Sea Cucumber Hydrolysate Alleviates Immunosuppression and Gut Microbiota Imbalance Induced by Cyclophosphamide in Balb/c Mice through the NF-κB Pathway

This study aimed to investigate the effect of sea cucumber hydrolysate (SCH) on immunosuppressed mice induced by cyclophosphamide (Cy). Our findings demonstrated that SCH could increase the thymus index and spleen index, decrease the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, increase the serum IgG and small intestinal sIgA levels, reduce small intestinal and colon tissue damage, and activate the nuclear factor-κB (NF-κB) pathway by increasing TRAF6 and IRAK1 protein levels, as well as the phosphorylation levels of IκBα and p65, thereby enhancing immunity. In addition, SCH alleviated the imbalance of the gut microbiota by altering the composition of the gut microbiota in immunosuppressed mice. At the genus level, when compared with the model group, the relative abundance of Dubosiella, Lachnospiraceae, and Ligilactobacillus increased, while that of Lactobacillus, Bacteroides, and Turicibacter decreased in the SCH groups. Moreover, 26 potential bioactive peptides were identified by oligopeptide sequencing and bioactivity prediction. This study’s findings thus provide an experimental basis for further development of SCH as a nutritional supplement to alleviate immunosuppression induced by Cy as well as provides a new idea for alleviating intestinal damage induced by Cy.