Lipid Metabolism in Bile Acid Malabsorption

Abstract

Malabsorption of bile acid increases cholesterol synthesis and activates hepatic LDL receptors which leads to enhanced elimination of cholesterol from the body. Interruption of enterohepatic circulation of bile acids may lead to a smaller bile acid pool, which, in turn, impairs cholesterol and fat absorption by reduced micellar solubilization. Together with reduced cholesterol absorption, the increased cholesterol loss as bile acids also reduces plasma cholesterol concentrations and the biliary cholesterol excretion, too. Diminished biliary cholesterol in bile acid malabsorption may contribute to the increased incidence of gallstones associated with ileal dysfunction. Malabsorption of bile acid leads to a fall in LDL-cholesterol concentration, and an increase of HDL-cholesterol concentration has been reported. VLDL-triglyceride concentrations are almost invariably raised. Enhanced cholesterol and bile acid synthesis in ileal dysfunction is reflected by raised concentrations of plasma cholesterol precursors, especially lathosterols, which can be used as an indicator of increased bile acid loss to faeces. Cholesterol absorption, in turn, correlates positively with plasma plant sterol concentrations levels and the ratio of lathosterols to campesterols can be used as a screening measurement for ileal dysfunction. Plasma fatty acid composition is also altered as a response to fat malabsorption associated with ileal dysfunction. The proportion of essential fatty acids is inversely correlated with faecal fat excretion and endogenous fatty acid synthesis is activated.

Reduction in cardiovascular risk by sodium-bicarbonated mineral water in moderately hypercholesterolemic young adults

“…Therefore, the present results could be explained by choleretic (stimulation of bile production) and cholagogue (stimulation of gallbladder contraction) properties of the study water which may involve a reduction of the size of the bile acid pool and increased conversion rate of cholesterol into bile acid, lowering total cholesterol and LDL-cholesterol levels. Malabsorption of bile acid leads to a fall in LDL-cholesterol and a tendency to increase HDL-cholesterol [38] without changes in serum TG [39]. We raise the hypothesis that the weakly alkaline mineral water used in the present assay may exert a similar influence on bile acids and consequently on circulating cholesterol levels.…”

Lathosterol and other noncholesterol sterols during treatment of hypercholesterolemia with lovastatin alone and with cholestyramine or guar gum.

“…32 In previous studies lovastatin has resulted in a 30-40% reduction of urinary mevalonate, 47% in FH patients treated with simvastatin. 9 Similarly, pravastatin has been recently shown to reduce the serum contents of lathosterol and desmosterol.…”

“…Cholesterol precursor sterols in serum, on the other hand, reflect cholesterol synthesis in many clinical conditions, 32 -39 while serum plant sterols and to some extent cholestanol reflect absorption and biliary elimination of sterols. 32 - 38 - 41 Serum levels of cholesterol precursor sterols are decreased during HMG-CoA reductase inhibitor treatment 9 -10 but increased during guar gum 28 or cholestyramine 34 -Therefore, the objective of this study was to examine the relation of different cholesterol synthesis precursors, cholestanol, and plant sterols in serum with cholesterol levels during the suppression of cholesterol synthesis by lovastatin alone and during subsequent possible increase of cholesterol synthesis by either cholestyramine or guar gum.…”

Alteration of gut microbiota in association with cholesterol gallstone formation in mice

“…Intestinal bacteria regulate bile acids metabolism through bile salt hydrolases (BSH) activity that de-conjugates bile acids and 7α-dehydroxylase activity that converts primary bile acids to secondary bile acids [14, 26, 27]. The enzymatic activity of 7α-dehydroxylation is known to only exist in limited number of intestinal microbiota belonging to genus Clostridium [28].…”