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

Dietary Biomarkers Laboratory, Project Scientist, Other contributors, Autoantibody Reference Laboratories, Cortisol Laboratory, Data Coordinating Center, Pennsylvania Satellite Center, Washington Clinical Center, Sweden Clinical Center, Finland Clinical Center, Germany Clinical Center, Georgia/Florida Clinical Center, for the TEDDY Study Group, SNP Laboratory, RNA Laboratory and Gene Expression Laboratory, Microbiome and Viral Metagenomics Laboratory, Metabolomics Laboratory, HbA1c Laboratory, HLA Reference Laboratory, OGTT LaboratoryProteomics Laboratory, Repository

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)20-28
Number of pages9
JournalJAMA Pediatrics
Volume170
Issue number1
DOIs
StatePublished - Jan 2016

Fingerprint

Probiotics
Autoimmunity
Type 1 Diabetes Mellitus
Genotype
Autoantibodies
Parturition
HLA-DQ Antigens
Infant Formula
Birth Order
Environmental Exposure
Maternal Age
HLA-DR Antigens
Finland
Breast Feeding
Sweden
Germany
Cohort Studies
Smoking
History
Prospective Studies

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Dietary Biomarkers Laboratory, Project Scientist, Other contributors, Autoantibody Reference Laboratories, Cortisol Laboratory, Data Coordinating Center, ... Repository (2016). Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. JAMA Pediatrics, 170(1), 20-28. https://doi.org/10.1001/jamapediatrics.2015.2757

Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. / Dietary Biomarkers Laboratory; Project Scientist; Other contributors; Autoantibody Reference Laboratories; Cortisol Laboratory; Data Coordinating Center; Pennsylvania Satellite Center; Washington Clinical Center; Sweden Clinical Center; Finland Clinical Center; Germany Clinical Center; Georgia/Florida Clinical Center; for the TEDDY Study Group; SNP Laboratory; RNA Laboratory and Gene Expression Laboratory; Microbiome and Viral Metagenomics Laboratory; Metabolomics Laboratory; HbA1c Laboratory; HLA Reference Laboratory; OGTT Laboratory; Proteomics Laboratory; Repository.

In: JAMA Pediatrics, Vol. 170, No. 1, 01.2016, p. 20-28.

Research output: Contribution to journalArticle

Dietary Biomarkers Laboratory, Project Scientist, Other contributors, Autoantibody Reference Laboratories, Cortisol Laboratory, Data Coordinating Center, Pennsylvania Satellite Center, Washington Clinical Center, Sweden Clinical Center, Finland Clinical Center, Germany Clinical Center, Georgia/Florida Clinical Center, for the TEDDY Study Group, SNP Laboratory, RNA Laboratory and Gene Expression Laboratory, Microbiome and Viral Metagenomics Laboratory, Metabolomics Laboratory, HbA1c Laboratory, HLA Reference Laboratory, OGTT Laboratory, Proteomics Laboratory & Repository 2016, 'Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study', JAMA Pediatrics, vol. 170, no. 1, pp. 20-28. https://doi.org/10.1001/jamapediatrics.2015.2757
Dietary Biomarkers Laboratory, Project Scientist, Other contributors, Autoantibody Reference Laboratories, Cortisol Laboratory, Data Coordinating Center et al. Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. JAMA Pediatrics. 2016 Jan;170(1):20-28. https://doi.org/10.1001/jamapediatrics.2015.2757
Dietary Biomarkers Laboratory ; Project Scientist ; Other contributors ; Autoantibody Reference Laboratories ; Cortisol Laboratory ; Data Coordinating Center ; Pennsylvania Satellite Center ; Washington Clinical Center ; Sweden Clinical Center ; Finland Clinical Center ; Germany Clinical Center ; Georgia/Florida Clinical Center ; for the TEDDY Study Group ; SNP Laboratory ; RNA Laboratory and Gene Expression Laboratory ; Microbiome and Viral Metagenomics Laboratory ; Metabolomics Laboratory ; HbA1c Laboratory ; HLA Reference Laboratory ; OGTT Laboratory ; Proteomics Laboratory ; Repository. / Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. In: JAMA Pediatrics. 2016 ; Vol. 170, No. 1. pp. 20-28.
@article{d388d96c95c84da2bc321e83d7771c30,
title = "Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study",
abstract = "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.",
author = "{Dietary Biomarkers Laboratory} and {Project Scientist} and {Other contributors} and {Autoantibody Reference Laboratories} and {Cortisol Laboratory} and {Data Coordinating Center} and {Pennsylvania Satellite Center} and {Washington Clinical Center} and {Sweden Clinical Center} and {Finland Clinical Center} and {Germany Clinical Center} and {Georgia/Florida Clinical Center} and {for the TEDDY Study Group} and {SNP Laboratory} and {RNA Laboratory and Gene Expression Laboratory} and {Microbiome and Viral Metagenomics Laboratory} and {Metabolomics Laboratory} and {HbA1c Laboratory} and {HLA Reference Laboratory} and {OGTT Laboratory} and {Proteomics Laboratory} and Repository and Ulla Uusitalo and Xiang Liu and Jimin Yang and Aronsson, {Carin Andr{\'e}n} and Sandra Hummel and Martha Butterworth and {\AA}ke Lernmark and Marian Rewers and William Hagopian and She, {Jin Xiong} and Olli Simell and Jorma Toppari and Ziegler, {Anette G.} and Beena Akolkar and Jeffrey Krischer and Norris, {Jill M.} and Virtanen, {Suvi M.} and Kimberly Bautista and Judith Baxter and Ruth Bedoy and Daniel Felipe-Morales and Brigitte Frohnert and Patricia Gesualdo and Michelle Hoffman and Rachel Karban and Edwin Liu and Adela Samper-Imaz and Andrea Steck and Kathleen Waugh and Hali Wright and Desmond Schatz and Jin-Xiong She and Leigh Steed and Jamie Thomas and Katherine Silvis and Michael Haller and Meena Shankar and Eleni Sheehan and Melissa Gardiner and Richard McIndoe and Ashok Sharma and Joshua Williams and Gabriela Foghis and Anderson, {Stephen W.} and Richard Robinson and Andreas Beyerlein and Ezio Bonifacio and Michael Hummel and McIndoe, {Richard A} and Sharma, {Ashok Kumar}",
year = "2016",
month = "1",
doi = "10.1001/jamapediatrics.2015.2757",
language = "English (US)",
volume = "170",
pages = "20--28",
journal = "JAMA Pediatrics",
issn = "2168-6203",
publisher = "American Medical Association",
number = "1",

}

TY - JOUR

T1 - Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study

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 - 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 - 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 - She, Jin-Xiong

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 - McIndoe, Richard A

AU - Sharma, Ashok Kumar

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

UR - http://www.scopus.com/inward/citedby.url?scp=84954121518&partnerID=8YFLogxK

U2 - 10.1001/jamapediatrics.2015.2757

DO - 10.1001/jamapediatrics.2015.2757

M3 - Article

C2 - 26552054

AN - SCOPUS:84954121518

VL - 170

SP - 20

EP - 28

JO - JAMA Pediatrics

JF - JAMA Pediatrics

SN - 2168-6203

IS - 1

ER -