A Genomics-Based Semirational Approach for Expanding the Postbiotic Potential of Collagen Peptides Using Lactobacillaceae

Food-derived bioactive peptides (BPs) have received considerable attention as postbiotics for human gut health. Here we used a genomics-based semirational approach to expand the postbiotic potential of collagen peptides (CPs) produced from probiotic fermentation. In silico digestion revealed distinct BPs embedded in fish collagen in a protease-dependent manner. Anaerobic digestion of collagen by representative Lactobacillaceae species revealed differential substrate utilization and collagen degradation patterns. Nanoliquid chromatography-mass spectrometry analysis of CPs showed that each species exhibited different cleavage patterns and unique peptide profiles. Remarkably, the 1-10 kDa CPs produced by Lacticaseibacillus paracasei showed agonistic activities toward G protein-coupled receptor 35 (GPR35). These CPs could repair intestinal epithelium through the GPR35-mediated extracellular signal-regulated protein kinase (ERK) 1/2 signaling pathway, suggesting that probiotic-aided collagen hydrolysates can serve as postbiotics for host-microbe interactions. Therefore, this study provides an effective strategy for the rapid screening of CPs for gut health in the gastrointestinal tract.