title: Compromised gut microbiota networks in children with anti-islet cell autoimmunity.
abstract: The gut microbiome is suggested to play a role in the pathogenesis of autoimmune disorders such as type 1 diabetes. Evidence of anti-islet cell autoimmunity in type 1 diabetes appears in the first years of life; however, little is known regarding the establishment of the gut microbiome in early infancy. Here, we sought to determine whether differences were present in early composition of the gut microbiome in children in whom anti-islet cell autoimmunity developed. We investigated the microbiome of 298 stool samples prospectively taken up to age 3 years from 22 case children in whom anti-islet cell autoantibodies developed, and 22 matched control children who remained islet cell autoantibody-negative in follow-up. The microbiome changed markedly during the first year of life, and was further affected by breast-feeding, food introduction, and birth delivery mode. No differences between anti-islet cell autoantibody-positive and -negative children were found in bacterial diversity, microbial composition, or single-genus abundances. However, substantial alterations in microbial interaction networks were observed at age 0.5 and 2 years in the children in whom anti-islet cell autoantibodies developed. The findings underscore a role of the microbiome in the pathogenesis of anti-islet cell autoimmunity and type 1 diabetes.
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, GermanyInstitute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Endesfelder
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: zu Castell
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Alexandria
authors.initials: A
authors.lastname: Ardissone
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Austin G
authors.initials: AG
authors.lastname: Davis-Richardson
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
authors.affiliation: Scientific Computing Research Unit, Helmholtz Zentrum München, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hagen
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Pflueger
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Gano
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Jennie R
authors.initials: JR
authors.lastname: Fagen
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Drew
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Brown
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kolaczkowski
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL.
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL.
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.affiliation: Center for Regenerative Therapies, Dresden, and Paul Langerhans Institute Dresden, Technische Universität Dresden, GermanyInstitute for Diabetes and Obesity, Helmholtz Zentrum München, Germany.
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.affiliation: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Triplett
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Germany anette-g.ziegler@helmholtz-muenchen.de.
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D015551:Autoimmunity; D001942:Breast Feeding; D016022:Case-Control Studies; D002675:Child, Preschool; D036861:Delivery, Obstetric / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D004781:Environmental Exposure / Q000009:adverse effects; D005243:Feces / Q000382:microbiology*; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007223:Infant; D007225:Infant Food; D007227:Infant Nutritional Physiological Phenomena; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D064307:Microbiota / Q000276:immunology*; D008895:Milk, Human / Q000276:immunology*; D012307:Risk Factors