title: The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats.
abstract: BACKGROUND
  Necrotising enterocolitis (NEC) is one of the most common and fatal intestinal disorders in preterm infants. Breast-fed infants are at lower risk for NEC than formula-fed infants, but the protective components in human milk have not been identified. In contrast to formula, human milk contains high amounts of complex glycans.
  
  
  OBJECTIVE
  To test the hypothesis that human milk oligosaccharides (HMO) contribute to the protection from NEC.
  
  
  METHODS
  Since human intervention studies are unfeasible due to limited availability of HMO, a neonatal rat NEC model was used. Pups were orally gavaged with formula without and with HMO and exposed to hypoxia episodes. Ileum sections were scored blindly for signs of NEC. Two-dimensional chromatography was used to determine the most effective HMO, and sequential exoglycosidase digestions and linkage analysis was used to determine its structure.
  
  
  RESULTS
  Compared to formula alone, pooled HMO significantly improved 96-hour survival from 73.1% to 95.0% and reduced pathology scores from 1.98 ± 1.11 to 0.44 ± 0.30 (p<0.001). Within the pooled HMO, a specific isomer of disialyllacto-N-tetraose (DSLNT) was identified to be protective. Galacto-oligosaccharides, currently added to formula to mimic some of the effects of HMO, had no effect.
  
  
  CONCLUSIONS
  HMO reduce NEC in neonatal rats and the effects are highly structure specific. If these results translate to NEC in humans, DSLNT could be used to prevent or treat NEC in formula-fed infants, and its concentration in the mother's milk could serve as a biomarker to identify breast-fed infants at risk of developing this disorder.
authors.affiliation: University of California-San Diego, Department of Pediatrics, Division of Neonatal Medicine, 200 West Arbor Drive, MC 8450, San Diego, CA 92103-8450, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jantscher-Krenn
authors.forename: Monica
authors.initials: M
authors.lastname: Zherebtsov
authors.forename: Caroline
authors.initials: C
authors.lastname: Nissan
authors.forename: Kerstin
authors.initials: K
authors.lastname: Goth
authors.forename: Yigit S
authors.initials: YS
authors.lastname: Guner
authors.forename: Natasha
authors.initials: N
authors.lastname: Naidu
authors.forename: Biswa
authors.initials: B
authors.lastname: Choudhury
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Grishin
authors.forename: Henri R
authors.initials: HR
authors.lastname: Ford
authors.forename: Lars
authors.initials: L
authors.lastname: Bode
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000032:analysis / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009844:Oligosaccharides; C576246:disialyllacto-N-tetraose