Mahmoud Ghannoum discusses his insights into Crohn’s disease and the mycobiome, as well as the new Entrepreneurship in Medicine pathway.
Mahmoud A. Ghannoum, PhD, MBA, FIDSA, FAAM is a professor in the department of dermatology at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at CWRU and University Hospitals Cleveland Medical Center, a multidisciplinary center that combines basic and translational research investigating fungi from the test tube to the bedside. He has been conducting infectious disease research for more than forty years.
Q. You named the mycobiome, which is the body's fungal community. Can you provide an overview of what it is? Where are we today in terms of researching the mycobiome?
A. Fungi and bacteria are present throughout the body. Both are microorganisms, which are minute forms of life that can only be seen with a microscope. Fungi are eukaryotes, meaning that they are organisms whose cells contain a nucleus. They are nearer to humans than bacteria, which are prokaryotes: single-celled forms of life without a nucleus. Collectively, the fungi that live in the human body are known as the mycobiome while our bacteria are called the bacteriome.
Disproportionately few studies have been done on the mycobiome compared to the bacteriome. Nonetheless, several recent investigations point to the importance of fungi in human health and disease.
Q. You led an international team identifying fungus in humans for the first time as a key factor in Crohn’s disease. Can you summarize what you found and what it could mean for the treatment of these conditions?
A. We have known for years that bacteria, in addition to genetic and dietary factors, play a major role in causing Crohn’s disease. Essentially, patients with Crohn’s have abnormal immune responses to these bacteria, which inhabit the intestines of everyone. While most researchers have focused their investigations on these bacteria, few have examined the role of fungi, which are also present in everyone’s intestines.
We assessed the mycobiome and bacteriome of patients with Crohn’s disease and their Crohn’s-free close relatives and others living nearby. We found 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 sick family members was considerably higher compared to their healthy relatives, suggesting that the bacteria and fungus interact in the intestines, making things worse for patients. Additionally, in test-tube and in animal research we found that the three indeed team up to produce a biofilm -- a thick, slimy layer of microorganisms that adheres to the intestines and which can prompt the inflammation that causes the painful symptoms of Crohn’s disease.
This was first time any fungus had been linked to Crohn’s in humans; previously it was only found in mice with the disease. We have to be cautious, though, and not exclusively attribute Crohn’s disease to the bacteria and fungi in our intestines. For example, family members often have similar diets and live in comparable environments. The bottom line, though, is that our study can be helpful in forming a new generation of treatments, including medications, probiotics, and dietary plans for Crohn’s patients and for gut health in general.
Q. You recently published a pathbreaking study on oral tongue cancer. What did you find and what are some potential implications for patients?
A. Squamous cell carcinoma of the tongue, which arises in the front two-thirds of the tongue and is also known as oral tongue cancer, is an aggressive disease that generally affects older people. It is different from back-of-the- tongue tumors, ninety percent of which are caused by human papillomavirus. Patients with oral tongue cancer often find it hard to eat, swallow food, or speak. It has been rapidly increasing and is now the second most common malignancy in the oral cavity.
My colleagues and I found that bacterial variety and richness, and fungal richness, are significantly reduced in tumor tissue compared to matched non-tumor tissues. This may mean that certain bacteria and fungi, in sufficient amounts and in possibly interactive ways, could play a part in the development of oral tongue cancer. Our findings mean that it may be feasible to carry out precautionary testing in patients at high-risk for oral tongue cancer. If the patterns of bacteria and fungi that we found are present in people who are not yet showing physical signs of the disease, such as lesions, we could begin treatment early, offering the opportunity for better patient outcomes. Such testing could also provide a less-invasive alternative to the biopsies currently used to diagnose oral tongue cancer.
Q. What is the potential for the mycobiome as a focus of research into human disease in general?
A. I think we are at the very early stage. While there have been some recent major findings, we’ve barely scratched the surface. For example, the oral mycobiome of HIV-infected patients differs from that of uninfected controls. There is less diversity in lung fungi in those who have cystic fibrosis. Greater presence of two fungal species, Candida and Saccharomyces, has been found in patients with more severe hepatitis B infections. And an excess of the gut fungal pathogen Candida tropicalis worsens inflammatory bowel disease. As more surveys of the mycobiome become available, such correlational data are likely to be found for many other diseases and can be further explored by trials in the lab. What is encouraging is that it is becoming clear both for scientists and lay persons that we cannot ignore the role of fungi in our health and wellness.
Q. You are preparing an Entrepreneurship in Medicine pathway for SOM students, which will begin in September 2018. Can you tell us your vision for the pathway as well as describe some of your own entrepreneurial activities?
A. The School of Medicine has introduced a series of optional pathways—or concentrations—that provide in-depth exposure to selected health care topics, such as health and wellness. One of the latest will be the two-year Health Innovation and Entrepreneurship in Medicine pathway, which is an exciting project for me, one I care deeply about. All of our discoveries won’t matter to patients if they can’t be converted into treatments for healing. The pathway, which is being developed in collaboration with the University’s Weatherhead School of Management, responds to the changing health care landscape resulting from an aging population and health care reform, which have created the need for new approaches to care.
The goal of the pathway is to expose students to the challenges and opportunities of taking health care innovations from early discovery to the market. We will meet for three hours each month; topics will include the history of innovation in health care, innovation in translational research, fundamentals of intellectual property (patents, copyrights, and trademarks), developing a business plan, and raising capital. At the end of the pathway, the students will present a health-care-related entrepreneurial idea and business plan to their peers, funders, and established health care entrepreneurs, who will provide feedback.
In terms of my own entrepreneurial activities, earlier this year I, along with several others including my son Afif, launched BIOHM, the first probiotic engineered to address the key role of fungi in digestive health. Current probiotics essentially only contain so-called good bacteria. They have left out fungi entirely, despite the role they play in the digestive process. BIOHM includes beneficial bacteria and beneficial fungi combined with an enzyme that helps break down digestive plaque—the biofilm that I referred to earlier. We also have recently launched several related products including BIOHM Children's Probiotic.