What are Malassezia?
Malassezia are fungal colonizers of humans and animals (Theelen et al 2018). They are best known as the cause of dandruff, a benign condition which affects about half of the adult population. They used to be called Pityrosporum, and many people still use the old name.
Can Malassezia on our skin make us sick?
Malassezia typically colonize our skin without causing any symptoms. In some people, Malassezia can cause seborrheic dermatitis, pityriasis versicolor and folliculitis. None of these are life threatening, and can be treated with fungicides such as ketoconazole shampoo.
Do we have Malassezia inside our bodies?
Until very recently, the textbook answer was: “No, Malassezia only colonize the skin of mammals”. In the 1980s, reports emerged of Malassezia causing acute infections inside the body, but this usually occurred in immunocompromised patients, so it was considered a rare exception (Shek et al 1989). We now know the textbook answer was flat out wrong: many research groups report finding Malassezia in the bodies of healthy adults (Dupuy et al 2014; Cleland et al 2014; Hallen-Adams et al 2015; Liguori et al 2016; Boix-Amoros et al 2017; Alonso et al 2018; Abusleme et al 2018; and many more), as well as in non-mammalian species (Amend 2014). So the answer is: “Yes, Malassezia are found in many organs of healthy humans.”
OK, Malassezia reach our internal organs, so what?
We know with certainty that Malassezia cause inflammatory skin conditions such as seborrheic dermatitis (Gupta et al 2004). Is it reasonable to assume that Malassezia never cause inflammation when inside the body? No! So what would seborrheic dermatitis inside the brain look like? Maybe it’s Parkinson’s disease. And so on, for each organ where Malassezia are found.
Which Malassezia species are found within our bodies?
Currently, the main species found within humans are Malassezia restricta and Malassezia globosa. There may be additional Malassezia species which often reach our internal organs, it’s too early to know for sure.
How can I “catch” Malassezia?
Shortly after birth, Malassezia have already colonized our skin for life (Nagata et al 2012), so we all “catch” Malassezia at a very young age. It seems Malassezia usually wait until puberty or early adulthood to permanently colonize our guts and genitals. This coincides with, and probably explains, the onset of chronic idiopathic inflammation of these organs in many people. The prevalence of Malassezia in other internal organs is not yet clear.
How can I eliminate Malassezia from my body?
Once an organ is colonized with Malassezia, our immune system doesn't seem able to clear them on its own. Antifungal shampoos can be used to reduce Malassezia populations on the scalp, and this cures dandruff. However, if this shampoo is no longer used, Malassezia and dandruff return. The efficacy of antifungal drugs on Malassezia inside the body has not been studied, so we don't know how well each drug works. A Crohn’s study suggests oral itraconazole may be effective against Malassezia in the gut (Samuel et al 2010).
What’s The Malassezia Project?
Until 2018, I was not sure which fungal genus was involved in prostate cancer, I only knew that our bodies produce the antimicrobial protein PSP94 to fight this fungus and protect us from this cancer. So from 2012 to 2017, I called it “The PSP94 Project”. During this period, my main goal was to determine which fungus was the culprit in prostate cancer. This phase is now complete. The next phase consists of funding university research groups to run clinical trials to determine which antifungal drugs can clear Malassezia from the body, and thus cure or prevent Crohn’s disease, ankylosing spondylitis, prostate cancer, benign prostatic hyperplasia, etc.
Who’s running this project?
My name is Martin Laurence. I’m a bioinformatician working for a small lab in Montreal, Canada. Previously, I designed computer chips for a living. Many academic researchers have directly contributed to this project in their respective fields (my coauthors), and many more have helped out without being credited. Patients have also helped: after reading my articles on Pubmed, they’ve pointed out important articles which I had not seen. I’m forever grateful to these folks for their encouragement, enthusiasm and generosity.
Are you credible?
I’d like to think so! I don’t have a graduate degree in biology, I am not affiliated with a university and my PCR machine is made of wood. Despite this, I’ve published peer reviewed articles with established researchers at Johns Hopkins, Yale, Washington University, Oregon Health & Science University and Universidad Complutense de Madrid. Imagine how high that bar was!
How are you going to make money with this?
I’m not. I’ve spent much of my retirement savings supporting basic research for this project already.
Why do you care about this then?
I know folks who have had prostate cancer, Crohn’s disease or spondyloarthritis. They’ve suffered a great deal. There are millions more like them, suffering right now. If tables were turned, would I want an obscure Canadian to do all he can to cure me? Absolutely! Enough said.
FAQ - My skeptical friend has questions
How can a single microbe possibly do all this?
