早产儿坏死性小肠结肠炎发病前肠道菌群失调：系统评价和荟萃分析。

BACKGROUND: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. METHODS AND RESULTS: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using culture-independent molecular techniques and reported α and β-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). CONCLUSIONS: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.

背景：坏死性小肠结肠炎（NEC）是早产儿的一种灾难性疾病，微生物失调与该病的发病机制有关。评估 NEC 和早产儿微生物组的研究缺乏效力，并且报告的结果不一致。

方法和结果：我们的目的是对早产儿粪便微生物组谱进行系统评价和荟萃分析，以辨别和描述 NEC 发病前的微生物失调，并探索研究之间的异质性。我们于 2016 年 4 月检索了 MEDLINE、PubMed、CINAHL 和儿科学会会议摘要以及相关确定文章的参考文献列表。研究比较了发生 NEC 的早产儿和对照组的肠道微生物组，使用了非培养的分子技术，并报告了α和β多样性指标以及微生物谱。此外，还要求纳入研究的作者提供或在公共数据存储库中搜索 16S 核糖体核糖核酸（rRNA）序列数据和临床元数据。我们通过统一分析流程重新处理了 16S rRNA 序列数据，然后通过荟萃分析进行综合分析。我们共纳入了 14 项研究，其中 8 项研究的数据可进行定量综合分析（NEC 病例 106 例，对照组 278 例，样本 2944 例）。NEC 发病的平均（±标准差）胎龄为妊娠后 30.1±2.4 周（n=61）。与 NEC 发病前相比，NEC 早产儿粪便微生物组中的变形菌相对丰度增加，厚壁菌门和拟杆菌门的相对丰度降低。NEC 早产儿的α或β多样性指数与对照组无明显差异，但我们发现与抗生素暴露、配方奶喂养和分娩方式有关的分类群谱存在差异。探索异质性发现，研究和 16S rRNA 基因（V1-V3 或 V3-V5）目标区域的微生物谱存在差异。

结论：NEC 早产儿发病前的微生物失调表现为变形菌的相对丰度增加，厚壁菌门和拟杆菌门的相对丰度降低。微生物组优化可能为预防 NEC 提供一种新策略。