Data-independent acquisition-based comparative analysis of whey proteomes in human colostrum, mature milk, and small ruminant milk for precision infant formula development.

Human milk is the gold standard for infant nutrition, evolving with developmental needs. This study identified 614 whey proteins from human, goat, and sheep colostrum and mature milk, with 76 conserved and 495 showing significant differences ( < 0.05). Compared to other samples, human colostrum (HC) exhibited higher levels of neutrophil extracellular trap formation-related proteins, with fold change (FC) ranging from 21.3 to 128.0, including neutrophil elastase, myeloperoxidase, and neurovascular development-related proteins such as platelet-derived growth factor C and neuropilin (FC = 1.8-29.6). Human mature milk showed higher levels of muscle metabolism-related proteins. Additionally, small ruminant colostrum exhibited a higher abundance of a greater variety of complement proteins than mature milk. In summary, the whey proteome of human milk emphasizes early protection and development, and incorporating development- and metabolism-related proteins into small ruminant colostrum as a base may be a promising direction for future formula optimization.