Multiple Sclerosis and fungi – is there a link?
Hello and welcome to The Mould Show. My name is Dr. Cameron Jones, and this week we are focusing on a neuroinflammatory disease called multiple sclerosis. We're going to be looking at whether or not there is a microbiological basis to this condition and, importantly, whether there are some fungal microorganisms that are linked to this particular illness and, importantly, whether or not we can use the identification of these microorganisms as a predictor of risk.
Also, we're going to be looking at some of the emerging literature showing that there is a connection with the gut microbiome, and specifically the gut microflora, the fungal microorganisms.
So what we're going to be doing is focusing on multiple sclerosis and fungi. Is there a link? To do this, I'm going to be going through two of the main publications that have come out in the last two years focusing on this specific topic.
Again, all of these references are going to be available in the show notes description to the podcast or to the Livestream. You'll be able to get this from Facebook as well as from my main website, as well as on YouTube, as well as on other social media networks.
But what I want to focus on, firstly, is what are we talking about with the gut microbiome? Well, obviously the gut microbiome contains trillions of different bacteria and yeasts and fungi and even viruses.
Now we all know that after taking antibiotics, for example, that can upset our gut microflora. We know that diet has an impact on gut microflora. But what about some of these neuroinflammatory conditions such as multiple sclerosis? And so, I'm going to dive in quickly now, go straight to some of the key research.
The first publication came out on April 26, 2022. This is a really, really, really important publication. In the first graph, I want to draw your attention to, we can see up here on the right-hand side that there is a difference between the levels of basidiomycetes and ascomycetes.
Now, why is this important? Well, basidiomycetes are commonly the higher fungi. Think of mushrooms that reproduce with sexual spores from their gills. There are about 25,000 common species. But ascomycetes also are a very diverse group.
You can see in this graph that the scientists have looked at the gut microflora and they found that there are differences between the healthy controls shown in purple on the left-hand graph and the right-hand box plot in teal blue. You can see that there is a definite difference between these two broad classes of fungi.
The basidiomycetes are characterized by club fungi in that they produce and eject their spores from essentially a club, whereas the ascomycetes are the sac fungi. And so, they produce or eject their spores from an ascus.
Now we don't need to get into the biology underpinning this. Just recognize that in taxonomy, or biological taxonomy, we classify different microbes really based upon their morphology or shape, and usually other characteristics like how they reproduce.
And so, this first key diagram from this publication from 2022 is showing that there are indeed significant differences between the levels of fungi or the diversity of fungi seen in normal patients or those with multiple sclerosis. Moving straight ahead, we can look at other ways of characterizing this diversity. We can look at some of the well-known water damage fungi even like Cladosporium and candida, and even some of the yeasts like Rhodotorula.
You can see again in this colored bar chart, between the normal controls on the left-hand side and the multiple sclerosis patients on the right-hand side, that there is a different microflora associated with these individual patients. This is really important information to be aware of. I'm going to drill into how we can take advantage of this on a practical level throughout this Livestream.
If we drill into other tables within this publication, we can also generate what are term box plots. These basically summarize the contribution of taxonomies for various different classes of microorganisms. In here, the taxonomies that we're looking at are Saccharomyces, Candida, your Penicillium molds, and Epicoccum moulds, which, again, is another common water damage fungus that we often see in sick building syndromes and even normal skin microflora like Malassezia.
Now, this particular fungus is found all around and on our skin, but certainly, people who are predisposed to acne and severe acne show very high levels of this particular fungus. It's really interesting when you look at the distribution between the normal control shown in purple and then the MS patients in teal blue.
You can see that there are various different differences between the species diversity or the species richness. There are a whole lot of statistical methods that scientists like myself use to characterize how diverse or how rich the species distribution is.
You can see that between normal and MS groups that there is a difference in certain types of microorganisms. When we drill into this a little bit further, the scientists were able to essentially work out certain key fungi that must be looked at. They were able to reject a whole lot of different classes or taxonomies of fungi that are not that important.
They were able to include fungi like Candida, Epicoccum, Penicillium, Malassezia, and Saccharomyces. That's right, baker's yeast, the yeast used to make bread and used throughout culinary endeavors worldwide has a connection with multiple sclerosis.
