Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis

Background & Aims: Mechanisms of diarrhea in ulcerative colitis (UC) are st ill unknown. Functional and structural characterization of epithelial barri er and transport properties in ulcerative colitis (UC) was performed. Metho ds: Inflamed sigmoid colon epithelium from UC patients was studied by alter nating current impedance analysis to determine the pure epithelial resistan ce as a measure of intestinal barrier function. Tight junction (TJ) structu re was investigated by freeze-fracture electron microscopy. Results: Althou gh total wall resistance was reduced in UC by 50%, impedance analysis uncov ered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 Omega . cm(2), which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 Omega . cm(2) caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0. 25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts. Conclusions: The inflamed colonic mucosa in UC has an impair ed barrier function that is much move pronounced than previously assumed. A n altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mecha nism contributes to the diarrhea in UC.