Microbiome-dependent phytosterol sulfates production and tissue distribution in mice

Microbial biotransformation of dietary lipids, such as cholesterol, influences host homeostasis. Despite extensive studies on animal sterols in host-microbiota interactions, the role of phytosterols in homeostasis remains unclear. In this study, we characterized phytosterol sulfates as microbiota-derived metabolites using untargeted lipidomic data mining. The levels of sitosterol sulfate (SIS), campesterol sulfate, and stigmasterol sulfate, the three major phytosterol sulfates, along with coprostanol sulfate, were reduced in the feces of germ-free mice compared with those of specific pathogen-free mice. We characterized a series of Bacteroidota species and their sterol sulfotransferases that produced phytosterol sulfates more efficiently than mammalian enzymes. Furthermore, SIS significantly accumulated in host tissues in a microbiota- and age-dependent manner, whereas unconjugated phytosterols were mostly undetectable. Our work provides insights into host-microbiome interactions via gut bacterial phytosterol metabolism.