Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation
- M Vivinus-Nébot1,2,
- G Frin-Mathy3,
- H Bzioueche2,
- R Dainese3,
- G Bernard1,2,
- R Anty3,4,
- J Filippi3,
- M C Saint-Paul5,
- M K Tulic2,
- V Verhasselt2,
- X Hébuterne3,
- T Piche2,3
- 1Department of Immunology, Pole of Biology, Hôpital Archet 1, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
- 2EA 6203, Université de Nice Sophia Antipolis Nice, Nice, France
- 3Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
- 4INSERM 895, Team 4, Centre Méditérrannéen de Médecine Moléculaire, Nice, France
- 5Department of Histopathology, Hôpital Pasteur, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
- Correspondence to Professor Thierry Piche, Gastroenterology and EA 6203, Hôpital Archet 2, CHU de Nice, France;
- Received 1 November 2012
- Revised 28 June 2013
- Accepted 29 June 2013
- Published Online First 22 July 2013
Objective To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD).
Design Caecal biopsies were collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grade inflammation was evaluated by counting cells, including intraepithelial lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and protein expression of tumour necrosis factor (TNF)-α in biopsies and culture supernatants.
Results IBS-like symptoms were present in 35.4 and 38% of CD and UC patients, respectively. Paracellular permeability was significantly increased in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01, respectively). Significantly lower expression of ZO-1 and α-catenin was detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-α were significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS.
Conclusions In quiescent IBD, IBS-like symptoms related to persistent subclinical inflammation associated with increased colonic paracellular permeability. A persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects associated with abdominal pain in quiescent IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered in quiescent IBD with IBS-like symptoms.