The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
    • Publication Information:
      Publication: Basingstoke : Nature Publishing Group
      Original Publication: London, Macmillan Journals ltd.
    • Subject Terms:
      Health Surveys*; Diabetes Mellitus, Type 1/*epidemiology ; Diabetes Mellitus, Type 1/*microbiology ; Gastrointestinal Microbiome/*physiology; Age of Onset ; Animals ; Bifidobacterium/enzymology ; Bifidobacterium/genetics ; Bifidobacterium/isolation & purification ; Breast Feeding ; Child, Preschool ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/prevention & control ; Disease Models, Animal ; Fatty Acids, Volatile/pharmacology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Gastrointestinal Microbiome/immunology ; Humans ; Infant ; Islets of Langerhans/immunology ; Longitudinal Studies ; Male ; Mice ; Milk, Human/immunology ; Milk, Human/microbiology ; Proteobacteria/enzymology ; Proteobacteria/genetics ; Proteobacteria/isolation & purification ; White People
    • Abstract:
      Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors 1 , including complex genetic elements 2 , patient exposures 3 and the gut microbiome 4 . Viral infections 5 and broader gut dysbioses 6 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 cohorts 7,8 and a T1D mouse model 9 , these data support the protective effects of short-chain fatty acids in early-onset human T1D.
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    • Grant Information:
      U01 DK063821 United States DK NIDDK NIH HHS; UC4 DK063863 United States DK NIDDK NIH HHS; UL1 TR002535 United States TR NCATS NIH HHS; UL1 TR001427 United States TR NCATS NIH HHS; U01 DK063790 United States DK NIDDK NIH HHS; UL1 TR001082 United States TR NCATS NIH HHS; R24 DK110499 United States DK NIDDK NIH HHS; UL1 TR000064 United States TR NCATS NIH HHS; HHSN267200700014C United States LM NLM NIH HHS; U01 DK063836 United States DK NIDDK NIH HHS; U01 DK063829 United States DK NIDDK NIH HHS; U01 DK063865 United States DK NIDDK NIH HHS; UC4 DK095300 United States DK NIDDK NIH HHS; UC4 DK063861 United States DK NIDDK NIH HHS; UC4 DK063829 United States DK NIDDK NIH HHS; UC4 DK063821 United States DK NIDDK NIH HHS; UC4 DK117483 United States DK NIDDK NIH HHS; UC4 DK063836 United States DK NIDDK NIH HHS; UC4 DK112243 United States DK NIDDK NIH HHS; U54 DE023798 United States DE NIDCR NIH HHS; U01 DK063861 United States DK NIDDK NIH HHS; UC4 DK063865 United States DK NIDDK NIH HHS; U01 DK063863 United States DK NIDDK NIH HHS; UC4 DK106955 United States DK NIDDK NIH HHS; UC4 DK100238 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Fatty Acids, Volatile)
    • Publication Date:
      Date Created: 20181026 Date Completed: 20190401 Latest Revision: 20240610
    • Publication Date:
      20240610
    • Accession Number:
      PMC6296767
    • Accession Number:
      10.1038/s41586-018-0620-2
    • Accession Number:
      30356183