Immunomodulatory mechanisms of low molecular weight peptides from Pinctada martensii: A network pharmacology and in vivo study on gut microbiota and immune function

Immunosuppression due to inflammation and tumor chemotherapy is becoming more severe and can be effectively treated by immunonutrient supplementation. The aim of this study was to elucidate the potential immunomodulatory mechanisms of low molecular weight peptides from Pinctada martensii (LPP) in conjunction with network pharmacology and in vivo . It was found that IL1B , AKT1 , STAT3 , and TLR2 were the core action targets of LPP. LPP activated immune signaling pathways by affecting them, influenced the expression of T-lymphocyte subpopulations, and promoted the secretion of cytokines and immunoglobulins to restore splenic injury and immune function. In addition, LPP increased the abundance of beneficial bacteria and produced more short-chain fatty acids (SCFAs) to maintain intestinal immune homeostasis. Overall, the administration of LPP effectively mitigates cyclophosphamide (CTX)-induced immunosuppression and disruption of the intestinal microbiota. These findings underscore the substantial potential of LPP as an immunoenhancing functional food ingredient. • Network pharmacology reveals potential targets of action for LPP immunomodulation. • LPP improves cytokine and immunoglobulin levels in immunosuppressed mice. • LPP ameliorates the effects of CTX on the mouse spleen. • LPP modulates gut microbial structure and SCFAs levels to enhance immunity in mice. • LPP has the potential to be a functional food for the treatment of immunosuppressive diseases.