OBJECTIVE: This study used next-generation sequencing (NGS) technologies to characterize the gut virome at the onset of islet autoimmunity. RESEARCH DESIGN AND METHODS: We conducted a case-control study nested within the Finnish Diabetes Prediction and Prevention (DIPP) cohort. The stool virome in 19 case children, who turned islet autoantibody positive before the age of 2 years and later developed clinical type 1 diabetes, and 19 tightly matched control subjects was analyzed using NGS performed from stool samples collected 3, 6, and 9 months before the onset of islet autoimmunity. Human virus findings were verified using real-time PCR. RESULTS: One or more human viruses were present in 10.4% and bacteriophages were in 54% of the samples. The virome composition showed no association with islet autoimmunity. NGS was less sensitive and specific than real-time PCR. CONCLUSIONS: The present data suggest no dramatic changes in the gut virome shortly before the emergence of islet autoimmunity and emphasize the need of verification of mass sequencing results when viral exposure is assessed in association studies.

Children's Hospital University of Helsinki and Helsinki University Central Hospital Helsinki Finland Diabetes and Obesity Research Program University of Helsinki Helsinki Finland Department of Pediatrics Tampere University Hospital Tampere Finland Folklhälsan Research Center Helsinki Finland

Department of Immunogenetics University of Turku Turku Finland

Department of Medical Biochemistry and Genetics University of Turku Turku Finland

Department of Pediatrics Oulu University Hospital and University of Oulu Oulu Finland

Department of Pediatrics Turku University Central Hospital Turku Finland

Department of Pediatrics University Hospital Motol and 2nd Faculty of Medicine Charles University Prague Prague Czech Republic

Department of Virology School of Medicine University of Tampere Tampere Finland

Department of Virology School of Medicine University of Tampere Tampere Finland Fimlab Laboratories Pirkanmaa Hospital District Tampere Finland

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