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P091 Increased paracellular permeability in colonic biopsies from patients with ulcerative colitis in remission compared with patients with irritable bowel syndrome

G. Katinios*1, S. A. Walter1, M. Vicario2, A. M. González-Castro2, J. D. Söderholm3, H. Hjortswang1, Å. V. Keita4

1Linköping University, Department of Gastroenterology, Linköping, Sweden, 2Vall d'Hebron Institut de Recerca, Digestive Diseases Research Unit, Barcelona, Spain, 3Linköping University, Department of Clinical and Experimental Medicine and Department of Surgery, Linköping, Sweden, 4Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden

Background

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are two chronic intestinal disorders where the pathophysiology is incompletely understood. Unlike IBS, UC goes with inflammation during active disease. Barrier dysfunction is well recognised as an important pathogenic factor in UC, and an impaired barrier function has become evident also in IBS. The aim of this study was to compare differences and similarities in epithelial barrier function between UC patients in remission, IBS patients and healthy controls (HCs).

Methods

Colonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed (Rome III) with moderate to severe symptoms (median IBS-SSS score 343 (range 167–462), and 15 HCs. UC patients had recently been treated for relapse and biopsies were taken from earlier inflamed areas but all patients had a macroscopically healed mucosa. IBS patients had no anti-inflammatory medication while UC patients had the following maintenance treatment: 5-ASA (n = 10), Remicade (n = 1) and azathioprine (n = 3). Biopsies were mounted in Ussing chambers directly after colonoscopy to measure paracellular permeability to 51chromium (Cr)-EDTA. Serosal samples were collected over time and permeability to 51Cr-EDTA was measured by γ-counting. In addition, biopsies were fixed in 4% PFA directly after dissection and further analysed for mast cells by tryptase immunofluorescence staining. Plasma was collected for measurements of TNF-levels by ELISA.

Results

Ussing chamber experiments revealed an increased 51Cr-EDTA permeability in both UC (2.18 ± 0.28, cm/s ×10−6, p < 0.0005) and IBS (1.24 ± 0.13, p < 0.05) compared with HCs (0.89 ± 0.1). Paracellular permeability was higher in UC compared with IBS, p < 0.005. Moreover, there were more mucosal mast cells present in the colon of UC (144.7 ± 19.2, cells/mm2) and IBS (132.1 ± 12.7) compared with HCs (79.0 ± 12.2), p < 0.05. ELISA revealed higher TNF-levels in plasma of UC (8.93 ± 0.34, pg/ml) compared with both IBS (6.18 ± 0.54) and HCs (5.5 ± 0.48), p < 0.0005. Results were presented as mean ± SEM and medications had no significant effect on the results.

Conclusion

The present results contribute to a better understanding of colonic paracellular permeability in patients with UC and IBS. Our findings indicate a more permeable mucosa in both UC patients in remission and IBS patients with moderate to severe disease compared with HCs. Interestingly, the UC patients, even during remission, possess a leakier barrier compared with the IBS patients. The increased TNF-levels in plasma of UC probably refers to the underlying inflammation, however, the leakier barrier in UC compared with IBS seems to be independent on mast cell numbers.