Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Computer Science, Aalto University, Espoo, Finland.
Nat Microbiol. 2019 Mar;4(3):470-479. doi: 10.1038/s41564-018-0321-5. Epub 2018 Dec 17.
The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.
人类肠道微生物组在生命的最初几年向成人组成成熟,并与早期免疫发育有关。在这里,我们使用在芬兰、爱沙尼亚和俄罗斯卡累利阿进行的 DIABIMMUNE 研究中收集的综合幼儿数据集,研究微生物基因组多样性对肠道微生物组发育的影响。我们表明,肠道微生物多样性与家庭位置和儿童的线性生长有关。基于单核苷酸多态性和宏基因组组装的菌株追踪显示出大量且高度动态的微生物泛基因组,特别是在拟杆菌属中,我们发现了源自针对拟杆菌的噬菌体的可变性的证据。我们的分析揭示了菌株多样性的功能后果;只有 10%的芬兰婴儿携带长双歧杆菌亚种。婴儿,一种专门用于人乳代谢的亚种,而俄罗斯婴儿在婴儿期通常保持益生菌双歧杆菌菌株。有助于多样化、特征代谢途径的细菌群在生命的头两年汇聚成高度个体特异性的结构。这项纵向研究扩展了基于菌株水平基因组变异的早期肠道微生物群落组装的现有观点。