Antibiotic overuse linked to immune defects and bowel disease
Two new studies have highlighted the importance of judicious antibiotic use. One study found antibiotics can increase a person’s risk of fungal infections by causing defects to immune system activity in the gut, while another study suggests heavy antibiotic use in old age is linked to higher rates of inflammatory bowel diseases such as Crohn’s.
While a great deal of attention has rightly been directed at the growing problem of antibiotic-resistant bacteria, that isn’t the only reason we should be cautious of how often we take a course of these common drugs. Two new studies offer potent reminders that antibiotics are not harmless drugs and should only be taken when necessary.
The first study, an international collaboration between US and UK researchers, wanted to understand why people in hospital treated with antibiotics tend to experience greater rates of fungal infections. The focus was a particularly dangerous fungal infection known as invasive candidiasis.
Many people may be familiar with a common yeast infection known as thrush. This is caused by a fungus called candida. Generally these infections are superficial but in some people they can enter the bloodstream leading to invasive candidiasis.
It has been hypothesized that antibiotics can increase a person’s risk of invasive candidiasis through the gut. But until now it wasn’t clear exactly how that process could be playing out.
Across a series of animal tests the new research first confirmed that antibiotic administration did indeed make fungal infections worse. And the fungal infection was heightened in the gut after antibiotics but it still wasn’t clear what was making the animals so sick.
The researchers discovered the antibiotics were causing an abnormal immune response in the gut which in turn allowed bacteria from the gut to cross over into the bloodstream. This led the animals to suffer from a bacterial and fungal infection at the same time, making them more ill than the animals not treated with antibiotics.
“To figure out why this was happening, we analyzed the immune cells in the gut to figure out how antibiotics caused a defective anti-fungal immune response,” explained lead author Rebecca Drummond in an article for The Conversation. “Immune cells in the gut make small proteins called cytokines that act as messages to other cells. We found that antibiotics lowered the amount of these cytokines in the gut, which we think is part of the reason the antibiotic-treated mice couldn’t control fungal infection in the intestines or stop the bacteria from escaping.”
The researchers subsequently found treating the mice with immune-boosting cytokines could help counteract the harm of antibiotics. This finding points to a potential treatment for those at high-risk of fungal infections but in need of crucial antibiotics.
“We knew that antibiotics make fungal infections worse, but the discovery that bacterial co-infections can also develop through these interactions in the gut was surprising,” said Drummond. “These factors can add up to a complicated clinical situation – and by understanding these underlying causes, doctors will be better able to treat these patients effectively.”
The second study, yet to be published in a peer-reviewed journal but set to be presented at the upcoming Digestive Disease Week conference, found a significant correlation between antibiotic use and the development of inflammatory bowel disease in those over the age of 60 years.
“In older adults, we think that environmental factors are more important than genetics,” said lead researcher Adam Faye, from the NYU Grossman School of Medicine. “When you look at younger patients with new diagnoses of Crohn's disease and ulcerative colitis, there's generally a strong family history. But that is not the case in older adults, so it's really something in the environment that is triggering it.”
To investigate the potential relationship between antibiotic use and the development of inflammatory bowel disease (IBD) the researchers looked at nearly 20 years of health record data encompassing more than two million people between the ages of 60 and 90.
The study found a distinct dose-response relationship between IBD risk and antibiotic use. One course of antibiotics increased a person’s risk of developing IBD within five years by 27 percent; two courses increased the risk by 55 percent; three courses by 67 percent; four courses by 96 percent; and five or more courses increased a person’s risk of IBD by 236 percent.
The association was consistent across most types of antibiotics, and the risk was greatest in the first one to two years after antibiotic use.
Faye said future research will need to unpack what mechanisms could potentially be underpinning this association. He speculates antibiotic-induced disruptions to the gut microbiome as possibly playing a role in this relationship.
Ultimately, Faye does make it very clear these findings do not mean people need to completely abstain from antibiotics. If you need these crucial drugs to treat infections then they should not be avoided, according to Faye. But he does suggest doctors exercise a little more caution when prescribing these drugs to older patients in the absence of a clear infection.
“Antibiotic stewardship is important; but avoiding antibiotics at all costs is not the right answer either,” said Faye. “If you’re not sure what you are treating, I would be cautious. If patients are coming in with clear infections, and they need antibiotics, they should not be withheld because of these findings.”
The fungal antibiotic study was published in the journal Cell Host & Microbe.
Sources: University of Birmingham, American Gastroenterological Association
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