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Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden

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Background

Use 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.

Methods

In 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.

Findings

We 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.

Interpretation

Higher 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.

Funding

National Institutes of Health. Crohn’s and Colitis Foundation.

https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30267-3/fulltext

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