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

Research output: Contribution to journalLetter

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.

Details

Authors
  • Christopher J. Stewart
  • Nadim J. Ajami
  • Jacqueline L. O’Brien
  • Diane S. Hutchinson
  • Daniel P. Smith
  • Matthew C. Wong
  • Matthew C. Ross
  • Richard E. Lloyd
  • Harsha Vardhan Doddapaneni
  • Ginger A. Metcalf
  • Donna Muzny
  • Richard A. Gibbs
  • Tommi Vatanen
  • Curtis Huttenhower
  • Ramnik J. Xavier
  • Marian Rewers
  • William Hagopian
  • Jorma Toppari
  • Anette G. Ziegler
  • Jin Xiong She
  • Beena Akolkar
  • Heikki Hyoty
  • Kendra Vehik
  • Jeffrey P. Krischer
  • Joseph F. Petrosino
Organisations
External organisations
  • Baylor College of Medicine
  • University of Newcastle upon Tyne
  • Broad Institute
  • University of Colorado
  • Pacific Northwest Diabetes Research Institute
  • University of Turku
  • Turku University Hospital
  • Helmholtz Zentrum München
  • Klinikum rechts der Isar
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • University of Tampere
  • Pirkanmaa Hospital District
  • University of South Florida
  • Technical University of Munich
  • Augusta University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)583-588
Number of pages6
JournalNature
Volume562
Issue number7728
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes