Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome (RNA-Seq I)

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. Overall design: Gut organ cultures were infused ex vivo with fecal samples collected from the first 3 patients that successfully completed the clinical phase (and exhibited positive clinical response), pre- and following 6 weeks of diet, at equivalent bacterial loads (107 CFUs/mL; Fig. S2A-B) (n=3 patients, pre- and post-diet, in duplicates, for a total of 12 samples).