December 2, 2022

Antibiotics disrupt the immune system in the gut leading to fungal infection

According to a new study from the University of Birmingham and the National Institutes of Health, patients who were prescribed antibiotics in hospital are more likely to get fungal infections due to disruption of the immune system in the gut .

Using immune-boosting drugs alongside antibiotics could reduce health risks from these complex infections, the researchers say.

Invasive candidiasis, a life-threatening fungal infection, is a major complication for hospitalized patients who receive antibiotics to prevent sepsis and other bacterial infections that spread rapidly in hospitals (such as C. diff). Fungal infections can be more difficult to treat than bacterial infections, but the underlying factors causing these infections are not well understood.

A team from the University Institute of Immunology and Immunotherapy, in collaboration with researchers from the National Institutes of Health, discovered that antibiotics disrupt the immune system in the intestines, which means that fungal infections were poorly controlled in this region. Unexpectedly, the team also discovered that where fungal infections were growing, gut bacteria could also escape, leading to an additional risk of bacterial infection.

The study, published in Host Cell and Microbe, demonstrates the potential of immune-boosting drugs, but the researchers also say their work also highlights how antibiotics can have additional effects on our bodies that affect how we fight infection and disease. This in turn highlights the importance of careful management of available antibiotics.

We knew that antibiotics made fungal infections worse, but the finding that bacterial co-infections can also develop through these interactions in the gut was surprising. These factors can add up to a complicated clinical situation – and by understanding these underlying causes, physicians will be better able to treat these patients effectively.”


Dr. Rebecca Drummond, lead author

In the study, the team used mice treated with a broad-spectrum antibiotic cocktail and then infected those animals with Candida albicans, the most common fungus that causes invasive candidiasis in humans. They found that although infected mice had increased mortality, this was caused by infection in the gut rather than the kidneys or other organs.

In a further step, the team identified the parts of the immune system that were missing in the gut after antibiotic treatment, then added them back to the mice using immune-boosting drugs similar to those used in humans. They found that this approach helped reduce the severity of the fungal infection.

The researchers continued the experiment by studying hospital records, where they were able to show that similar co-infections could occur in humans after being treated with antibiotics.

“These results demonstrate the possible consequences of antibiotic use in patients at risk of developing fungal infections,” Dr. Drummond added. “If we limit or change the way we prescribe antibiotics, we can help reduce the number of people who become seriously ill from these additional infections – while tackling the huge and growing problem of antibiotic resistance. “

Source:

Journal reference:

Drummond, RA, et al. (2022) Long-term antibiotics promote mortality after systemic fungal infection by causing lymphocyte dysfunction and systemic leakage of commensal bacteria. Cell host and microbe. doi.org/10.1016/j.chom.2022.04.013.