Search in the Abstract Database

Abstracts Search 2019

P097 Intestinal barrier dysfunction in association with fibrosis during experimental acute and chronic colitis in mice

T. Breugelmans*1, J. De Man1, B. De Winter1, A. Smet1

1University of Antwerp, Laboratory of Experimental Medicine and Pediatrics, Antwerp, Belgium


Intestinal barrier dysfunction is a significant contributor to the pathophysiology of Inflammatory bowel diseases (IBD). Furthermore, chronic inflammation and barrier dysfunction may result in the mucosal and submucosal deposition of the extracellular matrix, which progressively leads to structural fibrosis, a major complication in IBD. Here, we aimed at investigating intestinal inflammation, barrier function and the development of fibrosis using the dextran sodium sulphate (DSS) colitis mouse model.


Seven-week old C57BL6/J mice were treated with 3 subsequent cycles of 2% DSS in their drinking water for 7 days followed by a recovery phase of 7 days with normal drinking water to induce acute (cycle 1) and chronic colitis (cycle 2 and 3). Control animals received only drinking water. Disease activity was daily monitored. At the end of each DSS treatment (Day 7, 21 and 35), mice were used for compliance measurements to investigate the viscoelastic properties of the colon. Thereafter, at euthanasia, colonic tissue was collected to investigate inflammation (H&E), fibrosis (Masson’s trichrome), MPO activity and expression of tight junctions (Cldn1, Cldn2, Ocln, Cdh1, Zo-1, Zo-3), cell polarity proteins (Par3-Par6-aPKC, Crb3) and cytokines (Tnf-α, Il-1β, Il-6, Il-10, Il-22). Intestinal permeability was determined via oral gavage (4 h before euthanasia) of 4 kDa FITC-dextran, followed by measuring the fluorescence in the blood.


Acute colitis in mice was correlated with marked intestinal inflammation (Figure 1A-C), increased expression of several pro-inflammatory cytokines (Tnf-α, Il-1β and Il-22; Figure 1D-E), increased intestinal permeability (Figure 1F), aberrant expression of Cldn1, Cldn2, Zo-3 and Par3 (Figure 1G-M) and a remarkable decrease in colonic compliance at lower balloon distension volumes (<80 µl, p < 0.05). Progression towards chronic colitis resulted in intestinal inflammation (Figure 1A–C) with marked bowel wall thickening, reduced colonic compliance at higher distension volumes (>120 µl, p < 0.05) and fibrotic lesions. Although intestinal permeability was not significantly altered anymore at Day 21 and 35 (Figure 1F), barrier mediators, such as Cldn2, Zo-3 and Par3 (Figure 1G–M), were still changed.

Abstract PO97 – Figure 1. (A) Representative H&E stained colon sections of control and DSS-treated mice. (B) Scoring of microscopic inflammation which was based on immune cell infiltration, goblet cell loss and epithelial damage. (C) MPO measurement to analyse colonic neutrophil activation. (D-E) Colonic mRNA expression of II-lb and Tnf-α cytokines analysed by qPCR. (F) FITC-dextran intestinal permeability assay. (G–M) Colonic mRNA expression of the polarity protein genes Par3 and aPkcλ and tight junction protein genes Cldnl and 2, Zo-1 and -3 and Occludin analysed by qPCR. One-way ANOVA *p < .05; **p < .01; ***p < .401 vs. control (Ctrl) (n = 3–10 mice/group)


Colitis progression investigated in the DSS mouse model was associated with intestinal inflammation and barrier dysfunction in the acute phase and the additional development of fibrosis in the chronic phase. The underlying mechanisms involved in barrier dysfunction and existence of fibrosis, require further investigation.