4.5 Article

Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life

期刊

NATURE MICROBIOLOGY
卷 4, 期 3, 页码 470-479

出版社

NATURE RESEARCH
DOI: 10.1038/s41564-018-0321-5

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资金

  1. Juvenile Diabetes Research Foundation (JDRF)
  2. German Research Foundation [315980449]
  3. JDRF [3-SRA-2016-141-Q-R, 2-SRA-2016-247-S-B, 2-SRA-2018-548-S-B]
  4. National Institutes of Health [R24DK110499, DK43351, AI110498]
  5. European Union [202063]
  6. Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research [250114]
  7. Center for Microbiome Informatics and Therapeutics

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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.

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