Identification of Soy-Derived Peptides With Micelle Disruption Activity of Secondary Bile Acids

Bile acids, which originate in the liver as primary bile acids, facilitate the absorption of lipophilic components into the intestines and exist as micellar structures. Intestinal bacteria convert primary bile acids to secondary bile acids, such as deoxycholic acid (DCA), which is associated with colorectal cancer. Therefore, their elimination from the body is preferred. Soy protein hydrolysates are known for their bile acid-binding properties, which prompted our investigation of DCA-specific binding and micelle-disrupting peptides. We designed a peptide library from eight soy protein sequences and selected 42 candidate peptides based on their DCA-binding activity. These peptides were synthesized, and their ability to disrupt bile acid micelles was assessed using a 96-well high-throughput assay system. Of the 42 peptides evaluated, 41 exhibited significant DCA micelle degradation, and 21 showed specific activity only for DCA micelles. Further research involved preparing soy protein pepsin hydrolysates and identifying 1,354 free peptides. Among these, 10 peptides containing sequences from the initial peptide library were identified. All peptides exhibited DCA micelle-disrupting activity. These peptides are believed to facilitate the excretion of secondary bile acids. Notably, FGSLRKNAM and SLRKNAM selectively disrupted DCA micelles without affecting the micelles of other bile acids. As these two peptides were also identified in the undigested high molecular weight fraction, they are considered key peptides with high potential for efficiently promoting the excretion of DCA.