Inhibition of cholera toxin-induced salt and water secretion by short-chain fatty acids in vivo

Abstract

Objective: Determine the effect of SCFAs on cholera toxin-induced colonic secretion. Short-chain fatty acids (acetate, propionate, butyrate) produced by the fermentation of unabsorbed carbohydrates by the colonic bacteria have been shown to stimulate Sodium chloride absorption in the isolated colonic epithelium in vitro. Methods: The effects of SCFAs on cholera toxin (CT)-induced colonic ion and water secretion in adult rabbit have been determined in this study using a perfusion technique with polyethylene glycol as a non-absorbable marker. Facilities of the ICDDR,B's Dhaka-based hospital, the Clinical Research and Service Centre, and its Animal Resources Branch, were used for this study. Results: The study indicates that an 18-hour exposure to purified cholera toxin (5-100 |ig) resulted in colonic water and electrolyte secretion in a dose-dependent manner. Perfusion with different SCFAs significantly (p<0.001) inhibited net colonic water secretion; the rates (|jl/min"'.cm"^) of inhibition being 99%, 94%, and 86% for butyrate (30 mM), propionate (60 mM), and acetate (90 mM) respectively. The rates of net sodium secretion were also significantly less (p<0.0I) in the SCFA-treated colon than those treated with SCFA-free solution (Na+, mean ± SD, jiM/min^-cm'1: 5.17 ± 0.95, 7.31 ± 0.65, 12.7 ± 0.8 for butyrate, propionate, and acetate respectively; and 80.2 ± 20.6 for controls). Butyrate (30 mM) induced the highest inhibition of Na+ and water secretion followed by propionate and acetate. All 3 SCFAs significantly (p<0.01) inhibited Cl- secretion, whereas only butyrate and propionate inhibited K+ secretion. There was no significant alteration of the colonic HC03- secretion by the SCFAs, and none was able to reverse colonic secretion into net absorption. Conclusions: SCFAs stimulate salt and water absorption from CT-stimulated colon and may be useful as absorption-promoting agents in oral rehydration solutions.