Again, I certainly urge you to get the links to this Livestream on various different social media. Retrieve the links, read these papers for yourself, because it is absolutely dynamite reading going through this to see what is now possible to identify in your gut microflora, and then make this connection with how various different autoimmune conditions like MS are thought to now be connected with the gut microbiome, and specifically the mycobiome which are those fungi that inhabit the gut.
And so, we're going to go straight back here. I showed you this table before. Now what about this next publication, which is a little bit earlier. It came out in 2021. This is a really interesting publication because like all good science, it shows up some discrepancies with the 2022 research.
Back in 2021, in fact, they discovered that, yes, Saccharomyces and Aspergillus play a significant role in those patients classified as having MS. With MS, we must appreciate that most people, about two and a half million people, suffer from multiple sclerosis and 85% of those sufferers really have a relapsing condition or relapsing MS, meaning that there are periods of stasis followed by periods of symptoms being expressed. But overwhelmingly, over time, those symptoms become more predominant and are experienced at a much higher rate. Hence, why it's called relapsing MS.
This particular publication is talking about that particular group, and they were able to identify that Saccharomyces and Aspergillus were two of the key fungi which seemed to be measurable in stool samples from these patients. And so, with a simple stool test and some really elegant molecular biology identification, you can identify those individuals with issues.
Now where do we go from here? Well, what about if we just step back from multiple sclerosis and we say to ourselves, could there be a connection between the overgrowth of Saccharomyces cerevisiae or, for that matter, other types of microorganisms and something called 28-day mortality?
Why might we be interested in this? Well, patients who are particularly unwell and enter hospital often with underlying cancers or heart disease or serious lung complications, kidney complications, or even sepsis-like conditions, or serious COVID-like symptoms for that matter, may remain in hospital for prolonged periods of time.
And so, a group of scientists are interested in looking at the gut microflora to see if they could predict recovery, but also those patients that may be more susceptible to passing away.
And so, if we look at this companion research that sits alongside the autoimmune research looking at gut microflora, you can see some very clear differences. If you look at these similar box plots for different ways of measuring species diversity or richness in the gut, you're able to see that the box plots highlighted in red show that when species diversity is lower, that there is a greater probability over 28 days that those individuals will in fact die. Whereas when your species diversity is increased, it's a greater probability that you'll be alive 28 days from now.
I think this is absolutely fundamental and fascinating research because on the one hand, there's a whole lot of research showing that the gut microflora is linked with autoimmune conditions like multiple sclerosis. But then if we take the key fungi from that literature and look for those microbes also present in other clinical literatures looking at mortality outcomes, we see that there is in fact a connection with this concept of species diversity.
Now I'm going to be talking about how we can increase the species diversity in our own gut systems for positive therapeutic health outcomes. But I want to say a few more words about what the paper that was looking at all-cause mortality after 28 days found.
They found that in fact there were a couple of different fungi that appear also in the multiple sclerosis literature that are also strongly implicated as a microbial biomarker for mortality. I've put a box around on this table, because on the left-hand side shown in red and green whisker plots, we're looking at the bacteria that can be identified in the gut. But on the right-hand side, surrounded by the red box, those are the fungi which were able to be used as a biomarker.
Again, we see that Saccharomyces cerevisiae and also Malassezia, the skin microorganism, when this is present in the gut, these indicate a non-survivor relationship.
Now this is just really critical information because we now have a couple of different types of at least genus-identifiable fungi which are connected with not only adverse total health outcomes such as mortality but whether or not people are suffering from multiple sclerosis.
And so, if we go into some of the potential therapeutic methods because it would be pointless of me just doing this Livestream to talk about all-cause mortality and after 28 days, and it's linked with microflora, if I didn't bring to you some of the positive therapeutic or nutraceutical approaches that scientists like myself are looking into.
One of the key compounds which one can purchase and consume is something called astaxanthin. Now where is astaxanthin found and why might this be beneficial for changing your gut microflora? Well, firstly, I have to say that astaxanthin, in its unbound form, is found in shellfish and crayfish and also various different seaweeds and algae.
