Germination-Assisted LAB-Fermented Soy Protein Gel Matrices with Reduced Sensitizing Potential: Associations with Epitope Disruption, Epithelial Transport, and Mucosal Immune-Cell/Cytokine Shifts

Abstract Food allergenicity reflects gastrointestinal bioaccessibility, epithelial transport, and immune recognition rather than intrinsic protein properties alone. Using germination-assisted lactic acid fermentation to engineer soy protein matrices with distinct microstructures, we systematically examined allergen fate across digestion, epithelial transport, and immune responses. Germination-induced remodeling produced looser, more porous gel networks, enhancing gastrointestinal disintegration and proteolytic accessibility. Digestion of remodeled matrices yielded greater loss of epitope-containing peptides, fewer high-molecular-weight immunoreactive fragments, and reduced IgE binding. Multiscale epitope mapping showed fewer digestion-resistant epitope peptides and limited retention of immunoreactive regions. Remodeled matrices enhanced transepithelial peptide transport while lowering the immunoreactivity of transported fractions, indicating altered biological properties rather than reduced transport. In a mouse sensitization model with identical challenge, engineered matrices alleviated allergic responses, suppressing Th2 markers, mast cell activation, and improving barrier and mucosal immune profiles, supporting a multiscale framework for hypoallergenic food design.