Abstract: | The enterohepatic circulation and the inability of upper small intestine to actively absorb bile acid are physiological adaptations for maintaining adequate bile acid concentrations in the intestinal lumen for use in lipid digestion and absorption. Certain lipids inhibit bile acid absorption suggesting a possible role of lipids in this scheme. Using isolated intestinal villi preparations of hamster ileum, experiments were conducted to assess the degree of inhibition of bile acid absorption by lipids of various classes and to determine the possible mechanism of inhibition. At an initial bile acid concentration of 10.0 mM, triolein significantly reduced villus uptake of taurocholic acid by 50% and cholic acid by 38%. This inhibition was similar to the degree of inhibition produced by oleic acid (58 and 48%, respectively). Likewise, representative medium-chain and short-chain triglycerides inhibited taurocholic acid uptake by 35 and 39%, respectively. Results show that triglycerides as well as oleic acid inhibit ileal bile acid uptake. Neither oleic acid nor triolein altered bile acid uptake when micelles were absent from incubation solutions. Furthermore, lipids did not alter absorption of a nonmicelle-forming bile acid, taurodehydrocholic acid. These data imply that dietary lipids in general may inhibit intestinal bile acid absorption. Oleic acid significantly reduced the intermicellar bile acid concentration from 8.9 +/- 0.2 mM to 3.9 +/- 0.2 mM while tributyrin, tricaprylin, and triolein had no effect. Results from these studies suggest that the mechanism of inhibition appears to be an enhancement of micelle formation. We speculate that this mechanism may be an additional mechanism for maintaining adequate luminal bile acid concentrations and may be the pathophysiologic mechanism contributing to bile acid malabsorption in cystic fibrosis. |