How Your Gut Health Controls Your Immune System with Kiran Krishnan and Tina Andersson

Content By: Ari Whitten

In this episode, I am speaking with Kiran Krishnan and Tina Anderson. Kiran is a research microbiologist and an expert on gut health, and Tina is the founder of Just Thrive Probiotics. We will touch upon an array of topics, including the link between gut health and the immune system. 

Tina has been super generous and offers a 15% discount on your first purchase of Just Thrive Probiotics. Use the code TEB upon checkout. 

Table of Contents

In this podcast, we discuss:

  • How your microbiome relates to your immunity (and how lack of diversity may set you up for illness)
  • How an overactive immune system may be a problem for many people – and why children don’t get sick from novel viruses even though they haven’t got well-developed immune systems yet.
  • Why do diabetes, cardiovascular disease, depression, hypertension, and obesity reduce CV19 survival rates so massively? (The answer may surprise you!)
  • What are the biggest triggers for down-regulating our essential bacterial diversity and immunity – and how can they be avoided?
  • How a climate of media-driven fear may heighten the risk of serious health outcomes
  • Why you must use a high-quality spore-based probiotic supplement – and which supplements defeat leaky gut
  • The top tips to optimize the gut-immune axis

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Ari Whitten: Hey, this is Ari. Welcome back to the show. In this episode, I’m speaking with research microbiologist gut and microbiome experts, Kiran Krishnan, and the founder of Just Thrive Probiotics, Tina Anderson. We’re going to do an update on the COVID situation and talk about a lot of the latest research around the gut immune access and how your gut health influences your immune health.

There’s a lot of fascinating stuff in this episode and I hope you enjoy it. Welcome back, Tina and Kiran, such a pleasure to have you guys back.

Kiran Krishnan: All right, great to be with you. [crosstalk]

Tina Anderson: Nice to be back.

The relationship between the gut microbiome and immune function

Ari: Now that we’re a year and a half into this whole COVID thing, I thought it’d be a good time to do an update on the relationship of the microbiome to immune function. Especially now, as we were just talking about before, starting to record there’s been a number of studies that have come out on that relationship.

Let’s jump into, I guess, starting more broad with the relationship of the microbiome to immune function. Explain that to people what’s going on there.

Kiran: Yes, to really think about it, I think one of the things we want to establish is that the microbiome and the immune system are really one and the same. They’re just different components of the same ecological system. There are a couple of things that are important to keep in mind. Number one, that the microbiome acts as the eyes and ears of the immune system.

Number two, that the microbiome provides the thresholds signaling for the immune system to allow the immune system to understand when to react and when not to react. The microbiome is refereeing the immune system. Another thing to keep in mind is that the immune system is one of the only components of the body that is continuously adapting to the environment.

As your environment changes, your immune function, your immune capabilities, restrictions, actions, all of that change. If you leave the US and you go to Costa Rica, for example, for six months, your immune system’s going to change during that time. When you come back, it’s going to change to adapt to the environment around you because the job of the immune system is to protect the host, and the dangers to the host change based on the environment.

That conduit, that translation of what’s in the environment and what does the immune system need to protect the host from, all of that messaging comes from the microbiome. The microbiome are acting as the eyes and the ears, the microbiome is translating the outside world to the immune system, because the immune system is not in the forefront.

The immune system is not on the outside dictating what’s happening in the environment. The immune system gets translational messages from the microbes that are at the outside. It’s really quite intimate. The two claims that I tend to make with regards to the microbiome and the immune system, claim number one, is that the microbiome are the eyes and ears of the immune system.

The immune system will be blind and deaf, if you will, without the microbiome. Number two, the immune system to a certain degree would cease to function completely without the microbiome. There’s evidence of both of those, and we can unpack each of those two claims a little bit more.

Ari: Yes, let’s do that. Let’s start with claim number one. What does that mean to talk about the microbiome as the eyes and ears of the immune system?

Kiran: That is so interesting. In fact, through the course of the pandemic, some of this even became more relevant. In fact, the research papers that were coming out as all of this craziness was starting that really helped illuminate how the immune system functions to a certain degree. Let’s take the example of an influenza virus. If you get exposed to an influenza virus, you breathe in the virus.

The first thing the virus is going to do is start infecting your airway epithelial cells, your lung cells, if you will. The first organisms, the first components to detect the presence of the virus in the lungs or in the airways, anywhere in the airways, are the microbes that live there. The microbes that live there are the first things to realize that there is a disruption to that little ecosystem, assuming you have the right healthy commensal microbes in that space.

Now, if you have the right healthy commensal microbes, they’re the first to realize that disruption to that ecosystem. What those microbes will do, and this is a really fascinating part, is they will send a signal to the microbes in the gut. Alerting the gut microbes that, hey, there’s something going on in the lungs. Can you send the immune system over? Then the microbe– [crosstalk]

Ari: The microbes in the upper airways can communicate with the microbes in the gut?

Kiran: That’s exactly right, yes. This gut lung access is an amazing mystery in many ways. The question is how is it that the microbes in the lungs send a message to the microbes in the gut? We’re not exactly sure, but they do. That evidence is there. Then the microbes in the gut which manages most of the immune tissue, 70% to 80% of the immune tissue, then recruits the immune cells to make their way into the lungs to function.

