How a Probiotic Strain Calms Your Body & Brain Stress – Kiran Krishnan, Ph.D. : 927

You're listening to the Human Upgrade with Dave Asprey, formerly Bulletproof Radio. You're listening to the Human Upgrade with Dave Asprey. I promised that this year I'm going to tell you exactly what you're going to get in a podcast so that you know that it's worth your time to listen to it. Today we are going to talk about psychobiotics. And as you know, I'm kind of a fan of probiotics and I'm an investor and advisor to companies who are quantifying the human biome in new ways. And what we've learned over the past 20 years is that it's not just having a healthy gut, it's that there are specific species in your gut that make specific compounds if they get the right foods. And this has given us the ability to now say, I'm going to choose the strains in my gut. I'm going to create an environment where they will survive and then I can have onboard manufacturing that's different than what my mitochondria does, different than what I do in my endocrine system. And that you can get profound anti aging benefits or what we're going to learn about today is the cognitive benefits and the brain modifying benefits of certain species of gut bacteria. So if you want to cut your stress, have less anxiety and better moods, this is the episode for you, especially if you're interested in how the gut works with that. So welcome to the episode. Our guest today is a research microbiologist named Kiran Krishnan. He's a PhD and he's looking exactly at psychobiotics. Kiran studies something called gut commensal spore bacteria microbiology. And, and he is partnered with a company called Just Thrive, who's been on the show before, and he's been on the show before to talk about the latest stuff going on with gut bacteria. And the last time we talked about inflammation and immune function. This time we're talking about the gut brain axis and specific things you can do to hack it. So Kieran, welcome back.

Dave, thank you for having me. It's awesome to be back and exciting to have the collective in audience as well.

It's, it's really fun because they're getting some extra time, extra time to learn and they get to ask questions and a lot of times they're giving me a little, little reminders like hey, ask them about this. So I'm kind of crowdsourcing some of the questions I'm asking you. It's one of the many benefits of being a member of The Upgrade Collective. You can go to daveasprey.com and there's more info on how you can join. I also teach all of my books and things like that as small classes, so you can really go deep on biohacking. But our episode today is going to be available for everyone because it is part of a podcast with, at this point, about somewhere around 275 million downloads. So it's going to reach a lot of people. What I want to do is understand the new stuff that's happening with gut bacteria, because everyone knows, yeah, you should have a healthy gut. You should probably take some prebiotics, should probably take some probiotics. People don't really know which ones, but I want to laser in with you on what are the things that people don't know about that can change the brain. So what's new?

Yeah, you know, a couple of things and one really important message that I want to. I want people to really wrap their heads around and understand when we're talking about the gut brain axis.

What are the things that people don't know about that can change the brain? So what's new?

Yeah, you know, a couple of things and one really important message that I want to. I want people to really wrap their heads around and understand when we're talking about the gut brain axis is, of course, the gut. A healthy gut is incredibly supportive to the brain. It supports the brain in a number of really important critical functions, like recovery, for example, or production of serotonin and dopamine and all these important neurotransmitters. But on the other end of the spectrum, an unhealthy gut is not only not supportive, but it's arguably one of the most toxic things for the brain. Right. And that's not talked about as much when you talk about gut brain axis. So I want to make sure we cover both spectrums where we can talk about how the psychobiotics and new things in probiotics and the gut microbiome help the brain in a significant way. But then what happens if your gut is unhealthy? How is that actually toxic to the brain? And. And arguably the most toxic thing to the brain. So both of those things play in the same pod. So if you're, as someone listening and you're thinking to yourself, oh, my God, I have some digestive issues, I've got some IBS, like, symptoms, I've got loose bowels, I can't eat certain foods and all that, you've got gut dysfunctions. Right. And not only may that be affecting your mood and your ability to sleep, but it's actually acting in a toxic manner to your brain for a period over time and driving all kinds of long term neurodegenerative conditions. So what you may be experiencing now as indigestion and bloating and discomfort, and then the corresponding anxiousness, mood disorders, inability to sleep, are actually early symptoms of much more serious issues that are coming down the road. So such an important topic to be talking about and grateful to be here and do it.

So if you get bloating after meals or you have room clearing gas the way I did when my gut was really wrecked years ago, it means your brain's not working well or you're experiencing anxiety.

Exactly, yeah. And then if you're experiencing those things acutely, you also know that the same pathologies are in place that drive long term conditions like Alzheimer's, dementia and so on, even Parkinson's.

Parkinson's and Alzheimer's are tied to bad gut bacteria from years before.

Exactly. 100%. So whatever we're talking about today, not only is it applicable for how you feel and function at the moment, but as you improve those things, as you improve your gut brain connection, and you get your gut to be supportive of your brain, you're actually protecting your brain from long term damage that's occurring from a dysfunctional gut. And that's where psychobiotics come in. Right. So psychobiotics are incredibly powerful organisms that seem to have a natural capability of modulating brain function and very importantly, modulating stress response. And that's a new, exciting field because what we know is that stress response, normal innate stress response that everyone experiences, you know, the flight or fight, turn on the sympathetic nervous system, kick on the cortisol, increase. When we experience a stressor, that's all normal. But whether or not we can come down adequately from that stressor is the key. And psychobiotics and certain microbes within the gut make that determination.

Okay, so there's the baseline bacteria that we need to have for a healthy gut, and that removes some inflammation. But are there new species or is there new research about specific ones that will turn anxiety down? Or is it just, oh, I have less inflammation, therefore I have less anxiety?

No, there are new species. For example, one of the ones that we're working with, I think we've published now four or five studies on it, it's a keystone species. It's a Bifidobacterium longum. But what's unique about it is it has an exopolysaccharide Covering. And this exopolysaccharide is made up of a compound called peptidoglycan. And as it turns out, natural commensal bacteria that produce high levels of peptidoglycan are critically important, not only for balancing mood, reducing inflammation, but negating the negative effects that cortisol has in the gut. We could talk about what exactly happens when cortisol increases and ends up in the gut. And then it also has the capability of sending signals through the enteric nervous system, the nervous system that covers the gut, all the way up the vagus nerve to the brain to change brain chemistry and brain waves. We've studied and published on all of that. So these psychobiotics are amazing modulators of brain response to the environment around you.

