Immunomodulatory effects of

Introduction: Immunosuppression induced by chemotherapeutic agents such as cyclophosphamide (CTX) is frequently associated with gut microbiota dysbiosis. Methods: In this study, we investigated the immunomodulatory activity of SSP1 in CTX-induced immunosuppressed mice. Mice were treated with different doses of SSP1 orally. We assessed immune organ indices, histopathology of immune organs and colon, oxidative stress, splenocyte proliferation, T-cell subsets, and cytokine production. Additionally, 16S rRNA sequencing was used to analyze gut microbiota composition; targeted analysis was performed on short-chain fatty acids (SCFAs); and untargeted metabolomics was used to evaluate metabolic profiles. Results: Oral administration of SSP1 significantly alleviated immunosuppression in a dose-dependent manner, with the high dose (SSP1-H) showing the most pronounced effects. This was evidenced by restored body weight, increased spleen and thymus indices, improved histopathology, and attenuated oxidative stress. SSP1 promoted splenocyte proliferation, elevated CD45 Discussion: Collectively, these findings suggest that high-dose SSP1 treatment was associated with coordinated changes in gut microbiota composition, SCFA production, and immune parameters, supporting a potential microbiota-metabolism-immune axis. This implies that SSP1's protection against CTX-induced immunosuppression is associated with regulating immune cell functions and reshaping the gut microbiota to enhance SCFA production, providing new insights into the immunoregulatory mechanisms of Sanghuang polysaccharides and highlighting their potential as functional food ingredients or immune adjuvants.