Chinese yam (Dioscorea opposita Thunb.) has long been recognized for its medicinal and nutritional properties, particularly its immunomodulatory effects. This study aims to investigate the regulatory effects and underlying molecular mechanisms of microbial-fermented Chinese yam polysaccharides (CYPs) on a cyclophosphamide (CTX)-induced immunosuppressed mouse model. The research specifically focuses on whether CYPs can restore immune function by modulating systemic inflammation, repairing immune organ damage, and correcting the dysbiosis of gut microbiota and metabolic disruptions caused by CTX treatment.

To evaluate the immunoprotective potential of CYPs, a cyclophosphamide-induced immunosuppression model was established in mice. The experimental groups received varying doses of CYPs, and their physiological changes—including body weight and immune organ indices (spleen and thymus)—were systematically recorded. The concentrations of key pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), along with immunoglobulins (IgA, IgG, and IgM), were measured via enzyme-linked immunosorbent assay (ELISA). Histopathological examinations were conducted to assess tissue regeneration and lymphocyte proliferation in immune organs. Furthermore, 16S rRNA gene sequencing was employed to analyze the composition and diversity of the gut microbiota. Finally, untargeted metabolomics was performed to identify the metabolic pathways affected by CYP administration.

The findings demonstrated that CYPs effectively mitigated the weight loss and decreased immune organ indices typically observed in CTX-treated mice. At the biochemical level, CYPs significantly upregulated the secretion of cytokines (TNF-α, IL-6, and IL-1β) and immunoglobulins (IgA, IgG, and IgM), indicating a robust restoration of both innate and adaptive immunity. Histological analysis confirmed that CYPs alleviated pathological damage in the spleen and thymus by promoting lymphocyte proliferation. Regarding the gut-immune axis, CYPs effectively restored bacterial homeostasis by increasing the relative abundance of beneficial taxa like Mycobacterium while decreasing detrimental Micromonosporaceae. Crucially, CYPs corrected the imbalance in the Firmicutes/Bacteroidetes (F/B) ratio. Integrated metabolic analysis revealed that these immunomodulatory effects were closely linked to the regulation of arachidonic acid metabolism, amino acid biosynthesis, and aminoacyl-tRNA biosynthesis, providing a biochemical link between gut fermentation and systemic immunity.

In summary, microbial-fermented Chinese yam polysaccharides (CYPs) exhibit potent immunomodulatory activities in immunosuppressed mouse models. By synergistically regulating immune factors, promoting the structural recovery of immune organs, optimizing gut microbiota composition, and modulating key metabolic pathways, CYPs serve as effective biological response modifiers. This study provides a scientific rationale for the application of fermented CYPs as functional food ingredients or therapeutic agents for enhancing immune function and mitigating the side effects of immunosuppressive drugs.