In the JournalsPerspective

‘Mycobiome’ research suggests antifungals, probiotics could treat Crohn’s disease

Mahmoud A Ghannoum, PhD
Mahmoud A. Ghannoum

While recent efforts have improved the understanding of the gut microbiome’s role in inflammatory bowel disease, most research has focused on gut bacteria while overlooking the fungal communities in the GI tract, or the “mycobiome,” according to a review published today in Digestive and Liver Disease.

In the article, Mahmoud A. Ghannoum, PhD, professor and director of the Center for Medical Mycology at Case Western Reserve and University Hospitals Cleveland Medical Center, and co-author Christopher L. Hager, MD, discussed the role of the mycobiome in health and disease, highlighting their recent work showing how interactions between certain fungal and bacterial species may drive intestinal inflammation in Crohn’s disease, and the potential for the use of antifungals and probiotics in the treatment of IBD.

“The human gastrointestinal (GI) tract is home to trillions of microorganisms, some beneficial and others potentially harmful. Recent advances in science have allowed us to identify the multitude of organisms inhabiting the GI tract and parse out those that play a role in IBD,” Ghannoum said in a press release. “Unfortunately, most research has focused on studying only the bacteria while overlooking a key player, fungus. In order to address this issue, we have focused our efforts on studying the fungal community in the GI tract known as the mycobiome.”

Ghannoum and his colleagues’ work began in 2010, when they used deep-sequencing to show the fungal communities in the human mouth were unexpectedly complex and variable across individuals, like the bacteriome.

“Since then, few studies have characterized the mycobiome of the GI tract in health,” Ghannoum and Hager wrote, but the few that have “have laid the foundation for future research into how disruption/dysbiosis of the fungal community can lead to disease.”

In particular, these foundational studies have shown that the mycobiome in healthy individuals is primarily composed of Aspergillus, Cryptococcus, Penicillium, Pneumocystis and Saccharomycetaceae yeasts (Candida and Saccharomyces), and have also identified associations with diet and other components of the gut microbiome.

As Healio Gastroenterology and Liver Disease has previously reported, Ghannoum and colleagues’ most recent study found that patients with Crohn’s disease showed significantly higher levels of the fungus Candida tropicalis and the bacteria Escherichia coli and Serratia marcescens than their healthy relatives. Further in vitro studies showed that these three organisms interacted “in a strategic way” to form robust, pathogenic biofilms capable of driving intestinal inflammation.

Ghannoum also recently discussed this study in detail at the NIH’s conference on the Human Microbiome in August.

These findings show promise for the potential of new therapeutic approaches in patients with IBD, like antifungals and antibiotics, and they have “also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation,” Ghannoum and Hager wrote.

Unfortunately, research and development of probiotics is insufficient due to lack of funding, though large clinical trials of probiotics in GI diseases are warranted given their own data and small trials showing positive outcomes in ulcerative colitis and pouchitis, they added.

They concluded their discovery that both bacteria and fungi are implicated in IBD suggests that a promising new therapeutic approach could involve the use of antifungals to control fungal overgrowth paired with a probiotic containing beneficial bacteria and fungus to help restore the gut microbiome to a healthy balance.

“Our ground-breaking discovery that bacteria and fungi both play a critical role in health and disease has tremendous implications not only for understanding the disease process, but also for development of potentially life changing treatments for those who suffer from chronic digestive diseases,” Ghannoum said in the press release. – by Adam Leitenberger

Disclosures: The authors report no relevant financial disclosures.

Mahmoud A Ghannoum, PhD
Mahmoud A. Ghannoum

While recent efforts have improved the understanding of the gut microbiome’s role in inflammatory bowel disease, most research has focused on gut bacteria while overlooking the fungal communities in the GI tract, or the “mycobiome,” according to a review published today in Digestive and Liver Disease.

In the article, Mahmoud A. Ghannoum, PhD, professor and director of the Center for Medical Mycology at Case Western Reserve and University Hospitals Cleveland Medical Center, and co-author Christopher L. Hager, MD, discussed the role of the mycobiome in health and disease, highlighting their recent work showing how interactions between certain fungal and bacterial species may drive intestinal inflammation in Crohn’s disease, and the potential for the use of antifungals and probiotics in the treatment of IBD.

“The human gastrointestinal (GI) tract is home to trillions of microorganisms, some beneficial and others potentially harmful. Recent advances in science have allowed us to identify the multitude of organisms inhabiting the GI tract and parse out those that play a role in IBD,” Ghannoum said in a press release. “Unfortunately, most research has focused on studying only the bacteria while overlooking a key player, fungus. In order to address this issue, we have focused our efforts on studying the fungal community in the GI tract known as the mycobiome.”

Ghannoum and his colleagues’ work began in 2010, when they used deep-sequencing to show the fungal communities in the human mouth were unexpectedly complex and variable across individuals, like the bacteriome.

“Since then, few studies have characterized the mycobiome of the GI tract in health,” Ghannoum and Hager wrote, but the few that have “have laid the foundation for future research into how disruption/dysbiosis of the fungal community can lead to disease.”

In particular, these foundational studies have shown that the mycobiome in healthy individuals is primarily composed of Aspergillus, Cryptococcus, Penicillium, Pneumocystis and Saccharomycetaceae yeasts (Candida and Saccharomyces), and have also identified associations with diet and other components of the gut microbiome.

As Healio Gastroenterology and Liver Disease has previously reported, Ghannoum and colleagues’ most recent study found that patients with Crohn’s disease showed significantly higher levels of the fungus Candida tropicalis and the bacteria Escherichia coli and Serratia marcescens than their healthy relatives. Further in vitro studies showed that these three organisms interacted “in a strategic way” to form robust, pathogenic biofilms capable of driving intestinal inflammation.

Ghannoum also recently discussed this study in detail at the NIH’s conference on the Human Microbiome in August.

These findings show promise for the potential of new therapeutic approaches in patients with IBD, like antifungals and antibiotics, and they have “also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation,” Ghannoum and Hager wrote.

Unfortunately, research and development of probiotics is insufficient due to lack of funding, though large clinical trials of probiotics in GI diseases are warranted given their own data and small trials showing positive outcomes in ulcerative colitis and pouchitis, they added.

They concluded their discovery that both bacteria and fungi are implicated in IBD suggests that a promising new therapeutic approach could involve the use of antifungals to control fungal overgrowth paired with a probiotic containing beneficial bacteria and fungus to help restore the gut microbiome to a healthy balance.

“Our ground-breaking discovery that bacteria and fungi both play a critical role in health and disease has tremendous implications not only for understanding the disease process, but also for development of potentially life changing treatments for those who suffer from chronic digestive diseases,” Ghannoum said in the press release. – by Adam Leitenberger

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    Stephen B. Hanauer

    Clearly, the mycobiome, a component of the microbiome, deserves attention as do efforts to understand how the microbiome (including the mycobiome and virome) function in communities with bacteria.  

    This article does not mention that patients with small bowel Crohn’s disease often have increased serologic responses to Saccharomyces cervasia (baker’s yeast), a component of the mycobiome that provides further intrigue.

    However, these investigations are very preliminary and will require much more extensive research to clarify the different players and how they interact.

    • Stephen B. Hanauer, MD

    • Professor of Medicine
      Northwestern University Feinberg School of Medicine
      Medical Director, Digestive Health Center
      Northwestern Medicine

    Disclosures: Hanauer reports no relevant financial disclosures.

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