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

Show simple item record Vatanen, Tommi en Franzosa, EA en Schwager, R en Tripathi, S en Arthur, TD en Vehik, K en Lernmark, A en Hagopian, WA en Rewers, MJ en She, J-X en Toppari, J en Ziegler, A-G en Akolkar, B en Krischer, JP en Stewart, CJ en Ajami, NJ en Petrosino, JF en Gevers, D en Lähdesmäki, H en Vlamakis, H en Huttenhower, C en Xavier, RJ en 2019-03-20T04:12:17Z en 2018-10-24 en
dc.identifier.citation Nature 562(7728):589-594 24 Oct 2018 en
dc.identifier.issn 0028-0836 en
dc.identifier.uri en
dc.description.abstract 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. en
dc.publisher Nature Research en
dc.relation.ispartofseries Nature en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.rights.uri en
dc.title The human gut microbiome in early-onset type 1 diabetes from the TEDDY study en
dc.type Journal Article en
dc.identifier.doi 10.1038/s41586-018-0620-2 en
pubs.issue 7728 en
pubs.begin-page 589 en
pubs.volume 562 en
dc.rights.holder Copyright: Springer Nature en en
pubs.end-page 594 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 755472 en Liggins Institute en
pubs.record-created-at-source-date 2018-11-02 en
pubs.dimensions-id 30356183 en

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