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.
Bibliographical noteFunding Information:
We thank Ron Unger for helpful advice, Sara Gerstein for assistance with organ cultures, the Mathis/Benoist lab for microbial strains, Shani Brown and Sondra Turjeman for critical editing of the manuscript, and members of the Yissachar lab for insightful discussions. This work was supported by the Israel Science Foundation (grant no. 1384/18 ), the Israel Science Foundation —Broad Institute Joint Program (grant no. 2615/18 ), and the Gassner Fund for Medical Research, Israel.
© 2022 The Author(s)
- CP: Microbiology
- gut microbiota
- intestinal epithelial barrier
- irritable bowel syndrome
- low-FODMAP diet
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Orly Yaron (Manager)The Mina and Everard Goodman Faculty of Life Sciences