A team of UC Davis Health researchers discovered that a common anti-inflammatory drug, mesalamine, can replace the work of good bacteria in fighting the nasty fungus Candida albicans in the gut.
C. albicans, or candida, is known to cause fungal infections. In some cases, it develops into invasive candidiasis, a life-threatening infection that occurs primarily in patients with compromised immunity.
Researchers discovered that this fungus cannot grow without a supply of oxygen. Their study in mice showed that the drug can maintain a low-oxygen environment (hypoxia) that prevents the proliferation of fungi in the intestine.
His study appears today in Cellular host and microbe.
The use of antibiotics can cause the proliferation of fungi in the intestine
The team studied how C. albicans colonizes the intestine. The fungus, best known for causing vaginal yeast infection, is usually treated with a topical or oral antifungal without serious side effects. It also lives harmlessly in the intestines of about 60% of people.
However, when the body’s immunity decreases due to cancer or chemotherapy, the fungus can grow beyond the colon and spread throughout the body. In such cases, the patient develops invasive candidiasis.
“Invasive candidiasis is a life-threatening infection with a mortality rate of around 50%, even with the best available treatment,” explained the study’s lead author, Andreas Bäumler. Bäumler is a distinguished professor in the Department of Medical Microbiology and Immunology.
Patients with leukemia and other blood cancers may need to take antibiotics. This use can cause an imbalance in the gut microbial community. Reduces Clostridia, a group of bacteria that promote resistance to fungal colonization in the intestine. With less Clostridia, C. albicans grows and colonizes the tract.
“The proliferation of C. albicans in the intestine during antibiotic therapy is the most common cause of candidemia in people treated for blood cancer,” explained Bäumler. Candidemia is the presence of fungi or yeast in the blood.
Bäumler and his team wanted to understand the factors involved in antibiotic-induced colonization of C. albicans in the intestine.
Candida loves simple sugars and oxygen.
They first colonized germ-free mice with Candida to see what the fungus consumed to flourish. They realized that Candida really liked simple sugars, similar to those found in high-sugar diets. Then, they tested its growth in a Petri dish. They placed Candida with simple sugars in an aerobic environment (with oxygen) and the fungi flourished.
“A healthy intestine has little oxygen. That’s why we repeated the test in a hypoxic environment,” said Bäumler. The fungi did not grow despite the presence of sugars. This meant that oxygen is a necessary condition for the growth of Candida.
The role of probiotics in preventing fungal growth.
The team conducted a series of experiments that showed that the use of antibiotics reduced clostridia in the intestine. Giving the mice probiotics, such as Clostridia, prevented C. albicans from growing in the intestine. However, antibiotics and cancer therapy can eliminate probiotics. For this reason, probiotics would not help patients with leukemia or other blood cancers.
“Probiotics are often not safe in patients at increased risk for invasive candidiasis,” Bäumler said. “It was important to find a therapy that could work like probiotics but could withstand the impact of cancer treatment and antibiotics.”
Anti-inflammatory drugs as false biotics
The team explored 5-aminosalicylic acid (5-ASA) as a safer way to control C. albicans in the intestine. 5-ASA, also known as mesalamine, is an anti-inflammatory drug. It is used to treat inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis.
The team tested 5-ASA in mice treated with antibiotics. They found that the drug could replace the work of probiotics by preventing oxygen in the colon and C. albicans from expanding in the intestine.
“Limiting oxygen in the intestine by replacing the function of good bacteria could be a strategy to reduce invasive candidiasis,” Bäumler said. “Our study opens up an entirely new treatment option for deadly fungal infections, especially in cancer patients. After all, fungi cannot become resistant to hypoxia.”
The team proposed the term “fake biotics” to refer to products, such as 5-ASA, that mimic the function of probiotics such as Clostridia.
The study’s first co-authors are Hannah Savage, Derek Bays and Connor Tiffany. The other co-authors are Mariela González, Eli Bejarano, Thaynara Carvalho, Zheng Luo, Hugo Masson, Henry Nguyen, Renato Santos, Krystle Reagan and George Thompson of UC Davis.