In this episode, I am speaking with Kiran Krishnan – who is a research microbiologist and an expert on gut health. We will talk about the connection between gut health and immune function and how it pertains to protecting yourself against coronavirus.
Kiran has developed a probiotic that is called MegaSporeBiotic. You can get your own bottle here.
In this podcast, Kiran will cover:
- Why vitamin C, zinc, and other herbs might not be enough immune support.
- The critical importance of immune ‘crosstalk’ in your gut and what happens without it.
- How mucus and boogers can boost your immune response.
- Does stomach acid kill the coronavirus? Why you MUST have healthy gut microbes.
- Ventilators vs high flow oxygen in treating COVID-19. Why one works better than the other.
- Clearing the confusion around immunology – understanding the roles of adaptive and innate immunity
- The best tips for a fast-acting immune system
- The best prebiotics and probiotics for optimal gut health
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Ari Whitten: Hey, everyone, welcome back to the Energy Blueprint Podcast. I’m your host Ari Whitten. With me now is Kiran Krishnan who is a microbiologist. He is a research microbiologist, I should say. He’s an expert in gut health in particular. This is someone that I recently interviewed for my upcoming summit, the Superhuman Energy summit on the gut mitochondria axis. Absolutely, he just blew me away with his level of knowledge on this, so I said I need to have you back.
We need to do another interview, get it on my podcast, and since that time, the whole coronavirus epidemic that we all know about, obviously, has exploded and that’s on everybody’s mind and it’s the thing that we all can’t stop talking about. I said let’s do another one and let’s specifically talk about immune health and the relationship of the gut to immune health. All the different layers there. There’s a gut immune access, a gut lung access. He’s got some fascinating information to share with us. I am super excited to get into it. Welcome back, Kiran. Such a pleasure to have you.
Kiran Krishnan: Thank you so much for having me, and then the timing is great. This is an important topic to talk about, so it’s a pleasure to be here.
Ari Whitten: Yes, absolutely. I’ve done a bunch of podcasts recently on COVID-19. Let’s assume the listener has a good level of basic knowledge around this. What do you think are the biggest things to be aware of that not a lot of people know about?
Kiran Krishnan: One of the big things is obviously that at the moment, all we have in our defense is obviously our behaviors. If you’re a social distancing and things like that, you can reduce your risk of getting exposed to it, but the biggest thing we have in our favor is our immune system. It’s our immune system that has to deal with this particular pathogen should we come in contact with it. Of course, our immune system has never seen it before. It’s a different type of immune response when it comes to something that your immune system hasn’t seen before.
The angle that’s important that I don’t think people are talking about quite enough is the function of the gut in all of this because most people have heard 70% to 80% of your immune tissue is in your gut, but what does that actually mean, and what do we do in the gut to support our immune system? I think those are the things where people need a little bit more illumination and I’ve been talking a lot about because yes, we can take our vitamin C, we can do our zincs. There’s lots of herbs we can take to help the immune system and those are all really beneficial, but ultimately, the command and control center for our immune system is in the gut, and that’s the part that we really need to help people understand.
Ari Whitten: We know there’s a body of literature being built out. It’s pretty sizable already around the gut immune axis. There’s also some literature around the gut-lung access. What do you think are the most important elements that people should understand about the role of the gut in immune health? How does it relate to our immune health?
Kiran Krishnan: Let’s talk about the physiology involved here and how it is, in many ways, very counterintuitive to how you think the immune system would work. First and foremost, that saying of 70% to 80% of your immune system is in your gut is actually true, so it’s not just something people say. It is a reality, but what does that actually mean, what does that look like? Your immune system has different types of tissues. One of the major classes of tissues that your immune system has is called sampling tissues.
These are tissues whose job it is within the immune system to sample the world around it and to understand what the body’s being exposed to both chronically and then acutely as well, and then learn what those things are, and then learn whether or not it should be attacking them. That’s how you develop oral tolerance. The foods you eat every day, they’re perfectly healthy for you. Your immune system shouldn’t be detecting and fighting them. If they do, then it leads to, at the low-end, immune intolerance of those foods all the way up to serious anaphylactic responses to certain classes of food.
Those are some of the examples of why the immune system is always sampling things that are entering the body. Why would it be in your gut, the sampling tissue? As it turns out, the gut is the largest site of where foreign material enters your body. We get some stuff coming in through our eyes, our nose, our ears, your genital tract, some through our skin when the skin is broken, but for the most part, we are putting most of the things around us into our mouth. Our food contains lots of different compounds. Aside from the food, the nutritious side, it’s got toxins from the environment around it.
It’s gotten microbes, viruses, protozoans, it’s got chemical compounds in most of the Western diet. All of those things are things that your immune system needs to sample and understand, but now here’s the really complicated part for the immune system. Imagine you are an immune cell and you’ve put yourself in the immune cells shoes, and here you are on a particular part of the gut and your job is to sample all of the microbes, and food particles, and all that are coming through and make a decision on what is foreign, what’s not foreign, what you should attack, so you are an immune cell. Now, all the while being the immune cell, you are completely covered with microbes, that is your microbiome.
Imagine the arduous task of this cell where its job is to detect and identify microbes and all that that are potentially problematic, all the while, it’s covered in microbes because every square millimeter of our immune tissue in our gut is covered by microbes. How does all of that function? That’s actually played immunology for some time over the last several decades is understanding this concept that our immune tissue that is supposed to detect and protect us from microbes are also always covered in microbes, so how is it that they do what they do? As it turns out, this whole concept of immune crosstalk has been discovered.
Immune crosstalk is this conversation that our immune system in our gut has with the microbes that live in our gut. In fact, the microbes in large part train and tutor our immune system in our gut to help it understand what is normal to exist in that ecosystem and what is new and potentially harmful. That immune tutoring, that flagging, if you will, that amplification of response to new things that are entering the body are directed by the microbes that live in the gut. That crosstalk is a real intimate relationship between our immune system and the microbes that exist there, and without an effective crosstalk, our immune system would not function the way it’s supposed to function.
