Groundbreaking research finds fungus plays a central role in Crohn's disease

Researchers reported for the first time that the fungus Candida tropicalis appears to play a critical role—in conjunction with two bacteria—in the development of Crohn’s disease, according to a September 20, 2016 study in mBio.

The researchers found an abundance of C. tropicalis along with elevated levels of Serratia marcescens and Escherichia coli bacteria in the intestinal tracts of patients with Crohn’s disease, which suggested that these organisms interact. 

“Among hundreds of bacterial and fungal species inhabiting the intestines, it is telling that the three we identified were so highly correlated in Crohn’s patients,” said the senior and corresponding author, Mahmoud A. Ghannoum, PhD, Professor and Director of the Center for Medical Mycology at Case Western Reserve University School of Medicine, in Cleveland, OH.

This is the first study to find that a fungus is associated with Crohn’s disease in humans; previously it was only found in mice with the disease. The study is also the first to include S. marcescens in the analysis of the intestinal bacteriome of Crohn’s patients.

“Our study adds significant new information to understanding why some people develop Crohn’s disease,” Dr. Ghannoum noted. “Equally important, it can result in a new generation of treatments, including medications and probiotics, which hold the potential for making qualitative and quantitative differences in the lives of people suffering from Crohn’s.”

Because E. coli has already been associated with Crohn’s disease, most researchers have focused on the role of bacteria, Dr. Ghannoum observed. Only recently have they considered fungi, which are also widely present in the intestine.

For this investigation, the researchers analyzed fecal samples from members of 9 French and Belgian families—which included 20 subjects with Crohn’s disease and 28 relatives without it—as well as 21 Crohn’s-free control subjects from 4 families living in the same area.

After analyzing the samples, the researchers found that patients with Crohn’s disease had significantly higher levels of C. tropicalis, matched by higher levels of S. marcescens and E. coli, when compared with non-Crohn’s subjects. This indicated to the researchers that the fungus and the bacteria interact in the intestines.

The researchers also found that the increases in these harmful bacteria were associated with decreases in beneficial bacteria. In addition, the abundance of C. tropicalis correlated with higher titers of anti-Saccharomyces cerevisiae antibodies, which are known biomarkers of Crohn’s disease.

Following this analysis, the researchers conducted in vitro tests to observe how the fungus-bacteria combination interacted in biofilms. They found that the mass and thickness of the triple-species (C. tropicalis plus S. marcescens plus E. coli) biofilm were significantly greater than those of single- and double-species biofilms. 

They also discovered that E. coli cells fused to C. tropicalis cells, while S. marcescens used bridge-like fimbriae to link to the two other microbes. “Interestingly, in biofilms formed by the three organisms, S. marcescens cells interacted with both C. tropicalis and E. coli through these fimbriae,” the authors wrote. “Specific interkingdom microbial interactions may be key determinants in Crohn’s disease.”

“Furthermore, we found strong similarities in what may be called the ‘gut profiles’ of the Crohn’s-affected families, which were strikingly different from the Crohn’s-free families,” Dr. Ghannoum noted. “We have to be careful, though, and not solely attribute Crohn’s disease to the bacterial and fungal makeups of our intestines. For example, we know that family members also share diet and environment to significant degrees.”

Further research is needed to be even more specific in identifying precipitators and contributors of Crohn’s disease, he added.