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Webinar Replay: Gut & Microbiome: The Foundation of a Resilient Immune System with Kiran Krishnan, Part 1 – Transcript

Michael Roesslein:          And we are now recording. So, welcome. We are here with microbiologist Kiran Krishnan, Kiran, thank you. Apologize for the challenges, looks like Bill Gates is interfering. I don’t know if they own Zoom. Somebody probably owns Zoom. I’m sure it’s not an autonomous company.

Kiran Krishnan:                  Mm-mm (negative).

Michael Roesslein:          We are going to talk about the hottest topic in health today, which is immunity and how that ties into the gut, the microbiome, everything going on in there and how that relates to our overall immunity, immune resilience, susceptibility to infection, severity of infections. What we are not going to do, is we are not going to tell you how to prevent COVID-19 or cure COVID-19, or anything specific to treating COVID-19. So, I’m just throwing that out there right now, so this doesn’t get shut off before we get talking and I think that covers all the bases. We’re not treating, we’re not curing, we’re not diagnosing, we’re not preventing.

We are sharing information that might be relevant, especially now and … I see the chat box moving kind of, but it seems frozen. So, let me know, just pop it up again, test. Okay, cool. No. Test. Now, I’m seeing … I think everything’s okay. Hello from Ohio. All right. I think we’re okay and they’ll let me know if we’re not. So, I guess where we should probably start and also I would add that there is a Q&A box, which the chat tends to move really fast, you can enter questions in the chat and I’m pretty good at it, but this looks like it’s going to move fast. And so, sometimes questions get lost in the chat. So, there is a Q&A button as well, which are specific for questions and that might be a little bit easier with questions. We’re going to try to do some questions at the end.

I also have some in my email box that I’m going to try to decipher. Some of them are very long emails with a question tied in somewhere and then a couple from the Facebook post. So, I will carry on going and then I will try to manage the chat box and the questions from the other things and see how well we can do. So, without any more being in the way, if you would like to just give us the overview of, we all hear, “Oh, immunity starts in the gut or a certain percentage of immune function is in the gut.” That’s great and all, but can you give us a little bit more information in detail along those lines?

Kiran Krishnan:                  Yeah. In fact, this topic is so important I prepared PowerPoint slides today.

Michael Roesslein:          Perfect.

Kiran Krishnan:                  So, I’ll be sharing some PowerPoint slides, but I wanted to preface that by saying that I’ve heard a lot of good talks on the function of things like vitamin C and vitamin D and zinc and lots of herbals and all that. Those are all important and critical as well. I just haven’t heard enough about the role of the microbiome, and in fact, you can not have immunity without the microbiome. And that’s one of the things I want to illustrate for you today and go into some degree of detail on that. Our immune system is dependent, in large part, on our microbiome. We’ll go through how the immune system is dependent on the microbiome, what role the microbiome plays and provide evidence for that. And also, provide evidence that shows that how a disrupted microbiome leads to a significant dysfunction in immune response as well.

So, as we’re paying attention to self-care, and we’re thinking about important things like vitamin C and zinc and trying to improve mindfulness and all that, a lot of that, the effects of a lot of that is dependent on how healthy your microbiome is. So, that’s what we want to get across today. If you want, I can just jump right in Mike and can share my screen.

Michael Roesslein:          Yeah. Go for it.

Kiran Krishnan:                  Okay. I’ll do that.

Michael Roesslein:          And I’m going to be trying to pull some of these questions from the emails while you do that and I’ll get them succinctly listed for when we’re done.

Kiran Krishnan:                  Okay, cool. So, I am sharing my screen. Does this look like full screen?

Michael Roesslein:          It does.

Kiran Krishnan:                  Yeah. Okay.

Michael Roesslein:          I’m going to check the chat. Can everybody … It’s weird. I see the chats moving, but it moves as if somebody types something new, but then they’re all still in the same order. Okay. Yes. [inaudible] looks great. I think I’m just on a little bit of delay with the chat.

Kiran Krishnan:                  Cool.

Michael Roesslein:          So, it’s all good.

Kiran Krishnan:                  I’m going to, while I’m talking, I’ll turn off my video, so I don’t look like a crazy person as I’m talking and then I’ll click it back on for Q&A.

Michael Roesslein:          We’re all about crazy.

Kiran Krishnan:                  Okay. So, this talks all about the microbiome and immune function, we’ll delve a little bit deep into that. I’ll give a quick overview on the immune system itself and especially immune kinetics, which is really important in pathogen defense. And then we’ll illustrate how the microbiome plays a role in each of those aspects. Right? So, to begin with, I do want to remind people of this, that I always talk about that, we are really a holobiome, which is a superorganism. So, we are essentially made up of thousands of different organisms that live together in this human shell. And as a super organism, in order to perpetuate the health and wellness of the whole, each member of the superorganism has to really communicate with the others and they all play a different job. And this couldn’t be more true when it comes to immune response and I think you’ll see why.

So, remember this holobiome, we are a walking, talking rainforest, and every member of this rainforest plays a critical role in maintaining homeostasis. So, a quick review of the immune system, it begins to develop, even in the embryo itself, you see early immune cells starting to develop there. Most of the immune cells come from hematopoietic stem cells and those are continuously generated throughout one’s life. The stem cells differentiate into major classes within the immune system. Things like granulocytes, monocytes, lymphocytes, we’ll talk about each of these a little bit more. The only major system in the body designed to protect us is the immune system, that’s its entire goal, is protecting the collective. And then, of course, the ecosystem in which the immune system functions also plays a major role in the immune system’s capability of protecting us.

Immune system has a lot of capability, but no real information. It’s an army with no general. So, it requires training. It requires information from places like the microbiome. We’ll illustrate that as well. It takes at least six months for the immune system to start to work on its own, when you’re first born, within the first six months or so the baby, for example, is highly dependent on mom’s immunity, mom’s immunoglobulins, and so on, but then you start to develop your own immune system. And as you start to develop your own immune system, there is this intimate crosstalk between the immune system and the microbiota that then exists in your system. And then you create this long-term symbiotic relationship between the microbiota and the immune system that’s developing. Stem cells continue to be produced and differentiate throughout one’s lifetime, there is no significant measurable limit to the amount of immune response you can have, as long as all the systems are working. So, that’s an important thing to note.

The two main parts of the immune system that we really want to focus on is the innate immune system and then the adaptive immune system. And I’ll be talking about the kinetics between the two, because that’s really important when we talk about pathogen control, right? So, innate is our first line of cellular defense. Some of the players within the innate immune system are antigen presenting cells, so cells like macrophages and dendritic cells, they basically find antigens and then they present the problem to the next set of cells that will take over the immune response. So, they will phagocytize, meaning they’ll eat stuff, and then they will look for specific antigens within pathogens, within damaged cells, within viruses, bacteria, and so on, they’ll then present those cells to the rest of the immune system for learning and response.

These antigen presenting cells are produced in the thymus and other lymphoid centers, but then are recruited to the gut mucosa and other mucosal tissue, typically by commensal bacteria. We’ll give some examples of that as well. Now, the microbiome helps these cells by expressing things like toll-like receptors, which then help these cells identify commensal bacteria from pathogens that are coming in, both bacteria and viruses. So, this communication using toll-like receptors is a big part of expressing the presence of the commensal bacteria and their ability to help your immune system distinguish between friend and foe. Again, we’ll elaborate on that a little bit more. This part I’ll just give you very general overview. The microbiome even goes as far as producing energy for these circulating dendritic cells and macrophages. So, remember these are really important first line defense cells, their process that they use for defense requires a lot of energy, the production and the assimilation of energy for these cells comes from compounds that are produced in the microbiome like butyrate, for example.

Then you have neutrophils, which are key part of the first line of defense. These are killer cells that directly target harmful organisms and can eliminate these harmful organisms. They’re very important to maintaining a infectious free environment like in cold and flu season, when you’re exposed to lots of viruses all the time. They are dependent on the microbiota for stimulation and expression and even for equipping them with the tools that they use to kill invading pathogens, things like nitric oxide, super oxides, and so on. A lot of those tools actually come from the microbiome. Other parts of the innate immune system, natural killer cells, which are highly important in viral infections, in particular, these cells can identify infected cells of ours and eliminate it. And dysfunctions in natural killer cells, in individuals, these people would face chronic consistent infections, and there are genetic defects in natural killer cells.

And these individuals end up seeing chronic, non-stop infections because we’re continuously exposed to all types of viruses and bacteria and your natural killer cells in your innate immune system do a lot of the brunt work of the initial control. The microbiome stimulates a production of natural killer cells, and the microbiome also affects the potency of the cells as well. So, providing the cells their tools to be able to perform those elimination functions. Mast cells, many people know about mast cells, they’re highly important regulatory cells, especially in the lamina propria, that’s the place right below the intestinal epithelium. They control blood flow and coagulation in the lamina propria. And in fact, some of the issues that are going on right now with this particular pandemic and seeing the hypercoagulation may be effected by mast cells themselves. They control smooth muscle cell peristalsis, they’re an important part of that peristaltic movement in the gut.

They fight against gut permeability, so they play an important role there. They control electrolyte exchange and a poor microbiota with low diversity leads to actually fewer mast cells in the lamina propria in the gut, and ends up with more mast cells in circulation, which is one of the modes of increasing allergies, because most people know about mast cells with regards to their effect on increasing allergenic response, the IgE type of response. But mast cells in the lamina propria are really important for all of the things we just talked about. About blood flow, smooth muscle contraction, fighting against permeability and so on, electrolyte exchange. But there’s a correlation between having low diversity in the microbiota and the presence of these mast cells in the circulatory system, instead of the lamina propria. Intestinal epithelial cells actually act as a bonafide part of the immune system.

These barrier cells contain lots of immune function. They release key antimicrobials to protect the barrier, and they do a lot of that antimicrobial secretion based on stimulation from the microbiota. They release chemokines and cytokines to recruit immune cells to locations where there are active infections going on. So, they’re really important in that signaling cascade to alert the immune system. The microbiota stimulates intestinal epithelial cells to release antimicrobials and chemical messengers. So, a lot of the action that the microbiome wants the immune system to take, is done through the intestinal epithelium, which is the first line of communication with the microbiome and the immune system, right? Because remember the microbiome sits in the mucosa, which is right above the intestinal epithelium, so a lot of the signals that come from the microbiome get filtered through the intestinal epithelium and then those signals get propagated to the rest of the immune system.

So, that relationship is really, really important. Then looking at the adaptive immune system, which is the second line of defense and more of the longer-term protection, one of the key players, of course, in adaptive immune response is the antibody secreting cells, the B-cells. So, these are a gut associated B-cells, primarily are the secretors of IgA. This is the antibody that’s made in the highest concentration, it’s found in a lot of your secretory fluids in your tear ducts, so in tears and saliva, in your mucosa and so on. We make about seven grams of IgA a day. It’s a very important first line defense from an immunoglobulin standpoint and it is produced by B-cells and B-cells that mature in the Peyer’s patches in the gut ilium, they originate there and then they also mature and propagate there in the B-cells, in the Peyer’s patches as well. The amount of B-cells and Peyer’s patches, and their potency, is directly controlled by commensal bacteria.

So, the proliferation, the number of B-cells and the number of Peyer’s patches, and the size of the Peyer’s patches are controlled by the diversity within the microbiome. The more diverse your microbiome is, you have a higher proliferation of B-cells, you have higher surface area of Peyer’s patches. So, you’ve got better overall immune response because the Peyer’s patches are not only the proliferation site for B-cells, they are also for T-cells. IgA, unlike IgM, has a lower memory and is less specific to certain antigens. It is more of a broader binding antibody and it typically recognizes the current crop of commensals. And so, it helps distinguish between the current crop of commensals and invading organisms. A lot of the commensals, as they filter into the mucosa, get covered with IgA.

And because they’re covered with IgA, then the immune system negates a response to them. That’s one of the ways that the immune system distinguishes between commensal, that’s been there and is there all the time versus a new bacteria that’s coming in. A new bacteria that’s coming in, may not be bound by IgA because the antibody doesn’t have confirmational structure to bind that new pathogen. So, then when the immune system sees an unbound pathogen or microbe coming in, that signals to the immune system that this may be a new invading species and not part of the commensal microbiota. So, that helps upregulate some of the immune response in itself. So, that relationship of IgA helping recognize commensal bacteria is a really interesting angle in terms of the function of IgA.

Now, IgA also plays a big role in neutralizing things that we commonly see, bacteria and viruses that we commonly come across so that they don’t actually elicit much of an immune response, IgA takes care of them pretty quickly. Low microbiota diversity, and low microbiota exposure and then, of course, low antigenic species in our environment leads to lower levels of IgA. The production of IgA is dependent on microbial exposure, and that’s an important part to keep in mind, especially right now, and we’ll talk about some of that as well later on. And one thing that’s really interesting that I was able to find in the literature is that when you have lower levels of IgA production, which is again driven by lower levels of exposure to bacteria, lower diversity in the gut, you actually end up having a compensatory effect where your body produces more IgE instead, right? Because your body’s going, “Hey, we need a certain amount of antibody titer in circulation in our secretory fluids, because we need to keep defenses up. We have low IgA, so we’re going to produce more IgE instead.”

And the problem with IgE is that when it encounters things, it facilitates an inflammatory, allergic type of response. So, this may be one of the mechanisms by which allergenicity increases over time because of the reduced production of IgA, which stems from lower microbial diversity and lower microbial exposure. T-cells, T-cells are really important orchestrators of our immune system. They’re, of course, part of the adaptive immune response as well, CD4 T-cells are the T-cells that can differentiate into Th1, Th2, Th17. Th, by the way, stands for T helper cells. So, these T helper cells facilitate specific types of immune responses, Th1 response, Th2, 17 and then of course, Treg as well. Having a balance between these four subtypes is absolutely critical to help.

You can have disease states that are driven by an imbalance in any one of these types of T-cell responses, right? So, that is the critical aspect here. It’s not like one of them is really bad, the other one is good. They’re all really important. The important aspect here is balance, having a balance of all of them, right? So, Th one, for example, is one of the primary drivers of immune response and protects against intracellular, microbial infections and viral infections as well. So, Th1 typically comes to the rescue early on, when your body is being invaded by a new virus or bacteria. Th2 tends to protect against things like parasites and helps drive some of the adaptive immune response as well. Th17 is a pro-inflammatory responder, also one of the early responders, works in the heat of the battle, early on in an infection, but then should be dampened over time because you don’t want a continuous inflammatory response.

And, of course, Treg does a lot of that dampening. So, uncontrolled Th expression can cause disease, like I mentioned, too much Th1 or Th17 is linked to autoimmune disease. Too much Th2 is linked to allergic and sensitivity reactions. And Treg, the regulatory component is the one that keeps the balance and tolerance between all of these T-cell functions, right? And when Treg expression is low, it leads to autoimmune conditions, severe allergies, and it leads to things like cytokine storms, and so on. Treg in the immune kinetic response is really important, and I’ll touch on where that happens in the immune kinetic response.

Now, a weak microbiome leads to Th1, Th2 imbalance and typically leans towards more of a Th2 response. And so, a weak microbiome actually provides lower rate of response to pathogens, but a higher allergenic and sensitivity type of reaction, right? So, that’s where the T-cell function teeters a lot. And the microbiota is responsible for stimulation and the maturation of Treg cells, which is again, the regulatory component that is critically important to finding balance between each of these T-cell type of responses. And when the microbiota is weak, we see an increased colitis risk, for example, because we’re not getting a dampening of the inflammatory response in the colon. We’re not getting tolerance.

We find low levels of colonic Tregs, and so T-cells in the colon actually end up attacking the tissues and commensal bacteria, when T reg is not functioning. That is a pathophysiological finding in colitis, is lower Treg expression in different sites within the colon. And that Treg expression is required for reducing the autoimmune type of response to colonic cells.

So, looking at the immune kinetics, we always start off with the innate immune response, and here are some of the key players within the innate immune response, basophils, eosinophils, neutrophils. We talked about natural killer cells and mast cells. So, these are, again, nonspecific reactors, right? They know to find their way to a site of action, but they will start just destroying everything in that region, right? They are the equivalent of using a blowtorch to kill a bunch of mosquitoes that entered your house. They’re going to get the mosquitoes, but they will also do some collateral damage to the walls and things like that. So, although you need this innate immune response, that’s a first, very quick response, that happens within minutes to hours, with invading pathogen. You cannot have a sustained innate immune response because that will then lead to significant tissue damage.

The innate immune reactors, that bridge the gap between innate and adaptive response are the macrophages and dendritic cells. And in particular, the dendritic cells are really, really important because these guys show up in this early phase immune response, they look for the specific antigen that’s causing the problem. They’ll start digesting and killing the source of the antigen, but then they also present the antigen then to T-cells and B-cells, which will start mounting an adaptive immune response, right? And this adaptive immune response is not the inflammatory part. This part of the immune response is the inflammatory part, this is the part that you feel when you sick. If you’ve picked up a new virus and you got a fever or you started getting an itchy throat, you started getting shortness of breath, you started getting GI effects, loose stool, and so on.

All of those are driven by this innate part of the immune response, right? But this innate part of the immune response should be shuttling towards adaptive immune response, typically within a day or two. So, then you’ll have a period of time where you have both, you have an innate response going on still, because of higher viral load and titers. And these cells continuously being activated and trying to control the amount of viral load. And it’s taking time for the adaptive immune response to gear up and to start producing the neutralizing antibodies that are going to eventually neutralize all of the incoming pathogen, right?

So, you’ll have a period of time where you feel nothing. Where the innate immune system is starting to take over. Then the inflammatory response will kick in as you’re getting towards the late part of the innate immune response, when the macrophages and dendritic cells are doing their job you’ll feel a lot of the inflammation. Now, the severity of the response and the infection will dictate what the symptoms feel like. In many cases, the pathogen can be completely taken care of with very minimal inflammatory …

PART 1 OF 4 ENDS [00:25:04]

Speaker 1:                           The pathogen can be completely taken care of with very minimal inflammatory response that’s not even realized because the immune system is really functioning in tip-top shape. And then you shuttle very quickly to adaptive immune response. You start getting antibodies neutralizing the pathogen without really ever feeling much in terms of the inflammatory response at all. One of the key things that has to occur during this transition, this late innate to the early adaptive is there has to be an anti-inflammatory response that kicks in to start to dampen this initial inflammatory reaction for two main reasons. Number one, because remember this inflammatory reaction also damages your own cells. So your body has to have a way of starting to tone down that inflammatory response, so you don’t end up with a net of your own cells getting damaged through the process.

Then the other reason for that is because eventually if you keep having inflammatory damage, you’ll keep damaging your own tissues and releasing peptides of your own tissues. And then the dendritic cells and macrophages can accidentally swallow those peptides of our own tissue and present them to T cells and B cells, as antigen and the T cells and B cells need to mount immune responses to. That self antigen presentation occurs in areas where there’s lots and lots of inflammatory damage and your own tissues getting damaged and releasing peptides and antigens, or what may be perceived as antigens.

That will elicit an auto immune response. So that’s a bystander effect, your own tissue becomes a bystander in the battle because your own tissue gets damaged. And then antigen presenting cells accidentally present your own tissues, your own peptides as antigens that the B cells and T cells have to react to.

So that’s another really important reason why we have to dampen down the inflammatory response to move to a healthy, adaptive response. So keep in mind that there is an inflammatory response here, which is needed, but as it shuttles through to the adaptive response, the anti-inflammation process is really important to make sure the immune system is functioning properly. So looking a little bit more detail in the early part of the innate immune response, imagine a virus enters your system, and then the virus starts entering cells like epithelial cells, for example, in the airway. This is a very early part of the illness. This is what’s happening in the first couple of hours. As the cells get damaged, the epithelial cells can start releasing some inflammatory cytokines. These inflammatory cytokines will then start recruiting localized macrophages to show up and start swallowing up the cells.

