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Nature. 2018 Oct;562(7728):589-594. doi: 10.1038/s41586-018-0620-2. Epub 2018 Oct 24.

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

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Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmo, Sweden.
Pacific Northwest Research Institute, Seattle, WA, USA.
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Department of Pediatrics, Turku University Hospital, Turku, Finland.
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.
Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany.
Forschergruppe Diabetes, Technische Universität München, Klinikum Rechts der Isar, Munich, Germany.
Forschergruppe Diabetes e.V. at Helmholtz Zentrum München, Munich, Germany.
National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, USA.
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Janssen Human Microbiome Institute, Janssen Research and Development, Cambridge, MA, USA.
Department of Computer Science, Aalto University, Espoo, Finland.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA.


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.

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