Antibiotic Exposure Increases the Risk of New-Onset IBD

Long H. Nguyen, MD

Antibiotic use in early life has been linked to childhood inflammatory bowel disease. However, the data for adults is mixed and often based on smaller investigations that did not compare the risk among siblings with shared genetic or environmental risk factors.

A team, led by Long H. Nguyen, MD, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, investigated the link between antibiotic therapy and inflammatory bowel disease in a large, population-based study.

In the prospective case-control study, the investigators identified 23,982 individuals at least 16 years old with a diagnosis of IBD based on histology and at least 1 diagnosis code for IBD or its subtypes of ulcerative colitis and Crohn’s disease.

Of the patients included in the study, 15,951 had ulcerative colitis, 7898 had Crohn’s disease, and 133 had unclassified IBD. Each patient was diagnosed between 2007-2016.

The investigators identified consecutive patients with incident IBD from the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study and cross-referenced those participants with the Swedish Patient Register and the Prescribed Drug Register.

The team accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients, as well as up to 5 general population controls per patient that were matched on the basis of age, sex, county, and calendar year.

The investigators also included unaffected full siblings as a secondary control group, with a total of 117,827 matched controls and 28,732 sibling controls.

To conduct the final analysis, the investigators used logistic regression to estimate multivariable-adjusted odds rations (aOR) and 95% confidence intervals (95% CI) for the diagnosis of incident inflammatory bowel disease.

After the research team adjusted for several risk factors, the aOR in patients who had used antibiotics compared to those who had never used antibiotics was 1.88 (95% CI, 1.79-1.98) for the diagnosis of incident IBD, 1.74 (95% CI, 1.64-1.85) for ulcerative colitis, and 2.27 (95% CI, 2.06-2.49) for Crohn’s disease.

In addition, the aOR was higher in patients who had received 1 antibiotic dispensation (aOR, 1.11; 95% CI, 1.07-1.15), 2 antibiotic dispensations (aOR, 1.38; 95% CI, 1.32-1.44), and 3 or more antibiotic dispensations (aOR, 1.55; 95% CI, 1.49-1.61) than patients who had none.

There was especially an increased risk for ulcerative colitis (aOR with three or more antibiotic dispensations, 1.47; 95% CI, 1.40–1.54) and Crohn's disease (aOR with three or more antibiotic dispensations , 1.64; 95% CI, 1.53–1.76) with higher estimates corresponding to broad-spectrum antibiotics.

The investigators found similar, but attenuated results 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 3 or more dispensations when compared to the general population controls.

“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 authors wrote. “The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls.”

The investigators said the results warrant longer-term prospective studies in humans or mechanistic preclinical investigators. They also say the results suggest the need to emphasize antibiotic stewardships to prevent the rise in dysbiosis-related chronic diseases, including IBD.

The study, “Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden,” was published online in The Lancet Gastroenterology & Hepatology.