目的: 使用16S rDNA高通量测序技术检测全面性发育迟缓（global developmental delay,GDD）早产儿肠道菌群变化,探究肠道菌群与早产儿GDD发生的相关性。方法: 选取本院就诊胎龄32~36周初诊早产儿57例,其中23例GDD早产儿为实验组,34例无GDD的早产儿为对照组,均收集新鲜大便标本,使用16S rDN测序检测肠道菌群并进行生物信息学分析,比较分析两组早产儿肠道菌群的差异性。结果: 两组在肠道菌群的群落构成、物种丰度和代谢通路上均存在一定差异。在门水平上,广古菌门（Euryarchaeota）仅出现在实验组（0.023%,P<0.05）,经错误发现率（false discovery rate,FDR）校正后Q=0.42。线性判别分析效应大小（linear discriminant analysis effect size,LEfSe）软件分析则表明营发酵单胞菌属（Dysgonomonas）在GDD患者中表现出高丰度。实验组在MetaCyc模块、CAZY模块、GMM代谢模块和GBM神经递质模块的多个通路发生功能变化。结论: 与无GDD的早产儿相比,GDD早产儿存在肠道菌群失调,广古菌门、营发酵单胞菌属相对丰度可能增加,因此造成代谢通路和肠脑轴功能改变,但目前对于GDD早产儿肠道菌群的改变仍未有统一结论,仍需进一步深入研究。
Abstract
Objective To investigate changes in the gut microbiota of preterm infants with Global Developmental Delay (GDD) using 16S rDNA high-throughput sequencing technology and explore the correlation between gut microbiota and GDD in preterm infants. Methods A total of 57 preterm infants with a gestational age of 32-36 weeks were enrolled, including 23 GDD infants (experimental group) and 34 non-GDD infants (control group). Fresh stool specimens were collected from all participants.16S rDNA sequencing was performed to analyze gut microbiota composition, followed by bioinformatics analysis to compare differences between the two groups. Results Differences were observed in the community structure, species abundance, and metabolic pathways of gut microbiota between the two groups. At the phylum level, Euryarchaeota was exclusively detected in the experimental group (0.023%, P<0.05). After corrected by False Discovery Rate (FDR), Q value was 0.42. Linear Discriminant Analysis Effect Size (LEfSe) revealed a higher abundance of the genus Dysgonomonas in GDD infants. Functional changes were identified in multiple pathways within MetaCyc modules, CAZY modules, GMM metabolic modules, and GBM neurotransmitter modules in the experimental group. Conclusion Compared to non-GDD preterm infants, GDD preterm infants exhibit gut microbiota dysbiosis, characterized by increased relative abundances of Euryarchaeota and Dysgonomonas, which may contribute to altered metabolic pathways and gut-brain axis function. However, currently, the alterations in gut microbiota of GDD preterm infants remain inconclusive, warranting further in-depth research.
关键词
早产儿 /
肠道菌群 /
发育迟缓 /
16S rDNA测序
Key words
premature infants /
gut microbiota /
delayed development /
16S rDNA sequencing
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基金
湖南省自然科学青年基金项目“ERCC3截短突变促进乳腺癌发生发展的机制与靶向干预研究”（2025JJ60670）; 长沙自然科学基金项目“ERCC3基因突变通过调控TGF-β/SMAD信号通路参与乳腺癌发生发展的机制研究”（kq2403186）; 长沙市2022年度指导性科技计划项目“早产儿发育迟缓与肠道菌群关系的研究”（KZD22080）; 长沙市妇幼保健院院级科研项目“早产儿发育迟缓与肠道菌群关系的研究”（202205）
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