TY - JOUR
T1 - Temporal development of the gut microbiome in early childhood from the TEDDY study
AU - Stewart, Christopher J.
AU - Ajami, Nadim J.
AU - O’Brien, Jacqueline L.
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
AU - Vehik, Kendra
AU - Krischer, Jeffrey P.
AU - Petrosino, Joseph F.
N1 - Funding Information:
Acknowledgements We acknowledge the following members of the CMMR for their support in samples processing: T. Ayvaz, T. Bauch, L. Kusic, L. Railey, R. Berry, A. Tamegnon, E. Zavala, H. Moreno and N. Truong. In addition, we acknowledge the contribution of the Human Genome Sequencing Center at Baylor College of Medicine for their support in the data generation aspects of this work. We apologize to authors of existing work that we could not cite because of space constraints. This research was performed on behalf of the TEDDY Study Group, which is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and contract no. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082). R.J.X. was supported by funding from JDRF (2-SRA-2016-247-S-B and 2-SRA-2018-548-S-B).
Publisher Copyright:
© 2018, Springer Nature Limited.
PY - 2018/10/25
Y1 - 2018/10/25
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 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055452012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055452012&partnerID=8YFLogxK
U2 - 10.1038/s41586-018-0617-x
DO - 10.1038/s41586-018-0617-x
M3 - Article
C2 - 30356187
AN - SCOPUS:85055452012
SN - 0028-0836
VL - 562
SP - 583
EP - 588
JO - Nature
JF - Nature
IS - 7728
ER -