Okay, that's making some sense. You've got five new studies that are showing the specific species and it's a subspecies. How do you pick that out? I actually don't understand this. So there's all kinds of bifida longums that are out there. I don't know how many in total, how many different species of them are there, or subspecies, whatever you want to.

Call it, I would venture to guess over 150, 200.

Got it. So how do you know which one to focus your research on?

Yeah, so we do a lot of screening, right. So what we do, the way this particular strain was actually discovered is we started taking in cohorts of individuals looking at individual stress response. So you initiate a stressor to them, you look at their stress response, you look at cortisol levels. And then we are also doing something similar with sleep response. And so we were starting to group people into individuals that had really good stress response, good sleep efficiency compared to age match, cohort that did not have good stress response and good sleep efficiency. Then we dive into the microbiomes and we start comparing those microbiomes and looking for real clear differences between those two groups. And that's one of the ways in which we found this organism. We started seeing in individuals that had really good stress response, good cortisol cycling, good sleep cycles actually had higher levels of this particular bifidal longum. And then as we and the people that didn't have the bifidal longum had much worse stress response. So then as we started digging into what is this longum, we discovered that this Bifidobacterium longum actually has this unique exopolysaccharide covering. So we said, okay, that's unique for bifidal longum in itself. Most of them don't have this covering. So let's take this strain, let's knock out the, the, the ability to produce the peptidoglycan, the covering, and then let's test it in animal models of anxiety, stress, and inflammation. And sure enough, when we knock out the peptidoglycan, we come to find out that it doesn't do the same thing. Then compare it to the one that does have the peptidoglycan. It does reduce stress, it reduces anxiety, it reduces inflammation. So that's kind of the long screening process of identifying normal commensal organisms that are really important and related to certain functions.

I want to talk about glycans for just a minute. There's a bunch of polysaccharides and polysaccharides, basically sugars stuck together that cover a lot of our immune cells. And researchers like your predecessors probably used to call that junk sugar. And like, oh, you gotta scrape that all off the cell to find out what's going on in there. And I've just learned throughout my entire life, anytime science calls something junk, that's shorthand for we don't know what it does, so we're gonna ignore it and pretend it doesn't matter instead of maintaining curiosity. It's actually a really dangerous bias. So to me, junk means, look here, look here. And there's a company probably 10 plus years ago, who was making a product as just a powder you could put in your coffee that contained a bunch of these polysaccharides for immune function. And they got shut down by one of the regulatory authorities because they're saying that can't be. But it turns out there really is another compound people may know about is ahcc, which comes from mushrooms and has beta glucose glucans, which are in the same family. Right. So what you found is a unique species of gut bacteria that makes these polysaccharides on the outside of it that most of them don't. And those polysaccharides have direct effect on gut quality.

Yeah, that's exactly right. And, and in fact, this species, and what's so interesting about it is it's equally important in utero, when your brain was originally developing. Right. So now there's a lot of research showing that that bacterial glycans are picked up by mom's immune cells. As you mentioned, immune cells have a lot of glycan receptors on them. So they pick up mom's glycans that her bacteria are producing, take it through the placenta into the baby's brain, and in the baby's brain, there are glycan receptors that bind these glycans, and then that is the stimulus for developing the brain itself. And we know that when mom's gut bacteria is compromised and they're less exposure to glycans through the gestation period, then the baby has the risk of underdeveloping the brain, and then you've got risk of things like spectrum disorders and so on. So for immune function and neurological development and all that, these glycans are critically important. And this particular peptidoglycan from the 1714 strain seems to be able to completely negate the inflammatory response that stress causes in the gut. And the leakiness in that stress causes in the gut.

That's kind of a huge claim, completely eliminates.

We saw huge reductions in them. So in both the animal models and the human models, because you need some inflammation, right? Inflammation is utilized as a way of creating perfusion during the flight or fight response. The body is trying to go, hey, I need to get blood to the brain, to the heart, to the muscles. No more blood in the digestive tract, or reduce the blood in the digestive tract, and then so that you're ready to fight or flee. And so you need some inflammation because that inflammation directs the blood to the right place, but you're supposed to be able to come down from it. What tends to happen in the modern day is we experience those stressors and we keep getting that inflammatory increase and that cortisol increase, but we don't have the method of coming down from it because our guts are messed up, right? So our gut is a checkpoint for going, okay, here's your flight or fight response. You're now safe. You can come down from it. The modern day, it goes, here's your flight or fight response. Oh, and we're going to keep triggering the HPA axis over and over again from a single stressor, right? So the entire day after that single stressor, that one person that cut you off in traffic on the way to work, you're now experiencing continuous cortisol cycling and upregulation. And the resulting inflammation, we can't come down from it. So.

Well, this reminds me of conversations that I've had for years trying to define what adaptogenic herbs do. And it's exactly what you talked about. When people are taking adaptogenic herbs, then it means that you can more quickly turn on your stress response, but as soon as you're done with it, you can turn it off all the way. And this is why I've been recommending them For a very long time. And taking them, they were pioneered by, by mostly China and Russia. Pioneered as in thousands of years ago. They would use them before a fight, in a war, before a battle, because like, oh, our soldiers are actually much better able to return to baseline and then they can fight again. And if you have multiple skirmishes, it actually makes a huge difference because you're not tweaked after. After the fight. Exactly. So when the rest of us take those, that's one way to do it. And it sounds like this new strain, for some reason, probably those polysaccharides on it, it actually has an adaptogenic effect because it allows you to return to baseline faster than you otherwise would.

That's exactly right.

For some reason, probably those polysaccharides on it, it actually has an adaptogenic effect because it allows you to return to baseline faster than you otherwise would.

