzymes that increases risk for colorectal cancer) and significantly decreased (P < 0.05) the fecal pH. In conclusion, the results of this study open up the possibility that consumption of FL and CAM30 can offer various benefits to human health through acting as novel prebiotic agents via increasing the numbers of beneficial bacteria (lactobacilli and bifidobacteria) in the gut. PMID:23674271

  5. Tissue content of mercury in rats given methylmercuric chloride orally: influence of intestinal flora

    SciTech Connect

    Rowland, I.R.; Davies, M.J.; Evans, J.G.

    1980-05-01

    The effect of intestinal flora on the absorption and disposition of mercury in tissues was investigated using conventional rats, and rats treated with antibiotics to eliminate their gut flora. Antibiotic-treated rats given (/sup 203/Hg) -labeled methylmercuric chloride orally had significantly more mercury in their tissues, especially in kidney, brain, lung, blood, and skeletal muscle, and also excreted less mercury in the feces than conventional rats. Furthermore, in the kidneys of the antibiotic-treated rats, the proportion of mercury present as organic mercury was greater than in the kidneys of the conventional rats. The results support the hypothesis that the metabolism of methylmercuric chloride by the gut flora reduces the tissue content of mercury. When rats were administered 10 mg methylmercuric chloride/Kg.day for 6 days, four or five of those given antibiotics developed neurological symptoms of toxicity, whereas only one of five conventional rats given methylmercuric chloride was affected.

  6. Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing

    PubMed Central

    Hua, Xing; Zeller, Georg; Sunagawa, Shinichi; Voigt, Anita Y.; Hercog, Rajna; Goedert, James J.; Shi, Jianxin; Bork, Peer; Sinha, Rashmi

    2016-01-01

    Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect

  7. In vitro growth of four individual human gut bacteria on oligosaccharides produced by chemoenzymatic synthesis.

    PubMed

    Vigsnaes, Louise K; Nakai, Hiroyuki; Hemmingsen, Lene; Andersen, Joakim M; Lahtinen, Sampo J; Rasmussen, Louise E; Hachem, Maher Abou; Petersen, Bent O; Duus, Jens Ø; Meyer, Anne S; Licht, Tine R; Svensson, Birte

    2013-04-30

    The present study aimed at examining oligosaccharides (OS) for potential stimulation of probiotic bacteria. Nineteen structurally well-defined candidate OS covering groups of β-glucosides, α-glucosides and α-galactosides with degree of polymerization 2-4 were prepared in >100 mg amounts by chemoenzymatic synthesis (i.e. reverse phosphorolysis or transglycosylation). Fourteen of the OS are not naturally occurring and five (β-D-glucosyl-fructose, β-D-glucosyl-xylitol, α-glucosyl-(1,4)-D-mannose, α-glucosyl-(1,4)-D-xylose; α-glucosyl-(1,4)-L-fucose) have recently been synthesized for the first time. These OS have not been previously tested for effects of bacterial growth and here the ability of all 19 OS to support growth of four gastrointestinal bacteria: three probiotic bacteria Bifidobacterium lactis, Bifidobacterium longum, and Lactobacillus acidophilus, and one commensal bacterium, Bacteroides vulgatus has been evaluated in monocultures. The disaccharides β-D-glucosyl-xylitol and β-D-glucosyl-(1,4)-xylose noticeably stimulated growth yields of L. acidophilus NCFM, and additionally, β-D-glucosyl-(1,4)-xylose stimulated B. longum Bl-05. α-Glucosyl-(1,4)-glucosamine and α-glucosyl-(1,4)-N-acetyl-glucosamine enhanced the growth rate of B. animalis subsp. lactis and B. longum Bl-05, whereas L. acidophilus NCFM and Bac. vulgatus did not grow on these OS. α-Galactosyl-(1,6)-α-galactosyl-(1,6)-glucose advanced the growth rate of B. animalis subsp. lactis and L. acidophilus NCFM. Thus several of the structurally well-defined OS supported growth of beneficial gut bacteria. This reflects a broad specificity of their sugar transporters for OS, including specificity for non-naturally occurring OS, hence showing promise for design of novel prebiotics. PMID:23580006

  8. Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing.

    PubMed

    Vogtmann, Emily; Hua, Xing; Zeller, Georg; Sunagawa, Shinichi; Voigt, Anita Y; Hercog, Rajna; Goedert, James J; Shi, Jianxin; Bork, Peer; Sinha, Rashmi

    2016-01-01

    Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect

  9. MALDI-TOF Identification of the Human Gut Microbiome in People with and without Diarrhea in Senegal

    PubMed Central

    Samb-Ba, Bissoume; Mazenot, Catherine; Gassama-Sow, Amy; Dubourg, Grégory; Richet, Hervé; Hugon, Perrine; Lagier, Jean-Christophe; Raoult, Didier; Fenollar, Florence

    2014-01-01

    Background In Africa, there are several problems with the specific identification of bacteria. Recently, MALDI-TOF mass spectrometry has become a powerful tool for the routine microbial identification in many clinical laboratories. Methodology/Principal Findings This study was conducted using feces from 347 individuals (162 with diarrhea and 185 without diarrhea) sampled in health centers in Dakar, Senegal. Feces were transported from Dakar to Marseille, France, where they were cultured using different culture conditions. The isolated colonies were identified using MALDI-TOF. If a colony was unidentified, 16S rRNA sequencing was performed. Overall, 2,753 isolates were tested, allowing for the identification of 189 bacteria from 5 phyla, including 2 previously unknown species, 11 species not previously reported in the human gut, 10 species not previously reported in humans, and 3 fungi. 2,718 bacterial isolates (98.8%) out of 2,750 yielded an accurate identification using mass spectrometry, as did the 3 Candida albicans isolates. Thirty-two bacterial isolates not identified by MALDI-TOF (1.2%) were identified by sequencing, allowing for the identification of 2 new species. The number of bacterial species per fecal sample was significantly higher among patients without diarrhea (8.6±3) than in those with diarrhea (7.3±3.4; P = 0.0003). A modification of the gut microbiota was observed between the two groups. In individuals with diarrhea, major commensal bacterial species such as E. coli were significantly decreased (85% versus 64%), as were several Enterococcus spp. (E. faecium and E. casseliflavus) and anaerobes, such as Bacteroides spp. (B. uniformis and B. vulgatus) and Clostridium spp. (C. bifermentans, C. orbiscindens, C. perfringens, and C. symbosium). Conversely, several Bacillus spp. (B. licheniformis, B. mojavensis, and B. pumilus) were significantly more frequent among patients with diarrhea. Conclusions/Significance MALDI-TOF is a potentially

  10. Food and human gut as reservoirs of transferable antibiotic resistance encoding genes

    PubMed Central

    Rolain, Jean-Marc

    2013-01-01

    The increase and spread of antibiotic resistance (AR) over the past decade in human pathogens has become a worldwide health concern. Recent genomic and metagenomic studies in humans, animals, in food and in the environment have led to the discovery of a huge reservoir of AR genes called the resistome that could be mobilized and transferred from these sources to human pathogens. AR is a natural phenomenon developed by bacteria to protect antibiotic-producing bacteria from their own products and also to increase their survival in highly competitive microbial environments. Although antibiotics are used extensively in humans and animals, there is also considerable usage of antibiotics in agriculture, especially in animal feeds and aquaculture. The aim of this review is to give an overview of the sources of AR and the use of antibiotics in these reservoirs as selectors for emergence of AR bacteria in humans via the food chain. PMID:23805136

  11. CHARACTERIZATION OF MICROBIAL GUT FLORA OF HETEROPTEROUS INSECTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many insects harbor a robust complement of prokaryotes in their alimentary canals. These microorganisms may facilitate nutrient availability and utilization, detoxification of environmental toxins, or play other important roles in the insect's life history. Understanding insect-microorganism inter...

  12. Development and Validation of a Chemostat Gut Model To Study Both Planktonic and Biofilm Modes of Growth of Clostridium difficile and Human Microbiota

    PubMed Central

    Crowther, Grace S.; Chilton, Caroline H.; Todhunter, Sharie L.; Nicholson, Scott; Freeman, Jane; Baines, Simon D.; Wilcox, Mark H.

