Peptidomics as a tool to analyze endogenous peptides in milk and milk-related peptides

As a subset of the proteome, peptidomics is the best tool to analyze peptides in different food matrices. Milk peptides are produced by protease hydrolysis in the mammary gland, which plays an important role in the growth and development of infants. However, methods of probing endogenous peptides are limited because the concentration of peptides is low, the peptides are easily lost during extraction/enrichment, and database searches are complicated. Based on the peptidomics analysis process, this paper reviews the research progress and applications of endogenous peptides with a focus on extraction, fractionation, identification, and bioinformatics analysis. Additionally, in-depth analysis of endogenous peptides in milk and milk-related products using joint strategies (a combined analysis of proteome/peptidomics/metabolomic approaches) was also introduced. New methodologies are provided to study peptides through bioinformatics and tracking the release of bioactive peptides from various milk sources by in vitro digestion models, which can better track the utilization of endogenous peptides in vivo. Challenges and future perspectives are also discussed, with a goal of exploring more bioactive peptides in milk and dairy products as well as simulating human milk in formula milk powder in the future. • Peptidomics as a tool to present novel analysis strategy of endogenous peptides. • Proposing research progress of endogenous peptides in milk and dairy products. • Peptidomics coupled with proteome and metabolomic strategy is discussed. • Analytical strategies for endogenous short peptides in milk need to be improved. • Digestion of endogenous peptides from milk in the human body is traced.