Sanyin decoction alleviates psoriasis by reshaping gut microbiota and modulating the gut–spleen–skin axis

Background: Sanyin decoction (SYD) is an improved formulation based on Xiaoyinsan, commonly used as an adjunct treatment for psoriasis; however, its molecular mechanisms remain unclear. Methods: A psoriasis-like mouse model was established using imiquimod induction. Mice were treated with SYD via gavage, and their health status was assessed based on skin histopathology, PASI scores, and ear thickness measurements. Fecal samples were collected for 16S rRNA sequencing and short-chain fatty acid (SCFA) analysis to examine changes in gut microbiota and SCFA levels before and after SYD treatment. Additionally, transcriptomic sequencing was performed on the spleen and skin lesions to analyze gene expression changes and immune modulation in these tissues. Results: , with increased levels of SCFAs, particularly acetate, in the feces. Transcriptomic analysis of splenic tissue revealed a significant upregulation of IL-4 expression and activation of G protein-coupled receptor-related signaling pathways following treatment. In addition, the abundance of regulatory T cells in the spleen was significantly increased. Plasma IL-4 level was significantly higher after treatment. In lesional skin, SYD treatment was associated with significant suppression of the IL-17 signaling pathway, along with activation of keratinocyte differentiation-related pathways were activated, promoting tissue repair. Conclusion: Our study suggests that acetate derived from gut microbiota may serve as an important link between SYD treatment and systemic immune regulation in psoriasis, highlighting the potential of the gut-spleen-skin axis as a target for traditional herbal interventions.