Losing My Defenses: An Interview with Dr. Enusha Karunasena on the Neurological Effects of Satratoxin

031309-NM-E-Karunasena-Lab-300-485 (2)By Lisa Petrison

Back in 2008, a few other mold avoiders and I came upon a doctoral dissertation about the neurological effects of satratoxin (a trichothecene mycotoxin made by Stachybotrys chartarum). The paper had been written in 2005 by a Ph.D. candidate at the Texas Tech University Health Sciences Center, Enusha Karunasena, under the direction of the prominent mold researcher David Straus.

This particular research project (published in 2010 in the peer-reviewed journal Mycopathologia) continues to seem to me of particular importance in terms of considering the role that Stachybotrys toxins conceivably may be playing in ME/CFS and other chronic neuroimmune diseases.

I thus recently tracked down Dr. Karunasena (currently a research scientist focused on the microbiome at Virginia Tech) and convinced her to do an interview with me about her satratoxin research.

Here is a summary of some of my thoughts about why this research is particularly important, followed by a transcript of my discussion with Dr. Karunasena.


Satratoxin: Lowering Our Defenses

Part of the reason why people tend to underestimate the role of trichothecenes in diseases like ME/CFS, I believe, is that they reflexively are thinking only about the direct effects of the toxins.

While trichothecenes such as satratoxin do have the ability to cause some direct systemic effects, they are especially effective at causing damage to our own defense systems – thereby making us more vulnerable to other toxic substances as well as to pathogens.

For instance, more than 200 peer-reviewed articles discuss the harm that trichothecenes are capable of causing to various components of the immune system, especially the innate immune system such as the macrophages.

Dr. Karunasena’s work demonstrates that the endothelial cells that make up the blood-brain barrier (BBB) as well as the astrocytes can be compromised by satratoxin.

Since the endothelial cells constitute the brain’s primary protection mechanism against outside threats, damage to them means that the satratoxin can easily get into the brain and harm or kill the neurons.

In addition, damage by satratoxin to the blood-brain barrier appears to set up the conditions by which substances that are by and large harmless to the rest of our systems can get into our brains and then harm or kill the delicate neurons within.


What Kinds of Substances?

Take away the blood-brain barrier and pretty much anything could be harmful to our brains – as, indeed, a wide variety of substances have been reported to have inordinately harmful neurological effects on those with ME/CFS or related conditions.

The blood-brain barrier is specifically designed to keep out foreign chemicals such as – say – air fresheners or wood smoke.

Thus, the idea that individuals who have suffered harm to the BBB might become negatively affected by exposures to a wide variety of substances that appear to be harmless to other people is perfectly reasonable.

The idea that these kinds of chemical sensitivities might follow a Stachybotrys exposure – as has been reported by many patients to have occurred – is perfectly reasonable as well, based on findings of Dr. Karunasena’s research.


Stachybotrys growing inside a building.

Stachybotrys growing inside a building.


Effects of Pathogens

Another possibility that Dr. Karunasena’s research suggests is that the damage to the BBB and the astrocytes may allow whatever pathogens individuals host in their bodies to be much more damaging.

Certainly, the immunological damage that trichothecenes have been shown to inflict makes it reasonable to think that those who have been poisoned by these toxins may have problems with all kinds of pathogens (including viruses, bacteria, fungi, mycoplasma and parasites) that the immune systems of non-poisoned individuals keep under control without problems.

An additional possibility is that even if the systems of satratoxin-injured individuals are not hosting a larger amount of – say – borrelia than the systems of non-injured individuals, they may be more negatively affected by the presence of those pathogens due to the possibility that either the toxins made by the pathogens or the pathogens themselves are more likely to get into the brain and cause damage there.


Metals, Chemicals & Foods

Similarly, any inflammatory metals (such as mercury or aluminum) or irritating chemicals present in the system of a satratoxin-injured individual may have the potential of being particularly harmful, since they may be more likely to get into the brain.