That's exactly right. So what we did in some of our studies, what we do is we take individuals, these are healthy, normal individuals to begin with, and then we dose them up on the strain for 30 days versus a placebo. And then we induce stress in them experimentally. And as we induce stress in them, we're measuring the cortisol response and then their ability to recover from that cortisol response. And what we tend to find is that the cortisol peaks are lower in these individuals. So the perception of that stress is significantly lower. And I'll talk about why the perception of the stress changes as well. But then also the inflammatory cascading that occurs in response to the stress comes down much more dramatically in these individuals once they have enough of this organism in them. So it's absolutely correct where you can actually cycle up but then come down and actually recover from it. That's the fundamental difference between humans today and our ancestors that use the flight or fight response to survive. Right. It's such an important survival mechanism. The stress response is so critical for survival of our species. But they were able to flee away from the danger and then come down from it versus a modern human, you know, perceives danger most, most of it is not life threatening, but they perceive danger and then they can't come down from it. So that's a critical difference.

Okay, I love that. Now I'm already asking myself, so I take Just Thrive probiotics. Is this species in the ones that are the, the standard thing or is this a new.

So there's a, there's a new product called Just Calm. It's under a sub brand of Just Thrive Health called Jute and and one of the reasons why called jute J.

O O T so Jude Joo T and so if I go to just thrive, can I find it?

Totally, yeah. 100 it's called Just Calm. That's the idea behind it. And really it pairs amazingly well with the spores with the standard spore formula. And the reason for that is the spores, as we've talked about, dramatically reduces LPS lipopolysaccharides circulating in the body by slowing down the leakiness of the gut. LPS is one of those key triggers of inflammation in the brain and the central nervous system that drives anxiety, drives mood.

Let's talk about what LPS is because we're getting pretty nerdy here. But I know that listeners can handle this. So we talked about polysaccharides, sugars stuck together. Lipopolysaccharides are a fat stuck to sugars. And this is the bad stuff that happens in your gut. Even if your gut isn't leaky, some of it makes it through your liver, ideally detoxes some of it, but the rest of it goes through, crosses the blood brain barrier because of the lipo part of it and wreaks havoc in your brain. So a huge number of my anti aging and like the whole bulletproof diet thing is around managing LPS production and even things like activated charcoal binding to lipopolysaccharide, which we're going to call lps. So basically this is onboard highly, highly bad for the brain. Toxin made in the gut. And that polysaccharide thing I think is key because it's immune activating. And the polysaccharide that's in the new Just Calm formula you talked about, that's a good one, that's not stuck to a fat. So it works in the gut to protect the gut and stop the bad stuff, the LPS from crossing the barrier, which is really cool.

Yeah, absolutely. And it stops all the inflammatory cascading that the bad stuff the LPS causes not only in the brain, but the rest of the body as well. Right. And we know we mentioned Alzheimer's and Parkinson's earlier. There's good amount of research now showing that some of the initial insult to the central nervous system that leads to those kind of conditions is the overt presence of LPS in circulation. Right. So LPS is this because it's made in the gut, like you mentioned, it can continuously leak in, so it's continuous exposure to a pretty powerful toxin. And it's an endotoxin, meaning it's made within. So it's hard for us to get away from it. Right. All we can do is really try to reduce the amount of it being made and dramatically reduce the amount translocating into circulation. So the two products we know that the just thrive we've published on this, the original probiotic stops or slows down that LPs by about 60% in a 30 day period, which is magic.

Like that is a huge change.

Huge change. Right. And you feel that, right, because. Because we know that LPS creates all kinds of problems with throughout the body. And then here comes this other psychobiotic that not only helps reduce further the impact that LPS has, but more importantly, it actually stops what cortisol ends up doing in the gut. Right? And cortisol, when it cycles through the body in a stress response and dumps into the gut, and it's supposed to dump in the gut because there's a couple of things that happens to it in the gut that are important for the flight or fight response. In particular, cortisol gets metabolized by certain bacteria into byproducts that are sent to the kidneys and those byproducts change the mineral transportation in the kidneys. So you actually end up with more sodium in your, in your circulation to increase, increase blood pressure. Right. And in the fight or fight response, you want more blood pressure, you want more perfusion. But the other thing that cortisol does in the gut is it makes the gut leaky. And when the gut becomes leaky, you've got more LPs flowing through, you've got more inflammation, and you've got this critical compound that you and I talked about before, and I know you talk a lot about is Interleukin 6. Right. So IL6. IL6, right? Yeah, IL6. So IL6 scales up when cortisol levels go up and start dumping into the gut. The problem with IL6 in the stress response is IL6 has the ability to go into circulation and then re trigger the HPA axis, turning it back on, causing it to release even more cortisol. So a single external stressor that causes that cortisol release and that stress response can then become re triggering over the next several hours, if not days, if the gut continues to stay leaky. And the other thing that IL6 does that's especially egregious when it comes to stress response response is it reduces the expression of things called glucocorticoid receptors that are found all over the body, including the gut. These glucocorticoid receptors are Supposed to bind cortisol as it increases in circulation and then start sending negative feedback signals to tone down the sympathetic nervous system. Right. So that's the control mechanism for the stress response. The body goes, okay, you're stressed, you need to fight or flee cortisol shooting up to help you do that. But as cortisol gets to a certain level, it starts providing a negative feedback from itself by binding these receptors. But IL6, when it's up, it lowers the expression of those receptors, so there's fewer of them to actually provide the negative feedback.

It's really interesting. IL6 is one of those inflammatory signaling molecules that goes up when you have an infection. In fact, I got censored for a piece that I wrote about IL6 and how it goes up after a very popular viral infection and all of the many things you can do to lower your IL6 levels. Because I've dealt with chronic inflammation for most of my life. Partly 15 years of antibiotics will do that to your gut bacteria, but mold, exposure, lots of other things. So I know IL6 well because it's been stalking me for years. And this is fascinating that a probiotic can do this. I'm a little bit worried, though, because cortisol is not a bad thing.

Right.

