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Original research
Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study
  1. Adam S Faye1,
  2. Kristine Højgaard Allin2,3,
  3. Aske T Iversen2,
  4. Manasi Agrawal2,4,
  5. Jeremiah Faith5,
  6. Jean-Frederic Colombel4,
  7. Tine Jess2,3
  1. 1 NYU Departments of Medicine & Population Health, NYU Grossman School of Medicine, New York, New York, USA
  2. 2 Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
  3. 3 Department of Gastroenterology and Hepatology, Aalborg University, Aalborg, Denmark
  4. 4 The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  5. 5 Icahn School of Medicine at Mount Sinai, New York, New York, USA
  1. Correspondence to Dr Adam S Faye, Medicine/Population Health, NYU Langone Health, New York, NY 10016, USA; adam.faye{at}nyulangone.org

Abstract

Background There is an increasing incidence of inflammatory bowel disease (IBD) for which environmental factors are suspected. Antibiotics have been associated with development of IBD in earlier generations, but their influence on IBD risk in adults is uncertain.

Objective To assess the impact of antibiotic exposure, including dose–response, timing and antibiotic class, on the risk of IBD in all individuals aged ≥10 years.

Design Using Denmark nationwide registries, a population-based cohort of residents aged ≥10 years was established between 2000 and 2018. Incidence rate ratios (IRRs) for IBD following antibiotic exposure were calculated using Poisson regression.

Results There were a total of 6 104 245 individuals, resulting in 87 112 328 person-years of follow-up, and 52 898 new cases of IBD. Antibiotic exposure was associated with an increased risk of IBD as compared with no antibiotic exposure for all age groups, although was greatest among individuals aged 40–60 years and ≥60 years (age 10–40 years, IRR 1.28, 95% CI 1.25 to 1.32; age 40–60 years, IRR 1.48, 95% CI 1.43 to 1.54; age ≥60 years, IRR 1.47, 95% CI 1.42 to 1.53). For all age groups a positive dose–response was observed, with similar results seen for both ulcerative colitis and Crohn’s disease. The highest risk of developing IBD was seen 1–2 years after antibiotic exposure, and after use of antibiotic classes often prescribed to treat gastrointestinal pathogens.

Conclusion Antibiotic exposure is associated with an increased risk of IBD, and was highest among individuals aged 40 years and older. This risk increased with cumulative antibiotic exposure, with antibiotics targeting gastrointestinal pathogens and within 1–2 years after antibiotic exposure.

  • antibiotics
  • inflammatory bowel disease

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Further data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Further data are available upon reasonable request.

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Footnotes

  • Twitter @AdamFayeMD, @KristineAllin, @manasiagrawalmd, @PREDICTIBD

  • Contributors ASF: Conception and design of the study, data analysis and interpretation, drafting and revision of article and final approval. KHA, ATI: Conception and design of the study, acquisition of data, statistical analysis and interpretation of data, revision of article and final approval. MA: Conception and design of the study, data interpretation, revision of article and final approval. JF: Conception of the study, data analysis and interpretation of data, revision of article and final approval. J-FC: Conception and design of the study, data analysis and interpretation of data, revision of article, and final approval. TJ: Conception and design of the study, statistical analysis and interpretation of data, guarantor, revision of the article and final approval.

  • Funding ASF: National Institute of Aging (R03AG078927-01). MA: National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129762-01). TJ: Danish National Research Foundation (grant no. DNRF148).

  • Competing interests ASF: Research support from Crohn’s and Colitis Foundation; consultant for GLG, M3, Janssen, Guidepoint. JF: consultant Vedanta Biosciences and Innovation Pharmaceuticals; Scientific Advisory Board Vedanta Biosciences. JC: research grants from AbbVie, Janssen Pharmaceuticals and Takeda; payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microba, Novartis, PBM Capital, Pfizer, Sanofi, Takeda, TiGenix, Vifor; holds stock options in Intestinal Biotech Development.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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