Early Gut–Vascular Barrier Breakdown Precedes Colitis Onset in Murine Models

Mohamed Abdou M, Kreiß L, Schmid B, Thoma OM, Krüger R, Bénard A, Müller T, Knauß A, Gabel M, González-Acera M, Lyu Y, Petter K, Lindemann A, Saad Msa, Eichhorn P, Becker C, Naschberger E, Zundler S, Weigmann B, Rath T, Atreya R, Kühl AA, Trajanoski Z, Atreya I, Bacher P, Bojarski C, Bosch-Voskens C, Chang HD, Diefenbach A, Günther C, Hegazy AN, Hildner K, Klose CS, Koop K, Krug S, Leppkes M, López-Posadas R, Ludwig LS, Neufert C, Patankar J, Plattner C, Prüß M, Radbruch A, Romagnani C, Ronchi F, Sanders A, Scheffold A, Schulzke JD, Schumann M, Siegmund B, Triantafyllopoulou A, Weidinger C, Wirtz S, Friedrich O, Waldner M, Neurath M, Herrmann M, Schürmann S, Britzen-Laurent N, Stürzl M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cellular and Molecular Gastroenterology and Hepatology Elsevier

Book Volume: 20

Article Number: 101795

Journal Issue: 9

DOI: 10.1016/j.jcmgh.2026.101795

Abstract

Background & Aims The gut–vascular barrier plays a pivotal role in inflammatory bowel disease pathogenesis. We introduce a novel 3-dimensional multiphoton endomicroscopy approach for real-time and sensitive detection of vascular permeability in the colon to identify colitis-associated vascular changes in the early stages. Methods Using fluorescence-based multiphoton endomicroscopy, we visualized dynamic changes in vascular permeability in vivo during longitudinal observations in different experimental colitis models (dextran sodium sulfate– and T cell transfer–induced colitis). Vascular permeability changes were systematically compared with conventional inflammatory markers, including weight loss, endoscopic scoring, colon length, histopathology, and immune cell infiltration. To assess molecular regulation of barrier functions, the expression of key molecules of vascular (plasmalemma vesicle-associated protein, vascular endothelial cadherin) and epithelial (epithelial cadherin) barriers was investigated during development of colitis at the single-cell level. Results Multiphoton endomicroscopy provided unprecedented 3-dimensional visualization of vascular permeability dynamics and showed that vascular dysfunction occurs prior to epithelial barrier breakdown and the detection of traditional inflammatory markers across all colitis models. Distinct spatial vascular permeability patterns strongly correlated with mucosal damage severity, further supporting that early gut–vascular barrier disruption precedes mucosal barrier breakdown. Additionally, this sequence was confirmed at the molecular level, with the vascular upregulation of the transendothelial permeability channel plasmalemma vesicle–associated protein occurring before downregulation of the epithelial barrier molecule E-cadherin. Conclusions Multiphoton endomicroscopy with 3-dimensional imaging demonstrated gut–vascular barrier dysfunction in the very early stages of experimental colitis. Further development of multiphoton endomicroscopy-based vascular permeability analysis for use in routine clinical monitoring of patients may provide new perspectives to improve diagnosis and clinical decision-making in inflammatory bowel disease.

Authors with CRIS profile

Mariam Mohamed Abdou Professur für Molekulare und Experimentelle Chirurgie Lucas Kreiß Roohian Lehrstuhl für Medizinische Biotechnologie (MBT) Benjamin Schmid FAU Optical Imaging Competence Center (FAU OICE) Oana-Maria Thoma Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology René Krüger Department of Medicine 4 – Nephrology and Hypertension Tanja Müller Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Annkathrin Knauß Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Michael Gabel Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Yanmin Lyu Professur für Molekulare und Experimentelle Chirurgie Aylin Lindemann Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Mina saad aziz Saad Department of Surgery Philip Eichhorn Institute of Pathology Christoph Becker Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Elisabeth Naschberger Medizinische Fakultät Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Benno Weigmann Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Timo Rath Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Imke Atreya Medizinische Fakultät Caroline Voskens Department of Dermatology Claudia Günther Medizinische Fakultät Kai Hildner Juniorprofessur für Pneumologie/Immunologie Kristina Koop Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Clemens Neufert Medizinische Fakultät Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Cornelia Weidinger Department of Anaesthesiology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie (MBT) Maximilian Waldner Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Sebastian Schürmann Lehrstuhl für Medizinische Biotechnologie (MBT) Nathalie Britzen-Laurent Department of Surgery Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie

Involved external institutions

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

How to cite

APA:

Mohamed Abdou, M., Kreiß, L., Schmid, B., Thoma, O.-M., Krüger, R., Bénard, A.,... Stürzl, M. (2026). Early Gut–Vascular Barrier Breakdown Precedes Colitis Onset in Murine Models. Cellular and Molecular Gastroenterology and Hepatology, 20(9). https://doi.org/10.1016/j.jcmgh.2026.101795

MLA:

Mohamed Abdou, Mariam, et al. "Early Gut–Vascular Barrier Breakdown Precedes Colitis Onset in Murine Models." Cellular and Molecular Gastroenterology and Hepatology 20.9 (2026).

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