How gut health is tied to respiratory disease
Ari Whitten: Very interesting. I could see the relevance of this immediately and I’m sure everyone can too of, let’s say, food poisoning, where you have pathogens or toxins coming in and you need to sense that or to something like E coli poisoning or you’re exposed to a pathogen. Does this, what’s going on in the gut, what you’re describing there relate to respiratory infections in any way? Also, maybe you can tie in, I know you’ve talked about that coronavirus, this COVID-19 is not purely entering us through the respiratory route, so maybe you want to tie in all those elements.
Kiran Krishnan: Yes, absolutely. The thing is, anything that enters through the respiratory route will also end up in the gut to some degree because one of the things that happen is when things are in the upper respiratory tract, it gets trapped by mucus. That’s one of the important jobs of mucus in your respiratory system is trapping things so that your immune system has a chance to identify. Then we also have something called a mucociliary elevator, which is the cilia in your lungs and airways that move the mucus up, and then your sinus systems drain the mucus down and all of that ultimately gets swallowed.
Everything from your nose, and your ears, and your lungs, all of that stuff eventually comes into your throat and you end up swallowing it. The swallowing part is really important because that’s where whatever’s being trapped in your respiratory tract and in the upper airways gets presented to the immune tissue in your gut so that there is an additional and very important robust app action of learning about those pathogens.
Ari Whitten: Should we all swallow lots of mucus instead of spitting it out?
Kiran Krishnan: Yes, absolutely. That swelling of the mucus is actually a very important part of our immune process because then mucus is an immunoglobulin coded group or lump, if you will, of pathogens that your body is constantly exposed to. There’s a whole booger conversation we can have, which I’ve been really observing kids in booger eating, and trying to understand the evolutionary benefit of it because boogers essentially act as like a vaccine.
Ari Whitten: This is your work as a research microbiologist is sitting outside of a kindergarten playground and observing the kids that are drawing boogers?
Kiran Krishnan: Exactly, writing it down very [crosstalk] intricately, but yes, that’s important. Now, with COVID-19 in particular, SARS-Cov-2, the virus there, it is absolutely entering through the gut and causing a gut-based infection as well. In fact, at least 53% of the cases in one of the latest publications in the journal of gastroenterology shows that they first present with gastro symptoms rather than anything else. Before any shortness of breath or fever, anything like that, they present with nausea, they present with diarrhea, with cramping and pain to the gut.
Now, here’s another interesting thing, there’s a most recent study published, and this is especially on pediatric cases but also in adults. They found that they can detect the presence of the virus much longer in stool samples and they can even in the nasopharyngeal swabs. They will actually find patients who have recovered, meaning they have no more symptoms than their nasopharyngeal swabs are negative, and yet they can continue to find the virus persisting in the stool for a period of time, well beyond when the negative test showed up in the nasopharyngeal swab. So there’s a real gut thing going on here with this.
Ari Whitten: Just out of curiosity, is there any meaningful practical relevance that we can derive from that? Does it tell us anything useful to know that?
Kiran Krishnan: It does. A couple of things. It means, number one, that the virus does have the capability of infecting and persisting in the gut. Early on, in this pandemic, the assumption was that stomach acid would kill it because it’s an envelope virus. Envelope viruses are not that robust, to begin with. Soap kills it well, alcohol kills it well, and so on. The assumption was that the stomach acid would kill it so the oral route is not really a risk, but as it turns out, the oral route is a risk, somehow it’s surviving through the stomach acid, and maybe it’s because it’s embedded within food and it’s hiding from the stomach acid, so that may be a reason.
Number two, if there is an infection occurring in the gut, it’s occurring where the largest sampling site of their immune system is, so it’s a great opportunity for the immune system to elicit a robust response against this invading pathogen before it gets to other parts of the body.
If your gut, and I would presume this, we don’t have a study to show this, but my hypothesis and presumption would be, if we can start to manage and control the infection when it’s in the gut, then it may never be that prolific in the rest of the body because now you’ve got a chance to understand your immune system, has a chance to understand the pathogen, deal with it, and already start producing the important antibodies and so on against it before it makes its way into the upper respiratory tract or even the lower lungs, which is where it starts causing pneumonia and other questionable things.
That’s one significant thing is that yes, it probably can be transmitted through the oral-fecal route. That’s a really important thing because pathogens that can be transferred through the fecal-oral route or oral-fecal route have other care structures that we have to put around it, we have to secure the food system a little bit more and so on, but then it also means
that since it can persist in the gut, if we can initiate a more robust response in the gut, that may help with the overall defense against it.
Ari Whitten: Presumably, obviously, we don’t have a sizable body of research to show this with this specific strain of virus yet, but presumably, having better gut health would lead to a more prolific, a more robust immune reaction, and, I guess, faster immunity or potentially less-severe symptoms as a result of that when exposed to this virus?
Kiran Krishnan: Yes, absolutely because there’s something called the mesenteric lymphatic system and that’s intimately connected to the gut. Everything that the gut lymphoid tissue samples, so including a pathogen like this that may enter, the response to it gets amplified through the mesenteric lymphatic system which is centered around the gut and then it gets amplified and translated to the rest of the body. Then whatever happens in that part of the immune response, the signals go out to other parts of the body to say, “Hey, should you encounter this pathogen in another part, here’s the antibody, here’s the B cell, here are the T cells that are ready to fight that particular infection.
Now, we know this from other viral infections, we don’t know it from COVID yet, obviously, we don’t have a study on that, but looking at other viral infection like influenza, for example, or other types of RNA viruses, when you have a robust immune response in the gut, and microbes in the gut can actually facilitate a strong antiviral response. It’s not outlandish to think that, “Hey, if we improve our gut health or if we improve our community between our microbiome and immune system, that could be beneficial.”
