RT Journal Article SR Electronic T1 Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.08.15.456374 DO 10.1101/2021.08.15.456374 A1 Ayelet Pearl A1 Hadar Bootz A1 Ehud Melzer A1 Efrat Sharon A1 Shlomi Abuchatzera A1 Sivan Amidror A1 Elana Aretz A1 Irit Shoval A1 Orly Yaron A1 Stephen Malnick A1 Nissan Yissachar YR 2021 UL http://biorxiv.org/content/early/2021/08/15/2021.08.15.456374.abstract AB 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 colonized gut organ cultures with longitudinal microbiota samples collected from newly-diagnosed and 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.Competing Interest StatementThe authors have declared no competing interest.