Dataset Information

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.

SUBMITTER: Marild K

PROVIDER: S-EPMC3720284 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mårild Karl K Ye Weimin W Lebwohl Benjamin B Green Peter H R PH Blaser Martin J MJ Card Tim T Ludvigsson Jonas F JF

BMC gastroenterology 20130708

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 23834758

Similar Datasets

Project description:Antibiotics disrupt human microbiota and have been associated with several pediatric autoimmune diseases. Psoriasis activity has been linked to group A streptococcal and viral infections.To determine whether antibiotic exposure and infections are independently associated with incident psoriasis in children.This nested case-control study used data from the Health Improvement Network database, a population-representative electronic health records database from the United Kingdom, from June 27, 1994, through January 15, 2013. Data were analyzed from September 17, 2014, through August 12, 2015. Children aged 1 to 15 years with newly diagnosed psoriasis (n = 845) were compared with age- and sex-matched controls (n = 8450) randomly chosen at the time of psoriasis diagnosis from general practices with at least one case, excluding children with immunodeficiency, inflammatory bowel disease, and juvenile arthritis.Systemic antibacterial prescriptions and infections of the skin and other sites within 2 years before psoriasis diagnosis.Incident psoriasis as determined by validated diagnostic codes. The association of antibiotic exposure and infections with incident psoriasis was determined by conditional logistic regression, adjusting for confounders.After adjusting for matching, country, socioeconomic deprivation, outpatient visits, and infections within the past 2 years, antibiotic exposure in the last 2 years was weakly associated with incident psoriasis (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.5). The associations for infections of skin (aOR, 1.5; 95% CI, 1.2-1.7) and other sites (aOR, 1.3; 95% CI, 1.1-1.6) were similar. Untreated nonskin infections (aOR, 1.5; 95% CI, 1.3-1.8) but not antibiotic-treated nonskin infections (aOR, 1.1; 95% CI, 0.9-1.4) were associated with psoriasis. Results were similar when using a lifetime exposure window. Different classes of antibiotics and age of first antibiotic exposure were also not associated with psoriasis. The findings did not substantively change when excluding periods of varying length before diagnosis.Infections are associated with the development of pediatric psoriasis, but antibiotics do not appear to contribute substantially to that risk.

Project description:ObjectiveTo determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease.DesignCase-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016.SettingNorwegian population.ParticipantsChildren carrying the HLA genotype DR4-DQ8/DR3-DQ2 conferring increased risk of coeliac disease.ExposuresEnterovirus and adenovirus detected using real time polymerase chain reaction in monthly stool samples from age 3 to 36 months.Main outcome measureCoeliac disease diagnosed according to standard criteria. Coeliac disease antibodies were tested in blood samples taken at age 3, 6, 9, and 12 months and then annually. Adjusted odds ratios from mixed effects logistic regression model were used to assess the relation between viral infections before development of coeliac disease antibodies and coeliac disease.ResultsAmong 220 children, and after a mean of 9.9 (SD 1.6) years, 25 children were diagnosed as having coeliac disease after screening and were matched to two controls each. Enterovirus was found in 370 (17%) of 2135 samples and was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls (adjusted odds ratio 1.49, 95% confidence interval 1.07 to 2.06; P=0.02). The association was restricted to infections after introduction of gluten. High quantity samples (>100 000 copies/μL) (adjusted odds ratio 2.11, 1.24 to 3.60; P=0.01) and long lasting infections (>2 months) (2.16, 1.16 to 4.04; P=0.02) gave higher risk estimates. Both the commonly detected enterovirus species Enterovirus A and Enterovirus B were significantly associated with coeliac disease. The association was not found for infections during or after development of coeliac disease antibodies. Adenovirus was not associated with coeliac disease.ConclusionsIn this longitudinal study, a higher frequency of enterovirus, but not adenovirus, during early childhood was associated with later coeliac disease. The finding adds new information on the role of viral infections in the aetiology of coeliac disease.

Project description:INTRODUCTION:Haemorheological and haemostatic changes predispose to the development of arterial and venous thrombotic events; however, limited information is available on the status of these changes in coeliac disease (CeD) and inflammatory bowel disease (IBD). In this study, we aim to describe the haemorheological and haemostatic profiles of CeD and IBD patients in a Hungarian cohort of patients to investigate whether any alterations contribute to elevated thrombotic risk. METHODS AND ANALYSIS:This is a case-control study involving newly diagnosed and followed CeD and IBD patients with age-matched and sex-matched non-CeD, non-IBD subjects with an allocation ratio of 1:1:1.After informed consent is obtained, a detailed medical history will be collected, including venous and arterial thrombotic risk factors and medications. Symptoms in CeD patients will be assessed with the Gastrointestinal Symptoms Rating Scale, and disease activity in IBD patients will be determined by disease-specific scores. Dietary adherence will be assessed among CeD patients with a thorough interview together with a measurement of self-reported adherence, dietary knowledge and urine analysis (detection of gluten immunogenic peptides). In addition to routine laboratory parameters, haemorheological (ie, erythrocyte deformability and aggregation, viscosity of whole blood and plasma) and haemostatic parameters (eg, protein C, protein S and antithrombin) with immunological indicators (ie, coeliac-specific serology and antiphospholipid antibodies) will be measured from venous blood for every participant.Primary and secondary outcomes will be haemorheological and haemostatic parameters, respectively. Univariate and multivariate statistics will be used to compare CeD and IBD patients to control subjects. Subgroup analysis will be performed by disease type in IBD, (Crohn's disease and ulcerose colitis), dietary adherence in CeD, and disease activity in IBD and CeD. ETHICS AND DISSEMINATION:The study was approved by the Regional and Local Research Ethics Committee, University of Pécs (Ref. No. 6917). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER:ISRCTN49677481.

Project description:BackgroundUse of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study.MethodsIn this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD.FindingsWe identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79-1·98) for diagnosis of incident IBD, 1·74 (1·64-1·85) for ulcerative colitis, and 2·27 (2·06-2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07-1·15), two antibiotic dispensations (1·38, 1·32-1·44), and three or more antibiotic dispensations (1·55, 1·49-1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40-1·54) and Crohn's disease (1·64, 1·53-1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28-1·43) for patients who had received three or more dispensations, compared with general population controls.InterpretationHigher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD.FundingNational Institutes of Health. Crohn's and Colitis Foundation.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets