Effects of Lyophyllum decastes polysaccharides on immune activity and gut microbiota homeostasis in immunosuppressive mice

GAN Xiaokun; CHEN Kunzhui; SHEN Yingbin; ZHANG Lei; LI Zhan

doi:10.12187/2025.06.006

Abstract：[Objective]To investigate the immunomodulatory effects of Lyophyllum decastes polysaccharides(LDPS)on immune activity and gut microbiota dynamics in immunosuppressive mice.[Methods]An immunosuppressive mouse model was established via cyclophosphamide(CTX)administration.Following 20-day gavage of LDPS at varying doses,enzyme-linked immunosorbent assay(ELISA),hematoxylin-eosin(H&E)staining,Western blotting(WB),and 16S rDNA sequencing were employed to assess thymus/spleen indices,serum cytokines(IL-2/TNF-α),intestinal secretory immunoglobulin A(SIgA)levels,histopathological changes,tight junction protein(Claudin-1/ZO-1)expression,and gut microbiota composition.[Results]LDPS administration restored body mass/food intake and ameliorated splenic,thymic,and small intestinal tissue damage.Compared to the CTX model group,medium-dose(MLDPS)and high-dose(HLDPS)LDPS groups showed significantly elevated serum IL-2 levels(P<0.05)and small intestinal SIgA secretion,reduced TNF-α concentrations,and upregulated Claudin-1(45.36%/62.89%increase)and ZO-1(30.31%/31.35%increase)expression.High-dose LDPS significantly increased the relative abundance of beneficial taxa including Lachnospiraceae_NK4A136_group(93.49%),Rikenellaceae,and Alistipes(P<0.05),while decreasing potential pathogens like Staphylococcus(P<0.05),thereby reversing CTX-induced gut microbiota dysbiosis.[Conclusion]LDPS exhibits immunomodulatory effects in immunosuppressive mice,with mechanisms involving enhanced intestinal barrier function and restored gut microbiota homeostasis.