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Nature子刊:杨仕明团队揭示胆囊切除术加剧结直肠癌发生的新机制,并提出潜在干预方式
生物世界· 2025-08-20 08:45
Core Viewpoint - The incidence of gallbladder diseases, such as gallstones and gallbladder polyps, is increasing globally due to changes in dietary structure. Gallbladder removal surgery is the most common procedure in biliary surgery and is considered a standard treatment for patients with gallbladder diseases. However, emerging evidence indicates that post-cholecystectomy syndrome and the incidence of diseases related to metabolic syndrome have significantly increased. Notably, previous clinical studies have linked gallbladder removal surgery to an elevated risk of colorectal cancer, although the underlying mechanisms remain unclear [3][7]. Group 1 - A recent study published by a team led by Professor Yang Shiming from the Army Medical University in Nature Communications indicates that gallbladder removal surgery is associated with gut microbiota dysbiosis and impaired bile acid metabolism, which exacerbates colorectal tumorigenesis through disrupted FXR/β-catenin interactions. The FXR agonist obeticholic acid (OCA) has been shown to prevent colorectal tumors associated with gallbladder removal surgery [4][10]. - The study utilized mouse models to confirm that gallbladder removal surgery increases the occurrence of colorectal tumors. Metagenomic sequencing and targeted metabolomics revealed a reduction in Bifidobacterium breve and an increase in Ruminococcus gnavus, along with elevated levels of glycochenodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) in the body [8][10]. - Experiments involving fecal microbiota transplantation, single strain colonization, and bile acid supplementation demonstrated that dysbiosis related to gallbladder removal surgery promotes the production of TUDCA, thereby facilitating colorectal tumor development. Impaired bile acid metabolism inhibits FXR signaling, which ultimately exacerbates colorectal tumorigenesis [8][10].