ByNatalia Mesa
Photographs ByMartin Oeggerli
Published December 4, 2023
• 7 min read
The gut microbiome has gotten a lot of attention in recent years as a flood of scientific studies link it to a host of ailments, from irritable bowel syndrome to neurological disorders.
Of the many types of microscopic organisms that make up the gut microbiome, bacteria receive the most attention. But other tiny organisms in the gut might be just as important to overall health—and they’re often overlooked.
Your microbiome also has its own mycobiome, or fungal communities that live in the gut, skin, and respiratory tract. Recent studies show that the mycobiome might help keep dangerous microbes at bay and regulate the immune system—or cause chronic disease.
(Your gut health can affect your whole body. The gut microbiome, explained.)
Scientists have linked the fungal communities in the gut to myriad diseases, including long COVID, and dozens of other intestinal, neurological, and respiratory diseases. And although researchers are only just starting to piece together how fungi impact our health, here’s what we do know.
What makes up the gut microbiome?
Researchers have studied the bacterial microbiome for centuries, but they’ve largely ignored the mycobiome, says Mahmoud Ghannoum, a microbiologist and professor at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center who coined the term “mycobiome.” (Ghannoum also cofounded BIOHM Health, a biotechnology company that’s testing probiotic nutritional supplements and biotherapeutics.)
The mycobiome accounts for roughly 0.1% of the microbiome—a term that includes not only bacteria and fungi but also the archaea, viruses, and parasites that colonize our skin, gut, respiratory tract, and urogenital tract. While scientists have documented hundreds of fungal species in human guts, only a few dozen are common across individuals.
Although they make up a minority of the microbiome, fungi are still extremely important, researchers argue. Studies show that fungi influence the growth and diversity of bacteria, and together, these communities can help us digest food and protect us from disease. Siew Ng, a professor and clinician at the Chinese University of Hong Kong and the university’s director of Center for Gut Microbiota Research, likens the microbiome to a vibrant rainforest ecosystem. “They are there to protect us,” she says.
(Why do some people love to exercise? It might be their microbiome.)
But sometimes, these microbial communities can also get out of balance—and when certain fungi start taking over the microbiome, it can spell trouble. Ghannoum explains that both fungi and bacteria can form a dense digestive “plaque” known as a biofilm that is resistant to antibiotics and literally forms a barrier to keep the body from absorbing nutrients.
This state of microbial imbalance is known as dysbiosis, and some of the ways it can occur are from taking broad-spectrum antifungals or antibiotics or having a poor diet. Scientists have linked it to dozens of diseases, and not just intestinal ones.
What is the impact of the mycobiome on disease?
Modern genetic sequencing tools allow scientists to profile all the microbes in a person’s gut and other organs. By comparing the mycobiomes of healthy and sick individuals, studies show that patients with irritable bowel syndrome tend to have high levels of the fungus Candida albicans in their gut. Likewise, scientists have linked dysbiosis to celiac disease, inflammatory bowel disease, colorectal cancer, and various other intestinal disorders.
Ng, for example, studies the mycobiome of people with obesity and has found that they have different gut mycobiomes than individuals that aren’t obese. In a forthcoming study, she’s currently testing the theory that certain bacteria and fungi break down food more readily than others, and she thinks she’s isolated a fungus that may have a role in breaking down fat.
The COVID-19 pandemic gave scientists further insight into how the mycobiome influences disease. Iliyan Iliev, a mucosal immunologist and associate professor of microbiology and immunology in medicine at Weill Cornell Medical Institute, had studied fungi and irritable bowel syndrome for a decade. But when the pandemic hit, he switched his focus COVID research. That’s when he found something surprising: Patients with severe COVID had abnormally high levels of antigens that instruct the immune system to attack fungi, even if no fungal infection was detected. The more severe their disease, the more antigens those patients made.
(Humans aren’t prepared for a pandemic caused by fungal infections.)
By continuing to look at the blood and stool of patients with severe COVID, Iliev and his team found that gut fungi may cause destructive inflammation in the lungs after a COVID-19 infection by revving up immune cells called neutrophils. These cells produce high levels of an inflammation-boosting protein called cytokine IL6 and can remain elevated in patients for up to a year after infection.
“You get into a situation where your immune system is always alert,” Iliev says.
The mycobiome might also be a critical component of the gut-brain axis, the two-way mode of communication between the two organs. Studies show the mycobiomes of people with autism is different than the fungal gut flora in people without. Beyond the gut, fungal imbalances are also linked to respiratory diseases like asthma and chronic obstructive pulmonary disease, as well as several skin diseases.
How can you improve your mycobiome?
So far most studies have only shown correlations between fungal imbalances and disease, Ng says. The next step is to start looking at whether microbial imbalances cause disease. Scientists can do this by studying germ-free mice, she explains—a process that would involve introducing microbes into the guts of mice to see if they develop symptoms of gastrointestinal disease.
But the “holy grail,” Ng says, will be to leverage the mycobiome to treat disease.
That’s already underway. Scientists are looking for drugs or nutritional supplements that can rebalance the microbiome, fungi included. Ghannoum has recently published the results of clinical trials showing that nutritional supplements designed to break down fungal and bacterial biofilms and rebalance the gut can potentially reduce gastrointestinal symptoms.
(Probiotics, prebiotics, postbiotics. What’s the difference?)
“We are still at an early stage,” Ghannoum says.
Ng, who was not involved in the study says that these types of interventions are promising. “I think we will be able to treat a lot of different conditions using this sort of therapy,” she says.
Ng adds that she and her colleagues have shown that fecal transplants may be effective at treating certain diseases. She’s had success in treating graft-versus-host disease, which happens when a patient who receives a transplant rejects the new tissue. Ng has found that isolating the microbes from the stool of healthy individuals and transplanting them into a sick patients can reduce symptoms of graft-versus-host disease in children.
For healthy people, experts overwhelmingly say that the best way to a healthy mycobiome—and a healthy microbiome, too—is to eat a diverse diet full of fibrous fruits and vegetables, exercise, and manage stress. Meanwhile, alcohol use, smoking, and diets high in processed sugars and salts can disrupt the balance of the mycobiome, Ghannoum says.
“I always say it’s like a garden. In the summer, you fertilize the flowers and pull weeds,” Ghannoum says. “It’s in our hands: we can do the same to rebalance the gut and have good health.”
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