Why this system is important? I think some numbers will come into play here. When you look at the surface area of everything that the immune system has to monitor, it’s a massive surface area. The inside of our body, every aspect of the inside of the body’s covered by a mucosal layer. The biggest mucosal layer most of us are familiar with is in our digestive tract.

Every inch of that 20 something odd feet of digestive tract is covered with the mucosa, but every other part of the inside of our body is also covered with the mucosa. The respiratory tract, the urogenital tract, everything, even if something penetrates through your skin and enters into a mucosal surface. There’s about 4,000 square feet of mucosal surface inside the body. That’s a massive amount of surface area all folded in.

Now, when you look at the number of microbes in that mucosal surface, you have over 40 trillion microbes in there. At the same time, you only have about 200 million immune cells that are serving that entire area. It’s a 200,000 to one ratio of microbes to immune cells in any given area of the mucosa.

It becomes really physically impossible for the immune system to constantly monitor every square millimeter of surface area where a microbe might enter and cause an infection. We’ve adapted to this idea that the microbes that are much more abundant in that surface that mucosal surface are the ones that are actually looking out for ecological disruptions, and then will signal to the immune system when it recognizes something dysfunctional.

Almost any way you get an infection in your body, the first things that recognize that disruption are the microbes in that local area, and they’ll start shooting out flares and signals to try to attract the immune system to that area. Once they attract the immune system, then the process of immunological response goes on.

If there is a disruption in, A, the ability of the microbes to detect the presence of a foreign pathogen, or B, the ability of the microbes to signal to the immune system, we start seeing a significant amount of dysfunction.

Ari: Let’s talk about individual differences in how that might take place. Maybe as a point of contact to help illustrate the point, maybe I’ll throw in there– I’m sure you’re familiar with this. There’s some research, at least for some end points of various health outcomes, in animal experiments in rodents where they’ve used antibiotics or bred mice or rats to create an entirely sterile microbiome. There are no microbes there.

I know that there are some people even, for example, the controversial nutrition researcher named Ray Peat, who has argued in some of his articles that it’s actually a good thing to have an entirely sterile gut, to essentially not have a microbiome. Using that as a point of contact and understanding also that there are people who have a microbiome but may not have the optimal mix of different microbes.

How would you explain how that process that you’re talking about this relationship with the microbiome to the immune function, how it differs between someone with an optimal microbiome versus a sterile microbiome versus a certain non-optimal microbiome?

Kiran: Excellent question. One of the ways to think about it is let’s say you’ve got a compromised microbiome, which means you have low diversity. You tend to have higher levels of opportunistic organisms as an example. The nature of opportunistic organisms is they’re looking for the right opportunity to start expressing their virulence factors. A great opportunity for them to do that is in times of chaos and turmoil.

If there’s an outside infectious agent that comes in, that starts infecting the host cells and creating damage and tissue issues, then at some point immune activation towards that area, it’s a great opportunity for those opportunistic organisms to use that as an advantage for them to express their own virulence factors. It’s not in their best interests to bring in the immune system to quench the infection.

The analogy I gave is that if you lived in a building with lots of criminals in there, and then something funny is happening in the front of the building, the criminals aren’t going to be watching out and calling the police because they don’t want the attention of the police in the area at all. That’s how a dysbiotic microbiome functions.

You have less players within that microbiome that want to recruit the immune system to the area of action because they don’t want the attention from the immune system. In fact, they’re looking for chaos and they’re looking for imbalance for them to wear their own virulence factors. Versus a healthy diverse microbiome, there are enough players there. There are enough good citizens in that building to go “Hey, this looks weird. I’m calling the cops.”

That’s the function of the good commensal bacteria within the microbiome. You’ve got a much better chance in early detection of the pathogen and then more effective recruitment of the immune system to that area. Then there’s this other issue of loss signaling, which we can get into a little bit, but this builds on that concept as well. Then if you have no microbiome, if you go to that other end, and there’s clear studies on gnotobiotic mice.

The type of mice you’re talking about are called gnotobiotic mice. This was actually a good combination of papers that was started about 2002. Then a number of papers published to a more definitive information in 2020, where they showed that it’s the microbiome that provides a signaling to the early innate immune actors, like dendritic cells, to activate dendritic cells to even respond.

What they showed is that you can take a gnotobiotic mouse that has all the immune tissue, all the immune capability, every gland, every T cell, B cell, dendritic cell, macrophage, everything’s there. Then you infect that cell with the virus. That animal with the virus and the dendritic cells and the macrophages standby and watch. Watch the cells get infected and the animal finally die and don’t respond.

Versus then you implant a microbiome into those same mice, all of a sudden there’s a threshold signal given by the microbiome that, “Hey, there’s an infection going on. Activate dendritic cell.” Then all of a sudden you see the dendritic cells activating. The reason why this is important because it has to also make sense.

Biologically, ecologically, is that as big of a problem as it is if we have a non-functioning immune system, it is equally big if we have an over-functioning immune system. There has to be an activation threshold. It is up to this point that the immune system goes, “Nah, I’m tolerant of this. This is fine.” Then when we cross a certain threshold, the immune system has to go, “Okay, this is too much. We need to respond to this and take control.”

As it turns out, that activation threshold is in many ways dictated by the microbes that are in the system. It’s the microbes that are supposed to tell the immune system that this is not homeostatic. This is not the right balance, come and deal with this. That activation signal to the dendritic cells and macrophages come from the microbiome. If you had no microbiome, you wouldn’t get those signals, and your immune system would rarely respond to the presence of a pathogen.

