Do gut fungi play a role in brain health?

At first glance, the idea that the bacteria in your gut can influence your mind seems fairly unbelievable. How could a microscopic, single-celled lifeform impact your brain?

As researchers dig into the details, it’s become clear that these legions of microbes do indeed have some sway over your brain health.

Through various mechanisms, gut bacteria can talk with your brain, and your brain can talk back. Scientists call these lines of communication the gut-brain axis.

We have a long way to go before we truly get to the bottom of this complicated web of chatter, but there are some aspects of the gut-brain axis that we know even less about.

Bacteria are not alone

By weight, bacteria make up the largest proportion of the bugs in your gut. But they’re not your only onboard guests.

Your gut microbiome also includes some actors whose influence is even more mysterious. They include:

  • Viruses: including bacteria-killing phages

  • Fungi: such as Candida albicans, a common cause of fungal infections

  • Protists: a mixed bag of lifeforms that include amoeba and slime molds

  • Archaea: bacteria-like, single-celled organisms

In this article, we’ll focus on fungi and their potential links with brain function and brain health. The fungi living in your gut are called your gut mycobiome. 

Although scientists know much less about how fungi influence health, there are some interesting hints.

Many fungi

Gut bacteria have been the focus of most research into the gut microbiome. This is partly because they are so numerous. 

Fungi make up just 0.01% to 0.1% of the genes found in human stool.

It’s difficult to imagine such a small amount of fungi could have much impact, but experts estimate that your mycobiome includes around 1 billion organisms.

That’s much fewer than the trillions of bacteria, but it’s a substantial crowd.

As well as being less numerous, the gut mycobiome is also less diverse than gut bacteria. 

Yeasts make up most of the mycobiome, such as C. albicans and Saccharomyces — a group that includes brewer’s and baker’s yeast.

Like your gut bacteria, gut fungi also have close links with your immune system, but what about links to the brain? 

Below, we’ll outline some links that scientists have uncovered between the mycobiome, mental health, and other neurological conditions.

Then, we’ll investigate how fungi might be influencing brain health.

Before we get cracking, we should note that much of the research in this area is in small groups of humans, animals, or the laboratory. That means that it’s tricky to translate these findings into humans. 

In depression

Although there is growing evidence that depression is linked with changes in gut bacteria, scientists haven’t teased apart cause and effect yet. 

In other words, they don’t know whether the shifts in gut bugs influence depression or whether other factors related to depression influence gut bugs. 

Most researchers have only looked at changes in gut bacteria, but one group of scientists looked for changes in gut fungi, too. 

They compared poop samples from 16 people without depression with 24 people who were experiencing a depressive episode. 

In agreement with earlier studies, the researchers found differences in gut bacteria between the two groups. They also found changes in gut fungi. 

In particular, they showed that people with depression had less variety of fungi and more Candida in their poop.

This was a small study, though, so we’ll have to wait for more research to back this up. 

Schizophrenia and bipolar disorder

Another suggestion of a link between gut fungi and brain health comes from research into schizophrenia. 

In one study, for instance, scientists focused on levels of antibodies to the fungi C. albicans. Antibodies are produced by your immune system when faced with a foreign invader. 

According to the authors, measuring these antibodies is a way of determining lifetime exposure to the fungus.

The scientists recruited individuals with schizophrenia, bipolar disorder, and people without a psychiatric condition.

They found that males with schizophrenia were more likely to have higher levels of antibodies to C. albicans. But this link wasn't present in females. 

However, in females, those with higher levels of antibodies to C. albicans were more likely to score lower on cognitive tests.

In earlier studies, the same group of researchers found that, compared with healthy individuals, people with schizophrenia and bipolar disorder have higher levels of antibodies to a yeast called Saccharomyces cerevisiae.

S. cerevisiae is commonly used by bakers, and experts don’t consider it to be a health concern.

Of course, there is the classic problem of cause and effect: Do changes in fungi drive the condition, or does the condition lead to changes in fungi? 

One study, however, provides a tantalizing glimpse behind the cause-and-effect curtain. 

The scientists recruited 56 people with schizophrenia. They treated some of the participants with probiotics containing two species of bacteria. The other participants received a placebo as a control.

Compared with people in the control group, those receiving the probiotic had reduced levels of C. albicans antibodies and, importantly, improvements in psychiatric symptoms.

This isn’t proof that fungi drive the symptoms, but it’s another piece of the puzzle.

The authors of the study suggest that probiotics “restore the gut microbiota,” which helps curb the overgrowth of fungi. Although precisely why this leads to changes in symptoms isn’t clear. 

Gut fungi and Parkinson’s disease

In Parkinson’s disease, cells in a part of the brain that helps control movement slowly die off.

Although treatments can slow the progression of Parkinson’s, there’s no cure. And scientists are still trying to figure out how and why the condition starts.

One theory is called the hibernating spore hypothesis.

Hibernating spore hypothesis

Some experts believe that a fungus — entering through the nose or mouth — might produce spores that reach the brain. 

These spores then lie dormant. Later in life, as the body changes with age, they may become activated and start causing damage. 

