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

Ayelet Pearl, Hadar Bootz, Ehud Melzer, Efrat Sharon, Shlomi Abuchatzera, Sivan Amidror, Elana Aretz, Irit Shoval, Orly Yaron, Stephen Malnick, Nissan Yissachar
doi: https://doi.org/10.1101/2021.08.15.456374
Ayelet Pearl
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
2Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Hadar Bootz
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
2Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Ehud Melzer
3Department of Gastroenterology and Liver Disease, Kaplan Medical Center
5Hadassah Medical Center, the Hebrew University, Jerusalem, Israel
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Efrat Sharon
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
2Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Shlomi Abuchatzera
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
2Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Sivan Amidror
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
2Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Elana Aretz
3Department of Gastroenterology and Liver Disease, Kaplan Medical Center
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Irit Shoval
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Orly Yaron
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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Stephen Malnick
4Department of Internal Medicine, Kaplan Medical Center
5Hadassah Medical Center, the Hebrew University, Jerusalem, Israel
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  • For correspondence: stephen@malnick.net nissan.yissachar@biu.ac.il
Nissan Yissachar
1The Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel
2Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel
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  • For correspondence: stephen@malnick.net nissan.yissachar@biu.ac.il
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 15, 2021.
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Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome
Ayelet Pearl, Hadar Bootz, Ehud Melzer, Efrat Sharon, Shlomi Abuchatzera, Sivan Amidror, Elana Aretz, Irit Shoval, Orly Yaron, Stephen Malnick, Nissan Yissachar
bioRxiv 2021.08.15.456374; doi: https://doi.org/10.1101/2021.08.15.456374
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Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome
Ayelet Pearl, Hadar Bootz, Ehud Melzer, Efrat Sharon, Shlomi Abuchatzera, Sivan Amidror, Elana Aretz, Irit Shoval, Orly Yaron, Stephen Malnick, Nissan Yissachar
bioRxiv 2021.08.15.456374; doi: https://doi.org/10.1101/2021.08.15.456374

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