Abstract
The role of the microbiome in disease pathogenesis and anti-inflammatory effects of certain commensal microorganisms support the probiotic-based therapies for tumor treating. Saccharomycopsis fibuligera (S.fibuligera) is the major amylolytic yeast used in food fermentation. As a natural medicine, S.fibuligera has been found to protect the intestinal mucosa, while its role and related mechanisms in colorectal cancer (CRC) remain unexplored. In this study, we found that S.fibuligera could alleviate the development of CRC in mice, inhibit the proliferation of tumor cells and induce their apoptosis in vitro. Mechanistically, several metabolic pathways of tumor cells changed after S.fibuligera treatment, among which choline metabolism changed significantly. S.fibuligera inhibited choline metabolism of CRC cells by targeting and inhibiting the Ras/PI3K/AKT pathway, thereby reducing the expression of related metabolites, activating the AMPK pathway and inhibiting the mTOR pathway, which in turn induced apoptosis of CRC cells, ultimately alleviating CRC. Above all, our study has clarified anti-tumor effect of S.fibuligera and demonstrated that S.fibuligera alleviates CRC by inhibiting the choline metabolism, providing a promising new strategy for CRC treatment with high clinical translational value.