    2014-01-01

    The human gastrointestinal tract harbours a complex microbial community which exist in planktonic and sessile form. The degree to which composition and function of faecal and mucosal microbiota differ remains unclear. We describe the development and characterisation of an in vitro human gut model, which can be used to facilitate the formation and longitudinal analysis of mature mixed species biofilms. This enables the investigation of the role of biofilms in Clostridium difficile infection (CDI). A well established and validated human gut model of simulated CDI was adapted to incorporate glass rods that create a solid-gaseous-liquid interface for biofilm formation. The continuous chemostat model was inoculated with a pooled human faecal emulsion and controlled to mimic colonic conditions in vivo. Planktonic and sessile bacterial populations were enumerated for up to 46 days. Biofilm consistently formed macroscopic structures on all glass rods over extended periods of time, providing a framework to sample and analyse biofilm structures independently. Whilst variation in biofilm biomass is evident between rods, populations of sessile bacterial groups (log10 cfu/g of biofilm) remain relatively consistent between rods at each sampling point. All bacterial groups enumerated within the planktonic communities were also present within biofilm structures. The planktonic mode of growth of C. difficile and gut microbiota closely reflected observations within the original gut model. However, distinct differences were observed in the behaviour of sessile and planktonic C. difficile populations, with C. difficile spores preferentially persisting within biofilm structures. The redesigned biofilm chemostat model has been validated for reproducible and consistent formation of mixed species intestinal biofilms. This model can be utilised for the analysis of sessile mixed species communities longitudinally, potentially providing information of the role of biofilms in CDI. PMID

  13. Cospeciation of gut microbiota with hominids.

    PubMed

    Moeller, Andrew H; Caro-Quintero, Alejandro; Mjungu, Deus; Georgiev, Alexander V; Lonsdorf, Elizabeth V; Muller, Martin N; Pusey, Anne E; Peeters, Martine; Hahn, Beatrice H; Ochman, Howard

    2016-07-22

    The evolutionary origins of the bacterial lineages that populate the human gut are unknown. Here we show that multiple lineages of the predominant bacterial taxa in the gut arose via cospeciation with humans, chimpanzees, bonobos, and gorillas over the past 15 million years. Analyses of strain-level bacterial diversity within hominid gut microbiomes revealed that clades of Bacteroidaceae and Bifidobacteriaceae have been maintained exclusively within host lineages across hundreds of thousands of host generations. Divergence times of these cospeciating gut bacteria are congruent with those of hominids, indicating that nuclear, mitochondrial, and gut bacterial genomes diversified in concert during hominid evolution. This study identifies human gut bacteria descended from ancient symbionts that speciated simultaneously with humans and the African apes. PMID:27463672

  14. Strand-specific community RNA-seq reveals prevalent and dynamic antisense transcription in human gut microbiota

    PubMed Central

    Bao, Guanhui; Wang, Mingjie; Doak, Thomas G.; Ye, Yuzhen

    2015-01-01

    Metagenomics and other meta-omics approaches (including metatranscriptomics) provide insights into the composition and function of microbial communities living in different environments or animal hosts. Metatranscriptomics research provides an unprecedented opportunity to examine gene regulation for many microbial species simultaneously, and more importantly, for the majority that are unculturable microbial species, in their natural environments (or hosts). Current analyses of metatranscriptomic datasets focus on the detection of gene expression levels and the study of the relationship between changes of gene expression and changes of environment. As a demonstration of utilizing metatranscriptomics beyond these common analyses, we developed a computational and statistical procedure to analyze the antisense transcripts in strand-specific metatranscriptomic datasets. Antisense RNAs encoded on the DNA strand opposite a gene’s CDS have the potential to form extensive base-pairing interactions with the corresponding sense RNA, and can have important regulatory functions. Most studies of antisense RNAs in bacteria are rather recent, are mostly based on transcriptome analysis, and have been applied mainly to single bacterial species. Application of our approaches to human gut-associated metatranscriptomic datasets allowed us to survey antisense transcription for a large number of bacterial species associated with human beings. The ratio of protein coding genes with antisense transcription ranges from 0 to 35.8% (median = 10.0%) among 47 species. Our results show that antisense transcription is dynamic, varying between human individuals. Functional enrichment analysis revealed a preference of certain gene functions for antisense transcription, and transposase genes are among the most prominent ones (but we also observed antisense transcription in bacterial house-keeping genes). PMID:26388849

  15. Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome*

    PubMed Central

    Das, Debanu; Godzik, Adam; Lesley, Scott A.; Deacon, Ashley M.; Coombs, Graham H.; Elsliger, Marc-André; Wilson, Ian A.

    2016-01-01

    Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other families in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys147, resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. PMID:26940874

  16. Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome.

    PubMed

    McLuskey, Karen; Grewal, Jaspreet S; Das, Debanu; Godzik, Adam; Lesley, Scott A; Deacon, Ashley M; Coombs, Graham H; Elsliger, Marc-André; Wilson, Ian A; Mottram, Jeremy C

    2016-04-29

    Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other families in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys(147), resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys(147) to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca(2+) for activity. Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. PMID:26940874

  17. Crystal structure and activity studies of the C11 cysteine peptidase from Parabacteroides merdae in the human gut microbiome

    DOE PAGESBeta

    McLuskey, Karen; Grewal, Jaspreet S.; Das, Debanu; Godzik, Adam; Lesley, Scott A.; Deacon, Ashley M.; Coombs, Graham H.; Elsliger, Marc-André; Wilson, Ian A.; Mottram, Jeremy C.

    2016-03-03

    Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other familiesmore » in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys147, resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. Altogether, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms.« less

  18. Possible transfer of plasmid mediated third generation cephalosporin resistance between Escherichia coli and Shigella sonnei in the human gut.

    PubMed

    Rashid, Harunur; Rahman, Mahbubur

    2015-03-01

    Choice of antibiotic for treatment of serious bacterial infection is rapidly diminishing by plasmid mediated transfer of antibiotic resistance. Here, we report a possible horizontal transfer of plasmid carrying third-generation-cephalosporin (TGC) resistance between Escherichia coli and Shigella sonnei. Two different types of colonies were identified in MacConkey agar plate from a faecal specimen collected from a patient with shigellosis. The colonies were identified as E. coli and S. sonnei. Both of the isolates were resistant to ampicillin, chloramphenicol, co-trimoxazole, erythromycin, azithromycin, nalidixic acid, ceftriaxone, cefixime, ceftazidime, cefotaxime and susceptible to co-amoxiclave, amikacin, imipenam, astreonam, levofloxacin, moxifloxacin, mecillinam. These two strains were positive for extended spectrum β-lactamase. We were able to transfer ESBL producing property from both ceftriaxone-resistant isolates to the ceftriaxone susceptible recipient E. coli K12 and S. sonnei. Plasmid profile analysis revealed that the first-generation E. coli K12 and S. sonnei transconjugants harbored a 50MDa R plasmid, as two-parent ESBL-producing S. sonnei and E. coli strains. Similar patterns of ESBL producing plasmid and transferable antimicrobial phenotype suggests that the ESBL producing plasmid might transferred between E. coli and S. sonnei through conjugation in the human gut. PMID:25461693

  19. The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria

    PubMed Central

    Di Rienzi, Sara C; Sharon, Itai; Wrighton, Kelly C; Koren, Omry; Hug, Laura A; Thomas, Brian C; Goodrich, Julia K; Bell, Jordana T; Spector, Timothy D; Banfield, Jillian F; Ley, Ruth E

    2013-01-01

    Cyanobacteria were responsible for the oxygenation of the ancient atmosphere; however, the evolution of this phylum is enigmatic, as relatives have not been characterized. Here we use whole genome reconstruction of human fecal and subsurface aquifer metagenomic samples to obtain complete genomes for members of a new candidate phylum sibling to Cyanobacteria, for which we propose the designation ‘Melainabacteria’. Metabolic analysis suggests that the ancestors to both lineages were non-photosynthetic, anaerobic, motile, and obligately fermentative. Cyanobacterial light sensing may have been facilitated by regulators present in the ancestor of these lineages. The subsurface organism has the capacity for nitrogen fixation using a nitrogenase distinct from that in Cyanobacteria, suggesting nitrogen fixation evolved separately in the two lineages. We hypothesize that Cyanobacteria split from Melainabacteria prior or due to the acquisition of oxygenic photosynthesis. Melainabacteria remained in anoxic zones and differentiated by niche adaptation, including for symbiosis in the mammalian gut. DOI: http://dx.doi.org/10.7554/eLife.01102.001 PMID:24137540

  20. The human gut microbiome in health: establishment and resilience of microbiota over a lifetime.

    PubMed

    Greenhalgh, Kacy; Meyer, Kristen M; Aagaard, Kjersti M; Wilmes, Paul

    2016-07-01

    With technological advances in culture-independent molecular methods, we are uncovering a new facet of our natural history by accounting for the vast diversity of microbial life which colonizes the human body. The human microbiome contributes functional genes and metabolites which affect human physiology and are, therefore, considered an important factor for maintaining health. Much has been described in the past decade based primarily on 16S rRNA gene amplicon sequencing regarding the diversity, structure, stability and dynamics of human microbiota in their various body habitats, most notably within the gastrointestinal tract (GIT). Relatively high levels of variation have been described across different stages of life and geographical locations for the GIT microbiome. These observations may prove helpful for the future contextualization of patterns in other body habitats especially in relation to identifying generalizable trends over human lifetime. Given the large degree of complexity and variability, a key challenge will be how to define baseline healthy microbiomes and how to identify features which reflect deviations therefrom in the future. In this context, metagenomics and functional omics will likely play a central role as they will allow resolution of microbiome-conferred functionalities associated with health. Such information will be vital for formulating therapeutic interventions aimed at managing microbiota-mediated health particularly in the GIT over the course of a human lifetime. PMID:27059297

  1. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment.

