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Original Investigation |

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

Ulla Uusitalo, PhD1; Xiang Liu, PhD1; Jimin Yang, PhD, RD1; Carin Andrén Aronsson, MS2; Sandra Hummel, PhD3; Martha Butterworth, MS1; Åke Lernmark, PhD2; Marian Rewers, PhD4; William Hagopian, MD, PhD5; Jin-Xiong She, PhD6; Olli Simell, MD, PhD7; Jorma Toppari, MD, PhD7,8; Anette G. Ziegler, PhD3; Beena Akolkar, PhD9; Jeffrey Krischer, PhD1; Jill M. Norris, PhD10; Suvi M. Virtanen, MD, PhD11,12,13 ; for the TEDDY Study Group
[+] 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
JAMA Pediatr. 2016;170(1):20-28. doi:10.1001/jamapediatrics.2015.2757.
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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.

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Islet Autoimmunity Risk by First Probiotic Exposure Age of the Child
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Infants at Risk of Type 1 Diabetes Maybe Not Only Benefit from Early Probiotics
Posted on November 17, 2015
Li Peng,Jiaqing Shao
Department of Endocrinology, Jinling Hospital/Nanjing General Hospital of Nanjing Military Command
Conflict of Interest: None Declared
Type 1 diabetes is the most frequent autoimmune disease in childhood, leading to disability and even mortality in young adults. The gut immune system play an important role in the development of type 1 diabetes, because that factors control the gut immune system are also regulators of beta-cell autoimmunity. This article found infants at risk of type 1 diabetes benefit from early probiotics influencing the gut microbiota. As we know, human milk contains substances that promote the maturation of the immune system and also influence the gut microbiota, which protect against the onset of type 1 diabetes. Influencing the gut microbiota might be more effective very early in life, before a robust microbiome is established, due to the effect of probiotic exposure or breastfeeding. In this article, the author did not find statistically significant difference between children gave with exclusive breastfeeding at least 3 month or not. Maybe children gave with exclusive breastfeeding during the first 27 days of life or not should also analyze with early exposure to probiotics.
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