Condensation of Soy Protein Peptides Contributes to Sequester Bile Acids and Mitigate LPS-Induced Inflammation

Soy protein is widely known to have serum triglyceride (TG) and cholesterol-lowering effects associated with a reduced risk of cardiovascular disease. Recent studies highlighted that the extension region (ER) domain of soy 7S globulin (β-conglycinin) is a key component responsible for the serum TG-lowering effect via modulation of bile acid (BA) homeostasis. Here, we studied the sequestration of BAs by ER peptides during intestinal digestion in vitro and assessed the anti-inflammatory effects of ER peptides using Caco-2/HT29-MTX/RAW264.7 triple-cell cocultures as an intestine cell model. Results show that ER peptides, which share characteristics of intrinsically disordered regions (IDRs), are capable of forming peptide condensates and exhibit the capability to sequester BA-containing colloidal structures during intestinal digestion in vitro. Moreover, BAs enhance the penetration of peptide condensates within the mucus layer, enabling ER peptides to mitigate lipopolysaccharide (LPS)-induced gut inflammation. These results provide a possible explanation for the molecular mechanisms underlying the modulation of BA homeostasis by soybean proteins.