    PubMed

    Vaziri, Nosratola D; Zhao, Ying-Yong; Pahl, Madeleine V

    2016-05-01

    Chronic kidney disease (CKD) results in systemic inflammation and oxidative stress which play a central role in CKD progression and its adverse consequences. Although many of the causes and consequences of oxidative stress and inflammation in CKD have been extensively explored, little attention had been paid to the intestine and its microbial flora as a potential source of these problems. Our recent studies have revealed significant disruption of the colonic, ileal, jejunal and gastric epithelial tight junction in different models of CKD in rats. Moreover, the disruption of the epithelial barrier structure and function found in uremic animals was replicated in cultured human colonocytes exposed to uremic human plasma in vitro We have further found significant changes in the composition and function of colonic bacterial flora in humans and animals with advanced CKD. Together, uremia-induced impairment of the intestinal epithelial barrier structure and function and changes in composition of the gut microbiome contribute to the systemic inflammation and uremic toxicity by accommodating the translocation of endotoxin, microbial fragments and other noxious luminal products in the circulation. In addition, colonic bacteria are the main source of several well-known pro-inflammatory uremic toxins such as indoxyl sulfate, p-cresol sulfate, trimethylamine-N-oxide and many as-yet unidentified retained compounds in end-stage renal disease patients. This review is intended to provide an overview of the effects of CKD on the gut microbiome and intestinal epithelial barrier structure and their role in the pathogenesis of systemic inflammation and uremic toxicity. In addition, potential interventions aimed at mitigating these abnormalities are briefly discussed. PMID:25883197

  2. Modulation of genotoxic enzyme activities by non-digestible oligosaccharide metabolism in in-vitro human gut bacterial ecosystems.

    PubMed

    McBain, A J; MacFarlane, G T

    2001-09-01

    Supplementation of the human diet with prebiotic substances such as inulin and non-digestible oligosaccharides (NDO), e.g., galacto-oligosaccharides (GOS), has been associated with various health benefits. However, little information is available regarding the spatial location of their metabolism in human gut bacterial ecosystems. Therefore, the present study investigated the metabolism of inulin and GOS with respect to bacterial growth, bifidobacterial stimulatory properties and anti-mutagenicity potential, in a three-stage continuous culture model of the colon which reproduces the physicochemical characteristics of the proximal (V1) and distal (V2, V3) colons. Fermentation of both carbohydrates was rapid, and occurred primarily in V1, as evidenced by acid formation. Inulin metabolism was associated with 10-fold stimulation of lactobacillus populations, together with smaller increases in bifidobacterial cell counts in V1. However, peptostreptococci, enterococci and Clostridium perfringens also increased in this fermentation vessel. In contrast, GOS was only weakly bifidogenic in V1, although these bacteria did proliferate in V2. GOS also increased lactobacilli by an order of magnitude in V1. However, overall changes in microbial populations resulting from inulin or GOS addition were minimal in V2 and V3. Potential beneficial effects of inulin metabolism included minor reductions in beta-glucosidase and beta-glucuronidase, whereas GOS strongly suppressed these enzymes, together with arylsulphatase (AS). Growth of putatively health promoting micro-organisms was not only associated with reductions in enzymes linked to genotoxicity. For example, both carbohydrates stimulated synthesis of nitroreductase and azoreductase, throughout the fermentation system, while inulin increased AS. Colonic transit time is an important factor in bacterial metabolism in the large bowel, and these data suggest that, in some circumstances, NDO fermentation will occurprincipally in the

  3. Variability of arsenic bioaccessibility and metabolism in soils by human gut microbiota using different in vitro methods combined with SHIME.

    PubMed

    Yin, Naiyi; Du, Huili; Zhang, Zhennan; Cai, Xiaolin; Li, Zejiao; Sun, Guoxin; Cui, Yanshan

    2016-10-01

    Arsenic (As) speciation analysis is essential when evaluating the risks upon oral exposure to As-contaminated soils. In this study, we first investigated the variability in the As bioaccessibility and speciation using a combination of five common in vitro methods (SBRC, PBET, DIN, UBM and IVG) (gastric and small intestinal phases) and the SHIME model (colon phase). Our results indicate that the As bioaccessibility varies in the colon phase. An increase in the As bioaccessibility for SBRC and PBET, and a decrease for UBM and IVG were observed in the colon phase. In addition, we found different extents of methylation and large amounts of arsenite [As(III)] due to microbial reduction in the colon digests. The UBM-SHIME method displayed a higher methylation percentage of 13.5-82.1%, but a lower methylation percentage of 0.2-21.8% was observed in the SBRC-SHIME method. Besides, The MMA(V) levels in the colon digests were positively correlated with those of As(III) and DMA(V), so DMA(V) can be considered an indicator to evaluate the As metabolic speed of in vitro cultured human gut microbiota. Based on the standard reference soil of NIST 2710a, the As bioaccessibility in the colon phase of PBET-SHIME and SBRC-SHIME were the closest to the in vivo results. Combining in vitro methods and SHIME will remarkably affect the accurate assessment of potential risks to human health associated with oral exposure to soil As. PMID:27320743

  4. Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal

    PubMed Central

    Bui, Thi Phuong Nam; Ritari, Jarmo; Boeren, Sjef; de Waard, Pieter; Plugge, Caroline M.; de Vos, Willem M.

    2015-01-01

    Human intestinal bacteria produce butyrate, which has signalling properties and can be used as energy source by enterocytes thus influencing colonic health. However, the pathways and the identity of bacteria involved in this process remain unclear. Here we describe the isolation from the human intestine of Intestinimonas strain AF211, a bacterium that can convert lysine stoichiometrically into butyrate and acetate when grown in a synthetic medium. Intestinimonas AF211 also converts the Amadori product fructoselysine, which is abundantly formed in heated foods via the Maillard reaction, into butyrate. The butyrogenic pathway includes a specific CoA transferase that is overproduced during growth on lysine. Bacteria related to Intestinimonas AF211 as well as the genetic coding capacity for fructoselysine conversion are abundantly present in colonic samples from some healthy human subjects. Our results indicate that protein can serve as a source of butyrate in the human colon, and its conversion by Intestinimonas AF211 and related butyrogens may protect the host from the undesired side effects of Amadori reaction products. PMID:26620920

  5. In vitro fermentation of alternansucrase raffinose acceptor products by human gut bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this work, in vitro fermentation of alternansucrase raffinose acceptor products, previously fractionated according to their degree of polymerization (DP; from DP4 to DP10) was carried out using pH-controlled small scale batch cultures at 37ºC under anaerobic conditions with human faeces. Bifidog...

  6. Gut microbiota in autism and mood disorders

    PubMed Central

    Mangiola, Francesca; Ianiro, Gianluca; Franceschi, Francesco; Fagiuoli, Stefano; Gasbarrini, Giovanni; Gasbarrini, Antonio

    2016-01-01

    The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders. PMID:26755882

  7. Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.

    PubMed

    Reijnders, Dorien; Goossens, Gijs H; Hermes, Gerben D A; Neis, Evelien P J G; van der Beek, Christina M; Most, Jasper; Holst, Jens J; Lenaerts, Kaatje; Kootte, Ruud S; Nieuwdorp, Max; Groen, Albert K; Olde Damink, Steven W M; Boekschoten, Mark V; Smidt, Hauke; Zoetendal, Erwin G; Dejong, Cornelis H C; Blaak, Ellen E

    2016-07-12

    The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. PMID:27411009

  8. A Prebiotic Formula Improves the Gastrointestinal Bacterial Flora in Toddlers

    PubMed Central

    Chen, Ya-Ling; Liao, Fang-Hsuean

    2016-01-01

    We aimed to investigate the effect of enriched 3-prebiotic formula (including inulin, fructooligosaccharides, and galactooligosaccharides) on toddler gut health by measuring fecal microbiota. Our results revealed that the consumption of 3-prebiotic formula three times per day giving total intake of 1.8 g prebiotic ingredients significantly showed the increased number of probiotic Bifidobacterium spp. colonies and the reduced populations of both C. perfringens and total anaerobic bacteria on the fecal bacterial flora in toddlers at 18~36 months. In addition, total organic acids in the fecal samples significantly increased which improves the utilization of bifidus under acidic conditions after consumption of the 3-prebiotic formula. Therefore, using the formula enriched with prebiotic may maintain gut health in toddlers. PMID:27403155

  9. Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut

    PubMed Central

    Thompson, Andrew J.; Stepper, Judith; Sobala, Łukasz F.; Coyle, Travis; Larsbrink, Johan; Spadiut, Oliver; Goddard-Borger, Ethan D.; Stubbs, Keith A.; Brumer, Harry; Davies, Gideon J.

    2016-01-01

    The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta)genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-l-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins. PMID:27466444

  10. Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut.

    PubMed

    Hemsworth, Glyn R; Thompson, Andrew J; Stepper, Judith; Sobala, Łukasz F; Coyle, Travis; Larsbrink, Johan; Spadiut, Oliver; Goddard-Borger, Ethan D; Stubbs, Keith A; Brumer, Harry; Davies, Gideon J

    2016-07-01

    The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta)genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-l-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins. PMID:27466444

  11. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism.

    PubMed

    Cuskin, Fiona; Lowe, Elisabeth C; Temple, Max J; Zhu, Yanping; Cameron, Elizabeth A; Pudlo, Nicholas A; Porter, Nathan T; Urs, Karthik; Thompson, Andrew J; Cartmell, Alan; Rogowski, Artur; Hamilton, Brian S; Chen, Rui; Tolbert, Thomas J; Piens, Kathleen; Bracke, Debby; Vervecken, Wouter; Hakki, Zalihe; Speciale, Gaetano; Munōz-Munōz, Jose L; Day, Andrew; Peña, Maria J; McLean, Richard; Suits, Michael D; Boraston, Alisdair B; Atherly, Todd; Ziemer, Cherie J; Williams, Spencer J; Davies, Gideon J; Abbott, D Wade; Martens, Eric C; Gilbert, Harry J

    2015-01-01

    Yeasts, which have been a component of the human diet for at least 7,000 years, possess an elaborate cell wall α-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast α-mannan is a viable food source for the Gram-negative bacterium Bacteroides thetaiotaomicron, a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by B. thetaiotaomicron presents a 'selfish' model for the catabolism of this difficult to breakdown polysaccharide. Genomic comparison with B. thetaiotaomicron in conjunction with cell culture studies show that a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet. PMID:25567280

  12. Gut microbiota and metabolic syndrome

    PubMed Central

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-01-01

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

  13. Transcarboxylase mRNA: a marker which evidences P. freudenreichii survival and metabolic activity during its transit in the human gut.

