Stimulation of bicarbonate secretion by luminal short-chain fatty acid in the rat and human colon in vitro.

Acetic, propionic and butyric acids constitute the predominant luminal anions in the colon. Several in vivo studies have suggested that these short-chain fatty acids (SCFAs) induce HCO3- accumulation in the colonic lumen. The purpose of this study was to delineate the mechanism underlying the SCFA-induced HCO3- accumulation in chamber-mounted mucosae from the rat and human colon under short-circuit conditions. HCO3- transport from the serosa bathed with a HCO3(-)-containing solution to the lumen bathed with a HCO3- (and Cl-)-free solution was evaluated from the luminal alkalization rate (JOHSL) by using a pH-stat system. In the rat distal colon, luminal propionate (25 mM) enhanced JOHSL from 0.32 +/- 0.19 to 3.18 +/- 0.22 mumol/cm2/h (n = 5, means +/- SE). Luminal acetate and butyrate (25 mM) similarly enhanced JOHSL. The magnitude of the increase in JOHSL induced by SCFA did not significantly vary among these three SCFAs. On the other hand, luminal lactate (25 mM) failed to affect JOHSL. The SCFA-induced increase in JOHSL was greatly reduced to approximately 30% of the original level when HCO3- was removed from the serosal solution. The short-circuit current and the transepithelial conductance were barely altered by luminal SCFAs or lactate. In the human colon, luminal propionate (25 mM) also caused an increase in JOHSL from 0.54 +/- 0.36 to 1.57 +/- 0.62 mumol/cm2/h (n = 4), which was significantly attenuated by removing serosal HCO3-. These results demonstrate that luminal SCFAs stimulate HCO3- secretion in the colon.