Effect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo

Background and Aims: The effects of butyrate on colonic epithelial barrier function are poorly understood. The aim of this study was to examine the sh ort-term effects of butyrate on paracellular permeability of rat distal col onic epithelium. Methods: Mucosa mounted in Ussing chambers was treated with butyrate (1-10 mmol/L) for 4h. Transepithelial conductance, [Cr-51]-EDTA flux, mucosal bru sh border hydrolase activity and epithelial kinetics, using proliferating c ell nuclear antigen (PCNA) staining, were measured. Results: On exposure to butyrate (10 mmol/L, but not 1 or 5 mmol/L), transe pithelial conductance was 65 +/- 2% higher (mean +/- SEM; n = 8, P < 0.05, paired t-test) and the rate coefficient for [Cr-51]-EDTA flux was 65 +/- 25 % higher (P = 0.03) than those of control tissue. Histologically, the epith elium exhibited no signs of injury, but butyrate-treated tissue exhibited i nterstitial oedema consistent with water uptake in association with butyrat e absorption. Butyrate caused a reduction in crypt column height to 30.6 +/ - 1.6 cells from 33.4 +/- 1.8 cells in controls (n = 10, P< 0.03), bur: the number of cells per crypt column staining with PCNA was unchanged. Butyrat e significantly reduced the mucosal activities of alkaline phosphatase by 4 0 +/- 16%, maltase by 54 +/- 12% and dipeptidyl peptidase IV by 41 +/- 14%. Conclusions: Acute exposure to butyrate increased paracellular permeability in rat distal colon. The mechanism involved may relate to the loss of diff erentiated surface epithelial cells, or as a physiological response to Na+- coupled butyrate uptake. (C) 1999 Blackwell Science Asia Pry Ltd.