How an overactive immune system responds to COVID

Ari: Got it. Let’s go more into that, that topic you just mentioned about an overactive immune system. I think for some people, that might be a counterintuitive thought. We either have an immune system that’s not strong or we have an immune system that’s strong, but immune system that’s too strong seems like a weird idea. Wouldn’t you want the strongest possible immune system to fight off, let’s say, COVID for example?

In your response to that, maybe it might be worth addressing what does the immune response look like in, let’s say, a young healthy child versus an old person who maybe has diabetes and heart diseases and metabolic syndrome and is in otherwise poor metabolic health. Which one of those two has a strong immune system?

Kiran: Yes. It’s a really great question actually, because people do think of this as a linear thing like, oh, my immune system knows how to ramp up and it’s super strong and it’s going to deal with everything. Then that same overreaction is also is that strength or not strength, how is that– Right, confusing.

I think the thing that’s really important for people to note is that there are many different versions of immune response that have to happen in order for us to have a proper handling of the pathogen. COVID was a great example of that where most of the people, especially early on during the pandemic that were ending up in the hospital with respiratory distress and even dying, were doing so because of the- or too much immune response to the whole presence of the virus and so on.

It was the immune system damaging the host more so than anything else. What is happening there? One of the analogies I like to give to help people understand how this immune system response works is if we imagine our body as a home and there’s hundreds of windows all over the home that where things, bugs can fly into the home.

We have two groups of people that are responsible for controlling the bugs that are flying into the windows. The first group is the innate immune responders, and the second group are the adaptive immune responders. The innate immune responders have really big powerful tools but they’re very non-specific. Then the adaptive immune responses are highly adapted to single bugs that may enter into the windows.

Then the other part of it that’s really important to note is the innate immune responders are much faster. They run faster, they go up the stairs faster, they find the problem faster. They get to the problem first. If there’s some corner of the house where a window is open and a bunch of bugs are flying in, those innate immune responses are going to get there first. The problem is, they have a blowtorch to kill those mosquitoes and bugs.

They’re going to turn on the blowtorch. It’s going to kill the mosquitoes, and is also going to burn the wall behind it. Now, that can work for a few minutes. In our case, it’s a couple of days in the human actual system, but that works for a few minutes to control the flow of bugs coming in and the level of bugs.

If that blowtorch is on constantly, it’s going to eventually burn the house down. That shift from going from that blowtorch innate immune response to the highly adaptive guy that specializes in that particular type of bug who can very easily nip that bug out of the air one at a time without damaging anything else, that shift is really a critical part of a robust immune response.

Being able to get the innate immune respondents there fast, start controlling the scenario, but then shift from innate to adaptive, so that we’re going from this blowtorch non-specific response to a highly specific response that typically becomes asymptomatic. That’s the key.

The adaptive immune system

Ari: Let me overlay that with something else that seems on the surface at least to be contradictory to that. Which is my understanding is that in young children, especially the youngest children, babies and maybe toddlers, they have a very strong, robust, innate immune system, but not a developed adaptive immune system.

Whereas in contrast, older people, let’s say above 70, have a weaker innate immune system and a stronger adaptive immune system, relatively speaking. They’re more adaptive dominant than innate dominant. Given what you just said, how would you overlay that layer of information on that?

Kiran: Sure. What it means when we’re referring to having a strong adaptive or weak adaptive, it’s not necessarily the functionality of those immune systems, it’s the library. A young child has not been exposed to tons of things yet over the years, they may not have lots of B cells that produce lots of different antibodies against many different targets.

Their library of adaptive responders is much smaller. Because of that, it’s up to the innate immune response to really get there quick and start taking care of problems before they can actually differentiate B cells, naive B cells, into plasma cells that eventually make those antibodies for the rest of their life, hopefully. That’s really what it means. It means that they tend to be innate dominant because that’s the fast working part of the immune system.

That takes them longer to move to the adaptive because they don’t have ready to go program T cells and B cells that have seen that problem already. They have to differentiate those cells, make them specialize to that target, and then eventually that adaptive response gets there and controls it. Now, they have memories for the next time they encounter it.

For the adult population, we have an innate immune response, but we have a huge library of adaptive responders. More often than not, the place that adults and older people get caught is that transition between the innate to adaptive response. The innate goes on for too long, and the adaptive system takes longer to respond, even though they have a vast library of it, which means that the innate system goes on long enough to create enough damage into the system. Now, all in all, in there the microbiome plays a role. In order for the innate system to respond fast and quick, the microbiome has to be providing signals for the innate system to get to that area.

In order for the transition to happen from the innate to the adaptive, the microbiome has to be there to provide signals. Here’s another critical part. Towards that late phase of the innate response, there has to be this anti-inflammatory signaling that occurs as well to start bringing down the inflammation, which is the primary tool of the innate immune responders.

That allows kids to have low levels of symptomatic response, and yet bring in the adaptive once the innate system is managing the infection. In adults, because we have disrupted microbiomes and we have years of toxicity and all this stuff going on in our system, that anti-inflammatory response may not be as robust, so our innate response is much more symptomatic generally than it is in kids. Does that make sense?

Ari: Yes, it does. That explains why young kids and babies, despite not having much of a library in their adaptive immune system, are overwhelmingly resistant to COVID. COVID is not a particularly deadly thing for children.