Ari Whitten: I want to digress for a moment, and then I want to come back to the gut, and maybe practical strategies of how we can improve our gut. Just out of curiosity, there’s a new theory that has started to emerge around hemoglobin and how this virus may attack the hemoglobin, and attack red blood cells, and lead to free hemoglobin, and lead to less efficient oxygen delivery to the tissues. There’s been some debate back and forth about this.
There’s a guy who came out and wrote an article trying to debunk it, but the debunking, it wasn’t saying, “Hey, we have really strong evidence to say this is not true,” it was just saying, “Hey, we don’t really have strong evidence to say it is true,” but he framed it as kind of a debunking. Anyway, I’m just assuming you know the theory. I’m just curious if you have any thoughts if that’s taking place or any thoughts around that?
Kiran Krishnan: Yes, when you put the pieces together, the clinical manifestations of this condition, it does start to make sense that it is not the typical bilateral pneumonia, acute respiratory distress that we are thinking that it is. The typical response to those types of conditions of bilateral pneumonia and the acute respiratory distress, the ARDS is the ventilator and using a high-pressure ventilation to try to force oxygen into the alveoli. Now, that doesn’t seem to be working as well as it normally does in ARDS and bilateral pneumonia. Then there’s other issues as well, there’s the sepsis part of it.
A good percentage of the people that are succumbing to this are actually succumbing to sepsis, so how does sepsis play into the role here. There’s some thinking that I have, in particular, around that. I do think that we are seeing more of an issue of dislodging of iron from hemoglobin and the inability of our red blood cells to actually bind oxygen because what we’re starting to see clinically is that high flow oxygen therapy seems to be working as well as ventilators. Maybe hyperbaric chambers would be even better, that would be the next step up.
That systemic hypoxia is not quite characteristic of the ARDS because what we’re seeing, and this is being reported by clinicians on the front lines is their patients coming in with real frank hypoxia without having respiratory distress, so their lung seems to be working okay and yet their blood oxygen saturation is really low. It’s confusing. The knee jerk reaction is going to be because when you do the chest X-ray, you see the glass. That’s how clinicians diagnose that there’s some sort of pneumonia or some sort of acute respiratory distress going, you see that glass-like structure in the X-ray on the lungs, but that can also be explained by the oxidative stress that’s going on by the release of oxidative iron in the lungs.
There’s a clinical debate. I wish that what they would start doing, just as a precaution, is as soon as people come in to the hospital with that low blood oxygen saturation is just put them on high flow oxygen and crank that up as high as they can.
Why oxygen may be a good approach to treating COVID-19
Ari Whitten: It seems like we had this mad dash to get more ventilators, and that was there’s a shortage of ventilators, and so there was this huge effort, lots of money spent, companies hired to make more ventilators. I think a bunch of companies like Tesla and a few others even came to the rescue and said, “We’ll start making ventilators.” It seems now like that whole thing has largely been misguided and that maybe what we really needed to focus on was getting more oxygen machines like are used to treat altitude sickness.
Kiran Krishnan: Yes, exactly. Part of the explanation of why this malaria drug seems to have some effect, the hydroxychloroquine because that fights against this hypoxia type of distress now. There’s a lot of pieces that are leaning towards this other picture of what’s happening clinically. The sepsis part, to me, is interesting, and I set this into a Facebook group of a group of physicians that have been discussing this is that when you have a lot of free iron in the blood, which is what’s happening when they dislodge the ability of heme to hold oxygen, they’re dislodging the iron off of the heme group.
What happens when you have free iron is you have all of these circulating pathogens in the blood. That’s normal because we get pathogens entering the blood all the time through our mouth, our gums, teeth, even through the gut if your gut is leaky, but the pathogens in the blood are kept in check because the vast majority of them need iron for metabolism, and they need iron in order for them to multiply and then start creating their toxins and so on. You’ve got around a thousand bacteria per milliliter of blood. Our blood is not sterile, it’s got a lot of bacteria in it, but they’re, again, all dormant because there’s no free iron.
Now when you start increasing the free iron in the blood, you’re actually providing the metabolic capability of these pathogens to start multiplying and releasing toxins. That could be one of the reasons why we’re seeing a drive in sepsis and septicemia in these patients, after a period of battling this hypoxia. It all kind of comes together interestingly, and I’m hoping somebody is going to do a study on it and be more definitive about it because if it is the hypoxia, then there’s a whole suite of things that may work better than the whole intubation ventilator process that they’re trying to do right now.
There is some really early-stage disease stuff that can be done too. There’s some medications like altitude sickness medication that actually could work early on if they start looking at the clinical pathology the right way.
The gut-lung axis
Ari Whitten: Got it. There’s also some research around the gut-lung access, in particular, showing, and there’s even some research, for example, showing use of certain probiotics can decrease the incidence of respiratory infections and/or severity of respiratory infections. Do you have any thoughts on that and any practical relevance of that body of research to COVID-19?
Kiran Krishnan: Yes, so, in fact, one of the strains that we work with a lot, it’s called bacillus clausii is actually used a prescription drug in Latin America and parts of Europe for chronic upper respiratory infection in kids because there seems to be this connection between an overgrowth of gram-negative bacteria in the gut, and then there is a translational effect or the presence of that gram-negative bacteria into the lungs as well. So then you see people with hyperactive airways, with reactive airways, with asthma tending to have a higher incidence rate of gram-negative bacteria in the lungs as well.
A lot of that may come from the mouth, a lot of that may come through the mucosa or through a permeable intestine and then making its way into the lung tissue. We’ve bacteria all our body on the inside. We used to think, of course, certain areas of the body was sterile, we now come to find out really nothing is sterile in the body. The gut and the mouth tend to be big sources of bacteria, so when you’ve got this functional bacteria in those regions that can drive this function in other parts of the body. It seems like microbes that can control the presence of gram-negative bacteria can have then an impact on microbes in other parts of the body and the lungs for example.
