Pleurocinus ostreatus Polysaccharide Alleviates Cyclophosphamide-Induced Immunosuppression through the Gut Microbiome, Metabolome, and JAK/STAT1 Signaling Pathway

This study investigated the structure of <i>Pleurocinus ostreatus</i> polysaccharide (POP-1) and its effect on immunocompromised mice induced by cyclophosphamide (CY). Novel POP-1 was α- and β-glucopyranose, its molecular weight was 4.78 × 104 Da, it was mainly composed of glucose (88.9%), and it also contained galactose (2.97%), mannose (5.02%), fucose (0.3%), arabinose (0.21%), ribose (0.04%), galactose acid (0.17%), and glucose acid (1.45%). After POP-1 was administered to immunosuppressed mice, results showed that POP-1 increased the body weight, spleen, and thymus index and enhanced T lymphocyte proliferation in mice. POP-1 up-regulated the expression of CD3⁺, CD4⁺, and CD8⁺ lymphocytes and the ratio of CD4⁺/CD8⁺ in the mouse spleen to increase immunoglobulin (IgM, IgG, and IgA) and secrete cytokines (IL-2, IL-6, TNF-α, and IFN-γ) through activation of the JAK/STAT1 signaling pathway. Moreover, POP-1 remarkably reversed the gut-microbiota dysbiosis in immunosuppressed mice by increasing the abundance of <i>Muribaculaceae</i>, <i>Lactobacillaceae</i>, <i>Blautia</i>, and <i>Ligilactobacillus</i> and altered the fecal metabolites by increasing hexahomomethionine, DG(8:0/20:4(5Z, 8Z, 11Z, 14Z)-OH(20)/0:0, 2-((3-aminopyridin-2-yl)methylene)hydrazinecarbothioamide, Ginkgoic acid, and carboxy-ethyl-hydroxychroman, which is closely related to the immunity function. This study indicates that <i>P. ostreatus</i> polysaccharide effectively restores immunosuppressive activity and can be a functional ingredient in food and pharmaceutical products.