Effect of Marine-Derived Scallop Peptide Hydrolysate on Immune Modulation and Gut Microbiota Restoration in Cyclophosphamide-Induced Immunosuppressed Mice.

Cyclophosphamide (CTX), a chemotherapy agent, can weaken immune responses and disrupt gut microbiota, resulting in dysbiosis and inflammation. The gut microbiota, a composite community of microorganisms, plays a central role in regulating metabolism, supporting biological functions, and maintaining immune balance. Dysbiosis may lead to various systemic diseases and metabolic issues. This underscores the importance of immunomodulators to boost immune health and restore balance during CTX treatment. This study assessed the impact of scallop peptide hydrolysate (SCH), derived from scallops collected from a local seafood market in Dalian, China, on immune suppression, intestinal integrity, and gut microbiota composition in BALB/c mice with CTX-induced immunosuppression. The findings demonstrated that SCH significantly restored intestinal mucosal integrity of goblet cells, enhanced the levels of tight-junction proteins (Occludens, Zonula-1, Mucin-2, Claudin-1), and improved the histological state of both the colon and spleen. SCH treatment resulted in increased body weight, improved immune organ indices, and enhanced levels of pro-inflammatory cytokines and immunoglobulins, while reducing anti-inflammatory cytokines. Furthermore, SCH exhibited no cytotoxic effects on RAW264.7 macrophages, promoting the formation of pseudopodia and enhancing phagocytic activity, thereby improving cell-mediated immunity and splenic lymphocyte proliferation. Moreover, SCH therapy markedly increased the numbers of CD4+ and CD8+ T lymphocytes in the spleen, which CTX diminished. Additionally, SCH treatment decreased the Bacteroidetes/Firmicutes ratio and restored the biological balance of gut microbiota, increasing beneficial bacteria such as Muribaculaceae. These results indicate that SCH functions as a prebiotic and could serve as a functional food ingredient with potential therapeutic benefits for gastrointestinal disorders and immune regulation.