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.

Clinical and animal studies have demonstrated beneficial effects of early consumption of dairy lipids and a probiotic, Lactobacillus fermentum (Lf), on infant gut physiology. The objective of this study was to investigate their long-term effects on gut microbiota and host entero-insular axis and metabolism. Piglets were suckled with a milk formula containing only plant lipids (PL), a half-half mixture of plant lipids and dairy lipids (DL), or this mixture supplemented with Lf (DL + Lf). They were weaned on a standard diet and challenged with a high-energy diet until postnatal day 140. DL and DL + Lf modulated gut microbiota composition and metabolism, increasing abundance of several Clostridia genera. Moreover, DL + Lf specifically decreased the faecal content of 2-oxoglutarate and lysine compared to PL and 5-aminovalerate compared to PL and DL. It also increased short-chain fatty acid concentrations like propionate compared to DL. Furthermore, DL + Lf had a beneficial effect on the endocrine function, enhancing caecal GLP-1 and GLP-1 meal-stimulated secretion. Correlations highlighted the consistent relationship between microbiota and gut physiology. Together, our results evidence a beneficial programming effect of DL + Lf in infant formula composition on faecal microbiota and entero-insular axis function.

Breast milk is the gold standard in neonatal nutrition, but most infants are fed infant formulas in which lipids are usually of plant origin. The addition of dairy lipids and/or milk fat globule membrane extracts in formulas improves their composition with beneficial consequences on protein and lipid digestion. The probiotic Lactobacillus fermentum (Lf) was reported to reduce transit time in rat pups, which may also improve digestion. This study aimed to investigate the effects of the addition of dairy lipids in formulas, with or without Lf, on protein and lipid digestion and on gut physiology and metabolism. Piglets were suckled from postnatal days 2 to 28, with formulas containing either plant lipids (PL), a half-half mixture of plant and dairy lipids (DL), or this mixture supplemented with Lf (DL+Lf). At day 28, piglets were euthanized 90 min after their last feeding. Microstructure of digesta did not differ among formulas. Gastric proteolysis was increased (P < 0.01) in DL and DL+Lf (21.9 ± 2.1 and 22.6 ± 1.3%, respectively) compared with PL (17.3 ± 0.6%) and the residual proportion of gastric intact caseins decreased (p < 0.01) in DL+Lf (5.4 ± 2.5%) compared with PL and DL (10.6 ± 3.1% and 21.8 ± 6.8%, respectively). Peptide diversity in ileum and colon digesta was lower in PL compared to DL and DL+Lf. DL and DL+Lf displayed an increased (p < 0.01) proportion of diacylglycerol/cholesterol in jejunum and ileum digesta compared to PL and tended (p = 0.07) to have lower triglyceride/total lipid ratio in ileum DL+Lf (0.019 ± 0.003) as compared to PL (0.045 ± 0.011). The percentage of endocrine tissue and the number of islets in the pancreas were decreased (p < 0.05) in DL+Lf compared with DL. DL+Lf displayed a beneficial effect on host defenses [increased goblet cell density in jejunum (p < 0.05)] and a trophic effect [increased duodenal (p = 0.09) and jejunal (p < 0.05) weights]. Altogether, our results demonstrate that the addition of dairy lipids and probiotic Lf in infant formula modulated protein and lipid digestion, with consequences on lipid profile and with beneficial, although moderate, physiological effects.