Advances in neonatal nutrition: a step forward infant formula biomimetic of human milk structure and digestive behaviour

Lipids of human milk or infant formula convey most of the energy necessary to support the newborn growth. Until recently, infant formula chemical composition had been optimized but not their structure. And yet, more and more proofs of evidence have shown that lipids structure in human milk modulates digestion kinetics and is involved in metabolic programming. Indeed there is a striking difference of structure between human milk which is an emulsion based on dispersed milk fat globules (4 µm) secreted by the mammary gland and the submicronic neoformed lipid droplets (0.5 µm) found in infant formula. These droplets result from a series of operation units. This difference of structure modifies digestion kinetics and emulsion disintegration in the intestinal tract of the newborn. This difference persists along gastric phase which is mainly dominated by acid and enzyme-induced aggregation. Lipid droplets size is thus the key parameter to control gastric lipolysis, gastric emptying and intestinal lipolysis. This parameter also controls proteolysis since adsorbed proteins are more rapidly hydrolyzed than when in solution. In animal models, these differences of lipid structure would also impact digestive and immune systems’ maturation and microbiota. Lipid structure during neonatal period would also be involved in the early programming of adipose tissues and metabolism. The supplementation of infant formulas with bovine milk fractions (milk fat globule membrane extracts, triacylglycerol) or recent development of large droplets infant formula biomimetic of human milk lipid structure, along with new fields of innovation in neonatal nutrition, will be reviewed.Despite these recent innovations, more data on the structure of human milk throughout lactation and on the digestive behaviour of specific fractions of human milk lipids are still needed to build a sound basis for the optimization of infant formula. A better understanding of fractions that escape enzymatic digestion in the upper tract, and serve as substrates for microbiota, may help controlling microbiota shifts that exist between breast-fed and formula-fed infants. Combinations of factors (synbiotics and lipid structure) and more staging, seem important levers to further improve infant formula but their efficacy and safety still have to be assessed in clinical trials