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. 2025 Jun;31(6):2004-2015.
doi: 10.1038/s41591-025-03610-0. Epub 2025 Apr 2.

Gut microbiome evolution from infancy to 8 years of age

Affiliations

Gut microbiome evolution from infancy to 8 years of age

Sanjam S Sawhney et al. Nat Med. 2025 Jun.

Abstract

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.

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Conflict of interest statement

Competing interests: P.I.T. is a holder of equity in, a consultant to and a member of the Scientific Advisory Board of MediBeacon, Inc., which is developing a technology to non-invasively measure intestinal permeability in humans. P.I.T. is a co-inventor on patents assigned to MediBeacon (US patents 11,285,223 and 11,285,224, titled ‘Compositions and methods for assessing gut function’, and US patent application 2022-0326255, titled ‘Methods of monitoring mucosal healing’), which might earn royalties if the technology is commercialized. P.I.T. receives compensation for his roles as Chair, Scientific Advisory Board of the AGA Center for Microbiome Research and Education, and consultant to Temple University on waterborne enteric infections. He is a member of the Data Safety Monitoring Board of Inmunova, which is developing an immune biologic targeting Shiga toxin–producing E. coli infections, for which he receives no compensation, except for reimbursement of expenses. P.I.T. receives royalties from UpToDate from two sections on intestinal E. coli infections. G.D. is a consultant to and a member of the Scientific Advisory Board of Pluton Biosciences, which is developing methods for discovering environmental microbes for commercial applications. G.D. has consulted for SNIPR Technologies, Ltd. in the last 5 years but not presently. S.S. has consulted for Hypha Life Sciences and BioGenerator Ventures in the last 5 years but not presently. The authors declare no other competing interests.

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