Distal Fecal Wash Host Transcriptomics Identifies Inflammation Throughout the Colon and Terminal Ileum

Stav Dan; Bella Ungar; Shani Ben-Moshe; Keren Bahar Halpern; Miri Yavzori; Ella Fudim; Orit Picard; Chaya Mushka Abitbol; Sivan Harnik; Iris Barshack; Uri Kopylov; Shomron Ben-Horin; Shalev Itzkovitz

doi:10.1016/j.jcmgh.2023.02.002

Distal Fecal Wash Host Transcriptomics Identifies Inflammation Throughout the Colon and Terminal Ileum

Stav Dan, Bella Ungar, Shani Ben-Moshe, Keren Bahar Halpern, Miri Yavzori, Ella Fudim, Orit Picard, Chaya Mushka Abitbol, Sivan Harnik, Iris Barshack, Uri Kopylov, Shomron Ben-Horin, Shalev Itzkovitz^*

^*Corresponding author for this work

Department of Molecular Cell Biology

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

6 Citations (Scopus)

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Abstract

Non-invasive modalities for assessing active endoscopic and histological inflammation in Crohn’s disease and Ulcerative Colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histological inflammation in inflammatory bowel disease (IBD) patients with distal colitis 1. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown. 59 IBD patients and 50 controls were prospectively enrolled. Biopsies and fecal washes from the distal colon, proximal colon and terminal ileum were compared. Host transcriptomics was performed on the biopsies and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic and histological parameters. We found that host transcriptomics of distal fecal washes robustly classify histological inflammation in ileal and proximal colonic Crohn’s disease, even without distal colonic involvement (Area Under the Receiver Operating Characteristic Curve, AUC=0.94+-0.09). We further found that fecal washes consist of modules of co-expressed genes of immune, stromal and epithelial origin that are indicative of endoscopic disease severity. Fecal wash host transcriptomics also captures expression of gene modules previously associated with lack of response to biological therapies. Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal-colonic axis. [Display omitted]

Original language	English
Pages (from-to)	1-15
Number of pages	15
Journal	CMGH
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.jcmgh.2023.02.002
Publication status	Published - Jan 2023

Funding

Funding Information: Funding Supported by the Wolfson Family Charitable Trust, the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Dr Beth Rom-Rymer Stem Cell Research Fund, the Minerva Stiftung grant, the Weizmann-Sheba joint research program, the Israel Ministry of Innovation, Science & Technology, the Israel Science Foundation grant 1486/16, the European Research Council under the European Union's Horizon 2020 research and innovation program grant 768956, the Chan Zuckerberg Initiative grant CZF2019-002434, the Bert L. and N. Kuggie Vallee Foundation, and the Howard Hughes Medical Institute international research scholar award (S.I.); and by the Talpiot medical excellence grant and the Weizmann-Sheba joint research program (B.U.). Funding Information: Funding Supported by the Wolfson Family Charitable Trust , the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Dr Beth Rom-Rymer Stem Cell Research Fund, the Minerva Stiftung grant, the Weizmann-Sheba joint research program, the Israel Ministry of Innovation, Science & Technology, the Israel Science Foundation grant 1486/16, the European Research Council under the European Union’s Horizon 2020 research and innovation program grant 768956, the Chan Zuckerberg Initiative grant CZF2019-002434, the Bert L. and N. Kuggie Vallee Foundation, and the Howard Hughes Medical Institute international research scholar award (S.I.); and by the Talpiot medical excellence grant and the Weizmann-Sheba joint research program (B.U.). Publisher Copyright: © 2023 The Authors