In fact, many people don't know it, but they have low cortisol, whether it's because of adrenal dysfunction, genetic things, or other reasons. And I'd rather have high cortisol than low cortisol, because you can do stuff about high cortisol, but low cortisol you actually supplement with cortisol. And a lot of people with autoimmune conditions, that's exactly what's wrong, is they need more cortisol, not less. And I take cortisol as a bioidentical form. Is that. Is this going to eat my cortisol? Is it going to make me not have enough? Or is it going to work systemically, but it just takes it out of the gut where it's not helping.

Yeah. So this is. That's a really important distinction. I'm glad you brought that up, because this has no impact on your body's ability to make. Make cortisol at all. Right. Which is, of course, coming out of the adrenals. So you'll make all the cortisol you make. What it's doing is negating the negative effect that cortisol has on your gut microbiome. And cortisol in an unhealthy gut creates that intestinal permeability. In a healthy gut, it's perfectly fine. Right? It's exactly what we need. It does what it's supposed to do for the flight or fight response, to get you ready, awaken in the morning, and so on. So it's not gonna impact your cortisol's the ability to make cortisol. What it's doing is counteracting the negative effect of cortisol in an unhealthy gut.

Got it. It's gonna be game changing because people who have cortisol issues, whether it's high or low, their guts aren't gonna be working right. And it sounds like this is gonna modulate it. Whichever one you have, it's going to happen. Because low Cortisol equals higher IL6 as well, because cortisol is responsible for dampening that inflammatory signal. Now, if you're listening to this going, dave, I wanted to be into biohacking and living forever. Here's the thing. If you're IL6, which is a primary inflammatory signaling molecule in the body, if it's high, your brain will be inflamed. You're more likely to get Alzheimer's, you're more likely to get every bad thing that happens, including probably cancer. So having a gut bacteria on board that breaks this cycle, the one you described of lipopolysaccharides crossing the gut, creating inflammation, which creates cortisol and then which creates more inflammation, breaking that cycle means that your cortisol is probably going to be just better regulated regardless of whether you're high or low.

That's exactly right. Because remember, a key part of cortisol regulation is the presence of those glucocorticoid receptors, right? Because those are the guys that bind up cortisol and go, okay, we've got enough. Let's now shut down the negative effects that cortisol can have on your sympathetic nervous system. And then that also gets your body and your adrenals reset to be able to produce cortisol again. Because most people end up going into this adrenal fatigue area with continuous and overproduction of cortisol over time, right? Then there are adrenals that aren't designed to be production, producing it constantly, every minute of every day. It's supposed to cycle appropriately. Those adrenals go into a fatigue and can't function anymore. So now we're giving the body a chance to allow cortisol to function the way it's supposed to without all the negative effects. That increases IL6 and screws up the whole loop, the whole feedback system.

All right, so I'M really interested in this stuff. And full disclosure, I haven't tried the new Just Comm product. So I'm actually now sending a text message to my team going, guys, how come I don't have any of this stuff? So it's probably on its way. Living in Canada right now. It has to go through the Berlin Wall between Canada and the U.S. so we will. So I'll tell you guys how it's working for me, but the science behind this is it's pretty clear, to be honest, and the results are not what I would expect. I looked at the studies before deciding to do this interview, and one of the studies that just came out last year, improvements in sleep during exam stress from the specific strain that's in Just Comm. The Bifidobacterium longum 1714. So tell me about that study. What happened with exam stress?

Yeah, so what we're finding out, obviously, is that during exam stress or any periods of stress, the gut tends to become leaky and it actually drives dysbiosis. Right. So there are certain organisms that thrive under that condition of leakiness, inflammation, and so on, and in fact increase their virulence factors. So during those periods of stress, you can get an increase in opportunistic organism growth, which means that we start negating the microbes that produce serotonin and dopamine in particular, another precursor, which is tryptophan. So tryptophan can be metabolized in two different pathways in the body. You take tryptophan if you're healthy, your gut is. Is healthy, your immune system is healthy, it's going to get metabolized to serotonin and then dopamine, both of which that are important for resting, relaxing, sleeping, feeling happy, and so on. Now, if you have this continuous HPA activation due to stress and the inflammation that goes along with it, there's a shift to metabolizing tryptophan to something called kynurenin and quinolinic acid, which are actually neurotoxic. And those neurotoxic compounds prevent the release of things like melatonin and so on to be able to sleep and rest. So we know that it's all tied, right? So we know exam stress is going to impact your ability, ability to fall asleep, so the time to sleep and then the quality of sleep as well. Which means, of course, your brain's not absorbing that information. You know, it's inflamed. It's not really helping you when you're studying. So what we did is we said, okay, that's a great challenge scenario to see that if we can take people who are under certain amount of stress already and then see if we can improve their sleep patterns, then we're really breaking up that negative cycle of inflammation, leaky gut, lps, increase serotonin, melatonin production, compromise, and so on. So, yeah, and we saw very significant improvements in duration of sleep. So how long it took them to fall asleep and then the quality of sleep throughout the period that they're sleeping.

That's profound. And you also brought up something that may be the explanation for tryptophan restrictions. Tryptophan is an amino acid, and longtime listeners have heard me talk about. Amino acids are the building blocks of proteins. You string different ones together to make peptides, and pretty much every protein in the body is made of one of a relatively small number of aminos. Studies show that restricting tryptophan in the diet equals longevity. So eating a lot of tryptophan is bad for you. And then people say, but, but serotonin. And what you're saying is, here's the microbial pathway that's going to force the tryptophan to go down the it's good for you path versus the it's bad for you and increases all cause mortality path.

That's exactly right. Yeah.

Okay, I have to just underline that because I've written about tryptophan and methionine restriction and because of biohacking, because of all of the things we're learning about microbiology, all of a sudden saying, oh, here's a little tiny thing we can do to hack our system so that when we eat tryptophan, which comes from animal meats and things like that, there's probably some vegetarian sources too, but not that many. And when that happens now, it may not be causing aging. Do you know anything about this bacteria and MTOR by any chance?

I don't. We have not studied mtor. We do want to look next at epigenetic changes. My guess is that it could, could have an impact on it. But that's a super exciting area to look at as well.

