University of California-San Diego, Department of Pediatrics, Division of Neonatal Medicine, 200 West Arbor Drive, MC 8450, San Diego, CA 92103-8450, USA.
Gut. 2012 Oct;61(10):1417-25. doi: 10.1136/gutjnl-2011-301404. Epub 2011 Dec 3.
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.
To test the hypothesis that human milk oligosaccharides (HMO) contribute to the protection from NEC.
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.
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.
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.
坏死性小肠结肠炎（NEC）是早产儿最常见和最致命的肠道疾病之一。母乳喂养的婴儿患 NEC 的风险低于配方奶喂养的婴儿，但母乳中的保护成分尚未确定。与配方奶相比，人乳含有大量复杂的聚糖。
检验人乳低聚糖（HMO）有助于预防 NEC 的假设。
由于 HMO 的可用性有限，人体干预研究不可行，因此使用了新生大鼠 NEC 模型。通过口服灌胃给予配方奶而不给予和给予 HMO，并使幼鼠暴露于缺氧发作中。盲法对回肠切片进行 NEC 体征评分。二维色谱法用于确定最有效的 HMO，顺序外切糖苷酶消化和连接分析用于确定其结构。
与单独的配方奶相比，混合 HMO 可将 96 小时存活率从 73.1%显著提高至 95.0%，并将病理评分从 1.98±1.11 降低至 0.44±0.30（p<0.001）。在混合 HMO 中，鉴定出二唾液酸乳糖-N-四糖（DSLNT）的特定异构体具有保护作用。半乳糖低聚糖，目前添加到配方奶中以模拟 HMO 的某些作用，没有效果。
HMO 可减少新生大鼠的 NEC，且效果具有高度的结构特异性。如果这些结果转化为人类的 NEC，则 DSLNT 可用于预防或治疗配方奶喂养婴儿的 NEC，并且其在母乳中的浓度可作为识别有发生这种疾病风险的母乳喂养婴儿的生物标志物。
