title: Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Immunology, Pole of Biology, Hôpital Archet 1, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: M
authors.initials: M
authors.lastname: Vivinus-Nébot
authors.forename: G
authors.initials: G
authors.lastname: Frin-Mathy
authors.forename: H
authors.initials: H
authors.lastname: Bzioueche
authors.forename: R
authors.initials: R
authors.lastname: Dainese
authors.forename: G
authors.initials: G
authors.lastname: Bernard
authors.forename: R
authors.initials: R
authors.lastname: Anty
authors.forename: J
authors.initials: J
authors.lastname: Filippi
authors.forename: M C
authors.initials: MC
authors.lastname: Saint-Paul
authors.forename: M K
authors.initials: MK
authors.lastname: Tulic
authors.forename: V
authors.initials: V
authors.lastname: Verhasselt
authors.forename: X
authors.initials: X
authors.lastname: Hébuterne
authors.forename: T
authors.initials: T
authors.lastname: Piche
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D019108:Tight Junctions / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha
keywords: ABDOMINAL PAIN; INFLAMMATORY BOWEL DISEASE; IRRITABLE BOWEL SYNDROME; TIGHT JUNCTION; TNF-ALPHA