TY - JOUR
T1 - Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study
AU - RNA Laboratory and Gene Expression Laboratory
AU - Microbiome and Viral Metagenomics Laboratory
AU - Metabolomics Laboratory
AU - HbA1c Laboratory
AU - HLA Reference Laboratory
AU - OGTT Laboratory
AU - Proteomics Laboratory
AU - Repository
AU - Dietary Biomarkers Laboratory
AU - Project Scientist
AU - Other contributors
AU - Autoantibody Reference Laboratories
AU - Cortisol Laboratory
AU - Data Coordinating Center
AU - Pennsylvania Satellite Center
AU - Washington Clinical Center
AU - Sweden Clinical Center
AU - Finland Clinical Center
AU - Germany Clinical Center
AU - Georgia/Florida Clinical Center
AU - for the TEDDY Study Group
AU - SNP Laboratory
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.
AU - Bautista, Kimberly
AU - Baxter, Judith
AU - Bedoy, Ruth
AU - Felipe-Morales, Daniel
AU - Frohnert, Brigitte
AU - Gesualdo, Patricia
AU - Hoffman, Michelle
AU - Karban, Rachel
AU - Liu, Edwin
AU - Samper-Imaz, Adela
AU - Steck, Andrea
AU - Waugh, Kathleen
AU - Wright, Hali
AU - Schatz, Desmond
AU - Hopkins, Diane
AU - Steed, Leigh
AU - Thomas, Jamie
AU - Silvis, Katherine
AU - Haller, Michael
AU - Shankar, Meena
AU - Sheehan, Eleni
AU - Gardiner, Melissa
AU - McIndoe, Richard
AU - Sharma, Ashok
AU - Williams, Joshua
AU - Foghis, Gabriela
AU - Anderson, Stephen W.
AU - Robinson, Richard
AU - Beyerlein, Andreas
AU - Bonifacio, Ezio
AU - Hummel, Michael
AU - Foterek, Kristina
AU - Kersting, Mathilde
N1 - Funding Information:
This study was supported by grants U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, and UC4 DK100238 and contract HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, Juvenile Diabetes Research Foundation, and Centers for Disease Control and Prevention. This work is supported in part by the National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Awards UL1 TR000064 (University of Florida) and UL1 TR001082 (University of Colorado).
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, andWashington) 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, andWashington) 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.
UR - http://www.scopus.com/inward/record.url?scp=84954121518&partnerID=8YFLogxK
U2 - 10.1001/jamapediatrics.2015.2757
DO - 10.1001/jamapediatrics.2015.2757
M3 - Article
C2 - 26552054
AN - SCOPUS:84954121518
SN - 2168-6203
VL - 170
SP - 20
EP - 28
JO - JAMA Pediatrics
JF - JAMA Pediatrics
IS - 1
ER -
