Optimizing Gut Health For Superhuman Energy Levels with Kiran Krishnan

Content By: Ari Whitten & Kiran Krishnan

In this episode, I am speaking with Kiran Krishnan – who is a research microbiologist and an expert on gut health. We will talk about optimizing gut health for superhuman energy.

Click here if you want to learn more about Kiran’s gut health products

Table of Contents

In this podcast, Kiran and I will discuss:

  • What are Mitochondria?
  • The link between mitochondrial health and overall health
  • How free radical oxidative stress affects your health
  • How mitochondrial dysfunction is linked to cancer and neurodegenerative diseases
  • The important role of a diverse microbiome for health
  • The best steps to take to upgrade your mitochondria

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Ari: Hey there, this is Ari Whitten and welcome back to the Energy Blueprint podcast. In this interview, which I am incredibly excited about, I have someone who I’ve wanted to interview for literally probably three years now. He is one of the top experts out there on gut health. And really, I can’t think of anyone who I’m more impressed with in terms of their knowledge of gut health. 

So, Kiran Krishnan is a research microbiologist and has been involved in the dietary supplement and nutrition market for the past 20 years. He comes from a strict research background, having spent several years with hands on R&D research and development in the fields of molecular medicine and microbiology at the University of Iowa. He left university research to take several leadership positions in global companies in business development and product development.

And he’s also established a clinical research organization where he designed and conducted dozens of human clinical trials in human nutrition. Most recently, Kiran is acting as a co-founder and the chief scientific officer at Microbiome Labs, which is a leader in microbiome and probiotic research. He’s a frequent lecturer on the human microbiome at medical and nutrition conferences. He’s an expert guest on national radio and satellite radio and has been a guest speaker on several health summits as a microbiome expert, such as this one.                            

He’s also currently involved in over 18 novel human clinical trials on probiotics and the human microbiome. He’s also on the scientific advisory board for seven other companies in the industry. He’s published clinical trials and peer reviewed scientific journals and has several global patents in his name. So, welcome, Kiran, such a pleasure to finally connect with you.

Kiran: Thank you so much. It’s such a pleasure to be here. And I’m glad we finally got around to doing this.

Ari: Yes, me too. So, I’ve had a chance to look over your presentation. I am super excited to get into this topic with you. It’s all about optimizing gut health for superhuman energy levels. We’re going to be talking about the, you know a lot of people talk about the gut brain axis, and that’s kind of a, sort of a more known thing. But what’s not very well known for most people is the gut mitochondria axis, and it’s critically important information. So, I’m really excited to get into this with you. 

The mitochondria microbiome axis

Kiran: Yeah, same here. I don’t get to talk about this often enough. And as we go through it, I think people will start to understand and see why this is so critically important. This has an impact on every aspect of your life. Every cell in your body, with the exception of your red blood cells, contain mitochondria. And it’s that mitochondria and those mitochondria, because they can contain multiple mitochondria, that determine the function of the cell, and provide energy to the cells.

So, we cannot overstate the importance of the microbiome mitochondria axis, let alone the importance of mitochondria itself. So, this is going to be hopefully eye-opening for people and gives them a whole new area of focus in terms of how to optimize their health. ‘

Ari: Yeah, absolutely. So, let’s get into it. So, what is the mitochondria microbiome axis? 

Kiran: Yeah. So, let’s first talk about the mitochondria. I’m sure a number of experts will explain this on the summit, but it’s called the powerhouse of the cell, right. So, the reason why this even becomes an interesting topic with reference to the microbiome, is because mitochondria are actually ancient pleiotropic bacteria that exists within your cells. 

If you look through the history and the likely history of how multicellular organisms or eukaryotic cellular organisms, like ourselves, develop actually an ancient bacteria that is an energy producing machine, got together with something like an archaea, and then the archaea swallowed the bacteria and then the energy producing machine and the archaea formed this amazing symbiosis. Whereby the archaea would harvest nutrients that the mitochondria, the energy producing bacteria would need, and then the bacteria would then produce the energy it needs as well as what the archaea and the cell needs. 

So, that really interesting symbiotic relationship was a foundation of what eukaryotic cell is, which is the types of cells that we are made up of. So, you think of the 10 trillion cells that are in our body. The vast majority of them contain anywhere from four to twenty-four hundred mitochondria in them. 

