The protective effect of Auricularia auricula polysaccharides on cyclophosphamide-induced immunosuppression and intestinal injury: A fecal microbiota transplantation study

Abstract

Auricularia auricula polysaccharides (AHP) have potential immunomodulatory activities. However, the relationship between polysaccharides, intestinal microbiota, and immune activity remains unclear. Therefore, to explore this relationship, we performed immunosuppressive donor, fecal microbiota transplantation (FMT), and pseudo-sterile mouse validation experiments. Our results showed that AHP enhanced immunomodulatory activity, as evidenced by the alleviation of cyclophosphamide (Cy)-induced body weight loss, spleen and thymus atrophy, and splenic and colonic lesions. Additionally, AHP effectively regulated antioxidant enzyme activities (SOD, T-AOC, CAT, GSH-Px), lipid peroxidation product content (MDA), levels of immune factors (TNF-α, IFN-γ, IL-2, IL-4, IL-6), immunoglobulins (sIgA), and the expression of tight junction proteins (Muc2, ZO-1, Occuldin, and Claudin-1) in the colon of immunosuppressed mice. FMT results demonstrated that FAHP displayed superior immunomodulatory ability and could further affect the abundance of Dehydroepiandrosterone, Prostaglandin E2, Cholesterol and Pregnenolone by increasing the abundance of unclassified_Muribaculaceae, Desulfovibrio, Alloprevotella, and unclassified_Oscillospiraceae and decreasing that of Staphylococcus, Bacteroides, and Corynebacterium. Pseudo-sterilization experiments showed that AHP was unable to increase antioxidant enzyme activity, reduce lipid peroxidation content, or promote the release of immune factors. In brief, AHP did not alleviate Cy-induced immunosuppression after microbiota elimination. In summary, AHP exerted a protective effect against Cy-induced immunosuppression and intestinal damage by modulating intestinal microbiota and its metabolites. These findings provide new insights into the mechanisms by which AHP, as a functional food or drug, promotes immune response regulation and maintains intestinal health.