Potential far-reaching metabolic consequences of cholecystectomy.

[BACKGROUND] Cholecystectomy is one of the most commonly performed abdominal surgical procedures and is considered the gold standard for symptomatic gallstone disease. Removing the gallbladder, however, is not a neutral process. The gallbladder stores and concentrates diluted cholesterol- and bile acid-enriched hepatic bile and is dynamically involved in the daily enterohepatic circulation of bile acids, with critical local and systemic metabolic effects via agonism of nuclear and membrane-associated receptors such as FXR and GPBAR1.

[METHODS] We performed a narrative review to discuss the mechanisms driving cholecystectomy-associated dysmetabolism and disruption of the gut-liver axis. We reviewed studies that connect cholecystectomy to bile acid-mediated metabolic effects and examine the pathophysiological processes possibly involved in this scenario.

[RESULTS] Experimental and human evidence highlights that cholecystectomy may be linked to several metabolic disorders, also increasing the risk of colorectal cancer. After cholecystectomy, the reservoir and concentrating function of the gallbladder are absent and bile enters the intestine directly. This new anatomical and functional configuration represents a major change in the entero-hepatic circulation of primary and secondary bile acids and in their signalling functions, with altered effects on metabolic receptors and on the gut microbiome. Post-cholecystectomy gut dysbiosis may lead to reduced microbial diversity and diminished capacity to generate beneficial short-chain fatty acids, promoting a pro-inflammatory milieu and altered metabolic homeostasis.

[CONCLUSIONS] Cholecystectomy can predispose to metabolic changes leading to type 2 diabetes mellitus, obesity, metabolic dysfunction-associated steatotic liver disease and cardiovascular diseases.