And so, and each one of those mitochondria are descendants of ancient bacteria. Now, the beauty of that is the language, the molecular language between these ancient bacteria that we now incorporate as our mitochondria, and the existing bacteria that exists in our gut are still the same. They still require the same things. They still are stimulated by the same things. 

And there’s an ability for our microbiome to really effectively manage our mitochondria and some of the really important signals to maintain our mitochondria heath, we are completely dependent on our microbiome for. So, there’s so many things that we can ourselves do to maintain the health and the function of our mitochondria. And all of that is outsourced to the bacteria that exist within our system. 

Ari: Now, just to create a visual for people, we’re talking about sort of communication between two things in very different locations in the body. We have bacteria residing in our intestines, in our gastrointestinal tract. And those bacteria are somehow communicating via, I’m sure you’ll discuss what they’re communicating with, but they’re communicating with various biochemicals that are affecting the mitochondria that are residing in cells throughout our body. In our brain, in our organs, in our muscles, in our skin, in all these different mitochondria throughout our body. 

So, maybe I’m jumping ahead here, but I’m just, I love this topic so much. I’m so excited to get into this with you. So, how does this crosstalk work?

Kiran: Yeah, a lot of it is a quite simple ecosystem. We can simplify it, it’s actually very, very complex. But looking in the most simplistic sense, it’s an ecosystem that’s made up of extracellular matrices, right. So, our microbiome exists in an ecosystem where outside of every cell there is a medium. And that medium contains loads of nutrients and postbiotics, which are compounds that the microbes make from digesting the foods that we put in, by converting the nutrients that we put into our system. Those byproducts are excreted into this extracellular matrix. 

Now, because of the evolutionary connection between our microbes and our mitochondria, there is an affinity for those extra cellular compounds to travel to our cells in order to feed our cells. So, remember the big cell that swallowed the ancient bacteria that became the mitochondria within that cell is an archaea, right. So, it has also ancient connections to microbes because microbes and archaea all lived in harmony for millions of years and they still do now. 

So, there is a tropism, if you want to call it, that’s in science, where there’s a homing beacon, if you will, for these nutrients to make their way into our cellular receptors and organelles, so that it can get into the system. So, think of the bacteria sitting there in our gut, they’re spewing out really important nutrients from digesting the foods that we put into our system. 

And what’s spewed out into the extracellular matrix has an affinity through our circulatory system, through our lymphatic system, and in some cases through our neurological system, to get to our cells. And when they get to our cells, our cells have an affinity to pull them out of that extracellular matrix and feed it into the mitochondria. 

The link between mitochondria and health

Ari: Okay. So, that’s a very nice overview of this, how this crosstalk works. Let’s back up to just mitochondria specifically. And I know you have a bunch of slides here in your presentation related to the role of mitochondrial health in disease more broadly. So, can you kind of build out that element for people so they understand, first the picture of mitochondria and health, and then how the gut are influencing and regulating mitochondrial function? 

Kiran: Yeah, absolutely. So, first we’ll talk about mitochondria itself and kind of how they function in a general sense. And then we’ll talk about the most common dysfunctions that we see in mitochondria. The things that are supposed to occur in order to maintain homeostasis and maintain healthy mitochondria. We’ll elaborate then on how those things are not functioning and what happens when those things don’t function properly. What is the health and disease consequence of that? 

And then finally, we’ll get into then what is it that the microbiome produces that is critical to the health and function of the mitochondria? Right. So, we’ll jump into it first. What are the mitochondria? We talked about they are the powerhouse of the cell, as most people would have learned in science in junior high school. They are organelles that sit within the cell that produce all of the energy that our body needs. 

So, the ATP that they end up producing, the adenosine triphosphate, is the energy currency in the human body. Without ATP, we will cease to function as a species, whether you have high levels and good ATP production or low levels and poor ATP production, will determine how you feel each and every day, when you wake up in the morning. Whether your brain is functioning in an alert state, whether your muscles are responding well to the stresses that you put it through, how energetic you are throughout the day, completely dependent on how much ATP your mitochondria can produce in all of the various cells. 

So, ATP production is one of the most important things. Thermogenesis is another important thing. Your mitochondria can burn sugars, it can burn protein, it can burn fat, for it to make that ATP. There’s different mechanisms for each of those. All of those feed at some point into the Krebs cycle. The Krebs cycle then kicks out byproducts that then go through something called the electron transport chain, and the electron transport chain finally kicks out ATP. 

