Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 30, Pages E6166-E6175Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1706359114
Keywords
virome; microbiome; Circoviridae; type 1 diabetes; bacteriophages
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Funding
- Juvenile Diabetes Research Foundation [2-SRA-2015-305-Q-R]
- National Institutes of Health [R01 DK101354, R24 OD019793, R01 AI111918, DK43351, DK92405]
- Juvenile Diabetes Research Foundation
- European Union [202063]
- Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]
- [UL1 TR000448]
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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.
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