Antibiotics linked to inflammatory bowel disease

Research published in Gut shows an association between exposure to antibiotics and an increased risk of inflammatory bowel disease (IBD) in everyone aged over 10.
 
The risk was highest in people aged 40 years and older, in the first 1–2 years following antibiotic exposure, and with antibiotics that target gastrointestinal pathogens.
 
Those aged 10–40 who were exposed to antibiotics were 28% more likely to be diagnosed with IBD when compared to people who did not use antibiotics, while 40–60-year-olds were 48% more at risk and over-60s were 47% more likely to develop IBD.
 
Dr Adam Faye, lead researcher and Assistant Professor of Medicine and Population Health at NYU Langone Health, told newsGP he was surprised that the greatest effect was in mid-life.
 
‘Though in context, [it] seems to make sense from prior data … that the environment may play an increasing role in the pathogenesis of IBD as we age,’ he said.
 
He says they believe this is because older adults with new-onset IBD are less likely to have a family history of IBD compared to younger adults with new-onset IBD.
 
‘Also, we think that perhaps, based on some prior data, that the gut microbiome may become less resilient, meaning antibiotics or other changes can induce more lasting changes as we age,’ Dr Faye said.
 
‘[It] also appears that the microbial composition can change over time, with some ageing-related changes showing overlap with microbiomes of patients with IBD, which may explain the results – but this is just a hypothesis, with more data needed.’
 
The US team drew on national medical data from 2000 – 2018 for Danish citizens aged 10 and older who had not been diagnosed with IBD.
 
The study included 6.1 million people, with 5.5 million (91%) prescribed at least one course of antibiotics in that time.
 
There were 36,017 newly diagnosed cases of ulcerative colitis and 16,881 new cases of Crohn’s.
 
‘This study highlights the varying impact of the environment on the development of IBD across the ages,’ Dr Faye said.
 
‘In particular, antibiotics seem to play a larger role in the development of IBD in older adults. Further supporting this notion is that a lower percentage of older adults have a family history of IBD as compared to younger adults, suggesting that environment may play an increasing role in the development of IBD as we age.
 
‘It’s important to consider IBD in older adults with ongoing gastrointestinal symptoms, particularly if there is a history of antibiotic use [but it’s] also important to rule out Clostridium difficile in this context.’
 
Globally, approximately 7 million people have IBD, while in Australia the figure is close to 80,000.
 
In the study, the highest risk of all for IBD was observed in those prescribed five or more courses of antibiotics, with a 69% heightened risk for 10–40-year-olds, over 100% for 40–60-year-olds and 95% for the over 60s.
 
Timing was also influential, with the highest risk for IBD occurring 1–2 years after antibiotic exposure, with each subsequent year associated with a lowering in risk.
 
Dr Faye said they included a one-year lag time to limit the possibility of reverse causality.
 
‘More specifically, we wanted to exclude the possibility of antibiotics being used for undiagnosed IBD symptoms,’ he said.
 
Regarding antibiotic type, the highest risk of IBD was associated with nitroimidazoles such as metronidazole and fluoroquinolones such as ciprofloxacin. Both groups are commonly used to treat gut infections and are broad spectrum.
 
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.
 
‘It’s important to remember that antibiotics, including ones not used to treat gastrointestinal infections, can alter the microbiome,’ Dr Faye said.
 
‘For example, in our study narrow-spectrum penicillins, which are not classically prescribed to treat gastrointestinal infections, were still associated with the development of IBD.’
 
The researchers say this adds weight to the notion that changes in the gut microbiome may have a key role in IBD and that many antibiotics have the potential to alter the make-up of gut microbes.
 
As a gastroenterologist, Dr Faye would like to see future research exploring this field.
 
‘One main area I am interested in is the changing role of the environment on the development of IBD as we age. Determining the environmental factors that contribute to this will be critical for prediction and prevention of IBD, particularly in older adults,’ he said.
 
‘We hypothesise that antibiotics are contributing to the development of IBD through modulation of the intestinal microbiome, but this needs further exploration and research.
 
‘We do not know if the IBD phenotype is different for those who developed IBD in the context of prior antibiotic use, as compared to those who developed IBD and had no prior antibiotic use.’
 
Dr Faye says data looking at lifetime use of antibiotics, from birth on, will also add to what we know by looking at cumulative dosing over time.
 
‘Given the databases have only been operational for 20 years, we do not, as of yet, have that data,’ he said.
 
The World Health Organization recently declared antibiotic-resistance among ‘the global threats of deepest concern,’ and Dr Faye believes this research adds to the impetus for appropriate antibiotic stewardship.
 
‘One of the main take-home messages is not to avoid antibiotics when needed, but in those cases where an illness may be self-limiting,’ he said.
 
He says this is particularly pertinent for viral gastrointestinal or upper respiratory tract infections.
 
‘[Also] empirically prescribing an antibiotic when not indicated may have more harm than benefit,’ Dr Faye said.
 
‘We want patients to improve quickly, so we may be more apt to empirically prescribe an antibiotic in some of these settings, but in addition to exacerbating bacterial resistance patterns, this is another reason to practise antibiotic stewardship.
 
‘In other words, use antibiotics when needed [or] indicated, but be cautious about empirically prescribing for an infection that will likely be self-limiting or is more likely viral in nature.’
 
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