    PubMed

    Hervé, Christophe; Fondrevez, Marc; Chéron, Angélique; Barloy-Hubler, Frédérique; Jan, Gwénaël

    2007-02-15

    Dairy propionibacteria have recently been considered as probiotics which may beneficially modulate the intestinal ecosystem. However, appropriate vectors (food matrices containing the probiotic) which preserve their viability and offer good tolerance towards digestive stresses need to be developed. In addition, the development of efficient non-invasive methods which specifically monitor Propionibacterium freudenreichii concentration and activity within the human gut is required. To address this latter need, an enzyme involved in propionic fermentation, transcarboxylase, was evaluated in this study as molecular marker in P. freudenreichii. In vitro, the three transcarboxylase subunits were shown to be encoded by an operon and their expression regulated. It occurred during propionic fermentation, ceased in starved cells and was not affected by digestive stresses. The 5S subunit gene of transcarboxylase allowed specific detection of P. freudenreichii by real time PCR in the complex human faecal microbiota. A dairy vector harbouring P. freudenreichii was developed and afforded elevated probiotic faecal concentrations in humans. In vivo, this PCR method allowed rapid quantification of faecal P. freudenreichii in agreement with the cultural method (cfu counting). Moreover, real time Reverse Transcription (RT) -PCR evidenced transcription of the 5S subunit gene during transit through the human digestive tract. This work constitutes a methodological advance for survival and activity evaluation in human trials of the probiotics belonging to the P. freudenreichii species. It strongly suggests that this bacterium not only survives but remains metabolically active in the human gut. PMID:17156879

  14. The flora of Oktibbeha County, Mississippi

    USGS Publications Warehouse

    Leidolf, A.; McDaniel, S.; Nuttle, T.

    2002-01-01

    We surveyed the flora of Oktibbeha County, Mississippi, U.S.A., from February 1994 to 1996. Occupying 118 square kilometers in east-central Mississippi, Oktibbeha County lies among 3 physiographic regions that include, from west to east, Interior Flatwoods, Pontotoc Ridge, and Black Prairie. Accordingly, the county harbors a diverse flora. Based on field work, as well as an extensive review of published literature and herbarium records at IBE and MISSA, we recorded a total of 1,148 taxa (1,125 species, 7 hybrids, 16 infraspecific taxa) belonging to 514 genera in 160 families, over 85% of all taxa documented were native. Compared to 3 other counties in east-central Mississippi, Oktibbeha County has the second largest recorded flora. The number of state-listed (endangered, threatened, or of special concern) taxa (67) documented in this survey far exceeds that reported from any other county in the region. Three introduced species, Ilex cornuta Lindl. & Paxton, Mahonia bealei (Fortune) Carrie??re, and Nandina domestica Thunb., are reported in a naturalized state for the first time from Mississippi. We also describe 16 different plant communities belonging to 5 broad habitat categories: bottomland forests, upland forests and prairies, aquatic habitats, seepage areas, and human-influenced habitats. A detailed description of the vegetation associated with each of these communities is provided.

  15. Mining metagenomic whole genome sequences revealed subdominant but constant Lactobacillus population in the human gut microbiota.

    PubMed

    Rossi, Maddalena; Martínez-Martínez, Daniel; Amaretti, Alberto; Ulrici, Alessandro; Raimondi, Stefano; Moya, Andrés

    2016-06-01

    The genus Lactobacillus includes over 215 species that colonize plants, foods, sewage and the gastrointestinal tract (GIT) of humans and animals. In the GIT, Lactobacillus population can be made by true inhabitants or by bacteria occasionally ingested with fermented or spoiled foods, or with probiotics. This study longitudinally surveyed Lactobacillus species and strains in the feces of a healthy subject through whole genome sequencing (WGS) data-mining, in order to identify members of the permanent or transient populations. In three time-points (0, 670 and 700 d), 58 different species were identified, 16 of them being retrieved for the first time in human feces. L. rhamnosus, L. ruminis, L. delbrueckii, L. plantarum, L. casei and L. acidophilus were the most represented, with estimated amounts ranging between 6 and 8 Log (cells g(-1) ), while the other were detected at 4 or 5 Log (cells g(-1) ). 86 Lactobacillus strains belonging to 52 species were identified. 43 seemingly occupied the GIT as true residents, since were detected in a time span of almost 2 years in all the three samples or in 2 samples separated by 670 or 700 d. As a whole, a stable community of lactobacilli was disclosed, with wide and understudied biodiversity. PMID:27043715

  16. Changes in human gut microbiota influenced by probiotic fermented milk ingestion.

    PubMed

    Unno, Tatsuya; Choi, Jung-Hye; Hur, Hor-Gil; Sadowsky, Michael J; Ahn, Young-Tae; Huh, Chul-Sung; Kim, Geun-Bae; Cha, Chang-Jun

    2015-06-01

    We investigated the effect of consuming probiotic fermented milk (PFM) on the microbial community structure in the human intestinal tract by using high-throughput barcoded pyrosequencing. Six healthy adults ingested 2 servings of PFM daily for 3 wk, and their fecal microbiota were analyzed before and after 3 wk of PFM ingestion period and for another 3 wk following the termination of PFM ingestion (the noningestion period). Fecal microbial communities were characterized by sequencing of the V1-V3 hypervariable regions of the 16S rRNA gene. All subjects showed a similar pattern of microbiota at the phylum level, where the relative abundance of Bacteriodetes species increased during the PFM ingestion period and decreased during the noningestion period. The increase in Bacteroidetes was found to be due to an increase in members of the families Bacteroidaceae or Prevotellaceae. In contrast to PFM-induced adaptation at the phylum level, the taxonomic composition at the genus level showed a considerable alteration in fecal microbiota induced by PFM ingestion. As revealed by analysis of operational taxonomic units (OTU), the numbers of shared OTU were low among the 3 different treatments (before, during, and after PFM ingestion), but the abundance of the shared OTU was relatively high, indicating that the majority (>77.8%) of total microbiota was maintained by shared OTU during PFM ingestion and after its termination. Our results suggest that PFM consumption could alter microbial community structure in the gastrointestinal tract of adult humans while maintaining the stability of microbiota. PMID:25864056

  17. Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity

    PubMed Central

    Paulose, Jiffin K.; Wright, John M.; Patel, Akruti G; Cassone, Vincent M.

    2016-01-01

    Circadian rhythms are fundamental properties of most eukaryotes, but evidence of biological clocks that drive these rhythms in prokaryotes has been restricted to Cyanobacteria. In vertebrates, the gastrointestinal system expresses circadian patterns of gene expression, motility and secretion in vivo and in vitro, and recent studies suggest that the enteric microbiome is regulated by the host’s circadian clock. However, it is not clear how the host’s clock regulates the microbiome. Here, we demonstrate at least one species of commensal bacterium from the human gastrointestinal system, Enterobacter aerogenes, is sensitive to the neurohormone melatonin, which is secreted into the gastrointestinal lumen, and expresses circadian patterns of swarming and motility. Melatonin specifically increases the magnitude of swarming in cultures of E. aerogenes, but not in Escherichia coli or Klebsiella pneumoniae. The swarming appears to occur daily, and transformation of E. aerogenes with a flagellar motor-protein driven lux plasmid confirms a temperature-compensated circadian rhythm of luciferase activity, which is synchronized in the presence of melatonin. Altogether, these data demonstrate a circadian clock in a non-cyanobacterial prokaryote and suggest the human circadian system may regulate its microbiome through the entrainment of bacterial clocks. PMID:26751389

  18. Impact of Oral Typhoid Vaccination on the Human Gut Microbiota and Correlations with S. Typhi-Specific Immunological Responses

    PubMed Central

    Eloe-Fadrosh, Emiley A.; McArthur, Monica A.; Seekatz, Anna M.; Drabek, Elliott F.; Rasko, David A.

    2013-01-01

    The resident microbial consortia of the human gastrointestinal tract play an integral role in modulating immune responses both locally and systemically. However, detailed information regarding the effector immune responses after vaccine administration in relation to the gastrointestinal microbiota is absent. In this study, the licensed oral live-attenuated typhoid vaccine Ty21a was administered in a clinical study to investigate whether oral immunization resulted in alterations of the microbiota and to identify whether a given microbiota composition, or subsets of the community, are associated with defined S. Typhi-specific immunological responses. The fecal microbiota composition and temporal dynamics were characterized using bacterial 16S rRNA pyrosequencing from individuals who were either immunized with the Ty21a typhoid vaccine (n = 13) or served as unvaccinated controls (n = 4). The analysis revealed considerable inter- and intra-individual variability, yet no discernible perturbations of the bacterial assemblage related to vaccine administration were observed. S. Typhi-specific cell mediated immune (CMI) responses were evaluated by measurement of intracellular cytokine production using multiparametric flow cytometry, and humoral responses were evaluated by measurement of serum anti-LPS IgA and IgG titers. Volunteers were categorized according to the kinetics and magnitude of their responses. While differences in microbial composition, diversity, or temporal stability were not observed among individuals able to mount a positive humoral response, individuals displaying multiphasic CMI responses harbored more diverse, complex communities. In line with this preliminary observation, over two hundred operational taxonomic units (OTUs) were found to differentiate multiphasic and late CMI responders, the vast majority of which classified within the order Clostridiales. These results provide an unprecedented view into the dramatic temporal heterogeneity of

  19. In vitro activity on human gut bacteria of murta leaf extracts (Ugni molinae turcz.), a native plant from Southern Chile.