So bacillus clausii has a couple of well-done published clinical trials showing reducing the incidents of upper respiratory distress and upper respiratory infection, and it’s been used as a prescription drug for that reason. There is a real clear cut connection between the gut and the lungs. So if you’re just trying to improve your gut function, and your digestive function, and modulating the microbiome in a very positive way, it can have an impact on all of these things.
How COVID-19 affects the immune system
Ari Whitten: Very interesting. One of the other things I’ve heard you talk about is the immune system and the way you phrase it as two different types of immune reactions. Obviously, we have the innate and the adaptive immune system. In the context of COVID-19, there is a concern around the cytokine storm excess inflammation. Anyway, I know that you know what I’m referring to at this point, so I’d rather than try to explain it myself, I’ll let you explain it. What are these two different types of immune reactions, and in the context of COVID-19, which of the two do we need to shift towards?
Kiran Krishnan: Immunology can be extremely confusing, so I always like to use analogies so it helps people understand it a little bit better. One of the analogies that I’ve been using most recently is imagine that your body is a house, and in this house, there’s lots of windows open all the time and you’ve got a couple of groups of defensive individuals in the house to protect the house from things that enter into the windows. Let’s consider those things as bugs. Many different types of bugs, from little mosquitoes to gnats or to flies or whatever. The different types of bugs tend to enter into the house at different periods of time.
Now your defense people, there’s two types of people. You’ve got the first line of defense, which is the innate immune system. For analogy sake, let’s say that these are the people that are the fastest to respond. They move faster, they’re more agile, but their way of defending the home against that bug coming in is by using a blowtorch. So they will get to the window and that area where the bug flew in and it doesn’t matter what bug it is, they’re going to blow torch it and they’re definitely going to kill the bug, but they’re probably going to burn the wall behind it a little bit as well, but they are the fastest, so they’re going to get there first.
Then the second group of people are ones that are specialists in different kinds of bugs and they have specialized tools to be able to address that specific buck, but they’re much slower and they wait for signals from the blowtorch guys to say, “Hey, I’ve got here, there is a bug, there is a problem you need to come up as well.” The innate immune system are the blowtorch people, they are nonspecific, meaning they see that there’s a problem, they see that something’s happening, they rush to that area. One of the defense mechanisms they use it is inflammation.
Inflammation is a way of actually kind of quarantining an area off so that whatever is in that area doesn’t dissipate through the rest of the body as well. No different than if you get a cut on your skin, it’ll get red, it’ll get inflamed. That inflammation is trying to quarantine that space, so anything that entered through that cut doesn’t get dissipated into the rest of the blood system. Inflammation is the first thing that it uses, and then it has the innate immune system. Like the blowtorch, has all of these tools that just kills biological things in that area, including your own cells, so it’s going to cause a bunch of damage in that area.
It’s, again, like taking a blowtorch to kill a mosquito. You’re going to kill the mosquito, but you’re going to burn the wall behind it. Now the problem is if that blowtorch response is the one that stays and becomes the predominant response to the invading problem. If your immune system is working right, that blowtorch guy is going to rush to that area where the bug came in, he’s going to blowtorch things a little bit, but that just gives some degree of control until the specialist can come up. The specialist is going to tap him on the shoulder and go, “Hey, we don’t need any more blowtorch. I know exactly what this bug is, I can pick it out and deal with it specifically without damaging anything else.”
Then the body goes through a small process of repairing that brick wall. Now in COVID-19 and in many other chronic conditions well before COVID-19, which includes allergies, and autoimmune diseases, and food intolerance, and so on, what we have is an over-reactive blowtorch response. We’re not getting that tap on the shoulder, we’re not switching to the specialized responders, which is the adaptive immune system, we’re just getting nothing but blowtorch response.
In the body, once you start responding to everything with a blowtorch response because your immune system is not being trained effectively, not getting the signals it should typically from the microbiome, then everything it sees gets a blowtorch response and that becomes a sustained response in the body, especially when you have something like a pathogen that’s continuously multiplying and adding more and more stimuli for the immune system in the body itself. What’s happening with the COVID-19 disease itself, all of the feeling sick, all of the body aches, the fever, and then the death itself in the percentage of people, all of that is driven by our immune system.
We feel the infection because of the immune response to it. We become really sick and become really compromised because of the immune response. The virus is doing what viruses do. It just comes in, it’s trying to take over cells and multiply, and there is some effect from the virus damaging the cells that it takes over. A lot of what we feel and a lot of that negative response is our immune system responding to it and responding with a blowtorch and torching everything around it.
Ari Whitten: A quick question for you. We know that with COVID-19, young people, in particular, are, especially kids, generally have mild symptoms or asymptomatic. We also know that, in the words Dr. Robert Naviaux with the Cell Danger Response, the mitochondria are the central hub of the innate immune system. We talked, as I mentioned earlier, we talked a lot about the gut mitochondria access in the previous interview that we did that’s just going to come out in the summit in a couple of months, fascinating stuff, so I know you know a lot about mitochondria.
My question is, given that we know mitochondria are the central hub of the innate immune system, young people are generally asymptomatic or mild, is it reasonable to say that maybe a more robust, healthier mitochondria might be a factor in the strength, and the robustness, and the resilience of the innate immune system such that it makes us more likely to have mild symptoms as opposed to severe symptoms?
Kiran Krishnan: There is a deep connection there because one of the things that dictates a mild versus severe symptom is how fast does a virus multiply in your body? The ability of your immune system to detect cells that are now infected by the virus and sequester and, in fact, phagocytize, which is eating those infected cells so that it doesn’t release a bunch of virus into the system, that control mechanism is a big part of whether or not you’re going to just get it and feel just a little bit weird and down, maybe some sniffles and a slight cough, and then be fine in a couple of days or whether this is going to be a 14-day ordeal and you’re going to go through really bad periods during that 14 days is how fast is that virus multiplying, and how fast can the innate immune system keep that in check.
