The connections among different parts of the human body are full of surprises, but new research into the microbiome looks for connections that, on their face, seem absurd: Could a microbe that causes dandruff on your head also contribute to digestive problems?
That's one mystery that scientists are trying to unravel with research into the fungi that live in the area of human anatomy delicately referred to as the gut. While the bacteria that colonize our intestines have been a scientific focus for more than a decade, the fungal critters there are starting to get more attention.
Already, these studies have uncovered striking connections between fungi and several chronic illnesses, including Crohn's disease and ulcerative colitis. As is typical in medical science, a simple explanation (A causes B, which can be cured by C) is unlikely.
But the potential to improve the lives of hundreds of thousands of patients — and to uncover complex processes that we never realized were at the root of these diseases — has made the fungal field tantalizing to medical researchers.
"It's a very exciting area of science to be involved in," said David Underhill, research chair for inflammatory bowel diseases at Cedars-Sinai Medical Center in Los Angeles. "I think over the next five years, certainly 10 years, we will develop a very different understanding of this area."
Underhill's team is investigating the links between fungi in the gut and inflammatory bowel diseases like Crohn's.
Researchers first became interested in studying the microbiome when advances in DNA technology made it easier to identify microorganisms in and on the human body. Earlier work, Underhill said, focused mainly on bacteria because there are far more of them in our bodies, compared with any other type of organism.
There are trillions of bacteria in the digestive tract and as many as 100 different species. Fungi number in the hundreds of thousands, with just a handful of different species. For years, fungi were given scientific short shrift.
Now, with our understanding of the bacterial microbiome better established, researchers have turned their attention to the fungal microbiome, what some call the mycobiome. It has quickly became evident that these organisms play a distinct role in our health.
One fungus at the center of Underhill's research is Malassezia. Though its name may be unfamiliar, you're coated in it.
The fungus is ubiquitous on a healthy human body. It colonizes the skin shortly after birth. For some people, Malassezia on the scalp creates irritation that causes dandruff.
But it also turns up inside our bodies, along the digestive tract. In March, the journal Cell Host & Microbe published a study by Underhill and his colleagues that suggested a link between Malassezia in the gut and Crohn's disease.
They found that people with Crohn's had high concentrations of Malassezia on their intestine walls, while healthy patients had almost none. The researchers then demonstrated that simply adding this type of fungi to the gut — at least, in mice — was enough to exacerbate the inflammation seen in Crohn's.
This work built on a growing body of evidence linking fungi to inflammatory bowel diseases. As early as 2010, researchers reported that antifungal medications helped irritable bowel disease patients go into remission. By 2012, Malassezia, in particular, was found to be associated with these kinds of diseases.
In 2016, researchers in France published a study that showed the fungal populations in people with bowel conditions were wildly different from those in healthy patients.
"It's small pieces that we are putting together," said Mathias Lavie-Richard, a microbiologist at the Micalis Institute in France and a co-author of that study.
Crohn's disease is commonly treated using anti-inflammatory drugs known as TNF inhibitors. But these treatments are only effective for about 60% of patients, according to the Crohn's and Colitis Foundation.
The drugs are also costly: The anti-TNF drug Humira can run as much as $38,000 per year, depending on a patient's insurance.
The link between Crohn's and Malassezia raises the possibility — not yet proved — that something as simple as a generic antifungal drug could provide relief: wipe out the fungus, wipe out the inflammation. Underhill and his colleagues are moving into clinical trials now, just one of many teams eager to test the idea.
Scientists in Montreal are pursuing a similar clinical trial, with treatment beginning as early as this summer, according to Martin Laurence, a researcher and the creator of The Malassezia Project, which tracks the research published on this particular organism.
It's not just inflammatory bowel diseases that have been connected to the mycobiome. A study published by PLOS Pathogens in September found that altering the composition of gut fungi Wallemia mellicola in mice exacerbated symptoms of asthma. Some early evidence suggests a link between fungal infections and prostate cancer.
"The technology improves every year, we get better and better at identifying organisms and their role in disease and symptom processing," said Dr. J. Curtis Nickel, a urologist at Queen's University in Canada.
Nickel is the co-author of forthcoming research that suggests links between Malassezia and interstitial cystitis, a chronic and painful bladder condition. He said the next step for many researchers is to investigate how these fungi interact with and are affected by the other organisms that live alongside them.
"I personally suspect that it's an interaction of all the different bacteria, fungi and viruses," Nickel said. "An unhealthy population of these organisms exacerbates disease and perhaps even — this is the next step — causes it. But boy, we're not there yet."
Style on 10/21/2019