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

TitleTemporal development of the gut microbiome in early childhood from the TEDDY study.
Publication TypeJournal Article
Year of Publication2018
AuthorsStewart, CJ, Ajami, NJ, O'Brien, JL, Hutchinson, DS, Smith, DP, Wong, MC, Ross, MC, Lloyd, RE, Doddapaneni, H, Metcalf, GA, Muzny, DM, Gibbs, RA, Vatanen, T, Huttenhower, C, Xavier, RJ, Rewers, M, Hagopian, W, Toppari, J, Ziegler, A-G, She, J-X, Akolkar, B, Lernmark, A, Hyoty, H, Vehik, K, Krischer, JP, Petrosino, JF
JournalNature
Volume562
Issue7728
Pagination583-588
Date Published2018 10
ISSN1476-4687
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 such as persistent islet autoimmunity and type 1 diabetes. 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.

DOI10.1038/s41586-018-0617-x
Alternate JournalNature
PubMed ID30356187
Grant ListU01 DK063821 / DK / NIDDK NIH HHS / United States
UC4 DK063865 / DK / NIDDK NIH HHS / United States
UC4 DK063863 / DK / NIDDK NIH HHS / United States
U01 DK063836 / DK / NIDDK NIH HHS / United States
UC4 DK112243 / DK / NIDDK NIH HHS / United States
U01 DK063829 / DK / NIDDK NIH HHS / United States
UC4 DK095300 / DK / NIDDK NIH HHS / United States
U01 DK063865 / DK / NIDDK NIH HHS / United States
UC4 DK063861 / DK / NIDDK NIH HHS / United States
UC4 DK063829 / DK / NIDDK NIH HHS / United States
HHSN267200700014C / LM / NLM NIH HHS / United States
UC4 DK063821 / DK / NIDDK NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UC4 DK063836 / DK / NIDDK NIH HHS / United States
HHSN267200700014C / DK / NIDDK NIH HHS / United States
U01 DK063861 / DK / NIDDK NIH HHS / United States
U01 DK063863 / DK / NIDDK NIH HHS / United States
U01 DK063790 / DK / NIDDK NIH HHS / United States
UL1 TR000064 / TR / NCATS NIH HHS / United States
UC4 DK106955 / DK / NIDDK NIH HHS / United States
UC4 DK100238 / DK / NIDDK NIH HHS / United States
UC4 DK117483 / DK / NIDDK NIH HHS / United States