Digestion of nutrients is an essential function of the newborn infant gut to allow growth and development and understanding infant digestive function is essential to optimize nutrition and oral drug delivery. Ethical considerations prohibit invasive in vivo trials and as a consequence in vitro assays are often conducted. However, the choice of in vitro model parameters are not supported by an exhaustive analysis of the literature and do not mimic precisely the digestive conditions of the infant. This review contains a compilation of the studies which characterized the gastroduodenal conditions in full-term or preterm infants of variable postnatal age from birth up to six months. Important data about healthy full-term infants are reported. The enzymatic (type of enzymes and level of activity) and nonenzymatic (milk-based diet, frequency of feeding, bile salt concentrations) conditions of digestion in infants are shown to differ significantly from those in adults. In addition, the interindividual and developmental variability of the digestive conditions in infants is also highlighted.

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The first months of life correspond to a key period in human life where dramatic physiological changes (establishment of microbiota, development of the immune system, etc.) occur. In order to better control these changes it is necessary to understand the behaviour of food in the gastrointestinal tract of the newborn. Infant formula is the only food for the newborn when breast-feeding is impossible. The kinetics of digestion of milk proteins and the nature of the peptides liberated in the small intestine throughout infant formula digestion have never been extensively investigated so far and were therefore studied using the piglet as a model of the newborn child. Piglets were fed infant formula by an automatic delivery system during 28 d, and slaughtered 30, 90 and 210 min after the last meal. Contents of stomach, proximal and median jejunum and ileum were collected and characterised. The extent of b-lactoglobulin (b-lg), a-lactalbumin (a-la) and casein proteolysis was monitored by inhibition ELISA, SDS-PAGE, immunoblotting and MS. At 30 min after the last meal, caseins were shown to be extensively hydrolysed in the stomach. Nevertheless, peptides originating mainly from b-caseins (from 509 to 2510 Da) were identified in the jejunum and ileum of the piglets. b-Lg partially resisted gastric digestion but completely disappeared in the stomach after 210 min. a-La had a similar behaviour to that of b-lg. Two large peptides (4276 and 2674 Da) generated from b-lg were present in the ileum after 30 and 210 min and only one (2674 Da) after 90 min.Key words: Digestion: Milk proteins: Piglets: Infant formula Protein digestion is a complex process resulting in the concerted action of digestive enzymes on dietary proteins and depending on many factors such as the type of dietary proteins, gastric and intestinal pH, peptic activity, endogenous secretions, and motility.Major differences in the composition of breast milk and infant formula (protein content, lipids, lactose, growth factors, immunoglobulins, enzymes, etc.) can make the way proteins are digested by the newborn different and can therefore modulate the physiology of the gut (1) . Although studies have been performed on different aspects of digestion (metabolism, gastric emptying, protein flow, etc.), there is very limited information in the literature on protein digestion in the infant. During the neonatal period, the gastric hydrolysis of milk proteins by pepsin is limited due to the buffering capacity of milk that increases the pH, thus limiting the activity of this acid protease (2) . Gastric emptying was shown to be faster with human milk than with casein-based formula-and cows' milk-fed children (3,4) . However, identical gastric emptying was found in preterm infants fed either a soluble milk protein (SMP)-predominant (caseins:SMP ratio 40:60) or a casein-predominant (caseins:SMP ratio 82:18) formula, the amount of all other nutrients and osmolality being similar (5) . Several studies have been conducted in vitro on the digestion of milk proteins using v...

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

The incorporation of both milk fat and MFGM fragments in infant formula modifies protein digestion, the dynamic of the immune system maturation and the faecal microbiota composition.

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