J Cancer Prev.  2021 Mar;26(1):32-40. 10.15430/JCP.2021.26.1.32.

Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in Apc^Min/+ Mice: Relation to Metabolism and Gut Microbiota Composition

• Huang YW
• Lin CW
• Pan P
• Echeveste CE
• Dong A
• Oshima K
• Yearsley M
• Yu J
• Wang LS

• KMID: 2514693
• DOI: http://doi.org/10.15430/JCP.2021.26.1.32

Abstract

Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (Apc^Min/+). FFAR2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, Apc^Min/+, and Apc^Min/+-Ffar2^-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the Apc^Min/+-Ffar2^-/- mice compared to the Apc^Min/+ mice. In addition, knocking-down FFAR2 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, longchain 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 FFAR2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.

Keyword

Ffar2; Apc^Min/+; Colorectal cancer; Metabolomics; Gut microbiota