Table_2_Very Preterm Children Gut Microbiota Comparison at the Neonatal Period of 1 Month and 3.5 Years of Life.XLSX

Prematurity is a risk factor for dysbiosis of the gut microbiota due to particular birth conditions and frequent prolonged hospitalization of neonates. Although gut microbiota colonization after birth and its establishment during the hospitalization period have been studied in preterm infants, data on gut microbiota following discharge, particularly during early childhood, are scarce. The present study investigated the relationship between gut microbiota at 1 month after birth (hospitalization period) and 3.5 years of age in 159 preterm children belonging to the French EPIFLORE prospective observational cohort study. Analysis using bacterial 16S rRNA gene sequencing showed that the gut microbiota of preterm neonates at 1 month was highly variable and characterized by six distinct enterotypes. In contrast, the gut microbiota of the same children at 3.5 years of age showed less variability, with only two discrete enterotypes. An absence of association between enterotypes at 1 month and 3.5 years of age was observed. While the alpha diversity of gut microbiota significantly increased between 1 month and 3.5 years of age, for both alpha and beta diversities, there was no correlation between the 1-month and 3.5-years time points. Comparison at 3.5 years between children born either preterm (n = 159) or full-term (n = 200) showed no differences in terms of enterotypes, but preterm children harbored a lower Shannon diversity index and a different overall composition of microbiota than full-term children. This study suggests that the characteristics of the early gut microbiota of preterm children are not predictive of the microbial community composition at 3.5 years of age. However, the impact of gestational age is still noticeable on the gut microbiota up to 3.5 years of age.

早产是引发新生儿肠道微生物群（gut microbiota）失调的危险因素，这与特殊的分娩状况以及新生儿常需长期住院密切相关。尽管学界已针对早产婴儿出生后的肠道微生物群定植及其住院期间的菌群构建展开研究，但关于患儿出院后尤其是幼儿时期的肠道微生物群相关数据仍较为匮乏。
本研究依托法国EPIFLORE前瞻性观察队列研究，纳入159名早产儿童，分析其出生后1个月（住院阶段）与3.5岁时的肠道微生物群之间的关联。通过细菌16S核糖体RNA（16S rRNA）基因测序分析发现，早产新生儿在出生后1个月时的肠道微生物群具有高度异质性，且存在6种不同的肠型（enterotypes）。与之形成对比的是，同一批儿童在3.5岁时的肠道微生物群异质性更低，仅存在2种离散肠型。研究未观察到患儿1月龄与3.5岁时的肠型之间存在关联。尽管肠道微生物群的α多样性（alpha diversity）在出生后1个月至3.5岁间显著提升，但无论是α多样性还是β多样性（beta diversity），1月龄与3.5岁两个时间点之间均无相关性。
在3.5岁时对159名早产儿童与200名足月儿童进行对比分析发现，两组的肠型并无差异，但早产儿童的香农多样性指数（Shannon diversity index）更低，且肠道微生物群整体组成与足月儿童存在差异。本研究表明，早产儿童早期肠道微生物群的特征无法预测其3.5岁时的微生物群落组成。不过，胎龄对肠道微生物群的影响在儿童成长至3.5岁时仍较为显著。