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Open Access Highly Accessed Research article

Antibiotic exposure and the development of coeliac disease: a nationwide case–control study

Karl Mårild12*, Weimin Ye3, Benjamin Lebwohl4, Peter HR Green4, Martin J Blaser5, Tim Card6 and Jonas F Ludvigsson17

Author affiliations

1 Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden

2 Astrid Lindgren Children’s Hospital, Solna, Sweden

3 Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden

4 Celiac Disease Center, Department of Medicine, Columbia University Medical Center, Columbia University, New York, USA

5 Department of Medicine, New York University Langone Medical Center, New York, USA

6 Division of Epidemiology and Public Health, University of Nottingham, Nottingham City Hospital, Nottingham, UK

7 Department of Paediatrics, Örebro University Hospital, Örebro, Sweden

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Citation and License

BMC Gastroenterology 2013, 13:109  doi:10.1186/1471-230X-13-109

Published: 8 July 2013

Abstract

Background

The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce.

Methods

In this population-based case–control study we linked nationwide histopathology data on 2,933 individuals with CD (Marsh stage 3; villous atrophy) to the Swedish Prescribed Drug Register to examine the association between use of systemic antibiotics and subsequent CD. We also examined the association between antibiotic use in 2,118 individuals with inflammation (Marsh 1–2) and in 620 individuals with normal mucosa (Marsh 0) but positive CD serology. All individuals undergoing biopsy were matched for age and sex with 28,262 controls from the population.

Results

Antibiotic use was associated with CD (Odds ratio [OR] = 1.40; 95% confidence interval [CI] = 1.27-1.53), inflammation (OR = 1.90; 95% CI = 1.72–2.10) and normal mucosa with positive CD serology (OR = 1.58; 95% CI = 1.30–1.92). ORs for prior antibiotic use in CD were similar when we excluded antibiotic use in the last year (OR = 1.30; 95% CI = 1.08-1.56) or restricted to individuals without comorbidity (OR = 1.30; 95% CI = 1.16 – 1.46).

Conclusions

The positive association between antibiotic use and subsequent CD but also with lesions that may represent early CD suggests that intestinal dysbiosis may play a role in the pathogenesis of CD. However, non-causal explanations for this positive association cannot be excluded.

Keywords:
Celiac; Inflammation; Microbiota; Population-based case–control study