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Nature. 2018 Oct;562(7728):583-588. doi: 10.1038/s41586-018-0617-x. Epub 2018 Oct 24.

Temporal development of the gut microbiome in early childhood from the TEDDY study.

Author information

1
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. christopher.stewart@ncl.ac.uk.
2
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. christopher.stewart@ncl.ac.uk.
3
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
5
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
6
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
7
Pacific Northwest Research Institute, Seattle, WA, USA.
8
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.
9
Department of Pediatrics, Turku University Hospital, Turku, Finland.
10
Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany.
11
Forschergruppe Diabetes, Technische Universität München, Klinikum Rechts der Isar, Munich, Germany.
12
Forschergruppe Diabetes e.V. at Helmholtz Zentrum München, Munich, Germany.
13
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
14
National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, USA.
15
Department of Clinical Sciences, Lund University/CRC, Skane University Hospital, Malmö, Sweden.
16
Department of Virology, Faculty of Medicine and Biosciences, University of Tampere, Tampere, Finland.
17
Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
18
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
19
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. jpetrosi@bcm.edu.

Abstract

The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1-9 such as persistent islet autoimmunity and type 1 diabetes10-12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3-14), a transitional phase (months 15-30), and a stable phase (months 31-46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case-control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial-immune crosstalk for long-term health.

PMID:
30356187
PMCID:
PMC6415775
DOI:
10.1038/s41586-018-0617-x
[Indexed for MEDLINE]
Free PMC Article

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