Okay. And for listeners, MTOR is something that is a really big thing in the anti aging field right now. You need MTOR to grow tissues and stay young and build muscles. But if you have mtor, that's elevated all the time, it makes you age quickly and increases your cancer risk. So we have this weird thing, you want it, you don't want it. And part of the reason I recommend something cycling in and out of ketosis and things like that is because cycling back and forth seems to make a lot of sense. So going some time without protein, called intermittent fasting, it's to lower mtor. Right. And then MTOR can go back up when you exercise or when you eat some protein or very particularly carbs. But we don't know if this is going to affect that. But we do know that it's going to have a beneficial effect on specifically tryptophan. So maybe you won't get that aging effect from eating it. That is something that I don't think you've talked about much in research there. But from an aging perspective, if you do eat meat, which is correlated with living longer, to be really clear. So I think you should eat meat, this is probably going to make it even better. So I'm pretty excited, not from a psychobiotic perspective, but just from an aging perspective about the new the just calm The Phyto Longum 1714.

Yeah, absolutely. No. And when you think about all of the neuroinflammation that comes about from stress and having a dysbiotic gut that can't help you deal with stress adequately, that has a huge anti aging effect as well. Right. The neurodegenerative conditions, when the mitochondria and the neurons start to die off and we start to see reduced ATP production over time, that is a hallmark of aging. So as we can improve the inflammatory cascading, we can reduce the inflammatory response that stress has, we can improve what tryptophan does instead of going towards the neurotoxic side, becoming more neuroprotective, turning into serotonin and melatonin. Those are all going to be things that really improve not only your existing mood, your sleep, but it has long term implications for your overall health.

Wow, that's. That's a pretty serious stack of things for just a single species.

Yeah.

Second study that came up was modulating brain activity during social stress. So these are things. Okay. Exam stress is a really common thing, even if it's not because you're taking an exam. But it can be, I have a big presentation at work or whatever, but brief stressful periods where you have to perform well cognitively. So talk to me about social stress. What did you find it does there? Is the air you're breathing making you sick? Just because you don't see mold doesn't mean it isn't there. My friend Jason Earle has been on a mission for over two decades to help people understand the hidden role of indoor air in Their health. He's one of the world's leading experts on mold and indoor air quality. And he created the Got Mold test kit to make professional grade air testing since simple and accessible. It uses cutting edge air sampling tech that top inspectors trust. And it's engineered for you at a fraction of the cost. It takes just minutes to get samples using the patented Biovac air sampling pump. Then you send them prepaid to one of the most prestigious microbiology labs in the world. No guesswork, no paperwork, and no hidden fees. You get fast results, intuitive reports, and great, great support. And since you keep the pump, you can retest anytime for less. It even comes with a lifetime warranty. Mold may be invisible, but its impact isn't. This kit helps you understand your environment so you can take action for your health. Go to gotmold.com and use code DAVE10 to save 10% and see what's in your air. Because the best biohackers don't guess. They test. You're listening to the human upgrade with Dave Asprey. So talk to me about social stress. What did you find it does there?

Yeah. What we're looking at is a couple of different things. So we're looking specifically at brainwave activity. We wanted to see what areas of the brain was, were being triggered when you were on the probiotic or not on the probiotic. When you induce social stress in individuals. And the way we did that is actually a really cool thing. It's a, it's a professor in Germany that specializes in this in psychiatric medicine. And there's a machine system that you put people in and they play a virtual game. And it's a ball throwing game. And what's super interesting about it is it's a virtual game, but the other virtual components are AI components. And they avoid throwing the ball to you. Right. Just that little bit like kickball in.

Third grade or something.

So you get really stressed. Yeah, we all, I guess every adult has had that experience where they tap into it because man, do their anxiety go way up in that. In playing that virtual game, it's like being picked last gym class. Right. So.

Right.

That same old memory. So you can really induce an amazing amount of social stress in these individuals. And what we found was that when people took the probiotic for 30 days before doing this experiment, what we found was a dramatic increase in theta wave function. Right. That's the flow state. So we're changing that brain wave function and a lighting up of the coping centers of the brain. The coping centers of the brain is a Rational thinking that kind of helps you talk yourself out of being bothered by the situation too much. Right. It creates the negative emotions that come along with that stressor. And it's those negative emotions that keep eating away at you and you keep thinking about it and thinking about it, and then it has this prolonged effect. So we saw real and true brainwave changes from taking this strain, which is really fascinating.

Okay. I'm intrigued. Because social stress, for most people, it's not just they're not passing the ball to me, but they go into a crowded place, they don't know anyone. It's a much more common thing than people realize. And there are people say, I know I have social anxiety, but that's probably 10% of the people who actually have social anxiety.

Right?

So all of a sudden now it, it for some reason, I don't know if you can describe the mechanism, but it makes it easier for you to think about it instead of just feel about it and be tweaked.

Yeah, exactly. Yeah. Because, you know, think about social stress, right? And this is like you mentioned, different than the people with severe social anxiety that really can't do it. The panic and all that social stress is really a mix of confidence issues with a bunch of negative emotions that swell up. And because these negative emotions, as you're entering into a social situation really kind of eat at you in your brain, you really talk yourself out of being able to function in that environment. Right. Because all those negative emotions keep going and then the brain waves that drive that anxious, negative thoughts are firing. So what we've been able to see in this study is turning on the flow state wave, the theta wave. So now you're much more functioning cognitively, much more in a relaxed manner. And the coping centers of the brain help you negate some of that cycling of negative emotions. Right. So you get there, you might feel a little bit awkward still, but then you're able to go, now I'm fine. You know, I can deal with this. Go in there, pick and hone in on something and start working on it, whether it's a conversation with somebody or some other task, and really overcome it much more easy.

Have you ever had someone with stage fright or some kind of extreme anxiety try it? Have they seen differences?

Yeah, yeah, we have. So we had worked with a number of even people within the company itself that had a hard time getting up and speaking, which I think is, I think, maybe the second most common phobia. Right.

It's actually the number one fear, at least in the US The Top fear more than snakes and planes.

