Raw bovine milk improves gut responses to feeding relative to infant formula in preterm piglets

Abstract

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...

Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine

“…Because of the high cost of providing purified recombinant TGF-␤2 to preterm pigs, we first studied the relations between TGF-␤2 and IL-8 using colostrum as an exogenous natural source of TGF-␤2 and manipulating bacterial colonization with oral antibiotic treatment, and then coupled these in vivo studies with a series of in vitro cell studies on TGF-␤2, IL-8, and LPS. Additional results from the two in vivo studies can be found in our previous publications (14,16).…”

“…The animal protocol was approved by the Danish National Committee of Animal Experimentation and was performed as described in our previous work on the same animals (13,14,16). In brief, preterm pigs delivered at 105-106 days of gestation (term 116 -117 days) were fed with parenteral nutrition with or without minimal enteral nutrition for 2 days followed by 2 days of full enteral nutrition before euthanasia on day 5.…”

“…Tissue samples from the distal small intestine or colon were snap-frozen at Ϫ80°C before further analysis. In the present study, intestinal and colonic tissues and contents from these earlier studies (13,14,16) were used to measure TGF-␤2 and IL-8 in the present study and to relate this to NEC incidence and severity across treatments.…”

“…TGF-␤2 content in the two diets (colostrum and infant formula) was determined by Western blot with the protocol as indicated previously (3). Bovine colostrum used for the pig study was the pooled colostrum from various colostrum samples obtained from different healthy cows while formula was produced from commercial products (13,16). The intestinal tissues from pig studies were homogenized in 1% Triton X-100 solution (10 ml/g tissue) with the addition of protease inhibitor cocktail (Sigma-Aldrich, Copenhagen, Denmark) before Western blot analysis.…”

“…When preterm pigs are fed formula for up to 10 days, most pigs develop NEC, unless oral antibiotics are given to reduce gut bacterial colonization (14). On the other hand, a reduced risk of NEC and reduced levels of inflammatory mediators are observed in preterm pigs fed donor human milk, bovine colostrum, and amniotic fluid (16,36,37). These enteral diets have greater levels of bioactive components, such as TGF-␤2 and epidermal growth factor (10,17), which may reduce NEC, at least in the more artificial models of NEC in mice (10,19).…”