Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Gastroenterology. 2019 Jun;156(8):2217-2229. doi: 10.1053/j.gastro.2019.02.039. Epub 2019 Mar 2.
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.
背景与目的：除了遗传变异和饮食中的麸质，肠道微生物群也被认为与乳糜泻的发病机制有关。肠道微生物群受全身抗生素的影响很大，尤其是在生命早期。我们探讨了生命第一年接触全身性抗生素与乳糜泻诊断风险之间的关联。
方法：我们进行了一项观察性的全国范围内基于登记的队列研究。我们纳入了丹麦 1995 年至 2012 年期间或挪威 2004 年至 2012 年期间出生的所有儿童。在丹麦出生的儿童被随访至 2015 年 5 月 8 日（随访结束时年龄为 2.3-20.3 岁），在挪威出生的儿童被随访至 2013 年 12 月 31 日（随访结束时年龄为 1-10 岁）。我们从超过 170 万儿童中收集了医疗信息，其中包括 3346 例乳糜泻诊断病例。生命第一年接受全身抗生素治疗的定义为接受全身抗生素治疗。
结果：在丹麦和挪威队列中，生命第一年接受全身抗生素治疗与乳糜泻诊断呈正相关（合并比值比 1.26，95%置信区间 1.16-1.36）。我们发现，随着所开抗生素数量的增加，乳糜泻的风险呈剂量依赖性增加（每增加一种抗生素的比值比为 1.08，95%置信区间 1.05-1.11）。没有特定类型的抗生素或生命第一年的特定年龄阶段是突出的。在调整生命第一年因传染病住院的情况下，该估计值没有改变；在两个大子队列中，调整儿童母亲报告的感染数量后，关联略有下降（合并比值比 1.18，95%置信区间 0.98-1.39）。
结论：在丹麦和挪威的儿童全国性研究中，我们发现生命第一年接受全身抗生素治疗与乳糜泻的后期诊断有关。这些发现表明，儿童时期接触全身抗生素可能是乳糜泻的一个危险因素。
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