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

Pecan (<i>Carya illinoensis</i>) 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 <i>p</i> < 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%, <i>p</i> < 0.01; FLLR 21.2%, <i>p</i> < 0.05). Gut microbiota analysis showed that RWEF and LWPL enriched the family Lachnospiraceae and the genus <i>Eisenbergiella</i>, 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.