Comparative assessment on osteoprotective effects of bone collagen peptides from diverse animal sources: Insights from the characteristics of gastrointestinal digestion and absorption

Abstract

Abstract BACKGROUND Although livestock and poultry bone collagen peptides (LBPs) have been reported to exhibit protective effects against osteoporosis, the in vitro osteogenic and in vivo anti‐osteoporotic bioactivity of LBPs may vary depending on the animal sources, and the underlying mechanisms remain unclear. The present study aimed to investigate the divergence in the osteoprotective effects of yak (YBPs)/bovine (BBPs)/porcine (PBPs)/chicken (CBPs) bone collagen peptides, and to elucidate how gastrointestinal digestion and absorption characteristics contribute to their distinct osteoprotective mechanisms. RESULTS YBPs/BBPs exhibited the highest osteoprotective effects, whereas PBPs exhibited weaker in vitro osteogenic but stronger in vivo anti‐osteoporotic bioactivity than CBPs. Four osteogenic peptides were obtained by virtual screening, their retention rates after simulated gastrointestinal digestion and apparent permeability coefficients in a Caco‐2 monolayer model ranged from 12.95% to 30.13% and 0.15 to 0.55 × 10 −7 cm s −1 , respectively. Integrated in silico analyses, gastrointestinal digestion stability and intestinal absorption/transportation data suggest that the divergent osteoprotective effects of LBPs likely stem from distinct absorptive/digestive properties mediated by their structural differences. CONCLUSION The divergent osteoprotective effects of YBP/BBPs/PBPs/CBPs are likely attributable to their structural determinants including gastrointestinal digestion/absorption/transportation, and affinity/binding modes to epidermal growth factor receptor, as well as possible RGD (arginine, glycine and aspartic acid) sequence similarity. These findings provide mechanistic insights and identify potential molecular targets for optimizing peptide‐based functional food ingredients for bone health. © 2026 Society of Chemical Industry.