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology

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Cite this

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title = "Distal Fecal Wash Host Transcriptomics Identifies Inflammation Throughout the Colon and Terminal Ileum",

abstract = "Non-invasive modalities for assessing active endoscopic and histological inflammation in Crohn{\textquoteright}s disease and Ulcerative Colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histological inflammation in inflammatory bowel disease (IBD) patients with distal colitis 1. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown. 59 IBD patients and 50 controls were prospectively enrolled. Biopsies and fecal washes from the distal colon, proximal colon and terminal ileum were compared. Host transcriptomics was performed on the biopsies and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic and histological parameters. We found that host transcriptomics of distal fecal washes robustly classify histological inflammation in ileal and proximal colonic Crohn{\textquoteright}s disease, even without distal colonic involvement (Area Under the Receiver Operating Characteristic Curve, AUC=0.94+-0.09). We further found that fecal washes consist of modules of co-expressed genes of immune, stromal and epithelial origin that are indicative of endoscopic disease severity. Fecal wash host transcriptomics also captures expression of gene modules previously associated with lack of response to biological therapies. Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal-colonic axis. [Display omitted] ",

author = "Stav Dan and Bella Ungar and Shani Ben-Moshe and Halpern, \{Keren Bahar\} and Miri Yavzori and Ella Fudim and Orit Picard and Abitbol, \{Chaya Mushka\} and Sivan Harnik and Iris Barshack and Uri Kopylov and Shomron Ben-Horin and Shalev Itzkovitz",

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T1 - Distal Fecal Wash Host Transcriptomics Identifies Inflammation Throughout the Colon and Terminal Ileum

AU - Dan, Stav

AU - Ungar, Bella

AU - Ben-Moshe, Shani

AU - Halpern, Keren Bahar

AU - Yavzori, Miri

AU - Fudim, Ella

AU - Picard, Orit

AU - Abitbol, Chaya Mushka

AU - Harnik, Sivan

AU - Barshack, Iris

AU - Kopylov, Uri

AU - Ben-Horin, Shomron

AU - Itzkovitz, Shalev

PY - 2023/1

Y1 - 2023/1

N2 - Non-invasive modalities for assessing active endoscopic and histological inflammation in Crohn’s disease and Ulcerative Colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histological inflammation in inflammatory bowel disease (IBD) patients with distal colitis 1. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown. 59 IBD patients and 50 controls were prospectively enrolled. Biopsies and fecal washes from the distal colon, proximal colon and terminal ileum were compared. Host transcriptomics was performed on the biopsies and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic and histological parameters. We found that host transcriptomics of distal fecal washes robustly classify histological inflammation in ileal and proximal colonic Crohn’s disease, even without distal colonic involvement (Area Under the Receiver Operating Characteristic Curve, AUC=0.94+-0.09). We further found that fecal washes consist of modules of co-expressed genes of immune, stromal and epithelial origin that are indicative of endoscopic disease severity. Fecal wash host transcriptomics also captures expression of gene modules previously associated with lack of response to biological therapies. Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal-colonic axis. [Display omitted]

AB - Non-invasive modalities for assessing active endoscopic and histological inflammation in Crohn’s disease and Ulcerative Colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histological inflammation in inflammatory bowel disease (IBD) patients with distal colitis 1. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown. 59 IBD patients and 50 controls were prospectively enrolled. Biopsies and fecal washes from the distal colon, proximal colon and terminal ileum were compared. Host transcriptomics was performed on the biopsies and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic and histological parameters. We found that host transcriptomics of distal fecal washes robustly classify histological inflammation in ileal and proximal colonic Crohn’s disease, even without distal colonic involvement (Area Under the Receiver Operating Characteristic Curve, AUC=0.94+-0.09). We further found that fecal washes consist of modules of co-expressed genes of immune, stromal and epithelial origin that are indicative of endoscopic disease severity. Fecal wash host transcriptomics also captures expression of gene modules previously associated with lack of response to biological therapies. Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal-colonic axis. [Display omitted]

UR - https://www.scopus.com/pages/publications/85159423334

U2 - 10.1016/j.jcmgh.2023.02.002

DO - 10.1016/j.jcmgh.2023.02.002

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SP - 1

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JO - CMGH

JF - CMGH

IS - 1

ER -

Distal Fecal Wash Host Transcriptomics Identifies Inflammation Throughout the Colon and Terminal Ileum

Abstract

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