The next thing that shows up and it starts controlling the release of more virus because now it’s eating up virus infected cells before the cells can burst open and release more virus. So this becomes a kinetic game of how quickly can the macrophages eat up a lot of the virus infected cells so that you don’t get a huge load of new virus circulating around in your system there and then infecting more and more cells. So that’s the first part that again, happens within hours. Now, five, six, seven hours later, you’ve got dendritic cells that are now turned on and they really start the more robust part of the immune response. Dendritic cells are the ones that are going to facilitate the antigen presenting to T cells and then of course, B cells ultimately through T helper cells, and eventually you’ll start getting antibody production and starting to get clearance of the virus.

Now, this is the early stages of innate immune response. This is a later stage of innate immune response. And then of course, when you get down here to B cell activation, you’re going into the adaptive immune response as well. So remember early innate response, then the late part of the innate response, especially when dendritic cells start getting involved that’s when you start to see a lot of the inflammatory response going on as well, which is important for that part of recruiting immune cells, proliferating T cells and B cells so they can do their work. A lot of the inflammatory cytokines do that proliferation signaling, recruiting more innate cells to control larger and larger chunks of infection. And all of the signaling that’s important for the immune system comes through these inflammatory mediators. But then the next part is you do have to move to the early adaptive, and then you have to turn on the anti-inflammation pathways so that this inflammatory processes don’t do a net degree of damage to the tissues themselves.

And then eventually you get long-term adaptive response, which are B cells that then mature into plasma cells. These plasma cells now produce antibodies that are highly specific to that particular pathogen. And then eventually that provides true long-term immunity. That’s how you have long-term immunity where next time you encounter this pathogen, you won’t even feel it or realize it because what happens the next time you encounter it is a pathogen enters back again, the macrophages will still do their job, but dendritic cells will be able to kick in with their now equipped pattern recognition receptors. So one of the things I forgot to mention is every time a dendritic cell sees a new antigen or a pathogen, it develops a new set of pathogen recognition receptors. So it houses within itself, all of these different types of pattern recognition receptors. So it can very quickly recognize a whole of different pathogens.

So now you have dendritic cells circulating around that has receptor recognition of this previously seen infectious virus. And then this dendritic cell can get turned on faster and start presenting the antigens to your B cells, your T helper cells, and then eventually your B cells faster. So then the plasma cells that make the antibodies against this specific antigen start to activate much faster. This can now happen within a matter of a day or two versus earlier on the first time you encountered this particular pathogen to get to the plasma cell level, might’ve been six, seven, eight days.

Now, it can happen because these plasma cells already exists within one day and you won’t even notice that you’ve ever been infected. Now, all of these processes, all of this kinetic, this early innate response, late innate response, the inflammatory signaling that’s so critical to facilitate the immune response, the shuttling to an early adaptive response, the anti-inflammatory response as you start getting adaptive immune system going the long-term adaptive response, and finally the long-term true immunity. All of these things are dependent on the microbiome. And that’s what I want to illustrate for you in the next upcoming slides.

Now, to really understand immune response and what’s happening, we have to talk about the mucosa because the mucosa is the largest surface area in the body. It’s about 400 square meters. If you were able to fold out all of your mucosal surface in the body, compare that to the skin, which is two square meters in the body, you’ve got almost 200 times the size of the dermal layer in mucosal layers inside the body. It covers every orifice in your system. So any way that a pathogen can enter your system, it has to enter through a mucosal layer.

Speaker 2:                           Hold on, I got to interject. You said 400 square meters.

Speaker 1:                           Yeah.

Speaker 2:                           Okay. For Americans, that is 4,305 square feet.

Speaker 1:                           Isn’t that [inaudible]?

Speaker 2:                           So for people who have homes or apartments, which would probably be everyone on here and can translate that into size of home or apartment flooring, that’s 4,300 square feet. I just typed that into a calculator for mind-blowing [inaudible], because America doesn’t understand square meters. All right, go ahead. That’s all.

Speaker 1:                           No, it’s important. I’m glad you mentioned that because when you think about it, like a 4,300 square foot house is a massive house.

Speaker 2:                           That’s a big house.

Speaker 1:                           Right, it’s a big house. Most people are living in 1,000 square foot apartments. And so your mucosal system is that big. It’s a mansion, if you will, it’s an immune mansion in your body and it’s massive. It covers every office. And it’s the largest portion of the immune system. Most of it is found in the gut. So most of that mucosa is found in the gut. Now, it’s… Let me make sure the slide’s going to advance. And it lines every entry way into the body, the respiratory tract and digestive track, the reproductive track, through the skin, even if something penetrates through your skin, it will encounter a mucosal system once it gets past the top layers of the skin.

So every pathogen that enters your body basically enters into the mucosal system. Now, and that’s really important to understand, and you’ll know why in a second, but also keep in mind that the mucosal system then because it is the entryway into the body becomes a largest site of immune sampling in the body. Everything that possibly requires an immune response has to go through this important mucosal layers that are illustrated here. And your immune system has to sample what that thing is and decide whether or not it has to mount an immune response to it. That’s the largest site of immune sampling. So the function of the mucosal immune system’s absolutely critical to the function of your entire immune response. And the crazy thing about the mucosa is that the mucosa is covered in microbes. Every part of the mucosa in every part of your body, that 4,000 or so square feet of mucosa in your body is all covered with microbes, is covered every square meter of it.

So you’ve got this huge population density problem. So when you think about the job of the immune system, this is where you have to really appreciate the crosstalk and the connectivity between the microbiome and the immune system because imagine the mucosa is a primary site of sampling. Every pathogen has to enter the mucosa and the mucosa is completely loaded with microbes, with bacteria, viruses, fungi, and so on. So every one of these square millimeters is actually covered with microbes. You have about 40 trillion or more microbial cells sitting in your mucosa. All of these commensal viruses, bacteria, and all that are sitting in the mucosa, 40 trillion or so of them sitting in that mucosal structure. You’ve got only about 200 million immune cells to survey and monitor this entire region that is covered with microbes already. So you’ve got about 200,000 times more microbial cells than immune cells available to the entire system.

That’s a mind-boggling task for the immune system. So think about it, the immune system’s job is to monitor the mucosal surfaces, what things are entering. And it’s supposed to figure out what his friend and what is foe and what to attack and what not to attack, all the while the area that it’s monitoring is already covered in bacteria and viruses and fungi to the order of 200,000 times higher than there are immune cells to monitor that area. So the only possible way that your immune system can even function is if there is some sort of neighborhood watch going on. Because you could have little microbes pop in or viruses pop in in this sea of microbes and your immune system would have no idea they are even there because you only have 200 million immune cells monitoring the entire ecosystem of over 40 trillion microbial cells.

The only possible way your immune system can even start to function is if you have a neighborhood watch system where your microbes that inhabit the mucosa are signaling to your immune system what is happening in that ecosystem? That part is that thing called the microbiome immune crosstalk. Your immune system cannot function without the microbiome immune crosstalk. I want people to understand that whole problem really well because that will then help you illustrate how important of a role the microbiome plays in your immune function. Just understanding this part alone is enough to understand the scale in which your microbiome has to help the immune system function.

We keep talking about immune stimulants and immune support. We keep thinking about compounds that help your immune system function. We’re not talking enough about the role that the microbiome plays in even allowing your immune system to exist and conduct basic functions in the sea of microbes that exist inside your body. So this microbiome immune crosstalk is at the core of how the immune system functions. The immune system actually would not exist if it wasn’t for the microbiome. That’s important and I’m not going to go through this whole schematic that is somebody who [crosstalk].

Speaker 2:                           Yeah. I just got a headache and a flashback to my master’s program.

Speaker 1:                           Right. But-

Speaker 2:                           Which one was the one in the joker hat?

Speaker 1:                           Oh, is that funny?

Speaker 2:                           Yeah. I see that in the bottom left, that was the boss.

Speaker 1:                           I was trying to figure out what is this picture from? And where I found it, didn’t really illustrate what this picture is from or this seems like a crazy crowd.

Speaker 2:                           I would say [inaudible] they have coats on and way too much clothes. So-

Speaker 1:                           Right. And it looks like a much older population in general when you look at it. So it’s interesting. [crosstalk].

Speaker 2:                           Yeah. I mean, maybe it was a bunch of people trying to look like the microbiome.

Speaker 1:                           Right. Exactly. So I’m not going to talk through this schematic, but this is one of many, many you can find that really show a complicated relationship between the microbiome and the immune system. What I will do is go through very specific examples of viral infections, for example, and how certain parts of the microbiome play a role in signaling to the immune system. So that’s how I’ll go through it for you so you have a sense of how the microbiome really orchestrates an immune response. So and before we can even touch on that, we have to talk about the role of the microbiome in the development of secondary lymphoid organs that manage all of your immune tissue. So your lymphoid organs are section to primary and secondary lymphoid organs and tissues.

The primary lymphoid organs are the ones that we develop ourselves. We code for, we have the genetic components to develop them and that’s the thymus and the bone marrow. Outside of the thymus and the bone marrow, all of the other immune organs, all of the other immune tissue, the lymph nodes, the tonsils, the adenoids, the bronchus-associated lymphoid tissue, all of the lymph nodes all over your body, your spleen, your lamina propria in the gut, your Peyer’s patches, your mesenteric lymph nodes, your genital lymph tissue. All of those tissues are all matured and develop by the microbiome by signals from the microbiome.

Studies show in gnobiotic mice or mice that are treated with heavy levels of antibiotics is you get disrupted development of all of these secondary lymphoid tissues. So you might develop the thymus and the bone marrow, but you will not develop appropriately the secondary lymphoid tissues. And this is seen in microbiome disrupted conditions and models. Now, of course, this is not something you can study very well in humans, but they’ve done extensive pathophysiology and mechanistic studies of this in various types of animal models. So right off the bat, just the presence of the vast majority of your lymphoid tissues and organs, their maturation and their function is dependent on having diverse microbiome over a period of time throughout the development stage.

But let’s go through some examples of how commensal microbiota are required in fighting a viral infection, for example. So we’ll talk about a norovirus infection, for example, lactobacilli, some of the commensal lactobacilli and other commensal bacteria trigger the release of things like interferon beta, and interferon gamma, which then alerts the innate immune system to the presence of the virus.

Remember in that sea microbes, you might have a norovirus show up, but your immune system would never know it’s there because it’s sitting in a sea of 200,000 times more microbial cells than immune cells that can actually monitor all of this space. So the only way the immune system would even know that that virus has shown up is the commensal microbes detect the presence of the virus, and then start releasing these cytokines that then trigger the innate immune system to move to that location. And then certain nutrients like vitamin A, for example, provides a substrate for these commensal bacteria to make the interferons. But that’s where the nutrient comes into help facilitate some of this response. But if you don’t have adequate commensal bacteria, you’re not getting that response anyway.

Another example in rotavirus infection, for example, a bacterial flagellin from commensal bacteria can activate the expression of pattern recognition receptors. So those are those receptors that dendritic cells and all hold in them to recognize patterns on pathogens that your body’s tends just to see over and over again. And this triggers the expression of something called Toll-like receptor-5, which then stimulates the release of interleukin-22 and interleukin-18 because remember a rotavirus is a gut infection.

So one of the things that occurs is the intestinal epithelium gets infected and damaged by the virus. And then the flagellin from bacteria will stimulate more pattern recognition receptors so that your immune system can start to recognize commensals in that area and not the presence of the virus and start dampening immune response so that your body can start to heal. And that is done by the release of interleukin-22, which helps repair the damaged epithelial cells and interleukin-18, which induces apoptosis in the infected epithelial cells so they can die off and a new epithelial cell can be put in its place. So this is an example kind of the late phase, innate moving into the adaptive response when you want to start dampening the inflammatory response in the body.

The intestinal microbiota plays a role in that as well. In the case of rotavirus infection, additionally, things like bifidobacteria breve, for example, and the presence of oligosaccharides like galactooligosaccharides and fructooligosaccharides have been shown to prevent these infections by increasing the expression of interferon gamma IL-14 [inaudible] Toll-like receptor-2, which then increases mucosal immune defenses. So this would be an early part of the innate immune response, which starts recruiting immune cells to the site of infection when the rotavirus shows up. So now you’ve got these bacteria and these gut associated oligosaccharides, these beneficial oligosaccharides that conduct the facilitating of the cytokines that bring immune defense cells to that part of the mucosa to neutralize the virus.

And then once the virus has been neutralized, the flagellin from other bacteria start dampening the inflammatory response and allow for the repair so that the intestinal epithelium doesn’t get overtly damaged during the process. Commensal bacteria also produce things like short-chain fatty acids, which is required to increase and maintain the mucus production, which is again, the barrier system that prevents all of these microbes from entering into our cellular system and into our blood system, which then creates a stronger barrier against pathogen.

In addition, these commensals also increase the synthesis of antiviral compounds like reactive oxygen species, defensins and so on which prevents localized viral infection. So when your commensal microbiota notices a virus, for example, entering the space, an unknown virus that it’s not familiar with, it will then stimulate the production of antiviral compounds by your intestinal epithelial cells. So it’ll send signals through the mucosa, to the intestinal epithelial cells to increase the secretion and production of antiviral compounds like reactive oxygen species and defensins, for example, so that you can start quenching the viral replication right there in that localized region. That signaling again comes from the microbiota. Another example is during influenza infection, commensal bacteria will trigger the release of inflammasomes. Inflammasomes become really important to controlling influenza infection that inflammasome acts as a potent defense against the influenza replication.

So this inflammasome then induce dendritic cell migration to the area and then the dendritic cells will migrate to the localized lymph nodes where it starts stimulating specific T cells and B cells that exists against the influenza virus itself. And this occurs in localized tissues like the lungs, thereby shuttling the response more to a potent, less damaging early adaptive immune response. So to go over that again, influenza enters the system, one of the responses that the commensal bacteria will have in recognizing the presence of this viral pathogen is by triggering the release of these inflammasomes. These inflammasomes then recruit dendritic cells to that area.

Dendritic cells remember are the antigen presenting cells that then trigger T cells and B cells. So dendritic cells come to the area. They start grabbing antigens from the influenza and influenza-infected cells. They will then migrate to local lymph nodes near the lung tissue, where they will stimulate an influenza specific T cell response. The T cells will then stimulate B cells, and then cytotoxic T cells will come and start attacking influenza-infected cells while the B cells produce antibodies against the virus itself. So that whole process, that whole way of diminishing the influenza response starts with the triggering of the inflammasome by commensal bacteria that recognize the presence of the virus itself.

Other ways, for example, the gut microbiota can regulate a respiratory mucosal immune response in response to influenza infection through the simulation of secretory IgA and Th1 activation, and then the activation of and priming of cytotoxic T cells. They do this again through interferon signaling and inflammasome signaling. So the microbiota is doing that in the respiratory mucosa itself, the gut microbiota. So the gut microbiota is responding to a disruption in the respiratory mucosa by the presence of a pathogen like influenza. Then the gut microbiota stimulates the secretion of more IgA into the respiratory mucosa and activates Th1 and cytotoxic T cells to go to that spot and start fighting the infection. That’s the gut microbiota doing that-

PART 2 OF 4 ENDS [00:50:04]

Kiran Krishan:                    And start fighting the infection. That’s the gut microbiota doing that for the lungs. And that’s interesting because the gut microbiota can speak to the lungs through a connection with the lung microbiota itself.

So, another example of this is when the influenza virus is present in the lungs, the gut commensal bacteria increase the presence of innate immune cells into the lungs by causing the release of these types of cytokines, interleukin 1 alpha, beta 12, interferon gamma, interleukin 33. So, that’s the gut microbiota going, “hey, we need to increase these inflammatory signals to recruit more innate immune actors into the lungs.” So, this causes more natural killer cells, dendritic cells, macrophages, and all that to end up in the lungs.

But then when the virus is low and not present, the gut commensals do the exact opposite. They stimulate the release of the anti-inflammatory interleukin 10, which then dampens any sort of inflammatory response in the lungs, because we don’t want to end up with a net damage to the lung tissue. Because if the influenza infection and the innate immune response to that infection is allowed to take hold and carry on for too long, it may start to control the infection itself, but it’ll also do damage to the lung tissue.

So, the stopping of that overt response of the innate immune system also comes from the gut commensal bacteria. But how does the gut commensal bacteria know what’s going on in the lungs? Well, this really interesting balancing act is an example of the gut-lung axis, where microbes in the lungs actually communicate with microbes in the gut to inform of the presence of pathogens. So, microbes in your lungs will see the pathogen first, and then will signal through other cytokines that will be picked up by microbes in the gut. And then the microbes in the gut, which are managing the central command center for immune response, will recruit all of the immune actors to the lungs itself.

Now, there are other commensal microbes in the lungs that play important role. For example, Staph aureus exists on the airway surfaces and it has the capability of helping recruit monocytes, which then mature into macrophages through the activation of toll-like receptor two during a lung infection. And this leads to eventually a reduction in the damage by the acute infection in itself. Because eventually, as these commensal bacteria start to notice that there are lower and lower levels of the pathogen, they will start recruiting more of the cytokines to dampen the inflammatory response once the innate actors are already there.

Respiratory commensal bacteria called “Corneum bacteria” can modulate toll-like receptor three antiviral response of things like RSV, the Syncytial virus, respiratory virus, and enhance the production of things like TNF alpha, interleukin six, interferon gamma, interferon beta, all of that through increasing T-cell proliferation. So your commensal bacteria in your lungs are creating a cytokine response that then can be picked up by local immune cells. But it’s also picked up by your gut microbiota. And then the gut microbiota send more recruits to that site of action so that your body has a nice, profound impact. But then ultimately your local microbiota in the lungs and your gut microbiota will start stimulating the anti-inflammatory response. So you don’t end up with that inflammatory damage in that tissue. You don’t end up with that cytokine storm type of progression, even things like butyrate from commensal bacteria will lower inflammatory damage in the post early innate activation. And it does it through butyrate binding through G protein-coupled receptors, which are receptors on cell surfaces that can stimulate further expression of things like interleukin 22, which is again a dampening repair type of interleukin.

So your gut commensal bacteria plays such an important role in detecting the presence of an invading pathogen, eliciting the important innate immune response to the presence of that pathogen, and then shuttling the immune response from that innate response to adaptive in the middle of it, dampening the inflammatory damage so that your tissues themselves don’t get damaged overtly and then your immune system can move to that better protective longterm memory type of immune response in the adaptive side.

Another example of this is in the vaginal canal. There studies that show that lactoBacillus crispatus, when it’s the dominant bacteria in the vaginal mucosa in women, this is a study in South African women, they show that higher levels of lactoBacillus crispatus was able to decrease HIV1 infection by directly inhibiting viral function itself. And then the lactoBacilli in general, in the vaginal canal can inhibit viral replication through the lactic acid they produce and through the interleukins and cytokines that they induce, they can actually help reduce the infectivity of HIV exposure.

So a lot of what I talked about is indirect effects from the microbiome, helping the immune system recognize that there’s a pathogen present and then helping shuttle the immune system in various ways to get the innate immune reactors there. Once the innate immune reactors are there and starting to act shuttling it more towards an adaptive immune response. So you have that longer term immunity. All of that is being done by signals from the microbiota, both locally in local tissues, but then also through the central command center in the gut. But then there are commensal microbes that also tend to have a direct effect on viral pathogens for example. And these are some of our favorite bacteria that we talk about all the time.

For example, Bacillus. Bacillus subtilis has been shown to produce these surfactants. And this study showed that Bacillus subtilis and the surfactant that it produced, prevents the invasion of this specific type of coronavirus in the transmission to gastroenteritis. So this is the prevention of the cell entering into the epithelial cells and causing the infection. Let me note, this is not the SARS COV-2 that we’re dealing with right now. So we’re not saying that this is a way of preventing SARS COV-2, but this is another Coronavirus that has been tested against the surfactant that is produced by commensal Bacillus subtilis. So this is an example of a commensal bacteria that actually directly produces antiviral compounds that can affect it.

Another example of that with Bacillus subtilis anti-influenza activity, Bacillus subtilis produces a powerful antiviral compound called P18, that completely neutralizes influenza virus in vitro. This has been studied in vitro, not in humans, but it shows that these bacteria have the capability, not only of detecting the presence of these pathogens, but some of these bacteria, like the Bacillus species can actually produce antimicrobial and antiviral compounds to actually directly target and reduce the presence and the infectivity of the pathogen itself.

