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

被引：619

作者：

Vatanen, Tommi ^{[1
]}

Franzosa, Eric A. ^{[1
,2
]}

Schwager, Randall ^{[2
]}

Tripathi, Surya ^{[1
]}

Arthur, Timothy D. ^{[1
]}

Vehik, Kendra ^{[3
]}

Lernmark, Ake ^{[4
]}

Hagopian, William A. ^{[5
]}

Rewers, Marian J. ^{[6
]}

She, Jin-Xiong ^{[7
]}

Toppari, Jorma ^{[8
,9
]}

Ziegler, Anette-G. ^{[10
,11
,12
]}

Akolkar, Beena ^{[13
]}

Krischer, Jeffrey P. ^{[3
]}

Stewart, Christopher J. ^{[14
,15
]}

Ajami, Nadim J. ^{[14
]}

Petrosino, Joseph F. ^{[14
]}

Gevers, Dirk ^{[1
,20
]}

Lahdesmaki, Harri ^{[16
]}

Vlamakis, Hera ^{[1
]}

Huttenhower, Curtis ^{[1
,2
,21
]}

Xavier, Ramnik J. ^{[1
,17
,18
,19
,20
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[3] Univ S Florida, Hlth Informat Inst, Morsani Coll Med, Tampa, FL USA

[4] Lund Univ, Skane Univ Hosp SUS, Dept Clin Sci, CRC, Malmo, Sweden

[5] Pacific Northwest Res Inst, Seattle, WA USA

[6] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA

[7] Augusta Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA

[8] Turku Univ Hosp, Dept Pediat, Turku, Finland

[9] Univ Turku, Inst Biomed, Res Ctr Integrat Physiol & Pharmacol, Turku, Finland

[10] Helmholtz Zentrum Munchen, Inst Diabet Res, Munich, Germany

[11] Tech Univ Munich, Forschergrp Diabet, Klinikum Rechts Isar, Munich, Germany

[12] Helmholtz Zentrum Munchen, Forschergrp Diabet eV, Munich, Germany

[13] NIDDK, Bethesda, MD USA

[14] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[15] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[16] Aalto Univ, Dept Comp Sci, Espoo, Finland

[17] Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[18] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[19] Harvard Med Sch, Boston, MA 02115 USA

[20] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA

[21] Janssen Human Microbiome Inst Janssen Res & Dev, Cambridge, MA USA

来源：

NATURE | 2018年 / 562卷 / 7728期

关键词：

ENVIRONMENTAL DETERMINANTS; INTESTINAL MICROBIOTA; RISK-FACTORS; YOUNG TEDDY; CHILDREN; AUTOIMMUNITY; ASSOCIATION; CONTRIBUTES; DYNAMICS; SEQUENCE;

D O I：

10.1038/s41586-018-0620-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：589 / +

页数：17