Effect of Milk Formula Protein Content on Intestinal Barrier Function in a Porcine Model of LBW Neonates

Abstract

ABSTRACT:Our study aimed at investigating the impact of the level of protein in milk formula on intestinal structure, barrier function, and its nervous regulation in normal and LBW neonates using a porcine model. Normal birth weight (NBW) or LBW piglets were fed from d7 to d28 of age either with a high protein (HP) or with an adequate protein (AP) formula or stayed with their mother [mother fed (MF)]. The proximal jejunum and distal ileum were sampled at d28 for morphometry analysis and ex vivo permeability measurement in Ussing chambers. Formula feeding induced a trophic effect on the jejunum and ileum of both NBW and LBW piglets, which exhibited longer villi than MF animals, irrespective of the type of formula. In NBW piglets, intestinal permeability was not altered by formula feeding. On the contrary, LBW piglets fed with HP formula, but not AP, exhibited a greater ileal permeability than MF piglets. Feeding the HP formula also disturbed jejunal and ileal regulation of permeability by acetylcholine and vasoactive intestinal peptide (VIP) in LBW compared with MF LBW piglets. In conclusion, the level of protein in formulas did not modify intestinal structure and function in NBW individuals but dramatically modified intestinal barrier function physiology in LBW individuals. (Pediatr Res 69: 4-9, 2011) T he health benefits of breast feeding have been recognized for a long time. However, many infants are still formulafed for periods of their first months of life. Formulation is an area of intensive research to improve the nutritional quality of milk formulas. However, the amount of protein per energy content is generally higher in formula than in human milk to meet the protein and amino acid requirements of infants (up to 40 and 66% more proteins than human milk for healthy neonates and preterm and LBW babies, respectively) (1). Epidemiological data point out an increased risk of developing metabolic disease and obesity later in life with accelerated growth in early life (2). High protein (HP) formulas are suspected to be one of the major factors of such accelerated growth (3). Therefore, the actual tendency is to reduce protein content in formulas toward the minimal level (4), although HP formulas are still recommended for premature and LBW babies (5).Several studies have established that formula-feeding impacts intestinal development. Using endoscopic techniques to obtain biopsies from healthy infants, Thompson et al. (6) observed that crypt length was increased by 30% in formulafed infants. More extensive studies undertaken in rats also concluded to a trophic effect of formula-versus breast-feeding on the intestine (7,8). Besides structural modifications, formula feeding also impacts intestinal epithelial barrier function. The epithelium lining the intestine plays an integrated role in maintaining intestinal barrier function through the proteins forming the tight junctions (TJs), which constitute a selective barrier and regulate the passage of molecules according to their size. Intestinal barrier function is ...

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