In vitro models to measure effects on intestinal deconjugation and transport of mixtures of bile acids

Abstract

Bile acid metabolism and transport are critical to maintain bile acid homeostasis and host health. In this study, it was investigated if effects on intestinal bile acid deconjugation and transport can be quantified in vitro model systems using mixtures of bile acids instead of studying individual bile acids. To this end deconjugation of mixtures of selected bile acids in anaerobic rat or human fecal incubations and the effect of the antibiotic tobramycin on these reactions was studied. In addition, the effect of tobramycin on the transport of the bile acids in isolation or in a mixture across Caco-2 cell layers was characterized. The results demonstrate that both the reduction of bile acid deconjugation and transport by tobramycin can be adequately detected in vitro systems using a mixture of bile acids, thus eliminating the need to characterize the effects for each bile acid in separate experiments. Subtle differences between the experiments with single or combined bile acids point at mutual competitive interactions and indicate that the use of bile acid mixtures is preferred over use of single bile acid given that also in vivo bile acids occurs in mixtures.