Temporal Dynamics of Gastrointestinal Digestion–Transport–Immunity Crosstalk in Sprouted Seed-Derived Soymilk Matrices: Correlating Epitope Stability with Dendritic Cell Expression Profiles and Immunoreactivity

Soymilk allergenicity is shaped by the digestive stability and epithelial transport of immunodominant epitopes. While germination alters seed physiology and matrix composition, its impact on digestion-transport-immune interactions remains unclear. This study investigated how germination impacts soymilk allergenicity by analyzing digestion, transepithelial transport, and immune responses via dynamic digestion models, cell assays, and peptidomics. Germination remodels peptide profiles stage-dependently: early to mid germination (heated seed germination-derived soymilk 1/2, HSSM-1/2) enhanced allergen hydrolysis and peptide transport, whereas late germination (heated seed germination-derived soymilk 3, HSSM-3) formed a gel-like matrix that hindered substrate accessibility. HSSM-1 and HSSM-2 showed reduced antigenicity and IgE binding, consistent with higher epitope degradation. Transport further lowered immunoreactivity, with HSSM-2 exhibiting the lowest residual antigenicity. HSSM digestates attenuate dendritic cell maturation, and HSSM-2 most effectively disrupts key allergen epitopes in the β-sheet and α-helix domains. Collectively, midstage germination reduced allergenic potential and provides a basis for designing hypoallergenic soy products.