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

Proc Natl Acad Sci U S A
Authors
Keywords
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 -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.

Year of Publication
2017
Journal
Proc Natl Acad Sci U S A
Volume
114
Issue
30
Pages
E6166-E6175
Date Published
2017 07 25
ISSN
1091-6490
DOI
10.1073/pnas.1706359114
PubMed ID
28696303
PubMed Central ID
PMC5544325
Links
Grant list
R01 DK101354 / DK / NIDDK NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK092405 / DK / NIDDK NIH HHS / United States
R01 AI111918 / AI / NIAID NIH HHS / United States
UL1 TR000448 / TR / NCATS NIH HHS / United States
UL1 TR002345 / TR / NCATS NIH HHS / United States
R24 OD019793 / OD / NIH HHS / United States