New study findings suggest that Candida tropicalis infection may intensify colitis in patients with Crohn’s disease.
 
C. tropicalis is a species of yeast in the Candida family that typically resides in intestine, mucus membrane, and on the skin in small numbers. It is considered the second most common yeast-like fungus after Candida albicans.
 
“The type of microorganisms that live in our intestine, our microbiome, has been shown to be a key element for triggering Crohn’s disease,” said lead author Luca Di Martino, PhD. “Recent studies have shown that the abundance of the fungus Candida tropicalis is significantly higher in the intestine of Crohn’s disease patients compared to healthy people.”
 
For the study, investigators added low levels of dextran sodium sulfate––a chemical that causes acute intestinal injury, similar to a colitis flare––to the drinking water of mice to induce colitis symptoms.
 
Next, the investigators infected a subset of mice with C. tropicalis fungi to examine the mouse intestinal tracts and gut bacteria.
 
The results of the study showed that mice infected with C. tropicalis fungi had an increase in Crohn’s disease symptoms compared with uninfected mice. The findings suggest that anti-fungal medications could help combat painful symptoms associated with Crohn’s by lowering levels of C. tropicalis in the gut.
 
“Our data demonstrate that C. tropicalis may play a pro-inflammatory role in intestinal injury by exacerbating gut inflammation during the recovery phase of dextran sodium sulfate-induced colitis,” the authors wrote. “We speculate that infection with the fungus C. tropicalis may play a role in triggering flares during Crohn’s disease and that anti-fungal therapy may be beneficial in Crohn’s disease patients.”
 
The authors hypothesize that C. tropicalis fungus triggers gut inflammation by modulating levels of other gut bacteria.
 
“We found that high levels of C. tropicalis increases 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.”
 
In the colons of infected mice, endoscopies showed 4.5 times higher levels of IFN-y inflammatory molecules that are associated with colitis. Upon further investigation, the infected intestinal tracts were found to also have more severe visual signs of swelling compared with those from uninfected mice.
 
“We discovered that experimental mice infected with C. tropicalis were more susceptible to intestinal inflammation compared to uninfected mice,” Di Martino said. “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.
 
Limitations to the study were that investigators tested the effects of human gut bacteria in an animal model, and that the findings may not fully translate to human disease. Additionally, colitis was induced in mice acutely using dextran sodium sulfate, while colitis is typically a chronic condition in humans.
 
“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,” Di Martino said. “If our hypothesis is right, that would open the door to novel antifungal therapies to treat Crohn’s disease patients.”
 
The findings were presented at Digestive Disease Week in Chicago.