Higher risk of IBD after antibiotics

Antibiotics have been associated with an increased risk of inflammatory bowel disease (IBD), particularly in people aged 40 or older, in a population-based study conducted in Denmark.

In over 6 million people followed for approximately 19 years, antibiotic use was associated with an almost 50% increase in the incidence of IBD in people aged 40-60 years (IRR 1.48, 95% CI 1.43-1.54) and over 60 years (IRR 1.47, 95% CI 1.42-1.53) compared to no antibiotic exposure.

A positive dose-response relationship was observed in all age groups, but with a lower excess incidence risk of 28% for 10-40 year olds (IRR 1.28, 95% CI 1.25- 1.32), researchers led by Adam Faye, MD, of NYU Langone Health in New York, reported online in the journal Intestine.

Similar results were observed for ulcerative colitis and Crohn’s disease. Notably, “the highest risk of developing IBD was observed 1-2 years after exposure to antibiotics and after use of classes of antibiotics often prescribed to treat gastrointestinal pathogens,” Faye wrote. and his colleagues.

Changes in the gut microbial environment as people age can lead to decreased diversity and greater susceptibility to disruption, the researchers explained. Antibiotics can make these age-related changes worse, further reducing microbiome diversity and potentially leading to lasting changes in the gut, they said.

“The association between antibiotic exposure and the development of IBD underscores the importance of responsible antibiotic stewardship as a public health measure,” Faye and colleagues said, “and suggest that the gastrointestinal microbiome is an important factor in the development of IBD, especially in the elderly.”

In an email to MedPage todayFaye elaborated on these ideas: “One of the main points to remember is not to avoid antibiotics when needed, but in cases where a disease may be self-limiting (for example, gastrointestinal or respiratory superior, especially viral, for example), empirically prescribing an antibiotic (when not indicated) may do more harm than good.”

“We hypothesize that antibiotics contribute to the development of IBD through modulation of the gut microbiome, but this requires further exploration and research,” Faye explained. “Older adults in particular have a positive family history for IBD less often, suggesting that the environment may play an increasing role in the pathogenesis of IBD as we age. Determining contributing factors will also part of our future research.”

Faye’s group used national registers, including the Danish National Patient Register and the National Prescription Register, to identify a cohort of 6,104,245 people aged 10 and older who had not been diagnosed with IBD. . Half of the cohort was female.

The researchers followed these people from 2000 to 2018. During this period, 91% received at least one course of antibiotics. There were also 52,898 new cases of IBD (36,107 ulcerative colitis and 16,881 Crohn’s disease). Faye’s group used Poisson regression to calculate IBD incidence rate ratios following antibiotic exposure. They were adjusted for age, sex, and other demographic and socioeconomic factors.

“In addition, our study is unique in that it adjusts for the use of proton pump inhibitors, as well as the use of antifungal and antiviral agents, all of which can affect the microbiome. intestinal,” the study authors noted. They also adjusted previous antibiotic courses, which allowed for more accurate risk assessment for different classes of antibiotics, they said.

Two classes commonly used to target gastrointestinal pathogens – nitroimidazoles and fluoroquinolones – were associated with the highest risk of IBD. In people aged 60 and over, for example, exposure to nitroimidazole was associated with a 61% increased risk (IRR 1.61, 95% CI 1.41-1.83) and fluoroquinolones with an increased risk of 54% (IRR 1.54, 95% CI 1.41-1.69). The only antibiotic that was found not to affect IBD risk was nitrofurantoin.

“Furthermore, although the risk was mitigated among less commonly used antibiotics to target gastrointestinal pathogens (i.e. narrow-spectrum penicillins), their use was still associated with the development of IBD” , the study authors wrote. This finding indicates that many antibiotics, including those not used to treat gastrointestinal pathogens, can affect gut microflora, they said.

When investigators examined the effect of multiple courses of antibiotics, they found a positive dose-response relationship. For patients aged 40-60 years, the risk increased by 15% for each additional antibiotic treatment (IRR 1.15, 95% CI 1.14-1.16). For patients aged 60 and over who had completed five or more courses, the risk was almost double that of unexposed people (IRR 1.95, 95% CI 1.85-2.04).

The highest IBD risk occurred 1-2 years after antibiotic exposure, and it decreased each year. For people aged 40 to 60, for example, the risk was high at 66% at 1 or 2 years (IRR 1.66, 95% CI 1.59-1.73) but 21% at 4 or 5 years after exposure (IRR 1.21, 95% CI 1.13 -1.29).

An important limitation of the study noted by the authors was that the registers used did not contain information on the indication for which the antibiotics were prescribed or the pathogens targeted. Therefore, it is possible that the underlying infections themselves are driving the risk of IBD rather than the drugs, they said.

“In order to further our understanding of the underlying pathophysiology, future research should build on this work, investigating changes in the gut microbiome resulting from antibiotic use associated with the development of IBD.” they concluded.