Dataset Information

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

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.

SUBMITTER: Stewart CJ

PROVIDER: S-EPMC6415775 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Stewart Christopher J CJ Ajami Nadim J NJ O'Brien Jacqueline L JL Hutchinson Diane S DS Smith Daniel P DP Wong Matthew C MC Ross Matthew C MC Lloyd Richard E RE Doddapaneni HarshaVardhan H Metcalf Ginger A GA Muzny Donna D Gibbs Richard A RA Vatanen Tommi T Huttenhower Curtis C Xavier Ramnik J RJ Rewers Marian M Hagopian William W Toppari Jorma J Ziegler Anette-G AG She Jin-Xiong JX Akolkar Beena B Lernmark Ake A Hyoty Heikki H Vehik Kendra K Krischer Jeffrey P JP Petrosino Joseph F JF

Nature 20181024 7728

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<sup>1-9</sup> such as persistent islet autoimmunity and type 1 diabetes<sup>10-12</sup>. 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 ...[more]

PMID: 30356187

Similar Datasets

Project description:Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.

Project description:Temporal development of the human gut microbiome from infancy to childhood is driven by a variety of factors. We surveyed the fecal microbiome of 729 Chinese children aged 0-36 months, aiming to identify the age-specific patterns of microbiota succession, and evaluate the impact of birth mode, gender, geographical location, and gastrointestinal tract symptoms on the shaping of the gut microbiome. We demonstrated that phylogenetic diversity of the gut microbiome increased gradually over time, which was accompanied by an increase in Bacteroidetes and a reduction in Proteobacteria species. Analysis of community-wide phenotypes revealed a succession from aerobic bacteria and anaerobic bacteria to facultative anaerobes, and from Gram-negative to Gram-positive species during gut microbiota development in early childhood. The metabolic functions of the gut microbiome shifted tremendously alongside early physiological development, including an increase in alanine, aspartate, and glutamate metabolism, and a reduction in glutathione, fatty acid, and tyrosine metabolism. During the first year of life, the Bacteroidetes phylum was less abundant in children born by casarean section compared with those delivered vaginally. The Enterococcaceae family, a group of facultative anaerobic microorganisms with pathogenic potential, was predominant in preterm infants. No measurable effect of maternal antibiotic exposure on gut microbiota development was found in the first 3 years of life. The relative abundances of Coriobacteriaceae and Streptococcaceae families, and Megasphaera genus were found to be higher in girls than in boys. Among the three first-tier Chinese cities, children born and fed in Beijing had a higher abundance of Enterococcaceae and Lachnospiraceae families, and Shenzhen children had a higher abundance of Fusobacteriaceae. The families Alcaligenaceae, Bacteroidaceae, and Porphyromonadaceae were more abundant in children with constipation, whereas the relative abundance of the Clostridium genus was higher in those with diarrhea.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets