Table_1_Differences in Compositions of Gut Bacterial Populations and Bacteriophages in 5–11 Year-Olds Born Preterm Compared to Full Term.DOCX

Preterm infants are exposed to major perinatal, post-natal, and early infancy events that could impact on the gut microbiome. These events include infection, steroid and antibiotic exposure, parenteral nutrition, necrotizing enterocolitis, and stress. Studies have shown that there are differences in the gut microbiome during the early months of life in preterm infants. We hypothesized that differences in the gut microbial composition and metabolites in children born very preterm persist into mid-childhood. Participants were healthy prepubertal children aged 5–11 years who were born very preterm (≤32 weeks of gestation; n = 51) or at term (37–41 weeks; n = 50). We recorded the gestational age, birth weight, mode of feeding, mode of birth, age, sex, and the current height and weight of our cohort. We performed a multi'omics [i.e., 16S rRNA amplicon and shotgun metagenomic sequencing, SPME-GCMS (solid-phase microextraction followed by gas chromatography-mass spectrometry)] analysis to investigate the structure and function of the fecal microbiome (as a proxy of the gut microbiota) in our cross-sectional cohort. Children born very preterm were younger (7.8 vs. 8.3 years; p = 0.034), shorter [height-standard deviation score (SDS) 0.31 vs. 0.92; p = 0.0006) and leaner [BMI (body mass index) SDS −0.20 vs. 0.29; p < 0.0001] than the term group. Children born very preterm had higher fecal calprotectin levels, decreased fecal phage richness, lower plasma arginine, lower fecal branched-chain amino acids and higher fecal volatile (i.e., 3-methyl-butanoic acid, butyrolactone, butanoic acid and pentanoic acid) profiles. The bacterial microbiomes did not differ between preterm and term groups. We speculate that the observed very preterm-specific changes were established in early infancy and may impact on the capacity of the very preterm children to respond to environmental changes.

早产儿在围产期、产后早期及婴儿期暴露于可能影响肠道微生态群的一系列重大事件，这些事件包括感染、类固醇和抗生素暴露、肠外营养、坏死性小肠结肠炎和压力等。研究表明，早产儿在出生后早期数月的肠道微生态群存在差异。我们假设，在极早产儿中，肠道微生物组成和代谢物的差异在中童时期依然持续。参与者为5至11岁健康的青春前期儿童，其中极早产儿（孕周≤32周；n = 51）或足月儿（孕周37–41周；n = 50）。我们记录了孕周、出生体重、喂养方式、分娩方式、年龄、性别以及队列成员的当前身高和体重。我们对粪便微生物群（作为肠道微生态群的指标）的结构和功能进行了多组学分析[即16S rRNA 扩增子和宏基因组测序，SPME-GCMS（固相微萃取后气相色谱-质谱联用）]。极早产儿在年龄（7.8岁 vs. 8.3岁；p = 0.034）、身高[身高标准差分数（SDS）0.31 vs. 0.92；p = 0.0006]和体重[体重指数（BMI）SDS -0.20 vs. 0.29；p < 0.0001]方面均不如足月儿组。极早产儿的粪便钙卫蛋白水平较高，粪便噬菌体多样性降低，血浆精氨酸水平降低，粪便支链氨基酸含量降低，粪便挥发性物质（例如，3-甲基丁酸、丁内酯、丁酸和戊酸）谱增加。早产儿组和足月儿组的细菌微生物群没有差异。我们推测，观察到的极早产儿特有的变化是在婴儿早期确立的，并可能影响极早产儿对环境变化的响应能力。