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, HarshaVardhan 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 and Joseph F. Petrosino ()
Additional contact information
Christopher J. Stewart: Baylor College of Medicine
Nadim J. Ajami: Baylor College of Medicine
Jacqueline L. O’Brien: Baylor College of Medicine
Diane S. Hutchinson: Baylor College of Medicine
Daniel P. Smith: Baylor College of Medicine
Matthew C. Wong: Baylor College of Medicine
Matthew C. Ross: Baylor College of Medicine
Richard E. Lloyd: Baylor College of Medicine
HarshaVardhan Doddapaneni: Baylor College of Medicine
Ginger A. Metcalf: Baylor College of Medicine
Donna Muzny: Baylor College of Medicine
Richard A. Gibbs: Baylor College of Medicine
Tommi Vatanen: Broad Institute of MIT and Harvard
Curtis Huttenhower: Broad Institute of MIT and Harvard
Ramnik J. Xavier: Broad Institute of MIT and Harvard
Marian Rewers: University of Colorado
William Hagopian: Pacific Northwest Research Institute
Jorma Toppari: University of Turku
Anette-G. Ziegler: Helmholtz Zentrum München
Jin-Xiong She: Medical College of Georgia, Augusta University
Beena Akolkar: National Institute of Diabetes & Digestive & Kidney Diseases
Ake Lernmark: Lund University/CRC, Skane University Hospital
Heikki Hyoty: University of Tampere
Kendra Vehik: Morsani College of Medicine, University of South Florida
Jeffrey P. Krischer: Morsani College of Medicine, University of South Florida
Joseph F. Petrosino: Baylor College of Medicine

Nature, 2018, vol. 562, issue 7728, 583-588

Abstract: 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.

Keywords: The Environmental Determinants Of Diabetes In The Young (TEDDY); TEDDY Study; Birth Mode; Furry Pets; Metagenomic Sequence Data (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (26)

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DOI: 10.1038/s41586-018-0617-x

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