There is some elegant chemical research showing that when lobsters, for example, are cooked, they will form the astaxanthin compound, which is this characteristic orangey-red color. Now this orangey-red color, astaxanthin, of course, can be produced as a nutraceutical.
There is some stunning research showing that astaxanthin is in fact effective at preventing multiple sclerosis in an animal model. You might be asking, well, how? Again, it is a potent antioxidant. But we are going to drill into some of this literature, and I'm going to explain to you why.
So what else do we know about astaxanthin? Well, I've already mentioned that it is produced by a range of different marine creatures, but it can also be extracted from seaweeds and also counterintuitively from some yeast species as well.
And so, another group of scientists are looking at not autoimmune conditions like multiple sclerosis or whether or not there is a way of tracking particular microbes in the gut to determine which patients may be more likely to survive, but people are looking at whether or not nutraceuticals like astaxanthin might be beneficial as a natural antimicrobial, a little bit like a natural antibiotic.
Yes, there is some really good research. I've got one of the publications up here. Again, you can download this for yourself from the links in the show notes. But, yes, astaxanthin is very effective as an antimicrobial. But the only issue is that it needs to be used at very high concentrations.
The take-home message here, and what I want you to consider, is that if we are not trying to use supplements like astaxanthin to treat acute infections, but rather we want to alter the gut microbiome, then that is a very sensible approach.
What the literature shows is that there is excellent support for the use of astaxanthin in improving something called the demyelination cytology. When scientists are looking at the impact of ways or how multiple sclerosis actually damages the nerve fibers, they're looking for the Myelin sheath because that, of course, conducts the electrical impulses and the signal transmission throughout the body.
And so, if there is a way of controlling or limiting the loss of myelin, that should theoretically improve the outcome for multiple sclerosis patients. But there are a range of other neurodegenerative conditions, including Alzheimer's, dementia, and even chronic fatigue syndrome, leads to a loss of signal transduction pathways that are related to myelin.
And so, these motor neuron connections show in this research that there is a connection with the gut microflora, and, together, there's another group of literature that is suggesting the use of astaxanthins for their antiaging potential, because they are shown to mitigate and delay and even reverse disease because they suppress brain inflammation.
Whenever you suppress brain inflammation, that is a good thing, because we're learning so much about the impact of oxidative stress and a range of different diseases, which essentially progress to severe symptoms and become chronic due to this impact on the ability of the cells to actually respond to a localized inflammatory pathway.
Some of the other research that we're looking at down here is whether or not astaxanthin can be used for some of these mitochondrial dysfunction issues. Aging is all about a loss of cells able to properly respire. And so, this last publication is looking at whether astaxanthin can be used as a mitochondrial-targeting antioxidant that can reduce oxidative stress.
And so, taking all of this research together, we can see that not only is there excellent research support showing that targeting the identification of particular bacteria and fungi at the level of your gut can be used to predict risk for neurodegenerative conditions like multiple sclerosis.
But there are a range of therapeutic approaches apart from stopping smoking, maintaining a low body mass index, maintaining a healthy diet, and carrying out some type of functional exercise. What if you can actually modify your gut microflora to reduce the inflammation and the oxidative stress on your body organs?
If you can do that, and astaxanthin is capable of passing the blood-brain barrier, there is the opportunity to treat a whole range of different conditions. Remember, you're doing this by altering the microflora in your gut. And so, then your gut is actually contributing to positive health stasis in your body or at least a positive health condition that favors more optimal cell metabolism. That's what we want.
In any case, I hope this Livestream has been helpful to you to show that there is in fact a positive correlation between the identification of particular fungi and specific adverse health conditions. There is a lot of hope for supplementation with natural compounds that are capable of altering the gut microflora for positive health outcomes.
In any case, my name's Dr. Cameron Jones. I'll be back next week with another episode of The Mould Show. Bye for now.
