Crohn's disease symptoms exacerbated by Candida tropicalis

Candida tropicalis may trigger gut inflammation and worsen the symptoms of Crohn’s disease, according to researchers from Case Western Reserve University School of Medicine, Cleveland, OH.

“The type of microorganisms that live in our intestine, our microbiome, has been shown to be a key element for triggering Crohn’s disease. Recent studies have shown that the abundance of the fungus C. tropicalis is significantly higher in the intestine of Crohn’s disease patients compared to healthy people,” said lead author Luca Di Martino, PhD, postdoctoral research fellow, Digestive Health Research Institute, Case Western Reserve.

Dr. Di Martino and colleagues conducted this study to assess how C. tropicalis and other gut microorganisms may influence intestinal inflammation. They induced symptoms of colitis in mice by adding small amounts of dextran sodium sulfate, which causes acute intestinal injury similar to a colitis flare, to the drinking water. In addition, they infected a subset of mice with C. tropicalis and assessed the mouse intestinal tracts and gut bacteria.

They found that the mice infected with C. tropicalis exhibited intensified Crohn’s disease symptoms compared with uninfected mice. Infected mice also had several signs of debilitating gut inflammation, and upon endoscopies, their colons were found to have 4.5 times higher levels of IFN-γ, specifically associated with colitis. In addition, upon microscopic investigation, the intestinal tracts of these infected mice also demonstrated more severe visual signs of swelling compared with uninfected mice.

Dr. Di Martino and fellow authors suggested that C. tropicalis may trigger gut inflammation via the modulation of other gut bacteria levels.

“We found that high levels of C. tropicalis increase the abundance of harmful proteobacteria in the intestine, such as E. coli, disrupting the normal balance of the gut bacteria and creating a dysbiosis, a key element that triggers intestinal inflammation,” said Dr. Di Martino.

“The most exciting discovery was that in the infected mice there was a significantly higher abundance of proteobacteria, the same type of deleterious bacteria found increased in Crohn’s patients. This confirmed that the presence and the abundance of fungi in the intestine have the ability to modify the bacteria living in our intestine, leading to a dysbiosis which will eventually trigger an inflammatory syndrome,” he added.

These findings suggest, therefore, that treatment with anti-fungal medications may combat the symptoms of Crohn’s disease via lowering gut levels of C. tropicalis.

“As a next step, we want to confirm the role of the fungi in the pathogenesis of Crohn’s disease by treating infected mice with antifungal drugs to decrease symptoms of intestinal inflammation,” said Dr. Di Martino. “If our hypothesis is right, that would open the door to novel antifungal therapies to treat Crohn’s disease patients.”

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (awards P30DK097948 which supports the Silvio O. Conte Cleveland Digestive Diseases Research Core Center and P01DK091222).