Data_Sheet_7_Bacteroides abundance drives birth mode dependent infant gut microbiota developmental trajectories.DOCX

Background and aimsBirth mode and other early life factors affect a newborn's microbial colonization with potential long-term health effects. Individual variations in early life gut microbiota development, especially their effects on the functional repertoire of microbiota, are still poorly characterized. This study aims to provide new insights into the gut microbiome developmental trajectories during the first year of life.
MethodsOur study comprised 78 term infants sampled at 3 weeks, 3 months, 6 months, and 12 months (n = 280 total samples), and their mothers were sampled in late pregnancy (n = 50). Fecal DNA was subjected to shotgun metagenomic sequencing. Infant samples were studied for taxonomic and functional maturation, and maternal microbiota was used as a reference. Hierarchical clustering on taxonomic profiles was used to identify the main microbiota developmental trajectories in the infants, and their associations with perinatal and postnatal factors were assessed.
ResultsIn line with previous studies, infant microbiota composition showed increased alpha diversity and decreased beta diversity by age, converging toward an adult-like profile. However, we did not observe an increase in functional alpha diversity, which was stable and comparable with the mother samples throughout all the sampling points. Using a de novo clustering approach, two main infant microbiota clusters driven by Bacteroidaceae and Clostridiaceae emerged at each time point. The clusters were associated with birth mode and their functions differed mainly in terms of biosynthetic and carbohydrate degradation pathways, some of which consistently differed between the clusters for all the time points. The longitudinal analysis indicated three main microbiota developmental trajectories, with the majority of the infants retaining their characteristic cluster until 1 year. As many as 40% of vaginally delivered infants were grouped with infants delivered by C-section due to their clear and persistent depletion in Bacteroides. Intrapartum antibiotics, any perinatal or postnatal factors, maternal microbiota composition, or other maternal factors did not explain the depletion in Bacteroides in the subset of vaginally born infants.
ConclusionOur study provides an enhanced understanding of the compositional and functional early life gut microbiota trajectories, opening avenues for investigating elusive causes that influence non-typical microbiota development.

背景与研究目的：分娩方式及其他早期生命因素会影响新生儿的微生物定植，并可能带来长期健康影响。目前，人们对早期生命肠道微生物群（gut microbiota）发育的个体差异，尤其是其对微生物群功能组成的影响，仍知之甚少。本研究旨在为生命第一年的肠道微生物组（gut microbiome）发育轨迹提供新的见解。
方法：本研究纳入78名足月婴儿，分别在其出生后3周、3个月、6个月及12个月采集样本，总计获取280份样本；同时在妊娠晚期采集其母亲的样本，共50份。对粪便DNA进行鸟枪法宏基因组测序（shotgun metagenomic sequencing）。针对婴儿样本开展分类学与功能成熟度研究，并以母体微生物群作为参照。通过对分类学特征进行层次聚类（hierarchical clustering），识别婴儿肠道微生物群的主要发育轨迹，并评估其与围产期及产后因素的关联。
结果：与既往研究一致，婴儿肠道微生物群的组成随年龄增长呈现α多样性（alpha diversity）升高、β多样性（beta diversity）降低的趋势，逐渐趋近于成人样特征。但本研究未观察到功能α多样性（alpha diversity）的升高，其在所有采样时间点均保持稳定，且与母亲样本的功能α多样性水平相当。通过从头聚类（de novo clustering）方法，在每个采样时间点均鉴定出两类主要的婴儿肠道微生物群簇，分别由拟杆菌科（Bacteroidaceae）和梭菌科（Clostridiaceae）主导。这两类簇与分娩方式相关，其功能差异主要体现在生物合成及碳水化合物降解通路中，部分通路在所有时间点的簇间均存在持续差异。纵向分析表明，婴儿肠道微生物群存在三类主要发育轨迹，大多数婴儿在1岁前均保持其特征性的微生物群簇。多达40%的阴道分娩婴儿因拟杆菌属（Bacteroides）显著且持续的耗竭，被划分至剖宫产分娩婴儿的微生物群簇中。产时抗生素使用、各类围产期或产后因素、母体微生物群组成及其他母体因素，均无法解释该部分阴道分娩婴儿体内拟杆菌属的耗竭现象。
结论：本研究加深了我们对早期生命肠道微生物群组成与功能发育轨迹的理解，为探究影响非典型微生物群发育的潜在隐匿性病因提供了研究方向。