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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background & Aims: Noninvasive modalities for assessing active endoscopic and histologic 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 histologic inflammation in inflammatory bowel disease patients with distal colitis. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown. Methods: Fifty-nine inflammatory bowel disease patients and 50 controls were prospectively enrolled. Biopsy specimens and fecal washes from the distal colon, proximal colon, and terminal ileum were compared. Host transcriptomics were performed on the biopsy specimens and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic, and histologic parameters. Results: We found that host transcriptomics of distal fecal washes robustly classify histologic inflammation in ileal and proximal colonic Crohn's disease, even without distal colonic involvement (area under the receiver operating characteristic curve, 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 a lack of response to biological therapies. Conclusions: Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal–colonic axis.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalCMGH
Volume16
Issue number1
DOIs
StatePublished - Jan 2023

Funding

FundersFunder number
Fannie Sherr Fund
Howard Hughes Medical Institute
Vallee Foundation
Horizon 2020 Framework Programme
Chan Zuckerberg InitiativeCZF2019-002434
European Commission768956
Minerva Foundation
Israel Science Foundation1486/16
Ministry of Science and Technology, Israel
Wolfson Family Charitable Trust
Edmond de Rothschild Foundation

    Keywords

    • Histology
    • IBD
    • Therapy Outcome
    • Transcriptomics

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