Published by the New York Times April 9, 2019
By Kaleigh Rogers
Following extensive study of the body’s bacterial occupants, researchers are turning to how our fungal residents may contribute to inflammatory bowel diseases and other maladies.
The connections among different parts of the human body are full of surprises, but here’s one you might not have considered: Could a thing that causes dandruff on your head also be contributing to your digestive problems?
That’s one mystery that scientists are trying to unravel with research into the fungi that live in your 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 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.”
Dr. 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, Dr. 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 fungi, what some call the mycobiome. It has quickly become evident that these organisms play a distinct role in our health.
One fungus at the center of Dr. Underhill’s research is Malassezia. Though its name may be unfamiliar, you’re currently 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. Recently, Dr. Underhill and his colleagues published a study in the journal Cell Host & Microbe that suggested a link between Malassezia in the gut and Crohn’s disease.
Individuals 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 I.B.D. patients go into remission. By 2012, Malassezia in particular was found to be associated with these kinds of disease.
In 2016, researchers in France published a study that showed the fungal populations in people with bowel conditions were wildly different than those in healthy patients.
“It’s small pieces that we are putting together,” said Mathias L. Richard, a microbiologist at the Micalis Institute in France and a co-author of that study.
The race is on to make these connections and add to the growing body of evidence. The findings could benefit hundreds of thousands of people.
Crohn’s disease, for example, is commonly treated using anti-inflammatory drugs known as TNF inhibitors. But these treatments are only effective for about 60 percent 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 proven — that something as simple as a generic antifungal drug could provide relief: Wipe out the fungus, wipe out the inflammation. Dr. 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 last year showed that altering the composition of gut fungi 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.
Dr. 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,” Dr. 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.”
Although we’re far from declaring antifungals a panacea for gut ailments, scientists are optimistic that further research into the mycobiome will help solve the mysteries surrounding these inflammatory diseases, and may even offer new forms of treatment.
“When you speak about this research to the people who have these diseases, it’s like a new light in the dark,” Dr. Richard said. “It’s a new hope.”