Metabolic surgery reduces CRC disease progression through circulating bile acid diversion

Area of Science:

• Gastroenterology and Hepatology
• Oncology
• Metabolic Surgery

Background:

• Obesity is a global epidemic linked to increased colorectal cancer (CRC) risk.
• Metabolic surgery improves obesity-related conditions and may reduce cancer risk, but mechanisms are unclear.
• Understanding how bariatric surgery impacts CRC development is crucial for therapeutic strategies.

Purpose of the Study:

• To elucidate the antitumoral mechanisms of bariatric surgery in colorectal cancer.
• To investigate the role of bile acid (BA) diversion in RYGB-mediated CRC risk reduction.
• To validate findings in a translational study involving CRC patients.

Main Methods:

• Development of a Roux-en-Y gastric bypass (RYGB) mouse model for colorectal cancer (CRC).
• Analysis of bile acid profiles and their impact on tumorigenesis and metastasis.
• Utilizing cholecystointestinal shunt (CIS) surgery to isolate the effect of bile acid exclusion.
• Translational study correlating serum primary bile acid levels with metastasis time in CRC patients.

Main Results:

• RYGB surgery significantly reduced primary CRC tumor formation and prevented metastasis in mice.
• The protective effect was attributed to bile acid (BA) exclusion from the proximal small intestine, altering circulating BA profiles.
• Diversion of bile acids, independent of systemic metabolic changes, demonstrated antitumoral and antimetastatic properties.
• Reduced primary bile acid concentrations in human CRC patients correlated with a longer time to metastasis.

Conclusions:

• Metabolic surgery, specifically RYGB, exerts an antitumoral effect against colorectal cancer.
• Bile acid diversion is a key mechanism by which RYGB reduces CRC progression and metastasis.
• Targeting bile acid metabolism represents a promising strategy for CRC prevention and treatment.