References:
Yadav, M., Ali, S., Shrode, R. L., Shahi, S. K., Jensen, S. N., Hoang, J., Cassidy, S., Olalde, H., Guseva, N., Paullus, M., Cherwin, C., Wang, K., Cho, T., Kamholz, J., & Mangalam, A. K. (2022). Multiple sclerosis patients have an altered gut mycobiome and increased fungal to bacterial richness. PloS one, 17(4), e0264556. https://doi.org/10.1371/journal.pone.0264556
Shah, S., Locca, A., Dorsett, Y., Cantoni, C., Ghezzi, L., Lin, Q., Bokoliya, S., Panier, H., Suther, C., Gormley, M., Liu, Y., Evans, E., Mikesell, R., Obert, K., Salter, A., Cross, A., Tarr, P., Lovett-Racke, A., Piccio, L. and Zhou, Y., 2021. Alterations of the gut mycobiome in patients with MS. EBioMedicine, 71, p.103557. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00350-9/fulltext
Prevel R, Enaud R, Orieux A, Camino A, Berger P, Boyer A, Delhaes L, Gruson D. Gut bacteriobiota and mycobiota are both associated with Day-28 mortality among critically ill patients. Crit Care. 2022 Apr 13;26(1):105. doi: 10.1186/s13054-022-03980-8. PMID: 35418098; PMCID: PMC9007252. https://pubmed.ncbi.nlm.nih.gov/35418098/
Fadhel M, Patel S, Liu E, Levitt M, Asif A. Saccharomyces cerevisiae fungemia in a critically ill patient with acute cholangitis and long term probiotic use. Med Mycol Case Rep. 2018 Nov 12;23:23-25. doi: 10.1016/j.mmcr.2018.11.003. PMID: 30505677; PMCID: PMC6251791. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251791/
Veronese N, Yang L, Piccio L, Smith L, Firth J, Marx W, Giannelli G, Caruso MG, Cisternino AM, Notarnicola M, Donghia R, Barbagallo M, Fontana L. Adherence to a healthy lifestyle and multiple sclerosis: a case-control study from the UK Biobank. Nutr Neurosci. 2022 Jun;25(6):1231-1239. doi: 10.1080/1028415X.2020.1846357. Epub 2020 Dec 9. PMID: 33297884. https://doi.org/10.1080/1028415X.2020.1846357
Bidaran S, Ahmadi AR, Yaghmaei P, Sanati MH, Ebrahim-Habibi A. Astaxanthin effectiveness in preventing multiple sclerosis in animal model. Bratisl Lek Listy. 2018;119(3):160-166. doi: 10.4149/BLL_2018_031. PMID: 29536745. https://pubmed.ncbi.nlm.nih.gov/29536745/
Alugoju P, Krishna Swamy VKD, Anthikapalli NVA, Tencomnao T. Health benefits of astaxanthin against age-related diseases of multiple organs: A comprehensive review. Crit Rev Food Sci Nutr. 2022 Jun 16:1-66. doi: 10.1080/10408398.2022.2084600. Epub ahead of print. PMID: 35708049. https://pubmed.ncbi.nlm.nih.gov/35708049/
Karpiński TM, Ożarowski M, Alam R, Łochyńska M, Stasiewicz M. What Do We Know about Antimicrobial Activity of Astaxanthin and Fucoxanthin? Mar Drugs. 2021 Dec 29;20(1):36. doi: 10.3390/md20010036. PMID: 35049891; PMCID: PMC8778043. https://pubmed.ncbi.nlm.nih.gov/35049891/
Willis, A., 2019. Rarefaction, Alpha Diversity, and Statistics. Frontiers in Microbiology, 10. https://doi.org/10.3389/fmicb.2019.02407
Lotfi, A., Soleimani, M., & Ghasemi, N. (2021). Astaxanthin Reduces Demyelination and Oligodendrocytes Death in A Rat Model of Multiple Sclerosis. Cell journal, 22(4), 565–571. https://doi.org/10.22074/cellj.2021.6999 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211289/
Sztretye, M., Dienes, B., Gönczi, M., Czirják, T., Csernoch, L., Dux, L., Szentesi, P., & Keller-Pintér, A. (2019). Astaxanthin: A Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging. Oxidative medicine and cellular longevity, 2019, 3849692. https://doi.org/10.1155/2019/3849692 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878783/
