Cholecystectomy-associated gut microbiota dysbiosis promotes colorectal carcinogenesis: from epidemiological controversy to FXR-centered mechanistic insights.

BACKGROUND AND

OBJECTIVE

Cholecystectomy is one of the most common surgeries worldwide, yet its association with colorectal cancer (CRC) risk remains controversial. Recent advances have linked gut microbiota and bile acid alterations to this risk. This review synthesizes epidemiological evidence and molecular mechanisms, focusing on the microbiota-bile acid-FXR signaling axis, and proposes a personalized prevention framework. Epidemiological data reveal consistent patterns: proximal colon cancer predominance, higher risk in women, and peak incidence 5-15 years post-surgery. Cholecystectomy induces gut microbiota dysbiosis (decreased Bifidobacterium breve, increased Ruminococcus gnavus) and bile acid disturbances (elevated TUDCA/GUDCA, altered protective bile acids), which converge on FXR signaling.

CORE FINDINGS: The FXR signaling axis is a central hub. Yang et al. (Nat Commun 2025) showed that cholecystectomy-induced microbiota shifts alter bile acids, suppress FXR, disrupt FXR/β-catenin interaction, and promote tumorigenesis. The FXR agonist obeticholic acid prevents these effects preclinically, but systemic toxicity limits clinical use.

CONCLUSION AND SIGNIFICANCE: We propose personalized risk stratification integrating demographics, microbial signatures, and metabolic biomarkers. Interventions include gut-restricted FXR agonists, probiotics, and Mediterranean diet. Future directions include prospective validation and dynamic network modeling.