    PubMed

    Shene, Carolina; Canquil, Nelly; Jorquera, Milko; Pinelo, Manuel; Rubilar, Mónica; Acevedo, Francisca; Vergara, Carola; von Baer, Dietrich; Mardones, Claudia

    2012-06-01

    Despite the fact that murta infusions have been used to treat gut/urinary infections by native Chileans for centuries, the mechanisms promoting such effects still remain unclear. As a first attempt to unravel these mechanisms, human fecal samples were incubated in a medium containing water extract of murta leaves (ML) and the growth of different bacterial groups was evaluated. Control incubations were made in media containing fructooligosaccharides (FOS) and glucose as a carbon source. Phenolic compounds in the ML extract, likely promoters of bioactivity, were identified by HPLC-DAD-MS(n) . Concentrations (log₁₀ CFU/mL) of bifidobacteria and lactobacilli in media containing the extract and FOS were 7.33 ± 0.05/4.95 ± 0.20 and 6.44 ± 0.22/6.05 ± 0.06, respectively. Clostridia, anaerobes and Enterobacteriaceae grew to a similar extent in media containing murta extract and FOS. In vitro tests (disk diffusion) showed that Gram-positive (Bacillus and Paenibacillaceae) and Gram-negative (Enterobacteriaceae) bacteria isolated from fecal samples were sensitive to both water and 50/50 ethanol/water extracts of ML (28.4 μg gallic acid equivalents). At this concentration, the antimicrobial activity of ML extracts was significantly (P < 0.05) lower than that of penicillin (10 U), whereas the difference between activity of ML extracts and gentamicine (10 μg) was no significant (P > 0.05). No evidence of dependency between the antimicrobial activity of ML extracts and the enzymatic capability of the sensitive strains was found. PMID:22583138

  20. Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses.

    PubMed

    Eloe-Fadrosh, Emiley A; McArthur, Monica A; Seekatz, Anna M; Drabek, Elliott F; Rasko, David A; Sztein, Marcelo B; Fraser, Claire M

    2013-01-01

    The resident microbial consortia of the human gastrointestinal tract play an integral role in modulating immune responses both locally and systemically. However, detailed information regarding the effector immune responses after vaccine administration in relation to the gastrointestinal microbiota is absent. In this study, the licensed oral live-attenuated typhoid vaccine Ty21a was administered in a clinical study to investigate whether oral immunization resulted in alterations of the microbiota and to identify whether a given microbiota composition, or subsets of the community, are associated with defined S. Typhi-specific immunological responses. The fecal microbiota composition and temporal dynamics were characterized using bacterial 16S rRNA pyrosequencing from individuals who were either immunized with the Ty21a typhoid vaccine (n = 13) or served as unvaccinated controls (n = 4). The analysis revealed considerable inter- and intra-individual variability, yet no discernible perturbations of the bacterial assemblage related to vaccine administration were observed. S. Typhi-specific cell mediated immune (CMI) responses were evaluated by measurement of intracellular cytokine production using multiparametric flow cytometry, and humoral responses were evaluated by measurement of serum anti-LPS IgA and IgG titers. Volunteers were categorized according to the kinetics and magnitude of their responses. While differences in microbial composition, diversity, or temporal stability were not observed among individuals able to mount a positive humoral response, individuals displaying multiphasic CMI responses harbored more diverse, complex communities. In line with this preliminary observation, over two hundred operational taxonomic units (OTUs) were found to differentiate multiphasic and late CMI responders, the vast majority of which classified within the order Clostridiales. These results provide an unprecedented view into the dramatic temporal heterogeneity of

  1. Structural and Functional Characterization of BaiA, An Enzyme Involved in Secondary Bile Acid Synthesis in Human Gut Microbe

    PubMed Central

    Bhowmik, Shiva; Jones, David H.; Chiu, Hsien-Po; Park, In-Hee; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Farr, Carol L.; Tien, Henry J.; Agarwalla, Sanjay; Lesley, Scott A.

    2014-01-01

    Despite significant influence of secondary bile acids on human health and disease, limited structural and biochemical information is available for the key gut microbial enzymes catalyzing its synthesis. Herein, we report apo- and co-factor bound crystal structures of BaiA2, a short chain dehydrogenase/reductase from Clostridium scindens VPI 12708 that represent the first protein structure of this pathway. The structures elucidated the basis of co-factor specificity and mechanism of proton relay. A conformational restriction involving Glu42 located in the co-factor binding site seems crucial in determining co-factor specificity. Limited flexibility of Glu42 results in imminent steric and electrostatic hindrance with 2′-phosphate group of NADP(H). Consistent with crystal structures, steady-state kinetic characterization performed with both BaiA2 and BaiA1, a close homolog with 92% sequence identity, revealed specificity constant (kcat/KM) of NADP+ at least an order of magnitude lower than NAD+. Substitution of Glu42 with Ala improved specificity towards NADP+ by 10- fold compared to wild type. The co-factor bound structure uncovered a novel nicotinamide-hydroxyl ion (NAD+-OH−) adduct contraposing previously reported adducts. The OH− of the adduct in BaiA2 is distal to C4 atom of nicotinamide and proximal to 2′-hydroxyl group of the ribose moiety. Moreover, it is located at intermediary distances between terminal functional groups of active site residues Tyr157 (2.7 Å) and Lys161 (4.5 Å). Based on these observations we propose an involvement of NAD+-OH− adduct in proton relay instead of hydride transfer as noted for previous adducts. PMID:23836456

  2. Links between diet, gut microbiota composition and gut metabolism.

    PubMed

    Flint, Harry J; Duncan, Sylvia H; Scott, Karen P; Louis, Petra

    2015-02-01

    The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches. PMID:25268552

  3. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications.

    PubMed

    Bäckhed, Fredrik; Fraser, Claire M; Ringel, Yehuda; Sanders, Mary Ellen; Sartor, R Balfour; Sherman, Philip M; Versalovic, James; Young, Vincent; Finlay, B Brett

    2012-11-15

    Indigenous microbiota are an essential component in the modern concept of human health, but the composition and functional characteristics of a healthy microbiome remain to be precisely defined. Patterns of microbial colonization associated with disease states have been documented, but the health-associated microbial patterns and their functional characteristics are less clear. A healthy microbiome, considered in the context of body habitat or body site, could be described in terms of ecologic stability (i.e., ability to resist community structure change under stress or to rapidly return to baseline following a stress-related change), by an idealized (presumably health-associated) composition or by a desirable functional profile (including metabolic and trophic provisions to the host). Elucidation of the properties of healthy microbiota would provide a target for dietary interventions and/or microbial modifications aimed at sustaining health in generally healthy populations and improving the health of individuals exhibiting disrupted microbiota and associated diseases. PMID:23159051

  4. Evidence of Extensive DNA Transfer between Bacteroidales Species within the Human Gut

    PubMed Central

    Coyne, Michael J.; Zitomersky, Naamah Levy; McGuire, Abigail Manson; Earl, Ashlee M.

    2014-01-01

    ABSTRACT The genome sequences of intestinal Bacteroidales strains reveal evidence of extensive horizontal gene transfer. In vitro studies of Bacteroides and other bacteria have addressed mechanisms of conjugative transfer and some phenotypic outcomes of these DNA acquisitions in the recipient, such as the acquisition of antibiotic resistance. However, few studies have addressed the horizontal transfer of genetic elements between bacterial species coresident in natural microbial communities, especially microbial ecosystems of humans. Here, we examine the genomes of Bacteroidales species from two human adults to identify genetic elements that were likely transferred among these Bacteroidales while they were coresident in the intestine. Using seven coresident Bacteroidales species from one individual and eight from another, we identified five large chromosomal regions, each present in a minimum of three of the coresident strains at near 100% DNA identity. These five regions are not found in any other sequenced Bacteroidetes genome at this level of identity and are likely all integrative conjugative elements (ICEs). Such highly similar and unique regions occur in only 0.4% of phylogenetically representative mock communities, providing strong evidence that these five regions were transferred between coresident strains in these subjects. In addition to the requisite proteins necessary for transfer, these elements encode proteins predicted to increase fitness, including orphan DNA methylases that may alter gene expression, fimbriae synthesis proteins that may facilitate attachment and the utilization of new substrates, putative secreted antimicrobial molecules, and a predicted type VI secretion system (T6SS), which may confer a competitive ecological advantage to these strains in their complex microbial ecosystem. PMID:24939888

  5. Gut Wall Metabolism. Application of Pre-Clinical Models for the Prediction of Human Drug Absorption and First-Pass Elimination.

