title: Antibiotic exposure and the development of coeliac disease: a nationwide case-control study.
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.
authors.affiliation: Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden. karlmarild@gmail.com
authors.forename: Karl
authors.initials: K
authors.lastname: Mårild
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lebwohl
authors.forename: Peter H R
authors.initials: PH
authors.lastname: Green
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blaser
authors.forename: Tim
authors.initials: T
authors.lastname: Card
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Ludvigsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D016022:Case-Control Studies; D002446:Celiac Disease / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004751:Enteritis / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D005903:Gliadin / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000382:microbiology / Q000473:pathology*; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D011503:Transglutaminases / Q000276:immunology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins