Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome

Changes in microbiome composition are 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 infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a low-fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) 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 pathway discovery platform 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 a low-FODMAP diet and reinforce the potential feasibility of microbiome-based therapies in IBS.