All of those are energetic dependent. Your innate immune system also uses short-chain fatty acids from your colon as a big part of energy. Your macrophages and dendritic cells, whose job it is to go around and eat up all of the infected cells and eat up the virus, they require butyrate as a major fuel source for themselves. The function of the mitochondria to provide the energetics that are required for your immune cells to multiply quickly, go around, look for viruses, look for infected cells, sequester them, and then also the colonic production of butyrate, all of those things play a big factor.
I think kids are seeing less of a response to this for a couple of reasons. I think that may be one of the reasons that their energetics are way better than adults. We tend to have much more dysfunctional mitochondria. The second reason is they probably have less expression of that ACE2 receptor, which is a target for the virus. The ACE2 receptor on numerous tissues is the honing beacon for the virus and it latches onto that ACE2 receptor, and that’s how it enters the cells.
The ACE2 receptors typically express in tissues where there’s damage going on and the body’s trying to repair itself, and so kids tend to have less ACE2 receptor because they haven’t had years of chronic inflammation, and toxicity, and damage to the endothelial, the epithelial, and all the tissues on the inside. So they probably have less options for the virus in terms of targets, and then when they do see the virus, their immune system is much more funded with energy than our immune systems are, so they’re faster to react.
Ari Whitten: Got it. I want to come back to the ACE2 thing in a second, but to go back to the innate and the adaptive component, I know that the goal, from your perspective, is really shifting most people who are in an inflammation dominant state towards lowering the inflammatory response, and then shifting them more into the adaptive immunity and helping that system. What are your thoughts on how to effectively do that?
Kiran Krishnan: The gut microbiome plays a really important role in that. because what we see from research is that having a robust microbiome the signals from the microbes and the microbiome to those sampling tissues in the immune system can make that TH2, TH1 shift, and that’s a type of helper T cells that the microbiome helps proliferate.The microbiome recognizes that the host is under distress and they will actually stimulate your immune tissue to produce T helper cells that facilitate that transition.
These are the cells that go, “Okay, we’ve got the innate immune system trying to control things and sequester it, now we need the antibody-producing cells to come in,” which are the specialized people to actually take over the infection rather than letting the blowtorch response continue. Having that robust health in microbiome plays a big role in the immune system switching between that too. Then lots of herbal products that can help that as well. Beta-glucans have been shown to be able to provide nutrients that help that switch. One of the things that quercetin does, it helps modulate some of that switch from that really inflammatory response to that adaptive response.
That’s one of the reasons why people use it in allergies, for example, because allergies tend to have that really strong inflammatory response. Vitamin C helps that transition. That’s why those nutrients are becoming more and more important now in people’s systems, but ultimately, the command center for all of that is in the gut. If your microbiome is unhealthy, we know it’s going to switch the response to more of that inflammatory type of reaction because the microbiome is intimately connected in how the immune system response.
Probiotics can be a really big benefit. It’s hard for a lot of people to think probiotics in my immune system, well, yes, because so much of your immune system is in your gut and if you’re using the right type of probiotics, they will modulate the microbiome and they will help modulate their immune response, so probiotics play a big role. Prebiotics play a big role as well.
We wrote a white paper for our doctor-clientele that I work with closely on the importance of oligosaccharides in fueling the growth of certain bacteria, and then also fueling the growth of immune cells that are really important in shuttling that response between the blowtorch response and the specialized response, so the innate to the adaptive response. So the gut plays a really intimate role in that.
The best prebiotic for gut health
Ari Whitten: What specific prebiotic fibers do you feel have the biggest role? I know I’ve seen some research run, I believe it’s pronounced arabinogalactan, I’ve only read it, I’ve never said it, but arabinogalactan, I’m sure there’s some others. I know that one has some good research on its ability to decrease the incidence of respiratory infections.
Kiran Krishnan: Beta-glucans are a type of prebiotic, but they have that similar effect as well, oligosaccharides, we work with a lot of oligosaccharides, one class called xylooligosaccharides, and then fructooligosaccharides. Both of those have real strong impacts on the immune system. It’s interesting because we know, we’ve actually seen the kinetics of the immune response to this particular new pathogen. There’s a study published in Nature Medicine, it was a case study on a typical COVID infection that ended up being okay, which is what we see, thankfully, with most people.
This is a patient that came in with shortness of breath type of symptoms, fever, body aches, just standard things that we’re seeing with the COVID-19. She was admitted into the hospital, this was done in Australia. She was admitted into hospital and right away they started measuring all kinds of stuff, all of her immune kinetics and response to the virus. What they found was right at the early part of the onset of symptoms, she did have a little bit of elevated inflammatory response that was measured through CRPC-reactive protein.
They saw some elevation of C-reactive protein, but within the second day after having symptomology, she actually had a really robust proliferation of anti-SARS-Cov-2 antibodies in the B cells and make the antibodies. Her system was already shifted to a really robust adaptive immune response. What was interesting about it is none of the inflammatory markers and cytokines were elevated above normal, even though she was in active disease. Which is really interesting because typically, in any kind of acute active infection, your inflammatory cytokines are going to be up because your innate immune system is going nuts.
In her case, and this was the typical pattern that they’re seeing as like the best-case scenario is her innate immune response was really attenuated, and the adaptive response took over much faster. Then as her antibodies against the virus peaked, that’s exactly when her symptoms disappeared. Her symptoms disappeared, she was discharged from the hospital. She never needed any care in the hospital, they just kept her there for observation, for the study. They didn’t have to give her any supplemental oxygen, they just gave her some fluids. They didn’t use any sort of medication either. Then they found that as soon as her antibodies peaked, her symptoms went away.
They discharged her the next day, and then they followed her up to 22 days after being discharged. She had no symptoms that whole time, but she had remained with very elevated levels of anti-SARS-Cov 2 antibodies. That adaptive immune response was so upregulated and stoked and stayed that way for a long period of time.
