Immunomodulatory Activity of Pecan-Derived Peptides: Targeting Cyclophosphamide-Mediated Immune Dysregulation

Pecan (Carya illinoensis) contains bioactive peptides with immunomodulatory potential. This study identified three pecan peptides─RWEF, LWPL, and FLLR─and evaluated their effects in cyclophosphamide-induced immunosuppressed mice. Peptide treatment significantly restored immune organ indices and biomarkers. Specifically, RWEF increased spleen acid phosphatase (ACP) and lactate dehydrogenase (LDH) by 31.2 and 40.0%, respectively; FLLR elevated ACP by 39.3% and LDH by 17.6%; and LWPL increased by 29.3 and 27.8% (all p < 0.01 compared to the model). The peptides also normalized blood cell counts and serum cytokine levels, enhanced T-cell immunity, and noticeably promoted macrophage phagocytosis (RWEF 29.5%, p < 0.01; FLLR 21.2%, p < 0.05). Gut microbiota analysis showed that RWEF and LWPL enriched the family Lachnospiraceae and the genus Eisenbergiella, taxa linked to gut and immune health. These findings indicate that pecan peptides mitigate immunosuppression by modulating immune organs, cellular responses, and gut microbiota, supporting their therapeutic potential.