Sea cucumber peptides have been proven to exhibit a variety of biological activities. Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of the rectum and colon with increasing incidence and long duration, and is difficult to cure. The effect of sea cucumber peptide on UC is currently unknown. In this study, 1.5% dextran sulfate sodium (DSS) was added to the drinking water of mice to induce a UC model, and the daily doses of sea cucumber peptide (SP) solution of 200 mg/kg·BW, 500 mg/kg·BW, and 1000 mg/kg·BW were given to UC mice to detect the relieving effect of SP. The results showed that SP can reduce the disease activity index (DAI) of UC mice induced by DSS and can alleviate colon shortening, intestinal tissue damage, and the loss of intestinal tight junction proteins (Claudin-1, Occludin). SP decreased the spleen index, pro-inflammatory factors (IL-1β, IL-6, TNF-α), and myeloperoxidase (MPO) levels in UC mice. SP can alleviate the imbalance of gut microbiota in UC mice, increase the abundance of the Lachnospiraceae NK4A136 group, Prevotellaceae UCG-001, and Ligilactobacillus, and reduce the abundance of Bacteroides and the Eubacterium rum group, as well as alleviating the decrease in short-chain fatty acid (SCFA) content in the feces of UC mice. Notably, SP inhibited miR-155 expression in the colon tissue of UC mice and increased its target protein, suppressor of cytokine signaling 1 (SOCS1), which acts as an inflammatory inhibitor. In summary, the ameliorative effect of SP on UC may be achieved by improving the imbalance of gut microbiota and regulating the miR-155/SOCS1 axis. This study provides a new idea for developing SP as a nutritional supplement to maintain intestinal health.

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.