Kiran: Yes, absolutely. Then if you think about, in the case of COVID especially, because the target of the virus is the ACE2 receptor, that is another really important aspect because kids tend to be expressing less ACE2 receptors because they have less chronic, low-grade inflammation, and all the damage that we’ve done to ourselves right over the years.

We are constantly expressing viral targets for the virus. It’s much easier for the virus to bind, find targets, get into the cell, try to multiply and so on.

ACE2 and how it relates to COVID

Ari: Got it. Now, I know that the thinking around ACE2 has evolved somewhat since the beginning of this pandemic, where it was first being talked about. Can you describe the latest knowledge around the role of ACE2? I know you just alluded to some of it there, but what is the role, what is ACE2, and what’s the role of it as far as in COVID?

Kiran: Yes, so the ACE2 receptor is really a receptor that’s expressed on the vast majority of tissues in our body. It is a receptor that signals repair. It’s actually a good thing in a person because if you’ve got inflammatory damage, for example, to the inner endothelium of your vessels, the lining of your vessels or the gut lining, for example, there’s damage there.

As the repair is going on, your cells are going to start expressing this ACE2 receptor to differentiate this biochemical process to go into this repair phase rather than this inflammatory damage phase. ACE2 is good. It’s a good thing to have and it’s a good thing to express. This virus has evolved to take advantage of the presence of the ACE2 receptor, which signals a host that’s undergone lots of damage.

That’s how we are as adults. We live in a toxigenic world, we do toxic things to ourselves, and that causes lots of ACE2 receptors being expressed. That in the beginning was a primary viral target. The spike protein bound to the ACE2 receptor quite well, that became a site of viral docking, if you will.

Now there’s other ways for the virus to enter as well. There’s some evidence that the virus can actually use LPs, lipopolysaccharides, which is a big factor in leaky gut, so you have lots of lipopolysaccharides floating around in your system. The virus can actually bind lipopolysaccharides and get escorted into a cell that way as well. Again, that’s another feature of just having a dysfunctional gut high levels of inflammation and leaky gut.

That’s really still the general thinking around the ACE2 receptor, and that binding is quite complex. The spike protein binding the ACE2 receptor I think has somewhere around 300 different reactions that have to take place for it to actually dock properly and then utilize that receptor to enter the cell.

Ari: Got it. As far as on a practical side of this– Maybe before we get there, maybe you want do some overarching summary of everything you just went over, talking about this gut immune link, and then I want to move into the practical side of what we can do to optimize our gut functions to optimize our immune function?

Kiran: Yes. The overarching story here is that it’s pretty clear that you have to have a diverse, healthy microbiome, with high levels of keystone species, in order for your immune system to function optimally. One of the things I keep telling people is as good as all of the micronutrients are that we know about, the vitamin Cs, vitamin Ds, magnesium, zinc, all these things to support their immune system, you can’t take enough of that stuff to overcome the immune dysfunction related to a dysfunctional microbiome.

If a microbiome is dysfunctional, that becomes a fundamental issue in how the immune system responds to things. A big part of your immune support regimen and thinking should be around focusing on your microbiome as well. Keep in mind, even through this pandemic and COVID, there’s at least four published studies on looking at the microbiome dysfunctions among people that had high rates of hospitalization and even mortality.

What they showed very clearly in those studies was that people who had low diversity, low levels of keystone species, [unintelligible 00:26:14] bacteria [unintelligible 00:26:15] and so on. When they had low levels of those keystone organisms, low diversity, their risk for hospitalization and death went way up.

Then another link to that is, one of the things we also early on during the pandemic, people with certain chronic underlying conditions had a much higher rate of mortality than people that didn’t. The main ones are diabetes, cardiovascular disease, hypertension, obesity. Those are some of the key things where now the mortality rates are 10 times higher.

It’s not 50%, 80%, it’s a tenfold higher in some of those conditions. Then the big question is why? What is it about diabetes or hypertension that compromises the immune system so much? [crosstalk]

The consequences of a poor gut microbiome

Ari: Kiran, if you don’t mind, I’ll just interject one little [unintelligible 00:27:06] point from a CDC report that just came out a few weeks ago, which is that they said 95% of hospitalizations from COVID are in people that had at least one of those comorbidities. Primarily the ones you just mentioned that are essentially diseases of nutrition, lifestyle. Also anxiety disorders were high up there in the risk factors as well.

I just wanted to insert that just to emphasize how enormous of contributor it is to your risk of COVID to have one of those conditions that you just described.

Kiran: Yes, and here’s the thing. The big question is why? Why is it that anxiety or depression or cardiovascular disease or diabetes impacts immune response that much? The shared underlying mechanism there is all of those are conditions of chronic low-grade inflammation. All of those conditions are driven by intestinal permeability. That’s not even fringe science at all.

That’s research published by the American Diabetic Association, the NIH, and so on, showing that intestinal permeability and the resulting chronic low-grade inflammation are the biggest drivers of the risk of those conditions. People with those conditions inevitably have high levels of intestinal permeability and chronic low-grade inflammation.

Here’s another interesting connection there is one of the key markers to having elevated low-grade inflammation or elevated levels of low-grade inflammation, and also intestinal permeability is elevated interleukin-6. Interleukin-6 being a very quintessential inflammatory cytokine in the body.