Here’s another interesting one with the antiviral activity of an antimicrobial lipopeptide from Bacillus. So Bacillus produces this antimicrobial local peptide, which contains both the surfactant and a fengycin. This also has a strong antiviral effect, which effectively inactivates viruses. And they looked at a number of viruses like PRV, this Porcine parvovirus, parvovirus and dogs I’ve seen studies on. Newcastle disease, virus, infectious bruise cell disease virus, and so on. So they looked at the capability of this combination of compounds that are produced by commensal Bacillus against viruses. And they find lots of really interesting activity. And Bacillus also produces another antiviral called [inaudible 00:08:18], which is actually, this was isolated from honey and it’s found in honey, and it’s sows that this Lavonne, this antimicrobial compound, which is produced by Bacillus subtilis inhibits various forms of adenovirus, including respiratory RNA viruses, like H5N1 and enteric Edna virus type 40, which is a DNA virus.

So this was really interesting because as you guys know well, that bacillus is a commensal bacteria. So you’ve got commensal bacteria that do all of this important immune signaling to alert the immune system, to the presence of pathogens, to recruit innate immune cells to the area of action, so that innate immune cells can star the immune process. And then signals from the microbiota also shuttle the immune system from that innate to the adaptive response, where you get the non-damaging longterm, robust immunity against that pathogen. And then here are other commensals, especially in the Bacillus genus, that actually directly produce antimicrobials and antivirals that help the body defend against pathogens. And then overall, and this is some of the latest studies, this study, the second one here, was published just in may of this year. This very month itself, where they’re looking at the fitness of the immune system is dictated by the microbiome.

This is a study from I think, 2012. And this is more of like a follow-up study on some of the similar topics they concluded that collectively, the data indicates that commensal derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity. This is the conclusion from the study, and that’s really important because remember that the activation energy, the understanding of the basal level of microbial existence, the presence of pathogens, the ability to kind of rear up the immune response, all of that seems to be dictated by signals from commensal bacteria. This latest study here showed that type one interferon that is actually produced by the microbiota, signaling from the microbiome, was shown to be required to tone and poise dendritic cells to respond to pathogen entry.

Especially important for antiviral function, without the signal from the microbiome dendritic cells cannot Mount an immune response. So this is really important. You might have dendritic cells in your system. You might have the nutrients that the dendritic cell may require to conduct its function, but without these signals from the microbiome, in this case type one interferon, the dendritic cells cannot actually function and cannot actually go after the pathogens that are now present in the system. So the microbiome communication and signaling is absolutely critical to the activation of the immune system. And in this particular study, they went through and they did a bunch of animal model studies where they start to knock out or diminish the microbiome. And they find that the dendritic cells can not respond to the presence of pathogens. Even then, if they injected interferon, it didn’t have the same response without the interferon coming naturally from the microbiota itself.

So the energetics and the ability of the immune system to function depends highly on the presence of the microbiota itself. We also know that disruptions to the microbiota, a lead like dysbiosis, leads to disruptive immune response. There’s lots of studies on antibiotics weakening antiviral response in the immune system. This one shows “Antibiotics found to weaken in the body’s ability to fight off disease.” “Collateral damage.” “Detrimental effects of antibodies on the development of protective immune memory.” “Antibiotics bug the immune response.” So lots and lots of studies showing when you damage the microbiome through something like antibiotics and lots of studies have been done on antibiotics. That’s why I’m showing them not to pick on antibiotics. Anything that really damages the microbiota in a significant way, like glyphosate in a Roundup, things like dysbiosis driven by poor lifestyle, all of those things that lead to dysbiosis disrupt the immune response in the body and disrupts kind of normal basal immune response in a very significant way.

It cannot be seen more clearly than in the case of cancer immunotherapy. Because this is a big area of research right now, because it could save thousands and thousands of lives annually. So disruption to immune response due to dysbiosis has been shown in cancer Immunotherapy. What is cancer immunotherapy? Well, some of the most severe forms of cancer, things like lung, Non-Small Cell Lung Cancer, Melanoma that tend to have high mortality rates, can have success when being treated through immunotherapy. Immunotherapy, which is called anti PD-L1 checkpoint therapy, those therapies basically enhance the immune response against the cancer cells, that’s what the immunotherapy is doing. It’s basically trying to improve the T cell response against the tumor. And what they find is that if you take a hundred people who have melanoma or a hundred people who have a Non-Small Cell Lung Cancer, and you put them through immunotherapy, about 20, 25% of them will have a beautiful response to it.

Meaning, the cancer will be basically gone in about six months of therapy and rarely does it come back. There’s almost no side effects and everything is hunky Dory. Everything works beautifully well, but that’s only in about 20 to 25% of people. In another about 60 or so percent of people, they get no response at all. And then in a few percentage, in about five to 10% get really a toxigenic response. So then the big question in this whole immunotherapy is, “what is going on?” “What is the difference between the 2020 5% they get this beautiful response and a cancer is completely gone versus a 65, 70% that get almost no response at all.” And they find that the gut microbiota plays a critical role in the antitumor immune response. And there’s increasing data that shows that antibiotics treatment prior to immunotherapy changes the composition of the gut microbiota that affects the efficacy of these checkpoint inhibitors.

So what they’ve been able to show, and we actually got into this space with the idea of improving and modulating the microbiome prior to checkpoint therapy, so that we may be able to get a better response to checkpoint therapy by fixing dysbiosis. That’s the work that we started doing with, with Arthur Frankel now on hold, of course, because of the COVID-19, but they’ve shown this paper shows the meta-analysis that the findings of a meta-analysis indicate that antibiotic use is negatively associated with outcomes and progression free outcomes in cancer patients treated with immunotherapy. So survival and progression free outcomes in immunotherapy is negatively associated with the use of antibiotics before the start of immunotherapy. So this is a beautiful mechanism to show that the immune system has an amazing capability of controlling dysfunctions, like tumor productive progression, but when you disrupt the microbiome, it completely screws up that response of the immune system.

So that’s one of the most important messages I want you guys all to understand from this particular talk, is that not only does the microbiome play a significant role in the signaling and the activation of the immune system and all that, but a disruptive microbiome is at the core of a disrupted immune response to anything. Whether it’s tumor cells, viruses, bacteria, and so on. So now this next part is important because this plays a really important role, especially in the Western world, because remember the language used by the microbiome to communicate with the immune system is typically focused in these cytokines and interleukins and chemokines. So interleukin one alpha, interleukin one beta, interferon gamma, interferon beta, IL-12, TNF alpha, interleukin six. These are the signals that the microbiome is using to recruit and activate and alert the immune system to the presence of pathogens in all kinds of locations within the body. Whether it’s localized in somewhere like the upper respiratory track or it’s in the gut, it doesn’t matter.

These are the signals that the microbiome is using in order to trigger immune response in the body. The problem here is you guys will all be familiar, if you’ve listened to other talks that I’ve done, the many talks that you hear in “Rebel Health Tribe”, and so on. These are also the same players in chronic disease. Remember, 50% of Americans have at least one chronic disease. And one in four Americans have two or more chronic diseases. These are the main chronic diseases within Americans: heart disease, cancers, chronic lung disease, Alzheimer’s, strokes, type 2 diabetes. Chronic inflammation is the driver of all of these chronic diseases. And these are the same players in chronic inflammation. So chronic inflammation, driven by these cytokines, chemokines, interleukins, are the root cause of the signaling that the microbiome uses for immune activation.

Now, why is this important to know? Because it leads to loss of signaling. And I’ll explain that in a second. So remember when you have a gut that’s leaky like this, you’ve got all kinds of disruptions that occur to the immune system. For one, the mucosal immune system, the largest site of sampling in your body, the area where your immune system, through the help of the microbiome, decides what type of immune response it’s going to elicit to the antigen, the pathogen that it’s looking at. That immune system gets completely disrupted when your gut is leaky. When you have infiltration of commensal bacteria into the inner part of the mucosa, this completely disrupts mucosal immune response. Everything gets an inflammatory response. And then, other opportunistic pathogens in the system can take advantage. For example, segmented filamentous bacteria can increase inflammatory damage of tissue and can drive autoimmune development by being allowed to migrate into this inner sanctum and even past the barrier system in leaky gut.

Things like HSV, herpes simplex virus, and cytomegalovirus, when they are allowed to proliferate because of this inflammatory situation going on because of leaky gut, they tend to infect T cells, macrophages and monocytes, right? So the infection of the T cells and macrophages and monocytes, obviously it attenuates really important players in the immune system. Epstein BARR virus, for example, when it’s allowed to proliferate because of this chronic low grade inflammation, and this inflammatory picture during leaky gut, actually will infect B cells. So now you’ve got these B cells circulating around here in the lamina propria, in the basal lateral circulation, that are there to protect the body against future encounters with pathogens that it produces antibodies to. And then because of this chronic dysfunction through leaky gut, you get an activation of Epstein BARR virus, and then that Epstein BARR virus goes and infects the B cell that is there to protect against other pathogens.

So now the susceptibility of infection by the pathogen that is coded for by the B cell, becomes increased. Because now your B cell is compromised. Also, another really interesting thing. Remember a big driver of dysbiosis in the gut microbiome, and then a big driver of endotoxemia and leaky gut is that [inaudible] to gram negative bacteria. Gram negative bacteria are the ones that contain LPS. So you end up getting higher and higher levels of free LPS in the lumen of the gut and in the mucosa. And when you have higher levels of free LPS in the mucosa, there are a number of viral pathogens that can actually use LPS as a way of entering cells.

Because our immune cells and our epithelial cells are designed to engulf LPS when it sees it as a way of trying to protect the body from the inflammatory damage that LPS causes. Then the viruses, what they do is they attach an LPS to themselves so then they get accidentally engulfed, or in their purposes, engulfed, but then our immune system accidentally engulfs them. And then the virus can start trying to replicate in the cell that engulfed them. So they will use LPS as a carrier, into other cells within the system. And then of course, chronic inflammation can drown out the immune signals. So that’s one of the things I mentioned in the last slide, the drowning out off of the immune signals. That’s the part I want to emphasize in the second, because it’s important that people understand this.

So remember, when you’ve got an info invading pathogen, it’s like a flame. The presence of the flame will create a smoke. And that smoke is a disruption to the ecosystem. That disruption to the ecosystem can be picked up by the microbiome, which is like a smoke detector. So then the microbiome sees that there’s an invading pathogen and it’s causing disruption. It then signals to the immune system through cytokines, that’s how it sounds it’s alarm. That’s the analogy that the smoke detector, the microbiome is causing an alarm and it does it through interleukins and cytokines like IL-1, IL-6, interferon, and so on.

Then when your immune system, the firefighters hear that alarm, they know to come to that site of action and start eliciting the immune response. This is what is supposed to happen when your body encounters a new pathogen. The problem is when you have chronic low grade inflammation, what you tend to have is an overt presence of this cytokine response all over the body. You have it either in localized tissue, you have it systemically. You have systemic IL-6, systemic TNF alpha, systemic interferon gamma, systemic interleukin-1, always being propagated. You’ve got high levels of this alarm signal going on all the time.

So that in this scenario, when an invading pathogen comes in and the microbiome detects the presence of that invading pathogen, the microbiome sounds the alarm because of the invading pathogen, this alarm signal gets completely lost because this signal is all over the place. The immune system is constantly reacting to signals coming from all kinds of tissues in the body, because of the chronic low grade inflammation. So the really important potent signals from the microbiome to tell the immune system that a pathogen is present, gets lost in the mileu of lots of signaling from an inflammatory standpoint.

So that is a really important part to understand. How chronic low grade inflammation attenuates immune response to the presence of pathogens. Because the microbiome uses the exact same signals that are present in chronic low grade inflammation to try to signal the immune system. And if that signal is really loud and that signal is present all over the body, then the signal from the microbiome that a pathogen is there gets completely lost in that milieu. So it’s no surprise that the mortality rates for something like COVID-19, that people are being exposed to, are really high among people that have chronic low grade inflammation. So the non pre-existing mortality rate is around 1%. Which compared to something like the flu…

PART 3 OF 4 ENDS [01:15:04]

Kiran Krishnan:                  The rate is around one percent, which compared to something like the flu is in itself is high, and this is among symptomatic people. So these are among people that are symptomatic. This number is lower when you just take the population as a whole and include people that are asymptomatic. So among symptomatic people, it’s about one percent.

But among people with cardiovascular disease, it’s ten times higher, the mortality rate. Among people with diabetes the mortality rate is seven times higher. Among chronic respiratory disease, hypertension, cancer, five to six times higher.

So that chronic inflammatory signal that is going on in the body is dampening the immune system’s ability to understand that this new pathogen is there and control it and sequester it in a reasonable amount of time so that the pathogen doesn’t cause huge amounts of damage within the system. So that is the really important part here.

Again, if you’ve listened to my talks before, even though we’re talking about the immune system right now, the microbiome is the key to reducing the chronic low-grade inflammation in these conditions as well. The microbiome plays such an important role because leaky gut is the biggest driver of the chronic low-grade inflammation signal from these comorbidities.

So that is a really important thing that people need to really understand as we talk about resilience. When we talk about resilience of our immune system, it’s not just about loading yourself up with vitamin C and zinc and so on. Those things are important for immune function, but it’s about dampening and reducing the loud overbearing alarm calls from these inflammatory cytokines that are going on in the body due to the chronic low-grade inflammation that is so persistent within the US population. That is a really important part of it.

So let’s jump to some quick conclusions. A healthy, diverse microbiome provides critical signaling and energetics for the immune system to elicit a proper immune response. You cannot elicit a proper immune response without a healthy, diverse microbiome.

Higher pathogen load clearly disrupts the immune response. There’s studies that show that when you have higher pathobiome with relative abundances higher than the commensal bacteria, you will have disrupted immune responses because the pathogens do not want to trigger the immune system. So they have ways of working around immune stimulation, immune triggering, and of course they will not signal the immune system when other pathogens show up as well. So pathogens tend to do a good job becoming friends with one another to allow the existence of each other within the system.

A disrupted microbiome leads to improper and attenuated immune response. This is seen very clearly in studies on antibiotic damage to the microbiota, to in the case of immunotherapy when you use antibiotics first, there’s lots and lots of indications that disrupted and dysbiotic gut leads to improper and ineffective immune response.

A disrupted microbiome is also the most prevalent source of chronic low-grade inflammation. So you’re getting a double whammy here. If you have severe dysbiosis, you likely have high degrees or higher degrees of chronic low-grade inflammation, and when you have higher degrees of chronic low-grade inflammation the signals from the microbiome to the immune system are drowned out and lost anyway. That increases the susceptibility to more profound infection when you encounter a new pathogen, because the control mechanisms to stop the pathogen early on are not working and are not functioning appropriately.

Immune-support ingredients, things like vitamin C, D and zinc, are important for immune function, but they cannot overcome a dysfunctional microbiome. So it has to be used in conjunction with things that modulate the microbiome. This is the thing that I keep trying to understand with even just my friends and family that ask me thousands of questions about all this stuff. People will feel that-

Michael Roesslein:          I’m sure you haven’t become more popular at all in the last day or so.

Kiran Krishnan:                  Right. The most popular man.

Michael Roesslein:          Hey Kiran, we haven’t talked in forever. How are you doing? How’s the family. I’ve got a couple questions for you.

Kiran Krishnan:                  Yes. Do you have two hours, please?

Michael Roesslein:          Yeah. Can you please talk to me until next Wednesday.

Kiran Krishnan:                  The think I keep emphasizing to them is you absolutely should be making sure your vitamin D levels are adequate, your zinc and vitamin C and all that. But they also will not overcome the dysfunction that’s driven by dysbiosis in the immune system. So you have to fix dysbiosis as well. You cannot just walk around loaded up with vitamin C thinking that you’re supporting your immune system adequately enough. You have to think about the whole picture of how the immune system responds.

The success of preventative measures, things like vaccines, people talk a lot about vaccines, and of course the powers that be mentioned the vaccine is going to be a big savior. But again, a vaccine is not the illicitor. It doesn’t create the immune response. The microbiome still has to be the thing that elicits the immune response to the presence of the vaccine.

The vaccine itself is not a medicine. The vaccine itself is not immunity. You can inject an antigen into your system, the immune system has to be functioning properly in order for your immune system to actually respond to that antigen that’s being injected and then elicit immunity against it.

That’s one of the reasons in my view that the flu vaccine doesn’t work very well in general, because number one, you’re injecting it into someone’s arm, which is not where you typically sample influenza type of viruses. They come through the respiratory mucosa.

Then the second part is if you don’t have the adequate immune response to the presence of that antigen, you are not going to build immunity against it no matter how many times you take that injection. So that’s a really important part to understand ,is our ability to be resilient and actually develop some sort of immunity against the new pathogen and all the existing pathogens that we encounter, come from an appropriately functioning microbiome.

Simple measures can make a big difference in your microbiome. Many of you who’ve heard me talk about this before have heard me emphasize this. Diversifying your diet, lowering stress, because remember stress increases barrier dysfunction and leaky gut. Stress also increases the replication and the infectivity of latent viruses like cytomegalovirus, herpes simplex virus, Epstein-Barr virus. Those viruses, they respond when your stress hormones are high and they start to proliferate because they understand that the immune system is now under pressure and doesn’t function as well under the stress condition.

So them being opportunistic, latent pathogens will start proliferating in that condition. Because they’re proliferating then, they then start attacking your immune cells themselves. They attack B cells and T cells. So that compromises your immunity in a very significant way. So stress can compromise your microbiome, lead to more chronic, low-grade inflammation and directly compromise your immunity in a very significant way.

I know it’s hard to talk about stress right now because there’s lots of things that are stressing people out. Getting outdoors is really important. I know we’re all supposed to stay in as much as we can, but if you can go out into nature, that’s really the key. Because there are enough studies that show more exposure to outside environments, especially natural environments. I’m not talking about going and walking down the sidewalk having the same effect.

Going out into a place where you can do a hike or going out into a natural environment, that gives you exposure to microbes that actually increase the diversity in your microbiome and improve immune function. Using a spore-based research probiotic, we’ve got a bunch of studies that we’ve been doing, two recently published on the improvement of the HIPAA protection using the spores, modulation of the immune response, the upregulation of certain aspects of the immune system, and of course these spores, like I mentioned before, have direct antiviral type of effects to help the immune system with supporting that kind of healthy response against pathogens.

Focus on leaky gut solutions, because remember leaky gut is the biggest source of chronic low-grade inflammation and chronic low-grade inflammation drowns out the signals from the microbiome to alerting the immune system to the presence of pathogens. So if leaky gut is present, that’s going to become a serious comorbidity to reducing the impact and the functionality of the immune system.

You have to bring down inflammation. So whether that’s an antiinflammatory diet for you, behaviors that reduce inflammation, compounds, taking things like garlic and curcumin and all that, all of those things can help with bringing down that inflammation and that drowning out signal that occurs in the body in general.

Prebiotics like oligosaccharides can have a major impact on immune function, one, through the creation of butyrate and other short-chain fatty acids, but there are studies that show directly the impact of prebiotics on immune support against viral infections, and they’re really quite profound. So prebiotics really help, especially oligosaccharides, really help with providing signaling capability for the microbiome to inform the immune system of the presence of pathogens.

Things like polyphenols, omega fatty acids, can be powerful support tools. Omega fatty acids of course for dampening inflammatory response locally in the gut, especially if it tends to have higher EPA and higher DPA. Polyphenols act as a very potent prebiotic for the microbiota by increasing diversity, dampening inflammatory response in the microbiota itself.

Then facilitating the production of things like urolithin, which helps produce new cells, removes damaged mitochondria or damaged cells that occur. The damage occurs through infection and so on. So polyphenols can be really a important tool for your microbiome to help your immune system and help the body recover and also elicit an appropriate response to the presence pathogens. So I think that’s the last slide. Maybe I’ll leave it here for now.

Michael Roesslein:          Yeah. You can leave it there. I have bad news and hopefully good news.

Kiran Krishnan:                  Okay.

