早产儿益生低聚糖补充

Prebiotic Oligosaccharides in Premature Infants 

Hepatology and Nutrition (2014) 

DOI: 10.1097/MPG.0000000000000211 

Abstract

Objective: The aim of the study was to determine the impact of increasing doses of 2 prebiotic oligosaccharides and of an ‘‘all-human diet’’ on the intestinal microbiota of premature infants. 

Methods: Twelve premature infants receiving formula feedings were randomly assigned to receive either galacto-oligosaccharide (FtGOS) or a pooled concentrated donor human milk product containing human milk oligosaccharides (FtHMO) in increasing doses during a 5-week period. A second group of 15 premature infants received their mother’s own milk fortified with either a concentrated donor human milk product (HtH) or a bovine powdered fortifier (HtB). Serial stool specimens from each infant were analyzed by terminal restriction fragment length polymorphism and quantitative polymerase chain reaction for bacterial composition. 

Results: All of the infants studied had relatively low levels of bifidobacteria and no measurable Lactobacilli. Infants from the FtGOS and FtHMO groups demonstrated an increase in relative numbers of Clostridia with increasing doses. Compared with the HtB group, the infants in the FtHMO and the HtH groups showed an unexpected trend toward an increase in Proteobacteria over time/dose. Principal coordinate analyses and Shannon diversity scores were not significantly different among the 4 groups. Infants in the HtH group received more antibiotics during the study period than those in the other groups. Two of the infants receiving GOS developed feeding intolerance. 

Conclusions: None of the prebiotic interventions resulted in significant increases in bifidobacteriacompared with baseline specimens or the HtB group; however, many of the infants did not receive the highest doses of GOS and HMO, and antibiotic use in the HtH group was high.

坏死性小肠结肠炎（NEC）是早产儿常见疾病之一，其病因尚不完全清楚。与早产程度、肠道微生物群的改变、母亲因素（如吸烟）和遗传因素等有关。

迄今为止，预防NEC最有效的干预措施包括母乳、供者母乳和益生菌。用奶粉或液态牛乳制品强化母乳或供者母乳是常见的。“全人类饮食”（all human diet），用巴氏杀菌浓缩母乳产品强化的母乳，已被证明可以降低NEC的发生率。

不同于含有活生物体的益生菌，益生元是促进有益微生物生长的不可消化的食物成分，母乳低聚糖（HMO）是典型的益生元，具有几十种复杂的结构，只能被特定种类的细菌消化。

本研究即分析了增加剂量的2种益生寡糖和“全人类饮食”对早产儿肠道微生物群的影响。

研究对象：早产儿；在加州大学戴维斯分校萨克拉门托市儿童医院生儿重症监护病房进行。

入组条件：2009年6月开始至2011年6月结束；由该大学的机构审查委员会批准；纳入标准为出生体重<1500 g，胎龄<33周；排除标准为先天性胃肠道异常和配方奶粉和母乳组成的饮食；参与研究之前，所有婴儿的父母都已签署知情同意书。

实验设计：第一组为配方奶粉喂养，12名早产儿被随机分配在5周内接受低聚半乳糖（F+GOS）或含有母乳低聚糖（F+HMO）的混合浓缩供者母乳产品；第二组为母乳喂养，15名早产儿接受母亲母乳，母乳中添加了浓缩供体母乳产品（H+H）或牛奶粉强化剂（H+B）。

检测方法：末端限制性片段长度多态性（Terminal-restriction fragment length polymorphism，T-RFLP）；qPCR.

研究结论：

• 所有早产婴儿的双歧杆菌水平相对较低，没有检测到乳酸杆菌；

• F+GOS和F+HMO组婴儿的梭状芽孢杆菌相对数量随着剂量的增加而增加；

• 与H+B组相比，F+HMO组和H+H组的婴儿随时间/剂量的增加，G-变形杆菌的增加趋势明显；

• 4组的主坐标分析和香农多样性评分无显著差异；

• H+H组的婴儿在研究期间接受的抗生素比其他组多；

• 接受GOS的两名婴儿出现喂养不耐受；

• 与基线标本或H+B组相比，益生元干预均未导致双歧杆菌显著增加；

• “全人类饮食”也没有增加粪便中的双歧杆菌。

FIGURE 2. Universal Bacteria 16S-terminal restriction fragment length polymorphism analysis. Each color represents the mean percentage of the noted bacterial class present in the specimen by group with x-axis representing time/dose for the formula-fed infants and time for the human milk–fed infants. B1⁄4baseline specimen; GOS1⁄4galacto-oligosaccharide; HMO1⁄4human milk oligosaccharide.

图2. 通用细菌16S-TRFLP分析。每种颜色代表一组样本中所示细菌种类的平均百分比，X轴代表配方奶粉喂养婴儿的时间/剂量和母乳喂养婴儿的时间。B：基线样品；GOS：低聚乳糖；HMO：母乳低聚糖。

知几未来研究院正在搭建一个“疾病-肠道菌群”知识库。

你可以在公众号菜单栏“学术工具“版块直接查阅疾病和肠道菌群的相关信息；

也可以在公众号对话框回复疾病名称，如“IBD”或“肠易激综合征”，查看与疾病相关的菌群；

或回复菌种名称，如“双歧杆菌”或“Hp”，查看与细菌相关的疾病。

👇👇👇点击阅读原文，了解更多人体微生态研究。