Food allergy has become a global food safety issue, and inducing tolerance of the immune system to allergens is seen as an effective way to address this problem. In this study, shrimp () was covalently modified with fucoidan to explore its potential as an oral tolerance inducer. The results showed that this strategy not only had no adverse effect on the growth of mice but also achieved significant immune tolerance induction effects. Specifically, it significantly reduced specific antibody levels, improved vascular permeability and intestinal barrier function, and inhibited mast cell degranulation. Further studies showed that these positive results were related to tolerogenic peptides (SLLKANIQL, GLTEFQAV, GDFPGAFKVF, ALNLNPTLALI, and AALDIDSKPF) produced in shrimp allergens. Moreover, this strategy mainly down-regulated gene expression in exogenous substance metabolic and immune-related signaling pathways, thereby reducing immune response to antigens. Overall, fucoidan-mediated covalent modification promises to be an efficient method for producing oral tolerance inducers.
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