Michael Roesslein:          So my bad news is that I’m out of time. It’s an hour 40, and I don’t have unlimited time tonight unfortunately. I should have expected your presentation to go that long because I know better and we’ve done this before.

Kiran Krishnan:                  You know how we do it.

Michael Roesslein:          But the good news is your call because I would like to, once we’re done with this, perhaps we could try to figure out a time where next week we could do the Q&A.

Kiran Krishnan:                  Yeah. I would love to so that.

Michael Roesslein:          And to go into some details. Because you put on here, you have stuff about probiotics and leaky gut solutions and prebiotics and all that and you guys have a lot of solutions for that. I just saw your new study. I think you posted or email went out today on the combination of the megaspore and the prebiotic relating to something awesome. I don’t remember.

Kiran Krishnan:                  Short-chain fatty acids.

Michael Roesslein:          Oh yeah. Short chain fatty acid in obese [crosstalk] mice.

Kiran Krishnan:                  Diversity also.

Michael Roesslein:          So maybe we can chat offline and figure out the soonest time that we could get back on and do Q&A and then talk some specifics around the products and the research. Then I’ll put together a little guide to other steps people can take. I can take this slide and maybe we’ll make a little here’s your steps you can take.

Because I’ve got … So I typed this in the chat. You probably didn’t see it. But as soon as I went to start trying to copy over all the questions from the email and the Facebook and the chat boxes and everything, I usually put them into one Word doc that I have because I have a huge monitor here. So I can have this open on one side and I could have a Word doc open on the other side and I could read the questions off in an organized fashion.

My Microsoft license expired at the exact time that this webinar started. So it wouldn’t-

Kiran Krishnan:                  They get you somehow.

Michael Roesslein:          Yeah. Back to Bill Gates. I opened up the Microsoft Word and it’s like, screw you, you can’t use this. Here’s this 27 step thing you have to go through to turn it back on. So I spent a lot of the time writing this. Let’s exit your screen.

We’ll come back to the slides. Can you turn off your share screen?

Kiran Krishnan:                  Oh yeah. Sorry. Let’s see …

Michael Roesslein:          That’s a great slide. Did you just put this presentation together recently?

Kiran Krishnan:                  Today, yeah, just between lunch and now. I was like, you know what? This is important enough. I got to do it.

Michael Roesslein:          Oh, no big deal. That was only the best microbiome immune system presentation that I’ve seen.

Kiran Krishnan:                  Thank you.

Michael Roesslein:          So I’m going to have to watch it like four times, because I was doing this.

Kiran Krishnan:                  Oh yeah.

Michael Roesslein:          I have this many questions. So these are from the chat and they’re from the Q&A box, and some of the email that I got. There’s about 30 questions on here, so this would probably be about an equal duration webinar that we could do just on the Q&A, and maybe getting into some more specifics.

Some of the questions are more specific related to your product. Some of them are just a fine point questions on some of the stuff you went over, and then some of them are related to other immune simple questions. So let’s do that.

Kiran Krishnan:                  Yeah.

Michael Roesslein:          I see a lot of really happy people in the chat box, fire hose information once again. Yeah. That’s kind of how we roll. That’s why we give you guys recordings. So to the most popular question is, is there going to be recording? Yes.

Kiran Krishnan:                  Yeah.

Michael Roesslein:          We usually will get that out … Today is … What day is this? Wednesday? Is there days anymore? Do we still do days. Today is Wednesday. So Friday, we’ll probably get it out Friday with a transcription. Then I will talk to Kiran when we’re done here and try to figure out time soon that we can do a part 2 with a Q&A and some specifics around research, around products, because there’s a lot of questions there too.

Kiran Krishnan:                  Yeah, and we were able to capture most of these questions. Even I was able to just-

Michael Roesslein:          I’ve got them all.

Kiran Krishnan:                  Copy them too. Okay.

Michael Roesslein:          I either answered them, there was a couple of them in the Q&A that I answered.

Kiran Krishnan:                  Yeah.

Michael Roesslein:          Then I, hold on, yeah, and then I copied all of them into there’s three that I’m just going to take a screenshot of right here in the Q&A that I have not written down, which would have been the smarter way to go the whole time. But I always think of the smart answers after I’ve done all the work.

I have all the questions recorded.

Kiran Krishnan:                  Okay. Awesome.

Michael Roesslein:          So I can send them to you so that you can be somewhat prepared for them. Will our email questions be able to be answered next week? Yes. I have all the email questions, the Facebook questions, the chat box questions and the Q&A questions from this, I think, onto all of these, onto these pieces of paper. So I’ll get them to Kiran.

We will let you know as soon as we know when we can hang out again, and we will get into that. I apologize. I should have booked three hours knowing better.

Kiran Krishnan:                  You know, we’ve only done this 40 times Michael.

Michael Roesslein:          Yeah. And it’s weird to have a webinar ending and it’s light out where you are.

Kiran Krishnan:                  Right.

Michael Roesslein:          Summer’s happening.

Kiran Krishnan:                  Yeah.

Michael Roesslein:          I feel like, oh, we’re ending so early, but it’s almost two hours. So thank you everyone. Man, everybody’s super love. I don’t know if you have the chat box open, but everybody’s very excited.

Kiran Krishnan:                  Awesome. Well thank you so much. Yeah. I think people are, there’s a lot of anxiety right now. I think eventually we need to get out there. So we’re going to be going out, and this particular virus and many of the other viruses we have to deal with as well, aren’t going away anytime soon.

The good news to me is that our immune system is well equipped to deal with this. It’s well equipped to deal with almost anything it encounters. It has all the mechanisms.

The big point I was really hoping to get across today is how we have to make sure that our ecosystem and the terrain that the immune system functions within, is also adequate to respond to these types of things. The good news with the pandemic virus, for example, is still 80 percent or more people tend to have a very mild type of response, which means that people’s immune systems are handling it.

It’s pretty clear that the ones that aren’t handling it have lots of chronic inflammation. So we can deal with it, and I don’t think you need to be afraid. I don’t think you need to be anxious about it. I think you just need to be prepared.

One of the best ways you can prepare your immune system to encounter something like this is through shaping that microbiome. Then the other stuff you do as well, the nutrients you take and all that. We could talk about more of those details and things I do, for example, in our next Q&A. But hopefully people got something out of this. I’ll send you the PowerPoint, Michael, and [crosstalk 01:33:08]-

Michael Roesslein:          Yeah. People were asking for the slides.

Kiran Krishnan:                  I’m happy to share them. Yeah. I’m happy to send them to you so you can [crosstalk 00:18:15].

Michael Roesslein:          Don’t worry. Nobody could steal your slides and give that presentation because I would just click from slide to slide and go, here’s this slide.

Kiran Krishnan:                  And then this looks like-

Michael Roesslein:          Yeah. These people, one of them is wearing a joker hat. He’s the boss. Thank you, Tammy. Thank you. Everybody’s really fantastic. Blown away. Yeah. Thank you so much.

Kiran Krishnan:                  Of course.

Michael Roesslein:          I’m going to have to watch it so many times. I know to us mortals, when it comes to microbiology we’re like, “Oh man, that’s so much work that he just did,” but then people don’t realize you love this stuff like this.

Kiran Krishnan:                  Totally, yeah. Yeah.

Michael Roesslein:          You didn’t have to put together a slide show on immunity and microbiome this afternoon. You got to put together a slide show.

Kiran Krishnan:                  Right. Well before I put the slideshow together, when we decided to do this, I decided that I wanted to read up on the most latest papers on this topic. So I probably, between Monday and this afternoon, I probably read maybe like 40 published new publications on this topic, and there’s so much rich information. I was just going to come on and talk about it like I do often and that’s when I decided I was like what there’s too much stuff on here. I need to outline it for people on slides.

So that’s why I decided to put the site together and try to give people visuals, because a lot of this is really complicated and the visuals hopefully help understand the processes. Again, when we do the Q&A, we can explain things even deeper, clarify some questions.

I think if any of you go through and watch it again with this first base of level of understanding, it’ll start to click and make sense of how things are connected. That’s the part I really want you to get. I want you to understand how this response works, what’s going on when something enters the body, how your microbiome responds and why that response is so important.and you are in complete control of all of that. So that’s the beauty of all of this. You can manage how your immune system works.

Michael Roesslein:          Yeah. A lot of it’s under our control, which is great. So everybody, you’ve probably just got the first view of a presentation that’s going to find itself to medical conferences-

Kiran Krishnan:                  Yes.

Michael Roesslein:          Once those things start happening again.

Kiran Krishnan:                  That’s the part I was excited about.

Michael Roesslein:          I know how to multipurpose slides, so I know that doctors are going to be seeing this, but you’re going to have a leg up on your doctors. So thank you for doing that for our group.

Kiran Krishnan:                  Right.

Michael Roesslein:          That’s really special. There’s somebody in the chat says, “I’m a clinical microbiologist and this is frontier of our field. Totally awesome material.”

Kiran Krishnan:                  Awesome.

Michael Roesslein:          So you have a fellow-

Kiran Krishnan:                  That’s so good to hear.

Michael Roesslein:          Bug nerd in the chat there.

Kiran Krishnan:                  I love it.

Michael Roesslein:          And I mean that endearingly.

Kiran Krishnan:                  We need more.

Michael Roesslein:          Right. We need to get kids watching these. We’ll turn little kids into microbiologists.

Kiran Krishnan:                  Excellent.

Michael Roesslein:          Cool. Well, thanks a lot.

Kiran Krishnan:                  Thank you Mike.

Michael Roesslein:          We’ll talk soon and everybody will be back soon and we will get this finished.

Kiran Krishnan:                  Yeah. Take care.

Michael Roesslein:          All right. Thanks.

PART 4 OF 4 ENDS [01:36:14]

Webinar Replay: Gut & Microbiome: The Foundation of a Resilient Immune System with Kiran Krishnan, Part 2 – Transcript

Michael Roesslein:          Recording. We are recording. So welcome everyone. This is part two for the Rebel Health Tribe Gut Microbiome and Immune Webinar conglomerate masterpiece. My guest is Kieron Krishnan. Kieron, welcome back.

Keiron Krishnan:               Thank you. Thank you for having me back.

Michael Roesslein:          [crosstalk] turned off the last one. The reason we’re here again, is because your presentation was so packed and loaded, and huge, and awesome that we didn’t have time to do the questions. And we wanted to do the questions. So if anybody’s watching this-

Keiron Krishnan:               [crosstalk] this isn’t the first time that’s happened with me.

Michael Roesslein:          Yeah. The last time we went into a part three, right? That’s why I have the questions all written up in rapid fire succession. I told Mira what we were doing, and she goes, “Last time, didn’t that go to a part three?” And I said, “Yes, but we’re going to get it in part two this time.” So if you missed part one, go check it out. It’s on our blog.

It’s an amazing presentation that it’s really, really, really comprehensive. I’ve read and watched a lot of stuff on gut immune and microbiome interrelation in the last five years, and that was definitely the most complete picture of it I’ve seen. And I still need to watch it at least twice more, because I am not a microbiologist. I have to say I got the most emails about it, out of anything we’ve ever done.

Keiron Krishnan:               Wow. Awesome. Good.

Michael Roesslein:          From doctors, from practitioners, from scientists, there was a microbiologist that messaged me and said, “Her heart felt warm seeing this information go out to the public.”

Keiron Krishnan:               I love it.

Michael Roesslein:          So science nerds are uniting, and I’m glad to be stuck in the middle of it. So let’s do it. I have not ordered these in any specific way, so they will be completely random. I feel like this is some sort of microbiome game show we’re inventing. There should be some sort of ticker, or points, or score, somewhere on the screen, but we’ll do what we can to get through. Oh, somebody said they understood it on their first time through, and they are better at this than I am.

Keiron Krishnan:               Nice.

Michael Roesslein:          So let’s just kick it off. I will start question one. Do you have any knowledge or experience around the Ayurvedic diet, or something Ayurvedic kitchari, do you know that word? Kitchari? Kitchari. Okay. Just around Ayurvedic diets specific to individuals, and how Ayurvedic diets would relate to microbiome, or gut health at all. Do you have any knowledge there?

Keiron Krishnan:               No, very little. I mean, I know what I know about the Ayurvedic diets is they are designed to work well with your composition, whether you are like a Vata or depending on your tendencies, as an individual. And a really good Ayurvedic practitioner can basically look at you and assess which category you fall into.

So I’ve not seen any evidence of how that relates to the microbiome. But, what I do know is within Ayurvedic medicine, the gut is a big central focus as well. So I’m guessing that a lot of the interpretations of how people’s compositions are, will circulate around the core, also. So if Ayurvedic is working for you, and a particular prescribed diet is working, it may be a better fit for your particular microbiome.

Michael Roesslein:          Got you. That’s about my depth of it, too. And I know they do use a lot of really powerful herbs and spices. I used to have a book that was super cool, and I don’t remember what it was called, but it had recipes and herbs and spices in it. And it would break down like clinical research behind herbs and spices, and what they do in the body, and then recipes to use them. And it was pretty impressive, the line of study from India, specifically, around herbs and spices and clinical research, which we don’t really do here.

Keiron Krishnan:               Yep. Yeah. There are institutes, Ayurvedic institutes, that are equivalent to the Harvard’s here, the Ivy league schools here, and they’re quite amazing. I wish I had the chance to study Ayurvedic a little bit more, but I haven’t.

Michael Roesslein:          No worries. I am writing something down from one of our people here saying to look at Banyan Botanicals for kitchari. So I can learn what that means. Great, spores or any other products in your line have any impact, or relation to retroviruses?

Keiron Krishnan:               We haven’t studied retroviruses. Retroviruses are quite unique in their method of replication. There’s no specific data on spores being able to combat retroviruses that I’ve ever seen. But again, with any other virus, really the first initial key to stifling the viral replication; whether it’s a retrovirus, a DNA virus, an RNA virus, it doesn’t really matter. But it’s interferon that’s really the key, right? Interferon is the first line of defense against viral infections.

The cells themselves that get infected can release interferon signals, and then the microbiome triggers interferon release by adjacent cells. And then of course the recruitment of innate immune actors also causes a release of interferon’s. So no matter what kind of virus it is, that first line of defense is going to be the interferon release. And that is equally successful against any kind of virus, no matter what type it is.

The most commonly known retrovirus of course is HIV, human immunodeficiency virus. The reason why that virus become so deadly over time is because of its target. It’s target is the CD4T-cell. The CD4 is a really important helper T-cell that helps facilitate the immune response towards a more powerful, adaptive immune response, triggering B-cells and so on, because those cells start to diminish. And that part of the immune system starts to get really deficient.

You started becoming much more susceptible to all kinds of common illnesses. CD8 T-cells tend to go up, CD4 T-cells tend to go down. That’s why that virus in particular is difficult because it attacks the immune system itself. So just being a retrovirus in itself, doesn’t make it any more special than any other virus. The one that people know about is HIV and that targets immune cells. Interferon is the key. The interferon will negate the replication of almost any virus.

Michael Roesslein:          There we go. That’s question number six, where do type one and type two interferon’s fit into the overall picture you presented in part one?

Keiron Krishnan:               Yeah, that’s the first line of defense. Type one, type three, type two, all of them get released by the infected cell itself. The R-cells have a defense mechanism, if you will, and a self destruct [crosstalk 00:07:17]-

Michael Roesslein:          Kind of like a panic button.

Keiron Krishnan:               Totally. Panic button. Yeah. The moment they get infected, one of the first things, genes that we start turning on, our cells start turning on, is the interferon genes. Then the second genes they start to turn on are the chemokine genes. The chemokine genes are the flares that help the immune system understand that there’s a problem going on here. Now, here’s what’s crazy about it. A study just came out about a few days ago, maybe three days ago, on the mechanism of action on COVID.

COVID, what makes it really interesting is as it enters into the cell, one of the first things it codes for is a blocker for that cells interferon production, right? And that’s not unique because a lot of other viruses do that. Influenza does that, respiratory syncytial virus does that, lots of other viruses do that. That’s kind of how viruses fight against our immune system, or our detection system to combat it.

And then the second mechanism, the release of the chemokines to attract the immune system, most other viruses also inhibit that part, right? So most of the virus are trying to quiet both those signals in the cells of the infect. So that your body and your immune system doesn’t get alerted to the presence of the infection. The COVID does something completely different. It stops the interferon production, because that is the key thing that stops viral replication in its tracks, but it actually amplifies the inflammatory signal.

It amplifies a chemokine signal, which is really interesting. So it does it in a different way, and that’s not how the original SARS caused the infection as well. That’s why people tend to be very susceptible to this, what we call cytokine storm. Because the virus in itself is amplifying these inflammatory chemokines to attract the immune system to the site.

Now, and I don’t know this for sure because this study just came out, but my hypothesis then is the microbiome will play even a more important role in this kind of mechanism. Because, one of the things that the microbiome helps to do, is trigger the release of more interferon. That’s one of its jobs, initially, and it does that in influenza, it does that in other types of respiratory virus. It may do that in this case, we don’t know that for sure, a study hasn’t been done. But that’s where this becomes really interesting, is that the microbiome may play a role to try to undo some of that imbalance that the virus causes.

Michael Roesslein:          It’s like a battle that we don’t have even a player in.

Keiron Krishnan:               Yeah, exactly.

Michael Roesslein:          [crosstalk] it’s the other [inaudible] versus the virus trying to control the response of our cells. Like our cells are just the inner dumb objects, in a sense, versus the-

Keiron Krishnan:               Yeah. They’re just a victim sitting there going, “Oh, crap.”

Michael Roesslein:          [crosstalk] Which way do I do? Do I do this?

Keiron Krishnan:               Right.

Michael Roesslein:          Did you see a doctor Kharrazian and Aristo Vojdani study that came out this week? About the autoimmune markers in the COVID-19, cross [crosstalk 00:10:19]-

Keiron Krishnan:               I did not. No. That’s actually-

Michael Roesslein:          It’s pretty, they did some cross-reactivity in their lab with antibodies, ANA, DSDNA, and another antibody, and the COVID-19 antibodies that have been pulled from people, and saw that there was cross-reactivity. Which might explain some of the autoimmune-like responses that some people have. I didn’t fully understand the paper, I’m sure you would. But just in case, I’m going to bring Dr. Kay on to talk about it. So I’ll make sure to send you the video. I just want to put him in front of the camera and be like, “Can you explain what your study means?”

Keiron Krishnan:               Yeah.

Michael Roesslein:          Because he’s brilliant. They are too, Vojdani too, but I just don’t always follow exactly. So I’m going to bring him on, we’ll talk about it. I’ll make sure you get a link, but it seems like-

Keiron Krishnan:               That’ll be fascinating to see.

Michael Roesslein:          They seem to have connected some dots.

Keiron Krishnan:               Yeah.

Michael Roesslein:          Anything specifically different for kids regarding microbiome health, and gut health, that would be different than adults?

Keiron Krishnan:               In general, no. I mean, once a kid is above the age of around two, they have basically their adult microbiome. And the adult microbiome at that stage kind of functions in terms of its relationship to the immune system in a very similar way that adults do. Our goal really is to have the right balance of bacteria, and not have too many toxin producing members of the microbiome, keeping their relative abundance lower to the rest of the commensal species. Like one of the things that we test in that biome effects test, is your pathol biome.

Pathol biome is really interesting because it’s not unusual at all. In fact, it’s perfectly normal for people to have pathogens in your microbiome, or potential pathogens. So opportunistic pathogens, that’s a normal part of the ecosystem. And in fact, many of those pathogens play important roles. The question is, what is the relative abundance of that path of biome to the rest of the commensal species?

That’s when you get into trouble, if the relative abundance is too high compared to the rest of the commensal species, then you’re going to end up having a net of problems. You’re going to have too many toxins being produced here, too much inflammatory induction, maybe a net digestion of the mucosal layer, those issues start to creep up.

Whereas if you have the pathobiome within control, then the rest of the commensals, the mutualistic, all of those will keep those microbes under control, and under a certain distinct level where they’re not causing problems. That’s a big difference between the presence of pathogens, versus the absence of pathogens. You really can’t have an absence of pathogens at all within the microbiome.

