Disease duration impacts intestinal gene expression profiles in crohn's disease but not in ulcerative colitis

Susanne Ibing^{1

2

3}, Christopher Tastad⁴, Bernhard Y Renard^{1

2

3}, Louis J Cohen⁵, Carmen Argmann⁶, Drew Helmus⁵, Eric E Schadt^{7

8}, Miriam Merad^{9

10

11}, Anjli Kukreja¹², Sudha Visvanathan¹², Bruce E Sands⁵, Marla Dubinsky⁵, Mayte Suarez-Fariñas^{7

8}, Jean-Frédéric Colombel⁵, Erwin P Böttinger^{1

2

3}, Judy H Cho⁴, Francesca Petralia⁶, Ryan C Ungaro⁵

Affiliations

¹ Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Prof.-Dr-Helmert-Str. 2-3, Potsdam, 14482, Germany.
² Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, 10029, NY, USA.
³ Windreich Dept. of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, USA.
⁴ Department of Pathology, Molecular, and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁵ The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁶ Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁷ Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁸ Icahn Institute for Data Science and Genomic Technology, New York, 10029, NY, USA.
⁹ Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁰ Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, New York.
¹¹ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
¹² Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA.

PMID: 41063393
DOI: 10.1093/ecco-jcc/jjaf179

Disease duration impacts intestinal gene expression profiles in crohn's disease but not in ulcerative colitis

Susanne Ibing et al. J Crohns Colitis. 2025.

. 2025 Oct 8:jjaf179.

doi: 10.1093/ecco-jcc/jjaf179. Online ahead of print.

Authors

Affiliations

¹ Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Prof.-Dr-Helmert-Str. 2-3, Potsdam, 14482, Germany.
² Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, 10029, NY, USA.
³ Windreich Dept. of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, USA.
⁴ Department of Pathology, Molecular, and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁵ The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁶ Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁷ Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
⁸ Icahn Institute for Data Science and Genomic Technology, New York, 10029, NY, USA.
⁹ Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁰ Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, New York.
¹¹ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
¹² Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA.

PMID: 41063393
DOI: 10.1093/ecco-jcc/jjaf179

Abstract

Background: Disease duration is associated with lower treatment response and accrual of bowel damage in Crohn's disease (CD), but not in ulcerative colitis (UC). We aimed to understand intestinal transcriptomic changes associated with disease duration in CD and UC.

Methods: We analyzed intestinal tissue RNA sequencing data from two independent prospective cohorts of CD and UC patients, the Mount Sinai Crohn's and Colitis Registry (MSCCR; NCD = 498, NUC = 421), and the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD; NCD = 777, NUC = 440). We conducted differential expression analysis and subsequent pathway analyses of significantly up- or down-regulated genes, and examined cell type-specific expression of significant genes and pathways in ileal single-cell RNA sequencing data from CD patients (n = 18). We then assessed the association of significant pathways with treatment response in an infliximab-treated CD cohort.

Results: Significantly more genes were differentially expressed with increasing disease duration in CD compared to UC in both cohorts (MSCCR: NCD = 1,472, NUC = 227; SPARC: NCD = 1,248, NUC = 25; q-value < 0.05). A shared gene signature with 263 down- and 135 up-regulated genes in longer standing disease was identified. Pathway analyses revealed significant enrichment in pathways related to oxidative phosphorylation, mitochondrial dysfunction, cholesterol biosynthesis, LXR/RXR activation, and protein modifications. Pre-treatment intestinal gene expression of four disease duration-related pathways were associated with non-response to infliximab.

Conclusion: Disease duration influences intestinal gene expression in CD but significantly less in UC. The identified pathways and genes may inform development of differing biomarkers and treatment strategies in shorter versus longer standing CD.

Keywords: Crohn’s disease; disease duration; gene expression; treatment response.

© The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

PubMed Disclaimer

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Silverchair Information Systems
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Disease duration impacts intestinal gene expression profiles in crohn's disease but not in ulcerative colitis

Affiliations

Disease duration impacts intestinal gene expression profiles in crohn's disease but not in ulcerative colitis

Authors

Affiliations

Abstract

LinkOut - more resources

Full Text Sources

Miscellaneous