极低/超低出生体重儿出生后 28 天内肠道菌群与临床指标的关联性分析

An association between gut microbiota and clinical parameters in very/extremely low birth weight infants during the first 28 days of life

关键词:  肠道菌群  极低/超低出生体重儿  16S rRNA  全肠道喂养  LC-MS/MS

Key words:  gut microbiota  very/extremely low birth weight infants  16S rRNA sequencing  full enteral feeding  LC-MS/MS

摘要:

目的　了解出生后 28 d内极低/超低出生体重儿肠道菌群与临床指标之间相关性。方法　选取出生胎龄 ＜32 周且出生身体质量＜1.5 kg早产儿，收集其胎粪（D1）、出生后 14 d（D14）和 28 d（D28）时粪便样本，进行 16S rRNA 基因测序及液相色谱串联质谱（LC-MS/MS）分析。采用Spearman分析肠道菌群及代谢物与临床指标相关性。结果　达 到全肠道喂养时间对肠道菌群结构影响最大（r 2 =0.105，P=0.001）；达到全肠道喂养时间与葡萄球菌属、杜氏牙形石属、 乳酸菌属、粪杆菌属、约氏不动杆菌、啮齿粪杆菌呈正相关，而与副腐化梭状芽胞杆菌、丁酸梭菌呈负相关（P<0.05）。胎 龄、剖宫产与D1 肠道菌群呈正相关，正压通气时间、抗生素使用时间及达到全肠道喂养时间与D14 及D28 肠道菌群呈正 相关（P<0.01）。12-羟基十八烷酸、琥珀酸、5-氨基戊酸、十二烷基苯磺酸与达到全肠道喂养时间呈负相关（P<0.05）。结 论　肠道菌群及代谢物与临床指标之间存在明显关联，达到全肠道喂养时间对极低/超低出生体重儿早期肠道菌群的影 响最大。

Abstract:

Objective To investigate the association between gut microbiota and clinical indicators in very/extremely low birth weight (V/ELBW) infants within the first 28 days of life. Methods Preterm infants with<32 weeks’gestational age and<1.5 kg birth weight were recruited. Their stool samples were collected on days 1, 14 and 28, and then subjected to 16S rRNA sequencing and LC-MS/MS analysis. The relationship between gut microbiota and metabolites and clinical factors was investigated by Spearman correlation analysis. Results The time to full enteral feeding had the greatest influence on the gut microbiota (r2=0.105, P=0.001). The time to full enteral feeding was positively correlated with Staphylococcus, Dubosiella, Lactobacillus, Faecalibacterium, Acinetobacter johnsonii, Faecalibaculum rodentium, and negatively with Clostridium paraputrificum and Clostridium butyricum (P<0.05). Gut microbiota was positively associated with gestational age and cesarean section on D1, and negatively with positive pressure ventilation time, antibiotic course, and time to full enteral feeding on D14 and D28 (P<0.01). 12-hydroxyoctadecanoic acid, succinic acid, 5-aminopentanoic acid and dodecylbenzene sulfonic acid were negatively correlated with the time to full enteral feeding (P<0.05). Conclusion There is a significant correlation between gut microbiota and metabolites, and clinical indicators. The time to full enteral feeding has the greatest impact on early-stage gut microbiota of V/ELBW infants.