Ari Whitten: What did they attribute that to?
Kiran Krishnan: One of the things they were saying is that– At this time they didn’t have other data that I’m going to reference here. One of the things that they were saying is that that’s just the body’s way of maintaining a protective layer so you don’t get a re-infection. Right? They found both IgM and then IgG antibodies already. Typically, you get IgM in the early phase, for the first couple of weeks. It takes IgG a little bit longer, but they saw both IgM and IgG coming in pretty early.
Now, my hypothesis is that the reason that they probably saw continued elevated levels of the antibodies is because it likely was continuing to persist in the gut. I mentioned earlier that, most recent study shows that you can detect the virus in the gut much longer than you can in the upper respiratory tract. More than likely, even though she left the hospital, she has no symptoms, there was some viral replication going on in the gut itself. That maintained that higher level of protective antibodies.
It seems really important based on that publication of making sure the adaptive immune system is upregulated and is ready to take over the fight rather than the blowtorch guys. So much of that is dependent on how healthy your microbiome is.
The best tips for a fast-acting immune system
Ari Whitten: I know you’ve mentioned a few things already, obviously, you keep emphasizing the gut health, microbiome health. You’ve mentioned quercitin, you’ve mentioned a couple of other things in there, prebiotics as well, beta-glucans. What would you say is your full list, if you will, of strategies to make our adaptive immune system really robust and fast-acting?
Kiran Krishnan: Yes, so we cannot overestimate or overstate the impact of nutrition, right? Just a healthy diet in general, low inflammatory diet. So, foods that you know are triggering for you. Vast majority of people actually get some sort of inflammatory, transient leaky gut from eating gluten, as an example. There are some studies that have come out that showed it’s not just celiac people, it’s not just non-celiac gluten intolerant. In fact, 100% of people they tested get transient leaky gut from eating gluten. They may not feel it and their body might repair it relatively quickly, but it’s going to elevate your inflammatory response in that period of time.
The nutrition, if we can make it clean it and clean it up- I know it’s harder now. It’s hard to find things like we normally did, but the cleaner our nutrition can be the better. I know fast food is open still right now in a lot of places and that may be the easiest thing to go get–
Ari Whitten: Because only the essential businesses stay open. We need Burger King.
Kiran Krishnan: We need Burger King. I know exactly. The essential fast food is still available but try to refrain from those temptations. I know it’s easier in this time to order a pizza. So try to refrain from doing that four times a week because it’s the easier thing to do because the nutrition, the food that you’re putting into your system dictates a lot about how your microbiome looks and then how your immune system functions.
Sugar has a way of stoking the inflammatory response. Salt has a way of increasing something called interleukin 17, which up-regulates your Th17 response. Those are the T-helper cells that help the inflammatory response. You don’t need that as well.
Being able to do basic things like reduce sugar and salt, reduce the fast food, increase whole foods, and increase the diversity in your diet like polyphenols, carotenoids that come from lots of plant-based foods and so on as well. All of those are beneficial to the gut and beneficial to the immune system.
Stress is one of the biggest things. That’s something we cannot talk about enough nowadays because a 2015 study in the frontiers of immunology published a meta-analysis that showed that they could argue with a lot of scientific validation that stress is the number one driver of morbidity and mortality worldwide because one of the first things that stress does is creates significant intestinal permeability.
Stress also upregulates the reproduction of latent pathogens, viruses that have been sitting in your system, like cytomegalovirus, Epstein-Barr virus, herpes simplex, all of these things are sitting there, latent in your system, just waiting for the presence of stress hormones. The moment they sense stress hormones, they start proliferating, right? not only is the stress causing more inflammation in your body, causing more permeability, it’s allowing latent pathogens to start taking over, thereby, further compromising your immune system.
It’s really hard now; people are locked in their homes, they’re not connecting with others, everything you read is stressful over the year, so it becomes really important to really tend to work on the mindfulness side of things to bring down your stress. One of the things I recommended on a recent recording I did was, we shouldn’t be hypervigilant about every single number, every single day, right? To us, to a regular person who’s not involved in the frontline fight of this and so on, does it really matter if today we have 650,000 cases versus 640? Right?
We know it’s bad, we know it’s increasing and we know what’s going to happen is it’s going to go up for a period of time, hopefully, flatten and start to come down, right? That’s the inevitability of it, right? Does it matter what it is today versus yesterday, versus the next day and so on? That hypervigilance of following and tracking this causes a lot of angst and anxiety and stress in people, right? That is really devastating to the system; makes you more susceptible, makes you more inflammatory rather than adaptive.
Those two things: the nutrition side, the mindfulness side, we cannot overstate those that sound like holistic health things but they really have an impact on how your immune system responds to new pathogens and anything it’s ever seen.
How to modulate ACE2
Ari Whitten: I want to ask you briefly about exercise and ACE-2. Then I want to get into- I want to make sure we cover probiotics and the products from your company because I think they’re wonderful products. I want to make sure we give them some time before we have to end. ACE-2, you mentioned briefly, it’s this receptor, it seems to be a port of entry for this virus. The gist of it is that it’s, as you said, up-regulated through tissue damage. If we have lots of tissue damage through various sources of stress, whether it may be gut permeability leading to excess lipopolysaccharide leaking into the system, or a poor diet, or whatever the case may be, and lots of other sources, toxins and so on that we could list there–
Kiran Krishnan: Blood pressure, high blood sugar, all of those.
Ari Whitten: Exactly. So that we know that there’s this very clear link between hypertension, high blood sugar, cardiovascular disease, and a much higher risk of dying from COVID-19. What are your thoughts on the best ways to modulate ACE-2? I have one, also, particular question that’s an area of confusion for me because there’s some research showing that exercise seems to upregulate these two and that’s generally in the research looked at as a good thing. We know exercise generally protects against respiratory infections, but it seems to be maybe a tricky area here. What are your thoughts on that?