So, those couple of things are important to note. Obviously, unless you’re in graduate school or high-level science classes in college, you won’t need to know exactly what’s happening in the Krebs cycle or the electron transport chain. But I do want you to keep those two things in mind, that the fat metabolites, the sugar metabolites, and the protein metabolites, the way those are converted into this ATP energy currency is they feed first into some stage of the Krebs cycle. . 

And then the Krebs cycle kicks out components that then go through something called the electron transport chain. At the end of the electron transport chain is where ATP ends up ultimately getting generated. That’s important to remember because those are steps in where things can start to go wrong. Calcium signaling is an important part of the mitochondria as well. Calcium is used throughout the body for all types of nerve conduction, for your muscle contraction, for all kinds of things. So, mitochondria plays a role in calcium signaling. 

Heme and steroid synthesis also does occur in the mitochondria. It’s not as relevant to this particular talk, but just important to keep in note that that’s what happens. This next part is really important. Apoptosis, right. So, apoptosis is programed cellular death. That’s really important that the cells have a very strong program signal in there to essentially self-destruct at a certain given time when the cell gets to a certain age. The reason that’s important is because that allows for the regeneration of new cells, and healthier cells, and better functioning mitochondria.  

And when apoptosis fails, that becomes the onset of tumor genesis, right. So, when your programed cell death fails, that’s the onset of tumor genesis or tumor growth. So, apoptosis is extremely important, that is controlled by a healthy mitochondria. A dysfunctional and disrupted mitochondria has dysfunctional apoptotic signals. So, that can become a big problem with the risk for cancer and tumor genesis. 

Cellular homeostasis, of course, maintaining energy balance in the cell. And we’ll get into that a little bit more when we talk about something called redox balance. But insulin control is also a big function of the mitochondria. And lastly, the generation of reactive oxygen species. Most people have heard about ROS, or reactive oxygen species, or you might have heard about it as free radicals, or you might have heard about it as super oxides. These are all byproducts of energy production in the mitochondria, right. Think of it as exhaust that’s being produced when your internal combustion engine produces energy in the car. 

So, it’s an exhaust, if you will, from cellular respiration. Now it’s totally normal, it happens in every cell. And we’ve got things in place to help quench the toxicity of those reactive oxygen species, in particular the glutathione, and catalase, and superoxide dismutase systems in the body. Those are all there to quench that exhaust. But one significant issue happens when you don’t have cellular homeostasis, is you end up getting less energy production and more exhaust being kicked out, and the exhaust is not contained. 

So, imagine you turn on your car and you’ve got it in a closed garage, right. So, you’re producing energy, but you’re not utilizing the energy because you’re not moving, but you’re kicking out a lot of exhaust and it’s stuck in a confined place, and that creates significant toxicity. If there was any living species in that garage, they would succumb to that toxicity over a period of time. Same thing happens to the cells. 

If there’s no energy homeostasis, you have something called a redox imbalance. That redox imbalance will eventually drive inflammation, damage to the cells, and damage to the mitochondria, because the exhaust is too high. It’s not getting quenched. So, that’s a really important thing. Now, some of the control mechanisms to maintaining this energy balance, besides the quenching of this exhaust, is something called mitophagy. 

So, mitophagy is the removal of dysfunctional mitochondria, because as these mitochondria go through their work of producing energy every minute of every single day, and they continue to produce that exhaust, that exhaust will damage the mitochondria eventually, and that damaged mitochondria has to be recognized as being damaged and then removed from the system. You don’t want cells full of damaged mitochondria. That signifies aging, which I’ll talk about down the road. 

Ari: Just to interrupt briefly, just to give a little teaser. I know that there is a link specifically with certain metabolites from the gut microbiome processing of certain phytochemicals, and the production of compounds that directly relate and amplify mitophagy. 

Kiran: Exactly, yeah. In fact, that’s the most powerful signal of mitophagy comes from the microbiome. And that’s why this is so important to note that mitophagy’s such a key component to a healthy mitochondria within the microbiome, because inevitably, like any car engine when it runs for a period of time, the engine’s going to get worn out. It’s going to get toxic. It’s going to get gunked up. You can change the oil as much as you want, but you’re not going to run the engine out for half a million miles, or six hundred thousand miles. You’re going to have to replace it. 

