Kvistgaard AS, Sangild PT. Raw bovine milk improves gut responses to feeding relative to infant formula in preterm piglets. Am J Physiol Gastrointest Liver Physiol 306: G81-G90, 2014. First published October 24, 2013 doi:10.1152 doi:10. /ajpgi.00255.2013 neonates, the quality of the first milk is crucial for intestinal maturation and resistance to necrotizing enterocolitis (NEC). Among other factors, milk quality is determined by the stage of lactation and processing. We hypothesized that unprocessed mature bovine milk (BM; raw bovine milk) would have less bioactivity than corresponding bovine colostrum (BC) in a preterm pig model, but have improved bioactivity relative to its homogenized, pasteurized, spray-dried equivalent, whole milk powder (WMP), or a bovine milk proteinbased infant formula (IF). For 5 days, newborn preterm pigs received parenteral and enteral nutrition consisting of IF (n ϭ 13), BM (n ϭ 13), or BC (n ϭ 14). In a second study, WMP (n ϭ 15) was compared with IF (n ϭ 10) and BM (n ϭ 9). Compared with pigs fed IF, pigs that were fed BM had significantly improved intestinal structure (mucosal weight, villus height) and function (increased nutrient absorption and enzyme activities, decreased gut permeability, nutrient fermentation, and NEC severity). BC further improved these effects relative to BM (lactase activity, lactose absorption, plasma citrulline, and tissue interleukin-8). WMP induced similar effects as BM, except for lactase activity and lactose absorption. In conclusion, the maturational and protective effects on the immature intestine decreased in the order BCϾBMϾWMP, but all three intact bovine milk diets were markedly better than IF. The stage of lactation (colostrum vs. mature milk) and milk processing (e.g., homogenization, fractionation, pasteurization, spray-drying) are important factors in determining milk quality during the early postnatal period of preterm neonates. colostrum; mature milk; processing; preterm; intestinal maturation PRETERM NEONATES HAVE AN IMMATURE intestine that exhibits compromised nutrient absorption, reduced intestinal barrier function, and suboptimal immune responses toward microbes and food antigens (32). Consequently, preterm infants are very sensitive to enteral feeding and more prone to gastrointestinal complications, the most severe one of which is necrotizing enterocolitis (NEC). Early introduction of enteral feeding is beneficial for intestinal maturation and protection against NEC, but the quality of the diet may critically affect these positive effects. For example, the feeding of mother's milk matures the preterm gut and reduces the risk of NEC relative to bovine milk-based infant formula (IF) and possibly also banked donor milk (22,29,34,39,40). Donor milk (DM) is normally obtained at a relatively late stage of lactation, and therefore may not be appropriate as the first diet, when infants are supposed to receive mother's colostrum. Colostrum is the first milk after parturition (1-3 days) and contains trophic factors and immunoregulatory facto...

Threonine is an essential amino acid necessary for synthesis of intestinal (glyco)proteins such as mucin MUC2 to maintain adequate gut barrier function. In premature infants, reduced barrier function may contribute to the development of necrotizing enterocolitis (NEC). Human milk protects against NEC compared with infant formula. Therefore, we hypothesized that formula feeding decreases the MUC2 synthesis rate concomitant with a decrease in intestinal first-pass threonine utilization, predisposing the preterm neonate to NEC. Preterm pigs were delivered by caesarian section and received enteral feeding with formula (FORM; n = 13) or bovine colostrum (COL; n = 6) for 2 d following 48 h of total parenteral nutrition. Pigs received a dual stable isotope tracer infusion of threonine to determine intestinal threonine kinetics. NEC developed in 38% of the FORM pigs, whereas none of the COL pigs were affected (P = 0.13). Intestinal fractional first-pass threonine utilization was lower in FORM pigs (49 ± 2%) than in COL pigs (60 ± 4%) (P = 0.02). In FORM pigs compared with COL pigs, protein synthesis (369 ± 31 mg·kg(-1)·d(-1) vs. 615 ± 54 mg·kg(-1)·d(-1); P = 0.003) and MUC2 synthesis (121 ± 17%/d vs. 184 ± 15%/d; P = 0.02) were lower in the distal small intestine (SI). Our results suggest that formula feeding compared with colostrum feeding in preterm piglets reduces mucosal growth with a concomitant decrease in first-pass splanchnic threonine utilization, protein synthesis, and MUC2 synthesis in the distal SI. Hence, decreased intestinal threonine metabolism and subsequently impaired gut barrier function may predispose the formula-fed infant to developing NEC.

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