An observational study conducted in Denmark suggests that frequent use of antibiotics may heighten the risk of inflammatory bowel disease (IBD), researchers reported yesterday in the journal Gut.
The study, which included data on more than 6 million Danish citizens ages 10 and older, found that antibiotic exposure was associated with an increased risk of IBD compared with no antibiotic exposure for all age-groups. The risk was highest among those aged 40 and older, increased with cumulative antibiotic exposure, and was highest following the use of antibiotics commonly used for gastrointestinal pathogens, the researchers found.
The study authors say the findings provide further evidence that antibiotics affect the microbial environment in the gut in way that affects gastrointestinal health.
Risk increases with age, antibiotic courses
Genetics, family history, and environmental factors are all thought to play a crucial role in IBD and its two main subtypes, Crohn's Disease and ulcerative colitis, which affect close to 7 million people globally. In addition, a previous study in Denmark found that antibiotic use in early life was associated with increased risk of IBD in Danish children.
To see if that association extended to other age-groups, a team of researchers from the United States and Denmark used three nationwide Danish registries—the Danish Civil Registration System, the Danish National Prescription Register, and the Danish National Patient Register—to identify people ages 10 and over who had been diagnosed with IBD from 2000 to 2018 and their exposure to antibiotics. All individuals were followed until IBD diagnosis, emigration, or death.
The researchers also investigated whether there was a dose-response relationship between antibiotic exposure and the development of IBD, the impact of antibiotic timing, and the role of different antibiotic classes in development of IBD.
A total of 6,104,245 people (50.4% female) were included in the cohort, and 90.9% received at least one course of antibiotics over the study period. During follow-up, 36,017 new case of ulcerative colitis and 16,881 courses of Crohn's disease were recorded, for a total of 52,898 new cases of IBD.
Adjusting for age, sex, socioeconomic status, and use of proton pump inhibitors (which reduce stomach acid and can also alter the microbiome and may increase the risk of IBD), the researchers found that any antibiotic exposure was associated with a 28% increased risk of IBD in individuals aged 10 to 40 years compared with no antibiotic exposure (incidence rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.25 to 1.32). The risk was significantly higher for the 40- to 60-year age-group (IRR, 1.48; 95% CI, 1.43 to 1.54) and for those aged 60 and older (IRR, 1.47; 95% CI, 1.42 to 1.53).
The assessment of the dose-response relationship found that each subsequent antibiotic course received was associated with additional risk for each age-group, with the highest risk observed among adults over 60 who'd received five or more courses of antibiotics (IRR, 2.23; 95% CI, 1.85 to 2.04).
"Our results demonstrate a positive dose–response, highlighting the strong association between antibiotic exposure and the development of IBD, particularly among adults aged 40 years and older," the researchers wrote.
The highest risk for developing IBD was 1 to 2 years after exposure for all age-groups. The risk declined with each subsequent year after exposure.
The antibiotic classes with the highest risk for the development of IBD were nitroimidazoles and fluoroquinolones, which are both commonly used to treat gastrointestinal infections. The only antibiotic found not to be associated with IBD was nitrofurantoin, which has less of an impact on gastrointestinal flora.
Our results demonstrate a positive dose–response, highlighting the strong association between antibiotic exposure and the development of IBD, particularly among adults aged 40 years and older
Similar results were observed when the researchers conducted separate analyses for antibiotic exposure and development of Crohn's disease and ulcerative colitis.
Age-related gut changes may be compounded
When lead study author Adam Faye, MD, of NYU Grossman School of Medicine, presented a subset of the findings at the Digestive Disease Week conference in May 2022, he said the findings were an indication of the potential negative impact that antibiotics can have on the gut microbiome—the collection of bacteria and other microorganisms that inhabit the gastrointestinal tract.
"Maybe there's something in the microbiome that antibiotics are doing that's priming an individual to then later develop inflammatory bowel disease, and this really needs to be looked at further," Faye said in a media briefing.
Faye and his co-authors suggest that the impact of antibiotics on the microbiome may be even greater in older people, because as people age, the microbial environment in the gut become less diverse and may be even more susceptible to perturbations.
"These aging-related changes can be compounded by antibiotic use, which further deprives the gut microbiome of diversity, and has the potential to lead to longstanding microbial changes," they wrote, adding that the changes can become more pronounced with repeated course of antibiotics.
They also say that the findings, though they don't establish that antibiotic exposure causes IBD, provide another argument for judicious antibiotic use.
"The association between antibiotic exposure and the development of IBD underscores the importance of antibiotic stewardship as a public health measure," they wrote.