Gut microbiomes from Gambian infants reveal the development of a non-industrialized Prevotella-based trophic network.

Distinct bacterial trophic networks exist in the gut microbiota of individuals in industrialized and non-industrialized countries. In particular, non-industrialized gut microbiomes tend to be enriched with Prevotella species. To study the development of these Prevotella-rich compositions, we investigated the gut microbiota of children aged between 7 and 37 months living in rural Gambia (616 children, 1,389 stool samples, stratified by 3-month age groups). These infants, who typically eat a high-fibre, low-protein diet, were part of a double-blind, randomized iron intervention trial (NCT02941081) and here we report the secondary outcome. We found that child age was the largest discriminating factor between samples and that anthropometric indices (collection time points, season, geographic collection site, and iron supplementation) did not significantly influence the gut microbiome. Prevotella copri, Faecalibacterium prausnitzii and Prevotella stercorea were, on average, the most abundant species in these 1,389 samples (35%, 11% and 7%, respectively). Distinct bacterial trophic network clusters were identified, centred around either P. stercorea or F. prausnitzii and were found to develop steadily with age, whereas P. copri, independently of other species, rapidly became dominant after weaning. This dataset, set within a critical gut microbial developmental time frame, provides insights into the development of Prevotella-rich gut microbiomes, which are typically understudied and are underrepresented in western populations.

Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice.

BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5-8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points. RESULTS: Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment. CONCLUSIONS: These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.

Prevotella copri ameliorates cholestasis and liver fibrosis in primary sclerosing cholangitis by enhancing the FXR signalling pathway.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by bile duct inflammation, fibrosis, bile acid (BA) metabolism disorders and gut microbiota dysbiosis. At present, the aetiology and pathogenesis of PSC are not clear, and there is no specific or effective treatment available. Therefore, new research perspectives are needed to explore effective methods to treat PSC and improve symptoms. The intestinal microbiota of patients with PSC is known to be significantly different from that of healthy people. By comparing differentially abundant bacterial genera in PSC patients, it was found that the abundance of Prevotella copri (P. copri) was significantly decreased, suggesting that this species may have a protective effect against PSC disease. Therefore, comprehensively exploring the role and possible function of P. copri in the disease process is worthwhile. In this study, a PSC mouse model was established by feeding mice a customized diet supplemented with 0.1% (w/w) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for one week, and the abundance of P. copri was confirmed to be decreased in this model. Previous studies in patients and animal models have demonstrated that gut microbiota intervention is an acceptable treatment for some diseases. We found that intervention with P. copri could significantly improve cholestasis and liver fibrosis by enhancing the FXR-related signalling pathway in PSC mice. Together, through the overall effect of P. copri on intestinal microbiota structure and its association with BAs, we speculate that P. copri intervention might be as potential biological treatment of PSC.

Multivariate associative patterns between the gut microbiota and large-scale brain network connectivity.

Research on the gut-brain axis has accelerated substantially over the course of the last years. Many reviews have outlined the important implications of understanding the relation of the gut microbiota with human brain function and behavior. One substantial drawback in integrating gut microbiome and brain data is the lack of integrative multivariate approaches that enable capturing variance in both modalities simultaneously. To address this issue, we applied a linked independent component analysis (LICA) to microbiota and brain connectivity data.We analyzed data from 58 healthy females (mean age = â€¯21.5 years). Magnetic Resonance Imaging data were acquired using resting state functional imaging data. The assessment of gut microbial composition from feces was based on sequencing of the V4 16S rRNA gene region. We used the LICA model to simultaneously factorize the subjects' large-scale brain networks and microbiome relative abundance data into 10 independent components of spatial and abundance variation.LICA decomposition resulted in four components with non-marginal contribution of the microbiota data. The default mode network featured strongly in three components, whereas the two-lateralized fronto-parietal attention networks contributed to one component. The executive-control (with the default mode) network was associated to another component. We found that the abundance of Prevotella genus was associated with the strength of expression of all networks, whereas Bifidobacterium was associated with the default mode and frontoparietal-attention networks.We provide the first exploratory evidence for multivariate associative patterns between the gut microbiota and brain network connectivity in healthy humans considering the complexity of both systems.

Ecology impacts the decrease of Spirochaetes and Prevotella in the fecal gut microbiota of urban humans.

Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets - especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals and humans.By using a controlled study design with captive mammals we could verify that host phylogeny is the most dominant driver of mammalian gut microbiota composition. However, the effect of ecology appears to be able to overcome host phylogeny and should therefore be studied in more detail in future studies. Most importantly, our study could observe a remarkable decrease of Spirochaetes and Prevotella in westernized humans and platyrrhines, which is probably not only due to diet, but also to the social behavior and structure in these communities.Our study highlights the importance of phylogenetic relationship and ecology within the evolution of mammalian fecal microbiota composition. Particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities might be associated to lifestyle dependent rapid evolutionary changes, potentially involved in the establishment of dysbiotic microbiomes, which promote the etiology of chronic diseases.

Evaluation of hypoglycemic effect, safety and immunomodulation of Prevotella copri in mice.

The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes. In this study the hypoglycemic effect of live P. copri was confirmed in mice and pasteurization of P. copri was shown to further enhance its capacity to improve glucose tolerance. The safety of live and pasteurized P. copri was evaluated by a 29-day oral toxicity study in mice. P. copri did not induce any adverse effects on body growth. General examination of the mice, gross pathological and histological analysis showed no abnormalities of the vital organs. Though relative liver weights were lower in the pasteurized (4.574 g ± 0.096) and live (4.347 g ± 0.197) P. copri fed groups than in the control mice (5.005 g ± 0.103) (p = 0.0441 and p = 0.0147 respectively), no liver biochemical marker aberrations were detected. Creatinine serum levels were significantly lower in mice fed with live (p = 0.001) but not pasteurized (p = 0.163) P. copri compared to those of control mice. Haematological parameter analysis and low plasma Lipopolysaccharide Binding Protein (LBP) levels ruled out systemic infection and inflammation. Immunomodulation capacity by P. copri as determined by blood plasma cytokine analysis was limited and gut colonisation occurred in only one of the 10 mice tested. Taken together, no major adverse effects were detected in P. copri treated groups compared to controls.

Microbial interaction: Prevotella spp. reduce P. aeruginosa induced inflammation in cystic fibrosis bronchial epithelial cells.

BACKGROUND: In Cystic Fibrosis (CF) airways, the dehydrated, thick mucus promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, the vicious, self-perpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa (P. aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known. MATERIALS: We assessed innate immune signalling in CF airway epithelial cells in response to clinical strains of P. histicola, P. nigresens and P. aeruginosa. CFBE41o- cells were infected with P. aeruginosa (MOI 100, 2h) followed by infection with P. histicola or P. nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments. RESULTS: Our study shows that P. histicola and P. nigresens can reduce the growth of P. aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of the investigated Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-κB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections. CONCLUSION: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobic Prevotella spp.. The observed modified NF-κB and MAPK signalling indicates some mechanisms underlying this interaction that could offer a novel therapeutic approach to combat chronic P. aeruginosa infection in people with CF.

Prevotella diversity, niches and interactions with the human host.

The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host-Prevotella symbiotic relationship in the context of maintaining human health.

Prevotella histicola Protects From Arthritis by Expansion of Allobaculum and Augmenting Butyrate Production in Humanized Mice.

Bacterial therapeutics are the emergent alternatives in treating autoimmune diseases such as Rheumatoid Arthritis [RA]. P. histicola MCI 001 is one such therapeutic bacterium that has been proven to treat autoimmune diseases such as RA and multiple sclerosis [MS] in animal models. The present study characterized P. histicola MCI 001 isolated from a human duodenal biopsy, and evaluated its impact on the gut microbial and metabolic profile in a longitudinal study using the collagen-induced arthritis model in HLA-DQ8.AEo transgenic mice. P. histicola MCI 001 though closely related to the type strain of P. histicola, DSM 19854, differed in utilizing glycerol. In culture, P. histicola MCI 001 produced vitamins such as biotin and folate, and was involved in digesting complex carbohydrates and production of acetate. Colonization study showed that duodenum was the predominant niche for the gavaged MCI 001. A longitudinal follow-up of gut microbial profile in arthritic mice treated with MCI 001 suggested that dysbiosis caused due to arthritis was partially restored to the profile of naïve mice after treatment. A taxon-level analysis suggested an expansion of intestinal genus Allobaculum in MCI001 treated arthritic mice. Eubiosis achieved post treatment with P. histicola MCI 001 was also reflected in the increased production of short-chain fatty acids [SCFAs]. Present study suggests that the treatment with P. histicola MCI 001 leads to an expansion of Allobaculum by increasing the availability of simple carbohydrates and acetate. Restoration of microbial profile and metabolites like butyrate induce immune and gut homeostasis.

A Pilot Study on the Metabolic Impact of Mediterranean Diet in Type 2 Diabetes: Is Gut Microbiota the Key?

