Effect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo.
OBJECTIVE
The effects of butyrate on colonic epithelial barrier function are poorly understood. The aim of this study was to examine the short-term effects of butyrate on paracellular permeability of rat distal colonic epithelium.


METHODS
Mucosa mounted in Ussing chambers was treated with butyrate (1-10 mmol/L) for 4 h. Transepithelial conductance, [51Cr]-EDTA flux, mucosal brush border hydrolase activity and epithelial kinetics, using proliferating cell nuclear antigen (PCNA) staining, were measured.


RESULTS
On exposure to butyrate (10 mmol/L, but not 1 or 5 mmol/L), transepithelial conductance was 65 +/- 2% higher (mean +/- SEM; n = 8, P < 0.05, paired t-test) and the rate coefficient for [51Cr]-EDTA flux was 65 +/- 25% higher (P = 0.03) than those of control tissue. Histologically, the epithelium exhibited no signs of injury, but butyrate-treated tissue exhibited interstitial oedema consistent with water uptake in association with butyrate 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), but the number of cells per crypt column staining with PCNA was unchanged. Butyrate significantly reduced the mucosal activities of alkaline phosphatase by 40 +/- 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 differentiated surface epithelial cells, or as a physiological response to Na+-coupled butyrate uptake.
Mariadason
J M
JM
University of Melbourne Department of Medicine, The Royal Melbourne Hospital, Victoria, Australia.
Kilias
D
D
Catto-Smith
A
A
Gibson
P R
PR
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004594:Electrophysiology; D006867:Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008871:Microvilli; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D002087:Butyrates; D006867:Hydrolases; D000469:Alkaline Phosphatase; D018819:Dipeptidyl Peptidase 4