The same way the engine’s in your cell will run out, especially because they are susceptible to those reactive oxygen species exhaust that comes out. So, the key to maintaining healthy functional cells, is to have a really good, healthy process of identifying dysfunctional mitochondria and then getting rid of it through the process of mitophagy, and then stimulating the regeneration of new mitochondria called biogenesis. So, that balance is really critical. We want to emphasize that. 

Ari: Yeah. And just to connect the dots with energy, the concept of energy, superhuman energy and chronic fatigue. There’s a bunch of research that has linked mitochondrial dysfunction, and Dr. Robert Naviaux’s work around the cell danger response, which is sort of the shutdown of mitochondria and them shifting into this mode where they’re spewing out, in your terms, lots of exhaust, and very little energy, and lots of these damaging free radicals. And their cells, their mitochondria have been kind of locked in this state of not producing a lot of energy, but producing lots of damaging exhaust, damaging free radicals. 

Kiran: Exactly, yeah. And of course, if they’re not producing energy, what does that mean? Well, it means that they have no way of effectively breaking down things like proteins, fats and sugars in order to utilize it in their energy mechanisms, right. So, you get a net of inability to metabolize these compounds that you’re continuing to take in. So, a lot of those things end up getting stored. And that has, of course, all kinds of other effects within your system. 

So, the inability of these engines to break down the nutrients that are being fed to it and then the inability of the body to identify the damaged engines, the mitochondria, remove them and regenerate new mitochondria, causes a whole host of conditions. And, of course, at the base level drives energy dysfunction within a person. Now, again, this is all happening in every single organ in your body, including your brain, and your heart, and every single muscle in your body. 

So, when these muscle tissues are suffering from an energy imbalance, a redox imbalance, too much exhaust, not enough energy production. Mitochondria are not being cleared out and they’re not regenerating new mitochondria, your net result is that organ system starts to fail. And whether it’s your skeletal muscles, where you don’t have enough energy to move, or it’s your brain, where you’re going into brain fog and having memory recall issues and becoming slower. Whether it’s your heart and your cardiac output starts to go down, which means your heart is not pumping out as much blood with every beat. So, then the rest of your body doesn’t get enough blood or nutrients. Your whole system starts to degenerate down, right. 

So, it all starts with this mitochondria dysfunction. So, those are very important things to keep in mind. Redox imbalances within the mitochondria, that’s the imbalance between not producing enough energy and kicking out too much exhaust, is a big driver in what they call free radical diseases. The most well studied free radical diseases are all the various forms of cancer, right. 

In fact, if you look at all of the areas in which free radical diseases are prevalent because of this redox imbalance, it affects the heart with things like cardiac fibrosis, hypertension, tachycardia. It affects the skin, kidneys, joints, lungs, brains, immune system, blood vessels, multi organs, eyes, your vision, everything. These are all characteristics of degenerative conditions because your mitochondria within your cells are becoming more and more dysfunctional. This is all very well established. 

And in fact, in the case of cancer, they’re actually trying to change the definition of cancer as more of a mitochondrial metabolic disease, rather than the initial idea that cancer has a lot to do with genes that turn on tumor genesis and or not. It becomes more, and more of a metabolic problem, of an energy balance problem, that redox imbalance, then this genetic dysfunction within tumor genesis. So, that’s an important thing to note. 

And in fact, healthy mitochondria and animal studies can actually reverse the progression of cancer. They’ve been able to show in this example that I’m showing here, that introduction of noncancerous mitochondria into a highly malignant breast cancer cells could reverse the malignancy. They’ve been able to show that that you can mitigate the unregulated cell growth. You can decrease the viability and hypoxia. 

Well, what does that mean? Well, one of the problems with cancer cells is they become more and more viable in hypoxia, in conditions of low oxygen. And hypoxia is one of those ways in which the body controls cell death, right. And it tries to get the cells to shut down so they can get rid of those damaged cells. The cancer cells tend to have a high resistance to hypoxia. But when you add non-cancerous mitochondria into these cells, then you start to find more and more sensitivity to hypoxia starts to occur. 

And it, of course, turns off the unregulated cell death. All kinds of changes at the cellular level occur where you actually start reversing the process of cancer. Now, again, all of this hangs on the balance of this low biogenesis, or low regeneration of new healthy mitochondria, low mitophagy, meaning you’re not cleaning out the damaged mitochondria. And then this redox imbalance, too much exhaust, not enough energy. This is the metabolic crux of cancer. 

