Gut. 2008 Sep 29. [Epub ahead of print]
Impaired intestinal barrier integrity in the colon of irritable bowel syndrome patients: involvement of soluble mediators.
Piche T, Barbara G, Aubert P, Bruley des Varannes S, Dainese R, Nano JL, Cremon C, Stanghellini V, De Giorgio R, Galmiche JP, Neunlist M. IMAD, Universite de Nantes, France.
BACKGROUND: Growing evidences suggest that patients with irritable bowel syndrome (IBS) have increased intestinal permeability. In addition, mucosal soluble mediators are involved in the pathophysiology of pain in IBS. We aimed to investigate: (1) paracellular permeability in colonic biopsies of IBS patient (2) the ability of soluble factors from colonic biopsies to reproduce in vitro these alterations.
METHODS: Paracellular permeability was measured in colonic biopsies of IBS patients and healthy subjects mounted in Ussing chambers. Cleared supernatant (SUP) of culture from colonic biopsies was collected and applied to Caco-2 cells for 48h. Paracellular permeability and transepithelial resistance (TER) were evaluated. mRNA expression of the tight junction (TJ) proteins, zonula occludens (ZO)-1 and occludin, was assessed in colonic biopsies. Abdominal pain was assessed using a validated questionnaire.
RESULTS: Permeability of colonic biopsies was significantly higher in IBS compared to healthy subject. These changes were associated with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy subjects. SUP-induced increased paracellular permeability correlated with the severity of abdominal pain.
CONCLUSIONS: Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS patients. These findings might pave the way both to identify novel biomarkers as well as new therapeutic targets in IBS.
PMID: 18824556 [PubMed - as supplied by publisher]