"The groundwork of all happiness is health." - Leigh Hunt

An inflammatory fungus spreads that causes serious blood infections.

A team of UC Davis Health researchers discovered that a typical anti-inflammatory drug, mesalamine, can replace the work of excellent bacteria in fighting the nasty fungus Candida albicans within the gut.

C. albicans, or candida, is understood to cause yeast infections. In some cases, it develops into invasive candidiasis, a potentially fatal infection mostly in immunocompromised patients.

The researchers found that this fungus cannot grow with out a supply of oxygen. Their studies in mice show that the drug can maintain a low-oxygen (hypoxia) environment that inhibits fungal overgrowth within the gut.

Their study appears in Today.

Antibiotic use can result in fungal overgrowth within the intestines.

The team studied how C. albicans colonizes the gut. Fungus, essentially the most common reason for vaginal yeast infections, is normally treated with topical or oral antifungals without serious negative effects. It also stays harmless within the intestines of about 60% of individuals.

Still, when the body's immune system is weakened by cancer or chemotherapy, the fungus can spread beyond the colon and spread throughout the body. In such cases, the patient develops invasive candidiasis.

“Invasive candidiasis is a potentially fatal infection with a mortality rate of around 50 percent. This is even with the best available treatment,” explained Andreas Bömler, lead writer of the study. Bäumler is a distinguished professor within the Department of Medical Microbiology and Immunology.

Patients with leukemia and other blood cancers may have to take antibiotics. This use may cause an imbalance within the microbial community of the gut. It reduces clostridia, a gaggle of bacteria that promote resistance to fungal colonization within the gut. With fewer Clostridia, C. albicans grows and colonizes the pathway.

“An overgrowth of C. albicansin in the gut during antibiotic therapy is the most common cause of candidemia in people treated for blood cancer,” explained Bäumler. Candidemia is the presence of fungus or yeast within the blood.

Bäumler and his team wanted to know the aspects involved in antibiotic-induced colonization of C. albicans within the gut.

Candida loves easy sugars and oxygen

They first colonized sterile mice with Candida to see what the fungus ate to trigger the bloom. They found that Candida really likes easy sugars, like those present in high-sugar foods. Then, they tested its growth in a petri dish. They placed Candida in an aerobic (with oxygen) setting with easy sugars, and the fungus bloomed.

“A healthy gut has less oxygen. So, we repeated the test in a hypoxia setting,” Baumler said. Despite the presence of sugar, the fungus didn't grow. This implies that oxygen is a obligatory condition for Candida to grow.

The role of probiotics in inhibiting fungal growth

The team conducted a series of experiments showing that the usage of antibiotics reduced Clostridiain. Giving mice probiotics, similar to Clostridia, prevents C. albicans from growing within the gut. Still, probiotics might be killed by antibiotics and cancer treatments. For this reason, probiotics is not going to help patients with leukemia or other blood cancers.

“Probiotics are often not safe in patients who are most at risk for invasive candidiasis,” Bäumler said. “Finding a therapy that can act like probiotics but counteract the effects of cancer treatments and antibiotics.”

Anti-Inflammatory Drugs as Improper Biotics

The team discovered 5-aminosalicylic acid (5-ASA) as a protected method to control C. albicansin. 5-ASA, also generally known as mesalamine, is an anti-inflammatory drug. It is used to treat inflammatory bowel diseases (IBD) similar to Crohn's disease and ulcerative colitis.

The team tested 5-ASA in mice treated with antibiotics. They found that the drug could replace probiotics by blocking oxygen within the colon and stopping C. albicans from proliferating within the intestines.

“Limiting oxygen in the gut by altering the function of good bacteria may be a strategy to reduce invasive candidiasis,” Bäumler said. “Our study opens up a completely new option for the treatment of deadly fungal infections, especially for cancer patients. After all, the cocci cannot become resistant to hypoxia.”

The team proposed the term “faux-biotics” to discuss with products similar to 5-ASA that mimic the function of probiotics similar to Clostridia.

The first authors of the study are Hannah Savage, Derek Bays and Connor Tiffany. Other co-authors are Mariela Gonzalez, Eli Bejarano, Thenara Carvalho, Zheng Lu, Hugo Mason, Henry Nguyen, Renato Santos, Crystal Regan and George Thompson of UC Davis.