This also is a metabolic crux of things like Parkinson’s, and Alzheimer’s, and neurodegenerative diseases, right. So, aging and significant neurodegenerative diseases are driven by this same mechanism, the same dysfunction of mitochondria. Same thing, and this is a study looking at dysfunction in lung disease. Same emphasis on mitophagy. How important this process of cleaning out damaged mitochondria is. 

This is the same thing in oxidative stress and cardiolipin to mitochondrial dysfunction, in nonalcoholic fatty liver disease, which is becoming an epidemic in the Western world. Nonalcoholic fatty liver disease didn’t really exist in any prevalent rate 40 years ago, 50 years ago, 60 years ago. Any time you had liver disease, it was typically due to alcoholism or cirrhosis due to viral infection, hepatitis, right. Now, we’re seeing more and more that nonalcoholic, non hepatitis liver disease is at a much higher prevalence rate than the alcoholic and hepatitis version. 

So, it’s called nonalcoholic fatty liver disease. It moves into something called NASH, nonalcoholic steatohepatitis. And people start to go into liver failure. Once your liver fails, the rest of the system is quick to follow. This is driven by low biogenesis, low mitophagy, and redox imbalance as well. There’s another hepatic, study on hepatic disorders. Same thing. Low biogenesis, low mitophagy and redox imbalance. And then aging. There’s something called the Free Radical Theory of Aging. The Mitochondrial Free Radical Theory of Aging. Abbreviated MFRTA. 

Basically, what they’ve shown is that the biggest driver of degenerative conditions like aging, including diseases that can be named, is that the free radical generation within mitochondria causes disruptive mitochondrial function, lowers mitophagy, and lowers mitogenesis. If we can maintain those two things, we would age at a much slower rate. 

The one really, really landmark study that published, showed where they took tissue samples from a five-year-old and they compared it to tissue samples of a 90-year-old. They gave them to a pathologist, blinded. So, the pathologist did not know which tissue came from which subject. And then the pathologist were to assess the difference between the tissue samples. The only thing they could find as a difference between the two tissue samples, is that the 90-yearold had as much as 95 percent damaged dysfunctional mitochondria. And the five-year-old had a hundred percent functioning mitochondria. 

Ari: Wow. 

Kiran: That’s the only difference in eighty-five years of aging. That’s where they see the difference. 

Ari: Amazing. I want to add a little layer to this, because I’m pretty familiar with the research around this as well. And there’s research showing between the ages of 40 to 70, most people lose about half of their mitochondrial capacity. And there’s numerous studies, they’ve quantified it in different ways, about eight to 10 percent loss of mitochondrial capacity per decade of life. 

There’s also research that suggests between 20 to 40, you lose half. So, if you think about it from 20 to 70, most people are losing 75 percent of their mitochondrial capacity. But there’s also some really interesting research, I’m going off on a bit of a tangent here, but I just can’t help myself from interjecting because it’s related to this, showing that in people who are exercisers into old age, who have adequate hormetic stimuli into their mitochondria and are really challenging and stimulating their mitochondria on a regular basis through physical activity, they don’t lose half of their mitochondrial capacity between 40 to 70. 

So, this process, I mean, here we’re talking about the role of the gut health and microbiome health in regulating mitochondrial health. But it’s also intertwined with so many other factors and in particular hormetic stimuli that are driving this process of biogenesis and allowing you to not lose so many mitochondria as you age. 

Kiran: Yeah. But here’s the amazing connection there is that the hormetic stimuli also has an impact on the microbiome, right. So, those that exercise, especially if they’re doing, kind of a medium intensity exercise several times a week, they actually maintain diversity in their microbiome for longer. And it actually reduces leaky gut. 

So, one of the, we did University of North Texas, where we did our first leaky gut study. They’d also previously published a study showing 30 minutes of low intensity exercise prior to a meal reduced the endotoxemia, or the leaky gut that would arise from that meal. So, the exercise has a very deep connection to the effects of the mitochondria, sorry, the microbiome. And then here’s the other thing, as you mentioned, after the age of 40, losing mitochondrial function. Another hallmark of after the age of 40 to 70 is a significant loss in diversity in the microbiome. 

Ari: So, it just goes to show, nothing exists in isolation. Everything in the body is intertwined. 

