Weaning accelerates and transforms within-host adaptation in the infant gut microbiome

The human gut microbiome undergoes sweeping taxonomic changes in the first years of life. While changes in taxonomic architecture during this time are well described, it remains unknown how and to what extent individual strains colonize and persist, and how selective pressures define their genomic architecture. Here, we augment culture-enhanced metagenomics with deep short-and long-read sequencing of stools from densely-sampled twin pairs and their mothers from birth to 8 years of life, to define transmission, persistence, and evolutionary trajectories of gut species from infancy to middle childhood. We construct 3,995 strain-resolved metagenome-assembled genomes across 399 bacterial taxa, and find that 27.4% of these Reconstructed Genomes persist within individuals. We identify 726 strains shared between twin pairs, mother-infant dyads, or family triads, with Bacteroidales, Oscillospiraceae, and Lachnospiraceae, but not Bifidobacteriaceae, vertically transferred. Lastly, we identify weaning as a critical inflection point that accelerates bacterial mutation rates and separates functional profiles of genes accruing mutations.

人类肠道微生物组在生命最初数年中会经历广泛的分类学层面变化。尽管此阶段分类学结构的改变已有充分描述，但个体菌株如何定殖、持续存在，以及选择压力如何塑造其基因组结构，目前仍不明晰。为此，我们对从出生至8岁期间密集采样的双生子对及其母亲的粪便样本，结合培养增强型宏基因组学（culture-enhanced metagenomics）与深度短读长、长读长测序技术，以此阐明肠道菌种从婴儿期至童年中期的传播、持续存在与演化轨迹。我们构建了覆盖399个细菌类群的3995个菌株解析型宏基因组组装基因组（strain-resolved metagenome-assembled genomes），并发现其中27.4%的组装基因组可在个体体内持续存在。我们鉴定出726个共享于双生子对、母婴对或家庭三人组的菌株，其中拟杆菌目（Bacteroidales）、颤螺菌科（Oscillospiraceae）与毛螺菌科（Lachnospiraceae）可经垂直传播，而双歧杆菌科（Bifidobacteriaceae）则无此现象。此外，我们鉴定出断奶是一个关键转折点，其会加速细菌突变率，并区分出发生突变的基因的功能特征。