SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells

Short-chain fatty acids (SCFA), produced by colonic bacterial flora ferment ation of dietary carbohydrates, promote colonic Na absorption through mecha nisms not well understood. We hypothesized that SCFA promote increased expr ession of apical membrane Na/H exchange (NHE), serving as luminal physiolog ical cues for regulating colonic Na absorptive capacity. Studies were perfo rmed in human colonic C2/bbe (C2) monolayers and in vivo. In C2 cells expos ed to butyrate, acetate, proprionate, or the poorly metabolized SCFA isobut yrate, apical membrane NHE3 activity and protein expression increased in a time- and concentration-dependent manner, whereas no changes were observed for NHE2. In contrast, no significant changes in brush-border hydrolase or villin expression were noted. Analogous to the in vitro findings, rats fed the soluble fiber pectin exhibited a time- dependent increase in colonic NH E3, but not NHE2, protein, mRNA, and brush-border activity. These changes w ere region-specific, as no changes were observed in the ileum. We conclude that luminal SCFA are important physiological cues for regulating colonic N a absorptive function, allowing the colon to adapt to chronic changes in di etary carbohydrate and Na loads.