Kiran: Everything is in intertwined. All of these behaviors support the systems that we require. So, yeah. And then at the end of the day, looking at the microbiome, there’s so many things you can do to support its health, intermittent fasting being one of those things, right. So, you can take a lot of things which will help. And we’ll talk about some of those. And then some aspect of it is just not taking anything. Giving your microbiome a chance to rest. 

And then a recent study just published this week showed that intermittent fasting has a significant impact on ameliorating or preventing the cognitive decline that’s seen in type two diabetes. And of course, it even increases and improves metabolic function in type two diabetics. But it’s completely dependent on the presence of the microbiome. 

So, in animal models, when they remove the microbiome, those benefits went away, right. So, it all, every one of our behaviors has an impact somehow on the microbiome. And that impact on the microbiome will then translate to metabolic impact on our body. So, it’s really, really fascinating. Now, when we look at the defective mitochondria, I call it the defective mitochondria triad. What we’ve been beating into your brain for the last 15, 20 minutes is low biogenesis, low mitophagy, and redox imbalance. The consequence of each of these is pretty clear. 

With low biogenesis, of course, we get lower ATP production because we’re not regenerating new mitochondria to keep up with the energy needs. And that in itself starts to lower the ATP production, which then drives imbalance, redox imbalance. But that also leads to the most noticeable things are fatigue and tissue degeneration, right. And fatigue is a characteristic of virtually every chronic illness. It affects neurons, muscles, your mucosa, immune cells, tendons, and so on. It just makes it hard to get out of bed at the least, and at the worst it creates all kinds of chronic illnesses. 

Low mitophagy, of course, gets there from higher reactive oxygen species, low ATP, loss of apoptosis control. It also causes things like fatigue, tissue degeneration, overgrowth in the case of cancer cells, and again affects every single biological system in the body. Redox imbalance is the imbalance between the two. Also leads to fatigue, degeneration, impacts every single system in the body. 

So, what is then the connection between the mitochondria and the microbiome as it relates to these three really important dysfunctions that seem to occur inevitably in everybody as we get older, and if we don’t curb our behaviors? So, what I talked about earlier about the connection, the intimate evolutionary connection between your microbiome and your mitochondria still exists today. Mitochondria are ancient pleiotropic bacteria. They respond to signals from other bacteria. And most of the bacteria in our system lives in our gut. 

How the gut bacteria affect our mitochondria and energy production

So, what our gut bacteria produces has a significant effect on the mitochondria. So, there are three major things to keep in mind that the microbiome produces that has a huge impact on our mitochondria. Now there are other things as well, but these are three of the most well studied and most prevalent. And I would argue and say the most important things to focus on when it comes to impacting your mitochondria health through your microbiome. 

First one is short chain fatty acids. So, butyrate, propionate, acetate. Butyrate especially, is a really important primary energy source for many cells in your body, including all of the cells that line your large intestine, your colonocytes. Your large intestine is responsible for doing lots of things in your body. The colonocytes that make up your large intestine utilize butyrate as a primary energy source. Many of your immune cells, your macrophages dendritic cells all use butyrate as a primary energy source. 

Now, butyrate, beyond all of that, is also a very important metabolic signal. It activates something called cyclic AMP, which then tells all your cells, all the mitochondria and all your cells to start burning fatty acids for fuel, which makes you this sustainable, long acting, fat burning machine. Which is really the healthiest way to be as a human going through periods of being fed and fasted and so on, and to create a sustainable energy production. We all have a ton of fat on our system. Even if you’re very lean, you’ve got, you know, eight, nine percent of your body mass is fat. And all of that fat is there to sustain your energy needs for long periods of time. 

So, with your body not being able to burn fat efficiently, you’re going to suffer from energy slumps and your cells are going to suffer from not having nutrients it needs, because we only have so much sugar and glycogen in our system to sustain caloric needs. So, butyrate is a very important signal for that whole mechanism in your body and it comes predominantly from your microbiome digesting fermentable carbohydrates. 

So, the second one are urolithins. Urolithins are a very, very interesting class of compounds. They are derivatives of polyphenols. Now, we can’t really get high levels of urolithins in any food source. There isn’t a food that we can eat that is a very high, rich urolithin food. The way we get urolithins, and in particular one compound called your urolithin A, is our microbiome will convert polyphenols that are coming in through our diet, carotenoids and citrus polyphenols and all that from fruits and vegetables, and convert it in the microbiome into urolithins. 

