Bile Acid Sequestration by Soy Peptide Condensates Modulates the Digestion Fate of Soy 7S Protein Aggregates

Abstract The physiological functions of soy protein are commonly attributed to bioactive peptides released during digestion, whereas the roles of digestion-derived protein assemblies remain poorly understood. Here, we investigated two assemblies generated from soy 7S globulin, digestion-resistant core region (CR) aggregates and extension region (ER) peptide condensates. ER peptides formed condensates and remodeled CR aggregates from ordered amyloid-like structures into more disordered conformations. Bile acids promoted CR disassembly and proteolysis, whereas ER condensates sequestered bile acids and restricted their access to CR. Confocal imaging supported the spatial isolation of bile acids by ER condensates. Bile acids also enhanced epithelial transport and strengthened interactions between CR aggregates and mimetic lipid bilayers, whereas these effects were attenuated by ER-mediated bile acid sequestration. Our findings support a role for bile acid availability in modulating CR digestibility and transepithelial transport, linking peptide condensation, bile acid homeostasis, and protein functionality.