The Mediterranean diet (MD) has been recommended for type 2 diabetes (T2D) treatment. The impact of diet in shaping the gut microbiota is well known, particularly for MD. However, the link between MD and diabetes outcome improvement is not completely clear. This study aims to evaluate the role of microbiota modulation by a nonpharmacological intervention in patients with T2D. In this 12-week single-arm pilot study, nine participants received individual nutritional counseling sessions promoting MD. Gut microbiota, biochemical parameters, body composition, and blood pressure were assessed at baseline, 4 weeks, and 12 weeks after the intervention. Adherence to MD [assessed by Mediterranean Diet Adherence Screener (MEDAS) score] increased after the intervention. Bacterial richness increased after 4 weeks of intervention and was negatively correlated with fasting glucose levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Prevotella to Bacteroides ratio also increased after 4 weeks. In contrast, glycated haemoglobin (HbA1c) and HOMA-IR were only decreased at the end of study. Alkaline phosphatase activity was assessed in fecal samples and was negatively correlated with HbA1c and positively correlated with bacterial diversity. The results of this study reinforce that MD adherence results in a better glycemic control in subjects with T2D. Changes in gut bacterial richness caused by MD adherence may be relevant in mediating the metabolic impact of this dietary intervention.

A Korean-Style Balanced Diet Has a Potential Connection with Ruminococcaceae Enterotype and Reduction of Metabolic Syndrome Incidence in Korean Adults.

Metabolic syndrome is associated with usual dietary patterns that may be involved in enterotypes. We aimed to understand the potential relationship of enterotypes and dietary patterns to influence metabolic syndrome in the Koreans. Using the Korea National Health and Nutrition Examination Survey (KNHANES)-VI in 2014, metabolic parameters were also analyzed among the dietary patterns classified by principal component analysis in Korean adults. The fecal microbiota data of 1199 Korean adults collected in 2014 were obtained from the Korea Centers for Disease Control and Prevention. Enterotypes were classified based on Dirichlet multinomial mixtures (DMM) by Mothur v.1.36. The functional abundance of fecal bacteria was analyzed using the PICRUSt2 pipeline. Korean adults were clustered into three dietary patterns including Korean-style balanced diets (KBD, 20.4%), rice-based diets (RBD, 17.2%), and Western-style diets (WSD, 62.4%) in KNHANES. The incidence of metabolic syndrome was lowered in the order of RBD, WSD, and KBD. The participants having a KBD had lower serum C-reactive protein and triglyceride concentrations than those with RBD and WSD (p < 0.05). Three types of fecal bacteria were classified as Ruminococcaceae type (ET-R, 28.7%), Prevotella type (ET-P, 52.2%), and Bacteroides type (ET-B, 42.1%; p < 0.05). ET-P had a higher abundance of Prevotella copri, while ET-R contained a higher abundance of Alistipes, Akkermansia muciniphila, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. ET-B had a higher abundance of the order Bilophila (p < 0.05). Metabolism of propanoate, starch, and sucrose in fecal microbiome was higher in ET-P and ET-R, whereas fatty acid metabolism was enhanced in ET-B. Fecal microbiota in ET-P and ET-B had higher lipopolysaccharide biosynthesis activity than that in ET-R. The metabolic results of KBD and RBD were consistent with ET-R and ET-P's gut microbiota metabolism, respectively. In conclusion, Korean enterotypes of ET-P, ET-B, and ET-R were associated with RBD, WSD, and KBD, respectively. This study suggests a potential link between dietary patterns, metabolic syndrome, and enterotypes among Korean adults.

Human gut-derived commensal suppresses generation of T-cell response to gliadin in humanized mice by modulating gut microbiota.

The human intestinal tract is colonized by a large number of diverse microorganisms that play various important physiologic functions. In inflammatory gut diseases including celiac disease (CeD), a dysbiotic state of microbiome has been observed. Interestingly, this perturbed microbiome is normalized towards eubiosis in patients showing recovery after treatment. The treatment has been observed to increase the abundance of beneficial microbes in comparison to non-treated patients. In this study, we investigated the effect of Prevotella histicola or Prevotella melaninogenica, isolated from the duodenum of a treated CeD patient, on the induction and maintenance of oral tolerance to gliadin, a CeD associated subgroup of gluten proteins, in NOD.DQ8.ABo transgenic mice. Conventionally raised mice on a gluten free diet were orally gavaged with bacteria before and after injection with pepsin trypsin digested gliadin (PTD-gliadin). P. histicola suppressed the cellular response to gliadin, whereas P. melaninogenica failed to suppress an immune response against gliadin. Interestingly, tolerance to gliadin in NOD.DQ8.ABo mice may be associated with gut microbiota as mice gavaged with P melaninogenica harbored a different microbial diversity as compared to P. histicola treated mice. This study provides experimental evidence that gut microbes like P. histicola from treated patients can suppress the immune response against gliadin epitopes.

