The risk seems to be cumulative and greatest 1-2 years after use and for those antibiotics targeting gut infections, the findings indicate.

Mounting evidence suggests that environmental factors are likely implicated in the development of inflammatory bowel disease (IBD). Globally, close to 7 million people have the condition, with this number expected to rise over the next decade, say the researchers.

One factor associated with IBD risk in younger people is the use of antibiotics, but it’s not clear if this association might also apply in older people.

To explore this further, the researchers drew on national medical data from 2000 to 2018 for Danish citizens aged 10 upwards who hadn’t been diagnosed with IBD.

They specifically wanted to know if the timing and dose of antibiotic might be important for the development of IBD, and whether this varied by IBD and antibiotic type.

More than 6.1 million people were included in the study, just over half of whom were female. In total, 5.5 million (91%) were prescribed at least one course of antibiotics between 2000 and 2018.

During this period, some 36,017 new cases of ulcerative colitis and 16,881 new cases of Crohn’s disease were diagnosed.

Overall, compared with no antibiotic use, use of these drugs was associated with a higher risk of developing IBD, regardless of age. But older age was associated with the highest risk.

Those aged 10-40 were 28% more likely to be diagnosed with IBD; 40- 60 year olds were 48% more likely to do so, while the over 60s  were 47% more likely to do so.

The risks were slightly higher for Crohn’s disease than they were for ulcerative colitis: 40% among 10-40 year olds; 62% among 40-60 year olds; and 51% among the over 60s.

The risk seemed to be cumulative, with each subsequent course adding an additional 11%, 15%, and 14% heightened risk, according to age band.

The highest risk of all was observed among those prescribed 5 or more courses of antibiotics: 69% heightened risk for 10–40 year olds; a doubling in risk for 40–60 year olds; and a 95% heightened risk for the over 60s.

Timing also seemed to be influential, with the highest risk for IBD occurring 1–2 years after antibiotic exposure, with each subsequent year thereafter associated with a lowering in risk.

Specifically, among 10–40 year olds IBD risk was 40% higher 1–2 years after taking antibiotics compared with 13% 4–5 years later. The equivalent figures for 40–60 year olds were 66% vs 21% and for the over 60s 63% vs 22%.

As to antibiotic type, the highest risk of IBD was associated with the nitroimidazoles and fluoroquinolones, which are usually used to treat gut infections. These are known as broad spectrum antibiotics because they indiscriminately target all microbes, not just those that cause disease.

Nitrofurantoin was the only antibiotic type not associated with IBD risk at any age.

Narrow spectrum penicillins were also associated with IBD, although to a much lesser extent. This adds weight to the notion that changes in the gut microbiome may have a key role and that many antibiotics have the potential to alter the make-up of microbes in the gut.

This is an observational study, and as such, can’t establish cause. Nor was information available on what the drugs were for or how many of them patients actually took, note the researchers.

But there are some plausible biological explanations for the findings, they suggest, highlighting the natural diminution of both the resilience and range of microbes in the gut microbiome associated with aging, which antibiotic use is likely to compound.

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

Limiting prescriptions for antibiotics may not only help to curb antibiotic resistance but may also help lower the risk of IBD, they venture.

“The association between antibiotic exposure and the development of IBD underscores the importance of antibiotic stewardship as a public health measure, and suggests the gastrointestinal microbiome as an important factor in the development of IBD, particularly among older adults,” they conclude.

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“Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods,” the authors said.

Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, ready meals containing food additives, and reconstituted meat and fish products.

These products also often contain high levels of added sugar, fat and salt, but lack vitamins and fiber.

The researchers analyzed detailed dietary information from 116,087 adults aged 35-70 years living in 21 low, middle and high income countries who enrolled in the Prospective Urban Rural Epidemiology (PURE) study.

Subjects enrolled in PURE between 2003 and 2016, and they were evaluated least every three years.

The average follow-up was 9.7 years. During follow-up the researchers recorded new diagnoses of IBD, including Crohn’s disease or ulcerative colitis.

During follow-up, 467 subjects developed IBD, 90 with Crohn’s disease and 377 with ulcerative colitis.

After adjusting for other factors, the researchers reported that higher intake of ultra-processed food was associated with a higher risk of IBD.

Compared to those who consumed less than one serving of ultra-processed food per day, there was an 82% increased risk of IBD among those who consumed five or more servings per day, and a 67% increased risk for 1-4 servings per day.

Various subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher risks of development of  IBD.

Notably, white meat, red meat, dairy, starch, and fruit, vegetables and legumes were not associated with development of IBD.

While this is an observational study so can’t establish causality, the investigators said the findings “support the hypothesis that intake of ultra-processed foods could be an environmental factor that increases the risk of IBD.”

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