The bile–gut axis and metabolic consequences of cholecystectomy

Abstract Cholelithiasis and cholecystitis affect individuals of all ages and are often treated by surgical removal of the gallbladder (cholecystectomy), which is considered a safe, low-risk procedure. Nevertheless, recent findings show that bile and its regulated storage and excretion may have important metabolic effects and that cholecystectomy is associated with several metabolic diseases postoperatively. Bile acids have long been known as emulsifiers essential to the assimilation of lipids and absorption of lipid-soluble vitamins, but more recently, they have also been reported to act as metabolic signaling agents. The nuclear receptor, farnesoid X receptor (FXR), and the G protein–coupled membrane receptor, Takeda G protein–coupled receptor 5 (TGR5), are specific to bile acids. Through activation of these receptors, bile acids control numerous metabolic functions. Cholecystectomy affects the storage and excretion of bile acids, which in turn may influence the activation of FXR and TGR5 and their effects on metabolism including processes leading to metabolic conditions such as metabolic dysfunction–associated steatotic liver disease and metabolic syndrome. Here, with the aim of elucidating mechanisms behind cholecystectomy-associated dysmetabolism, we review studies potentially linking cholecystectomy and bile acid–mediated metabolic effects and discuss possible pathophysiological mechanisms behind cholecystectomy-associated dysmetabolism.