Most studies to date have assessed a link between antibiotics and IBD in younger patients, lead researcher Adam S. Faye, MD, said during a media briefing that previewed select research for the annual Digestive Disease Week® (DDW).
The impact of antibiotic use on the incidence of IBD in older adults is really unknown, he added.
In contrast to younger people with IBD, who tend to have a strong family history or genetic predisposition to developing Crohn’s disease or ulcerative colitis, the cause is likely different in older populations.
“There’s clearly something in the environment that’s driving this new older-onset IBD,” said Dr. Faye, who is an assistant professor of medicine and population health at New York University.
Antibiotics as a contributing link
Dr. Faye and colleagues took a closer look at antibiotics as contributing to this link. They studied 2.3 million patient records in Denmark’s national medical registry from 2000 to 2018. They identified people aged 60 years and older who were newly diagnosed with IBD, and they then assessed the number, frequency, and timing of any antibiotic prescriptions.
They found that IBD was 27% more likely in this age group if the patients had received any antibiotic prescription.
They also found that the chance of developing IBD was higher as the number of antibiotic prescriptions increased. For example, IBD was 55% more likely if a person had received two prescriptions, and it was 96% more likely with four prescriptions. The risk really jumped with five or more antibiotic prescriptions – a person with this many prescriptions was more than 2.3 times (236%) more likely to be diagnosed with IBD than those who had not been prescribed antibiotics in the prior 5 years.
Not all antibiotics were equal, however. For example, the investigators found no link with nitrofurantoin, an antibiotic commonly prescribed for urinary tract infections. In contrast, all other antibiotic agents that were evaluated, and especially fluoroquinolones, nitroimidazoles, and macrolides, were associated with IBD.
Timing made some difference.
“The risk was highest if antibiotics were prescribed within the 1- to 2-year period before diagnosis, and it declined as you go farther out. But the risks persist,” Dr. Faye said. He noted that they even found that risk was elevated 10 years out.
The investigators also considered whether the antibiotic agent or infection was behind the association.
Dr. Faye cited previous research, again in younger people with IBD, that revealed that “infections plus antibiotics substantially increase the odds or risk of developing IBD more than the infection alone.
“So there really does seem to be something that the antibiotics are doing here,” Dr. Faye said.
A leading theory is that antibiotics disrupt the gut microbiota and increase the risk for developing IBD. “But, obviously, it’s quite complicated,” he said.
Clinical implications
The findings suggest that older people who may have IBD should be screened for prior antibiotic use, Dr. Faye said.
“This is a result that really has important implications for diagnosing older adults with new gastrointestinal symptoms,” he said. “Inflammatory bowel disease often can be overlooked in older adults because there’s a lot of different diagnoses you’re thinking of.”
IBD “should be considered, especially if you have a patient who’s reporting multiple courses of antibiotics in the last few years,” he added.
The results suggest another reason that antimicrobial stewardship programs should promote judicial use of these agents beyond concerns about resistance.
“We think of antibiotic stewardship to prevent the development of multidrug-resistant organisms, but we should be thinking about it to also prevent the development of inflammatory bowel disease,” Dr. Faye said.
Although this study adds to the evidence implicating antibiotics and expands the concept to an older population, “we really don’t have a great handle on what all of the environmental and other factors are,” he said.
Some researchers point to smoking and diet, among other factors, but the interplay remains unknown, Dr. Faye added.
The study is important because the incidence of IBD is increasing within the older population, “and this is one of the first studies to look at it,” he said.
Dr. Faye and colleagues plan to start a new study to evaluate other environmental factors.
“Hopefully, we’ll have more within the next few years to report,” he said.
Shedding more light on older-onset IBD worldwide
“It’s a well-done study,” Aline Charabaty, MD, said in a comment. “We are seeing that there’s an increase of incidence of IBD in the entire population, but even more so in the elderly.”
IBD is likely caused by a combination of factors, including genetics, environmental influences, and dysfunction of the gut immune system, agreed Dr. Charabaty, who is an assistant clinical professor in the division of gastroenterology at Johns Hopkins University, Baltimore.
The research “goes along with other studies that we’ve done in the pediatric and adult populations that show antibiotics exposure increases the risk of developing inflammatory bowel disease,” she said.
For a broader perspective of the study’s findings, Dr. Faye was asked during the media briefing if the results of this Danish registry study would be generalizable to the U.S. population.
“The simplest answer is we’ll need to redo this study within the U.S. to make absolutely sure,” Dr. Faye said. She noted that prior studies in the United States and elsewhere have found a risk associated with antibiotics, although again these studies focused on younger patients.
Dr. Charabaty was more certain that the findings were meaningful outside of Denmark.
“I definitely think this will apply to our U.S. population,” added Dr. Charabaty, who is also the clinical director of the IBD Center at Johns Hopkins–Sibley Memorial Hospital, Washington. “We have very similar practices in terms of how we approach antibiotic use.
“This could be one of the risk factors that’s promoting an increase in IBD everywhere,” she added.
The study was conducted in partnership with the Danish National Center of Excellence PREDICT Program. Dr. Faye and Dr. Charabaty did not report any conflicts of interest related to this study.
A version of this article first appeared on Medscape.com.