If you measure someone with obesity, someone with diabetes, hypertension, any of those preexisting conditions, and intestinal permeability, they tend to have high levels of Interleukin-6.

In fact, high levels of Interleukin-6 activate the HPA access and reduce the expression of glucocorticoid receptors, making you much more susceptible to anxiety, depression, stress-induced cognitive dysfunction as well. All of these conditions are tied together by chronic low-grade inflammation elevated Interleukin-6.

There was a study called the Boston-Dublin study during COVID looking at what was one best predictable biomarkers for your response to COVID that could predict your hospitalization or mortality rates. The one thing that they found that was predictive of how bad your response was going to be to COVID was elevated Interleukin-6 levels.

Individuals who had elevated Interleukin-6 at the start of the infection had a much worse response over time than those that did not. It’s all tied together to this lifestyle dysfunction that drives the underlying problem of dysbiosis, which is low diversity, low keystone species, which leads to intestinal permeability. That intestinal permeability sets up chronic low-grade inflammation.

Elevated interleukin-6, which gives you the risks for all those chronic conditions, and that’s the same molecular link as to why your immune system gets compromised as well. One note on why that chronic low-grade inflammation impacts the immune system so much. There’s this issue of loss signaling.

As I mentioned earlier, when you encounter a virus, or a bacteria, any infectious agent, the first responders to that, before the innate immune system can even get there, are the microbes in that area. The microbes in that area the first things to notice a disruption and start signaling to the immune system to get to that area and get activated, so that it can control the reproduction of the pathogen, so that the viral or the bacteria loads are low.

Now, the signal that the microbiome uses to attract the immune system are inflammatory markers, like interleukin-6, interferon, beta, TNF-alpha and so on. What’s happening here is if you imagine the human body as a neighborhood, imagine you had a neighborhood with 500 homes. One of those 500 homes was on fire, and there’s a small fire starting, but all of the 500 homes are ringing a fire alarm.

It’d be impossible for the firefighters to figure out which home is actually on fire if all of them are ringing fire alarms. By the time the firefighters even notice the actual home that’s on fire, the fire has to get big enough for them to see the smoke and so on. That’s exactly what’s happening in the body. Chronic low-grade inflammation to the immune system looks like fire alarms all over the body.

It becomes much easier for a virus or a bacteria that enters into the system to have more time to replicate and produce high numbers before the immune system ever notices them. The microbiome, if it’s healthy, may be there and signaling, but it takes forever for the immune system to respond because they’re responding to all the fires all throughout the body. That’s the big, big crux here.

Then the big question becomes how do we deal with that diversity issue in the microbiome, how do we deal with the leakiness in the gut, how do we increase those keystone species, and then ultimately, all of that will help with the intestinal permeability and that chronic fire alarms going off all throughout the body. Tina has wonderful, amazing practical applications for all of those things.

Tina: Yes. We see that all the time with the the spore-based probiotic that we carry, of course, goes in, reconditions the gut, it’s going in there. These strains have the ability to get to the intestines alive and attach to the cell wall. Like if you envision a garden, it was attached to the soil, and then it has the ability to feed the beneficial bacteria and actually get rid of some of the pathogenic bacteria in the gut.

We always say the spore-based probiotic acts as a gardener of the gut. Then, of course, we have the prebiotic, which is reinforcing all the great things that the probiotic is doing. The probiotic is actually increasing diversity. It’s doing all the great things that we just talked about. Then we have the prebiotic that’s actually further increasing the diversity in the gut microbiome.

Then we have the Gut 4-tify, which is what I always say– One of our customers said to us, “It’s like it took us past the goal line when I got on the Gut 4-tify.” We’ve done all these things, we’re getting the probiotic in there, we’re fixing up the gut. Then you’ve got the prebiotic that’s reinforcing everything, but that Gut 4-tify is actually going in and rebuilding that mucosal layer, which is so critical.

We have four amino acids in there that are actually rebuilding the mucosa. It is literally taking customers over that goal line. It’s helping people who have had conditions and gastrointestinal issues for years and years and years. They start to see improvement with the probiotic, but then when they get in and actually start repairing that gut mucosal layer, they are seeing drastic improvements in overall condition. It’s been really exciting.

Ari: Beautiful. Those supplements obviously are playing a key role in fixing a lot of the microbiome and gut disturbance that has occurred. Let’s jump just back just one step from that and let me ask the question. What is fundamentally causing those disturbances in the first place?

Understanding that taking the probiotics and the prebiotics are a very good idea to help repair those problems. Presumably, it’s also important to address the underlying root causes of those as well. Can you talk a bit about that as well?

Tina: Yes. Unfortunately, the world we live in is so antibacterial. I mean, everything from hand sanitizer to household cleaning products. Some of the biggest offenders probably are glyphosate, the active ingredient, Roundup, that’s sprayed all over our food supply, and then antibiotic use is really detrimental to us. Again, it’s not just the antibiotics that we take, but it’s the antibiotics that are found in our food supply, the toxins in our environment.

The household cleaning products is interesting. There was a study that came out that showed that households that use cleaning products that kill off 99.99% of the bacteria actually have children with a higher incidence of asthma and allergies and other autoimmune type of issues because they’re not getting the bacteria that they need. We have to remember that bacteria is our friend.

