Enteral feeding induces diet-dependent mucosal dysfunction, bacterial proliferation, and necrotizing enterocolitis in preterm pigs on parenteral nutrition

Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G1092-103. doi: 10.1152/ajpgi.00414.2007. Epub 2008 Sep 25.


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- to 3-day 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 (+60-80% 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-day-old TPN pigs fed enterally showed that formula feeding decreased villus 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, whereas 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Animals, Newborn
  • Cattle
  • Colostrum
  • Diet
  • Enteral Nutrition
  • Enterocolitis, Necrotizing / diet therapy*
  • Enterocolitis, Necrotizing / microbiology
  • Female
  • Infant Formula
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Organ Size
  • Parenteral Nutrition / adverse effects*
  • Pregnancy
  • Premature Birth
  • Swine
  • alpha-Tocopherol / metabolism


  • Amino Acids
  • alpha-Tocopherol