Stine Dydensborg Sander1, Anne-Marie Nybo Andersen2, Joseph A Murray3, Øystein Karlstad4, Steffen Husby5, Ketil Størdal6. 1. Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: stine.dydensborg.sander@rsyd.dk. 2. Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. 4. Department of Non-Communicable Diseases, Norwegian Institute of Public Health, Oslo, Norway. 5. Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 6. Department of Non-Communicable Diseases, Norwegian Institute of Public Health, Oslo, Norway; Department of Pediatrics, Ostfold Hospital Trust, Fredrikstad, Norway.
Abstract
BACKGROUND & AIMS: The intestinal microbiota is believed to be involved in the pathogenesis of celiac disease, in addition to genetic variants and dietary gluten. The gut microbiota is strongly influenced by systemic antibiotics-especially in early life. We explored the association between exposure to a systemic antibiotic in the first year of life and risk of diagnosed celiac disease. METHODS: We performed an observational nationwide register-based cohort study. We included all children born in Denmark from 1995 through 2012 or Norway from 2004 through 2012. Children born in Denmark were followed until May 8, 2015 (age at end of follow-up was 2.3-20.3 years) and children born in Norway were followed until December 31, 2013 (age at end of follow-up was 1-10 years). We collected medical information from more than 1.7 million children, including 3346 with a diagnosis of celiac disease. Exposure to systemic antibiotics was defined as a dispensed systemic antibiotic in the first year of life. RESULTS: Exposure to systemic antibiotics in the first year of life was positively associated with diagnosed celiac disease in the Danish and Norwegian cohorts (pooled odds ratio 1.26, 95% confidence interval 1.16-1.36). We found a dose-dependent relation between an increasing number of dispensed antibiotics and the risk of celiac disease (pooled odds ratio for each additional dispensed antibiotic 1.08, 95% confidence interval 1.05-1.11). No specific type of antibiotic or age period within the first year of life was prominent. Adjustment for hospital admissions with an infectious disease in the first year of life did not change the estimates; adjustment for the number of maternally reported infections in the child in 2 large sub-cohorts decreased the association slightly (pooled odds ratio 1.18, 95% confidence interval 0.98-1.39). CONCLUSION: In a nationwide study of children in Denmark and Norway, we found exposure to systemic antibiotics in the first year of life to be associated with a later diagnosis of celiac disease. These findings indicate that childhood exposure to systemic antibiotics could be a risk factor for celiac disease.
BACKGROUND & AIMS: The intestinal microbiota is believed to be involved in the pathogenesis of celiac disease, in addition to genetic variants and dietary gluten. The gut microbiota is strongly influenced by systemic antibiotics-especially in early life. We explored the association between exposure to a systemic antibiotic in the first year of life and risk of diagnosed celiac disease. METHODS: We performed an observational nationwide register-based cohort study. We included all children born in Denmark from 1995 through 2012 or Norway from 2004 through 2012. Children born in Denmark were followed until May 8, 2015 (age at end of follow-up was 2.3-20.3 years) and children born in Norway were followed until December 31, 2013 (age at end of follow-up was 1-10 years). We collected medical information from more than 1.7 million children, including 3346 with a diagnosis of celiac disease. Exposure to systemic antibiotics was defined as a dispensed systemic antibiotic in the first year of life. RESULTS: Exposure to systemic antibiotics in the first year of life was positively associated with diagnosed celiac disease in the Danish and Norwegian cohorts (pooled odds ratio 1.26, 95% confidence interval 1.16-1.36). We found a dose-dependent relation between an increasing number of dispensed antibiotics and the risk of celiac disease (pooled odds ratio for each additional dispensed antibiotic 1.08, 95% confidence interval 1.05-1.11). No specific type of antibiotic or age period within the first year of life was prominent. Adjustment for hospital admissions with an infectious disease in the first year of life did not change the estimates; adjustment for the number of maternally reported infections in the child in 2 large sub-cohorts decreased the association slightly (pooled odds ratio 1.18, 95% confidence interval 0.98-1.39). CONCLUSION: In a nationwide study of children in Denmark and Norway, we found exposure to systemic antibiotics in the first year of life to be associated with a later diagnosis of celiac disease. These findings indicate that childhood exposure to systemic antibiotics could be a risk factor for celiac disease.
Authors: Rebecca M Lebeaux; Juliette C Madan; Quang P Nguyen; Modupe O Coker; Erika F Dade; Yuka Moroishi; Thomas J Palys; Benjamin D Ross; Melinda M Pettigrew; Hilary G Morrison; Margaret R Karagas; Anne G Hoen Journal: Pediatr Res Date: 2022-05-14 Impact factor: 3.953
Authors: Lucy McDonnell; Alexander Gilkes; Mark Ashworth; Victoria Rowland; Timothy Hugh Harries; David Armstrong; Patrick White Journal: Gut Microbes Date: 2021 Jan-Dec
Authors: Ulla Uusitalo; Carin Andren Aronsson; Xiang Liu; Kalle Kurppa; Jimin Yang; Edwin Liu; Jennifer Skidmore; Christiane Winkler; Marian J Rewers; William A Hagopian; Jin-Xiong She; Jorma Toppari; Anette-G Ziegler; Beena Akolkar; Jill M Norris; Suvi M Virtanen; Jeffrey P Krischer; Daniel Agardh Journal: Nutrients Date: 2019-08-02 Impact factor: 5.717