Fungi living in the human body may have a much greater impact on health than researchers have long believed.
Among the millions of tiny life forms that live on and inside the human body, there are countless species of fungi. The skin is a mosaic of fungi, the membranes inside the nose and genitals are full of fungi, and they even live together with bacteria in the intestines.
While people can get some fungi from their mothers at birth, new fungi are also constantly introduced into the body by consuming yeast every time (when we drink
beer or eat
bread), and by inhaling steaming fungal spores with every breath.
Many of these fungi are quickly destroyed by the immune system, but others are temporary passengers or lifelong acquaintances. Recently, scientists have been investigating how inhabitants of a fungal nature can affect the brain and behavior.
The neurological effects of fungi
Doctors have long known that fungi can cause dangerous brain infections. But now researchers are also finding curious, though sometimes contradictory, hints that these microorganisms may have other neurological effects on humans. This idea may conjure up images of the fungus that turns people into zombies from HBO's apocalyptic series The Last of Us ("One of Us").
But while scientists agree that the idea of fungi having complete control over the body is implausible, they are seriously investigating whether some fungi inside humans could contribute to brain-damaging diseases such as Alzheimer's, or whether fungi living in the gut could influence behavior and mental health.
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Experts say this is a new area of research, so there are more questions than answers. But these possibilities are important to explore - both to understand the deep and complex relationships with microbes and to find new ways to promote health.
In general, humans are pretty good at resisting fungi (warm body temperatures make it difficult for them to reproduce). And many of the fungi that do reproduce may be beneficial to humans, perhaps by supporting the immune system or helping wounds heal, according to microbiologist Matthew Olm from the University of Colorado at Boulder, USA. "I would say that fungi are definitely an important part of human health," he says.
Infections caused by fungi
But many other fungi can cause infections, from foot mycosis to thrush. This happens when people encounter new harmful fungi in the environment or when fungi that naturally co-exist with humans begin to multiply in huge numbers under certain conditions, according to Rebecca Drummond, a mycological immunologist at the University of Birmingham, UK.
Fungi rarely enter the brain, thanks to protective barriers in the lungs and intestines, as well as the brain's own defense system - the blood-brain barrier - and immune cells that are ready to destroy any fungi that enter the brain.
But fungal infections of the brain do happen, and the number of such cases has increased in recent decades. This is due to the growing number of people with weakened immune systems, partly because of the global spread of the immune-damaging HIV virus, especially in parts of Africa, but also because of the increasing use of immunosuppressant drugs in cancer patients and organ transplant recipients.
"The more we use these immunomodulatory drugs, the more often we're going to encounter these fungal infections," Drummond says.
Fungi that affect the brain sometimes originate from the lungs, including Aspergillus or Cryptococcus, which are inhaled as airborne spores that can germinate, grow and spread if left unchecked.
Less commonly, Drummond said, common intestinal inhabitants such as Candida albicans overgrow uncontrollably and, once in the brain, branch out and produce nerve-killing toxins. Cryptococcus, meanwhile, can grow into tumor-like growths. "It's obviously causing a lot of damage," she says.
Fungal infections of the brain are often fatal, with Aspergillus deaths reaching over 90%. They can be difficult to treat, Drummond says: There aren't many antifungal drugs available, and not all drugs penetrate the blood-brain barrier to kill fungi living in the brain. Some fungi have already developed resistance to these drugs.
People who survive fungal infections of the brain are often left with long-term brain damage. AIDS patients who survive cryptococcal meningitis resulting from Cryptococcus x brain infection suffer from visual impairment, memory loss and dizziness.
Alzheimer's disease and fungus.
Scientists have long known about the dangers of fungal infections of the brain. But in recent years, some have been exploring the possibility that fungi infiltrate the brain much more frequently than previously thought, and may even contribute to the nerve cell death that occurs in diseases such as Alzheimer's.
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According to Richard Lath, a molecular biologist at the University of Edinburgh in the United Kingdom, some of the most interesting evidence for this theory comes from several cases in which fungal and other microbial infections of the brain were accidentally discovered in people initially diagnosed with Alzheimer's disease.
In several cases, when doctors prescribed drugs to fight the infection, "the dementia symptoms disappeared," says Lat. "What's remarkable is that some of them returned to work."
Microbes penetrate the blood-brain barrier quite often but are usually suppressed or destroyed in people with a healthy immune system, but as it weakens with age, this can lead to a buildup of microbes in the brain, possibly causing inflammation that destroys nerve cells.
"It's only when the immune system is weakened that you can see the damage," says Lath. Scientists have long linked Alzheimer's disease to the accumulation of certain proteins in the brain, but there is currently an active debate about whether the presence of these proteins is a cause or just a symptom of the disease.
Laith argues that these proteins are actually produced as a defense mechanism against microbial entry, based on research that shows the proteins have infection-fighting properties.
