Human milk is the ideal food for infant nutrition and optimal growth. When breastfeeding isnot available, infant formulas are often administrated. The chemical composition of infant formulashas been optimized but human milk structure and bioactive compounds are not mimicked1. Theseinitial differences may modulate the kinetics of digestion and of disintegration of the emulsion inthe digestive tract of the newborns. To check this hypothesis, the digestive behaviors of acommercial infant formula (IF) and raw human milk (HM) were compared using a dynamic in vitrodigestion system (DIDGI®)2.Supported by an exhaustive literature review3, the dynamic digester was set to mimic asclosely as possible the digestive conditions of term newborns. Pooled term HM (n=5 donors)4 anda liquid commercially available IF were digested in triplicate. Samples were collected from thegastric and intestinal compartments throughout digestion. Initial emulsions and digesta werecharacterized. Lipolysis and proteolysis kinetics were monitored by SDS-Page, thin-layer and gaschromatography methods. Structural changes were evaluated by confocal microscopy and laserlight scattering.Our findings indicated that the initial differences in structure, composition and prehydrolysisstate of the two emulsions strongly impacted digestion kinetics and deconstruction.Lipolysis levels were higher in HM than in IF before digestion, during gastric phase and this orderwas reversed at the beginning of the intestinal phase. Gastric proteolysis of caseins wasaccelerated in IF compared to HM, probably in link with their partition at the interface of thesubmicronic droplets. As observed by confocal microscopy and in coherence with previous resultson model infant emulsions5, the differences in initial structure of the emulsions were maintainedduring the gastric phase of the digestion: the presence of native human milk fat globule in HM (5.1± 0.2 μm) and of submicronic lipid droplets in IF (0.2 ± 0.0 μm). HM presented a structuraldestabilization from 60 min of gastric digestion, with a bimodal distribution of the particles size(mode 1 = 76.5 μm, mode 2 = 6.5 μm). IF gastric digestion was marked by average modediameter changing drastically from 90 min (16.6 ± 2.2 μm). A progressive disruption of theseaggregates was observed in the intestinal phase for both HM and IF.Despite in constant evolution, infant formulas are not yet biomimetic of human milkdigestive behavior. These differences may have important physiological implications andunderline the need for developing soft processes with minimal impact on milk native emulsionstructure in the near future.