A new review explores how targeting gut bacteria and fungi interactions may help manage chronic intestinal inflammation

Research in the gut microbiome field has usually only focused on resident bacteria and the related bacterial-host interactions. However, emerging scientific evidence suggests that studying the human fungal community (called mycobiome) could help us better understand the role of the microbiome in health and disease, specifically in inflammatory gastrointestinal diseases.

A recent review article, led by Dr. Christopher L. Hager and Dr. Mahmoud A. Ghannoum from the Centre for Medical Mycology at the Case Western Reserve University and University Hospitals Cleveland Medical Centre (Cleveland, USA), explores the role of the interactions between bacteria and fungi in Crohn’s disease and potential strategies to target the gut microbiota in gastrointestinal diseases.

In 2010 the same research group published the first study that identified the “basal mycobiome” of 20 healthy individuals using a novel pyrosequencing approach and provided the basis for a detailed characterization of fungi present in the oral cavity. Based on these results, the authors emphasized that beyond bacteria and viruses, the associations of the mycobiome with host health and disease should be taken into account when focusing on maintaining a healthy balance of the gastrointestinal total microbial communities. Since then, only few studies have characterized the mycobiome of the gastrointestinal tract in health (here; here).

In the context of investigating the role of mycobiome in inflammatory bowel disease (IBD), selecting the appropriate control cohort matters. This is based on a recent study in humans that has shown the diversity of gut microbial communities of both Crohn’s disease (CD) patients and their first-degree healthy relatives were different from unrelated healthy individuals.

When focusing on the role of the mycobiome in IBD, a first experimental study in a dextran sodium sulfate-induced colitis mouse model showed that fungi are involved in aggravating the severity and inflammation of IBD. These data support the idea that fungi also cooperate with commensal bacteria in a way that could exacerbate inflammatory symptoms of IBD patients. In a previous study by the same group, the researchers found that the fungus C. tropicalis and the bacteria E. coli and S. marcescens were elevated in the gastrointestinal tracts of patients with Crohn’s disease (CD) -compared to their non-Crohn’s healthy relatives- and together cooperate to form a large biofilm capable of activating the host immune response.

The researchers have also reported in the review that when all three microorganisms were grown separately in lab dishes, they grew fine without any interference. However, when all of them were mixed together they started growing out of control and formed large robust biofilms. Indeed, transmission electron microscopy revealed that in the presence of E. coli and S. marescens, the fungus C. tropicalis stretches out into long filaments and both E. coli and S. marescens fuse to the fungal growths being more stable; this may lead to gut inflammation that worsens CD. These results suggest the importance of studying the role of the gut mycobiome in health and disease and considering maintaining balance of both fungal and bacterial communities for a proper gastrointestinal health.

Based on recent next generation sequencing data, the authors propose that giving IBD patients antifungal drugs and then adding a probiotic containing beneficial fungi, such as Saccharomyces cerevisiae, could be a potential way to balance gut health in chronic intestinal inflammation. Therefore, it seems targeting the gut (bacterial and fungal) microbiome could help in the future treatment of IBD and could be a novel complementary treatment for alleviating, in part, side effects of monoclonal antibodies currently used for IBD management.

In conclusion, recent research has shown that both bacteria and fungi are implicated in IBD. Based on the observation that bacteria and fungi cooperate in exacerbating intestinal chronic inflammation, the use of antifungals and probiotics could be a potential new treatment for restoring the balance of beneficial microorganisms. Further clinical trials, well designed and with large enough samples, may help add to the existing tools for treating IBD.

Reference:

Hager CL, Ghannoum MA. The mycobiome: Role in health and disease, and as a potential probiotic target in gastrointestinal disease. Dig Liver Dis. 2017; 49(11):1171-6. doi: 10.1016/j.dld.2017.08.025.