Mus musculus Transcriptome or Gene expression

We report increased levels of the hydrophobic bile acid T-ßMCA during intestinal cancer progression using the APCmin/+ mouse tumor model. Likewise, HFD induced a shift in BA composition towards T-ßMCA. T-ßMCA 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-ßMCA levels and restores FXR activity. We find that proliferation of intestinal organoids was stimulated by T-ßMCA 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.