The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats

Evelyn Jantscher-Krenn, Monica Zherebtsov, Caroline Nissan, Kerstin Goth, Yigit S. Guner, Natasha Naidu, Biswa Choudhury, Anatoly V. Grishin, Henri Ford, Lars Bode

Research output: Contribution to journalArticle

146 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1417-1425
Number of pages9
JournalGut
Volume61
Issue number10
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

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Necrotizing Enterocolitis
Human Milk
Oligosaccharides
Infant Formula
Breast
disialyllacto-N-tetraose
Glycoside Hydrolases
Ileum
Premature Infants
Polysaccharides
Chromatography
Digestion
Milk
Biomarkers
Mothers
Pathology

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Jantscher-Krenn, E., Zherebtsov, M., Nissan, C., Goth, K., Guner, Y. S., Naidu, N., ... Bode, L. (2012). The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut, 61(10), 1417-1425. https://doi.org/10.1136/gutjnl-2011-301404

The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. / Jantscher-Krenn, Evelyn; Zherebtsov, Monica; Nissan, Caroline; Goth, Kerstin; Guner, Yigit S.; Naidu, Natasha; Choudhury, Biswa; Grishin, Anatoly V.; Ford, Henri; Bode, Lars.

In: Gut, Vol. 61, No. 10, 01.10.2012, p. 1417-1425.

Research output: Contribution to journalArticle

Jantscher-Krenn, E, Zherebtsov, M, Nissan, C, Goth, K, Guner, YS, Naidu, N, Choudhury, B, Grishin, AV, Ford, H & Bode, L 2012, 'The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats', Gut, vol. 61, no. 10, pp. 1417-1425. https://doi.org/10.1136/gutjnl-2011-301404
Jantscher-Krenn E, Zherebtsov M, Nissan C, Goth K, Guner YS, Naidu N et al. The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut. 2012 Oct 1;61(10):1417-1425. https://doi.org/10.1136/gutjnl-2011-301404
Jantscher-Krenn, Evelyn ; Zherebtsov, Monica ; Nissan, Caroline ; Goth, Kerstin ; Guner, Yigit S. ; Naidu, Natasha ; Choudhury, Biswa ; Grishin, Anatoly V. ; Ford, Henri ; Bode, Lars. / The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. In: Gut. 2012 ; Vol. 61, No. 10. pp. 1417-1425.
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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. Conclusion: 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.",
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AU - Goth, Kerstin

AU - Guner, Yigit S.

AU - Naidu, Natasha

AU - Choudhury, Biswa

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AU - Ford, Henri

AU - Bode, Lars

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N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

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