title: Effect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo.
abstract: 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.
authors.affiliation: University of Melbourne Department of Medicine, The Royal Melbourne Hospital, Victoria, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Mariadason
authors.forename: D
authors.initials: D
authors.lastname: Kilias
authors.forename: A
authors.initials: A
authors.lastname: Catto-Smith
authors.forename: P R
authors.initials: PR
authors.lastname: Gibson
mesh_terms: 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
chemical_list: D002087:Butyrates; D006867:Hydrolases; D000469:Alkaline Phosphatase; D018819:Dipeptidyl Peptidase 4