An additional fact about trichothecenes:  just as they are known to disturb the endothelial cells in the brain (thus making it “leaky”), a number of studies show that at least some kinds of trichothecenes have the ability all by themselves to disturb the endothelial cells in the small intestine (causing leaky gut).

The idea that trichothecene-injured individuals would suffer from food reactivities thus seems pretty reasonable as well.

Gluten, for instance, is a relatively inflammatory food that nonetheless is consumed without incident by the majority of individuals.

Insofar as a trichothecene toxin compromises the gut lining (so that gluten particles can get into the bloodstream), and also compromises the blood-brain barrier (so that gluten particles in the blood can pass into the brain), it is no surprise that gluten then would seem to have a disproportionately negative effect on individuals injured by satratoxin.


LPS & Oxidative Stress

The final component of Dr. Karunasena’s study that seems to me of interest with regard to the understanding of ME/CFS was the extent to which the addition of LPS (a toxic substance made by certain bacteria) or H202 (hydrogen peroxide, a substance used to model the presence of oxidative stress) dramatically increased the negative effects of even small amounts of satratoxin.

The interaction between Stachybotrys and LPS-manufacturing bacteria (such as Streptomyces californicus) present in buildings has frequently been cited as having the potential of making individuals much more sick than would be expected if either type of microorganism toxin were present on its own.

In addition, the presence of LPS-manufacturing bacteria in the human gut seems to have the ability to explain why patients with ME/CFS and other diseases may benefit to a disproportionate extent by a variety of treatments that have an effect on gut bacteria (including things such as herbs, fasting, HBOT or fermented foods).

While certainly immune system abnormalities (possibly at least in part due to the negative effects of trichothecenes) may lead to dysbiosis, it also may be that even trivial amounts of dysbiosis may lead to disproportionately negative effects in patients who have been injured by satratoxin, due to the synergetic effects of LPS and satratoxin.

Finally, as Dr. Paul Cheney has often reiterated, oxidative stress is in many ways the centerpiece of ME/CFS – with the widely discussed exercise intolerance apparently related to that. In Dr. Karunasena’s studies, application of H202 to the cells (to simulate oxidative stress) created almost no damage at all – but the combination of satratoxin and H202 was much more damaging than the satratoxin alone.

The idea that low amounts of oxidative stress (such as that caused by exercise) might be notably damaging to satratoxin-damaged individuals but not harmful to non-injured individuals seems possibly consistent with Dr. Karunasena’s work as well, therefore.



Several other peer-reviewed papers now have examined the effects of other trichothecenes (made by the outdoor mold Fusarium) on the blood-brain barrier and on the astrocytes.

Also at the link are a number of additional peer-reviewed papers looking at the effects of trichothecenes on the immune system, the intestinal system and the rest of the neurological system.


Pink Stachy

Stachybotrys spores.


Interview with Dr. Karunasena 

Following is a transcript of the conversation that I had with Dr. Karunasena. I am very grateful for her willingness to share her knowledge on this blog.


How did you get started studying mycotoxins?

When I came in to do my Ph.D., I was very interested in studying immunology. At the time Dr. Straus’s lab was studying sick building syndrome. And I thought it was really interesting how they were trying to understand how the conditions of a building could make you sick.

So there were some opportunities to do some studies that were associated with immunology.


What did you learn in your research?

I think that what we really discovered is that because the toxins are very small in size, they are too small for the body to specifically detect. So the body cannot produce antibodies against these agents. They are disruptive to certain biological processes that activate our immune system.

Our immune system is sort of a double-edged sword. The body sees something that it thinks might be foreign to the body, and it starts to provide an immune response in order to protect itself. But ultimately what happens is that that prolonged immune response ends up damaging the normal cells themselves.


What if you just turned off the immune system?

The problem is that we can’t really turn it off, because that would in itself cause more problems.

If someone is in an environment where there are mycotoxins present, then the body is trying to do its best to eliminate the source of the problem. But the body can’t attack the mycotoxins, because they are too small for it to recognize. So the best way to help is to get those individuals removed from those environments.


