Original Investigation
January 2016

Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study

Author Affiliations
  • 1Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa
  • 2Department of Clinical Sciences, Lund University, Malmö, Sweden
  • 3Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München and Forschergruppe Diabetes e.V., Munich, Germany
  • 4Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora
  • 5Pacific Northwest Diabetes Research Institute, Seattle, Washington
  • 6Medical College of Georgia, Georgia Regents University, Augusta
  • 7Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
  • 8Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland
  • 9National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
  • 10Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora
  • 11National Institute for Health and Welfare, Nutrition Unit, Helsinki, Finland
  • 12School of Health Sciences and Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
  • 13The Science Center of Pirkanmaa Hospital District, Tampere, Finland

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Pediatr. 2016;170(1):20-28. doi:10.1001/jamapediatrics.2015.2757

Importance  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.

Design, Setting, and Participants  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).

Exposures  Early intake of probiotics.

Main Outcomes and Measures  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 and Relevance  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.