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

  • 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
  • Ake Lernmark
  • Heikki Hyoty
  • Kendra Vehik
  • Jeffrey P. Krischer
  • Joseph F. Petrosino
Publishing year: 2018
Language: English
Pages: 583-588
Publication/Series: Nature
Volume: 562
Issue: 7728
Document type: Journal article (letter)
Publisher: Nature Publishing Group

Abstract english

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.


  • Microbiology in the medical area


  • Diabetes and Celiac Unit
  • ISSN: 0028-0836
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79


Jan Waldenströms gata 35, Malmö


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00