نبذة مختصرة : Immunosuppression is associated with impaired immune responses and increased susceptibility to disease, highlighting the need for safe and effective immunomodulatory strategies. Oligosaccharides derived from natural sources have attracted growing interest due to their bioactivity and regulatory effects on host immunity. The present study was designed to evaluate the immune-enhancing potential of Periplaneta americana oligosaccharides (PAOSs) and to explore their association with SCFA-producing gut microbiota and metabolic regulation in an immunosuppressed mouse model. PAOS administration significantly increased serum immunoglobulin levels (IgG and IgM), promoted the secretion of immunoregulatory cytokines (IFN-γ, IL-2, TNF-α, IL-10, and IL-4), and elevated the proportion of CD4+ T cells in the spleen. In addition, PAOSs alleviated oxidative stress by reducing malondialdehyde accumulation while promoting the activity of key antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. Metabolomic analysis revealed that PAOSs altered host metabolic profiles, particularly enhancing pyrimidine metabolism. Furthermore, PAOSs markedly enriched short-chain fatty acid (SCFA)-producing bacteria, and elevated colonic short-chain fatty acid levels. These changes were closely associated with the observed improvement in immune function. Collectively, this study demonstrated that PAOSs exerted immunomodulatory effects through coordinated regulation of SCFA-producing gut microbiota and host metabolism, elucidating the mechanisms underlying the bioactivity of insect-derived oligosaccharides.
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