Yeah, crazy. Or snakes on planes, which is even worse. And so yes, we, so we've been working with that empirically with our employees and it seems to make a world of difference. So we do some up 25, 30 days before we know they're going to have to get up and do a presentation. And it completely changes how relaxed they are, how they feel before it and how well they can prep for it. You know, because people who have that fear are prepping with the fear mindset similar to that stress during studying for exams. Which means your brain's not absorbing all that information. Right. You're not in that flow state, you're not picking up the information and feeling confident about.

Sounds like it's, it's kind of magic if it can lower that stress even a little bit for most people. I have a couple friends who actually take beta blockers and beta blockers, they're not blocking cortisol, but they're blocking adrenaline receptors in the brain and it's the only way they can go on stage.

Right.

And so this is something that's kind of well known in, in nootropic circles, is that you can do that. These are prescription drugs that lower blood pressure. Problem is lower blood pressure is also less blood flow to the brain when you might need it when you're speaking. And also if someone asks a hard question, you need a squirt of adrenaline.

It won't do anything. Right.

So you can be caught flat footed. It's not a great hack unless it's the only way you can speak. So this might actually mean some of those people don't need to use a beta block blocker when they go on stage just because they've now changed this gut bacteria, it's, it's really profound actually.

Yeah, It'll bring out, it'll bring out their natural personality, their natural capabilities. Right. Because it allows them to, to actually be themselves and have that kind of level of confidence to be themselves without all of that negative bandwave function that occurs in them. And so, you know, we, we've seen the most profound effects when you pair the two. When you pair the spores with the Longam 1714, they work on slightly different mechanisms. The spores sealing up the leaky gut, reducing that lps, this particular microbe reducing the negative impact that cortisol can have, reducing the inflammatory response, modulating brainwave activity between the two when you add them together. We think of this as really great total brain support when it comes to the gut brain access.

That's that's so cool. There's more, though, from these studies. That's why I want to have you back on to talk about this, because this is a brand new probiotic. Yeah, it was a study. This is actually going back in the early days, it's 2016, but it talked about electrophysiology and neurocognition as in addition to modulation of stress. What did they find about cognitive function and neurocognition and the electrical brainwave stuff?

Yeah, so that was part of one of the early studies on looking at whether or not we can trigger the theta wave, which is that flow state that people want to be in, and then having them do recall exercises and so on. And what we found was that we can actually improve brain function, especially under a stress state and even under a non stress state. Right. So we know under a stress state, we've all been there, when you're stressed, your brain is rambling in a hundred different ways. You're not really functioning properly. So we know that we can improve cognitive function in a stress state, but we also know that if you're not dealing with daily stress, it's still going to improve brainwave function and put you more in that flow state. And the flow state is that where the artists and athletes and all feel like they're running and they're moving at their highest peak. And it's really about shifting that brainwave.

Wow. It's interesting though, theta during the day. Theta is the daydream state. When people have a trauma response to stress, quite often they'll disassociate and they'll go into a theta state. I typically don't want too much theta during the day, unless I'm meditating, in which case you want alpha. And these are broad. You need it at the right frequency within theta at the right part of the brain, Brain at the right time. Like it's a symphony. You can't say, oh, it's a tuba. Tubas are good. It has to play at the right time, right?

Totally. Yeah.

So do you have like data showing this is a healthy theta response during the day?

It is, yeah. Because then we measure it against cognitive ability. Right. So what we're seeing is that what you're doing is rescuing people from the disruptive brain waves. Right. And then putting them in a better theta function, which means that they're calming down from that disruptive brainwave and getting to this more kind of coping, high functioning state where then when we test their cognitive capability, they're actually responding better and they're actually performing better. So, you know, it's different than like what you mentioned with trauma, where you actually go into this full theta wave state. And that's because you're trying to escape the trauma. Right? Like, like you said, going into a trance or dreamwave state. What we're really looking at is kind of bringing back some of the theta wave that's not present and then allowing them to be calm so that they can actually function a little bit better.

Okay, I, I like that. And this is the first time that this has been available commercially. Right. Even though the studies have been going on for a while.

It is, yeah. Yeah. We're doing one more study which is super interesting, which is at the Concordia station, which is in the Antarctic. And the, the researchers that live there live what would be a very exaggerated and accelerated version of how a lot of people in the, the modern world live, which is in isolation and they live in a lot of darkness, you know, because there's a good part of the year where there's no sunshine at all, in a very sterile environment. Because that station is especially sterilized because they're so far removed remote, they can't afford to get sick, they can't afford to pick up a virus, so it's so sterilized. And what they find, which is similar to what happens in the space station is the, is their health declines so rapidly and one of the first things they notice is brain function. Right. Stress response, sleep, cognitive ability and so on. So we're doing a one year long study where we're dosing up some of those researchers on the 1714 strain to see if we can negate some of that negative effect. And that's exciting because the conditions that they're in are much more accelerated form of what a lot of people do here. More people live more and more in isolation and don't interact with others and stay indoors a lot and so on. So that's another super exciting study that's going on.

It's weird. This has very broad effects. I was really impressed when you guys reached out and said, hey, we should talk about this. I'm like, oh, we already talked about probiotics and gut. I talk about this a lot on the show. I don't want to, I don't want to recover too much territory. It's helpful for listeners if we repeat some important things like corn oil is bad for you. You might have heard me say that before. Right? And that's because not everyone hears every show and all, but this is really big new stuff. And really the studies are mostly like from 2014 and on, and it's taken about, that means about six, no, eight years for it to come to market. One of the other things that stood out though, and this is one of the earlier studies as well, was looking at not just anxiety and depression and all the neurocognition stuff, but looking at visceral pain. Talk to me about that study.