    PubMed

    Jones, Christopher R; Hatley, Oliver J D; Ungell, Anna-Lena; Hilgendorf, Constanze; Peters, Sheila Annie; Rostami-Hodjegan, Amin

    2016-05-01

    Quantifying the multiple processes which control and modulate the extent of oral bioavailability for drug candidates is critical to accurate projection of human pharmacokinetics (PK). Understanding how gut wall metabolism and hepatic elimination factor into first-pass clearance of drugs has improved enormously. Typically, the cytochrome P450s, uridine 5'-diphosphate-glucuronosyltransferases and sulfotransferases, are the main enzyme classes responsible for drug metabolism. Knowledge of the isoforms functionally expressed within organs of first-pass clearance, their anatomical topology (e.g. zonal distribution), protein homology and relative abundances and how these differ across species is important for building models of human metabolic extraction. The focus of this manuscript is to explore the parameters influencing bioavailability and to consider how well these are predicted in human from animal models or from in vitro to in vivo extrapolation. A unique retrospective analysis of three AstraZeneca molecules progressed to first in human PK studies is used to highlight the impact that species differences in gut wall metabolism can have on predicted human PK. Compared to the liver, pharmaceutical research has further to go in terms of adopting a common approach for characterisation and quantitative prediction of intestinal metabolism. A broad strategy is needed to integrate assessment of intestinal metabolism in the context of typical DMPK activities ongoing within drug discovery programmes up until candidate drug nomination. PMID:26964996

  6. The pattern of parasitic infection in human gut at the Specialist Hospital, Benin City, Nigeria.

    PubMed

    Obiamiwe, B A

    1977-03-01

    In a survey of 6213 persons conducted between January 1973 to December 1974, at the Specialist Hospital, Benin City, the most common helminths were Necator americanus (16.8%), Ascaris lumbricoides (19l5%) and Trichuris trichiur (5-9%). Dicrocoelium hospes (0-06%) was also recorded and this may become an important liver parasite of man in Nigeria. Its snail vectors are believed to be species of Limicolaria and Achatina which are widely dispersed in Nigeria. Entamoeba coli and E. histolytica showed peaks during the "fly seasons", indicating that the housefly, as well as water, may be an important source of contamination. Trichomonas hominis showed peaks in the rainy seasons, and this suggests that in Benin City transmission is chiefly via contaminated domestic water-supply. The incidence of A. lumbricoides and N. americanus was high throughout the rainy and dry seasons, indicating poor disposal of human excreta and a continuous pattern of infection. The type of food and method of cooking prevented or reduced the incidence of Taenia solium, T. saginata, Diphyllobothrium latum and Fasciola gigantica. PMID:849017

  7. In Sickness and in Health: The Relationships Between Bacteria and Bile in the Human Gut.

    PubMed

    Hay, A J; Zhu, J

    2016-01-01

    Colonization of a human host with a commensal microbiota has a complex interaction in which bacterial communities provide numerous health benefits to the host. An equilibrium between host and microbiota is kept in check with the help of biliary secretions by the host. Bile, composed primarily of bile salts, promotes digestion. It also provides a barrier between host and bacteria. After bile salts are synthesized in the liver, they are stored in the gallbladder to be released after food intake. The set of host-secreted bile salts is modified by the resident bacteria. Because bile salts are toxic to bacteria, an equilibrium of modified bile salts is reached that allows commensal bacteria to survive, yet rebuffs invading pathogens. In addition to direct toxic effects on cells, bile salts maintain homeostasis as signaling molecules, tuning the immune system. To cause disease, gram-negative pathogenic bacteria have shared strategies to survive this harsh environment. Through exclusion of bile, efflux of bile, and repair of bile-induced damage, these pathogens can successfully disrupt and outcompete the microbiota to activate virulence factors. PMID:27565580

  8. Gut microbiota: a source of novel tools to reduce the risk of human disease?

    PubMed

    Collado, Maria Carmen; Rautava, Samuli; Isolauri, Erika; Salminen, Seppo

    2015-01-01

    Modern civilization is faced with a progressive increase in immune-mediated or inflammatory health problems such as allergic disease, autoimmune disorders, and obesity. An extended version of the hygiene hypothesis has been introduced to emphasize the intimate interrelationship among diet, the immune system, microbiome, and origins of human disease: the modern infant, particularly when delivered by cesarean section and without the recommended exclusive breastfeeding, may lack sufficient stimulation of the mucosal immune system to generate a tolerogenic immune milieu and instead be prone to develop chronic inflammatory conditions. These deviations may take the form of allergic or autoimmune disease, or predispose the child to higher weight gain and obesity. Moreover, evidence supports the role of first microbial contacts in promoting and maintaining a balanced immune response in early life and recent findings suggest that microbial contact begins prior to birth and is shaped by the maternal microbiota. Maternal microbiota may prove to be a safe and effective target for interventions decreasing the risk of allergic and noncommunicable diseases in future generations. These results support the hypothesis that targeting early interaction with microbes might offer an applicable strategy to prevent disease. PMID:25335085

  9. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy.

    PubMed

    Dalmasso, Marion; Strain, Ronan; Neve, Horst; Franz, Charles M A P; Cousin, Fabien J; Ross, R Paul; Hill, Colin

    2016-01-01

    With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages) is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI) between 10-3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections. PMID:27280590

  10. Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy

    PubMed Central

    Dalmasso, Marion; Strain, Ronan; Neve, Horst; Franz, Charles M. A. P.; Cousin, Fabien J.; Ross, R. Paul; Hill, Colin

    2016-01-01

    With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages) is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, ɸAPCEc01, ɸAPCEc02 and ɸAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI) between 10−3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections. PMID:27280590

  11. Bovine colostrum improves neonatal growth, digestive function, and gut immunity relative to donor human milk and infant formula in preterm pigs.

    PubMed

    Rasmussen, Stine O; Martin, Lena; Østergaard, Mette V; Rudloff, Silvia; Li, Yanqi; Roggenbuck, Michael; Bering, Stine B; Sangild, Per T

    2016-09-01

    Mother's own milk is the optimal first diet for preterm infants, but donor human milk (DM) or infant formula (IF) is used when supply is limited. We hypothesized that a gradual introduction of bovine colostrum (BC) or DM improves gut maturation, relative to IF during the first 11 days after preterm birth. Preterm pigs were fed gradually advancing doses of BC, DM, or IF (3-15 ml·kg(-1)·3 h(-1), n = 14-18) before measurements of gut structure, function, microbiology, and immunology. The BC pigs showed higher body growth, intestinal hexose uptake, and transit time and reduced diarrhea and gut permeability, relative to DM and IF pigs (P < 0.05). Relative to IF pigs, BC pigs also had lower density of mucosa-associated bacteria and of some putative pathogens in colon, together with higher intestinal villi, mucosal mass, brush-border enzyme activities, colonic short chain fatty acid levels, and bacterial diversity and an altered expression of immune-related genes (higher TNFα, IL17; lower IL8, TLR2, TFF, MUC1, MUC2) (all P < 0.05). Values in DM pigs were intermediate. Severe necrotizing enterocolitis (NEC) was observed in >50% of IF pigs, while only subclinical intestinal lesions were evident from DM and BC pigs. BC, and to some degree DM, are superior to preterm IF in stimulating gut maturation and body growth, using a gradual advancement of enteral feeding volume over the first 11 days after preterm birth in piglets. Whether the same is true in preterm infants remains to be tested. PMID:27445345

  12. RECIPROCAL RELATION BETWEEN POPULATION AND ENVIRONMENT: INNOVATIONS ON FLORA DATA COLLECTION.

    PubMed

    Dangol, D R

    2009-01-01

    In recent years, social and natural scientists have gained interest in understanding reciprocal relations between human populations and the environment. Research methods have been developed for investigating the secrets of interations of human and environment. This paper describes the flora data collection methods used in a longitudinal research project "Reciprocal Relation Between Population and the Environment" and highlights how the research sites were selected, how the research plots were designed in each site and how the qualitative and quantitative data of flora found in each research plot were recorded. This paper also discusses how the flora data can be linked with sociodemographic data and how the data can be used to unfold the effect of human activities on flora diversity and/or the effect of flora on the life of the human population in the study area. PMID:22923985

  13. Functional Environmental Screening of a Metagenomic Library Identifies stlA; A Unique Salt Tolerance Locus from the Human Gut Microbiome

    PubMed Central

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

    2013-01-01

    Functional environmental screening of metagenomic libraries is a powerful means to identify and assign function to novel genes and their encoded proteins without any prior sequence knowledge. In the current study we describe the identification and subsequent analysis of a salt-tolerant clone from a human gut metagenomic library. Following transposon mutagenesis we identified an unknown gene (stlA, for “salt tolerance locus A”) with no current known homologues in the databases. Subsequent cloning and expression in Escherichia coli MKH13 revealed that stlA confers a salt tolerance phenotype in its surrogate host. Furthermore, a detailed in silico analysis was also conducted to gain additional information on the properties of the encoded StlA protein. The stlA gene is rare when searched against human metagenome datasets such as MetaHit and the Human Microbiome Project and represents a novel and unique salt tolerance determinant which appears to be found exclusively in the human gut environment. PMID:24349412

  14. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

    PubMed

    Endt, Kathrin; Stecher, Bärbel; Chaffron, Samuel; Slack, Emma; Tchitchek, Nicolas; Benecke, Arndt; Van Maele, Laurye; Sirard, Jean-Claude; Mueller, Andreas J; Heikenwalder, Mathias; Macpherson, Andrew J; Strugnell, Richard; von Mering, Christian; Hardt, Wolf-Dietrich

    2010-01-01

    Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att), sseD) causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed a sIgA response, and most had cleared the pathogen from the gut lumen. sIgA limited pathogen access to the mucosal surface and protected from gut inflammation in challenge infections. This protection was O-antigen specific, as demonstrated with pathogens lacking the S. typhimurium O-antigen (wbaP, S. enteritidis) and sIgA-deficient mice (TCRβ(-/-)δ(-/-), J(H) (-/-), IgA(-/-), pIgR(-/-)). Surprisingly, sIgA-deficiency did not affect the kinetics of pathogen clearance from the gut lumen. Instead, this was mediated by the microbiota. This was confirmed using 'L-mice' which harbor a low complexity gut flora, lack colonization resistance and develop a normal sIgA response, but fail to clear S. tm(att) from the gut lumen. In these mice, pathogen clearance was achieved by transferring a normal complex microbiota. Thus, besides colonization resistance ( = pathogen blockage by an intact microbiota), the microbiota mediates a second, novel protective function, i.e. pathogen clearance. Here, the normal microbiota re-grows from a state of depletion and disturbed composition and gradually clears even very high pathogen loads from the gut lumen, a site inaccessible to most "classical" immune effector mechanisms. In conclusion, sIgA and microbiota serve complementary protective functions. The microbiota confers colonization resistance and mediates pathogen clearance in primary infections, while sIgA protects from disease if the host re-encounters the same pathogen. This has

  15. 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

  16. Miocene floras from Fingerrock Wash, southwestern Nevada

    USGS Publications Warehouse

    Wolfe, Jack A.

