Human milk is generally recognized as the gold standard in neonatal nutrition. The structure andcomposition of human milk are better mimicked in infant formulas that include cow s milk lipids andmilk fat membrane extracts, which could also improve physiological properties. Nevertheless, very fewinfant formulas use cow' s milk lipids that are more expensive than vegetable lipids. The potential impactof milk lipid structure and composition on neonatal digestive hydrolysis, intestinal physiology, and gutmicrobiota was recently underlined by several scientific teams. In this context, the purpose of the presentreview was to summarize the specificity of composition and structure of human milk and to highlight therecent results on the modulation of infant formula interfacial composition and fat source on neonataldigestive hydrolysis, intestinal physiology, and gut microbiota. More specifically, the interfacialcomposition of model emulsions stabilized with milk polar lipids will be unraveled as well as the additionof apolar milk fat extracts in replacement to vegetable lipids in infant formulas. The impact of partiallyreplacing vegetable lipids by milk lipids stabilized by milk fat membranes was investigated in the piglets.This replacement in fluenced the neonatal intestinal physiology through the release of immune-modulatory lipids, the modulation of proteolysis, and the modification of gut microbiota.PracticalApplications:The potential development of infant formulas including cow’s milk lipid fractions with a structure closer to human milk is discussed. These more biomimetic formulas should result in enhanced nutritional benefits concerning neonatal digestive hydrolysis, physiology, and gut microbiota developmen

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