Oyster polysaccharides (OPS) have garnered growing attention due to their anti-inflammatory, antioxidant, and gut microbiota-modulating properties. However, the underlying immunomodulatory mechanisms of OPS remain incompletely elucidated. This study aimed to investigate the effects of OPS on immune function of mice with cyclophosphamide (Cy)-induced immunosuppression. OPS effectively modulated immune cell profiles in both spleen and intestinal tissues, significantly increased the percentages of CD4+ and CD8+ T cells and repaired intestinal mucosal damage. Furthermore, OPS enhanced the secretion of intestinal immune cytokines by activating MAPK signaling pathway, leading to notable increases in IL-2 (from 44.25 ± 17.39 to 82.56 ± 17.50 pg/mL), IFN-γ (from 176.05 ± 28.08 to 308.71 ± 53.75 pg/mL), IL-1β (from 35.74 ± 6.17 to 54.12 ± 4.54 pg/mL), and TNF-α (from 117.06 ± 8.34 to 241.46 ± 66.11 pg/mL). Additionally, OPS ameliorated Cy-induced intestinal microbiota dysbiosis by significantly boosting the relative abundance of beneficial bacteria, including Ligilactobacillus, Alloprevotella, Odoribacter, and Alistipes. Meanwhile, OPS upregulated levels of key intestinal metabolites such as short-chain fatty acids, glycine, and imidazoleacetic acid. These findings indicate that OPS could improved Cy-induced immunosuppression and modulate gut microbiota, which highlights its potential as a promising candidate for novel immunoregulatory agents.
