Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

Guoyan Zhao, Tommi Vatanen, Lindsay Droit, Arnold Park, Aleksandar D. Kostic, Tiffany W. Poon, Hera Vlamakis, Heli Siljander, Taina Härkönen, Anu Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Jorma Ilonen, David Wang, Mikael Knip, Ramnik J. Xavier, Herbert W. Virgin

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74 Scopus citations

Abstract

Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.

Original languageEnglish
Pages (from-to)E6166-E6175
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number30
DOIs
StatePublished - Jul 25 2017

Keywords

  • Bacteriophages
  • Circoviridae
  • Microbiome
  • Type 1 diabetes
  • Virome

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    Zhao, G., Vatanen, T., Droit, L., Park, A., Kostic, A. D., Poon, T. W., Vlamakis, H., Siljander, H., Härkönen, T., Hämäläinen, A. M., Peet, A., Tillmann, V., Ilonen, J., Wang, D., Knip, M., Xavier, R. J., & Virgin, H. W. (2017). Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children. Proceedings of the National Academy of Sciences of the United States of America, 114(30), E6166-E6175. https://doi.org/10.1073/pnas.1706359114