A Q&A On Candida With The Scientist Who Named The Mycobiome

Mahmoud Ghannoum, Ph.D., is a NIH-funded researcher since 1993, who's spent his career studying fungi in the body, about 50 different species living in our gut. He has published over 400 papers and has been cited over 18,000 times. Dr. Ghannoum is credited with uncovering the significant interplay between bacteria and fungi, which affects the critical balance of the body's microbiome. Much of this interaction occurs at a digestive plaque wall that Dr. Ghannoum discovered with his research team at Case Western Reserve University in 2016. Dr. Ghannoum also came up with the name that is now used by the scientific community for the body’s fungal ecosystems: the mycobiome. Most recently, Ghannoum's research led him to develop the first probiotic, BIOHM, designed to balance the body's larger microbiome by addressing both good and bad native fungi, as well as bacteria. Here, he shares his expertise on Candida.

So, what is Candida? 

Candida is the most dominant fungal species in our body's mycobiome that can be both helpful or potentially harmful to our body. Candida is sort of the chameleon of the fungal community, because it's really good at adapting to the various environments in our body, which has allowed it  to successfully live in humans.

Can you talk a little about your research experience working with Candida?

My academic career spans almost 4 decades where I have concentrated my research mainly in systemic invasive fungi, with a special focus on Candida. I have been involved in the study of microbial Candida virulence factors (i.e. what makes a fungus cause disease) and I was one of the first scientists to study the biology and resistance of Candida plaque, scientifically known as biofilms.

More recently, I steered my research to use an inter-disciplinary approach to decipher the complex interactions within biological systems. Over the last 10 years we successfully analyzed the bacteriome (bacterial community), the mycobiome (fungal community), metabolomics, proteomics, transcriptomics and lipidomics.  The following is a highlight of some of the work I have done.

• Candidal adherence studies: I have a longstanding interest in the study of Candida albicans ability to stick (called adherence) to our cells, which is believed to be the first step in how Candida invades our systems.

Without getting too much into the weeds, we established a link between adherence, and the level of hamfulness of various strains of Candida albicans. We also studied the role of various antifungals and natural products on candidal adherence and identified drugs that can interfere with Candida's ability to adhere to our systems.

This work culminated in the publication of a number of research articles and a book, Candida Adherence to Epithelial Cells (it's a real page turner!). 

• Contribution of extracellular phospholipases to candidal virulence: Building on my Candida adherence studies, I wanted to determine the role of how Candida secretions contribute to its harmfulness. What we found was that there were specific sub-genes of Candida that were particularly harmful due to their secretion levels.

Our work provided unequivocal evidence that certain secretions can determine how harmful a particular strain of Candida albican can be.  This work was funded by the National Institutes of Health.

We also conducted further studies to prove the mechanism by which harmful Candida albicans cause direct damage to cell membranes.  Specifically, as a fungus migrates across the digestive tract, it penetrates the gut's lining.

• Lipid and sterol biochemistry: I am always trying to go deeper with my research, and part of that was studying fungal lipids and sterols because of their importance in understanding how Candida albicans become harmful.

We investigated the role of lipids in changing the shape of Candida, effecting Candida's ability to stick to our systems and form plaques (biofilms). I have published extensively in this area, including a CRC Volume “Lipids of Pathogenic Fungi”. Recently we characterized the lipidomics of candidal biofilm. 

• Biology and drug resistance of Candida Plaque (Biofilms): Candida biofilms are problematic since they are associated with serious wellness issues. We performed various biofilm studies that proved that candidal biofilm formation proceeds through 3 distinct phases. These studies formed the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance.

Our studies represent a breakthrough in the treatment of invasive Candida infections. We also demonstrated that antifungal resistance in biofilms is a multifactorial phenomenon and is biofilm-phase dependent. I recently received an NIH grant to continue our studies into the biology and drug resistance of Candida biofilms, using state-of-the-art genomic and proteomic approaches.

These studies allowed us to identify genes and proteins involved in the formation of biofilms, as well as development of drug resistance.

• Systems Biology: Recent advances in system biology have ushered the "omics" era. My group has been at the forefront of these developments where we integrated the biology of microorganisms with the state-of-the-art technologies including bacteriome, mycobiome, proteomics, metabolomics, transcriptomics, and lipidomics in order to gains deeper insight into the role of microorgranisms in health and wellness.

We utilized these resources to profile the bacteriome and mycobiome in people with HIV, and we identified the interactions between various members of the microbial communities in our total microbiome.

This allowed me to identify safe fungal strains that disrupt harmful candida. I've been lucky enough to do this research through funding from the NIH funded RO1. More recently, we have turned our attention to the study of the bacterial and fungal community in people suffering from Crohn's disease and showed that not only bacteria but also fungi, particularly Candida, cooperate together to form digestive plaques.

I could go on and on, but I think you can see that I have dedicated my career to not only fungal research, but Candida in particular. I am so fascinated by it. I literally dream about it. (Sad I know!)