    1964-01-01

    Two floras of Miocene age, the Fingerrock and Stewart Spring, are found in a stratigraphic section that also contains fossil mammals. The Fingerrock flora occurs in beds below the Stewart Spring local fauna of transitional HemingfordianBarstovian (middle-late Miocene) age, and the Stewart Spring flora occurs above that fauna but below the Cedar Mountain local fauna of Cerrotejonian (earliest Pliocene) age.The late Hemingfordian Fingerrock flora was dominated by the live oak, Quercus chrysolepis, but most of the flora is composed of species found in contemporaneous floras of the Columbia Plateau. These species include lobed Quercus, Carya, Ulmus, Zelkova, Platamis, and Acer. The lack here of certain other species found in this association to the north indicates that the Fingerrock flora lived in a drier climate than prevailed at the same time on the Columbia Plateau. Nevertheless the Fingerrock flora was a warm-temperate mesophytic flora. Twenty-four species are described from the Fingerrock flora, none of which are new. The early, or more probably middle, Barstovian Stewart Spring flora is, besides the expected lacustrine element, dominated by Quercus chrysolepis, Picea breweriana, and Chamaecyparis nootkatensis. This assemblage is typically found only in western Nevada and is further restricted to floras of Barstovian and Clarendonian age. Most of the species in the Stewart Spring flora appear to be descended from northern mesophytic forms, although the flora has a subhumid aspect different from the northern floras. Only a small element in the Stewart Spring flora may contain species of southern origin. Several phylads in the Stewart Spring flora are now found on the margins of and in the Great Basin. The Stewart Spring flora contains 42 described species, 9 of which are new.

  17. Engineering the gut microbiota to treat hyperammonemia

    PubMed Central

    Shen, Ting-Chin David; Albenberg, Lindsey; Bittinger, Kyle; Chehoud, Christel; Chen, Ying-Yu; Judge, Colleen A.; Chau, Lillian; Ni, Josephine; Sheng, Michael; Lin, Andrew; Wilkins, Benjamin J.; Buza, Elizabeth L.; Lewis, James D.; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Bushman, Frederic D.; Wu, Gary D.

    2015-01-01

    Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility. PMID:26098218

  18. Engineering the gut microbiota to treat hyperammonemia.

    PubMed

    Shen, Ting-Chin David; Albenberg, Lindsey; Bittinger, Kyle; Chehoud, Christel; Chen, Ying-Yu; Judge, Colleen A; Chau, Lillian; Ni, Josephine; Sheng, Michael; Lin, Andrew; Wilkins, Benjamin J; Buza, Elizabeth L; Lewis, James D; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Bushman, Frederic D; Wu, Gary D

    2015-07-01

    Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility. PMID:26098218

  19. Metagenomic identification of a novel salt tolerance gene from the human gut microbiome which encodes a membrane protein with homology to a brp/blh-family β-carotene 15,15'-monooxygenase.

    PubMed

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

    2014-01-01

    The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane. PMID:25058308

  20. 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

  1. 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

  2. Probiotics, gut microbiota and health.

    PubMed

    Butel, M-J

    2014-01-01

    The human gut is a huge complex ecosystem where microbiota, nutrients, and host cells interact extensively, a process crucial for the gut homeostasis and host development with a real partnership. The various bacterial communities that make up the gut microbiota have many functions including metabolic, barrier effect, and trophic functions. Hence, any dysbiosis could have negative consequences in terms of health and many diseases have been associated to impairment of the gut microbiota. These close relationships between gut microbiota, health, and disease, have led to great interest in using probiotics (i.e. live micro-organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate the gut microbiota to prevent or treat some diseases. This review focuses on probiotics, their mechanisms of action, safety, and major health benefits. Health benefits remain to be proven in some indications, and further studies on the best strain(s), dose, and algorithm of administration to be used are needed. Nevertheless, probiotic administration seems to have a great potential in terms of health that justifies more research. PMID:24290962

  3. Effect of ceftazidime and gentamicin on the oropharyngeal and faecal flora of patients with haematological malignancies.

    PubMed

    Murdoch, D A; Gibbs, S; Price, C G; Easmon, S; Franklin, J; Lister, T A; Tabaqchali, S

    1990-09-01

    Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro-intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria. PMID:2228830

  4. A catalog of the mouse gut metagenome.

    PubMed

    Xiao, Liang; Feng, Qiang; Liang, Suisha; Sonne, Si Brask; Xia, Zhongkui; Qiu, Xinmin; Li, Xiaoping; Long, Hua; Zhang, Jianfeng; Zhang, Dongya; Liu, Chuan; Fang, Zhiwei; Chou, Joyce; Glanville, Jacob; Hao, Qin; Kotowska, Dorota; Colding, Camilla; Licht, Tine Rask; Wu, Donghai; Yu, Jun; Sung, Joseph Jao Yiu; Liang, Qiaoyi; Li, Junhua; Jia, Huijue; Lan, Zhou; Tremaroli, Valentina; Dworzynski, Piotr; Nielsen, H Bjørn; Bäckhed, Fredrik; Doré, Joël; Le Chatelier, Emmanuelle; Ehrlich, S Dusko; Lin, John C; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2015-10-01

    We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies. PMID:26414350

  5. Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome

    PubMed Central

    McNulty, Nathan P.; Wu, Meng; Erickson, Alison R.; Pan, Chongle; Erickson, Brian K.; Martens, Eric C.; Pudlo, Nicholas A.; Muegge, Brian D.; Henrissat, Bernard; Hettich, Robert L.; Gordon, Jeffrey I.

    2013-01-01

    The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism's 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight

  6. Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome

    SciTech Connect

    McNulty, Nathan; Wu, Meng; Erickson, Alison L; Pan, Chongle; Erickson, Brian K; Martens, Eric C; Pudlo, Nicholas A; Muegge, Brian; Henrissat, Bernard; Hettich, Robert {Bob} L; Gordon, Jeffrey

    2013-01-01

    The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising .90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism s 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight

  7. Insights into bread melanoidins: fate in the upper digestive tract and impact on the gut microbiota using in vitro systems.

    PubMed

    Helou, Cynthia; Denis, Sylvain; Spatz, Madeleine; Marier, David; Rame, Véronique; Alric, Monique; Tessier, Frédéric J; Gadonna-Widehem, Pascale

    2015-12-01

    Bread melanoidins are heterogeneous, nitrogen-containing, brown macromolecules generated during the last stages of the Maillard reaction in bread. The aim of this study was to investigate the impact and fate of these bread melanoidins in the human gastrointestinal tract using in vitro systems. Batch systems as well as the TNO gastrointestinal tract were used for studying the digestion of various bread samples. These samples included bread crumb, bread crust and two bread-crust-simulating models: a fiber-free model (gluten, starch and glucose heated together) and its control, free of Maillard reaction products (gluten heated separately than starch and glucose). Furthermore, the impact of these two bread-crust-simulating models on the gut microbiota was assessed using a static anaerobic batch system. Bread melanoidins from bread crust and its model were shown to be partially digested by amylases and proteases, suggesting that these melanoidins have peptidic as well as glycosidic bonds in their skeleton. The impact of bread melanoidins from the bread-crust-simulating models and their digestion products on the gut microbiota revealed an individual-dependent response for most flora except for enterobacteria. This flora decreased by -22%, -48% & -100% depending on the individual. Thus, bread melanoidins seem to exert an anti-inflammatory effect by inhibiting enterobacteria. PMID:26364594

  8. Numidum massiliense gen. nov., sp. nov., a new member of the Bacillaceae family isolated from the human gut.

    PubMed

    Tidjani Alou, M; Nguyen, T-T; Armstrong, N; Rathored, J; Khelaifia, S; Raoult, D; Fournier, P-E; Lagier, J-C

    2016-07-01

    Numidum massiliense gen. nov., sp. nov., strain mt3(T) is the type strain of Numidum gen. nov., a new genus within the family Bacillaceae. This strain was isolated from the faecal flora of a Tuareg boy from Algeria. We describe this Gram-positive facultative anaerobic rod and provide its complete annotated genome sequence according to the taxonogenomics concept. Its genome is 3 755 739 bp long and contains 3453 protein-coding genes and 64 RNA genes, including eight rRNA genes. PMID:27354918

  9. Vaginal flora in asymptomatic women.

    PubMed

    Tashjian, J H; Coulam, C B; Washington, J A

    1976-09-01

    Four groups of 25 asymptomatic women--pregnant, premenopausal and taking oral contraceptives, premenopausal and not taking oral contraceptives, and postmenopausal--were studied for the presence in vaginal specimens of aerobic bacteria, anaerobic bacteria, fungi, Mycoplasma, Chlamydia, herpes simplex virus, mycobacteria, and Trichomonas. No significant differences in microbial flora were found among the groups. PMID:957791

  10. Ulmaceae for Flora of Missouri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The family Ulmaceae is treated for the Flora of Missouri, a detailed floristic manual for the state published by the Missouri (State) Department of Conservation. Three genera and 11 species are recognized; full morphological descriptions, dichotomous keys, and brief summaries of geographical and ec...

