Yogurt Prevents Colitis-Associated Colorectal Cancer in Mice.

ABSTRACT

SCOPE Epidemiological studies indicate an inverse correlation between yogurt consumption and colorectal cancer (CRC), but whether there is a cause-and-effect relationship has not yet been validated. This study aims to investigate the effects and possible mechanisms of yogurt on colitis-associated colorectal cancer (CAC) in mice. METHODS AND RESULTS: Experimental CAC is induced by azoxymethane (AOM, 10 mg kg-1 , ip) followed by three cycles of dextran sulfate sodium (DSS, 3%) treatment. Colitis is induced by adding DSS (3%) in drinking water for 5 days. Primary mouse macrophages are isolated for mechanistic studies. Data clearly show that yogurt (15 g kg-1 body weight) significantly reduces the multiplicity of colonic neoplasms by 38.83% in mice. Yogurt protects mice from colitis dependent on lactate receptor GPR81. The deficiency of Gpr81 exacerbates colitis and CAC in mice. Further investigation reveals that GPR81 may be dispensable for gut barrier function but essential for colonic mucosal repair. d-lactate in yogurt can activate GPR81 to suppress proinflammatory macrophage polarization, thereby facilitating inflammatory resolution after colonic injury and consequently suppressing CAC progression. CONCLUSION: Yogurt effectively protects against colitis-associated colorectal tumorigenesis in mice, and this study provides a rationale for introducing yogurt supplementation to patients with chronic inflammatory bowel diseases.