Bile acid synthesis and composition is tightly controlled through the mechanisms involved in the enterohepatic circulation, also referred to as the gut–microbiota–liver axis (Figure 1A). Disruptions in the balance—be it through genetic, metabolic, or environmental influences—may lead to the formation of gallstones.1 Although most gallstones are silent, symptomatic disease is a considerable health problem with 1.4 million ambulatory visits and 750,000 cholecystectomies per year in the United States alone.