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

Hadar Bootz-Maoz; Ayelet Pearl; Ehud Melzer; Stephen Malnick; Efrat Sharon; Yifat Bennet; Rotem Tsentsarevsky; Shlomi Abuchatzera; Sivan Amidror; Elana Aretz; Shalhevet Azriel; Chen Gam Ze Letova; Maria Naama; Irit Shoval; Orly Yaron; Sarit Karako-Lampert; Shai Bel; Nissan Yissachar

doi:10.1016/j.celrep.2022.111657

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

Hadar Bootz-Maoz, Ayelet Pearl, Ehud Melzer, Stephen Malnick, Efrat Sharon, Yifat Bennet, Rotem Tsentsarevsky, Shlomi Abuchatzera, Sivan Amidror, Elana Aretz, Shalhevet Azriel, Chen Gam Ze Letova, Maria Naama, Irit Shoval, Orly Yaron, Sarit Karako-Lampert, Shai Bel, Nissan Yissachar

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English
Article number	111657
Journal	Cell Reports
Volume	41
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.111657
State	Published - 15 Nov 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Funding

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.

Funders	Funder number
Gassner Fund for Medical Research, Israel
Broad Institute	2615/18
Israel Science Foundation	1384/18

Keywords

CP: Microbiology
gut microbiota
intestinal epithelial barrier
irritable bowel syndrome
low-FODMAP diet

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2022.111657

Cite this

Bootz-Maoz, H., Pearl, A., Melzer, E., Malnick, S., Sharon, E., Bennet, Y., Tsentsarevsky, R., Abuchatzera, S., Amidror, S., Aretz, E., Azriel, S., Gam Ze Letova, C., Naama, M., Shoval, I., Yaron, O., Karako-Lampert, S., Bel, S., & Yissachar, N. (2022). Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome. Cell Reports, 41(7), Article 111657. https://doi.org/10.1016/j.celrep.2022.111657

@article{7ea13808609944f39e3542189d6c0309,

title = "Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome",

abstract = "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.",

keywords = "CP: Microbiology, gut microbiota, intestinal epithelial barrier, irritable bowel syndrome, low-FODMAP diet",

author = "Hadar Bootz-Maoz and Ayelet Pearl and Ehud Melzer and Stephen Malnick and Efrat Sharon and Yifat Bennet and Rotem Tsentsarevsky and Shlomi Abuchatzera and Sivan Amidror and Elana Aretz and Shalhevet Azriel and {Gam Ze Letova}, Chen and Maria Naama and Irit Shoval and Orly Yaron and Sarit Karako-Lampert and Shai Bel and Nissan Yissachar",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = nov,

day = "15",

doi = "10.1016/j.celrep.2022.111657",

language = "אנגלית",

volume = "41",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

}

Bootz-Maoz, H, Pearl, A, Melzer, E, Malnick, S, Sharon, E, Bennet, Y, Tsentsarevsky, R, Abuchatzera, S, Amidror, S, Aretz, E, Azriel, S, Gam Ze Letova, C, Naama, M, Shoval, I, Yaron, O, Karako-Lampert, S, Bel, S & Yissachar, N 2022, 'Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome', Cell Reports, vol. 41, no. 7, 111657. https://doi.org/10.1016/j.celrep.2022.111657

TY - JOUR

T1 - Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome

AU - Bootz-Maoz, Hadar

AU - Pearl, Ayelet

AU - Melzer, Ehud

AU - Malnick, Stephen

AU - Sharon, Efrat

AU - Bennet, Yifat

AU - Tsentsarevsky, Rotem

AU - Abuchatzera, Shlomi

AU - Amidror, Sivan

AU - Aretz, Elana

AU - Azriel, Shalhevet

AU - Gam Ze Letova, Chen

AU - Naama, Maria

AU - Shoval, Irit

AU - Yaron, Orly

AU - Karako-Lampert, Sarit

AU - Bel, Shai

AU - Yissachar, Nissan

PY - 2022/11/15

Y1 - 2022/11/15

N2 - 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.

AB - 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.

KW - CP: Microbiology

KW - gut microbiota

KW - intestinal epithelial barrier

KW - irritable bowel syndrome

KW - low-FODMAP diet

UR - http://www.scopus.com/inward/record.url?scp=85142157389&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.111657

DO - 10.1016/j.celrep.2022.111657

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 36384106

AN - SCOPUS:85142157389

SN - 2211-1247

VL - 41

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 111657

ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Genomics

מיקרוביום [הסכת]

Cite this

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Equipment

Genomics

Press/Media

מיקרוביום [הסכת]

Cite this