title: Diet-dependent mucosal colonization and interleukin-1beta responses in preterm pigs susceptible to necrotizing enterocolitis.
abstract: OBJECTIVE
  Intestinal colonization challenges the neonatal innate immune system, especially in newborns with an immature immune response lacking the supportive bioactive components from mother's milk. Accordingly, formula-fed preterm pigs frequently show bacterial overgrowth, mucosal atrophy, and gut lesions reflecting necrotizing enterocolitis (NEC) within the first days after birth. We hypothesized that NEC development is related to a diet-dependent bacterial adherence and a subsequent proinflammatory cytokine response in the gut mucosa immediately after introduction of enteral food.
  
  
  METHODS
  Premature piglets (92% gestation) received 2 to 3 days of total parenteral nutrition followed by 0, 8, or 17 hours of enteral formula or sow's colostrum feeding.
  
  
  RESULTS
  Following 8 hours, but not 17 hours, of colostrum feeding, a reduced number of intestinal samples with adherent bacteria (both Gram-negative and Gram-positive bacteria) was counted compared with 0 or 8 hours of formula feeding. Besides a more dense colonization, formula feeding leads to higher intestinal interleukin-1beta (IL-1beta) levels and more NEC-like lesions from 8 hours onward. The load of adherent bacteria was especially high in NEC lesions. Toll-like receptor 4 was detected in enteroendocrine, neuronal, and smooth muscle cells, potentially mediating the increase in IL-1beta levels by Gram-negative bacteria.
  
  
  CONCLUSIONS
  Formula feeding facilitates bacterial adherence and the development of a proinflammatory state of the intestine, which may be among the key factors that predispose formula-fed preterm neonates to NEC.
authors.affiliation: Department of Veterinary Medicine, University of Antwerp, Wilrijk, Belgium.
authors.forename: Els R
authors.initials: ER
authors.lastname: Van Haver
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.forename: Marijke
authors.initials: M
authors.lastname: Oste
authors.forename: Jayda L A
authors.initials: JL
authors.lastname: Siggers
authors.forename: Andre L M
authors.initials: AL
authors.lastname: Weyns
authors.forename: Christa J
authors.initials: CJ
authors.lastname: Van Ginneken
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001422:Bacterial Adhesion; D015169:Colony Count, Microbial; D003126:Colostrum / Q000276:immunology*; D004032:Diet; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D008070:Lipopolysaccharides; D010288:Parenteral Nutrition; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4