Maillard reaction upgrades silver carp hydrolysates into prebiotic with immunomodulatory potential: The synergistic effects on immune function and gut microenvironment

Immunosuppression is closely linked to intestinal barrier dysfunction and gut microbial imbalance. Our previous studies demonstrated that the Maillard reaction can effectively enhance the prebiotic function and antioxidant capacity of silver carp hydrolysates (SCH) in vitro, suggesting their potential immunomodulatory value. Therefore, this study investigated the prebiotic and immunomodulatory effects of Maillard reaction-modified silver carp hydrolysates (SCH-MRPs) in a cyclophosphamide-induced immunosuppression model. SCH-MRPs significantly improved both humoral and mucosal immunity by increasing serum immunoglobulins, normalizing colonic cytokine balance, and re-establishing CD4⁺/CD8⁺ T-cell homeostasis. They also improved colon index, body weight, and colonic antioxidant capacity. Mechanistically, SCH-MRPs reactivated TLR4/NF-κB signaling, enhancing immune responsiveness, and reinforced intestinal barrier integrity through the upregulation of zonula occludens-1 (ZO-1), Occludin, Claudin-1, and Muc-2. Additionally, SCH-MRPs reshaped the gut microbiota composition toward a more beneficial profile, characterized by enrichment of short chain fatty acid (SCFA)-producing bacteria such as Bacteroidetes and a reduction in potentially harmful genera like Candidatus_Saccharimonas. These microbial shifts were accompanied by increased total SCFA levels, particularly propionic acid and butyric acid, along with upregulation of SCFA receptor expression. Overall, this study provides scientific evidence supporting SCH-MRPs as promising peptide-based prebiotic candidates for modulating gut-immune homeostasis and advancing functional food development.