Fungus Identified As Key Factor in Crohn’s Disease

The study was conducted by an international research team, co-led by Mahmoud A Ghannoum, PhD, professor at Case Western Reserve University School of Medicine, (Cleveland, OH, USA) at University Hospitals Cleveland Medical Center. “We already know that bacteria, in addition to genetic and dietary factors, play a major role in causing Crohn’s disease,” said Prof. Ghannoum, “Essentially, patients with Crohn’s have abnormal immune responses to these bacteria, which inhabit the intestines of all 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.”

Bacteria as well as fungi are present throughout the body; Prof. Ghannoum’s lab previously found that people harbor 9-23 fungal species in their mouths. In the new study, by analyzing fecal samples, the researchers assessed the mycobiome and bacteriome of: (a) 20 Crohn’s disease patients and 28 Crohn’s-free individuals from among their first-degree relatives in 9 families; and of (b) 21 Crohn’s-free individuals from 4 Crohn’s-free families.

The results showed strong fungal-bacterial interactions in those with Crohn’s disease: two bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis) moved in lock step. The presence of all three in the Crohn’s patients was significantly higher compared to their healthy relatives, suggesting that the bacteria and fungus interact in the intestines. In vitro experiments showed that the three work together to produce a biofilm – which can prompt intestinal inflammation that results in the symptoms of Crohn’s disease. The researchers observed that E. coli cells fused to the fungal cells and S. marcescens formed a connecting bridge.

This is first report linking a fungus to Crohn’s in humans; previously it was only found in model Crohn’s disease mice. The study is also the first to include S. marcescens in the Crohn’s-linked bacteriome. The researchers also found that the presence of beneficial bacteria was significantly lower in the Crohn’s patients, corroborating previous findings.

“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 Prof. Ghannoum, “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.”

The study, by Hoarau G, Mukherjee PK, et al, was published September 20, 2016, in the journal mBio.

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