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

John M. Mariadason, Diana Kilias, Anthony Catto-Smith, Peter R. Gibson

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Abstract

Background and Aims: 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 4h. 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.

Original languageEnglish
Pages (from-to)873-879
Number of pages7
JournalJournal of Gastroenterology and Hepatology
Volume14
Issue number9
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

Keywords

  • Butyrate
  • Cell proliferation
  • Colon
  • Epithelium
  • Permeability

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