Circulating Bile Acid Profiles: A Need for Further Examination

Abstract

Context: Bile acids (BAs) are increasingly recognized as metabolic and chronobiologic integrators that synchronize the systemic metabolic response to nutrient availability. Alterations in the concentration and/or composition of circulating BAs are associated with a number of metabolic disorders, such as obesity, type 2 diabetes mellitus (T2DM), insulin resistance (IR), and metabolic associated fatty liver disease (MAFLD). This review summarizes recent evidence that links abnormal circulating BA profiles to multiple metabolic disorders, and discusses the possible mechanisms underlying the connections to determine the role of BA profiling as a novel biomarker for these abnormalities.

Evidence acquisition: The review is based on a collection of primary and review literature gathered from a PubMed search of BAs, T2DM, IR, and MAFLD, among other keywords.

Evidence synthesis: Obese and IR subjects appear to have elevated fasting circulating BAs but lower postprandial increase when compared with controls. The possible underlying mechanisms are disruption in the synchronization between the feeding/fasting cycle and the properties of BA-regulated metabolic pathways. Whether BA alterations are associated per se with MAFLD remains inconclusive. However, increased fasting circulating BAs level was associated with higher risk of advanced fibrosis stage. Thus, for patients with MAFLD, dynamically monitoring the circulating BA profiles may be a promising tool for the stratification of MAFLD.

Conclusions: Alterations in the concentration, composition, and rhythm of circulating BAs are associated with adverse events in systemic metabolism. Subsequent investigations regarding these aspects of circulating BA kinetics may help predict future metabolic disorders and guide therapeutic interventions.

Keywords: Bile acid; circadian rhythm; insulin resistance; metabolic associated fatty liver disease; obesity; type 2 diabetes mellitus.