An animal model of necrotizing enterocolitis induced by infant formula and ischemia in developing piglets

Gastroenterology. 1994 May;106(5):1215-22. doi: 10.1016/0016-5085(94)90012-4.


Background/aims: The lipid component of piglet formula (0.5% fat) causes increased mucosal permeability in 1-day-old piglets after ischemia/reperfusion. The present study examined if luminal exposure to infant formulas (3.5% fat) and ischemia/reperfusion result in an animal model of necrotizing enterocolitis and if injury is dependent on the formula fat composition.

Methods: Plasma-to-lumen clearance of 51Cr-ethylenediamine-tetraacetic acid was measured, and morphology was evaluated during luminal perfusion with preterm, term, and delipidated preterm cow milk-based infant formulas before and after ischemia/reperfusion in 1-day-old and 1-month-old piglet jejunoileum. In a separate set of experiments, a 1-2-cm segment of ileum was exteriorized and opened to expose the mucosal surface, and the villi were superfused with the above formulas (no ischemia).

Results: Before ischemia, clearances were markedly higher for intestinal loops perfused with preterm formula than for loops perfused with term and delipidated formulas in 1-day-old animals. After ischemia, clearances in loops perfused with preterm formula were significantly greater and grossly hemorrhagic and histologically necrotic compared with loops perfused with delipidated formula (minimal injury). Superfusion with preterm formula caused diffuse hyperemia and hemorrhage into intestinal villi.

Conclusions: Luminal perfusion of 1-day-old piglet jejunoileum with predigested and bile acid-solubilized preterm infant formula, in combination with ischemia/reperfusion, produces an animal model of necrotizing enterocolitis, but only if the lipid fraction of the formula is present.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animal Feed / adverse effects
  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Edetic Acid / pharmacokinetics
  • Enterocolitis, Pseudomembranous / chemically induced*
  • Enterocolitis, Pseudomembranous / etiology*
  • Enterocolitis, Pseudomembranous / pathology
  • Female
  • Food, Formulated / adverse effects*
  • Ileum / chemistry
  • Ileum / pathology
  • Ileum / ultrastructure
  • Jejunum / chemistry
  • Jejunum / pathology
  • Jejunum / ultrastructure
  • Male
  • Microvilli / chemistry
  • Microvilli / ultrastructure
  • Reperfusion Injury / complications*
  • Swine / growth & development*
  • Triglycerides / analysis


  • Triglycerides
  • Edetic Acid