Grifola frondosa Polysaccharides Alleviated Cyclophosphamide—Induced Intestinal Injury Based on Microbiota, Metabolite and Immune Axis Modulation

<i>Grifola frondosa</i> polysaccharides (GFP), which possess antitumor properties, can counteract intestinal injury induced by cyclophosphamide (CTX). The objective of this research was to evaluate the efficacy of GFP in protecting the intestinal barrier of mice and investigate the mechanisms behind this effect. Using a CTX-induced intestinal barrier injury model, we found that GFP treatment significantly alleviated body weight loss and organ atrophy, while enhancing serum IgG and IgM levels. Histological analysis showed that GFP effectively repaired the intestinal mucosal structure, increased goblet cell numbers, and led to an upregulation in the gene expression of ZO-1, Occludin, and MUC2. GFP modulated cytokine expression, including IFN-γ, IL-4, IL-10, and IL-22. According to 16S rDNA sequencing results, GFP enhanced the abundance of <i>unclassified</i>_<i>Muribaculaceae</i> while reducing the prevalence of <i>Escherichia_Shigella</i>. Furthermore, GFP elevated the concentrations of several metabolites, including SCFAs and pyridoxal, which are closely related to intestinal barrier protection and mucosal immunity. Overall, this study demonstrated that GFP has strong potential as an immune-enhancing adjuvant and may represent a promising intervention strategy to mitigate chemotherapy-induced intestinal injury.