Human Commensal Prevotella histicola Ameliorates Disease as Effectively as Interferon-Beta in the Experimental Autoimmune Encephalomyelitis.

Gut microbiota has emerged as an important environmental factor in the pathobiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Both genetic and environmental factors have been shown to play an important role in MS. Among genetic factors, the human leukocyte antigen (HLA) class II allele such as HLA-DR2, DR3, DR4, DQ6, and DQ8 show the association with the MS. We have previously used transgenic mice expressing MS susceptible HLA class II allele such as HLA-DR2, DR3, DQ6, and DQ8 to validate significance of HLA alleles in MS. Although environmental factors contribute to 2/3 of MS risk, less is known about them. Gut microbiota is emerging as an imporatnt environmental factor in MS pathogenesis. We and others have shown that MS patients have distinct gut microbiota compared to healthy control (HC) with a lower abundance of Prevotella. Additionally, the abundance of Prevotella increased in patients receiving disease-modifying therapies (DMTs) such as Copaxone and/or Interferon-beta (IFNß). We have previously identified a specific strain of Prevotella (Prevotella histicola), which can suppress experimental autoimmune encephalomyelitis (EAE) disease in HLA-DR3.DQ8 transgenic mice. Since Interferon-ß-1b [IFNß (Betaseron)] is a major DMTs used in MS patients, we hypothesized that treatment with the combination of P. histicola and IFNß would have an additive effect on the disease suppression. We observed that treatment with P. histicola suppressed disease as effectively as IFNß. Surprisingly, the combination of P. histicola and IFNß was not more effective than either treatment alone. P. histicola alone or in combination with IFNß increased the frequency and number of CD4+FoxP3+ regulatory T cells in the gut-associated lymphoid tissue (GALT). Treatment with P. histicola alone, IFNß alone, and in the combination decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4+ T cells in the CNS. Additionally, P. histicola alone or IFNß alone or the combination treatments decreased CNS pathology, characterized by reduced microglia and astrocytic activation. In conclusion, our study indicates that the human gut commensal P. histicola can suppress disease as effectively as commonly used MS drug IFNß and may provide an alternative treatment option for MS patients.

Relative abundance of the Prevotella genus within the human gut microbiota of elderly volunteers determines the inter-individual responses to dietary supplementation with wheat bran arabinoxylan-oligosaccharides.

BACKGROUND: The human colon is colonised by a dense microbial community whose species composition and metabolism are linked to health and disease. The main energy sources for colonic bacteria are dietary polysaccharides and oligosaccharides. These play a major role in modulating gut microbial composition and metabolism, which in turn can impact on health outcomes. RESULTS: We investigated the influence of wheat bran arabinoxylan oligosaccharides (AXOS) and maltodextrin supplements in modulating the composition of the colonic microbiota and metabolites in healthy adults over the age of 60. Male and female volunteers, (n = 21, mean BMI 25.2 ± 0.7 kg/m2) participated in the double-blind, cross over supplement study. Faecal samples were collected for analysis of microbiota, short chain fatty acids levels and calprotectin. Blood samples were collected to measure glucose, cholesterol and triglycerides levels. There was no change in these markers nor in calprotectin levels in response to the supplements. Both supplements were well-tolerated by the volunteers. Microbiota analysis across the whole volunteer cohort revealed a significant increase in the proportional abundance of faecal Bifidobacterium species (P ≤ 0.01) in response to AXOS, but not maltodextrin, supplementation. There was considerable inter-individual variation in the other bacterial taxa that responded, with a clear stratification of volunteers as either Prevotella-plus (n = 8; > 0.1% proportional abundance) or Prevotella-minus (n = 13; ≤0.1% proportional abundance) subjects founded on baseline sample profiles. There was a significant increase in the proportional abundance of both faecal Bifidobacterium (P ≤ 0.01) and Prevotella species (P ≤ 0.01) in Prevotella-plus volunteers during AXOS supplementation, while Prevotella and Bacteroides relative abundances showed an inverse relationship. Proportional abundance of 26 OTUs, including bifidobacteria and Anaerostipes hadrus, differed significantly between baseline samples of Prevotella-plus compared to Prevotella-minus individuals. CONCLUSIONS: The wheat bran AXOS supplementation was bifidogenic and resulted in changes in human gut microbiota composition that depended on the initial microbiota profile, specifically the presence or absence of Prevotella spp. as a major component of the microbiota. Our data therefore suggest that initial profiling of individuals through gut microbiota analysis should be considered important when contemplating nutritional interventions that rely on prebiotics. TRIAL REGISTRATION: Clinical trial registration number: NCT02693782 . Registered 29 February 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02693782?term=NCT02693782&rank=1.

Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring.

In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri.

Dominant gut Prevotella copri in gastrectomised non-obese diabetic Goto-Kakizaki rats improves glucose homeostasis through enhanced FXR signalling.

AIMS/HYPOTHESIS: Drug and surgical-based therapies in type 2 diabetes are associated with altered gut microbiota architecture. Here we investigated the role of the gut microbiome in improved glucose homeostasis following bariatric surgery. METHODS: We carried out gut microbiome analyses in gastrectomised (by vertical sleeve gastrectomy [VSG]) rats of the Goto-Kakizaki (GK) non-obese model of spontaneously occurring type 2 diabetes, followed by physiological studies in the GK rat. RESULTS: VSG in the GK rat led to permanent improvement of glucose tolerance associated with minor changes in the gut microbiome, mostly characterised by significant enrichment of caecal Prevotella copri. Gut microbiota enrichment with P. copri in GK rats through permissive antibiotic treatment, inoculation of gut microbiota isolated from gastrectomised GK rats, and direct inoculation of P. copri, resulted in significant improvement of glucose tolerance, independent of changes in body weight. Plasma bile acids were increased in GK rats following inoculation with P. copri and P. copri-enriched microbiota from VSG-treated rats; the inoculated GK rats then showed increased liver glycogen and upregulated expression of Fxr (also known as Nr1h4), Srebf1c, Chrebp (also known as Mlxipl) and Il10 and downregulated expression of Cyp7a1. CONCLUSIONS: Our data underline the impact of intestinal P. copri on improved glucose homeostasis through enhanced bile acid metabolism and farnesoid X receptor (FXR) signalling, which may represent a promising opportunity for novel type 2 diabetes therapeutics.

Prevotella copri is associated with carboplatin-induced gut toxicity.

As a widely used cancer drug, carboplatin often results in serious side effects, such as gut toxicity. In this study, we examined the effects of gut microbiota on mice with carboplatin-induced intestinal mucosal damage. Carboplatin resulted in intestinal mucositis, as indicated by weight loss, diarrhoea, and infiltration of inflammatory cells. It markedly increased the expression of inflammatory cytokines/chemokines in intestine. Carboplatin also altered the diversity and composition of the gut microbiota. A significantly higher abundance of Prevotella copri (P. copri) was observed in carboplatin-treated mice. Moreover, the content of P. copri was positively correlated with the severity of intestinal mucositis. Pretreatment with metronidazole reduced the content of P. copri and relieved the intestinal mucosal injury and inflammation that was induced by carboplatin. Further study revealed that supplementation with P. copri in carboplatin-treated mice resulted in more severe tissue damage, lower tight junction protein expression and higher cytokine expression, and it enhanced both local and systemic immune responses. These data demonstrated that P. copri was involved in the pathological process of carboplatin-induced intestinal mucositis, suggesting a potential attenuation of carboplatin-induced intestinal mucositis by targeting P. copri.

Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults.

Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.

Disruption of sleep architecture in Prevotella enterotype of patients with obstructive sleep apnea-hypopnea syndrome.

INTRODUCTION: Intermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea-hypopnea syndrome (OSAHS). Those manifestations independently affect similar brain regions and contribute to OSAHS-related comorbidities that are known to be related to the host gut alteration microbiota. We hypothesized that gut microbiota disruption may cross talk the brain function via the microbiota-gut-brain axis. Thus, we aim to survey enterotypes and polysomnographic data of patients with OSAHS. METHODS: Subjects were diagnosed by polysomnography, from whom fecal samples were obtained and analyzed for the microbiome composition by variable regions 3-4 of 16S rRNA pyrosequencing and bioinformatic analyses. We examined the fasting levels of interleukin-6 and tumor necrosis factor-alpha of all subjects. RESULTS: Three enterotypes Bacteroides, Ruminococcus, and Prevotella were identified in patients with OSAHS. Arousal-related parameters or sleep stages are significantly disrupted in apnea-hypopnea index (AHI) ≥15 patients with Prevotella enterotype; further analysis this enterotype subjects, obstructive, central, and mixed apnea indices, and mean heart rate are also significantly elevated in AHI ≥15 patients. However, blood cytokines levels of all subjects were not significantly different. CONCLUSIONS: This study indicates the possibility of pathophysiological interplay between enterotypes and sleeps structure disruption in sleep apnea through a microbiota-gut-brain axis and offers some new insight toward the pathogenesis of OSAHS.