It’s mind boggling that a single microbe can do so much seemingly unrelated harm: prostate cancer, benign prostatic hyperplasia, Crohn’s disease, ulcerative colitis, psoriatic arthritis, ankylosing spondylitis, uveitis, multiple sclerosis, etc. If it wasn’t for syphilis, aka “The Great Imitator”, I wouldn’t believe it either! We now know syphilis is caused by a single microbe, Treponema pallidum, which colonizes our internal organs. Had we not discovered Treponema pallidum, we would believe symptoms of syphilis (such as gummas, syphilitic aortitis, neurosyphilis) are completely unrelated diseases! Each medical specialty would study syphilis symptoms affecting their organs without ever putting the whole puzzle together. Worse, we would just treat symptoms with immunosuppressants and palliative care instead of addressing the root cause, Treponema pallidum. We would not know that antibiotics cure patients. Sounds familiar?
If Malassezia are so prevalent, why isn’t everyone sick?
By and large, Malassezia are well tolerated by our body. Except when they're not. For example, people who take drugs that reduce their T cell counts often develop seborrheic dermatitis. This is because T cells keep microbial colonizers in check, including Malassezia on our skin. These T cells are like police officers, who keep crime rates at a normal level in a non-violent manner. Remove the police for a while, and the crime rate shoots up! How does the body stop looting and rioting? One way is to send in the military. The problem with this approach is that the military shoot first and ask questions later, causing much collateral damage. Calling in the military makes sense to fend-off dangerous microbes like Salmonella, but it’s no way to run a body on a day-to-day basis. The immune response against Malassezia must be just right to avoid being sick. There are many ways this immune response can go wrong, and each way produces a different set of symptoms. When the air force is called in to fight Malassezia (CD8+ T cells), you get ankylosing spondylitis. When the navy is called in (B cells), you get multiple sclerosis. And so on.
Why did it take so long to figure this out?
Good question. Historians have spent the last two decades trying to figure out how we overlooked Helicobacter pylori’s role in stomach ulcers and stomach cancer for nearly a century. I think Bunk from The Wire has the best answer: “If you've got soft eyes, you can see the whole thing. If you've got hard eyes you’re staring at the same tree, missing the forest." When I started this project, I had soft eyes. I did not know much about any of these diseases, so I ended up studying all of them. Only after reading many prostate cancer, Crohn’s disease, psoriasis and spondyloarthritis studies did an unambiguous picture emerge. And there were a few technical problems too:
Malassezia are so prevalent that establishing a link between their presence and disease is almost futile. This means pinning Malassezia to conditions such as dandruff was very difficult: it took nearly a century (Shuster 1984)!
Malassezia are fungi, and nearly all studies focus on bacteria. Very few research groups investigate fungi in the studies they perform.
Malassezia do not grow in typical culture conditions, so they’re missed by routine testing.
Malassezia have very thick cell walls: they are the Brazil nut of microbes! This means it’s hard to break them open to sample their DNA, so even modern culture-independent testing methods often miss them.
Malassezia are on everyone’s skin, so they end up everywhere! I detected Malassezia in the prostate in 2013, but I ignored them for four years. I thought they were contaminants.
Malassezia are hard to spot in tissue using routine staining (H&E).
Are you the first person to figure this out?
No, not even close. Many research groups had solved nearly every aspect of The Malassezia Project in their respective fields. They simply needed to read-up on each other’s work to put all the pieces together, and realize how strong their case really was. Research occurs in isolated silos, so this rarely happens: researchers study a few diseases at most, due to institutional and funding constraints. Who could have imagined that all these diseases share a common cause? These researchers’ publications were necessary to piece the puzzle together:
William Rosenberg, Robert Skinner, Patricia Noah, who studied psoriasis and showed that it was likely caused by Malassezia.
John Kurtzke and Christopher Hawkes, who studied infectious etiologies for multiple sclerosis.
Howard Strickler and James Goedert, who studied infectious etiologies for prostate cancer.
John Garst, who studied a possible fungal etiology for chronic prostate pain.
If this is so important, why did you wait until 2018 to make this website?
The strongest evidence was in spondyloarthritis, and it took several years to get this evidence published in a peer reviewed rheumatology journal. It was finally published in April 2018. Without peer review, I could not credibly comment on spondyloarthritis, so I could not make the case that Malassezia were the culprits. Without peer review, critics would have been able to dismiss The Malassezia Project without even considering the evidence.
FAQ - My skeptical friend has a PhD
My friend has a PhD and is very smart: she says this is an unproven hypothesis
There are enough studies from different research groups reporting that Malassezia are in our internal organs to accept this as fact. Malassezia’s presence in our internal organs is the simplest explanation for dozens of long-standing open questions in medicine. When such a simple mechanism explains so many seemingly unrelated open questions, it means that it is probably right. If your friend contends that Malassezia colonize our internal organs but never cause any symptoms, then you should consider challenging her to a long bet: it'll be easy money for the charity of your choice!
