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| Item Type: | Article |
|---|---|
| Title: | Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD |
| Creators Name: | Gonzalez-Acera, Miguel, Patankar, Jay V., Erkert, Lena, Cineus, Roodline, Gamez-Belmonte, Reyes, Leupold, Tamara, Bubeck, Marvin, Bao, Li-Li, Dinkel, Martin, Wang, Ru, Schickedanz, Laura, Limberger, Heidi, Stolzer, Iris, Gerlach, Katharina, Diemand, Leonard, Mascia, Fabrizio, Gupta, Pooja, Naschberger, Elisabeth, Koop, Kristina, Plattner, Christina, Sturm, Gregor, Weigmann, Benno, Günther, Claudia, Wirtz, Stefan, Stürzl, Michael, Hildner, Kai, Kühl, Anja A., Siegmund, Britta, Gießl, Andreas, Atreya, Raja, Hegazy, Ahmed N., Trajanoski, Zlatko, Neurath, Markus F. and Becker, Christoph |
| 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. |
| Keywords: | Animal Disease Models, Colitis, Gene Expression Profiling, Gene Regulatory Networks, Inflammatory Bowel Diseases, Transcriptome, Animals, Mice |
| Source: | Gut |
| ISSN: | 0017-5749 |
| Publisher: | BMJ Publishing Group |
| Volume: | 74 |
| Number: | 10 |
| Page Range: | 1602-1615 |
| Date: | 8 September 2025 |
| Additional Information: | Leif S. Ludwig and Ashley D. Sanders are collaborators of the TRR241 IBDome Consortium. |
| Official Publication: | https://doi.org/10.1136/gutjnl-2024-333729 |
| PubMed: | View item in PubMed |
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