Antibiotic use as a risk factor for inflammatory bowel disease across the ages

BMJ Journals: Gut: Published on March, 2023

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the bowel, comprising two main subtypes: Crohn’s disease (CD) and ulcerative colitis (UC).

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

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

TAKE-HOME MESSAGE

In this study, a population-based cohort of residents aged ≥10 years was established between 2000 and 2018 using Denmark nationwide registries to assess the impact of antibiotic exposure on IBD risk.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Environmental factors are thought to play a pivotal role in the development of inflammatory bowel disease (IBD).

Antibiotics have been implicated in the development of IBD among younger individuals; however, limited data are available assessing this among adults.

WHAT THIS STUDY ADDS

Antibiotic exposure increased the risk of IBD in all individuals aged ≥10 years, but was highest among those aged 40–60 years and ≥60 years.

A positive dose–response was observed, with highest risk seen in the 1–2 years following exposure, and persisted across antibiotic classes affecting the gastrointestinal microbiome and was associated with the development of both UC and CD.

This finding is showing that antibiotic classes targeting gastrointestinal specific pathogens carry the highest risk for developing IBD.

This risk was highest when using nitroimidazole or fluoroquinolones, which particularly target bacterial pathogens in the gastrointestinal tract, and persisted when evaluating UC and CD separately.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

As a public health measure, antibiotic stewardship may be important to limit the development of multidrug-resistant organisms and also to reduce the risk of IBD and suggests the gastrointestinal microbiome as an important factor in the development of IBD, particularly among older adults.

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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.

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