Daily supplementation with Lactobacillus reuteri DSM 17938 to extremely preterm infants modulated the gut microbiota during the first month of life in a randomised placebo-controlled trial

Extremely low birth weight (ELBW; <1000 g) preterm infants often develop severe clinical complications such as necrotising enterocolitis, sepsis and growth failure, which may be reduced by probiotic supplementation. The aim of this study was to investigate how the supplementation with Lactobacillus reuteri DSM 17938 affected the gut microbiota composition in ELBW infants. 134 ELBW infants born before post-menstrual week (PMW) 28 were enrolled in a randomised, double-blind, placebo-controlled trial, and supplemented with L. reuteri or placebo from birth to PMW36. Stool samples were collected weekly during the first month of life, at PMW36, and at two years of age. The bacterial composition in 558 stool samples was characterized by 16S amplicon sequencing. Our results show that the microbiota composition differed between the two groups during the first month of life, with higher bacterial richness and diversity in the probiotic group. At one week of age, the differences were mainly explained by higher relative abundance of Enterobacteriacea and Staphylococcacea in the placebo group, and higher relative abundance of L. reuteri in the probiotic group. From two weeks of age the differences were mainly explained by a higher relative abundance of L. reuteri in the probiotic group. At PMW36 and two years of life there were no differences in the gut microbiota composition. In conclusion, daily supplementation of L. reuteri in ELBW preterm infants modulated the gut microbiota composition, with increased bacterial diversity and high abundance of the supplemented strain during the first month of life in the probiotic group.

出生体重<1000g的极低出生体重（Extremely low birth weight, ELBW）早产儿常罹患坏死性小肠结肠炎、败血症及生长发育迟缓等严重临床并发症，而益生菌补充疗法可降低此类并发症的发生风险。本研究旨在探究罗伊氏乳杆菌（Lactobacillus reuteri）DSM 17938补充干预对极低出生体重早产儿肠道菌群组成的影响。本研究共纳入134名月经后周（post-menstrual week, PMW）<28周出生的极低出生体重早产儿，采用随机双盲安慰剂对照试验设计，自出生至校正胎龄36周（PMW36）期间，为受试者每日补充罗伊氏乳杆菌或安慰剂。粪便样本采集方案如下：出生后第一个月内每周采集1次，同时在PMW36及受试者2岁时分别采集样本。本研究采用16S扩增子测序（16S amplicon sequencing）技术，对共计558份粪便样本的细菌组成进行解析。结果显示，两组受试者在出生后第一个月的肠道菌群组成存在显著差异：益生菌组的细菌丰富度与多样性均显著更高。出生后1周时，两组差异主要体现为：安慰剂组的肠杆菌科（Enterobacteriaceae）、葡萄球菌科（Staphylococcaceae）相对丰度更高，而益生菌组的罗伊氏乳杆菌相对丰度更高；自出生后2周起，两组差异则主要源于益生菌组的罗伊氏乳杆菌相对丰度显著升高。在校正胎龄36周及2岁时，两组肠道菌群组成均无显著差异。综上，对极低出生体重早产儿每日补充罗伊氏乳杆菌可调节其肠道菌群组成：益生菌组在出生后第一个月的细菌多样性显著提升，且定植了高丰度的补充菌株。