Michael Roesslein:          That makes sense.

Keiron Krishnan:               Oh, and then back to the kids thing. That’s the same thing with kids at that stage in life. Now in the first year, the microbiomes going through all kinds of complications. In the first six months or so before you introduce solid foods, the microbiome tends to be very bifido genic. It is really heavy in the bifido side. Lots of facultative bacteria are in the small intestine, and proximal part of the large intestine, eating away the oxygen, so that eventually the most of the gut becomes anaerobic.

Once you start introducing solid foods, you start seeing a diversification of the child’s microbiome. After the first year, you start to see more diversification and a striation of the different types of microbes in the different sections of the gut. So things are kind of tenuous and fluctuating quite a bit in that first year or so.

And then between one and two years, the child is starting to establish their adult microbiome. So I would say in the beginning, in the first six months, the big focus is to continue to improve bifido bacteria levels in the infant. Most of that comes from oligosaccharides in the breast milk, and mothers milk. But you can also utilize some oligosaccharides, or some well-researched infanticide strains to help if the baby doesn’t have adequate bifidobacteria.

But from six months to about a year, year and a half, the most important thing is diet. The most important thing is diversification of the diet, eating lots of roots, tubers resistant starches in, some polyphenols, carotenoids, all of the colored, fruits and vegetables, all of those things play an important role in starting to the diet. Now, from the age of about two or so, all the way until around 10 that’s when you’re really building your oral tolerance.

That’s a really important time to build out your immune system’s tolerance of all of the things that you’re going to get exposed to, that you shouldn’t be attacking. And at that stage, the microbiome was really important in order to present antigens in the right way to the immune system, in order to dampen immune responses that are not necessary, by up regulating something called a Treg system. So that’s when kids started developing lots of allergies, if their microbiomes are dysfunctional. So that’s why studies show that in the first four or five years of life, if they’ve had multiple rounds of antibiotics, then their risk for developing allergies and other immune dysfunction’s kind of go way up, right? So that’s a really important time to maintaining diversity and a growing a healthy microbiome.

Michael Roesslein:          Interesting. Because I noticed that the kids, when I was growing up that had the strictest diets, like where they weren’t allowed to eat anything, or touch anything, or do anything, they had the most issues by the time we were in high school with foods.

Keiron Krishnan:               Totally. Yeah, absolutely. And that’s because they didn’t get the exposure. And without the exposure, you don’t build a tolerance. Or if you have the exposure and you have a damaged microbiome, let’s say your child has had multiple ear infections and all that. And so they’ve gone through multiple rounds of antibiotics in the first few years of life. Then their risk for having that dysbiosis, which means a negation of the tolerance generation and the immune system goes up quite a bit. If you’re a 45 year old adult, or if you are a two and a half, three year old kid, the object should be the same.

It is about increasing the diversity of the microbiome, dampening the presence of those pathogens and getting adequate amounts of Butyrate, short chain fatty acid production. Because, all of those things actually dramatically improve the function of the microbiome. Another thing about the interferon, one of the things that triggers interferon expression adequately is acetate from short chain fatty acids. Butyrate provides energy for dendritic cells, and macrophages and all that, to go out and do the job that they do surveying the system, and going after things that are invading. So all of those same rules still apply, whether you’re two and a half years old, or if you’re 45 years old.

Michael Roesslein:          Makes sense. One other kid question, how does it help baby if mom can’t breastfeed? Just as much diversity of what you can feed them, getting them outside, getting them in contact with this, get them a dog.

Keiron Krishnan:               Yeah. Get them a dog. Absolutely. And doing as much skin to skin contact, if you can, this is assuming mom is healthy. But one of the primitive things that we’ve been doing as a species is often moms will chew the food and then give it to the baby. There is a study on pacifier cleaning, for example. The studies compared two different groups of moms, ones who, if the baby drops a pacifier on the floor, they will clean it with a sterile wipe and then give it back to the baby. Versus the moms that clean it in their own mouth and give it to the baby. The study showed that the moms had cleaned up with their own mouth and give it to the baby, had babies with lower incidents rate of allergies. Right?

So that seems to make a difference. So any contact, physical contact with your baby will help diversify the baby’s microbiome, if you’re not able to breastfeed. Now, once you start introducing solid foods, it becomes extremely important to provide the baby foods that are high in oligosaccharides, right? Fructooligosaccharides and resistant starches because those are the types of compounds that the really important colonic bacteria need that they will typically get from the oligosaccharides from mother’s milk. Mother’s milk contains over 200 different oligosaccharides as prebiotics for the baby. So if you can’t get that from others milk, you’ve got to try to get those prebiotic oligosaccharides from other sources.

Michael Roesslein:          Right. That makes sense. Where did that one go? All right I deleted that. Different topic. Does taking supplemental D3 thin the blood? I’m on cancer treatments and told not to take aspirin, but I want to take D for immune support. I don’t get in the sun a lot, would D be harmful to me? Now, we’re not doctors, we can’t talk to you about your cancer treatment specifically, but can you talk to that just a second?

Keiron Krishnan:               Yeah. So thinning of the blood is really an effect of the thrombin pathway, right? So that’s the coagulation pathway; the thrombin pathway, all the thromboxane and that whole complex pathway. As far as I know, vitamin D doesn’t play any role in that pathway at all. So it shouldn’t have any of that effect at all. Talk to your doctor about it, of course. But vitamin D shouldn’t play any effect in that role, in that pathway.

Michael Roesslein:          How does the body compensate for removed thymus gland? Is it possible to have optimal, or even decent, immune function without it?

Keiron Krishnan:               I think it is. So the thymus is an interesting place the lymphocytes are made in the bone marrow and they go to the thymus for maturation. Now, assuming you can’t go to the thymus for maturation. I’ve seen some data that the maturation can occur in lymph nodes, as well. And especially with the gut associated lymphoid tissue, areas like the Peyer’s patches, which are a really potent site of a T-cell and B-cell proliferation. So I think you probably could. It’s not that if you had no thymus, you wouldn’t have immune function. I think there’s probably going to be some degree of compromise to the immune function. But I think certainly your immune system would provide a certain degree of protection.

The gut associated lymphoid tissue is still the largest component of your immune system, and it still plays a significant role in the maturation, and the tutoring, if you will, of your lymphocytes. And again, the lymphocytes are still being made in the bone marrows, that’s still good. So you’re still making lymphocyte. Then the hope is that you’ll get adequate maturation and tutoring, or training, of the lymphocytes then in the Peyer’s patches or in the mesenteric lymph nodes. My guess is that there would be some compromise to the immune response, but it wouldn’t be like your immune system not functioning.

Michael Roesslein:          Got you. The body has a lot of amazing redirects for when it loses capacity in some regards. There’s almost, other than the heart, the lungs, the brain, like the major organs, and even there’s like workarounds. Like when we lose a tissue or a certain piece of equipment, the body seems to be able to… Like, they’re just learning that like for a while, they didn’t even know that fat adipose tissue produced hormones, or other tissue. And how everything was sterile, and now none of its sterile.

And we’re just learning that there’s a lot of backup plans involved in the body, which is how it can survive when we treat it like hell. How do might taking MegaSpore impacts a parasite overgrowth or would I want heavier artillery?

Keiron Krishnan:               If you have a true parasitic infestation infection, then you should look at anti-parasites, anti-parasitics. You should get a parasite culture done though. The stool tests that you have available to you in the market, aren’t adequate for that. These would be highly specialized parasitology tests. They’ve been doing them for decades now. They’re very common, easy to do tests. They do need stool samples and a good amount of stool samples, actually. You’ll have to poop a good amount into a big tray and then scoop it into four or five different little jars-

Michael Roesslein:          Is it the parasitology center? Do you know that place? Is that who you’re talking about?

Keiron Krishnan:               Oh, any doctor can order it.

Michael Roesslein:          Oh, okay.

Keiron Krishnan:               Yeah. [crosstalk 00:23:29].

Michael Roesslein:          It’s a different thing. It’s not your biometrics. It’s not a GI map. None of these doctor’s data stool tests that market parasite, like there’s a lot of false negative, false positive, false everything.

Keiron Krishnan:               Yeah. Because all of those are looking genetics, the parasite genes. These are actual culture tests, where they’re culturing up the parasites and trying to grow them, and identify them more accurately. They’ll look at them under a scope, and all of that stuff. So you need larger samples of stool to do that. If you do suspect a parasite is an issue, I would go that route. Because you need to know, and you need to have that more definitively known.

You can go to almost any urgent care center and walk in and they can order a parasitology tests. It’s a simple, straightforward test, so your insurance will cover if you have insurance. Now, let’s say that the test comes back that your parasitology test is really negative. You still suspect that something going on then you just do all the things that you normally do to balance out the microbiome.

The spores can certainly help if there are egregious bacteria in there that need to be brought under control. That’s part of the function of the spores, and also improving the growth and the presence of a lot of the other commensals, that help compete against problematic fungi, and bacteria, and so on. So you can work to bring about balance. If you have a really low level of parasites, and you’re not comfortable with doing an antiparasitic, you might try the probiotic.

We don’t have data showing that the spores will competitively exclude parasites, so it’s hard to say. We know people that have used it for what they suspect to be parasitic issues. But again, they didn’t confirm the presence of the parasites using the parasitology test.

Michael Roesslein:          I had another spores [inaudible] on that. Do probiotic supplements in foods actually survive the stomach or stomach acid? I’ve read that they don’t. Why are the spores any different?

Keiron Krishnan:               Yeah. They don’t and bacteria in food, fermented like food, are going to die in the stomach. And you’re going to get some component of that bacteria moving through the system, which is fine. If it’s a true fermented food, then there’s a lot of other benefits to the food outside of the bacteria being present in your gut. Right? The benefit of fermented food, keep in mind, is the ferment itself. All of the amazing things that were produced during the fermentation process; the organic acids, and the peptides, and the vitamins, and all that.

So that’s where the true benefit of fermented foods come from. Spores are different because they have that spore capsule. They have this harden, calcified protein shell that they wrap around themselves, and acts like a biological armor, if you will. So they can survive through the gastric system, low pH is fine. They’re tolerant in the bile salts. And then when they get to the end of the duodenum, they start to come out of this shell and then they start to work for you in your gut, both in your small and large intestines.

Michael Roesslein:          You guys talked a lot about bacteria and other organisms in the microbiome, communicating directly with ourselves, how do they do that? And then in parentheses, this may be a silly question, but I don’t understand how they talk.

Keiron Krishnan:               Yeah. And so it’s not a silly question. And in fact, we know a good amount about that, but there’s also still a lot that we don’t understand. What’s interesting is there’s a couple of different ways. One is bacteria themselves can produce compounds like chemical signals, that your immune system can read, right? So bacteria have complex genomics. They can start producing chemical proteins and signals that can attract your immune system, or alert your immune system.

The second way is they can stimulate the cells around them, which are your cells, just to release those same inflammatory signals. So they do it through chemical messengers. So things called cytokines, or chemokines. So cytokines and chemokine are chemical messengers that alert to things, or create a cascade of other signals, or act as an attractant to the immune system to that area. So a chemokine is actually defined as a chemical attractant to that area.

So they do it in those couple of different ways. They themselves can produce signals, and in most cases they will trigger adjacent cells, which are your cells, to release signals as well. All of our cells, for the most part, with the exception of red blood cells and a couple other cells, all of our cells have the capability of producing these types of chemical signatures. That’s how cells defend themselves when they come into contact with pathogens, like viruses or bacteria.

And so if the microbiome sitting here, if I’m a bacteria in the microbiome, and I notice adjacent to me, the cell, which is the human cell, the host cell, is getting infected. And I sense this chemical signature of this infection, then I can get the human cell that I’m sitting closest to, to release some of these chemical signatures as well. So that it attracts the immune system to that area.

Because remember, the microbiome is the neighborhood watch for your immune system, right? It is virtually impossible for your immune system to survey the whole landscape of microbes in your mucosa and go through every second of every day and pick out areas where there may be infections. Because remember I mentioned, you’ve got roughly 40 trillion microbial cells all over your mucosal tissue, and you’ve got about 200 million immune cells that are surveying all this area.

So you’ve got 200,000 times more microbial cells and components in your system, than you have immune cells. So that differential makes it that the immune system cannot, in any possible way, survey the entire field effectively every second of every day. So it needs that neighborhood watch, it needs the microbiome to alert it when it notices things going wrong around it. Right? And it does it through these chemical signatures, either releasing itself or triggering the cells near it, to release it, to alert the immune system.

Michael Roesslein:          So some direct way, some indirect ways, some nudging and almost bating, pulling, kind of ways, and then some completely unknown magic.

Keiron Krishnan:               Yeah, exactly. And there’s a bunch of unknown. Because number one, we know, for example, when you look at the gut lung access, there is clear data that when the lungs get infected with a virus or bacteria, that the microbes in the lungs, will signal to the microbes in the gut. And then the microbes in the gut, will trigger the gut associated lymphoid tissue to respond to the lungs. How do the microbes in the lungs communicate with the microbes in the gut? That’s still kind of unknown.We’re not sure what the signals are.

Michael Roesslein:          I bet its [inaudible 00:31:02].

Keiron Krishnan:               And it could be.

PART 1 OF 4 ENDS [00:31:04]

Speaker 2:                           … unknown. We’re not sure what the signals are.

Michael Roesslein:          I read it’s quantum.

Speaker 2:                           And it could be. That’s the beauty of this, right? So they all live in what we call the singular mucosal theory system. So the mucosa, which is this 400 square meters of real estate inside your body… And again, for Americans, that’s what, 4,000 square-

Michael Roesslein:          Yeah. It was 4,000 plus square feet.

Speaker 2:                           Yeah. So it’s a huge piece of surface area. They all live in that same lattice. And one of the things that’s true about microbes all over the bodies, they produce and they live within biofilms. The communication that occurs in biofilms is really interesting. Think of the space time continuum, the fabric of space and time. All of them are connected together through these biofilms and through the mucosa. They can communicate instantaneously from different parts of the body. How they do that exactly, still unknown in large part.

That’s one of the reasons why we made the big donation to Sacramento State, because that’s one of the things in that microbiome research division that they have an interest in studying. And we have a very strong interest in understanding, how do bacterial communities communicate with one another? Because the beauty of it is, if we can understand their language, maybe we can listen in on their conversations. Maybe we can influence their language in some way. Or maybe we just learn something about how the natural world functions, which is a whole level that’s more complex and fascinating than we could ever imagine right now. So there’s unknown magic communication as well. There’s a couple ways that we know about, but there’s likely some magic. Microbiome magic.

Michael Roesslein:          I read a book called The Field this year, and it talks about the quantum field, which we don’t really understand. It was the biggest book for dummies of quantum physics that exists. If you can take quantum physics and dumb it down to the dumbest, dumbest, dumbest, dumbest point, I could almost understand a little of it. And it talked about biochemical processes and reactions in the body that happen at speeds that we can’t explain. Like if something communicates with something else faster than a chemical messenger could possibly be released from that part of the body, get into the blood, and then circulate to get to the other point, there are reactions in the body, especially within the nervous system, that happen much faster than that. And that they think that it has to be photons, like light. It’s in a quantum matrix. And that the microbes likely communicate in a similar way. They were talking about it in the book. That’s as much as I understood out of about 100 pages of that.

Speaker 2:                           Well, that’s a very significant part of quantum mechanics itself. There’s the mechanics of couple particles that could be on either end of the universe, and when one changes, the other instantly changes as well, and that’s much faster than the speed of light. So there’s this quantum coupling among particles. So microbes, which are replications of one another, in many ways almost exact replications, there may be some quantum coupling. You don’t know where. There’s a whole level of science that-

Michael Roesslein:          Interesting. So it’d be an interesting few decades of science, I think, as quantum science starts to merge with microbiome science. Nature versus nurture argument seems to be similar to germ versus terrain argument. Where do you stand on germ versus terrain? Personally, I would answer that I’m somewhere in the middle, that I think both are relevant. But I think the prevailing theory used to be fully germ. Well, originally it was fully terrain, then it was fully germ. And I think we’ve looped back to some middle ground.

Speaker 2:                           Yeah. And when you really look at the data, it can’t be either one by itself. It has to be both. Number one, the germ has to be present in order for it to cause an illness. There is a villain here, if you will. Let’s take an infection of some sort. Let’s take an E. coli foodborne illness infection. You could have 10 people eat the same thing that is contaminated with this E. Coli, but only three out of 10 will get an illness out of it. So they all have the germ, but the difference in whether or not the germ has the capability to elicit an infection is that person’s terrain. What does that person’s microbiome and the immune system look like? Does it allow the germ to function the way it’s trying to function?

Now, here’s an interesting thing that we do know about lots of pathogens, lots of germs, is they won’t necessarily trigger their virulence factors or their toxins unless they can reach a certain threshold amount. A great example of that is listeria monocytogenes. Listeria is one of the most common foodborne illness pathogens. And listeria, we know once it gets into the body will not trigger any of its virulence factors or toxin production until it can reach a certain threshold concentration within the body, within the system, within the gut, in this case. And if it doesn’t reach that threshold level, it’s not going to turn on the virulence factors at all. Because it knows that under a certain threshold, if it starts turning on its virulence factors, there’s not enough listeria there to cause a profound infection. It’s going to get quenched right away by the immune system and other microbes in that area.

So it knows that. It uses the quorum sensing to talk to the other listeria that it’s multiplying by to say, hey, have we reached that critical mass? Can we turn on the genes? And if the terrain, meaning you’ve got lots of strong competitive bacteria, you’ve got really strong ecosystem in the gut, you’ve got a well functioning immune system, you’re producing lots of short chain fatty acids to fuel your immune cells, you’ve got a strong barrier function, meaning you’ve got a strong mucosal layer and you’ve got a tight intestinal epithelium. All of those things are working well. Listeria may never get a chance to reach that threshold level. So it may never elicit its response or its virulence factors.

So it’s both. So the germ is present. The germ has certain capabilities, certain wants, certain goals. And the terrain is going to either allow the germ to do that or not allow it to do that. And you can’t have an infection without either of them. You can’t have an infection without the germ and you cannot have infection without the terrain allowing the germ to do what it does.

Michael Roesslein:          Suggestions for increasing low sIgA. And sIgA is an immune cell. If you could just give a quick on sIgA. And then I know of Saccharomyces boulardii, I’ve seen… Of course, here comes a lawnmower. I’ll deal with that. Suggestions for increasing low sIgA. I know Saccharomyces boulardii. Is there anything else you’d want to throw in there?

Speaker 2:                           Yeah. So sIgA, for those who are not familiar, is secretory IgA. It’s the most abundant immunoglobulin in your secretory fluid, so in things like tears and saliva and into your mucosa and so on. IgG is the most abundant antibody in your blood, in your circulation, but secretory IgA is in your excretory or secretory fluids. Your microbiome stimulates the production of secretory IgA. So this data that suggests that the more diverse your microbiome is, the more interaction it has with the immune system, the more secretory IgA you would actually elicit. Because one of the things that causes secretory IgA to be released is the activation of pattern recognition receptors in your immune cells. Those pattern recognition receptors are triggered by the presence of more microbes and diversity in microbes within your microbiome.

And then there’s other microbes that have a particularly good capability of pushing the immune system. Well, that’s one of the things that spores do really well, is because they can actually make their way towards mesenteric lymph nodes from the Peyer’s patches, and then stoke the immune system to release more antibodies and trigger more lymphocyte proliferation and so on.

So having a diverse, healthy microbiome will play a role in that. We’re actually setting up a study on MegaSpore to see if we can increase sIgA in low sIgA people. But there are some nutrients, like you mentioned, Saccharomyces boulardii has data on that as well. But there are some nutrients like zinc, vitamin B, that have been shown to be able to increase sIgA production. If you have a genetic deficiency in sIgA, I don’t know if there’s much that can be done there. But certainly getting outside, getting more exposure to bacteria, improving the diversity of your microbiome, those will all be things that increase sIgA production.

