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

被引:306
作者
Jantscher-Krenn, Evelyn [1 ,2 ]
Zherebtsov, Monica
Nissan, Caroline [1 ]
Goth, Kerstin [3 ]
Guner, Yigit S. [3 ]
Naidu, Natasha [4 ]
Choudhury, Biswa [4 ]
Grishin, Anatoly V. [3 ]
Ford, Henri R. [3 ]
Bode, Lars [1 ]
机构
[1] Univ Calif San Diego, Dept Pediat, Div Neonatal Med, Div Gastroenterol & Nutr, San Diego, CA 92103 USA
[2] Inst Pharmaceut Sci, Dept Pharmaceut Technol, Graz, Austria
[3] Childrens Hosp, Saban Res Inst, Los Angeles, CA 90027 USA
[4] Univ Calif San Diego, Glycotechnol Core, San Diego, CA 92103 USA
关键词
BIRTH-WEIGHT INFANTS; BREAST-MILK; ADHESION; OUTCOMES; EXPRESSION;
D O I
10.1136/gutjnl-2011-301404
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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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收藏
页码:1417 / 1425
页数:9
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