Peptidomics Reveals That Goat Milk Is Closer to Human Milk Than Cow Milk in Proline-Rich Oligopeptide Release during In Vitro Dynamic Infant Digestion

Abstract Human milk is the gold standard for infant nutrition. This study employed an in vitro dynamic infant gastrointestinal digestion model coupled with peptidomics to profile oligopeptide release from human, goat, and cow milk. Peptidomics identified 717, 658, and 514 oligopeptides from human, goat, and cow milk, respectively. Goat milk closely mirrored human milk in length distribution, with both peaking at 4–5 residues, whereas cow milk exhibited a peak at 6–7 residues. Proline was the most abundant amino acid residue across all sources, and goat milk generated significantly higher numbers of short oligopeptides (≤10 residues) than cow milk. Notably, 38 oligopeptides were exclusively shared between human and goat milk, predominantly proline-rich, casein-derived sequences with multiple predicted bioactivities. These findings indicate that goat milk is predicted to offer functional advantages over cow milk for human milk-oriented infant nutrition, primarily through its capacity to generate proline-rich bioactive oligopeptides.