Ulla Uusitalo1, Xiang Liu1, Jimin Yang1, Carin Andrén Aronsson2, Sandra Hummel3, Martha Butterworth1, Åke Lernmark2, Marian Rewers4, William Hagopian5, Jin-Xiong She6, Olli Simell7, Jorma Toppari8, Anette G Ziegler3, Beena Akolkar9, Jeffrey Krischer1, Jill M Norris10, Suvi M Virtanen11. 1. Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa. 2. Department of Clinical Sciences, Lund University, Malmö, Sweden. 3. Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München and Forschergruppe Diabetes e.V., Munich, Germany. 4. Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora. 5. Pacific Northwest Diabetes Research Institute, Seattle, Washington. 6. Medical College of Georgia, Georgia Regents University, Augusta. 7. Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland. 8. Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland8Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland. 9. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 10. Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora. 11. National Institute for Health and Welfare, Nutrition Unit, Helsinki, Finland12School of Health Sciences and Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland 13The Science Center of Pirkanmaa Hospita.
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, 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.
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.
Authors: A Kilkkinen; S M Virtanen; T Klaukka; M G Kenward; M Salkinoja-Salonen; M Gissler; M Kaila; A Reunanen Journal: Diabetologia Date: 2005-12-13 Impact factor: 10.122
Authors: Ezio Bonifacio; Liping Yu; Alastair K Williams; George S Eisenbarth; Polly J Bingley; Santica M Marcovina; Kerstin Adler; Anette G Ziegler; Patricia W Mueller; Desmond A Schatz; Jeffrey P Krischer; Michael W Steffes; Beena Akolkar Journal: J Clin Endocrinol Metab Date: 2010-05-05 Impact factor: 5.958
Authors: John Penders; Carel Thijs; Cornelis Vink; Foekje F Stelma; Bianca Snijders; Ischa Kummeling; Piet A van den Brandt; Ellen E Stobberingh Journal: Pediatrics Date: 2006-08 Impact factor: 7.124
Authors: William A Hagopian; Henry Erlich; Ake Lernmark; Marian Rewers; Anette G Ziegler; Olli Simell; Beena Akolkar; Robert Vogt; Alan Blair; Jorma Ilonen; Jeffrey Krischer; JinXiong She Journal: Pediatr Diabetes Date: 2011-05-12 Impact factor: 3.409
Authors: Erkki Savilahti; Taina Härkönen; Emma M Savilahti; Kaarina Kukkonen; Mikael Kuitunen; Mikael Knip Journal: Diabetologia Date: 2018-09-20 Impact factor: 10.122
Authors: Laura M Jacobsen; Brittney N Newby; Daniel J Perry; Amanda L Posgai; Michael J Haller; Todd M Brusko Journal: Curr Diab Rep Date: 2018-08-30 Impact factor: 4.810
Authors: Mehmet Kanbay; Emine M Onal; Baris Afsar; Tuncay Dagel; Aslihan Yerlikaya; Adrian Covic; Nosratola D Vaziri Journal: Int Urol Nephrol Date: 2018-05-04 Impact factor: 2.370