Project description:Changes in microbiome composition have been associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infused gut organ cultures with longitudinal microbiota samples collected from therapy-naïve irritable bowel syndrome (IBS) patients under low-FODMAP (fermentable Oligo-, Di-, Mono-saccharides and Polyols) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene-sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a unique pathway discovery approach for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of low-FODMAP diet and reinforce the potential feasibility of microbiome based-therapies in IBS.
Project description:Changes in microbiome composition have been associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infused gut organ cultures with longitudinal microbiota samples collected from therapy-naïve irritable bowel syndrome (IBS) patients under low-FODMAP (fermentable Oligo-, Di-, Mono-saccharides and Polyols) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene-sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a unique pathway discovery approach for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of low-FODMAP diet and reinforce the potential feasibility of microbiome based-therapies in IBS.
Project description:Changes in microbiome composition have been associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infused gut organ cultures with longitudinal microbiota samples collected from therapy-naïve irritable bowel syndrome (IBS) patients under low-FODMAP (fermentable Oligo-, Di-, Mono-saccharides and Polyols) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene-sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a unique pathway discovery approach for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of low-FODMAP diet and reinforce the potential feasibility of microbiome based-therapies in IBS.
Project description:Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis, characterized by altered gut function and frequent psychiatric co-morbidity. Although altered intestinal microbiome profiles have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role of the microbiota, we colonized germ-free mice with fecal microbiota from healthy controls or IBS patients with accompanying anxiety, and monitored gut function and behavior. Mouse microbiota profiles clustered according to their human donors. Despite having taxonomically similar composition as controls, mice with IBS microbiota had distinct serum metabolomic profiles related to neuro- and immunomodulation. Mice with IBS, but not control microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation and anxiety-like behavior. These results support the notion that the microbiota contributes to both intestinal and behavioral manifestations of IBS and rationalize the use of microbiota-directed therapies in ameliorating IBS.
Project description:The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease pathogenesis has been difficult due to the apparent disconnect between animal and human studies and a lack of an integrated multi-omics view in the context of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.
Project description:IBS-D is a disease with multi-factor interaction between environment, central system, gut and gene, and its pathogenesis is relatively complex. In order to find the regulation of miRNA in the pathogenesis of IBS-D, intestinal tissue samples of IBS-D patients and healthy subjects were obtained (5 IBS-D patients,5 healthy subjects), Changes in miRNA expression profiles were detected by high-throughput sequencing.
Project description: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. RNA-Seq analysis of the human gut microbiome during consumption of a plant- or animal-based diet.
Project description:IBS-D is a disease with multi-factor interaction between environment, central system, gut and gene, and its pathogenesis is relatively complex. In order to find the regulation of mRNA in the pathogenesis of IBS-D, intestinal tissue samples of IBS-D patients and healthy subjects were obtained (5 IBS-D patients,5 healthy subjects), Changes in mRNA expression profiles were detected by high-throughput sequencing.
Project description:Micro-inflammation and gut dysfunction are features of diarrhea-irritable bowel syndrome (d-IBS) patients, although the underlying interacting molecular mechanisms remain mostly unknown. Therefore, we aimed to identify critical networks and signaling pathways active in chronic diarrhea-associated inflammation. Experiment Overall Design: Healthy volunteers and d-IBS patients were studied. Jejunal biopsies were subjected to chip analysis (Affymetrix Human Genome U133 Plus 2.0 GeneChips).