The chemical structure for Satratoxin G.

The chemical structure for Satratoxin G.

You mentioned size. Just how small are these particles?

I think that when people think of a particle, a lot of times they think of something like pollen, something visible. These are chemicals that are essentially not visible to us. They are several magnitudes smaller than even a grain of pollen.

Viruses can range in size as well. Probably these toxins are a couple of thousand-fold smaller than viruses.


You mention in the paper that these molds are ubiquitous in the environment. Why should we be concerned about them then?

In nature you can find fungal growth on decomposing plant material. Their natural biological function is to help with the breaking down of organic materials.

Processed plant materials are used inside buildings. The spores don’t recognize that this is a building material vs. plant material that is outdoors.

When there is water damage in a building, then these spores can germinate and grow. And then they can produce mycotoxins.

The indoor environment is significantly different than the outdoor environment. In these closed environments in our homes, the concentrations of these mycotoxins can be very different than if they were outdoors. We are being exposed to them under very different circumstances than what is natural.


The trichothecene-producing mold Fusarium, which is often present in food products.

The trichothecene-producing mold Fusarium, which is often present in food products.


Trichothecenes have been studied extensively in the agricultural literature. Is what we know about ingestion of the toxins relevant to what we can expect when people inhale them inside buildings?

The effects of these toxins have been demonstrated. They’ve been measured in terms inhalation vs. digestion. They’ve gone through lots of different toxicological studies.

We know how they measure relative to some of the other biologically produced toxins from other organisms.

Our understanding of them really comes from a lot of agricultural studies. We know that these toxins can grow on plants. Ingestion can produce certain symptoms in animals – it will induce vomiting and cause many different kinds of ailments. The animals may lose significant weight.

For inhalation, one of the considerations with regard to toxicity is that our lungs are intended to carry oxygenated blood. The function of the lungs is to bring oxygenated blood to the heart, and then the heart pumps that blood throughout the body.

The lungs are very vasculature organs compared to many of our other organs. And they are a primary organ that interacts with the environment.

When we inhale, anything that comes in through the lungs is then carried throughout the body. So our sensitivity to things that are inhaled can have a very direct impact compared to something that has to go through secondary means.

Some strains of Fusarium also produce trichothecenes. So it’s really relative to the chemical composition of the toxin. They can have certain differences in their chemistry, and that can lead to different effects in the body.

Some of the trichothecene toxins, such as those that we are concerned with with regards to Stachybotrys, can have irreversible binding to certain biological components in our cells, such as the ribosomal subunits discussed in my dissertation. So this irreversible binding keeps the cell from producing the protein that can lead to cell death.

It essentially can get into the cell and bind to machinery in the cell that is very important or fundamental in terms of the cell being able to produce other necessary activity for the cell to survive. And then it doesn’t let go. That gives it a higher degree of toxicity compared to something that can let go.

When it holds onto a ribosome, it’s not going to let go of that site, so it can cause the cell to then die.

In other words, Stachybotrys is producing mycotoxins that can be lethal to cells.


Molds like Stachybotrys are often recognized as causing asthma. If people are living in a building but don’t have asthma, can they still be suffering harm by the toxins in the Stachybotrys?

Asthma is an inflammation process in the lungs that can be produced by certain agents.

But trichothecenes are not causing asthma.

There are other fungi such as Penicillium species that can induce asthma. But asthma is a separate condition with regard to what we’re demonstrating with regard to trichothecenes.


In your studies, you took human cell lines and then exposed them to satratoxin, which is a toxin made by Stachybotrys mold. How accepted is that as a research methodology in the scientific community?

This is how research is done with toxicology studies or disease models with regard to cancer. So this is very much an accepted system to study these sorts of things.


What about the dosage?

One of the problems that we see with buildings is that there is no specific concentration of mycotoxins that are identifiable. Part of that is because detecting them is so difficult.

So what we tried to do was to create – relative to previous work where people have done studies testing these mycotoxins and trying to figure out what the lethal dosage is – a study to measure concentrations that might induce biological responses without just killing the cells.