Yeah, one of the things that we find is that the type of inflammation that is triggered by leakiness in the gut and that the increase in IL6 and especially with an increase in LPS, because when the gut becomes leaky in response to stress, you're going to get LPS flowing through into circulation. One of the things that LPS can do that is pretty egregious is bind into these parts of the neurons called nociceptors. And when it binds into these nociceptors, it triggers pain signaling. So your body thinks you're injured. Right. It's the same pain signaling that would occur if you have a physical injury. But you don't have a physical injury, you just have LPS in that part of the neuron triggering an inflammatory response which is causing that nerve to send a pain signal to the brain. And so you've got all of these peripheral pains that you have no physical explanation for. And it can be not only, of course, really impactful in your quality of life just because pain sucks, but pain also leads to anxiety and depression. Right. We know chronic pain, people suffer from pain all the time, tend to be in a very depressed state. And so we took a look at that to see, wait, is that something that can also be modulated? Because it works through very similar mechanisms. And sure enough, we saw some benefits in that area as well.

It's interesting, this week we accidentally bought the wrong gluten free baked thing. And one of the local places where we live loves to use gar fava flour, which is garfa garbanzo and fava beans. And these are just nasty substances. It's one thing if you're going to pressure cook your garbanzos or whatever, maybe they're going to be tolerable. They're probably still not going to be great. But fava beans are just as a flower, they're not something you should eat. So, you know, one of the kids on my neck is hurting and my son, he's like, my foot hurts. It's never hurt like this. And it lasted for three or four days. And it's probably what's going on here. This Stuff causes leaky gut. It's got lectins that cause localized inflammation, et cetera, et cetera. And if we measured it as cytokines, his IL6 would have almost certainly been high, 100%. And if he'd have had this stuff on board, maybe that response would have been different.

Totally.

So I'm. I'm pretty darn excited to give this stuff a try. And so it's. It's like I said, it's probably on its way to me, but the studies here really blew me away when you shared these with me.

One of the exciting things we noticed, which a lot of people report to us within, I'd say the first four or five days, is the vivid dreams that they're having, because it does. Yeah. It puts you into really high quality sleep. Right. So that is an exciting part. And I'd be super curious to know what kind of dreams you end up having, Dave, when you take it, because they're going to be pretty vivid and fun.

What if they're just kind of embarrassing? Is that going to be a problem?

I think you should disclose it anyway. I think everyone will to want to know.

Full transparency. All right. I don't know what the giraffe was doing in there. That's all I can say.

Mystic animals, they are.

Giraffes are weird. You ever seen two giraffes fight?

Yes. It's the weirdest thing.

I love watching those videos. Like, their necks are wrapping around like that. Like, it's like, how could Mother Nature invent that? And the answer is the same way that Mother Nature invented a bacteria covered in polysaccharides that turn off stress and pain and cortisol. All right. There's a lot of freaky stuff out there, which is also why maybe we should stop spraying glyphosate on our soil, because we're killing all of these species of bacteria that actually run the world. So I'm kind of pissed off about that, too. But that's a question for you. What kills 17, 14? This new strain in just come. Is it. Is glyphosate going to take it out? I'm guessing antibiotics take it out. What are the things that it hates?

Yeah. So, absolutely. Glyphosate will take it out. Antibiotics. Most antibiotics will take it out. It's a more resistant strain than your typical bifidobacterium because of that peptidoglycan layer. So it will survive the digestive tract, the stomach acid and so on. But most antibacterial chemicals will kill it, unlike the spores that can survive through most of those things, it is sensitive in that way. So, you know, with the spores, we always tell people, hey, you can pull it out of the capsule, mix it in almost anything and take it, and it's still good. With this, it's probably better to keep taking in the capsule. And then, you know, by the same token, those things going into your body, glyphosate, antibiotics and all that will kill these kind of species. And part of that's probably one of the reasons why when you look at fluoroquinolines, that whole class of antibiotics, one of the key side effects of that and that type of antibiotic is panic disorders and anxiety. Right. So you, you take that kind of broad spectrum antibiotic, it kills off these kind of bacteria, and then now you're much more susceptible to anxiety and panic disorders.

What is it like in terms of prebiotics? And I've been from my anti aging book, there was so much evidence for soluble fiber. And if you're on a carnivore diet, I hate to tell you, you're not getting that stuff. And it's fine to go carry carnivore for a week.

Right.

But you need to feed the stuff you want to have surviving. Does this strain eat meat? Does it eat collagen? Does it eat, you know, acacia gum? Like, what are the types of prebiotics that you should take with it to make sure it sticks around?

It's. It's exactly what you mentioned, soluble fiber. And that peptidoglycan is made from a lot of the same carbohydrates that come from soluble fiber, different bacteria. Yep.

So the standard prebiotic stuff that, that I know just thrive makes a really good prebiotic that tastes fruity. I don't know, I wouldn't put it in my coffee. I like it in just a glass of water. And they also make capsules. So when I travel, I usually take the just thrive prebiotic capsules so that I know I've got some of that on board. So that's at least enough to feed things even if I'm not getting, you know, 30 or 40 grams of prebiotic fiber day like I normally.

100%. Yeah. And those are, those are oligosaccharides. And bifidobacteria in general, love oligosaccharides. Oligosaccharides being these unique prebiotic compounds. And you don't need a whole lot of it to really increase the growth of bifidobacteria in general, including this longum strain. Like the exopolysaccharide that we work with, the Xos, or the one from Kiwi, the actazin, those will actually drop dramatically, increase bifidobacterial growth. So they love polysaccharides. Sorry, they love oligosaccharides, and they love soluble fibers as well.

