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Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children : The TEDDY study

Lindfors, Katri ; Lin, Jake ; Lee, Hye Seung ; Hyöty, Heikki ; Nykter, Matti ; Kurppa, Kalle ; Liu, Edwin ; Koletzko, Sibylle ; Rewers, Marian and Hagopian, William , et al. (2020) In Gut 69(8). p.1416-1422
Abstract

Objective: Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children. Design: The Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case-control design. From this design, 83 CDA... (More)

Objective: Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children. Design: The Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case-control design. From this design, 83 CDA case-control pairs were identified. Median age of CDA was 31 months. Stool samples collected monthly up to the age of 2 years were analysed for virome composition by Illumina next-generation sequencing followed by comprehensive computational virus profiling. Results: The cumulative number of stool enteroviral exposures between 1 and 2 years of age was associated with an increased risk for CDA. In addition, there was a significant interaction between cumulative stool enteroviral exposures and gluten consumption. The risk conferred by stool enteroviruses was increased in cases reporting higher gluten intake. Conclusions: Frequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
coeliac disease, gluten, small bowel
in
Gut
volume
69
issue
8
pages
7 pages
publisher
BMJ Publishing Group
external identifiers
  • pmid:31744911
  • scopus:85075363584
ISSN
0017-5749
DOI
10.1136/gutjnl-2019-319809
language
English
LU publication?
yes
id
82e9df96-c693-4c0a-b2b2-01a80a4b97e5
date added to LUP
2019-12-11 15:05:37
date last changed
2024-06-12 05:39:54
@article{82e9df96-c693-4c0a-b2b2-01a80a4b97e5,
  abstract     = {{<p>Objective: Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children. Design: The Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case-control design. From this design, 83 CDA case-control pairs were identified. Median age of CDA was 31 months. Stool samples collected monthly up to the age of 2 years were analysed for virome composition by Illumina next-generation sequencing followed by comprehensive computational virus profiling. Results: The cumulative number of stool enteroviral exposures between 1 and 2 years of age was associated with an increased risk for CDA. In addition, there was a significant interaction between cumulative stool enteroviral exposures and gluten consumption. The risk conferred by stool enteroviruses was increased in cases reporting higher gluten intake. Conclusions: Frequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA.</p>}},
  author       = {{Lindfors, Katri and Lin, Jake and Lee, Hye Seung and Hyöty, Heikki and Nykter, Matti and Kurppa, Kalle and Liu, Edwin and Koletzko, Sibylle and Rewers, Marian and Hagopian, William and Toppari, Jorma and Ziegler, Annette Gabriele and Akolkar, Beena and Krischer, Jeffrey P. and Petrosino, Joseph F. and Lloyd, Richard E. and Agardh, Daniel}},
  issn         = {{0017-5749}},
  keywords     = {{coeliac disease; gluten; small bowel}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1416--1422}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Gut}},
  title        = {{Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children : The TEDDY study}},
  url          = {{http://dx.doi.org/10.1136/gutjnl-2019-319809}},
  doi          = {{10.1136/gutjnl-2019-319809}},
  volume       = {{69}},
  year         = {{2020}},
}