So that’s how we developed these concentrations to test. We didn’t want to just kill the cells. We wanted to see how are they going to affect the cells that are living and what kind of response living cells produce from the toxins. And in what concentrations.


Your study exposed cells to the toxins over a short period of time, just a few days. Would it be different if cells were exposed over a long period of time?

Part of the limitations of any sort of human research into a biological system is that we study outside of a perfect system, which is an individual.

Since we can’t do biological testing on people, we have to create these model systems. And these model systems have limitations on evaluating the biological events that are specific to our agent, relative to the conditions of that model.

So that’s why our model is set up to a certain period of time relative to what someone might be experiencing in an actual building.

An individual in a building might experience symptoms for much longer relative to what our study design is. But our study is specific to the environment of the model.

Ultimately there are going to be biological variations relative to individuals. So I think it would require sampling a large population of individuals who have been exposed to those two scenarios.

It would be difficult to determine without being able to flesh out a lot of other variables.

Those individuals might be exposed to other agents in addition to trichothecene toxins.

That would require a pretty big study. That’s something that I think is difficult for those reasons.


One substance that you looked in combination with the satratoxin was LPS. Would you talk a little bit about that?

Lipopolysaccharide is a part of the cell membrane of bacteria. We know that component of the cell membrane can induce an inflammatory response.

We needed some kind of system to compare the results of our study on the trichothecene toxins. We needed something that had been vetted as well. We used LPS as a biological agent that we know is going to induce an inflammatory response.

We compared the response of our trichothecene toxins to LPS. And we also looked at the additive effects.

We know that individuals in sick buildings have frequent colds and prolonged chronic lung ailments. And so we wanted to see comparatively what sort of response the cell produces with the trichothecenes – but also if someone were to have some sort of bacterial infection as comparable to some sort of concentration of LPS being present.

What we were able to observe was that in the presence of both LPS and mycotoxins, we saw an additive effect in our cells in terms of the inflammatory responses and the other biological events that occurred.


Can you talk a bit more about LPS?

LPS is produced by organisms that are gram negative. The gram stain is what this is. It’s a staining mechanism to identify bacteria. Those organisms that are gram negative will have a thick layer of LPS matrix.

So there are organisms that are gram negative and gram positive.

We have a magnitude more of bacterial cells in and on our bodies compared to the number of human cells. We do have both gram negative and gram positive bacteria that are necessary for our bodies as well.

What we were really trying to do was to look at what could happen if you were sick, if you were compromised, with some kind of bacterial infection with a gram negative organism – and then if you were exposed to satratoxin at the same time.

We know that LPS is able to trigger the immune system and that it can have very disruptive effects with regard to the immune system. So in this case, we are trying to use this to assist in our model to understand some of the immunological effects of the trichothecene toxin.


How about the hydrogen peroxide?

We were using hydrogen peroxide as an agent to induce oxidative stress. If there is too much oxidation in the cell, it can lead to cell death.

With compounds such as hydrogen peroxide, too much of it can induce cell damage.

Our own cells will produce a certain amount of hydrogen peroxide as a way to kill foreign agents. If we have an infection with bacteria, we’ll have certain cells that produce peroxide and release it to try to kill that harmful bacteria.

When mycotoxins like trichothecenes are in the cell, we observe that they can also trigger the cell to produce an oxidative response. Unfortunately, like the overactivity of the immune system, you can also have overactivity of this oxidative response, which leads to oxidative stress.

That can cause damage to the cell and can cause cell death as well.

Someone who is a smoker is going to have a lot of oxidative stress as there are lots of oxygen free radicals that are produced in their bodies. Those agents can attack the cell and damage the cell.


The blood-brain barrier.

The blood-brain barrier.


Now let’s talk about your first study, where you looked at the endothelial cells.

The capillary endothelial cells form the blood-brain barrier. They have these tight junctions between the cells and they protect the central nervous system. They protect the brain from being exposed to bacterial agents and viral agents.

