TY - JOUR
T1 - Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study
AU - TEDDY Study Group
AU - Uusitalo, Ulla
AU - Liu, Xiang
AU - Yang, Jimin
AU - Aronsson, Carin Andrén
AU - Hummel, Sandra
AU - Butterworth, Martha
AU - Lernmark, Åke
AU - Rewers, Marian
AU - Hagopian, William
AU - She, Jin-Xiong
AU - Simell, Olli
AU - Toppari, Jorma
AU - Ziegler, Anette G
AU - Akolkar, Beena
AU - Krischer, Jeffrey
AU - Norris, Jill M
AU - Virtanen, Suvi M
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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.
KW - Autoantibodies/analysis
KW - Autoimmunity
KW - Child
KW - Child, Preschool
KW - Diabetes Mellitus, Type 1/genetics
KW - Dietary Supplements
KW - Female
KW - Follow-Up Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - HLA Antigens/genetics
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Islets of Langerhans/immunology
KW - Male
KW - Probiotics/administration & dosage
KW - Risk
U2 - 10.1001/jamapediatrics.2015.2757
DO - 10.1001/jamapediatrics.2015.2757
M3 - Article (Academic Journal)
C2 - 26552054
VL - 170
SP - 20
EP - 28
JO - JAMA Pediatrics
JF - JAMA Pediatrics
SN - 2168-6203
IS - 1
ER -