Sodium Alginate Modification as a Promising Strategy for Inducing Oral Immune Tolerance to Fish Gelatin-Based Cell Scaffolds to Control Allergenic Risks

Abstract The allergenic risks of fish gelatin-based cell scaffolds remain an unresolved issue. The study proposed a sodium alginate modification strategy to solve allergenic risks by inducing oral immune tolerance. The strategy significantly reduced antibody production, mast cell degranulation, inflammatory mediator release, and Th2 immune response. Peptidomics and bioinformatics prediction revealed that the strategy protected CD4+ T cell epitopes (FTGASGLPG) and CD8+ T cell epitopes (e.g., GATGPTGL). Additionally, intestinal barrier function, integrity, and Th1/Th2/Th17/Treg immune balance were restored. Notably, compared with the positive control group, RORγt expression was suppressed by 73.42%, and FOXP3 expression was increased by 5.34-fold in the 1% group. Gut microbiota analysis suggested that sodium alginate modification significantly downregulated the abundance of Faecalibaculum and Lactobacillus, while increasing Prevotella. It regulates the intestinal microbiota, thereby contributing to immune tolerance induction. Overall, sodium alginate modification represents a promising strategy to promote immune tolerance.