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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

Jake Lin; Katri Lindfors; Jorma Toppari; Edwin Liu; Marian Rewers; Joseph F Petrosino; Kalle Kurppa; Annette-Gabriele Ziegler; Daniel Agardh; the TEDDY Study Group; Hye-Seung Lee; Jeffrey P Krischer; Sibylle Koletzko; Beena Akolkar; Heikki Hyöty; Matti Nykter; Richard E Lloyd; William Hagopian

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

Jake Lin
Katri Lindfors
Jorma Toppari
Edwin Liu
Marian Rewers
Joseph F Petrosino
Kalle Kurppa
Annette-Gabriele Ziegler
Daniel Agardh; the TEDDY Study Group
Hye-Seung Lee
Jeffrey P Krischer
Sibylle Koletzko
Beena Akolkar
Heikki Hyöty
Matti Nykter
Richard E Lloyd
William Hagopian
Katso/Avaa
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BMJ Publishing Group
doi:10.1136/gutjnl-2019-319809
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042827356
Tiivistelmä

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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