Kiran Krishnan: Yes, so I think exercise can be broken down into the type of exercise, right? Really high-intensity stuff that requires- that actually causes tissue damage, then the adaptation to that damage is what brings about more fitness, more strength and so on. In an acute period, that damage can make you more susceptible, right? There are studies that show that ultra-marathon runners, and Ironman athletes, and all that, are more susceptible to respiratory infections, than people who do more moderate exercise, especially during their training period because they are putting a lot of stress, inflammation, oxidative stress and damage into those tissues. During that period you are more susceptible.
General, medium grade or low-grade exercise, weight lifting, where you’re causing more tissue injury on your skeletal muscles, that’s a little bit different, right? That actually will give you some adaptive benefits and not create the vulnerability. One of the things I was recommending to people is, this is not a time to go outside and do really intense sprints. This is not the time to go up and do really intense hill runs and things that just really put stress and burden on your body and your respiratory system because, should you encounter the virus during that period of burden, it’ll actually increase your risk of getting an infection.
In fact, and this is anecdotal, but the first two people I found out that I have connections to that got the virus were both Ironman triathletes. These are people in their thirties, fit as all can be, because they’re Ironman triathletes. They were hospitalized on ventilators and they were still in the training mode.
Ari Whitten: On a personal note, this is my burden. My personal weakness is, every time in the last 10 years, 15 years that I’ve gotten sick, it usually it’s right after a period of, like, three days in a row of super-intense activity. Maybe I’d go rock climbing and do a really hard workout, weightlifting and surfing. I’m doing like four hours of exercise every day for three days straight and then boom, get a cold.
Kiran Krishnan: Absolutely. Yes. We see that in professional athletes all the time. In professional cycling, that’s one of the plagues that really affects a professional cyclist, is that, getting sick during the training for a big tour. Your body is most susceptible. You’re putting it through stress, which the adaptation to the stress is where you become stronger, but in that period, you are more vulnerable. ACE-2 is the receptor that shows up to repair the damage issues. ACE-2 is wonderful. It’s an amazing thing. If we didn’t have it we would all just wither away.
But ACE-2, the reason why the virus targets it, is because the presence of it indicates a compromised system. It’s a ubiquitous receptor. It’s found in so many tissues in the gut, in the lungs, in the heart in the skeletal, in the soft tissue, sorry, smooth muscles. Everything that lines the inside of your body will express ACE-2 in response to damage.
This virus has basically evolved to find a very ubiquitous receptor as its target. There’s lots of targets for it to enter the body and to the cells. Then, it also is a flag for a compromised system, so that, the virus knows that if it enters a cell that has an ACE-2 expression, that there’s an immune compromization that that tissue is probably more sequestered, there’s more inflammation there. That allows the virus a chance to take over and reproduce.
Exercise in general is a great thing obviously, no doubt about that, but this may be more of a time to be more moderate about the exercise and maybe focus more on lifting things and not putting your body through really stressful cardiovascular work.
MegaSporeBiotic gut supplement
Ari Whitten: No triathlon training right now or Crazy CrossFit and high intensity interval workout. Yes, I’ve personally toned back my exercise routine a lot. I’m doing a lot of hiking right now and hiking with breath holds, working on stimulating some of those pathways.
I want to make sure we cover, and I wish we had more time to do this. I want to go a little bit over time. I was just emailing my next interview to let them know I’m going to be a few minutes late, but MegaSporeBiotic is a phenomenal probiotic. I know you guys have done a lot of research on this. I’m personally taking this myself. I know you have another great product related to immune health, the IgG product. Talk to me about those two things and the uniqueness of MegaSpore because it’s got a lot of these bacillus strains and not the typical lactobacillus and bifido species that we see in most other probiotics. What’s the difference there and then talk to me about the IgG product as well.
Kiran Krishnan: Yes, so, a quick overview on that. The old thinking on probiotics has been, let’s just bombard the system with a bunch of good bacteria. Then the doses started going up and up and up, a hundred billion, 200 billion, 800 billion and so on. The problem is that we’re focusing on one or two genuses, lactobacillus and bifidobacteria, they make up one or two of the hundreds of geniuses that are in the gut. What about the rest of the microbes?
That’s how we looked at probiotics when we first came in, we said, surely, there’s some documented benefits of getting certain types of lactobacillus into your system, certain types of bifidobacteria. Ultimately, if we’re going to make any profound change in the microbiome, we have to be able to affect the rest of the microbiome. Even if you have a product that has a 500 billion CFU dose, it sounds like a lot, but you’re putting it into a sea of a hundred trillion bacteria. It’s a blip in the ocean of the microbiome, so you’re really not going to get any profound therapeutic benefit until you can make measurable changes in the rest of that population.
We were looking for orchestrating bacteria, ones that have shown the ability to influence the rest of the microbiome so that there’s broader sweeping change going on in the microbiome. We honed it in these spores because they’ve been in the prescription drug industry since 1952 and still are today, whether you use them for gut infections, for dysentery and other types of gut infections. Our thinking was, wait a minute, these bacteria can go in the gut, they can read the microbial environment, something called quorum sensing, they can find dysfunctional or overgrown bad bacteria, sit next to them and bring their levels down without hurting any of the other beneficial bacteria around it. That’s why in many countries, they’re used in lieu of antibiotics for gut infections.
Our thinking was, okay, if they can find and bring down the growth of bad bacteria, maybe they can also influence the growth of good bacteria, and by that rationale maybe they can bring back balance and fix dysbiosis. That’s how we thought of them. We thought of them as the orchestrators, the conductors, the SEAL Team Six, if you will, of the gut. Sending them in will allow them to modulate what the rest of the microbiome looks like.
Sure enough we saw that- we published a study in August of last year showing that when you add the spores into the microbiome, it increases the diversity of all of this species by about 30%. They bring about certain amounts of uniformity. They increase the growth of these really important keystone strains; these are strains that are really important for overall health and wellness. They increase the growth of those strains by 10 to 100- 10 to 100, not percent, but 10 to 100 times higher. They do a lot of modulatory work in the gut microbiome. They look like orchestrators of the microbiomes.
