The control of bile acid pool size: Effect of jejunal resection and phenobarbitone on bile acid metabolism in the rat

Abstract

In patients with cholesterol gallstones, there is a diminished bile acid pool and the bile becomes supersaturated with cholesterol. Medical treatment has been aimed at re-expanding the pool to improve cholesterol solubility in bile but as yet the factors controlling the size of the bile acid pool' are unknown. Therefore the role of the liver and intestine in controlling bile acid pool size in the rat was studied and the effect of experimental expansion of the pool on bile acid metabolism and bile lipid composition examined. Bile acid absorption was increased from ileum made hyperplastic by previous jejunectomy and hepatic bile acid synthesis was increased by phenobarbitone treatment. Both jejunal resection and phenobarbitone significantly increased the size of the bile acid pool from 32.2 +/- SEM 0.94 mumoles/100 g body weight to 42.2 +/- 1.71 and 44.4 +/- 2.03 respectively. However, the effects of these experimental manipulations on bile acid secretion rate, enterohepatic cycling frequency, and synthesis rates were quite different. Jejunectomy caused a 56% increase in bile acid secretion and more rapid cycling of the bile acid pool but the enhanced absorption did not depress bile acid synthesis. In contrast, phenobarbitone markedly increased synthesis from 14.5 +/- 1.42 mumoles.100 g BW(-1). 24 hr(-1) to 25.9 +/- 3.19 but there was no significant change in bile acid secretion and the choleresis seen after phenobarbitone was mainly due to an increase in the bile acid-independent fraction of bile flow. In these experimental studies in the rat, expansion of the bile acid pool did not significantly change bile lipid composition or cholesterol solubility in bile.