Increased Fecal Bile Acid Excretion and Changes in the Circulating Bile Acid Pool Are Involved in the Hypocholesterolemic and Gallstone-Preventive Actions of Psyllium in Hamsters

Abstract

The lipid-lowering effect of psyllium (PSY) is well established. Enhanced fecal bile acid excretion and a stimulation of hepatic bile acid synthesis are discussed as primary mechanisms of this action. To further examine the effect of bile acid excretion and specifically of compositional alterations in the bile acid pool on the cholesterol-lowering and gallstone-preventing action of PSY, male golden Syrian hamsters were fed lithogenic diets containing 5 g/100 g fat, 0.4 g/100 g cholesterol and 0 (control), 4 or 6% PSY or 1% cholestyramine (CHY). PSY significantly lowered plasma total cholesterol and triacylglycerol at a magnitude comparable to that induced by CHY. Although hepatic cholesteryl ester accumulation was completely inhibited by CHY, PSY did not prevent the hepatic storage of esterified cholesterol. PSY and CHY caused distinct alterations in the bile acid profile. PSY caused a selective reduction of taurine-conjugated bile acids, especially of taurochenodeoxycholate. As a result, the glycine:taurine conjugation and the cholate:chenodeoxycholate ratios were significantly higher in PSY-fed hamsters. PSY and CHY normalized the lithogenic index and prevented cholesterol gallstone formation compared with controls. Daily fecal bile acid excretion was ∼400% greater in hamsters fed 6% PSY, whereas CHY caused an 11-fold increase. Daily neutral sterol excretion did not differ in PSY-fed hamsters but was >100% greater in those fed CHY than in controls. These data emphasize the potent lipid-lowering effect of PSY. Increased fecal bile acid excretion and alterations of the circulating bile acid pool by removal of dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators of the hypocholesterolemic action of PSY by leading to an up-regulation of hepatic bile acid synthesis.