In the Journals

Fungus linked to dysbiosis in Crohn's disease

Researchers have for the first time identified a species of fungus that is associated with microbial dysbiosis in Crohn’s disease, according to research published in mBio.

The researchers also identified new bacterial species associated with dysbiosis in Crohn’s disease. These findings could ultimately lead to potential new treatments, they wrote.

Mahmoud A. Ghannoum, PhD

Mahmoud A. Ghannoum

“We already know that bacteria, in addition to genetic and dietary factors, play a major role in causing Crohn’s disease,” Mahmoud A. Ghannoum, PhD, professor and director of the Center for Medical Mycology at Case Western Reserve and University Hospitals Cleveland Medical Center, said in a press release. “Essentially, patients with Crohn’s have abnormal immune responses to these bacteria, which inhabit the intestines of most people. While most researchers focus their investigations on these bacteria, few have examined the role of fungi, which are also present in everyone’s intestines. Our study adds significant new information to understanding why some people develop Crohn’s disease. 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.”

Ghannoum and colleagues collected fecal samples from nine families that included 20 Crohn’s patients and 28 of their first-degree relatives without Crohn’s, as well as from four unrelated families that included 21 individuals without Crohn’s. All of these families lived in the same geographic regions in northern France and Belgium.

The researchers used ion torrent sequencing to evaluate their mycobiomes and bacteriomes, and validated the significant microbial interactions they identified using single- and mixed-species biofilms.

Higher abundance of two bacterial species (Escherichia coli and Serratia marcescens) was observed in the patients with Crohn’s disease, while the abundance of beneficial bacteria was reduced. Significantly higher abundance of the fungal species Candida tropicalis was also observed in the patients with Crohn’s disease compared with their relatives (P = .003), and was positively correlated with levels of anti-Saccharomyces cerevisiae antibodies, a known Crohn’s disease biomarker.

The abundance of E. coli, S. marcescens and C. tropicalis was also positively correlated, suggesting that they interact with each other in the gut.

The researchers then investigated the three species’ ability to form in vitro biofilms and found the thickness of the triple-species biofilms was significantly greater (P < .0001) than that of single- and double-species biofilms. Further microscopic analysis confirmed the E. coli cells fused to the C. tropicalis, while S. marcescens closely interacted with both species to create a biofilm associated with pathogenic conditions.

The researchers concluded that these findings suggest C. tropicalis interacts with potential bacterial pathogens, which might play an important role in Crohn’s disease.

“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,” Ghannoum said in the press release. “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. 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.” – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures.

Researchers have for the first time identified a species of fungus that is associated with microbial dysbiosis in Crohn’s disease, according to research published in mBio.

The researchers also identified new bacterial species associated with dysbiosis in Crohn’s disease. These findings could ultimately lead to potential new treatments, they wrote.

Mahmoud A. Ghannoum, PhD

Mahmoud A. Ghannoum

“We already know that bacteria, in addition to genetic and dietary factors, play a major role in causing Crohn’s disease,” Mahmoud A. Ghannoum, PhD, professor and director of the Center for Medical Mycology at Case Western Reserve and University Hospitals Cleveland Medical Center, said in a press release. “Essentially, patients with Crohn’s have abnormal immune responses to these bacteria, which inhabit the intestines of most people. While most researchers focus their investigations on these bacteria, few have examined the role of fungi, which are also present in everyone’s intestines. Our study adds significant new information to understanding why some people develop Crohn’s disease. 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.”

Ghannoum and colleagues collected fecal samples from nine families that included 20 Crohn’s patients and 28 of their first-degree relatives without Crohn’s, as well as from four unrelated families that included 21 individuals without Crohn’s. All of these families lived in the same geographic regions in northern France and Belgium.

The researchers used ion torrent sequencing to evaluate their mycobiomes and bacteriomes, and validated the significant microbial interactions they identified using single- and mixed-species biofilms.

Higher abundance of two bacterial species (Escherichia coli and Serratia marcescens) was observed in the patients with Crohn’s disease, while the abundance of beneficial bacteria was reduced. Significantly higher abundance of the fungal species Candida tropicalis was also observed in the patients with Crohn’s disease compared with their relatives (P = .003), and was positively correlated with levels of anti-Saccharomyces cerevisiae antibodies, a known Crohn’s disease biomarker.

The abundance of E. coli, S. marcescens and C. tropicalis was also positively correlated, suggesting that they interact with each other in the gut.

The researchers then investigated the three species’ ability to form in vitro biofilms and found the thickness of the triple-species biofilms was significantly greater (P < .0001) than that of single- and double-species biofilms. Further microscopic analysis confirmed the E. coli cells fused to the C. tropicalis, while S. marcescens closely interacted with both species to create a biofilm associated with pathogenic conditions.

The researchers concluded that these findings suggest C. tropicalis interacts with potential bacterial pathogens, which might play an important role in Crohn’s disease.

“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,” Ghannoum said in the press release. “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. 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.” – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures.