Structural Differences Modulate In Vitro and In Vivo Digestion and Absorption of Milk Phospholipids: Insights from Human Milk and Infant Formula Analog Models

The phospholipid composition of human milk and infant formula differs. To evaluate how the structure and distribution of phospholipid classes affect digestion and the bioavailability of fatty acids, our study employed simplified phospholipid-composition model emulsions comprising purified phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM), and phospholipid analogs mimicking human milk (HMPA) or infant formula (IFPA). In simulated infant gastrointestinal digestion, phospholipid hydrolysis and free fatty acid release followed the order PE > PC > SM. HMPA showed greater interfacial charge changes, faster phospholipid degradation, and higher fatty acid release than IFPA. In mice, it also produced higher dose-normalized serum AUCs for major fatty acids. These findings indicate that phospholipid class composition modulates digestion characteristics and the rate of fatty acid absorption. However, these purified models do not reproduce human milk or formula. Thus, the results should be interpreted as mechanistic evidence rather than direct infant nutritional outcomes.