And those urolithins become really important signaling compounds for our mitochondria. The ancient pleiotropic bacteria that our mitochondria are, respond really well to the presence of urolithin A. And imagine this was occurring in the primordial soup, the carotenoids from fish, and crustaceans, and all of these plant life in that primordial soup in the primordial world, if you will. 

And then bacteria develop this capability of metabolizing those polyphenols for energy. And as a byproduct, they kick out things like urolithins, and then other bacteria around them go, hey, here’s a free waste stream. We’re going to figure out a way to metabolize that. They start figuring out a way to metabolize urolithins and using them for signals within the system. 

So, ancient bacteria had to use what was around them and in their extracellular matrix for signaling, for metabolism, for communication between other cells, and urolithins happen to be one of those compounds that they still use today as a really important signaling molecule within the microbiome and the mitochondria itself. And then the last thing, which most people know about, is lactate, right. And lactate is a really important precursor to short chain fatty acids and other really important compounds as well. 

So, just keep those three things in mind as we talk through this over the next few slides. But at the end of the day, the cycle of how these compounds affect the microbiome, which then affects the mitochondria, is the more short chain fatty acids you have, the more lactate and the more urolithins, it selfperpetuates diversity in the microbiome. So, it feeds more bacteria within the microbiome who in turn make more short chain fatty acids, more urolithins, and more lactate. 

So, it’s a self-perpetuating cycle. And then the excess urolithins, short chain fatty acids, and lactate gets into our system, our circulatory system and our cells and mitochondria can use it ultimately, right. So, let’s dig a little bit more into these things. And this is just an example of a review paper that shows that this kind of dysbiosis in the gut, which leads to lowering short chain fatty acid production, lowering polyphenol metabolism, and urolithin  production, and lowering lactate production, is implicated in diseases like obesity, inflammatory bowel disease, irritable bowel syndrome, type two diabetes, colorectal cancer, and so on. 

They talk about how intelligent modulation of the microbiome could be of significant impact and interest in modulating all of these really prevalent chronic illnesses. There’s another study that shows that low diversity, so remember diversity is a really key, important factor in a healthy microbiome that then impacts the mitochondria, they show that diversity, for example, was the most consistent observation they found in people with inflammatory bowel disease, IBD. So, Crohn’s, colitis, and colorectal cancers. 

And again, it’s because the colonocytes that are getting damaged, in the case of IBD, require butyrate, they require urolithins, they require all these important things, metabolites that are being produced by the microbiome. And as you lose diversity, you lose the production of those compounds. 
Now, for the interests of your audience, all of those compounds are called postbiotics. And these are things that are produced and metabolized or metabolize byproducts of your microbiome. And those are called postbiotics as opposed to prebiotics, which are foods that feed your microbiome or probiotics, which are bacteria that have a biological impact on your microbiome. 

And this is one study I wanted to show because it talks about the impact of aging and your microbiome. We talked about all these things we can do, exercise, diet changes, and all that that have an impact on our aging process. One of the things that our studies are showing, is that a characteristic of someone who’s 90 years old, who has a really healthy outcome, good energy, living basically a normal life, is that they tend to have the diversity in the microbiome of a 30 year old. Not the diversity of a 40-year-old, right. 

So, that critical point that you mentioned, Ari, about at 40 we start to see this degeneration of the mitochondrial energy output is critical, I think. Because we have our optimum kind of homeostatic for most people in their thirties, homeostasis. And you look at most endurance athletes, they tend to peak in their high twenties, low thirties, right. 

That’s when you are really at your best in terms of your performance. But your microbiome is also the healthiest and most diverse, assuming you’re doing good things for yourself in your thirties. And if you can maintain or get back to that level of diversity in your microbiome, it has a huge impact on your longevity. We cannot overstate that.   

Ari: Yeah, absolutely. I want to add just one layer of something to this point you’re making about diversity. Obviously, the diversity of the diet impacts the diversity of the microbiome. I know you’re kind of skipping over that and you’ve talked about it in other presentations that I’ve heard. But that diversity at the dietary level, that influences the diversity at the microbiome level. And that, just to draw a specific point here, you mentioned a variety of different phytochemicals and carotenoids go into urolithins, but specifically urolithin A, and please correct me if I’m wrong, but from what I’ve seen, it’s primarily ellagitannin. 