So if you're just tuning in or you're sort of your head spinning, what kind of saccharides, the basic deal is that you have prebiotics, which are a type of carbohydrate that your body can't eat, but that bacteria love. And there's different kinds of prebiotics that different kinds of good bacteria love. If you get enough of those from food or probably these days from supplements, you're going to have abundant good bacteria which fight off the bad bacteria. And then there's probiotics, which is what we're talking about here, the Just Calm, which is made by just Thrive. And the probiotics are the specific species that eat the prebiotics. And then you have postbiotics, which is basically what the good bacteria poop out when they're done metabolizing something. And the most famous one of those is butyrate or butyric acid, which is made in the gut. Funny enough, butter is named that way for butyric acid. Or maybe butyric acid is named because it's found in butter, more likely. But the idea here is that there's a whole bunch of different postbiotics that we're just discovering. I've done several shows on. Oh, wow, look, you can't get this postbiotic because you don't have the right probiotic because you don't have the right prebiotic. So what I'm hearing you say is that if you want the Just Calm strain, the Bifidobacteria 1714, with all these special powers, you would take the probiotic. You could hope that you're getting enough prebiotic, or you could take some prebiotic along with it. Guys, you need to be taking a prebiotic if you want to live a long time. The evidence is very clear and you probably want to take a lot of it. Unless you have sibo, which is we're not going to go into but small intestine bacteria overgrowth. So if you take a prebiotic and then you fart death for a week, well, then you need to clean that up. That's a different episode. And then we get into postbiotics. What are the compounds that are being made by this strain of bifida that's causing all this, do we know?

Yeah. So the main one is that peptidoglycan that it's making and releasing into the cell system. We know that it also impacts serotonin and melatonin production. It also impacts dopamine production. That may not be a direct, you know, synthesis of those compounds by the strain, but it's certainly helping the system create that. One of the things we talked about earlier is tryptophan metabolism, right? So if it's bringing down that inflammatory process that occurs during a stress response, it's allowing tryptophan to actually be metabolized or synthesized down into serotonin and melatonin. So we'll see all of those protective neurotransmitters going up as you start taking this strain. So at the end of the day, I think it's that peptidoglycan that's really important. We also know, and we don't know exactly what this is just yet, but we do know that the strain has a way of binding to receptors on the intestinal lining and creating a neurotransmitter release that impacts the brain. That may be part of how the brain wave changes occur. We don't know exactly what those neurotransmitters are, which we're working on right now, but we do know that it does some positive neurotransmitter effect that goes directly up the vagus nerve and impacts the brain.

Wow, that's incredible. Do you think that, well, we'll have a time when we can just take the glycans directly or it seems more efficient to just have onboard production here.

That's exactly right, yeah. I mean, I think you could probably take the glycans to a certain degree, but having that peptidoglycan factory in the gut is going to be, I mean, that's where you really get the long term benefit. Right? Because the goal is, let's say you take this for some time and you take the right prebiotic with it and you grow enough of this bacteria within your system, then maybe you can go to not having to take it every single day. Right. And knowing that if you miss it for a little bit, you're still going to have that on board effect.

So that was my next question. So I take the Just Thrive, their standard probiotic that reduces lipopolysaccharides, just stupid amounts. And I think it's been beneficial for me and I take that almost every day. Some days I miss it for whatever reason. Do I take the new Just calm every Day as well. Can I take it every other day? I mean, people are always trying to economize. What's the regular dosing schedule? Do you take in the morning, take it at night? Just how do you use it?

Yeah, so this one is just one a day, and you can take it at any time during the day. You can take it with a meal or without a meal. We haven't found there to be a big difference between whether take it in between or with a meal. My recommendation to people is always for the first almost two months to try to take it every single day, because more than likely you tend to be low in peptidoglycan producing microbes in our gut. That's just the fact of living in a sterilized, antimicrobial modern world. And so getting a lot of this organism back in and starting that peptidoglycan metabolism in the body is going to become really important. Typically after month two, you'll find that you could start forgetting some doses and be okay. You might even be able to go two or three times a week on a regular basis of taking it and not seven days a week and so. And people can play around with it a little bit. Once they feel the mood changes, they feel the stress response change, they feel the sleep changes, they can kind of dose it back and scale it back. For me, for example, right now, and I've been taking it now since I think September, and by December, I was able to forget to take it two, three days and be totally fine and still feel the ongoing effects.

So what we're doing here is kind of like a farmer, right? First you till the soil, that's your prebiotic, then you plant the seeds. And you got to plant enough of them because some aren't going to make it. And eventually it can become self reproducing. But you probably still need to tend the system by adding more. And it makes sense. I think most probiotics are like that. You take them religiously for a while and then you take them often enough to get the benefits and it will colonize the gut and reproduce by itself. If you're taking prebiotics, but you still want to keep the strain coming in. Okay, I get it. I'm really excited about this. The research, I mean, it's eight years of research just coming onto the market. And I tend to cover stuff like that on the show where we didn't know we could do this before. And for every one of these that I find, people always bring me like 10 other things. Like there hasn't any research to that or, you know, kind of, you know, copying something that's already out there. This, this is new and really, really interesting. So I appreciate all the work you've done on it. And we've got what, five studies we just talked about, and there's probably some other ones too. Guys, go to justthrivehealth.com, use code ASPREY. It'll give you 15% off if you want to give it a try. I am. As soon as it arrives to my house. I'm going to be doing this for several months. And if I see the changes in that first month and I'm having crazy dreams about giraffes, I have no idea why I mentioned giraffes, but I'm just picturing them fighting again and it makes me laugh. But whatever crazy dreams I may have, if you see a change in dreaming, that's a sign something very substantial is happening. And that could be from the Theta state, because Theta is where dreams happen. But also all the stress reduction and things like that and cortisol regulation. This is apparently like a really strong mega multiple channel probiotic that didn't exist before. So I hope you enjoy giving it a try. It's called Just Calm and it's made by justthrivehealth.com code asprey. And thank you, Karen, for just doing cool and interesting research and knowing what you're talking about and also for being able to talk coherently about it. We got pretty geeky here, but not so geeky that I think someone who's paying attention would be unable to follow it. Except I was watching the Upgrade Collective here, you know, our live studio audience. And I was noticing in particular Larry, he looked just completely like he just didn't understand a single thing here. And I was, I was feeling embarrassed on his behalf. I'm just kidding, Larry. But if you guys are interested in joining the Upgrade Club collective, go to daveasprey.com there's information. This is my mentorship and membership group where you get to be a part of a small studio audience during the podcast and part of all the classes I teach on my work. I'd love to see you there. And it's, it's a lot of fun to do it. And again, just thrive health.com use code ASPREY for 15 off. This one is worth a try. You're listening to the Human Upgrade with Dave Asprey.

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