title: Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes.
abstract: The incidence of the autoimmune disease, type 1 diabetes (T1D), has increased dramatically over the last half century in many developed countries and is particularly high in Finland and other Nordic countries. Along with genetic predisposition, environmental factors are thought to play a critical role in this increase. As with other autoimmune diseases, the gut microbiome is thought to play a potential role in controlling progression to T1D in children with high genetic risk, but we know little about how the gut microbiome develops in children with high genetic risk for T1D. In this study, the early development of the gut microbiomes of 76 children at high genetic risk for T1D was determined using high-throughput 16S rRNA gene sequencing. Stool samples from children born in the same hospital in Turku, Finland were collected at monthly intervals beginning at 4-6 months after birth until 2.2 years of age. Of those 76 children, 29 seroconverted to T1D-related autoimmunity (cases) including 22 who later developed T1D, the remaining 47 subjects remained healthy (controls). While several significant compositional differences in low abundant species prior to seroconversion were found, one highly abundant group composed of two closely related species, Bacteroides dorei and Bacteroides vulgatus, was significantly higher in cases compared to controls prior to seroconversion. Metagenomic sequencing of samples high in the abundance of the B. dorei/vulgatus group before seroconversion, as well as longer 16S rRNA sequencing identified this group as Bacteroides dorei. The abundance of B. dorei peaked at 7.6 months in cases, over 8 months prior to the appearance of the first islet autoantibody, suggesting that early changes in the microbiome may be useful for predicting T1D autoimmunity in genetically susceptible infants. The cause of increased B. dorei abundance in cases is not known but its timing appears to coincide with the introduction of solid food.
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Austin G
authors.initials: AG
authors.lastname: Davis-Richardson
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Alexandria N
authors.initials: AN
authors.lastname: Ardissone
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Dias
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Simell
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Leonard
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Kaisa M
authors.initials: KM
authors.lastname: Kemppainen
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Drew
authors.affiliation: Department of Pediatrics, University of Florida Gainesville, FL, USA.
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida Gainesville, FL, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kolaczkowski
authors.affiliation: Department of Clinical Microbiology, University of Eastern Finland Kuopio, Finland ; Immunogenetics Laboratory, University of Turku Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: Department of Pediatrics, 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.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: School of Medicine, University of Tampere Tampere, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Nurminen
authors.affiliation: School of Medicine, University of Tampere Tampere, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.affiliation: Department of Pediatrics, University of Oulu, and Oulu University Hospital Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Simell
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Mykkänen
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida Gainesville, FL, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Triplett
keywords: Bacteroides dorei; Bacteroides vulgatus; autoimmunity; microbiome; type-1 diabetes