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

The human gut microbiome is most dynamic in early life. While 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. Here, we combine shotgun sequencing of 1,203 stools from 26 densely-sampled twins (52 infants) and their mothers from childbirth to 8 years post-birth, with culture-enhanced, deep short-read, and long-read sequencing of stools from a subset of 10 twins (20 infants), 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 taxa, and find that 27.4% persist within individuals. We identify 726 strains shared within families, 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.