title: Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study.
abstract: OBJECTIVE
  Probiotics have been hypothesized to affect immunologic responses to environmental exposures by supporting healthy gut microbiota and could therefore theoretically be used to prevent the development of type 1 diabetes mellitus (T1DM)-associated islet autoimmunity.
  
  
  OBJECTIVE
  To examine the association between supplemental probiotic use during the first year of life and islet autoimmunity among children at increased genetic risk of T1DM.
  
  
  METHODS
  In this ongoing prospective cohort study that started September 1, 2004, children from 6 clinical centers, 3 in the United States (Colorado, Georgia/Florida, and Washington) and 3 in Europe (Finland, Germany, and Sweden), were followed up for T1DM-related autoantibodies. Blood samples were collected every 3 months between 3 and 48 months of age and every 6 months thereafter to determine persistent islet autoimmunity. Details of infant feeding, including probiotic supplementation and infant formula use, were monitored from birth using questionnaires and diaries. We applied time-to-event analysis to study the association between probiotic use and islet autoimmunity, stratifying by country and adjusting for family history of type 1 diabetes, HLA-DR-DQ genotypes, sex, birth order, mode of delivery, exclusive breastfeeding, birth year, child's antibiotic use, and diarrheal history, as well as maternal age, probiotic use, and smoking. Altogether 8676 infants with an eligible genotype were enrolled in the follow-up study before the age of 4 months. The final sample consisted of 7473 children with the age range of 4 to 10 years (as of October 31, 2014).
  
  
  METHODS
  Early intake of probiotics.
  
  
  METHODS
  Islet autoimmunity revealed by specific islet autoantibodies.
  
  
  RESULTS
  Early probiotic supplementation (at the age of 0-27 days) was associated with a decreased risk of islet autoimmunity when compared with probiotic supplementation after 27 days or no probiotic supplementation (hazard ratio [HR], 0.66; 95% CI, 0.46-0.94). The association was accounted for by children with the DR3/4 genotype (HR, 0.40; 95% CI, 0.21-0.74) and was absent among other genotypes (HR, 0.97; 95% CI, 0.62-1.54).
  
  
  CONCLUSIONS
  Early probiotic supplementation may reduce the risk of islet autoimmunity in children at the highest genetic risk of T1DM. The result needs to be confirmed in further studies before any recommendation of probiotics use is made.
authors.affiliation: Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Ulla
authors.initials: U
authors.lastname: Uusitalo
authors.affiliation: Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Jimin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Carin Andrén
authors.initials: CA
authors.lastname: Aronsson
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München and Forschergruppe Diabetes e.V., Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hummel
authors.affiliation: Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Martha
authors.initials: M
authors.lastname: Butterworth
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora.
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, Washington.
authors.forename: William
authors.initials: W
authors.lastname: Hagopian
authors.affiliation: Medical College of Georgia, Georgia Regents University, Augusta.
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.affiliation: Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland8Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München and Forschergruppe Diabetes e.V., Munich, Germany.
authors.forename: Anette G
authors.initials: AG
authors.lastname: Ziegler
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Beena
authors.initials: B
authors.lastname: Akolkar
authors.affiliation: Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.affiliation: National Institute for Health and Welfare, Nutrition Unit, Helsinki, Finland12School of Health Sciences and Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland 13The Science Center of Pirkanmaa Hospita.
authors.forename: Suvi M
authors.initials: SM
authors.lastname: Virtanen
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D019587:Dietary Supplements; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D019936:Probiotics / Q000008:administration & dosage*; D012306:Risk
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens