Influence of pH on the phase distribution of nascent deoxycholic acid in fresh human cecal aspirates

Prolonged large bowel transit time and an associated increase in the propor tion of deoxycholic acid (DCA) in serum and bile have been implicated in th e development of cholesterol-rich gallstones and colon cancer. Prolongation of intestinal transit also increases intracolonic pH that, we hypothesized , should favor the solubilization and absorption of newly formed DCA within the colon. To test this hypothesis, we performed in vitro studies on homog enized cecal aspirates (obtained at colonoscopy) that were incubated anaero bically with [C-14] cholic acid for 16 h after which the pH was adjusted to between 4.0 and 7.0 in 0.5-pH unit steps. The resultant reaction mixtures were centrifuged to separate the supernatant from the precipitate, and the specific activity of [C-14] DCA was quantitated in both phases. As the pH i n the aspirates was manipulated from 4.0 to 7.0, the proportion of newly fo rmed, labeled DCA increased in the supernatant and fell in the precipitate, particularly at a hydrogen ion concentration of <100 x 10(-7) (equivalent to pH 5.0- 7.0). These results show that the solubility of DCA in colonic c ontents increases with increasing pH. If solubility is rate limiting, this should lead to increased absorption that, in turn, would explain why the pr oportion of DCA in serum and bile increases with the prolongation of large bowel transit time.