Growing research points to the importance of environmental variables in the etiology of inflammatory bowel disease (IBD). Researchers say that close to 7 million people around the world have the condition, and that number is likely to rise over the next 10 years.

The use of antibiotics is one factor linked to IBD risk in younger people, but it’s unclear if this relationship holds true for older individuals.

To investigate this further, researchers used national medical data from 2000 to 2018 for Danes aged 10 and older who had not been diagnosed with inflammatory bowel disease.

They especially wanted to determine whether the kind of antibiotic and the timing and dosage of the antibiotic could be factors in the development of IBD.

The survey included more than 6.1 million participants, slightly over half of whom were female. Between 2000 and 2018, 5.5 million people (91%) were given at least one course of antibiotics.

About 36,017 cases of ulcerative colitis and 16,881 cases of Crohn’s disease were identified during this time frame.

Regardless of age, using these drugs was generally linked to an increased risk of developing IBD compared to not using antibiotics. But the largest risk was linked to a later age.

IBD diagnoses were 28% more common in those aged 10 to 40, 48% more common in people aged 40 to 60, and 47% more common in people over 60.

The chances for Crohn’s disease were 40% among 10 to 40-year-olds, 62% among 40 to 60-year-olds, and 51% among those over 60, which were somewhat higher than the risks for ulcerative colitis.

According to age band, the risk seemed to be cumulative, increasing by 11%, 15%, and 14% with each additional course.

The risk for individuals who had five or more courses of antibiotics was found to be the greatest of all: 10 to 40-year-olds had a 69% increased risk, 40 to 60-year-olds had a doubling in risk, and those beyond 60 had a 95% increased risk.

Another factor that seemed to be important was timing; IBD risk peaked 1-2 years after antibiotic exposure, and then began to decline each year following that.

In particular, the risk of IBD was 40% greater among those aged 10 to 40 1-2 years after using antibiotics compared to 13% 4-5 years later. For those over 60, the similar numbers were 63% vs. 22% and 66% vs. 21% for people aged 40 to 60.

Regarding antibiotic class, nitroimidazoles and fluoroquinolones, which are often used to treat gut infections, were linked to the greatest risk of inflammatory bowel disease (IBD). These antibiotics are called “broad spectrum” because they kill all microbes, not just the ones that make people sick.

Nitrofurantoin was the only type of antibiotic that did not increase the risk of IBD at any age.

Although considerably less so, narrow spectrum penicillins were also linked to IBD. This supports the idea that changes in the gut microbiome may play a key role and that many antibiotics may change the kinds of microbes in the gut.

Since this was just an observational research, no causal relationships could be determined. The researchers point out that there was no information on the purpose of the drugs or how many of them patients actually took.

However, they indicate that there are reasonable scientific reasons for the results, emphasizing the natural decline in resilience and diversity of microorganisms in the gut microbiome associated with age, which antibiotic use is likely to exacerbate.

“Furthermore, with repeated courses of antibiotics, these shifts can become more pronounced, ultimately limiting recovery of the intestinal microbiota,” they write.

Source: 10.1136/gutjnl-2022-327845

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