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 SheBeena Akolkar, Ake Lernmark, Heikki Hyoty, Kendra Vehik, Jeffrey P. Krischer, Joseph F. Petrosino

Research output: Contribution to journalLetter

68 Citations (Scopus)

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 diseases 1–9 such as persistent islet autoimmunity and type 1 diabetes 10–12 . 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.

Original languageEnglish (US)
Pages (from-to)583-588
Number of pages6
JournalNature
Volume562
Issue number7728
DOIs
StatePublished - Oct 25 2018

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Microbiota
Bacteroides
Human Milk
Autoimmunity
Type 1 Diabetes Mellitus
Parturition
Metagenomics
Bifidobacterium
Pets
Breast Feeding
rRNA Genes
Gastrointestinal Microbiome
Siblings
Health
Population

ASJC Scopus subject areas

  • General

Cite this

Stewart, C. J., Ajami, N. J., O’Brien, J. L., Hutchinson, D. S., Smith, D. P., Wong, M. C., ... Petrosino, J. F. (2018). Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature, 562(7728), 583-588. https://doi.org/10.1038/s41586-018-0617-x

Temporal development of the gut microbiome in early childhood from the TEDDY study. / Stewart, Christopher J.; Ajami, Nadim J.; O’Brien, Jacqueline L.; Hutchinson, Diane S.; Smith, Daniel P.; Wong, Matthew C.; Ross, Matthew C.; Lloyd, Richard E.; Doddapaneni, Harsha Vardhan; Metcalf, Ginger A.; Muzny, Donna; Gibbs, Richard A.; Vatanen, Tommi; Huttenhower, Curtis; Xavier, Ramnik J.; Rewers, Marian; Hagopian, William; Toppari, Jorma; Ziegler, Anette G.; She, Jin-Xiong; Akolkar, Beena; Lernmark, Ake; Hyoty, Heikki; Vehik, Kendra; Krischer, Jeffrey P.; Petrosino, Joseph F.

In: Nature, Vol. 562, No. 7728, 25.10.2018, p. 583-588.

Research output: Contribution to journalLetter

Stewart, CJ, Ajami, NJ, O’Brien, JL, Hutchinson, DS, Smith, DP, Wong, MC, Ross, MC, Lloyd, RE, Doddapaneni, HV, Metcalf, GA, Muzny, D, Gibbs, RA, Vatanen, T, Huttenhower, C, Xavier, RJ, Rewers, M, Hagopian, W, Toppari, J, Ziegler, AG, She, J-X, Akolkar, B, Lernmark, A, Hyoty, H, Vehik, K, Krischer, JP & Petrosino, JF 2018, 'Temporal development of the gut microbiome in early childhood from the TEDDY study', Nature, vol. 562, no. 7728, pp. 583-588. https://doi.org/10.1038/s41586-018-0617-x
Stewart CJ, Ajami NJ, O’Brien JL, Hutchinson DS, Smith DP, Wong MC et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018 Oct 25;562(7728):583-588. https://doi.org/10.1038/s41586-018-0617-x
Stewart, Christopher J. ; Ajami, Nadim J. ; O’Brien, Jacqueline L. ; Hutchinson, Diane S. ; Smith, Daniel P. ; Wong, Matthew C. ; Ross, Matthew C. ; Lloyd, Richard E. ; Doddapaneni, Harsha Vardhan ; Metcalf, Ginger A. ; Muzny, Donna ; Gibbs, Richard A. ; Vatanen, Tommi ; Huttenhower, Curtis ; Xavier, Ramnik J. ; Rewers, Marian ; Hagopian, William ; Toppari, Jorma ; Ziegler, Anette G. ; She, Jin-Xiong ; Akolkar, Beena ; Lernmark, Ake ; Hyoty, Heikki ; Vehik, Kendra ; Krischer, Jeffrey P. ; Petrosino, Joseph F. / Temporal development of the gut microbiome in early childhood from the TEDDY study. In: Nature. 2018 ; Vol. 562, No. 7728. pp. 583-588.
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AU - Stewart, Christopher J.

AU - Ajami, Nadim J.

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AU - Hutchinson, Diane S.

AU - Smith, Daniel P.

AU - Wong, Matthew C.

AU - Ross, Matthew C.

AU - Lloyd, Richard E.

AU - Doddapaneni, Harsha Vardhan

AU - Metcalf, Ginger A.

AU - Muzny, Donna

AU - Gibbs, Richard A.

AU - Vatanen, Tommi

AU - Huttenhower, Curtis

AU - Xavier, Ramnik J.

AU - Rewers, Marian

AU - Hagopian, William

AU - Toppari, Jorma

AU - Ziegler, Anette G.

AU - She, Jin-Xiong

AU - Akolkar, Beena

AU - Lernmark, Ake

AU - Hyoty, Heikki

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AU - Petrosino, Joseph F.

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N2 - 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 diseases 1–9 such as persistent islet autoimmunity and type 1 diabetes 10–12 . 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.

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