My PhD friend says you have not published your experimental results yet
They are coming. Publishing scientific findings in peer reviewed journals is an excruciatingly slow process. Ask your PhD friend, she'll tell you horror stories about how inefficient the system is. The peer reviewed articles I have published so far—as well as the videos on this site—are based on replicated results from credible research groups. This is as solid evidence as one can get, much more solid than the unreplicated experimental results filling the headlines, which are often contradicted or retracted shortly thereafter (see “Why Most Published Research Findings Are False” by John Ioannidis).
My PhD friend says bacteria are known to cause Crohn’s disease and reactive arthritis, not Malassezia.
Your friend is partly right: bacteria which are sometimes present in our guts (such as Mycobacteria, Klebsiella and Shigella) can trigger spondyloarthritis symptoms, including Crohn’s disease and reactive arthritis. However, these are not necessary factors, and in many cases no specific bacterial cause can be found. In contrast, Malassezia are a necessary factor: if they are absent from an organ, spondyloarthritis symptoms will not occur there.
My PhD friend says molecular mimicry causes autoimmunity, not Malassezia.
This is a popular hypothesis, especially to explain how HLA-B*27 increases the risk of reactive arthritis. It goes something like this: “HLA-B*27 efficiently presents to CD8+ T cells a microbial peptide which is very similar to a human peptide. These T cells activate, clonally expand and attack both microbial and human cells which contain a similar HLA-B*27 restricted peptide.” Though plausible at the surface, there are many problems with this hypothesis. First, reactive arthritis can be triggered by a very wide variety of microbes (bacteria, but also viruses and protists). This hypothesis implies that all these different types of infections have an abundant peptide recognized by HLA-B*27, which also matches an abundant human peptide. That’s highly unlikely, because unrelated species don't share abundant peptides. Second, animal models of reactive arthritis are triggered by injecting microbial lipids and sugars, not proteins or peptides. This means molecular mimicry cannot explain these models at all—disease is triggered by injecting cord factor, mannan or beta-glucan only, with no microbial proteins or peptides in the mix. Third, despite 40 years of research looking for molecular mimicry peptides presented by HLA-B*27, we still haven't found them. Fourth, many cases of spondyloarthritis are HLA-B*27 negative. They occur in individuals carrying any HLA-B allele. Other HLA-B alleles restrict completely different sets of microbial peptides. This means causative microbes would need to contain dozens of different molecular mimicry peptides (at least one per HLA-B allele). This is implausible at best. Lastly, T cells are thoroughly screened in the thymus to make sure they do not recognize human peptides. This process has been honed by evolution for hundreds of millions of years. It works. Self-reactive T cells are not produced by the thymus, unless critical genes are missing or defective. Selection pressure against alleles which make thymic screening defective is immense. While defective thymic screening does happen in a miniscule subset of the population, it is extremely rare and cannot explain the observed spondyloarthritis rate.
My PhD friend says Crohn’s disease and spondyloarthritis have nothing to do with each other.
Your friend is wrong. Genes which increase the risk of these diseases are very similar. For example HLA-B*27, CARD9 and IL23R increase the risk of both. Antibodies against fungi increase the risk of both. Having spondyloarthritis increases the risk of Crohn’s more than ten-fold, and vice versa. Age at onset is nearly identical for Crohn’s disease and ankylosing spondylitis. Flares of Crohn’s disease and spondyloarthritis tend to occur simultaneously. Histological gut inflammation is present in a majority of spondyloarthritis patients, though it is usually subclinical. Most importantly, vedolizumab (a drug which sends T cells from the gut to other parts of the body) causes spondyloarthritis symptoms in isolated Crohn’s patients about 10% of the time. This means T cells in the gut which are causing Crohn’s are detecting the same antigenic peptide in the spine, joints and skin. Even if your friend adheres to the improbable molecular mimicry hypothesis, the vedolizumab studies prove that Crohn’s disease and spondyloarthritis are caused by T cells detecting the same peptides, so they are the same disease. Fortunately for patients, symptoms don’t usually occur in all susceptible organs.
My friend is still not convinced
Barry Marshall (2005 Nobel prize winner who discovered that a microbe causes stomach ulcers and stomach cancer) also had many detractors who were not as polite as your friend. This is what he answered them. Skeptical friend: “Oh, Dr. Marshall, it’s not proven,” Marshall: “Well, there’s a lot at stake here. People are dying from peptic ulcers. We need to accelerate the process.” Marginalization of his research resulted in hundreds of thousand of preventable deaths: “It sat there as a hypothesis for another 10 years”. If already approved antifungal drugs can cure Crohn’s disease, ankylosing spondylitis and prostate cancer, it would be a tragedy to delay this by even a single day.