title: Gangliosides protect bowel in an infant model of necrotizing enterocolitis by suppressing proinflammatory signals.
abstract: OBJECTIVE
  Necrotizing enterocolitis (NEC) has high morbidity in premature infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors associated with NEC, whereas feeding human milk is protective. Vasoactive and inflammatory mediators in NEC remain elusive. Gangliosides are found in human milk and enterocyte membranes. An infant bowel model of NEC was developed to test the hypothesis that gangliosides modulate the inflammatory response to infection and hypoxia.
  
  
  METHODS
  Viable, noninflamed bowel was obtained from 9 infants between 26 and 40 weeks' gestational age. Infant bowel was treated in culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the presence or absence of preexposure to gangliosides. Bowel necrosis and production of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and proinflammatory cytokines were measured.
  
  
  RESULTS
  Ganglioside preexposure reduced bowel necrosis and endothelin-1 production in response to LPS. Gangliosides suppressed infant bowel production of nitric oxide, leukotriene B4, prostaglandin E2, hydrogen peroxide, interleukin-1beta, interleukin-6, and interleukin-8 in response to LPS exposure and hypoxia.
  
  
  CONCLUSIONS
  A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression.
authors.affiliation: Alberta Institute of Human Nutrition, 4-10 Agriculture/Forestry Centre, Canada.
authors.forename: Kareena L
authors.initials: KL
authors.lastname: Schnabl
authors.forename: Bodil
authors.initials: B
authors.lastname: Larsen
authors.forename: John E
authors.initials: JE
authors.lastname: Van Aerde
authors.forename: Gordon
authors.initials: G
authors.lastname: Lees
authors.forename: Mark
authors.initials: M
authors.lastname: Evans
authors.forename: Miodrag
authors.initials: M
authors.lastname: Belosevic
authors.forename: Catherine
authors.initials: C
authors.lastname: Field
authors.forename: A B R
authors.initials: AB
authors.lastname: Thomson
authors.forename: Michael T
authors.initials: MT
authors.lastname: Clandinin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D019332:Endothelin-1 / Q000096:biosynthesis; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000382:microbiology; D004926:Escherichia coli; D005732:Gangliosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008892:Milk / Q000737:chemistry; D009336:Necrosis / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D005732:Gangliosides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides