Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in Mice: Relation to Metabolism and Gut Microbiota Composition.

Free fatty acid receptor 2 () has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model ( ). deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, , and - mice. The relative abundance of and was significantly increased in the - mice compared to the mice. In addition, knocking-down in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.