What we were testing specifically is that we have these trichothecene toxins. They are small chemical agents. We know that individuals who are in the environments of sick buildings experience more memory loss and other sorts of neurological issues.

So we were trying to understand whether or not these mycotoxins were able to penetrate the blood-brain barrier.

What we were able to learn was that these trichothecene toxins can compromise the endothelial cells. When they’re compromised, they essentially cause the integrity of that barrier to loosen. And that allows for other materials to even cross the blood-brain barrier and enter into the central nervous system.


Are there other kinds of toxic agents that also can compromise the blood-brain barrier in this way?

There are other compounds that can move through the blood-brain barrier, with regard to treating things like brain tumors. Generally it’s very difficult to get chemotherapeutic agents across the blood-brain barrier. But there are certain types of compounds that are used to compromise that barrier to get a compound across.

So there are agents that can be medically used for that purpose. There are nanoparticles that are being synthesized that can move across the blood-brain barrier. Those are being used for the same reason, to get chemotherapeutic agents across the blood-brain barrier.

Certainly there are particles in our building environment that are relatively small and capable of carrying mycotoxins without the fungal spores.

There might be other agents that are present that could compromise the blood-brain barrier in the same way, but I think it would be an issue of dosage and exposure. The capacity of something to induce those effects might be present, but it would be relative to those parameters.


If the blood-brain barrier is compromised, what kinds of negative effects should we expect to see?

The blood-brain barrier being compromised is a very significant effect in itself. That’s not something that should happen altogether. That in itself is a big physiological event.

Additional effects that could happen from that – if there are other biological agents that the individual is exposed to, then those agents can potentially gain access to the central nervous system whereas previously they would not have.


Screenshot (11)

A chart showing the effects of various amounts of toxins in terms of creating permeability in the endothelial cells of the blood-brain barrier. Administering LPS or hydrogen peroxide along with the satratoxin vastly increased the effects of even small amounts of the mycotoxin.


Does the blood-brain barrier repair itself eventually?

That’s a very good question. The cells of the blood-brain barrier can repair themselves. Whereas with neurons, it’s relative to the damage. They’re a little more sensitive. So you can have neurons that are incapable of repair.

I think if you’re in an environment where you’re exposed to it chronically, then the trichothecenes are present in your body all the time. It’s difficult to know what the integrity of your blood-brain barrier is relative to a normal status.

The question that you’re asking is repair. So what I am thinking is, is your definition of repair going back to what was previously a healthy condition? That’s a difficult question to answer.

There can be repair to where the integrity of the blood-brain barrier is healthy, essentially, but is it back to what was the health status prior to exposure to trichothecenes? That’s difficult for me to answer.


Astrocyte5 (2)

An astrocyte.


The second study in your dissertation looked at the effects of satratoxin on astrocytes. What do the astrocytes do?

The astrocytes kind of act like macrophages, except that they are very specific to the nervous system.

When I say macrophages – macrophages are a group of immune cells that protect us from foreign biological agents. They are usually first to attack things like viruses or bacteria. They help protect our body.

The astrocytes have that same protective function, except that they’re specific to the central nervous system.

So what we did was that we tested how the astrocytes responded to exposure to trichothecene mycotoxins. We observed that the astrocytes were affected by trichothecenes and they do produce immunological responses and oxidative events that can lead to harmful activity in the nervous system that can then damage the neurons themselves, the astrocytes themselves and even the endothelial cells.

The effects produced by the astrocytes can compromise the astrocytes themselves but they can also affect the cells that they’re there to protect.


If the astrocytes are harmed, how would we expect that to manifest clinically?

I don’t know that you can specifically correlate the effects that we observed to clinical symptoms. I think that’s kind of a jump there. But ultimately, what I think we’re able to observe is that there is a harmful effect to the cells of the central nervous system.

The astrocytes are a component of our defense to protect our nervous system. If they are compromised, then similar to the blood-brain barrier being compromised, you are potentially losing another source of defense that protects your neurons.