I could talk a while about sIgA, but there’s two things I want to mention about it that’s really interesting. That’s part of how your body builds tolerance to your own microbiome. So often what happens is you’ve got those two layers of your mucosa, which I explained before, but let me use this illustration to show you this. I’ve got it handy dandy nowadays. But remember there’s two distinct layers of your mucosa. You’ve got the top layer where most of your microbiome lives, and then you’ve got this inner layer, the clean layer, called the mucin-2 layer where there shouldn’t be a lot of microbes entering into this layer. If there are a lot of microbes that enter this layer, like in the case of leaky gut, then you’re going to get profound inflammatory responses going on here.

But from time to time, your own commensals do make their way into this area. But what they look like typically when they’re found in this area, which means it doesn’t elicit a negative immune response, is they come in and they’re covered with secretory IgA. So your own secretory IgA recognizes all of your commensal bacteria, and you continuously release secretory IgA that binds to the surface of your commensal bacteria. That’s one of the ways your immune system knows not to attack the commensals, because it doesn’t attack it because it has sIgA on its outer layer, especially if that vector is allowed to migrate on the inner part of the mucosa. So part of the way this whole mechanism of sIgA works is that the presence of commensal bacteria stoke the release of more sIgA.

And sIgA is an antibody that’s interesting, because it’s not designed to be highly specific to any one antigen. It has enough variation in its binding sites where one sIgA antibody can bind to a lot of different things that look like its target. IgG, for example, is highly specific to very specific antigens. It’s a very lock and key mechanism. This IgG only fits this antigen and it specifically binds to that. sIgA has a lot of flexibility in the things it can recognize, and it can bind many different antigens. So the more your microbiome causes the release of sIgA, the more sIgA you’ll have floating around that will bind to cells within your microbiome. But then will also latch on to other things within your mucosa, including viruses that may be coming in, bacteria that may be coming in, toxins and may be coming in, and so on.

Michael Roesslein:          Oops, I was muted due to the lawnmower. The lawnmower is now gone. Someone was actually driving it down the road. Okay, just real quick with Saccharomyces boulardii. If people have sensitivity to yeast on an IgG or an ASCA antibody or a known tested positive for yeast sensitivity, will they react to Saccharomyces boulardii? You can’t say that for sure.

Speaker 2:                           Yeah, it’s possible. But I have not seen much reports of people being sensitive to Saccharomyces boulardii. So I would approach that with caution. If you’re an anaphylactic to yeast, then no.

Michael Roesslein:          Yeah, IgE, then no.

Speaker 2:                           Yeah.

Michael Roesslein:          That’s IgE, right?

Speaker 2:                           That’s IgE. But if you have IgG, doesn’t necessarily mean you’re sensitive. So remember, IgG, and this is one of the dysfunctions in some of the testing, when you look at food sensitivity tests and you see IgG antibodies to it, it doesn’t necessarily mean that you’re sensitive to that food. The presence of IgG means you’ve been exposed to that food and your body’s developed a response to it, but it doesn’t mean your immune system will react to it.

Michael Roesslein:          That’s my big problem with the food tests.

Speaker 2:                           Yep. That’s a big issue. And in fact, globally, all of the immunology allergy institutes in the world have written editorials and papers against the use of IgG based antibody tests for food sensitivities, citing all of the research that indicates that IgG presence actually indicates tolerance, not sensitivity. IgE, on the other hand, would be a sensitivity reaction.

Michael Roesslein:          That makes sense. I have IgG1 subclass immune deficiency. Do you know anything about this? Will taking the MegaIgG2000 or SBIs be helpful for me or potentially harmful?

Speaker 2:                           So if you have a subclass dysfunction and if it’s IgG type one, IgG type one is the highest amount of all the four IgG subclasses. I think it makes up 60% to 70% of the IgG in your system. IgG type one typically binds to protein antigens, like in the case of a coronavirus, it’d be the spike protein that it recognizes, versus IgG type two and four bind more to envelopes or fatty acid recognition sites.

Now, if you have a type one deficiency, then the question is, have you been diagnosed with total IgG deficiency? So typically what happens is when you have a deficiency in one of the four subtypes of IgG, you may not actually have a total IgG deficiency because your body makes up for it by making more of the other subtypes. Now, type one is the highest percentage. So if you have a type one deficiency, depending on how severe that deficiency is, you could have a total IgG deficiency. If that’s the case, then there is some immune compromise going on. However, IgM could be making up for it. So what you really need to understand, and this is between you and your doctor to figure out the diagnosis and treatment, but what you really need to understand, what does your total immunoglobulin picture look like?

So then back to your question about will the MegaIgG have a negative or positive impact? The MegaIgG stays in your gut. It doesn’t enter into the blood. So all of your IgG is in the blood. All the IgG you make yourself is in the blood, it’s circulating around in your blood. The MegaIgG, the bovine IgG, stays in the gut and functions in the mucosa. So it doesn’t affect the IgG that’s going on in the blood. So it shouldn’t have any effect on the condition itself, either positive or negative, that we know of. Because the positive side of the equation is that if you are suffering from immune dysfunction, meaning you get chronic infections, typically people with IgG subclass deficiency will have chronic upper respiratory infection, chronic sinus infection, ear infections, those things just keep coming up. If that’s what you’re suffering from, then we don’t have any indication that taking the MegaIgG actually will reduce any of those effects. So we can’t say that it’s going to benefit your condition.

We do know that the MegaIgG benefits the gut, the toxicity, the issues going on in the gut. So certainly it will help your gut. But will it help your overall condition with deficiency? We’ve got no data to support that. Typically people with real severe IgG subclass dysfunction or deficiency will do immunoglobulin therapy. That’s something to talk to your doctor about.

Michael Roesslein:          That’s something different.

Speaker 2:                           Yeah.

Michael Roesslein:          Okay. While we’re on it, the SBIs, the MegaIgG, what would be the main reason… How does one know when taking SBIs or IgG is warranted? And then a followup to that, which was a different question. Are the effects of SBIs or your MegaIgG specific to the gut or are they systemic?

Speaker 2:                           Right. So as I mentioned, the IgG doesn’t go systemic, so it stays in the gut. You can see, if you measure inflammatory cytokine systemically, you could see those change to a certain degree. But that’s because what happens in the gut has a systemic effect. So it’s not that the IgGs are going in and floating around inside your body and doing work. They’re working in the gut, but any time you bring down toxicity or inflammation of the gut, you’ll see it systemically. So that’s the connection there.

How do you know when you need to take it? It’s something I take every single day. It’s probably, I think our second or third. It’s typically tied with the MegaMucosa as far as biggest selling products in terms of volume. So a lot of people have found a lot of utility in it as a way of bringing down the toxic load in the system. Because these are immunoglobulins, they do bind things like mold toxins, they’ll bind things like bacterial toxins, environmental toxins. It basically helps neutralize and reduce the number of things that cause inflammatory or toxigenic load in the gut. That’s its biggest effect. And so-

Michael Roesslein:          So it binds to things. So your immune system doesn’t essentially. It doesn’t trigger the immune system, it catches it before that.

Speaker 2:                           Exactly.

Michael Roesslein:          [crosstalk] as a food antigen buffer. Like if she’s going to eat something that might be marginal or questionable that her body may or may not like, we load up the IgG with that meal. And then we used it as a binder, essentially, with mold toxicity in between meals.

Speaker 2:                           Yeah, exactly. It’s about bringing down the toxic load in the system. It’s about reducing the things in the system that can trigger inflammatory response in the body. It’s essentially giving the immune system a helping hand. Going, hey, we’re going to deal with all of these things so you can worry about the more sinister things that may be coming in through other parts of the body. So that’s the way we look at it.

Michael Roesslein:          Which can reduce an overall freak-out response from your immune system, if there’s not as many things that get to it.

Speaker 2:                           Totally. Yeah. And again, remember one of the main points of my talk was that the inflammatory pathways and the inflammatory signaling is the way that your microbiome signals to your immune system the presence of pathogens and infective agents and contagions and so on. And so when you have lots of inflammatory signals going on, then the microbiome can’t effectively signal to your immune system when something is present. That’s one of the reasons why, especially in this case, this virus seems to trigger inflammatory responses. Because it’s trying to dampen the signal so that your body doesn’t know exactly where that signal is coming from.

And that’s a really important part of it, is that overall in being resilient, overall in having a tiptop functioning immune system, one of the features is keeping inflammatory responses lower and dampened. If you can have a lower net rate of inflammatory response in your body, then when the inflammatory response is needed, it’s going to be much more effective. So one of the ways that I think about doing that is utilizing something like this that binds up and neutralizes lots of things that can come in and stoke that inflammatory response in the body.

Michael Roesslein:          Okay. All right, great. This is interesting, and I’ve heard you talk on it before. Given microbiome’s role in immune response, is there any research showing possibility of a better vaccine delivery response if given orally in some manner?

Speaker 2:                           Yeah. One of the things that really troubles me when I look at vaccine research is why do they keep doing intramuscular injection of vaccines? It’s just not a great sampling site for your immune system. The vast majority of things that enter your body enter through the respiratory or the digestive tract. And the respiratory mucosa, the digestive tract mucosa, is a huge site of sampling of things, and that’s where you elicit a really good immune response to antigens that you encounter into your system. So that part, I still am not still quite wrap my head around why they keep going the intramuscular side. I know with a lot of kid vaccines, they do it as a respiratory one, which makes more sense.

Now, the work of Simon Cutting is really interesting. This is actually one of the reasons why we ended up getting in contact with him, because he’s got a bunch of work in a company called SporeGen, which is based in the UK, where they are putting antigens on spores. Like say tetanus antigen, it’s for tetanus vaccine. So instead of injecting yourself with a tetanus vaccine, which is a tetanus antigen, they’re sticking it under the spore and then delivering the spore orally.

What they’ve shown in published research is that you get a much better amplified immune response, especially the adaptive side of their immune response, to the presence of the tetanus antigen when sent in with the spore than compared to when it is injected into the arm. So that’s the whole focus of the company called SporeGen, is they are trying to develop orally derived vaccine vehicles using things like spores to take it into the Peyer’s patches, which is the largest area of your immune cells, sampling, and then deliver it to the immune system going, hey, take a look at this and pay attention to it. Then your immune system elicits a beautiful antibody response against it, and then you have some degree of protection against an antigen next time you see it.

So one of the ways I think about, as you’re going through and encountering antigens from different places, one of the reasons I like keeping my spore count up in my system is the spores tend to help with antigen presentation. So as your body encounters antigens, the presence of spores may help the immune system respond better to the presence of those antigens.

Michael Roesslein:          I remember we talked about that years ago, so I wasn’t sure if anything happened there. But it makes more sense because that’s how we would encounter an antigen.

Speaker 2:                           Totally. Yeah.

Michael Roesslein:          One of the problems with vaccine reactions is… Well, I don’t want to go down a rabbit hole that’s going to get us taken off the internet. But is that never in the world, it’s literally impossible for an antigen to just appear in your blood.

Speaker 2:                           Right. Yeah.

Michael Roesslein:          It’s in your arm. You don’t get smallpox in your arm.

Speaker 2:                           Especially something like a respiratory virus, like influenza, for example. If you were to encounter influenza, which we all do, you get it through your respiratory tract, you breathe it in, you touch your eyes, nose. That’s how it comes in. You never get influenza naturally getting injected into your arm. So I don’t understand why they don’t use the more natural sampling site as a way of delivering the vaccine. That may be an issue of production packaging. I don’t really know. But it would make more sense to use the natural areas of sampling to develop an immune response.

Michael Roesslein:          Makes sense. That’s really interesting. Do you have a theory as to why healthcare workers are getting such severe and dangerous cases of COVID-19 compared to the general public? And I’ve noticed this too. And my own theory is that with viruses, it comes down to load, and healthcare workers are exposed to the highest viral load when working around a room full of positive patients, and with masks and re-breathing and all of that. Is that a good layman guess?

Speaker 2:                           That’s an absolutely great guess. I would put that as probably one of the first reasons. Viral load makes a big difference. You can actually get a small load where there’s not enough virus to create enough replication to actually make you ill, but it’s just enough to elicit an immune response and your immune system recognizes it, deals with it, and then you’re fine. But if you get a huge load, then that huge load makes it much harder for your immune system to start bringing it under control. And remember with this particular virus, one of its functions is it amplifies the cytokine of the chemokine response in the cells. So when you get a big viral load, you get a bigger inflammatory chemokine response right off the bat, which makes you feel sicker and makes you feel more lethargic, more muscle pain, all of that stuff. Remember, all of the symptoms that you feel from the illness is part of the immune response to the illness, not the virus itself. So the load is a big part of it.

The other part of the guess I would create is that they are under a tremendous amount of stress. The work conditions, what they’re dealing with, they’re on the front lines of this. We know stress dramatically suppresses the immune response. And stress also increases the virulence of latent viruses. So now you’ve got other things your immune is also trying to deal with that are proliferating because of the stress levels. Things like cytomegalovirus and Epstein-Barr virus and papilloma viruses, all of those things start flourishing in your body the moment they sense the stress signals. So to me, it’s a combination of those two things, probably stress, lack of sleep, and then of course, viral load itself.

One of the things that we’re seeing maybe is that this particular virus doesn’t transmit as easily in just a general sense. And not everybody is equally contagious. Some people are more super spreaders. And that was actually a really interesting exercise that was done before this pandemic started in a documentary that the BBC did on pandemics. Is that typically in pandemics, the vast majority of people get infected by a very small number of people. You’ve got single individuals that can infect, 500, 600 people in a chain of events from over a few day period because they are highly contagious. Why are they highly contagious? Well, whatever the composition of their bodies, they’re immunocompromised or suppressed, the virus gets lots of chance to replicate. Then their viral load that they spew out in their respiratory droplets and all that, it tends to be much higher than the next individual next to them. Because remember, a lot of people could have active viral infection and you can’t even pick up virus through the nasal pharyngeal swab. So the amount that they’re putting out is actually really quite small to almost nothing at all.

So those factors play a role in how well it gets spread from person to person. If you are a medical person in a ward with a lot of people spreading COVID, you’re getting saturated with it all over the place.

Michael Roesslein:          Giving that clotting seems to be part of the COVID-19 presentation for many patients, and we are not doctors, we’re not treating or curing or preventing COVID, are there concerns around vitamin K2?

Speaker 2:                           No, it’s a different kind of clotting. Number one, vitamin K2 doesn’t really impact the clotting cascade much. It’s vitamin K1 that’s really doing it, and that’s in the liver. The clotting that’s occurring in COVID is more systemic. It’s occurring in tissues that are getting damaged because they’re triggering of a particular type of inflammatory pathway. One of the responses to that inflammatory pathway is clotting in that local area. So these aren’t people that are getting clots created through platelet aggregation in their liver or increased clotting factors in the liver. The studies show that it’s driven by an inflammatory process, not driven by increased clotting factors. So it’s a different mechanism that’s going on.

And again, maybe many of you don’t follow me on social media, but I posted a study recently, in the last couple weeks, that showed that K2 status, in a study in Norway, was a very close correlation and determining factor in the severity of the COVID infection. This a well published study. So in fact, K2 seems to help with the functionality of the system.

Michael Roesslein:          Yeah. I saw that. You’re good at the Instagram. Do you do that yourself?

Speaker 2:                           I try to, yeah. I should be posting every day.

Michael Roesslein:          Instagram’s a pain in the ass.

Speaker 2:                           Oh, it is. I’m still learning how to do it, and I’m-

PART 2 OF 4 ENDS [01:02:04]

Michael Roesslein:          … pain in the ass.

Kiran:                                    Oh, it is. I’m still learning how to do it and I’m [crosstalk 00:00:04].

Michael Roesslein:          The stories … we’re too old. It’s always, Jesus … I always admire anyone, I live on a side street with a 20 mile an hour speed limit. Did you hear that?

Kiran:                                    That did not sound like they were doing 20.

Michael Roesslein:          No. I always admire anyone our age or older that actually has an active Instagram. It’s so much more work than Facebook.

Kiran:                                    It is. Oh, my God, it is.

Michael Roesslein:          It’s not like a one-button share, you have to type things in the phone and use hashtags. It’s exhausting. Anyways. Let’s see, why do we react to foods after being on elimination diets? Does Mega IgG help with this? I think they mean for like a long period of time. Because people, now the elimination diets were a huge thing, and they still have their place, but then it’s reintroducing the diversity, which we’ve talked about a lot.

And a lot of people are now noticing like, oh, I’ve been on a super strict diet for four years and now I can’t eat anything. And they weren’t originally reacting to all those foods, they just took out all the foods that they say people react to, to be precautionary. And then all of a sudden they are reacting to things they didn’t use to. Can you just briefly explain, that goes back to tolerance and diversity, right?

Kiran:                                    Totally. Yeah. Again, the tolerance is built by exposure. So if you go through a long period of time where you’re not getting exposed to certain antigens, your body might forget that tolerance, because remember the antibodies and all that don’t last forever, necessarily, in the system. The antibodies that afford some of the tolerance. So then instead of getting this really mild, really non-consequential antibody response, then you start getting an inflammatory response instead, because to your body now it looks like something new that it’s never encountered.

So that’s part of the problem with the shortening of the exposure to normal antigens, especially proteins from different sources. So again, tolerance is maintained by having continuous immune response to those antigens. And it’s the adaptive immune response that comes along with the Treg response, the T regulatory cell response, that dampens any immune response to that food antigen.

The way all of that happens is in the context of the microbiome, the microbiome is the thing that upregulates the Treg system, the regulatory system. So if you’re continuously introducing food, like on a regular diet, those antigens are entering the system. They’re being presented to the immune system in the context of the microbiome, the microbiome helps the immune system upregulate the T regulatory cells. So then you build immune tolerance against those antigens.

Now, if those antigens go away, and one of the consequences of elimination diets is that your microbial diversity goes away too and start shrinking dramatically. So now you’ve got a two prong reason for developing immune dysfunction, is you don’t have the antigen to continually get exposure and tolerance to. And you don’t have adequate microbiome diversity to elicit that tolerance response. So you’ve got a double whammy in creating intolerance of food particles.

Michael Roesslein:          That makes sense, double whammy.

Kiran:                                    Double whammy.

Michael Roesslein:          What’s your opinion overall on pathogen protocols, parasite detoxes, parasite cleanses, things of that nature?

Kiran:                                    In my view, they’re often used for wrong reasons. I think, especially with parasites, as I mentioned earlier, if you truly think parasites are a problem, then you should definitely get a good pair of cytology tests to understand if they really are a problem. In general, in the Western world, and in the modern developed world, parasites are typically not a problem for people. Looking at CDC data and other national databases, you really see very few true parasitology problems in people in the Western world. Unless you’ve traveled overseas, and you were in the Amazon for a while, or you went to Asia and you were eating a lot of street food and so on.

Then you could have picked up a parasite or two that could be causing you lots of issues. But for the most part in North America, parasites aren’t really a major issue. So I would encourage people to get a full, comprehensive parasitology test before doing any of those kind of detox things. Because a lot of those things can really put a lot of stress on your liver, on your gallbladder, on your gut microbiome. And it’s not necessarily good for you, you may not be needing it.

Michael Roesslein:          Yeah. Those can be pretty harsh. [Kiran’s] Instagram is @KKiran_00. I looked it up.

Kiran:                                    Yeah, so that, actually, is another piece of evidence that I’m terrible at Instagram and social media, because that’s a terrible Instagram name. Because it’s not logical and it’s hard for people to find it.

Michael Roesslein:          I don’t even use mine professionally. So you’re way ahead of me and I don’t ever put anything on it. It’s just a time waster that I scroll through and watch your stuff. So someday I will effectively use Instagram. All right, do you have any knowledge about … How does mucosal immunity and microbiome help trigger T-cell reactions and other immune reactions and which are specific to COVID-19? I think you talked about this in part one.

Kiran:                                    Yeah. Yeah. I mean, all of the immune response occurs in the mucosa. That’s the primary site of action. Every pathogen that enters your body enters through a mucosal layer, so it’s going to end up in the mucosa. The mucosa has immune cells, they’re floating around; dendritic cells, macrophages, and then of course the epithelial cells, or the endothelial cells, depending on which one the mucosa covering. If they start getting infected, they will release the cytokines and chemokines, and then your microbiome in that area will also release the cytokines and chemokines to alert your immune cells that there’s a problem there.