  11. 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

  12. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid

    PubMed Central

    Collado, Maria Carmen; Rautava, Samuli; Aakko, Juhani; Isolauri, Erika; Salminen, Seppo

    2016-01-01

    Interaction with intestinal microbes in infancy has a profound impact on health and disease in later life through programming of immune and metabolic pathways. We collected maternal faeces, placenta, amniotic fluid, colostrum, meconium and infant faeces samples from 15 mother-infant pairs in an effort to rigorously investigate prenatal and neonatal microbial transfer and gut colonisation. To ensure sterile sampling, only deliveries at full term by elective caesarean section were studied. Microbiota composition and activity assessment by conventional bacterial culture, 16S rRNA gene pyrosequencing, quantitative PCR, and denaturing gradient gel electrophoresis revealed that the placenta and amniotic fluid harbour a distinct microbiota characterised by low richness, low diversity and the predominance of Proteobacteria. Shared features between the microbiota detected in the placenta and amniotic fluid and in infant meconium suggest microbial transfer at the foeto-maternal interface. At the age of 3–4 days, the infant gut microbiota composition begins to resemble that detected in colostrum. Based on these data, we propose that the stepwise microbial gut colonisation process may be initiated already prenatally by a distinct microbiota in the placenta and amniotic fluid. The link between the mother and the offspring is continued after birth by microbes present in breast milk. PMID:27001291

  13. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid.

    PubMed

    Collado, Maria Carmen; Rautava, Samuli; Aakko, Juhani; Isolauri, Erika; Salminen, Seppo

    2016-01-01

    Interaction with intestinal microbes in infancy has a profound impact on health and disease in later life through programming of immune and metabolic pathways. We collected maternal faeces, placenta, amniotic fluid, colostrum, meconium and infant faeces samples from 15 mother-infant pairs in an effort to rigorously investigate prenatal and neonatal microbial transfer and gut colonisation. To ensure sterile sampling, only deliveries at full term by elective caesarean section were studied. Microbiota composition and activity assessment by conventional bacterial culture, 16S rRNA gene pyrosequencing, quantitative PCR, and denaturing gradient gel electrophoresis revealed that the placenta and amniotic fluid harbour a distinct microbiota characterised by low richness, low diversity and the predominance of Proteobacteria. Shared features between the microbiota detected in the placenta and amniotic fluid and in infant meconium suggest microbial transfer at the foeto-maternal interface. At the age of 3-4 days, the infant gut microbiota composition begins to resemble that detected in colostrum. Based on these data, we propose that the stepwise microbial gut colonisation process may be initiated already prenatally by a distinct microbiota in the placenta and amniotic fluid. The link between the mother and the offspring is continued after birth by microbes present in breast milk. PMID:27001291

  14. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics.

    PubMed

    Pastorelli, Luca; De Salvo, Carlo; Mercado, Joseph R; Vecchi, Maurizio; Pizarro, Theresa T

    2013-01-01

    The gut mucosa is constantly challenged by a bombardment of foreign antigens and environmental microorganisms. As such, the precise regulation of the intestinal barrier allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation. In support of this concept, emerging evidence points to defects in components of the epithelial barrier as etiologic factors in the pathogenesis of inflammatory bowel diseases (IBDs). In fact, the integrity of the intestinal barrier relies on different elements, including robust innate immune responses, epithelial paracellular permeability, epithelial cell integrity, as well as the production of mucus. The purpose of this review is to systematically evaluate how alterations in the aforementioned epithelial components can lead to the disruption of intestinal immune homeostasis, and subsequent inflammation. In this regard, the wealth of data from mouse models of intestinal inflammation and human genetics are pivotal in understanding pathogenic pathways, for example, that are initiated from the specific loss of function of a single protein leading to the onset of intestinal disease. On the other hand, several recently proposed therapeutic approaches to treat human IBD are targeted at enhancing different elements of gut barrier function, further supporting a primary role of the epithelium in the pathogenesis of chronic intestinal inflammation and emphasizing the importance of maintaining a healthy and effective intestinal barrier. PMID:24062746

  15. [Gut microbiota: Description, role and pathophysiologic implications].

    PubMed

    Landman, C; Quévrain, E

    2016-06-01

    The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. PMID:26749318

  16. Gut microbiota and host metabolism in liver cirrhosis

    PubMed Central

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-01-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  17. Gut microbiota and host metabolism in liver cirrhosis.

    PubMed

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  18. GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION

    PubMed Central

    Yang, Tao; Santisteban, Monica M.; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J.; Raizada, Mohan K.; Mohamadzadeh, Mansour

    2015-01-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  19. Gut dysbiosis is linked to hypertension.

    PubMed

    Yang, Tao; Santisteban, Monica M; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J; Raizada, Mohan K; Mohamadzadeh, Mansour

    2015-06-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  20. Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

    SciTech Connect

    Zaborin, A.; Smith, D.; Garfield, K.; Quensen, J.; Shakhsheer, B.; Kade, M.; Tirrell, M.; Tiedje, J.; Gilbert, J. A.; Zaborina, O.; Alverdy, J. C.

    2014-09-23

    We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.

  1. Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

    DOE PAGESBeta

    Zaborin, A.; Smith, D.; Garfield, K.; Quensen, J.; Shakhsheer, B.; Kade, M.; Tirrell, M.; Tiedje, J.; Gilbert, J. A.; Zaborina, O.; et al

    2014-09-23

    We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candidamore » taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.« less

  2. Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

    PubMed Central

    Zaborin, Alexander; Smith, Daniel; Garfield, Kevin; Quensen, John; Shakhsheer, Baddr; Kade, Matthew; Tirrell, Matthew; Tiedje, James; Gilbert, Jack A.

    2014-01-01

    ABSTRACT We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style. PMID:25249279

  3. Gut Microbiota and Type 1 Diabetes

    PubMed Central

    Vaarala, Outi

    2012-01-01

    The gut immune system has a key role in the development of autoimmune diabetes, and factors that control the gut immune system are also regulators of beta-cell autoimmunity. Gut microbiota modulate the function of the gut immune system by their effect on the innate immune system, such as the intestinal epithelial cells and dendritic cells, and on the adaptive immune system, in particular intestinal T cells. Due to the immunological link between gut and pancreas, e.g. the shared lymphocyte homing receptors, the immunological changes in the gut are reflected in the pancreas. According to animal studies, changes in gut microbiota alter the development of autoimmune diabetes. This has been demonstrated by antibiotics that induce changes in the gut microbiota. Furthermore, gut-colonizing microbes may modify the incidence of autoimmune diabetes in animal models. Deficient toll-like receptor (TLR) signaling, mediating microbial stimulus in immune cells, prevents autoimmune diabetes, which appears to be dependent on alterations in the intestinal microbiota. Although few studies have been conducted in humans, recent studies suggest that the abundance of Bacteroides and lack of butyrate-producing bacteria in fecal microbiota are associated with beta-cell autoimmunity and type 1 diabetes. It is possible that altered gut microbiota are associated with immunological aberrancies in type 1 diabetes. The changes in gut microbiota could lead to alterations in the gut immune system, such as increased gut permeability, small intestinal inflammation, and impaired tolerance to food antigens, all of which are observed in type 1 diabetes. Poor fitness of gut microbiota could explain why children who develop type 1 diabetes are prone to enterovirus infections, and do not develop tolerance to cow milk antigens. These candidate risk factors of type 1 diabetes may imply an increased risk of type 1 diabetes due to the presence of gut microbiota that do not support health. Despite the complex

  4. Germ warfare: probiotics in defense of the premature gut.

    PubMed

    Hammerman, Cathy; Bin-Nun, Alona; Kaplan, Michael

    2004-09-01

    The potential benefits of a predominantly lactic acid bacterial flora include an improved balance of gut microbial ecology and decreased susceptibility of the gut mucosa to bacterial translocation via adherence to the intestinal mucosa, strengthening mucosal barrier function. These properties should be especially beneficial to the premature neonate with (1) delayed establishment of nor-mal flora, increasing the potential for proliferation of pathogenic bacteria and (2) immature development of the intestinal mucosa, rendering it more susceptible to the translocation of these pathogenic bacteria and leading to extra-intestinal spread and systemic disease. Early probiotic supplementation in preterm infants is theoretically sound and associated with minimal risk. Clinical data remain preliminary but are supportive of a reduction in feeding intoler