Sawhney Sanjam S, Thänert Robert, Thänert Anna, Hall-Moore Carla, Ndao I Malick, Mahmud Bejan, Warner Barbara B, Tarr Phillip I, Dantas Gautam
Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Nat Med. 2025 Apr 2. doi: 10.1038/s41591-025-03610-0.
The human gut microbiome is most dynamic in early life. Although sweeping changes in taxonomic architecture are well described, it remains unknown how, and to what extent, individual strains colonize and persist and how selective pressures define their genomic architecture. In this study, we combined shotgun sequencing of 1,203 stool samples from 26 mothers and their twins (52 infants), sampled from childbirth to 8 years after birth, with culture-enhanced, deep short-read and long-read stool sequencing from a subset of 10 twins (20 infants) to define transmission, persistence and evolutionary trajectories of gut species from infancy to middle childhood. We constructed 3,995 strain-resolved metagenome-assembled genomes across 399 taxa, and we found that 27.4% persist within individuals. We identified 726 strains shared within families, with Bacteroidales, Oscillospiraceae and Lachnospiraceae, but not Bifidobacteriaceae, vertically transferred. Lastly, we identified weaning as a critical inflection point that accelerates bacterial mutation rates and separates functional profiles of genes accruing mutations.
人类肠道微生物群在生命早期最为活跃。尽管分类结构的巨大变化已有详细描述,但个体菌株如何以及在多大程度上定殖和持续存在,以及选择压力如何定义其基因组结构,仍是未知的。在本研究中,我们将对26位母亲及其双胞胎(52名婴儿)从分娩到出生后8年采集的1203份粪便样本进行鸟枪法测序,与从10对双胞胎(20名婴儿)子集中进行的培养增强、深度短读长和长读长粪便测序相结合,以确定肠道物种从婴儿期到童年中期的传播、持续存在和进化轨迹。我们构建了跨越399个分类单元的3995个菌株解析的宏基因组组装基因组,发现27.4%的菌株在个体内持续存在。我们鉴定出726个在家族内共享的菌株,其中拟杆菌目、颤螺菌科和毛螺菌科(而非双歧杆菌科)是垂直传递的。最后,我们确定断奶是一个关键转折点,它加速了细菌突变率,并分离出积累突变的基因的功能谱。