I mean, most of our bacteria is very, very beneficial to us, and we shouldn’t be trying to kill it all off. We live in this very antibacterial world, and yet we are 10 times more bacteria than we are human. It’s really important to avoid the glyphosate, try to eat clean, avoiding foods with antibiotics or even a single course of antibiotics could wreak havoc on your gut for a year. Stress is another big offender.

People don’t always see it that way but stress really does. There’s the vagus nerve connecting the brainstem and the digestive tract. We send signals back and forth to each other, to the gut and the brain all the time. When we are calm, it sends those signals to our gut, and the reverse is true.

The gut is dysbiotic and unsettled, it’s sending signals back up to the brain, and so you start seeing anxiety. Unfortunately, like I said, the world we live in is very, very offensive to our gut health.

Kiran: Then unfortunate side effect of the pandemic, of course, is lack of interaction between people. That’s one key way in which we share microbes and an increase the robustness of our microbiome, and thereby support the immune system. Of course, the over-sterilization of things, that has a huge impact on it. Then the lack of diversity in our food also.

Our intake of diverse food items, the lack of that intake reduces our diversity in the microbiome quite a bit. We have endless things in our environment. The fluoride in our drinking water, the chlorine in our drinking water. As Tina mentioned, stress is a critical thing because a 2015 publication in Frontiers of Immunology was a meta-analysis on the biggest drivers of loss of diversity and leakiness in the gut and then translocation of toxins and so on.

What they concluded was stress-induced dysbiosis and intestinal permeability was the biggest driver of morbidity and mortality worldwide in the developed nations. The problem with that is its self-perpetuating loop, because as external stressors impact your microbiome by activating the HPA axis and then releasing cortisol. Cortisol has an effect on creating intestinal permeability.

Then the presence of cortisol in circulation also act as a signal for opportunistic organisms to start thriving and turning on their virulence factors. Continuous bouts of stress will actually change your microbiome over time and make your intestines more permeable. The problem with that is as your intestines become more permeable, it becomes easier and easier to get stressed by more things.

Our resistance and resilience against stress-induced inflammation goes down, so it becomes a self-perpetuating cycle. We have to arrest that at some point, get in there, intervene with improving diversity, improving keystone species, sealing up the lining of that gut, and stopping that inflow of toxins and all that increases inflammation.

Ari: Yes. I just want to link up what you were saying just now with two things I think it would be miss not to point out. One is what I was saying before that they found anxiety disorders, severe anxiety, to be a major risk factor for having severe COVID outcomes.

Counterintuitively, I think for many people is the fact that for the last 18 months, a lot of people have been living in tremendous fear. We have media that drive their own ratings and have their own financial incentives, very, very strong financial incentives to drive as much fear and negativity as possible and as much anxiety as possible because it increases their own- from a self interested perspective, it increases their own ratings and viewership and attention on people on their channel.

I think it might be worth pointing out just that there may be a connection there. I think for many people, there’s this intuition that the more we’re in fear, the more we are promoting fear and telling people to be concerned about this, the more we’re helping people be prepared. I think that there’s another side of that.

There’s obviously some truth to that, but obviously being in a state of constant fear and anxiety is creating that HPA axis over-activation chronic stimulation that you was describing. We already know that chronic stress, chronic anxiety, chronic fear states are linked with you’re more likely to have a bad outcome.

Kiran: For sure.

Ari: This may be one of, at least one, maybe the major one, physiological mechanism that is facilitating that process.

Kiran: Yes. The problem is that that chronic stress is a driver of all other conditions as well. Not only is it compromising your immune response should you encounter this infectious agent, but it’s also driving other chronic illnesses, heart disease, dementia, all of these things. The anxiety related to the fear activates the sympathetic nervous system that drives not only inflammatory responses systemically as we think about, but also in the brain, it activates microglial cells in the brain and activates inflammatory cytokines in the brain.

It’s really quite detrimental. I think that whole delineation between being scared versus being informed is so important. There are things we should be concerned about, but we should be informed and we should know what tools we have at our disposal and all of that is so important for us to really navigate through the concern and be prepared in some form or the other. I think that to me is a huge aspect of it.

Ari: I will just to digress for a moment longer on that point. There was a poll that was just done where they showed about 70% of the American public thinks that the hospitalization rate from COVID is over 50% of people who get infected.

Kiran: Wow.

Ari: The actual hospitalization rate is between 5%. We have literally, this is how bad- how far we’ve deviated from being informed about the facts to being in a state of radical, wildly overestimating the actual risks into an Ebola-like illness. Where people are literally overestimating the risk of severe outcomes of hospitalization by 2,500% to 5,000% above what the actual statistics are.

70% of the population is in that state. This is a really big problem, and I would argue is truly in itself a major contributor to severe COVID outcomes to have that much of the population who was overestimating their risks that severely.

Kiran: With that in mind, when we think about- one of the reasons I was very excited to have this conversation with you, as we think about the immune system and immune health and as it relates to the microbiome which is a major controlling component of the immune system. Not only then does the immune system become an important conversation in context that should you encounter this virus, you want to be able to handle it fine.

Then the other aspect of it is just having lived through the last 18 months. We know our microbiomes are now compromised just because of the fear, the stress, the lack of exposure, all of that stuff, which means that not only is our immune system compromised to dealing with this virus, but it’s dealing with everything else that’s out there that can harm us and compromise us. I think the timing of this is really relevant and it’s exciting to be able to talk about it.

