A team of researchers from UC Davis Health has made an important discovery regarding the treatment of fungal infections in the gut. Their study, published in Cell Host & Microbe, reveals that a commonly used anti-inflammatory drug, mesalamine, can effectively replace the role of beneficial bacteria in combating Candida albicans, a fungus that can cause yeast infections.

C. albicans, also known as candida, is particularly problematic as it can develop into invasive candidiasis, a potentially fatal infection, especially in individuals with weakened immune systems. The researchers found that this fungus requires an oxygen supply to grow. By creating a low oxygen (hypoxia) environment through the use of mesalamine, the drug can prevent the growth of the fungus in the gut.

The study focused on how C. albicans colonizes the gut. While it usually coexists harmlessly in the gut of approximately 60% of people, its growth can become problematic when the body's immune system is compromised due to conditions like cancer or chemotherapy. In such cases, the fungus can spread throughout the body, leading to invasive candidiasis, which has a mortality rate of around 50%, even with the best available treatment.

The team discovered that antibiotic use can disrupt the microbial balance in the gut and reduce the presence of a group of bacteria called Clostridia, which helps prevent fungal colonization. This imbalance allows C. albicans to flourish and leads to a condition known as candidemia, where fungi or yeast are present in the blood.

In order to further understand how C. albicans thrives in the gut, the researchers conducted experiments using germ-free mice. They found that the fungus favored simple sugars, similar to those found in high-sugar diets, for its growth. However, the team also observed that when the environment was oxygen-deprived (hypoxia), the growth of C. albicans was inhibited, indicating the significance of oxygen in its growth process.

To prevent fungal growth, the researchers explored the use of probiotics, particularly Clostridia. However, they found that probiotics were not suitable for patients with leukemia or other blood cancers, as they could be killed by antibiotics and cancer therapy. This prompted the team to investigate alternative methods.

Their attention turned to 5-aminosalicylic acid (5-ASA), also known as mesalamine, which is commonly used as an anti-inflammatory drug for the treatment of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. The researchers tested 5-ASA in mice treated with antibiotics and found that it could effectively replace the role of probiotics, preventing the expansion of C. albicans in the gut by limiting oxygen supply.

Lead author of the study, Andreas Bäumler, emphasized the significance of this finding, stating that "limiting oxygen in the gut by replacing the function of good bacteria could be a strategy for reducing invasive candidiasis." He also coined the term "faux-biotics" to describe products like 5-ASA that mimic the function of probiotics.

This breakthrough offers promising treatment options for fatal fungal infections, particularly in cancer patients. Unlike traditional antibiotics, fungi cannot develop resistance to hypoxia, making mesalamine a potential solution for combating fungal infections in the gut. Further studies will be required to explore the full potential of this approach.

The findings of this study provide hope for improving patient outcomes and reducing the mortality rate associated with invasive candidiasis. The use of mesalamine as a faux-biotic holds the potential to transform the treatment landscape for fungal infections, especially for individuals with compromised immune systems.