Mus musculus Transcriptome or Gene expression. Mus musculus

We report increased levels of the hydrophobic bile acid T-βMCA during intestinal cancer progression using the APCmin/+ mouse tumor model. Likewise, HFD induced a shift in BA composition towards T-βMCA. T-βMCA is an antagonist of the Farnesoid X Receptor (FXR), which is reflected in downregulation of the FXR transcriptional network during cancer progression. We found that the modified gut-biased FXR agonist Fexaramine D (FexD) protects against tumor progression. FexD lowers T-βMCA levels and restores FXR activity. We find that proliferation of intestinal organoids was stimulated by T-βMCA but inhibited by FexD. In summary, we demonstrate that preservation of FXR signaling and maintenance of a healthy BA pool are paramount in the prevention/treatment of colon cancer.