Then the antigen presenting cells come along, they start eating up the antigens, they start eating up the viruses, eating up the bacteria, eating up the infected cells. And then presenting that contagion’s antigens to your T cells. And then your T cells will then often go to a localized lymph node where they will start proliferating and that’s where the battle occurs. So that’s why when you have an infection somewhere, you can find a tender lymph node somewhere in that proximity. Because that’s where the T cells are going to be draining into, to proliferate and then mount up and get ready and then come back out to the site of infection to neutralize the infection. So all of it occurs in the mucosa, that is the battleground for infection.

Michael Roesslein:          All right. I have a few questions about your BiomeFX test and I’m going to just lump them into one, to bang out a at once. Does it test for calprotectin or any other type of inflammatory or LPS markers? Does it help identify dysfunctional microbiome and how?

Kiran:                                    So, yeah, so we do not test for calprotectin or zonulin. We do not find those to necessarily be that indicative of anything. So what do you do with the calprotectin test? Well, it tells you that there’s something messed up in your gut. So if you do a fecal calprotectin and the fecal calprotectin is elevated, you go, oh, okay. That means something is wrong with the gut. Well, what is wrong with the gut? You still don’t know.

But if you’re even doing the tests, it already indicates that something’s off in the gut because you’re feeling symptomology. You’re feeling cramping, bloating, indigestion, whatever it may be. Bloody stools, whatever it may be, calprotectin is just telling you, hey, something is wrong with your gut. It still doesn’t tell you what is wrong with your gut. So we are very focused on identifying the what, we’re very focused on giving you a clue as to what may be the problem in the gut.

So that’s why we focus our tests on the microbiome component of the gut. So we’re not measuring markers, we’re not measuring inflammatory markers, anything like that. We’re looking at the personality of your microbiome and specifically focus on the functionality of various groups of microbes within the microbiome itself. And a lot of it will tell you that these groups of microbes, based on relative abundance data, tend to be higher in your sample than they are in a large cohort of healthy normals.

Meaning that this function that you have going on in your microbiome may be the cause of your symptomology or your problems. And that’s the only way you can know and understand what may be going wrong in your microbiome. I’ll give you one quick example of that. Look at sulfate reducing bacteria, that’s one of the things we measure. There’s a few bacteria that are sulfate reducing bacteria. Now it’s normal, obviously, to have sulfate reducing bacteria within your microbiome. They do a job within the microbiome, but if your abundance of sulfate reducing bacteria is too high, then what tends to happen is they will tend to take sulfates from your food and convert them into hydrogen sulfide.

And that hydrogen sulfide is very inflammatory to the large bowel and can cause lots of symptoms like, loose stool, constantly cramping, in some cases even bloody stool. And in fact, in some cases it’s actually tied to a risk factor for colitis. So you would never know, and here’s the thing, lots of healthy foods are high in sulfates. Things like fish and garlic and leeks and artichoke, all these things tend to be high in sulfates. So you might be eating a diet that you think is healthy, and it is a healthy diet, those foods themselves are fine. But because your sulfate reducing bacteria are too high, what happens to the food in your gut actually leads to negative symptomology and then negative results.

Those are the kinds of things that we look at. At the moment we have something like 18 or 19 of those kinds of functions. We have a 2.0 version of the test that’s coming out in June that has, I think, 31 of those functions. So it’s ultimately the true functional microbiome test, looking at the functions and dysfunctions within your microbiome. It’s not a list of, here’s all the bacteria you have. Oh, and this one bacteria is high and that one bacteria is low. None of that is meaningful at all. What’s meaningful in your microbiome is a functionality of different groups of [crosstalk 00:11:38].

Michael Roesslein:          What’s happening, what’s not happening.

Kiran:                                    Exactly. It’s a personality test for your microbiome is one of the ways-

Michael Roesslein:          Perfect, that should be on the box.

Kiran:                                    Yeah, because really, if you just look at a personality test for somebody, these aren’t absolutes. And nothing is absolute in microbiome analysis either. But if you do a personality test on somebody, you get an understanding, or you can be predictive to a certain degree, of how that person’s going to respond in a particular situation. It’s not an absolute, it’s not 100% sure they’re going to respond that way, but you can make predictions. And that’s exactly what we want to do with this microbiome test. It’s functional, it’s focused on function/dysfunction, and it’s a personality test.

Michael Roesslein:          All right. I’m going to do a few more and then we got to get to some recommendations, tips, research. Because there’s a lot of people in the chat are wanting to talk about the products too. So I just want to do a few more. I’m almost through them. I might not make it to all of them. If there’s a handful I don’t get to, I’ll email them to Kiran and we’ll get them to you at some point.

Trying to just pick out ones that have been asked, some people are persistent and put them in the chat and the Q&A, and my email. Someone who’s had, for six years, staph. No, reoccurring … Oh, where did it go? I’ll find it in a second. How about, does having lost part of a colon effect the microbiome and does MegaSpore or anything else that you’ve produced help with a situation like that?

Kiran:                                    Yeah, I think having lost part of the colon will certainly have a impact on your microbiome because you have less surface area in the microbiome, of course, which means you have less microbes and less functionality. A very recent study on colonic colonization of the microbiome actually showed that you have completely different types of microbes in different sections of the colon. So it’s not just this big fermentation vat where you’ve got lots of similar bacteria all over the place. So there are very specific functionalities within specific areas of the colon.

The sigmoid colon looks very different than the transverse and the ACE ending and so on. So it depends on which section you lost, some of those microbes may not be present and thus may not be providing their functionality. Now taking MegaSpore and all that, that’s not going to replace the functionality of that part of the colon, but certainly the focus has to be, how do we optimize the rest of the colonic function?

And we know, in general, that in looking at the different sections of the colon … Because in our publications, we did look at the changes in different sections of the colon. So we do know that that taking the combination of the spores and the prebiotic do improve the microbial diversity and the ecosystem within each section of the colon. So minus the part that you’re missing, taking that stuff is really going to enhance the function of the microbes within the remaining parts of your colon. Which is, at this point, the best thing you can do,

Michael Roesslein:          Partner has had strep for six years on and off after course of anti-malarial antibiotics, thoughts on ways to change this cyclical infection.

Kiran:                                    So in part it’ll depend on where this strep infection is. Strep, remember, is a normal part of our ecosystem in our bodies. Strep and staph, both of them. They are very present in the sinus cavities. More research has come out that they are probably, the strep and staph, are probably the two biggest drivers of infection in the sinus cavity. So we’ll take that as an example, because I don’t know where in the body you’re talking about. Because you can have strep infection on your skin, you can have it in your heart, if you have rheumatic fever, different areas of the body. So let’s take the sinus cavities, for example.

The studies show that the difference between people that get continuous rhinosinusitis versus those that don’t, in the case of continuous rhinosinusitis, it is still the strep and staph that are driving it, but the difference between people that don’t get it and the people that get it is not the presence or the absence of staff or strep, it’s the diversity of the rest of the microbes within the sinus cavities. So when you have higher diversity in that ecosystem, strep and staph have less infectivity rate. So they don’t infect in the same way.

They are opportunistic organisms. So given the right terrain, as we talked about earlier, they will express some of their virulence factors. One of the best ways to keeping them under control is having a higher diversity of other microbes that keep them in check. So depending on what the condition is, you should be talking to a doctor if they’ve got continuous infections, there may be other risks there. But aside from that, the thing that we could talk about is having a better diversity in their microbiome keeps those under check. And obviously using the spores will help the diversity, improving the diet will help the diversity, and then getting outside more helps the diversity significantly as well.

Michael Roesslein:          Describe any specific ideas, probiotic, food, lifestyle, or otherwise for controlling reoccurring staph aureus, I think aureus. A-U-R-E-U-S, staph aureus skin infections. I don’t know if that’s a specific type of staph or …

Kiran:                                    Staph aureus is a very common vector. We all have it on our skin, we all have it in our guts, in our eyes, in our nose, everywhere. Staph aureus is everywhere. Staph aureus is on the skin and typically battles with something called staph epididymitis, or epidermidis, and typically what they show is that when staph epidermidis is lower then staph aureus has a chance of actually rearing its head and causing more infection. So in that case, it’s really the terrain issue because the staph is always there. It’s there on everybody.

But if the other microbes are at lower level, then it’s going to rear its head. There’s a couple of things. One, MRSA, which most people have heard of, methicillin resistant staph aureus, is one of the types of staph aureus that people can have. There was a large NIH study that was published about a year and a half ago that showed that people who were well colonized with bacillus subtilis actually had no MRSA levels at all. Those that weren’t colonized with bacillus subtilis tended to have more MRSA colonization.

So the bacillus does a good job of fighting with the staph aureus. So that’s one of the things to consider is getting some spores into your system. If it’s a skin area, now let’s say it’s just one area of your skin that tends to have more of that staph type infection, of the aureus infection, and you have other areas of the skin that are normal. One of the things I’ve recommended to people is to engraph normal stuff to this side.

So let’s say you’ve got a patch here that you typically get staph aureus infection and the rest of this arm is completely normal, which means that the microbes are normal here. One of the things I would recommend people doing is taking a wet Q-tip and swabbing the normal area and transferring it a few times a day to the affected area. I actually had a few people do this and they actually saw some measurable improvements. You’re basically engrafting from the unaffected side to the affected side. And hopefully you’re bringing more staph epidermidis to this area that can then combat the aureus. So that may be something to look at doing as well.

Michael Roesslein:          Makes sense. All right. I think I’m going to have to type the rest of them to you because I want to get to product questions and a little bit of recommendations, tips, suggestions, overall for … I mean, you had the one slide at the end of your presentation. So go back to part one, it’s the last slide. So if you go to the end of part one replay, the last slide had a bunch of recommendations on it.

Kiran:                                    If you want, do you want me to pull that up and show it-

Michael Roesslein:          Yeah, if you’ve got it we can just have it on the screen while we talk about this.

Kiran:                                    Oh yeah, I think you have to enable screen share.

Michael Roesslein:          Oh, screen share. Okay. That should be on. How does earthing grounding effect the microbiome. I know that it has effects on the nervous system and I know that being in contact with nature has a positive effect on the microbiome. That’s all that I know.

Kiran:                                    No, and I think that’s about right. I have not seen any studies that show that earthing and grounding specifically change certain microbes, but I think just the act of being in nature in itself, and getting in contact with dirt or natural ground, is going to have a positive impact.

Michael Roesslein:          Oops.

Kiran:                                    Okay, so I’ll just run through these recommendations real quick. And these are things, many of the things I’ve mentioned, and these are no different when it comes to trying to optimize immune function through the microbiome, which is obviously a really big, important part of immune function. Number one is diversifying the diet. I’ve given lots of recommendations on that. And again, that’s about increasing more of the foods, the types of foods, that you consume on a regular basis. And that’s more on the plant based side of the foods.

You can, of course, try to increase the diversity in the various proteins and meats that you eat, but that’s not going to give you the same kind of impact on diversity. Because ultimately when it comes to protein, ultimately they get broken down into their amino acids. When it comes to carbohydrates and fibers and soluble/insoluble, resistant starches, oligosaccharides, all of those have very different carbohydrates structures that only certain microbes within your large intestine, especially, can utilize.

And so it provides an increase in diversity in those microbes. So that’s an important thing. Another way of increasing diversity is, of course, just fasting. Fasting does a couple of things for your microbiome and immune system. Number one, it increases the diversity within your microbiome, which is great for your immune system. You have a bigger neighborhood watch, a more diverse neighborhood watch for your immune system. But the second part is, fasting also helps the housekeeping mechanisms. So it cleans up damaged cells and it turns on autophagy and mitophagy. So it cleans up damaged DNA and cells and debris and cellular debris, and it helps fix damaged mitochondria and replace it with better functioning mitochondria.

So all of this housekeeping, cleanup stuff is really important for your immune system to function in tip top shape in general. So fasting, add that to the diversifying diet, lowering stress is really important. It sounds really casual, but just a couple of main points on the lowering stress. Number one, stress is one of the biggest drivers of leaky gut. Stress induced intestinal permeability in a 2015 publication in The Frontiers of Immunology, and that’s a tough journal. I can tell you, I just had a paper of ours that we were trying to get published in Frontiers of Immunology and we had to go through quite a rigor on the peer review process. So it’s a good journal with really good peer review.

That study showed, and they concluded based on meta analysis of lots of other studies, that intestinal permeability driven by stress is the largest driver of mortality and morbidity worldwide. And the relate that to the types of chronic illnesses that stress induced leaky gut endotoxemia drives. And then of course, all of the immune dysfunctions that it drives as well. So that’s a big part of it is lowering stress. The other thing that occurs during a stressful state is all of your latent viruses and bacterial pathogens start to rear their ugly heads at that point.

So there are lots of viruses and all that within your system that learn to recognize your stress hormones as a signal to tell them that your body is compromised and your immune system isn’t functioning well. So this is a good time to proliferate. For example, herpes simplex virus, cytomegalovirus, Epstein-Barr virus. They all tend to increase their virulence factors. Streptococcus, staphylococcus are another example, we just talked about those kinds of bacteria. They all increase their virulence factors during a stress state.

So if you imagine your immune system is potentially encountering a new contagion, and then at the same time, if you’re highly stressed and your body is dealing with all of your resident contagions amplifying themselves as well. So stress becomes a really important thing to manage. And again, there’s lots of mindfulness work you can do, breathing exercises, there’s endless recommendations out there of how you can try to manage your stress. Getting outdoors is really important, and I don’t mean just walking around the sidewalk of your neighborhood. That’ll have some benefit, of course, but if you can get out into a natural environment, like an area where you can go on a hike, be within the forest a little bit, be within natural soil.

Around here, around my house, we have lots of forest preserves. I’ve been going, over the last couple of weeks, doing lots of mountain biking in the single track trails in the forest, and then you stop and you enjoy and absorb that an environment. That has a huge impact on the diversity of microbiomes. The spore based probiotics, of course, we’ve got a bunch of research on their functions, but one of the key things when it comes to the immune system is the ability to train the immune system and trigger those pattern recognition receptors. Trigger toll-like receptors, different things that keep the immune system ramped up and keep the immune system functioning.

They also bring about the ability to diversify the microbiome, which of course is a very important part of immune function. They also compete against pathogens that are within your system so that you can bring down the negative impact that pathogens may have on the system. Which may stoke a more inflammatory response, which will then dampen the inflammatory signals from new contagions entering the system. Focus on leaky gut solutions, because remember leaky gut causes system-wide inflammatory response. The same exact inflammatory cytokines that are being used by the microbiome to alert the immune system to the presence of a pathogen.

Those are the same inflammatory messengers that get amplified because of leaky gut. And that becomes systemic. So imagine if a fire alarm is a signal that a fire exists, you want to make sure that throughout the day, you don’t have any other fire alarms except for when a fire exists. So that then the firefighters can hone in on that singular fire alarm. If you’ve got fire alarms ringing all throughout the system all the time, then when there is an actual, really dangerous fire, that signal is going to get drowned down and you’re not going to get firefighters getting to that area.

So leaky gut is a big, big driver of systemic inflammation and can compromise immune response in a dramatic way. And that, again, goes hand in hand with bringing down inflammation. In the case of diet, if you do have foods that stoke inflammation, for example, gluten. Gluten is a food that does stoke inflammation in virtually everybody, even if you’re not gluten sensitive. Even if you are, if you’re not gluten intolerant, even if you’re not celiac, studies show that everybody gets transient permeability when you’re exposed to gluten.

And for that reason that transient permeability can cause a phase of inflammation for a period of time after you’ve been exposed to the gluten. So if you can avoid certain things, like gluten, in your diet. If dairy’s inflammatory to you then avoiding dairy for a period of time to bring down that inflammatory response. Those are things that can help from a dietary standpoint. Of course, we know that processed foods are inflammatory. We know foods that tend to be high in oxidized fats, like deep fried foods that are fried in old oxidized vegetable oils. Those things all can be very inflammatory. So reducing the exposure to inflammatory foods.

Prebiotics are huge, major components to the function of the immune system. We cannot say enough, and people don’t think of prebiotics as part of your immune regimen. But the oligosaccharides, in particular, and the short chain fatty acids that they elicit are really critical for immune function. The acetate, as I mentioned earlier, plays an important role in stoking that interferon response in the body. That interferon is the first and most powerful antiviral response in the body, that is dependent on acetate.

Butyrate, which is also produced as part of the short chain fatty acid collection, is a very important energy molecule for your circulating dendritic cells and macrophages. Those are the first antigen presenting cells that are going to go find those antigens and present it to the T cells and B cells for immune response. So your short chain fatty acids are going to be really important, and those are typically stoked by oligosaccharides. So oligosaccharides are really critical.

Right now, I kind of wax and wane a little bit with the prebiotic that we use. I use the Mucosa product every day, I use the IgG product everyday, and the spores everyday, but I wax and wane a little bit with a prebiotic. But over the last several weeks, month and a half or so, I’ve been doing the prebiotic religiously because the studies are so clear on the importance of oligosaccharides in immune function. So, in fact, that’s what I’m drinking right now. And then polyphenols and omega fatty acids, now this is really important to speak to because omega fatty acids bring down inflammation in that arachidonic acid pathway. And that’s really important. That’s inflammation that’s stoked and triggered …

PART 3 OF 4 ENDS [01:33:04]

Kiran:                                    …and that’s really important. That’s inflammation that’s stoked and triggered by tissue damage that’s going on in the body. The tissue damage in the gut lining, in the vascular tissue, and so on. So tissue damage triggers that inflammatory response through the arachidonic acid pathway. That is a very powerful inflammatory pathway. And again, it causes a lot more inflammatory alarms in the body. Now, that inflammatory alarm, when you couple it with a cytokine storm response, really creates lots of issues within the body from an inflammatory damage perspective. Not to mention, of course, it drowns out the inflammatory signals that are required where the microbiome is alerting the immune system to the presence of a contagion.

So using something like omega fatty acids, especially ones high in EPA and DPA and pre-resolving mediators, that’s what we created with the MegaOmega, that plays a significant role in dealing with the inflammatory response and the arachidonic acid pathway. Polyphenols are extremely important for diversification of the microbiome, for production of things like urolithin so that you get better mitochondria function, better energy production. Your immune system has better fuel. In order to function as an immune system, it cleans up damaged mitochondria, which can suppress immune response. And then polyphenols also have been shown to bring down inflammatory response in the gut. So again, lowering that net inflammatory blanket in the body so that the signals from localized areas that are getting infected are much louder and much clearer, so the immune system can get to that site. So those are the most basic recommendations, and I don’t know if we want to jump into questions from there.

Michael Roesslein:          Yeah, that makes total sense, and I do have some product questions that would be great to follow that up. You have Ava, whose Mira’s mother. Hi, Ava. She’s on here. She’s a case study actually on our website. Ava was the first person that I ever gave your products to, was the MegaSpore to her. And then her pet allergies and dust and mold, all these allergies and asthma, she had forever just went away really quickly. And then I called your company and was like, “What is going on?” And then we talked.

Kiran:                                    Yeah, I remember that was the first thing we talked about.

Michael Roesslein:          Yeah. I was like, “Can you explain to me why this woman no longer has asthma?” And then two hours later, I was like, “Can you come on a webinar?” And then that all happened, but said “I’ve had a major reduction in asthma from household pets.” She actually comes over to see ours all the time. And we brought pets to their home and we’re able to live there for a little while. And she’s a therapist and she couldn’t see clients who had pets.

Kiran:                                    Yeah.

Michael Roesslein:          It was so severe. So she said she’s been taking two MegaSpore a day for the past five years. Is it safe to take that amount indefinitely? And should I add prebiotics?

