A physiologically-based model of bile acid metabolism in humans

Abstract

Altered serum BA profiles have been reported for several chronic liver diseases. However, relevant modifications in bile acid disposition are difficult to investigate mechanistically due to the interference of the various physiological processes involved at various levels of bile acid metabolism. In this regard, validated computational models represent a promising tool to understand the functional effect of disease-related alterations on bile acid composition along the gut-liver-axis through mechanistic analyses of the underlying physiological processes. We applied a physiologically-based models of bile acid metabolism in humans comprising the five predominant bile acids. The model describes various physiological aspects of bile acid metabolism including synthesis, enterohepatic circulation, hepatic and microbial conversions, postprandial gall bladder emptying as well as excretion via feces and urine. Model development was based on 39 previously published studies in patients without any liver diseases. In the future, the established model may serve as reference for analysis of the role of bile acids in health and disease.