Therapeutic role of ursodeoxycholic acid in colitis-associated cancer via gut microbiota modulation.

ABSTRACT

Inflammatory bowel disease (IBD) is a predisposing factor for colitis-associated cancer (CAC). The association between bile acids and the gut microbiota has been demonstrated in colon neoplasia; however, the effect of ursodeoxycholic acid (UDCA) on gut microbiota alteration in development of colitis and CAC is unknown. Our analysis of publicly available datasets demonstrated the association of UDCA treatment and accumulation of Akkermansia. UDCA-mediated alleviation of DSS-induced colitis was microbially dependent. UDCA treatment significantly upregulated Akkermansia colonization in a mouse model. Colonization of Akkermansia was associated with enhancement of the mucus layer upon UDCA treatment as well as activation of bile acid receptors in macrophages. UDCA played a role in CAC prevention and treatment in the AOM-DSS and ApcMin/+-DSS models through downregulation of inflammation and accumulation of Akkermansia. This study suggests that UDCA intervention could reshape intestinal gut homeostasis, facilitating colonization of Akkermansia and preventing and treating colitis and CAC.