Ari: Let’s do a summary of everything we talked about. The big picture, what’s leading to those gut dysfunctions and then what are the keys to fixing your gut health so that we can optimize our immune function?

Kiran: I can do it and then, Tina, jump in and please add in anything that I may forget. One of the inevitabilities of being in the modern world today is we’re constantly and chronically exposed to things that compromise our gut microbiome. Whether it’s things that we purposefully choose to expose ourselves to, like highly processed foods with antimicrobials and antifungals in it, or in a lots of drinking and social partying.

All of the things that we do to ourselves. Lack of sleep, poor stress management, all of these things, or things that are inevitably an exposure we’re going to encounter that are outside of our control, and that’s the pollutants in the air and the water and the soil and so on. There’s no doubt at all among any area of scientific research that our microbiome is constantly under attack and being compromised by the world we live in.

We constantly need something that’s reversing and helping rebalance the system. The way we look at it is the most important aspects, and I think this is well supported by the research, the most important aspects of addressing rebalance of the microbiome are addressing diversity and then the presence of the keystone species and then addressing the leakiness of the gut.

What Tina and team working together with me have been able to do is create these important tools that first address the microbes themselves. The dysfunctional microbes that just thrive the spore-based probiotics, which will go in there. We’ll use quorum sensing to read the microbial environment. It’ll bring down the growth of the overgrown and problematic bacteria. It’ll increase the growth of the beneficial bacteria.

At the same time, increasing the expression of tight junction proteins which make up the intestinal lining. They’re starting to fix the problem. Then when you add in the prebiotic, just throw in prebiotic, it enhances all of those effects of the probiotic by almost double or triple, two to three times. One of those key effects is a production of short chain fatty acids like butyrate.

Butyrate is a big healing component of the gut lining and diversification of the gut microbiome. When you add in the prebiotic, it increases butyrate by 150%. Then the Gut 4-tify are the building blocks of that mucosal lining because that’s the key thing that becomes damaged when you’ve got dysbiotic. We’ve got to rebuild that mucosal lining, it does so with the polyphenols and the amino acids that are in there.

Those tools are the tools that you can utilize to strategically repair the constant damage and constant dysfunction that’s going on within the gut microbiome. That, of course not only compromise your immune system, but compromises your endocrine system, your metabolic system, everything. Everything’s controlled by the microbiome.

Ari: Got it.

Tina: We didn’t really touch too much on the leaky gut study, but we have a double blind human clinical published leaky gut study that was used. They use the spore based probiotics strains that are used in Just Thrive. Really important that– We actually have a study that showed that it decreased the LPs toxins from seeping into the bloodstream by 42%. This was just over 30 days. [crosstalk]

Ari: Which is an indication you’re decreasing leaky gut.

Kiran: Yes. It’s the best indication. It’s a most well-published model for reducing leaky gut is to reducing endotoxemia, which is a translocation of that toxin from the lumen of the gut into circulation. The presence of that toxin in circulation is the most compounding factor on disease risk. Being able to stop that is really significant in terms of supporting a healthy system.

Tina: Yes.

Ari: I saw an interesting study yesterday. Do you guys have a hard cutoff? Do you have to go right this second?

Kiran: I’m good for another five minutes.

Ari: Okay, let’s do it. I saw a study yesterday where they were talking about quercetin and luteolin. Luteolin and quercetin are very similar structures molecularly. There’s one part of it that is slightly different between the two. They specifically mentioned that while they’re extraordinarily similar, luteolin, but not quercetin, was able to block the increase in inflammation that’s associated with LPS leaking into the bloodstream.

Anyway, I just thought that was an interesting little link up to what you’re talking about of this particular phytochemical helping to block some of the pro-inflammatory effects of gut permeability.

Kiran: That’s super interesting. Then maybe because of the mechanism by which LPS increases inflammation, and that’s through activation of dendritic cells and macrophages and so on. We know quercetin helps with a lot of things like allergies and all that. Through a different mechanism, through a luteolin mechanism, so that’s really interesting. We know also definitively that LPS induced inflammation is very significant in chronic disease risk, because of the way it increases inflammation.

The fact that it increases cytokine not only interleukin-6 that we talked about earlier, but it increases something called interleukin 1 beta. The interleukin 1 beta is a real problem because that is one that’s expressed not only by immune cells, but also your own cells, like your endothelial cells.

When one endothelial cell sees the one next door expressing it, it also expresses it.

Studies are showing that interleukin 1 beta can increase the expression of somewhere around 200 or 300 other types of inflammatory markers. It becomes this real significant driver of inflammatory tsunamis in the body. In fact, in the world of pharmaceuticals and heart disease, that’s the number one target right now, because they show that elevated interleukin 1 beta is the biggest driver of inflammation in the arteries and the veins.

Companies are trying to develop interleukin 1 beta antagonists to stop that progression. Yes, that LPS signal inflammation is so significant. One of the super exciting things we saw in our leaky gut study was not only of course should we bring down LPS, but we significantly reduced interleukin 1 beta expression. That was really nice to see as well.

Tina: I think another finding in that study that’s worth mentioning is that when the subjects came back after 30 days, the treated group saw a 42% reduction in LPS levels, but the placebo group actually saw a 32% increase in LPS toxins. These are healthy college students. These are not people with underlying condition. It’s like that leaky faucet that’s just dripping and dripping and dripping.

