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1 Animal and Veterinary Basic Science, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark
2 Department of Human Nutrition, Faculty of life Sciences, University of Copenhagen, Denmark
3 Department of Surgery, Maastricht University, Maastricht, Netherlands
4 Children's Nutritional Research Center, Baylor College of Medicine, Houston, Texas, United States
5 Animal Health, Welfare and Nutrition, Faculty of Agricultural Sciences, University of Aarhus, Tjele, Denmark
6 Tjele, Denmark; Animal Health, Welfare and Nutrition, Faculty of Agricultural Sciences, University of Aarhus, Tjele, Denmark
7 Veterinary Institute, Technical University of Denmark, Frederiksberg C, Denmark
8 Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark
9 Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark
* To whom correspondence should be addressed. E-mail: psa{at}life.ku.dk.
Preterm neonates have an immature gut and metabolism and may benefit from total parenteral nutrition (TPN) before enteral food is introduced. Conversely, delayed enteral feeding may inhibit gut maturation and sensitize to necrotizing enterocolitis (NEC). Intestinal mass and NEC lesions were first recorded in preterm pigs fed enterally (porcine colostrum, bovine colostrum or formula for 20-40 h), with or without a preceding 2-3 d TPN period (n = 435). Mucosal mass increased during TPN, and further after enteral feeding to reach an intestinal mass similar to that in enterally-fed pigs without TPN (+60-70% relative to birth). NEC developed only after enteral feeding, but more often after a preceding TPN period for both sow's colostrum (26 vs. 5%) and formula (62 vs. 39%, both P < 0.001, n = 43-170). Further studies in 3 d-old TPN pigs fed enterally showed that formula feeding decreased villous height and nutrient digestive capacity, and increased luminal lactic acid and NEC lesions, compared with colostrum (bovine or porcine, P<0.05). Mucosal microbial diversity increased with enteral feeding, and Clostridium perfringens density was related to NEC severity. Formula-feeding decreased plasma arginine, citrulline, ornithine and tissue antioxidants, while tissue nitric oxide synthetase and gut permeability increased, relative to colostrum (all P < 0.05). In conclusion, enteral feeding is associated with gut dysfunction, microbial imbalance and NEC in preterm pigs, especially in pigs fed formula after TPN. Conversely, colostrum milk diets improve gut maturation and NEC resistance in preterm pigs subjected to a few days of TPN after birth.
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