Although the theory has not been proven, the idea has spurred scientists to look for changes in the gut mycobiome of people with Parkinson's.

One study compared the gut mycobiome of 35 people with Parkinson’s with 20 individuals without Parkinson’s. The scientists found significant differences.

Another study compared 34 people with Parkinson’s and 25 healthy participants. In particular, they found that almost 40% of people with Parkinson’s had Geotrichum molds in their gut compared with just 0.05% of the healthy controls.

Experts don’t consider Geotrichum a significant threat to health, so it’s not yet clear whether this is a meaningful finding.

We should also note that, although other researchers have also identified changes in gut fungi, not all studies have found differences.

Why the link?

Scientists are still trying to understand why (and if) there are relationships between certain neurological conditions and gut fungi. 

However, they’ve uncovered some potential ways that these organisms might interact with our nervous system.

For instance, studies have shown that some species of fungi can produce norepinephrine — a neurotransmitter — while others can produce histamine. Both of these compounds have effects in the brain. 

According to the experts, it’s not clear whether these products would reach the brain. 

However, they might interact with nerves in the gut, which could then send messages up the chain to the brain.

Going in the other direction — from brain to gut — the neurotransmitter serotonin appears to reduce the potency of C. albicans in the lab. In this way, the brain could potentially influence the gut mycobiome.

Complicated relationships

Scientists have measured changes in gut bacteria linked to all of the conditions we’ve mentioned above. Could these shifts in bacteria help explain the changes in gut fungi?

These microorganisms all live in close quarters, so changes to one type of bug can influence the others.

As just one example, some bacteria can produce fungus-killing chemicals. So, if there are more of those bacteria in the gut, there are likely to be fewer fungi. Alternatively, there might be more fungi if there are fewer fungi-killing bacteria.

Although we know relatively little about how gut fungi and gut bacteria play together, we can safely assume it’s complicated. Like any ecosystem, changes in just one species can affect them all.

Leaky gut?

The authors of the studies looking at schizophrenia and bipolar suggest that if a fungus grows out of control, it might disturb the lining of the gut, causing a “leaky gut.” 

A leaky gut means that your gut walls let through compounds they would normally keep locked in.

This includes chemicals produced by bacteria and fungi, including toxins. If these breach the gut walls, they can enter your blood supply and perhaps reach your brain.

Another theory is that an abundance of Candida — a fungus that has cropped up throughout this article — might stimulate the release of immune cells. Then, once they reach the brain, they might trigger depressive symptoms.

However, at this point, it’s mostly theoretical. Any or all of these explanations might play a part, alongside a range of others.

Scientists still have many relationships to examine: interactions between bacteria and fungi, interactions between different types of fungi, and interactions between the fungi and you. And that’s just for starters.

No doubt, as science plumbs the depths, we’ll get to the bottom of this conundrum. It’s likely to be a fascinating journey.

Sources

A human gut microbial gene catalogue established by metagenomic sequencing. Nature. (2010). https://www.nature.com/articles/nature08821 

Association between Parkinson’s disease and the faecal eukaryotic microbiota. Npj Parkinson’s Disease. (2021). https://www.nature.com/articles/s41531-021-00244-0  

Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity. (2015). https://pubmed.ncbi.nlm.nih.gov/25882912/  

Altered gut bacterial–fungal interkingdom networks in patients with current depressive episode. Brain and Behavior. (2020). https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.1677  

Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophrenia. (2016). https://www.nature.com/articles/npjschz201618  

Gastrointestinal inflammation and associated immune activation in schizophrenia. Schizophrenia Research. (2012). https://www.sciencedirect.com/science/article/abs/pii/S0920996412001478  

Geotrichum. (n.d.). https://www.sciencedirect.com/topics/medicine-and-dentistry/geotrichum 

Immunity to Commensal Fungi: Detente and Disease. Annual Review of Pathology: Mechanisms of Disease. (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573037/  

Interaction of serotonin with Candida albicans selectively attenuates fungal virulence in vitro. International Journal of Antimicrobial Agents. (2005. https://www.sciencedirect.com/science/article/abs/pii/S0924857905002001  

Investigating colonization of the healthy adult gastrointestinal tract by fungi. mSphere. (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874442/  

P329 Faecal mycobiome disparities of individuals afflicted with Parkinson's diseases versus control. Gut. (2021). https://gut.bmj.com/content/70/Suppl_1/A211  

Parkinson's disease; the hibernating spore hypothesis. Medical Hypotheses. (2017). https://pubmed.ncbi.nlm.nih.gov/28673590/  

Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study. Brain, Behavior, and Immunity. (2017). https://www.sciencedirect.com/science/article/abs/pii/S0889159116305219  

Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Bipolar Disorders. (2013). https://pubmed.ncbi.nlm.nih.gov/24313887/  

The gut mycobiome in Parkinson’s disease. IOS Press. (2021). https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd202237  

The gut mycobiome of the Human Microbiome Project healthy cohort. Microbiome. (2017). https://pubmed.ncbi.nlm.nih.gov/29178920/  

The mycobiome: A neglected component in the microbiota-gut-brain axis. Microorganisms. (2018). https://www.mdpi.com/2076-2607/6/1/22/htm