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Mankind’s Delicate and Complex Relationship with Fungi

Mankind’s Delicate and Complex Relationship with Fungi
April 26
12:59 2016
There are trillions of microorganisms inside a single human body. In fact, our genes are outnumbered 100:1 by microbial genes. Together, these tiny organisms (microbes) are referred to as the “human microbiome.”

You hear a lot about bacteria and its relationship to human health, but your biota is also comprised of fungi and viruses (yes, there are fungi in your body). In recent years, more and more researchers have started to look into the way fungi affects human health and function. Case Western Reserve mycologist Mahmoud Ghannoum coined the term “mycobiome” to refer to the fungal community inside the human body.

“Back around 2008, I was attending meetings and noticed people were really starting to talk about the microbiome,” says Ghannoum. “But for the most part they were only talking about bacteria, not the fungus and viruses that also comprise our biome. I thought to myself that we should also start looking at fungal communities.”

Ghannoum’s revelation led him to conduct a study of the fungi within the human mouth. His study, which was published in PLoS Pathogens in 2010, was the first of its kind to utilize advanced genetic sequencing technology to define what makes up a “normal” mycobiome inside the human mouth.

His goal was to establish a baseline that could be compared to the distorted fungal populations in diseased patients.

Before Ghannoum’s study, little was known about mouth fungi. Using just 20 participants, Ghannoum’s team identified 101 fungal species inside the human mouth – each with between 9 and 23 strains.

Ghannoum found that a typical human mouth contains:

• Several species of Candida (imbalance causes thrush)
Cladosporium (an asthma trigger)
Aureobasidium (has been known to cause infections after organ transplant)
• Numerous beneficial species including Saccharomyces boulardii
• Numerous harmful species including Aspergillus, Fusarium, and Cryptococcus

Further Studies

lulo0041Ghannoum was surprised to find several potentially harmful fungi species in the human mouth. His team surmised that under normal conditions, other species keep these dangerous strains in check.

This assumption led him to the conclusion that a disruption in fungal equilibrium could bring on disease. Ghannoum pursued his theory by examining the mouths of those with HIV.

Next, Ghannoum conducted an experiment involving mice with compromised immune systems. His team found that Pichia (a type of yeast) was able to inhibit the growth of Candida and other pathologic species.
“By growing Pichia in the lab, we found that it secretes a compound that can treat fungal infections in animals,” he reports.

Ghannoum’s efforts convinced other researchers to begin studying mankind’s relationship with fungi. In 2013, a team from the National Institute of Health set out to determine what constitutes a “normal” skin mycobiome.

More recently, scientists in France compared the fungi present in the lungs of healthy humans with fungi found in the lungs of cystic fibrosis victims.

Gut Fungi

Hand on belly

In 2012, UCLA professor David Underhill and his team used tools similar to those used in Ghannoum’s study to profile what makes up a “normal” gut mycobiome in mice.

Underhill and his team found between 50 and 60 fungi genera in each rodent. “We showed that there is considerable fungal diversity in mice,” says Underhill, “but we were also interested in how these fungi might be contributing to disease.”

Underhill also found a relationship between the immune system and mammalian fungi; specifically, the fungi work to control inflammation. The team’s findings led them to identify a gene variant in humans that was associated with ulcerative colitis, a severe form of inflammatory bowel disease.

Underhill concludes that alterations in a person’s gut fungi could be a factor in causing inflammatory bowel disease.

“None of these factors are working in isolation,” says Underhill. “I think it’s probably a confluence of them all interacting with each other and with us – what we eat, what kind of nutrients they have, genetic influences and how our immune system reacts to both fungi and bacteria in the gut.”

Ghannoum agrees that its important to look at the big picture: “We know that when somebody takes an antibiotic they can develop fungal infections, so clearly there is interaction between these communities. From my point of view, I say, look, it’s not bacteria alone, it’s not fungi alone – you have to put them together.”

Treating Disease

What does all this research mean in regards to treating disease? Interestingly enough, the most promising treatment is fecal transplantation – taking stool from a healthy donor and putting it inside a patient affected with Clostridium difficile colitis (a serious bacterial infection that occurs as a side effect of antibiotic therapy).

It sounds gross, but patients receiving healthy stool have good odds of recovery. There is also growing evidence that probiotic approaches (including fungi and bacteria) may have benefits treating numerous disorders.

As New York University rheumatologist Dr. Jose Scher points out, however, this avenue of research is still in adolescence: “This is just the beginning of the field, but I think understanding how bacteria, viruses, and fungi can play a role in health maintenance and disease will help us develop more effective therapies.”

Ghannoum also has high hopes about potential treatment opportunities. “I think that the idea of probiotic and antibiotic therapies is a very important question. Should we use antifungals? Should we use antibiotics? Finally, should we use probiotics? They all make sense to me.”

First we must identify the “friendly fungi,” adds Ghannoum. This isn’t as easy as it may sound. Modern DNA sequencing has shown that many of our previous fungi classifications were wrong. “Fungal taxonomy is really complicated and not quite what we learned in school,” says Underhill.

Some fungi haven’t been classified at all.

Today, mycologists are hard at work trying to create a precise taxonomy that will hopefully illuminate fungi’s relevance in diagnosing and treating diseases in the future.

“We’re in a stage where we’re recognizing the biological significance of the fungi in our systems to help develop a common language and set of research approaches,” explains Underhill. “Soon, hopefully, we’ll know how they can be good for us, bad for us, and manipulated to our benefit.”

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April Kuhlman

April Kuhlman

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