The role of deoxycholic acid in macrophage polarization and remodeling of the tumor microenvironment during colorectal adenoma-carcinoma transition.

During the progression from colorectal adenoma to colorectal cancer (CRC), the inflammatory state of the tumor microenvironment (TME) evolves in parallel with the epithelial‒mesenchymal transition (EMT) process. Among the key players, macrophages serve as pivotal mediators of inflammation-cancer transformation and are closely associated with these dynamic changes. Deoxycholic acid (DCA), a critical bile acid metabolite involved in CRC development, has been implicated in tumorigenesis; however, its role in macrophage polarization and the adenoma-carcinoma sequence remains unclear. In this study, we analyzed clinical cell types and DCA levels in colorectal adenomas and carcinomas to elucidate the correlation between DCA and macrophages in CRC. Furthermore, we investigated the mechanistic role of DCA in promoting M2-like polarization of tumor-associated macrophages and validated the impact of DCA on the EMT-associated Wnt/β-catenin pathway and inflammation-associated NF-κB signaling pathway in CRC model mice. Our findings may provide novel strategies for prognostic biomarkers and precise bile acid metabolism-based interventions in CRC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-025-00416-z.