Antibiotics can lead to life-threatening fungal infection because of disruption to the gut microbiome – new study

Fungal infections kill about the same number of people as tuberculosis every year. They mainly target people who are vulnerable because they have a faulty immune system caused by an underlying disease, such as cancer, or a viral infection, such as HIV or COVID. Our new study shows that antibiotics can cause immune system defects that increase the risk of dangerous fungal infections.

candida is a fungus that is a common cause of yeast infections in humans. The yeast infection thrush is caused by: candida† But it can also cause a life-threatening bloodstream infection called invasive candidiasis.

One of the risk factors for getting invasive candidiasis is antibiotics. When we take antibiotics, we kill some of our gut bacteria. This can create space for intestinal fungi (such as candida) grow. And if your gut is damaged by chemotherapy or surgery, the candida can come out of the gut and cause a bloodstream infection.

But the most common way people get invasive candidiasis is not from their gut, but from their skin. Patients in the ICU who have an intravenous catheter can develop invasive candidiasis, especially if they have been treated with antibiotics.

We wanted to know exactly why antibiotics make fungal infections like invasive candidiasis more likely. To investigate this, we treated mice with a broad-spectrum antibiotic cocktail and then infected them with candida fungi. We compared them with a control group of mice that we infected with the Candida fungus, but which we did not treat with the cocktail of antibiotics.

We found that antibiotic treatment made mice sicker when infected with the fungus. In this fungal infection, it is normally the kidneys that become the target of the infection and mice get sick because their kidneys stop working. But that was not the case here. Although antibiotics made the mice sicker, they controlled the fungal infection in the kidneys just as well as the mice that had not been given antibiotics. So what made them sick?

It turned out that the antibiotics caused a defect in the anti-fungal immune response, particularly in the gut. Antibiotic-treated mice had much higher levels of fungal infection in the gut than the untreated mice. As a result, gut bacteria subsequently escaped into the blood. Antibiotic-treated mice now had both a bacterial and fungal infection to deal with. This made them much sicker than the mice that had no antibiotics.

To find out why this happened, we analyzed the immune cells in the gut to find out how antibiotics caused a faulty anti-fungal immune response. Immune cells in the gut make small proteins called cytokines that act as messages to other cells. For example, cytokines called IL-17 and GM-CSF help immune cells fight fungal infections. We found that antibiotics reduced the amount of these cytokines in the gut, which we believe is one of the reasons why the antibiotic-treated mice were unable to control the fungal infection in the gut or allow the bacteria to escape.

Candida fungus can cause life-threatening bloodstream infections.
Science Photo Library / Alamy Stock Photo

Possible solution

Some of these cytokines can be given to patients as immune-boosting drugs to help fight infection. To see if this could be an option for antibiotic-treated patients at risk for fungal infections, we injected our antibiotic-treated mice with some of these cytokines and found that we could make them less sick. Our findings mean we may have a way to help patients who need antibiotics and are at risk for a yeast infection.

Next, we wanted to know if there was a specific antibiotic that increases the risk of fungal infections. We treated mice with different antibiotics and found that vancomycin, an antibiotic commonly used to treat C diff infections in hospitals, made mice sicker after a fungal infection. Vancomycin removed immune-enhancing bacteria from the gut microbiome that are needed to instruct the immune system to make IL-17.

Is any of these studies relevant to humans? Our analysis of patient records suggests so. We looked at a large database of hospital records and found that similar bacterial/fungal infections can occur in humans after being treated with antibiotics.

Given the increasing problem of antibiotic resistance, it is now more important than careful use of antibiotics. Our research shows that antibiotics can pose an additional risk of dangerous fungal infections. However, antibiotics are a risk factor that we can control. Fungal infections remain an important human health problem, but studies like ours are helping us understand how to fight them.

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