Higher abundance of enterovirus A species in the gut of children with islet autoimmunity

Sci Rep. 2019 Feb 11;9(1):1749. doi: 10.1038/s41598-018-38368-8.


Enteroviruses (EVs) are prime candidate environmental triggers of islet autoimmunity (IA), with potential as vaccine targets for type 1 diabetes prevention. However, the use of targeted virus detection methods and the selective focus on EVs by most studies increases the risk for substantial investigation bias and an overestimated association between EV and type 1 diabetes. Here we performed comprehensive virome-capture sequencing to examine all known vertebrate-infecting viruses without bias in 182 specimens (faeces and plasma) collected before or at seroconversion from 45 case children with IA and 48 matched controls. From >2.6 billion reads, 28 genera of viruses were detected and 62% of children (58/93) were positive for ≥1 vertebrate-infecting virus. We identified 129 viruses as differentially abundant between the gut of cases and controls, including 5 EV-A types significantly more abundant in the cases. Our findings further support EV's hypothesised contribution to IA and corroborate the proposal that viral load may be an important parameter in disease pathogenesis. Furthermore, our data indicate a previously unrecognised association of IA with higher EV-A abundance in the gut of children and provide a catalog of viruses to be interrogated further to determine a causal link between virus infection and type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmunity*
  • Biodiversity
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / etiology*
  • Disease Susceptibility
  • Enterovirus Infections / epidemiology
  • Enterovirus Infections / virology*
  • Enterovirus* / genetics
  • Enterovirus* / immunology
  • Feces / virology
  • Female
  • Gastrointestinal Microbiome* / immunology
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology
  • Male
  • Prevalence
  • Viral Load