PSM exhibited various biological activities, such as anti-inflammation, anticancer and antiviral, but its effects on lipid profile have not been extensively investigated. In the present study, we found PSM treatment can effectively ameliorate colitis and improve lipid profile including reduced FA uptake and induced DNL. Interestingly, recent studies revealed certain compound with poor intestinal absorption exert remarkable therapeutic effects through modulating gut microbiome. PSM also exhibits remarkable effects on the composition of gut microbiota, characterized by increasing the ratio of Firmicutes and Bacteroidota at the phylum level.