Further evidence that microbes that penetrate the brain can cause Alzheimer's disease comes from experiments on mice, where scientists observed how the fungus Candida albicans infiltrated the brain after the rodents' immune systems were weakened.
And in one preliminary study, which has yet to be peer-reviewed by other scientists, Late and his colleagues examined brain slices from deceased healthy people and Alzheimer's patients. They found high levels of bacteria,
viruses and fungi in both groups, but more in the brains of Alzheimer's patients.
"If microbes are indeed a factor in Alzheimer's disease, we may be able to mitigate or even prevent the disease by boosting people's immune defenses, such as with vaccines, which have been shown to boost overall immunity. But this theory is still young," Laith says. And it's also controversial.
Olm and other scientists argue that it is difficult to rule out the possibility that microbial genetic material could have come from contamination, since microbial fragments tend to be ubiquitous. Laith, however, thinks this is unlikely, citing reports that microbial fragments in brain tissue are as abundant inside the samples as they are on their surface, while pollution from the air is mostly deposited on the surface of the brain.
However, Olm argues that finding more microbial fragments in the brains of Alzheimer's patients is not proof that these microbes cause the disease. For example, these people could simply have a weaker blood-brain barrier or some other problem, causing more germs to enter their brains over time before being destroyed by the immune system.
Animals and fungi
But new evidence that microbes can enter the brains of animals such as
fish strengthens the suggestion that it can also occur in mammals and perhaps even humans. In the 2024 study, scientists placed bacteria with tiny fluorescent green molecules in tanks of salmon and trout.
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"After a week, you could see these microbes entering the brain of the fish, staining it green," Olm says. "And curiously, the microbes appear to live there without serious consequences for these fish throughout their lives."
In any case, the idea that fungi and other microbes enter the brain in old age - either because the brain's immune system is weakened or the blood-brain barrier is worn down - seems more plausible.
"I think we've now reached the threshold where there's enough smoke around this hypothesis that it's it's worth spending money to find out if it's happening," Olm says.
Interestingly, the fungi may not need to enter the brain to affect it. In a 2022 study, immunologist Iliyan Iliev from Weill Cornell Medical Center in the US and colleagues found that adding Candida albicans to the intestines of mice made them more resistant to intestinal mucosal damage caused by bacterial infections or heavy antibiotic use.
Strengthening the intestinal wall may be the body's defense mechanism, preventing fungi and other microbes from the gut from reaching other tissues. But the big surprise came when the team observed rodent behavior.
Notably, mice colonized with fungi were much more likely to sniff, socialize, and interact with other mice, meaning that exposure to fungi also seemed to have some effect on behavior.
Based on other experiments, the scientists theorized that certain molecules secreted by the mice's immune cells enter the bloodstream and somehow stimulate certain nerve cells in the brain that are involved in behavior. "This was a big surprise to us," Iliev recalls.
Why, at least in mice, there is such a relationship between gut fungi and the brain remains a mystery. Is it a coincidence that immune signals triggered by fungi affect the brain, or "is this really done by fungi on purpose to ensure their survival?"," says Iliev. "Perhaps the mammalian organism somehow benefits from changing its behavior in response to fungi."
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There is no evidence yet that such a relationship between gut fungi and the brain exists in humans, but the possibility is worth exploring, Olm said. In recent years, there has been mounting evidence that gut bacteria may send signals to the brain through the immune and nervous systems or by producing substances associated with symptoms of depression, anxiety and relaxation. Basically, Olm says, "there's no reason to believe that fungi don't do the same."
Mental disorders associated with fungi
Some scientists are even investigating whether fungi may be linked to mental disorders. Several studies have found differences in the composition of gut fungi in people suffering from depression or bipolar disorder.
According to a 2016 study by neuroscientist Emily Severance of Johns Hopkins University and her colleagues, women with schizophrenia who showed signs of exposure to the gut fungus Candida albicans tended to score lower on tests of memory and other cognitive abilities.
Severance is exploring the possibility that Candida overgrowth, caused by, for example,
stress or antibiotics, triggers an imbalance of gut microbes, altering the substances they produce in a way that makes susceptible people more likely to develop schizophrenia.
If this is true, doctors will be able to treat the symptoms of schizophrenia by prescribing probiotics to people to help reverse the overproduction of Candida, which would be helpful anyway.
However, finding a link does not mean that the fungus causes schizophrenia. Perhaps these patients are simply more prone to high levels of Candida. For now, "we can only hypothesize," Severance says. "I think this is typical of an area of research that is very interesting but still in its early stages of development."
Which - if any - of the fungal inhabitants actually affect the brain, scientists hope to find out in the coming years. "Fungi are definitely important," Drummond says. "But exactly how important they are, I think, remains to be seen."
One thing is already clear: bacteria have long been at the center of research; perhaps it's time to pay serious attention to fungi, which discreetly affect the body's health from the inside out.