Abstract: Objective To analyze the characteristics of structural changes of intestinal flora in infants with neonatal respiratory distress syndrome (NRDS), in order to provide theoretical basis for the clinical application of probiotics for NRDS assisted therapy. Methods A total of 15 premature infants with NRDS who were hospitalized in the Neonatology Department of Jinan Central Hospital from January to May 2020 were selected into the NRDS group in this study. Meanwhile, 15 non-NRDS hospitalized premature infants were selected as the control group.The clinical data, blood sample, stool sample of the participants were collected. The stool DNA was extracted, high-throughput 16S rRNA gene sequencing was conducted, and bioinformatics analysis was conducted to compare the differences of intestinal flora between the two groups. Results 1) Compared with the control group, the OTU number of intestinal flora in the NRDS group was lower in each level of bacteria classification, including species, genus, family, order, class and phylum.2) The β diversity analysis showed that there were significant differences in intestinal flora structure between NRDS group and control group. 3) At the level of "family", Enterobacteriaceae was enriched in the NRDS group (Z=2.78, P=0.009). At the level of "phylum", Firmicutes were enriched in the control group (Z=2.18, P=0.021) and Proteobacteria were enriched in the NRDS group (Z=2.02,P=0.014). Conclusions The ecological imbalance of intestinal flora is found in NRDS infants, and the richness and diversity of flora species are decreasing. The structural distribution of intestinal flora in infants with NRDS is significantly different from that of normal preterm infants.

Key words: neonatal respiratory distress syndrome, gut microbiota, short-chain fatty acids, 16S ribosomal RNA

摘要： 目的 分析新生儿呼吸窘迫综合征(NRDS)患儿肠道菌群结构变化的特征,为临床应用益生菌进行NRDS辅助治疗提供理论基础。方法 选择2020年1—5月因NRDS在济南市中心医院新生儿科住院治疗的早产儿15例为NRDS组。同时选择在本科排除NRDS诊断的早产儿15例作为对照组。收集研究对象的临床资料、血浆标本和粪便标本,提取粪便 DNA,进行高通量16S rRNA基因测序,并进行生物信息学分析,比较两组间肠道菌群的差异。结果 1)与对照组相比,NRDS组肠道菌群在种、属、科、目、纲、门各水平细菌分类OTU数均较少;2)β多样性分析说明 NRDS组和对照组新生儿肠道菌群结构存在明显差异;3)“科”水平上,肠杆菌科在NRDS组富集(Z＝2.78,P=0.009);“门”水平上,厚壁菌门在对照组中富集(Z＝2.18,P=0.021)、变形菌门在NRDS组富集(Z＝2.02,P=0.014)。结论 NRDS患儿存在肠道菌群生态失衡,并且菌群物种的丰富度及多样性降低;NRDS患儿与正常早产儿肠道菌群结构分布存在明显差异。

关键词: 新生儿呼吸窘迫综合征, 肠道菌群, 短链脂肪酸, 16S rRNA测序