Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD

Gonzalez-Acera M, Patankar J, Erkert L, Cineus R, Gamez-Belmonte R, Leupold T, Bubeck M, Bao L, Dinkel M, Wang R, Schickedanz L, Limberger H, Stolzer I, Gerlach K, Diemand L, Mascia F, Gupta P, Naschberger E, Koop K, Plattner C, Sturm G, Weigmann B, Günther C, Wirtz S, Stürzl M, Hildner K, Kühl AA, Siegmund B, Gieβl A, Atreya R, Hegazy AN, Trajanoski Z, Neurath M, Becker C (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Gut BMJ Publishing Group

Article Number: gutjnl-2024-333729

DOI: 10.1136/gutjnl-2024-333729

Abstract

Background: IBD is a chronic inflammatory condition driven by complex genetic and immune interactions, yet preclinical models often fail to fully recapitulate all aspects of the human disease. A systematic comparison of commonly used IBD models is essential to identify conserved molecular mechanisms and improve translational relevance. Objective: We performed a multimodel transcriptomic analysis of 13 widely used IBD mouse models to uncover coregulatory gene networks conserved between preclinical colitis/ileitis and human IBD and to define model-specific and conserved cellular, subcellular and molecular signatures. Design: We employed comparative transcriptomic analyses with curated and a priori statistical correlative methods between mouse models versus IBD patient datasets at both bulk and single-cell levels. Results: We identify IBD-related pathways, ontologies and cellular compositions that are translatable between mouse models and patient cohorts. We further describe a conserved core inflammatory signature of IBD-associated genes governing T-cell homing, innate immunity and epithelial barrier that translates into the new mouse gut Molecular Inflammation Score (mMIS). Moreover, specific mouse IBD models have distinct signatures for B-cell, T-cell and enteric neurons. We discover that transcriptomic relatedness of models is a function of the mode of induction, not the canonical immunotype (Th1/Th2/Th17). Moreover, the model compendium database is made available as a web explorer (http://trr241.hosting.rrze.uni-erlangen.de/SEPIA/). Conclusion: This integrated multimodel approach provides a framework for systematically assessing the molecular landscape of intestinal inflammation. Our findings reveal conserved inflammatory circuits, refine model selection, offering a valuable resource for the IBD research community.

Authors with CRIS profile

Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Lena Erkert Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Tamara Leupold Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Lili Bao Professur für Molekulare Gastroenterologie Martin Dinkel Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Ru Wang Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Laura Schickedanz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Heidi Limberger Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Iris Stolzer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Katharina Gerlach Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Fabrizio Mascia Medizinische Fakultät Pooja Gupta Professur für Stammzell-Modelle seltener neuraler Erkrankungen Elisabeth Naschberger Department of Surgery Kristina Koop Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Benno Weigmann Medizinische Fakultät Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Kai Hildner Juniorprofessur für Pneumologie/Immunologie Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Medizinische Universität Innsbruck AT Austria (AT)

How to cite

APA:

Gonzalez-Acera, M., Patankar, J., Erkert, L., Cineus, R., Gamez-Belmonte, R., Leupold, T.,... Becker, C. (2025). Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD. Gut. https://doi.org/10.1136/gutjnl-2024-333729

MLA:

Gonzalez-Acera, Miguel, et al. "Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD." Gut (2025).

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