Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants
Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants
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DOI：
10.1136/gutjnl-2016-312819
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发表时间：
2018-06-01
期刊：
影响因子：
24.5
通讯作者：
Bode, Lars
中科院分区：
文献类型：
--
作者：
Autran, Chloe A.;Kellman, Benjamin P.;Bode, Lars
目的坏死性小肠结肠炎（NEC）是早产儿最常见、最致命的肠道疾病之一。识别高危婴儿的标志物以及预防和治疗NEC的疗法是有限的，迫切需要的。与配方奶喂养的婴儿相比，母乳喂养的婴儿NEC发生率明显较低。婴儿配方奶粉缺乏人乳低聚糖（HMO），如二唾液酸乳糖-N-四糖（DSLNT），可预防新生大鼠的NEC。然而，它是未知的，如果DSLNT也保护人类早产儿。设计我们进行了多中心的临床队列研究，并招募了200名母亲和他们的极低出生体重的婴儿，主要是母乳喂养。我们分析了HMO组成母乳喂养的婴儿产后28天内，匹配每个NEC的情况下，5个控制和使用Logistic回归和广义估计方程来检验这一假设，即婴儿谁开发NEC接收牛奶的DSLNT比婴儿谁不开发NEC.Results八个婴儿在队列开发NEC（贝尔阶段2或3）。与对照组相比，NEC病例中几乎所有乳汁样本中的DSLNT浓度均显著降低，其丰度可以在发病前识别NEC病例。综合评估的DSLNT在多天增强分离NEC病例和对照subjects.Conclusions母乳中的DSLNT含量是一个潜在的非侵入性标志物，以确定婴儿在发展NEC的风险，并筛选高风险的供体奶。此外，DSLNT可以作为天然模板来开发针对这种破坏性疾病的新疗法。
Objective Necrotising enterocolitis (NEC) is one of the most common and often fatal intestinal disorders in preterm infants. Markers to identify at-risk infants as well as therapies to prevent and treat NEC are limited and urgently needed. NEC incidence is significantly lower in breast-fed compared with formula-fed infants. Infant formula lacks human milk oligosaccharides (HMO), such as disialyllacto-N-tetraose (DSLNT), which prevents NEC in neonatal rats. However, it is unknown if DSLNT also protects human preterm infants.Design We conducted a multicentre clinical cohort study and recruited 200 mothers and their very low birthweight infants that were predominantly human milk-fed. We analysed HMO composition in breast milk fed to infants over the first 28 days post partum, matched each NEC case with five controls and used logistic regression and generalised estimating equation to test the hypothesis that infants who develop NEC receive milk with less DSLNT than infants who do not develop NEC.Results Eight infants in the cohort developed NEC (Bell stage 2 or 3). DSLNT concentrations were significantly lower in almost all milk samples in NEC cases compared with controls, and its abundance could identify NEC cases prior to onset. Aggregate assessment of DSLNT over multiple days enhanced the separation of NEC cases and control subjects.Conclusions DSLNT content in breast milk is a potential non-invasive marker to identify infants at risk of developing NEC, and screen high-risk donor milk. In addition, DSLNT could serve as a natural template to develop novel therapeutics against this devastating disorder.