Then one day, all of a sudden, it overflows. If somebody says, “Oh my gosh, I developed IBS, and I didn’t know. I was completely healthy for so long.” It’s that constant drippiness of the faucet that LPS are seeping into the bloodstream. The study that we did showed 55% of otherwise healthy college students had leaky gut. They estimate that over 80% of the adult population probably has a leaky gut, and they don’t really realize it.

Ari: Fascinating. My last question to you guys is for somebody listening to this who might be thinking, “Oh, yes, okay, you’ve got a probiotic, and you have a prebiotic.” What is unique about this compared to the thousand other prebiotics and probiotics that are on the market?

Tina: Yes, well, the probiotic is a spore-based probiotic, and it has the ability to survive the gastric system. The overwhelming majority of probiotics on the market simply don’t make that journey to the intestines alive. The very definition of a probiotic is to arrive alive in the intestines and confer a benefit onto the host.

The overwhelming majority of probiotics on the market just aren’t making that journey to the intestines alive. Where the spores get their 100% alive, we’ve studied this, we’ve tested it over and over again. When they’re there, they do something called quorum sensing, where they read the microbial environment. They’re doing something different in your intestines than they would do in my intestines. They are making a functional change.

We actually have a study that show that these strains, actually, after two weeks, about two and a half weeks, showed a 30% favorable shift in the gut. That’s a profound finding. I don’t know of any other probiotic that showed that type of shift in the microbiome. With the prebiotic, there’s actually a huge distinction with our prebiotic.

We call it the precision prebiotic because most prebiotics on the market have difficulties distinguishing between the beneficial and the pathogenic bacteria. Prebiotics, of course, are like the fertilizer of the garden. They’re feeding, they’re reinforcing all the good things that the probiotic are doing, but if you have a prebiotic that’s feeding the pathogenic bacteria, oftentimes they can make the problem worse.

In our case, with the precision prebiotic, they’re made up of oligosaccharides that are only targeting the beneficial bacteria. Really, really important that you choose your probiotic carefully because it could literally make the problem worse for people.

Ari: Wonderful. Kiran, do you want to say any final words?

Kiran: Yes. I think at the end of the day, two things to keep in mind when it comes to product choice. Number one, you want to make sure you’re choosing products that have some research behind it. You have an actual understanding of what the product may do inside your system, especially as it relates to the microbiome because any given probiotic, the cells within the probiotics themselves, they have limited functionality.

The way you really get a profound effect is their ability to influence the 40 trillion other organisms in the system. They may influence it in a good way or bad way, and you really don’t know what way it’s going to go unless you really study it in-depth. That’s an important paradigm for us that if we’re doing anything within the microbiome, we have to study and understand how these products impact the rest of the microbes in the microbiome.

That’s our big focus. Of course, we’ve published lots of papers over the last five, six years. I think we’ve published 10 or 11 papers already, and we’ve got 15 other studies going on right now. One more important message is the exciting thing about the age of the microbiome, which is what we’re living in, is that we’re coming to find out that we have a lot more control of our outcomes in our health and our destiny than we thought, than we previously thought.

We gave a lot of credence to our genetics prior to the microbiome. That certain many diseases were just a genetic mishap, “Oh, I’ve got the heart disease gene,” or, “Oh, I’ve got the Alzheimer’s gene or the diabetes gene,” and so it’s just bad luck. We knew that lifestyle factors had an impact, but now we know definitively that the vast majority of chronic illnesses can be governed and driven whether in a good way or a bad way by dysfunctional microbes in the microbiome or functional microbes in the microbiome.

You have a lot more control of your outcomes. There’s a lot more you can do to impact yours and your family’s health, and it’s all about the little choices you make. What you choose to eat, who you choose to be around, where you choose to bathe, what you choose to use on your body, and then of course, what supplements you choose as well.

We’re here as a company to help illuminate some of that research for people, provide people some simple solutions, and give you a little bit more power back into your hands for your own outcome and your own fate.

Ari: Wonderful. Well, thank you guys so much. I really appreciate your time. Thank you for sharing such great information and for making such great products. These and the microbiome labs products which are similar are the specific products that I personally take and recommend and I have my family and my kids taking. Thank you guys so much for the work you’re doing. I really appreciate the time, and I look forward to talking to you again soon.

Kiran: Thank you, Ari,

Tina: Yes, thank you, Ari. The other thing I just want to tell you is that we have a coupon code, too. TEB, if you go to, we have the TEB coupon code for 15% off.

Ari: Wonderful, and that TEB, for people listening, stands for The Energy Blueprint. Yes, thank you so much, Tina, for doing that for the discount for my audience. I really appreciate it.

Tina: Yes, you bet. Thank you, Ari. I love your platform.

Ari: Thank you. I appreciate it. Talk to you guys soon. Hopefully, we won’t have to do any more COVID updates and we can be done about that.

Kiran: [laughs] Exactly.

Tina: That’ll be nice.

Ari: Talk about something else.

Tina: Yes, that’ll be great.

Kiran: Fantastic.

Ari: Take care, guys.

Kiran: Thank you.

Tina: Take care.

Show Notes

The relationship between the gut microbiome and immune function (00:45)
How an overactive immune system responds to COVID (13:30)
The adaptive immune system (17:35)
ACE2 and how it relates to COVID (22:10)
The consequences of a poor gut microbiome (27:00)

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