Antibiotic exposure and the development of coeliac disease: A nationwide case-control study

Karl Mårild, Weimin Ye, Benjamin Lebwohl, Peter H.R. Green, Martin J. Blaser, Tim Card, Jonas F. Ludvigsson

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Article number109
JournalBMC Gastroenterology
Volume13
Issue number1
DOIs
StatePublished - Jul 8 2013

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Celiac Disease
Case-Control Studies
Anti-Bacterial Agents
Odds Ratio
Confidence Intervals
Wetlands
Serology
Mucous Membrane
Dysbiosis
Inflammation
Population
Atrophy
Comorbidity
Biopsy

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Keywords

  • Celiac
  • Inflammation
  • Microbiota
  • Population-based case-control study

Cite this

Mårild, Karl ; Ye, Weimin ; Lebwohl, Benjamin ; Green, Peter H.R. ; Blaser, Martin J. ; Card, Tim ; Ludvigsson, Jonas F. / Antibiotic exposure and the development of coeliac disease : A nationwide case-control study. In: BMC Gastroenterology. 2013 ; Vol. 13, No. 1.
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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.",
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Antibiotic exposure and the development of coeliac disease : A nationwide case-control study. / Mårild, Karl; Ye, Weimin; Lebwohl, Benjamin; Green, Peter H.R.; Blaser, Martin J.; Card, Tim; Ludvigsson, Jonas F.

In: BMC Gastroenterology, Vol. 13, No. 1, 109, 08.07.2013.

Research output: Contribution to journalArticle

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T1 - Antibiotic exposure and the development of coeliac disease

T2 - A nationwide case-control study

AU - Mårild, Karl

AU - Ye, Weimin

AU - Lebwohl, Benjamin

AU - Green, Peter H.R.

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N2 - 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.

AB - 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.

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