I have published over 400 peer-reviewed articles in the fields of biofilms, microbial pathogenesis (how microorganisms cause disease) and the evaluations of antimicrobials. I have edited two American Society of Microbiology books on microbial biofilms.

Over the last 6 years recognizing the role of the microbial community, bacterial and fungal, we published the first study describing the oral fungal microbiome (mycobiome) of healthy individuals. This lead me to coining the term, "mycobiome."

In a separate study, we described the bacterial microbiome (bacteriome) and mycobiome in HIV-infected patients.

In summary, my team consists of the leading scientists in characterizing the interaction between bacteria and fungi as they relate to health and wellness.

In fact, I just published an opinion piece in The Scientist on the contribution of the mycobiome to health (http://www.the-scientist.com/?articles.view/articleNo/45153/title/The-Mycobiome/).

As I previously mentioned, my study characterizing the bacterial and fungal communities in Crohn's patients resulted in my discovery of how bacteria and fungi work together to create digestive plaque.

One of my passions has been helping people infected with HIV and AIDS.

I have been lucky to lead some very important studies in how fungi affects people with HIV and AIDS, and I was the Chairman of the Oral HIV-AIDS Research Alliance (OHARA).

In 2009, I was appointed as the Chairman of the Subcommittee on Antifungal Susceptibility Testing, Clinical Laboratory Standards Institute (CLSI) and served as an Advisor to the CLSI Consensus Microbiology Committee. CLSI develops the standards for laboratory work across the entire healthcare community.

Based on my research, I was recently appointed as a permanent member of the NIH's Drug Development and Resistant Study section.

Have you written or lectured about Candida?

As I mentioned, I have published over 400 peer-reviewed articles in the fields of biofilms, microbial pathogenesis and preclinical studies of antimicrobials.
I Authored or edited eights book on fungi:

1. Ghannoum MA, Moore KE, and Al-Hassan RH. 1984. Techniques for the Microbiological Analysis of Water. That ES-Salsil, Kuwait.

2. Ghannoum MA, and Radwan SS. 1990. Candida Adherence to Epithelial Cells. CRC Press, Boca Raton, Florida.

3. Prasad R, and Ghannoum M. 1996. Lipids of Pathogenic Fungi. (eds). CRC Press, Boca Raton, Florida. 

4. Ghannoum MA and O’Toole G (editors). 2004. Microbial Biofilms. Publisher, American Society for Microbiology Press. (Reviewed in New England Journal of Medicine, February 2005.)

5. Ghannoum M, Isham N. 2005. Antifungal susceptibility testing. ASM Clinical Microbiology Procedures Handbook. American Society for Microbiology

6. Ghannoum M, Perfect J. 2010. Antifungal Therapy. Informs Healthcare 50

7. Ghannoum, Mahmoud, Parsek, Matthew, Whiteley, Marvin, and Mukherjee, Pranab. 2015. Microbial Biofilms. Second Edition, Publisher, American Society for Microbiology Press.

8. Ghannoum M, Perfect J. 2017. Antifungal Therapy. CRC Press

I have given over 300 lectures on the role of fungi in health and wellness across the world. I have been so lucky to travel the globe as I speak on my research, visiting everywhere from New Zealand and Australia, to South America, Japan and China, and literally everywhere in between.

Is Candida only bad, or is there such a thing as "good" Candida?

As a positive, Candida, especially Candida albicans, colonizes our mouths, digestive tract, our skin and the vagina. In fact, it's found in 70% of healthy adults. We first come into contact when we are infants.

So while the word "Candida" is widely looked at as the boogeyman of the microbiome, it is completely normal to be present in the digestive tract. Healthy Candida levels are vital for proper nutrient absorption and to protect the intestinal tract from other infections.

It all comes back to the fact that since the gut has its own immune and neurological systems, keeping your gut’s balance is key. Therefore, you never want to completely get rid of a fungus like Candida.

However, Candida's benign existence in our body can become problematic if we develop immunodeficiency, epithelial damage to our cells or our gut's microbiome becomes unbalanced.

In fact, the problems Candida causes can largely be to the way we live, and the way we practice medicine. As an example, the infection with C. albicans has increased with the availability of modern medical treatments such as antibiotics, cancer chemotherapy and solid organ transplantation. These predisposing factors provide Candida with an optimal chance to overgrow and affect our health and wellness.

Regarding the digestive tract itself, keeping Candida levels in check is critical since its overgrowth is a common cause of digestive disturbance.

What role can BIOHM play when it comes to Candida? 

BIOHM can play several roles when it comes to Candida. First, people can use the BIOHM Gut Report to know the exact strains and levels of bacteria and fungus in their digestive systems, including Candida. 

They can also use BIOHM probiotics to help maintain the total balance of their gut's microbiome. We specifically designed BIOHM to not only balance the bacteria in the digestive system, but the fungal community as well. It's critical you balance both bacteria and fungi, otherwise, you only are dealing with part of the issue. Importantly, BIOHM is only engineered to balance the total balance of the gut's microbiome, not to treat or cure candida related diseases.