Kiran:                                    Yeah. So it’s absolutely safe. And not only is it safe, it’ll continue to help. It’ll continue to help maintain the system. It’ll continue to keep your immune system in the right balance, which is really important. Because keep in mind, we’ve got lots of things all around us that continually drive the microbiome into the wrong direction. That continuously drives the immune system in the wrong direction. So having those spores in there to try to elicit some balance is always useful. And for me the IgG is really important. While you may consider using the MegaIgG. I know that’s a key thing that Mary uses. We’ve all got all kinds of toxicity around us and bringing down that toxic load, and bringing down the, the impact on the micro, on the immune system is a big help to a lot of people’s systems.

That’s one of the products I use religiously, the MegaIgG. And I would say the prebiotic, if you can start adding it in the increase in butyrate, the increase in the keystone strains that we see from using the prebiotic cannot be overstated, as to how important that is for just overall health and function in a longterm. You’ll see some short term benefits on it, but in general, the longterm health of your microbiome, maintaining the diversity of your microbiome is absolutely critical to longterm health.

One of the features of getting older is that your microbiome diversity starts to shrink over time. And as your microbiome diversity starts to shrink, you become more susceptible with higher risk for chronic illness. That’s a very clear interaction between microbial diversity and then increased risk for chronic illness. And so one of the keys to aging more gracefully and with more resilience, is maintaining that diversity. So the prebiotic plays such an important role in that aspect. So those are the two things you should think about adding into your daily regimen.

Michael Roesslein:          Yeah, you just had that study get published with the prebiotic and the MegaSpore together too. So the two of them are pretty powerful. I actually noticed more in the way of my own digestion optimization when I started the prebiotic than I had with the spores alone.

Kiran:                                    Yeah. And that’s exactly why we have it. These are all really important adjuncts to what the spores do in the gut, the IgG, the prebiotic, the omega, they really enhance aspects of what the MegaSpore is already trying to do in the gut.

Michael Roesslein:          And I should say this out loud, I’ve put it in the chat. We are doing a special right now in our shop for every Microbiome Labs product in our shop, for the next few days, you get five bucks off for each product added to the cart. That’s something we’ve never done before. And it’s only for the Microbiome Labs products. So you order five of anything, it’s 25 bucks off. And there’s a code there ML5OFF it’s in the chat box. ML5OFF. It’s not case sensitive. I put it all caps. The links to the shop is there. That’s a sale we’ve never done before. I wanted to celebrate this amazing presentation and give people an option to try a whole bunch of different things. So I have a question here that would be really good to answer, that I’m going to paraphrase because it’s about a four year old, but it could be about anybody.

And it says, “My four year old is taking MegaSpore for the last two weeks.” And to answer the question, I just posted Ava’s case study link in the chat too, if you want to read about Ava’s story with the pet allergies. But four year old is taking MegaSpore for the last two weeks. When and how to add the Prebiotic and or the MegaMucosa, how to stagger titrate or introduce. I know you guys have a preferred way to kind of do that. And I think a couple of weeks in on the MegaSpore is a perfect time anyway, to go with that. So can you just go… Because you guys call that trio, the total gut restoration. That was the first three products and that’s kind of the foundational thing is the MegaSpore the Prebiotic and the Mucosa. Where the rest of the products kind of have like unique uses or situational uses. That would be more specific at times.

Kiran:                                    Yeah.

Michael Roesslein:          So how do you stagger those, I guess, how do you answer this? Stagger, titrate, introduce?

Kiran:                                    Yeah. So he’s been taking the probiotic for four weeks?

Michael Roesslein:          Two weeks, four years old.

Kiran:                                    Two weeks. Okay. So in the next week or two, you would look at adding in the Prebiotic. For a four year old, you would add somewhere around a quarter with scoop. You don’t need to do a full scoop. You would add it in… My kids, for example, take it in a smoothie, which they both seem to like smoothies and are happy to drink them. One of our ways of getting more vegetables into their system, but they’re happy to take it in a smoothie. So you would add about a quarter scoop of the… And there’s a scoop in the jar itself. So you do about a quarter of that scoop. Mix it in water juice whatever you’d like that he would be more comfortable taking. And then give that to him daily and have him sip it throughout the day.

He doesn’t have to sit and drink it all at once. It can be kind of his drink for the day as he’s playing around and you would have him keep taking sips of it. After a couple of weeks of introducing that, you can try to go to a half a scoop. You will never need to really exceed half a scoop or four year old, typically somewhere between a quarter and a half of scoop is perfectly fine. He’s getting plenty of oligosaccharides into a system. And, and it’s having a huge impact on his microbiome. That may be all he needs at that point. You may or may not need to move to the MegaMucosa, which typically happens in month three of the cycle. So you can assess him at the end of that second month, once you’ve already introduced the MegaPrebiotic. And remember you maintain the spores throughout that time, you can kind of assess, and whatever the end points are that you’re looking at.

If he’s doing really well, you may not need to go to the MegaMucosa at all. At four, they’ve got a lot of flexibility in the microbiome. They can make significant changes in their gut lining in a very short amount of time. So you may be in a perfectly good place just right there itself. If he’s continuing to have issues, then you can go again with about a quarter scoop of the MegaMucosa added into that mix. You can mix both the prebiotic and MegaMucosa together and again, shake it up in juice or water or whatever is a preferred way for him to eat it, get it, and then have them sip it throughout the day.

Michael Roesslein:          Yeah, we really… I do about a half a scoop of day right now myself too. We make a drink, Mira calls it, her hydration beverage in the afternoon. It is a full big water bottle like this size.

Kiran:                                    Mm-hmm (affirmative). Oh yeah.

Michael Roesslein:          With a half a scoop of Prebiotic, a half a scoop of Mucosa. And then we put a little electrolytes in there, a little vitamin C, a little magnesium and some sea salt for minerals. And just shake that all up and drink that every afternoon.

Kiran:                                    Nice.

Michael Roesslein:          Over the course of a couple hours. See anyone experienced constipation… So someone asking me, they experienced constipation with MegaIgG and was wondering if you knew anything that there could be a mechanism there, or…

Kiran:                                    It’s interesting. I mean the medical food version, the prescription version of the MegaIgG is for chronic diarrhea. So it’s there to treat basically diarrhea induced by pathogens or inflammatory processes in the gut. So that’s what it’s there for. The indication is, I think it’s something like the dietary management of chronic diarrhea from irritable bowel syndrome, inflammatory bowel disease, and so on. There’s a number of conditions mentioned. So if it’s caused constipation in you, and maybe it should be a temporary thing. And the question is, did you go from loose stool to constipation, or regular stool to constipation? That would be part of the question. Let’s say you went from loose stool to constipation. That’s a normal transition. And then you should go into regular stool formation because it seems like the microbes that were controlling the bowel movements were driving constipation.

And then now they’ve basically, those microbes have been dampened. And then now you’ve got nobody really in control of the bowel movements, but that should shift over a few days. And then you should have regular bowel movements. If you went from regular bowel movements to constipation, then maybe back down to the dose, and see if that changes. If it doesn’t, if it lasts more than two or three days. It’s hard to say if it’s related, it’s not a report that we get very often. I’m trying to think of if we’ve had anyone that I know of-

Michael Roesslein:          We haven’t. It says, “No loose stool tend toward constipation.” So it sounds like it was already near that spectrum. To me, the thing that got things really moving was the prebiotic more than the IgG.

Kiran:                                    Yeah.

Michael Roesslein:          But your answer, I think, speaks to that. We just got a couple more. Won’t the prebiotic feed yeast?

Kiran:                                    No. Yeast have no capability of breaking down these oligosaccharides. They’re not able to do that. Yeasts do really well with sugars, with simple sugars, monosaccharides, disaccharides, they did not do well with complex oligosaccharides. These oligosaccharides are very complex carbohydrates. They’ve got lots of branches, unique carbon bonds, and they require very specialized enzymes in order to break them. That’s why we call them precision prebiotics, because most of the bacteria in your microbiome can’t break them down either they really are specialized towards certain groups of bacteria like [faecalim] bacteria. Like akkermansia. So some of those keystone strains, so they will not feed yeast.

Michael Roesslein:          Okay. I have a family member who avoids FODMAPs, can they take the MegaSpore? We’ve actually had… when MegaSpore, I’ll speak for Krian and let him answer. When MegaSpore first kicked off, the way so many people found Rebel Health Tribe and our webinars and the MegaSpore and all of that was because there’s all these groups on Facebook, like low FODMAPs and salicylate groups and histamine, low histamine groups, and SIBO groups, and all these various GI related illness groups. And people from those groups would try it and see that they no longer had the issue with FODMAPs or had the issue with salicylates or had the issue with whatever. And all it took was one person posting that. And then that entire group would be on our next webinar.

Kiran:                                    Yeah. Right.

Michael Roesslein:          And so FODMAPs is generally avoided due to suspecting SIBO, I guess, would be the word suspected SIBO. And also some other dysbiotic situations. But the spores definitely wouldn’t make that worse.

Kiran:                                    No, if anything they’d improve them. I mean, so one of the big issues with intolerance to FODMAPs is the inability to break down, digest carbohydrates more completely. So you don’t get the fermentation of them, which then produces the gas and the bloating and the sensations that you feel in the gut. And one of the roles at the spores plays, is improving the diversification of enzyme activity in the bowel. Exactly which enzyme activities we don’t know. That’s one of the studies that we’re doing where we’re trying to quantify the different types of enzymes that they produce. We know that they produce certain proteases. We know that they can produce certain cellulases. But in general, what we see is that there’s a help for those who have FODMAP intolerances. It doesn’t necessarily mean you’re going to take spores and then you can eat a big FODMAP meal and be fine. But in general, we see people having significant digestive improvement who were intolerant of FODMAPs to begin with. It’s certainly not going to make anything worse.

Michael Roesslein:          I can’t find MegaMucosa on your site. Do you have a link? I can post that in the chat. You said that the Prebiotic got things going. What did you mean? I have a patient with chronic diarrhea and small intestinal inflammation. I just mean that my digestion and elimination got awesome. And there were champion poop stories going around in our Facebook group for about three months when that product first came out, that were pretty graphic. And I don’t think, I wouldn’t worry if someone with chronic diarrhea could be really to do a dysbiosis that might actually be helped with the Prebiotic. And it’s not that it pushes you more towards diarrhea. It just, everybody just commented on how amazing their poops were.

Kiran:                                    Right. And again, that’s all because of the increase in short chain fatty acids, and organic acids that are produced in the large bowel and the protective keystone strains, all of which have an impact on bowel movement. If you have a patient with chronic diarrhea, then the best thing is the MegaIgG. I mean, that is a-

Michael Roesslein:          Yeah, that’s what it’s for.

Kiran:                                    That’s what it’s for. That’s what it’s designed for. That’s what the studies are based on. It does a lot of other things, but the root, the anchor for what it’s used for the medical community, and this is in gastroenterology offices and all that as a prescription product is for chronic diarrhea. But you’ll have to get them somewhere around four gram dose would be the key,

Michael Roesslein:          Which is eight of the capsules.

Kiran:                                    Wight of the capsules. Yep. You can do that either once a day or you could split it up and try to do split two grams, get two grams twice a day.

Michael Roesslein:          I have multiple myeloma. Has high IgG, is giving someone IgG then a problem? It doesn’t have a systemic effect like that.

Kiran:                                    Right.

Michael Roesslein:          It wouldn’t further raise their systemic IgG. Is the FOS and MegaPrebiotics different than the usual FOS or inulin that cannot be tolerated. It often tolerated so well when one has SIBO, according to the Wikipedia article, FOS can also feed pathogenic bacteria. I’ve seen most people with SIBO do okay on the prebiotic. I have seen some need to go really low and slow with it. Do you want to speak to that?

Kiran:                                    Yeah. The FOS is different. So, fructooligosaccharides is a big general category of oligosaccharides. It just means it’s an oligosaccharide derived from fruits from sugar containing fruits. And so fructooligosaccharides versus galactooligosaccharide versus, the xylooligosaccharides they are bigger. Terms that represent big categories of oligosaccharides. So not all fructooligosaccharides are the same. There are different FOS is with different structures and different functions. What we really like about this FOS, which comes from golden green kiwis, it comes from New Zealand and it has just an extensive amount of studies on its ability to specifically increase keystone strains in the large bowel. Which speaks to its specificity for those keystone trains in the large bowel.

That’s why we started working with this particular fructooligosaccharides. It really speaks to that specificity that it has. And that is different than the response you get from other fructooligosaccharides. Inulin has a bunch of tolerance issues, and inulin also has more of a sweet taste to it. So it’s got different structure to it, inulin can be used both as a sweetener and a prebiotic. These fructooligosaccharides have much different sweet perception to it because the structures are different. The sugars that make it up are different. So they have different functions in the body.

Michael Roesslein:          Okay. I think we have time for one more and then we’re going to hit the time limit to two hours. I think we’ve gone three hours once before, but we will..

Kiran:                                    Yeah. Oh, I’m surprised it’s even at two hours, wow. Time flies.

Michael Roesslein:          I’m trying to see, histamine intolerance. So there was a histamine group where we had a lot of people come back with just the MegaSpore. So in addition to MegaSpore and your IgG would love to know any suggestions we can do for histamine intolerance probably caused by antibiotics for eczema wounds that became infected with staph A, we have been using your IgG and MegaSpore for one year already. Thank you. Are there any other suggestions?

Kiran:                                    Yeah. I would go high dose of the HU58. That could make a measurable difference. That’s a standalone product, which is a strain that’s in MegaSpore obviously, but in MegaSpore, it’s at about a 2 billion dose per two caps. But in the HU58 product, it’s at 5 billion per cap. You actually could go two caps a day, if you wish and try that. That might be enough to make the difference for you.

Michael Roesslein:          And I’m just typing that out. The HU58’s a high dose bacillus subtilis, generally used for infections, overgrowths, things like that. It’s more of a powerful shot. In the shop. 10 billion CFU versus the 2 billion in the MegaSpore.

Kiran:                                    Yeah.

Michael Roesslein:          Cool. I just typed it there, for someone said high dose of what for his… It’s possible that would be helpful at we can’t make blanket diagnosis and prescriptions and things like that. I cannot have dairy. Why does the MegaPrebiotics have dairy and what can I do instead?

Kiran:                                    Yeah. So it doesn’t have dairy in it. It has the galactooligosaccharides, which comes from dairy. But remember dairy that the thing that causes intolerance with people and dairy are the proteins in the dairy, right? Those, the caseins and so on. There’s none of that in the product. These are the carbohydrates oligosaccharides that are purified from that source. So there isn’t any dairy in the product. Now because of allergen labeling laws. If a product derived from a potential allergen source, you have to put that warning on the label. So people often misinterpret that there’s actual dairy in the product. So there isn’t, if you are anaphylactic to dairy we say, okay, stay away from it. You just don’t know how you’re going to respond and it’s too risky. But if you are dairy intolerant, you should not have any issues with it then.

Michael Roesslein:          We haven’t had a single person that has dairy issues complain. Mira’s got dairy issues. It’s dairy free entirely and she drinks it every day and we’ve never had an issue. I get congested when I eat dairy, even though cheese is my favorite food group.

Kiran:                                    Yes.

Michael Roesslein:          And every time I eat it, I end up like walking away all congested. And it’s never done that before. The link is right above there, it’ll also be in the email. Like I said, the code is ML5OFF. It’s five bucks off per product added to the cart. That is probably the biggest sale that we’ve ever done. So I wanted to celebrate this. We also in the blog, for people who don’t know, we have fully comprehensive posts on almost every one of the products. We don’t think we have them all yet, but most of them, if you go to and go to the blog, there are at least four or five posts. As you scroll through the blog articles that are fully comprehensive, detailed posts on each product. The research behind it, the ingredients, the best uses the contraindications, the using with other products, all of that stuff, it’s all there. So head to the blog, you’ll be able to find that. I think that’s all of the product questions. Terrible spring allergies allergies, for me personally, I would just go with that trio and possibly some MegaIgG.

And I think that is it for today. So I think, let me see. There’s one more message. Great job. Thank you. Awesome. Can I order more than one of HU58 and get percent off for each bottle? It will be $5 off per product. So per bottle of anything. So yes, that’s how it’s set up. Let me know if that doesn’t work. Because it’s the first time we’ve ever tried to set that up and it’s excluding products that are not Microbiome Labs. And backend coupon tech things don’t always go exactly how they’re supposed to. So let me know if something gets screwy and we’ll have somebody fix it for you, but it should work just with that. And we will get this recorded. There is no three months container of MegaSpore. It’s just a 60 capsule bottle.

Kiran:                                    Oh, we do have the big one now.

Michael Roesslein:          Oh.

Kiran:                                    The 90 day version of it. Yeah.

Michael Roesslein:          Well, geez. I didn’t know about that. So we will have to get some of those. Write that down.

Kiran:                                    Yeah. We launched it a couple of months ago and it’s become really popular now.

Michael Roesslein:          Get big MegaSpore. That’s the note I’m writing to myself here. And then I’m also going to turn in what you did at the end here with your slide and everything that you went into with words that weren’t on the slide. I’m going to watch this, use your slides, use your words. And I’m going to create a little PDF ebook.

Kiran:                                    Awesome.

Michael Roesslein:          That I’m going to send out to everybody with recommendations for optimizing the gut, immune, microbiome axis.

Kiran:                                    Love it.

Michael Roesslein:          And I’ll share that with you. You can put it wherever, if it’s up to your standards or you can look at it and say, “This thing sucks. You need to change it to this.” So let me know. Okay. So I’m going to put an email there. Send him an email with the issue you’re having with the tech stuff. I’ll reach out to him now and let him know that somebody is having that issue. We’ll try to get that fixed really quick. Thanks to everyone. So this will probably be up Friday afternoon, I just got to wait on the transcript. So it’ll probably be Friday. We’ll put the two parts together. So you’ll have three and a half hours of microbiome, gut immune craziness to dive into and I’ll create the PDF. I will not have that done by Friday. Please give me email of Doctor Danenberg. Doctor Al, I will have on a video very soon, but if you google Doctor Al Danenberg, he will come up. He will come up. He’s very well published on the internet. And let me see.

He might even still be on here. Doctor Al Danenberg. His website is He’s a nutritional periodontist. He’s a functional medicine dentist.

Kiran:                                    You should spell the Danenerg.

Michael Roesslein:          Yeah. D-A-N-E-N-B-E-R-G. The code is ML5OFF. All upper case. I don’t think it matters. So all one word ML5OFF it’ll all go out in an email. We’re going to run the sale through probably Saturday. So I’ll send it out on Friday and we’ll let everybody know. Kiran, thank you so much.

Kiran:                                    Of course.

Michael Roesslein:          That was a record for questions in one webinar, we did like 36 started with 32. We did 36 because about another 20 piled in as we were answering them. And I’ve got a small handful of them. I might send you in an email to try to [crosstalk 02:00:44].

Kiran:                                    Okay. That sounds good. And we of course did our tangents that we went on, which hopefully we were helpful for people, but this is always fun to be able to do this.

Michael Roesslein:          Yeah.

Kiran:                                    And thank you for everyone for hanging in there. Hanging with us.

Michael Roesslein:          We had very little drop off. The highest, it was… Yeah, it was, people started to drop off like 10 minutes ago. So most people met the two hours and stayed and hung out, which I’ve watched a lot of things about hosting the best webinars and doing the best webinars. Rule number one, never go over 60 minutes ever.

Kiran:                                    Right.

Michael Roesslein:          That’s what they say because no one will watch anything for more than 60 minutes. And rule number two is if you have Q and A, don’t put the Q and A on recordings ever, because it will incentivize the people to stay to the end of the webinar, if you don’t include the Q and A on the recordings so that they can get the Q and A, as an incentive teaser to get people to actually stay. We put everything on the recordings and just did a 90 minute standalone Q and A.

Kiran:                                    Right. Or two hours, right?

Michael Roesslein:          Two hours. Yeah. Screw the experts and…

Kiran:                                    So much do they know.

Michael Roesslein:          Maybe we should be the webinar experts.

Kiran:                                    All about the content.

Michael Roesslein:          Thanks guys. Thanks everyone.

Kiran:                                    Thank you. Have a good night.

Michael Roesslein:          Yeah. All right, everyone have a good night. Thank you.

PART 4 OF 4 ENDS [02:02:03]


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