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Gut. 2019 Nov 19. pii: gutjnl-2019-319809. doi: 10.1136/gutjnl-2019-319809. [Epub ahead of print]

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.

Collaborators (230)

Barbour A, Bautista K, Baxter J, Felipe-Morales D, Driscoll K, Frohnert BI, Stahl M, Gesualdo P, Hoffman M, Karban R, Norris J, Peacock S, Shorrosh H, Steck A, Stern M, Villegas E, Waugh K, Simell OG, Adamsson A, Ahonen S, Åkerlund M, Hakola L, Hekkala A, Holappa H, Ikonen A, Ilonen J, Jäminki S, Jokipuu S, Karlsson L, Kero J, Kähönen M, Knip M, Koivikko ML, Koskinen M, Koreasalo M, Kytölä J, Latva-Aho T, Lönnrot M, Mäntymäki E, Mattila M, Miettinen M, Multasuo K, Mykkänen T, Niininen T, Niinistö S, Nyblom M, Oikarinen S, Ollikainen P, Othmani Z, Pohjola S, Rajala P, Rautanen J, Riikonen A, Riski E, Pekkola M, Romo M, Ruohonen S, Simell S, Sjöberg M, Stenius A, Tossavainen P, Vähä-Mäkilä M, Vainionpää S, Varjonen E, Veijola R, Viinikangas I, Virtanen SM, She JX, Schatz D, Hopkins D, Steed L, Bryant J, Silvis K, Haller M, Gardiner M, McIndoe R, Sharma A, Anderson SW, Jacobsen L, Marks J, Bonifacio E, Gavrisan A, Gezginci C, Heublein A, Hoffmann V, Hummel S, Keimer A, Knopff A, Koch C, Ramminger C, Roth R, Scholz M, Stock J, Warncke K, Wendel L, Winkler C, Lernmark Å, Aronsson CA, Ask M, Bennet R, Cilio C, Engqvist H, Ericson-Hallström E, Fors A, Fransson L, Gard T, Hansen M, Jisser H, Johansen F, Jonsdottir B, Jovic S, Larsson HE, Lindström M, Lundgren M, Maziarz M, Månsson-Martinez M, Markan M, Melin J, Mestan Z, Nilsson C, Ottosson K, Rahmati K, Ramelius A, Salami F, Sjöberg A, Sjöberg B, Svensson M, Törn C, Wallin A, Wimar Å, Åberg S, Killian M, Crouch CC, Skidmore J, Chavoshi M, Hervey R, Lyons R, Meyer A, Mulenga D, Radtke J, Romancik M, Schmitt D, Zink S, Becker D, Franciscus M, Smith MD, Daftary A, Klein MB, Yates C, Austin-Gonzalez S, Avendano M, Baethke S, Brown R, Burkhardt B, Butterworth M, Clasen J, Cuthbertson D, Dankyi S, Eberhard C, Fiske S, Garmeson J, Gowda V, Heyman K, Hsiao B, Karges C, Laras FP, Li Q, Liu S, Liu X, Lynch K, Maguire C, Malloy J, McCarthy C, Merrell A, Parikh H, Quigley R, Remedios C, Shaffer C, Smith L, Smith S, Sulman N, Tamura R, Tewey D, Toth M, Uusitalo U, Vehik K, Vijayakandipan P, Wood K, Yang J, Abbondondolo M, Ballard L, Hadley D, McLeod W, Meulemans S, Yu L, Miao D, Bingley P, Williams A, Chandler K, Ball O, Kelland I, Grace S, Chavoshi M, Radtke J, Zink S, Ajami NJ, Ross MC, O'Brien JL, Hutchinson DS, Smith DP, Wong MC, Tian X, Ayvaz T, Tamegnon A, Truong N, Moreno H, Riley L, Moreno E, Bauch T, Kusic L, Metcalf G, Muzny D, Doddapaneni H, Gibbs R, Ke S, Mulholland N, Bourcier K, Briese T, Johnson SB, Triplett E.

Author information

1
Faculty of Medicine and Health Techology, Tampere University, Tampere, Finland katri.lindfors@tuni.fi.
2
Faculty of Medicine and Health Techology, Tampere University, Tampere, Finland.
3
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
4
Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
5
Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland.
6
The University Consortium of Seinäjoki, Seinäjoki, Finland.
7
University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
8
Digestive Health Institute, Children's Hospital Colorado, Aurora, United States.
9
Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany.
10
Division of Paediatric Gastroenterology and Hepatology, Dr von Hauner Children's Hospital, Munchen, Germany.
11
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Denver, Colorado, USA.
12
Pacific Northwest Research Institute, Seattle, Washington, USA.
13
Research Centre for Integrative Physiology and Phamacology, Institute of Biomedicine, University of Turku, Turku, Finland.
14
Department of Paediatrics, Turku University Hospital, Turku, Finland.
15
Kliikum Rechts der Isar, Technische Universität München, Munchen, Bayern, Germany.
16
Institute of Diabetes Research, Helmholtz Zentrum München, Germany.
17
Forschergruppe Diabetes e.V, Neuherberg, Germany.
18
National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland, USA.
19
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
20
The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
#
Contributed equally

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 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.

KEYWORDS:

coeliac disease; gluten; small bowel

PMID:
31744911
DOI:
10.1136/gutjnl-2019-319809
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Conflict of interest statement

Competing interests: HH is a shareholder and chairman of the board of Vactech Ltd, which develops vaccines against picornaviruses.

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