Polysaccharides from Psoralea corylifolia alleviate CTX-induced immunosuppression in mice by modulating gut microbiota- metabolite-immune signaling

Introduction Although polysaccharides from Psoralea corylifolia L. (PPs) have been reported to possess immune-stimulatory effects, their precise mechanisms of action remain unclear. Methods In this study, the potential mechanism of PPs in alleviating CTX-induced immunosuppression was investigated by analyzing the gut microbiota, metabolomics, and immune parameters in mice. Results The results showed that PPs significantly alleviated CTX-induced immunosuppression, as evidenced by increased immune organ indices, improved intestinal mucosalintegrity, elevated serum levels of IL-6 and TNF-α, enhanced activities of ACP, LDH, SOD, and GSH-Px, and reduced MDA content. Western blot analysis indicated that PPs activated the NF-kB and MAPK signaling pathways and upregulated the expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). Immunohistochemical results further revealed that PPs modulated the numbers of CD4 + and CD8 + T cells in the small intestine. Based on 16S rDNA sequencing and untargeted metabolomics analysis, PPs promoted the proliferation of Lachnospiraceae_NK4A136_group and Lactobacillus , while reducing the abundance of Prevotellaceae_UCG-001, f:Lachnospiraceae_Unclassified, and Alloprevotella , thereby ameliorating metabolic disorders and counteracting CTX-induced immunosuppression. Spearman’s correlation coefficient analysis indicated significant associations among gut microbiota, serum metabolites, and immune as well as antioxidant indicators. Discussion These results suggested that PPs enhanced the immune response in immunocompromised mice by boosting antioxidant capacity, improving the intestinal barrier, modulating gut microbiota structure, and correcting metabolic disturbances.