If the astrocytes are compromised, then the issue with the other toxins is that if they are similar in size to the trichothecenes, they’re not really being recognized specifically by the cells. What could happen is that the chemical could compromise the cells differently, certainly.

Overall, your susceptibility increases.


Screenshot (13)

The combination of satratoxin plus either LPS (7) or hydrogen peroxide (8) was especially damaging in this study. VCAM expression is a measure of inflammation.


In the third study, you looked at the effects of satratoxin on the neurons. What did you learn from that?

I think that what we really observed in Study 3 is that the neurons are very sensitive.

I like to think of our study as almost like a chessboard. You can think of the pawns on the chessboard as being the endothelial cells. And the astrocytes are pieces that are more like the knight.

Your neurons are more like the queen. All those other pieces are there in order to keep anything from getting to the queen. If the queen is compromised, everything is lost.

The neurons are very delicate. What we observed with that was when we exposed them to trichothecenes, we didn’t see these mechanistic events as we saw cell death.  Because they’re just sensitive.

So all of those barriers – the endothelial cells and the astrocytes – they’re there to defend the neurons. If something reaches the neurons, there aren’t really specific mechanisms within the neurons that protects them at that point.


How damaging is satratoxin to the neurons, compared to other environmental agents that we might encounter?

I think that there are other agents that can be harmful to the nervous system when they reach the nerurons. We know that lots of recreational drugs or even alcohol can cause severe effects on neurons and cell activity. So there are lots of chemical agents that can be harmful to the neurons that we know of.

What’s different with the trichothecenes is that the concentration that can lead to the damage can be much lower relative to some of the other agents that can cause neurological damage.

These cells are susceptible as all cells are to certain chemicals that are going to inhibit certain biological processes.

Sometimes it’s not so much a specific biologic agent as it is, with regards to the trichothecene toxins, they can inhibit biological processes such as protein translation. So the magnitude of effects of that can be greater than maybe another chemical compound.


In general, what did we learn as a result of your research into this topic?

I think what is most important is that we were able to identify the mechanism by which these mycotoxins can induce neurological damage. That was something that was not understood before. We could see that people who were in those environments where they might have been exposed to the mycotoxins had these symptoms, these neurological problems. But we didn’t know how the mycotoxins could compromise these fundamental cells that are important to maintaining the central nervous system.

So we’ve learned now some biological effects that are produced when the brain is compromised.

Understanding the effects of these trichothecenes on a human neurological cell system was needed. And we were able to do that work. So I think we’ve contributed to everyone’s understanding with regard to how these mycotoxins can potentially induce brain damage.


If you were going to do more research into trichothecenes and could get funding for it, what in particular would you want to pursue?

I think if we could develop better systems to detect trichothecenes in buildings and develop better systems to identify what is a high concentration of agents in a home or in a building, that would contribute toward allowing a lot of institutions to accommodate people who have had water damage in their home. I think that would probably contribute to better healthcare but also to better building care, ultimately.


The structure of a neuron.

The structure of a neuron.


What kind of work are you doing now?

While I was in graduate school, I became very interested in the gut microbiota and how that contributes to our health and well-being. There also was kind of a branch of the gut being the second brain. So I am still studying how microbial agents ultimately contribute to our nervous system. In some ways, we think of the gut as being separate from the nervous system, but I think what we’re finding is that there are lots of elements with regard to microbial agents that also contribute beneficially to our well-being. That includes our nervous system and neurological health.


There has been a lot of discussion about how antibiotics might affect the microbiome. But of course, antibiotics are often made from mycotoxins. Do you think that environmental mycotoxins could have a negative effect on the microbiome?

I think that would be difficult to say without looking at some studies.

There’s a lot of work that we’re all doing with regard to understanding the gut microbiome. There are studies that show that modifications to the gut microbiome with the use of antibiotics, especially during childhood, can contribute to asthma in children. So I think we’re still learning and that it’s too early to pinpoint what might be specific.


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