Boston—More frequent use of antibiotics, especially broad-spectrum types, is associated with higher risk of developing inflammatory bowel disease (IBD), according to a new study.

That is the case with both ulcerative colitis and Crohn’s disease, according to the report in The Lancet Gastroenterology & Hepatology.
Researchers from Harvard Medical School and Karolinska Institutet in Sweden point out that the association remained when patients were compared with their siblings. They also emphasize that IBD is becoming more common, especially in Europe, the United States and other countries where antibiotic use is more frequent. 

The study says that concern is growing that that antibiotics might permanently alter fragile microbial communities in the gut, leading to gastrointestinal disease.

“I think this affirms what many of us have suspected—that antibiotics, which adversely affect gut microbial communities, are a risk factor for IBD,” said lead author, Long Nguyen, DO, of Massachusetts General Hospital and Harvard Medical School. “However, despite this compelling rationale and seemingly intuitive presumption, there have been no population-scale investigations to support this hypothesis until now.”

Background information in the articles notes that use of antibiotics in early life has been linked with childhood IBD, but data for adults are mixed. The goal of the current researchers was to investigate the association between antibiotic therapy and IBD in a large, population-based study.

For their prospective case-control study, the authors focused on Swedes aged 16 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. Consecutive patients with incident IBD were identified from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study and also cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. 

Ultimately, the focus was on 23,982 new patients with IBD—15,951 with ulcerative colitis, 7,898 Crohn’s disease, 133 unclassified IBD—diagnosed between January 1, 2007, and December 31, 2016. Those patients were compared with 117,827 matched controls, as well as 8,732 siblings who were also identified. 

Researchers report that, 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. 

The study determined that 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,” the authors advise. “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.”

That led to the conclusion that higher cumulative exposure to systemic antibiotic therapy, especially in those with greater spectrum of microbial coverage, appear to be associated with a greater risk of new-onset IBD and its subtypes. 

“Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasize antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD,” the researchers conclude.

“To identify risk factors for IBD is important, and ultimately our aim is to prevent the disease,” added senior author, Professor Jonas F Ludvigsson, MD, PhD, pediatrician at Örebro University Hospital, and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “Our study provides another piece of the puzzle and even more reason to avoid using antibiotics needlessly.”
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