Then we started saying, “Okay, we can change the microbiome with this tool. There’s lots of stuff we should be able to effect.” The first thing we wanted to test was, can we affect leaky gut, leaky gut being the primary and the predominant source of chronic low grade inflammation. Also, the thing that disrupts immune response in a very significant way and makes your immune system have a tendency towards a blowtorch response to everything.
Our first study was on leaky gut and sure enough we showed that in a 30-day period, without changing anything else, just adding in the spores, we were bringing down leaky gut and all its associated inflammation by over 60%. We were fixing metabolic dysfunctions like ghrelin response, hunger hormone response in the body. It’s a profound probiotic that creates a fundamental change in the microbiome. When you change the microbiome, you really change how your body responds to the world around you and how your immune system works and so on.
It’s been exciting. Since then, we’ve published five other trials, most recently on on triglycerides. We showed that people with elevated triglycerides, when they take the probiotic, it actually brings down the triglyceride levels by almost 38%, which is quite significant because then you look at– Triglycerides are major risk factor for all chronic issues. How does a probiotic bring down triglycerides? It all speaks to the leakiness in the gut, the impact on the liver and so on.
Right before that, we published a study on [unintelligible] protection with the probiotic. How it protects the liver against purposefully induced damage. This was an animal model study because we can’t do that to humans, but sure enough it protects the liver, protects the metabolic system, it protects the immune system and it changes the microbiome and it seals up the gut. That’s a really important factor.
The IgG is really interesting. Immunoglobulins are proteins that your immune system makes. Those are the antibodies that neutralize stuff that the immune system sees. Getting Bovine Immunoglobulins are really interesting and important because cows are out there grazing in the pastures and, being in the outdoor space, their immune systems are encountering all kinds of stuff; bacteria, viruses, molds, toxins and so on. They’re building constantly antibodies against all of these things, neutralizing antibodies against all of these things, IgG antibodies.
These are the most powerful neutralizing form of the antibodies against all of these offending compounds. What we do is we take the serum out of the cows and we spin out and purify those antibodies. When you add them back into our system, they go to work in our digestive tract right away, neutralizing all those things, neutralizing viruses, bacteria, toxins, compounds, mold toxins, bacterial toxins and so on, thereby lending a really important helping hand to our immune system who’s dealing with this stuff all day long in a typically the compromised system because of microbiomes are messed up too.
We found a profound effect when you add in the probiotic and the IgG together in terms of modulating the response that occurs in the gut and providing the immune system that really important helping hand.
Ari Whitten: Kiran, I seriously, and this is very high compliment because I interview a lot of people, but I seriously want to talk to you for like the next three hours.
Kiran Krishnan: [chuckles] Thank you so much.
Ari Whitten: I don’t want to stop this interview. I have so many more questions that I would love to ask you, including some particular things of an area of interest of mine related to phytochemicals, and all the people I’ve talked to, I’ve never been able to get good answers. I have a feeling you might have some good answers for me. I would love to have you back. I have one final question for you, rapid fire, without any explanation because we got to end; you got to go, I got to go.
If you could list out your top five things for Coronavirus prevention and optimizing the immune system and obviously mentioning a lot of the things that you’ve already mentioned here, but what would be your quick top five list?
Kiran Krishnan: Just to provide the disclaimer, none of this has been tested against Coronavirus. This is just what the science shows in terms of supporting the body’s resiliency. A really good probiotic is absolutely paramount, a spore-based probiotic. What I’m taking personally right now to improve my resilience is a spore-based probiotic with IgG. I’m using vitamin D with K2. We’re not getting as much sun as we need here in the Chicago land area so we need to increase vitamin D. I am using a fermentation product called EpiCor, which is a yeast fermentation. I’m doing my fasting.
Ari Whitten: That’s for, real quick, for beta-glucans, the yeast.
Kiran Krishnan: No. This one is actually a yeast ferment itself that comes out, great data, clinical research on colds and flus. It does have some part ability to increase the antiviral part of the body. I’m using that personally quite a bit right now as well. I am doing [unintelligible] and B vitamins to help the energetics, helping the mitochondria as well which helps. Then the fasting, the fasting is absolutely critical.
I don’t typically get stressed much but I’m still trying to do mindfulness work. When I wake up in the morning, first thing I’m doing is breathing exercises to try to kind of tamper down any sort of elevation of stress hormones, and I’m trying to get lots and lots of sleep. The probiotic and IgG, vitamin C, The EpiCor, those are the kind of the core things that I’m doing right now to keep my immune system tip top shape should it ever encounter this pathogen.
Ari Whitten: Beautiful. Kiran, and for everybody listening, I want to mention we’ll have links to everything he mentioned on the podcast page for this episode. It’s theenergyblueprint.com/kiran-krishnan. You can google his name or just go to the energyblueprint.com/podcast and you’ll see it there if you don’t want to worry about spelling a very exotic name, beautiful name, very exotic name.
Thank you again, my friend. This has been awesome. Really, really excellent. You’re brilliant, I love talking to you. Like I said, I could talk to you for three more hours. I think we need to have an automated scheduling where I interview you every two months or something. I would love to get like 10 more interviews out with you. Really, thank you so much, such a pleasure and have a wonderful rest of your day.
Kiran Krishnan: You too. Take care.
What most people may not be aware of when it comes to coronavirus (08:28)
How gut health is tied to respiratory disease (14:18)
Why oxygen may be a good approach to treating COVID-19 ( 25:45)
The gut-lung axis (28:39)
How COVID-19 affects the immune system (30:58)
The best prebiotic for gut health (43:34)
The best tips for a fast-acting immune system (48:16)
How to modulate ACE2 (53:20)
MegaSporeBiotic gut supplement (59:25)