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

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。

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(r^(2)=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.