Background Tripterygium hypoglaucum (H. Lév.) Hutch . (THH) exerts anti-inflammatory and immunosuppressive effects against psoriasis. However, the extent to which and the mechanisms by which it ameliorates psoriasis-like dermatitis through modulation of the gut microbiota-metabolite axis remain unclear. Methods This study investigated the therapeutic effects and underlying mechanisms of THH in a murine model by employing 16S rRNA gene sequencing, intestinal metabolomic profiling, fecal microbiota transplantation (FMT), and co-housing experiments. Results Our results demonstrated that THH treatment significantly decreased PASI scores, alleviated epidermal hyperplasia and skin inflammation, and reversed IMQ-induced gut dysbiosis by restoring the Firmicutes/Bacteroidota ratio and modulating the abundance of beneficial and pathogenic bacteria. Metabolomic analysis revealed that THH normalized multiple metabolic pathways disturbed by IMQ, including arachidonic acid metabolism, sphingolipid metabolism, and primary bile acid biosynthesis. Correlation analyses further revealed significant associations among the altered gut microbiota, key metabolic pathways, and psoriasis-related phenotypic indices. Moreover, FMT from THH-treated mice conferred significant anti-psoriatic efficacy. Similarly, co-housing experiments resulted in the alleviation of skin lesions, reduction of spleen weight, and downregulation of inflammatory cytokines. Conclusion These findings demonstrate that THH attenuates psoriasis-like dermatitis partly by reshaping gut microbiota composition and regulating key metabolic pathways, supporting a potential gut-targeted therapeutic strategy for psoriasis.
Wang et al. (Tue,) studied this question.