So, specifically ellagic acid rich foods that get translated by a very specific species of bacteria or maybe a couple of different species of bacteria, that not everybody has… 

Kiran: Right. 

Ari: That take those ellagitannins and make them into urolithin A, which is this compound that profoundly influences mitophagy. So, to this point of diversity, if someone doesn’t have good diversity of bacteria in the gut, they might not even have this particular species of bacteria that is responsible for producing urolithin A. 

Kiran: Yeah. Now, one of the things that’s beautiful about the microbiome is functional redundancies, right. More and more, we’re coming to find out there are typically numerous microbes that perform similar functions. Some may be really prevalent at performing that function. For example, oxalobacter formigenes, it’s named that because its job is to break down oxalates coming in from in the diet. And the thinking earlier was that if oxalobacter was knocked out, which it’s a pretty sensitive organism, a couple of courses of antibiotics may do it, then your ability to break down oxalates kind of goes away. 

But as it turns out, because microbes in the gut will share genes and will create functional redundancies. There are other bacteria that can do the same effect. So, and that’s the case for estrobolome, for sulfate reduction, for ammonia production, all of these things that occur in the gut as

functionalities, more and more, we’re seeing that if you increase and maintain diversity, you’ll get a certain level of functional redundancy where you can be pretty assured that that biochemistry will occur in your system. And the only way to know that and feel assured about that, is by increasing diversity. And I think, and here’s the beauty of it, we can pick up those organisms from one another, right. Just the same as we pick up bad organisms from one another, we pick up good organisms from one another as well. 

Ari: Hopefully through a mechanism other than coprophagia. 

Kiran: Yes, actually, that’s probably really low on the list of what I would recommend. 

Ari: Just for people not familiar with that term, that means eating each other’s poop. 

Kiran: Right. We all saw that that might have been one of the first things many of us saw on the internet itself. There was a video I saw in college, it just threw me off the Internet for a while. And that shows you how old I am because the internet really started become prevalent when I was in college. But yeah, there’s a lot of mechanisms. I’ll give an example of this. This is, it’s really fascinating. It’s something called a microbiome cloud that surrounds all of us. And in fact, surrounds our households, and our workplaces, and all that as well. 

There was a study that was published by researchers at Johns Hopkins University, and he basically showed, what he did was first he got patients that were prescribed an antibiotic from the hospital for various reasons. And before they started taking the antibiotic, he got a couple of good stool samples from them. And then he did an analysis on their microbiome. Then he did the same analysis when they were taking the antibiotic. And then up to six months after they finished the antibiotic. 

With no surprise to everyone, what he saw was that there was a significant change in the microbiome, for the most part, a negative change in the microbiome when they were taking the antibiotics. And then that same negative change persisted for up to six months after they stopped taking the antibiotic, right. So, it was clear that the antibiotic had an impact on their microbiome. Now, that part wasn’t that surprising because other studies showed that before. 

But what was surprising, is he also did the same thing for those that lived in the same household with that individual taking the antibiotic, who did not take any antibiotics. And they were both romantic partners and platonic partners, as well. And so, what he found was that those that lived in the household who did not take the antibiotic also saw the same dysfunction occurring in their microbiome. And that same dysfunction lasted up to six months, right. 

So, we share our dysfunction and our function with one another. In fact, there are microbes in your microbiome that increase your altruism within society, actually it encourages you to go out and be more physically social with people because they’re trying to transfer from one another. 

Ari: Wow.

Kiran: So, microbes are everywhere. So, it becomes really important to hang out, and spend time, and be physically close with people who are fit, who are leading a healthy lifestyle, who are eating right, because that has an impact on your outcome as well.  So, if we don’t have the right microbes to do all these things for us, we should be able to pick them up from people as well. 

How to heal your mitochondria and your microbiome

Ari: So, Kiran, we talked about these three layers of how our mitochondrial function kind of gets damaged and the relationship of that to gut health to the microbiome. So, we’ve talked about low biogenesis, low mitophagy, and redox imbalance. We’ve talked about these layers of how the gut interacts, short chain fatty acids, butyrate, lactate, the urolithins, et cetera. So, how do we kind of tie all of this together? And then what can we do with all of this information on a practical level to improve our gut health, our microbiome health, and this gut mitochondria axis? 

Kiran: Yeah. So, that’s where that’s a million dollar question and where the rubber hits the road in all of this, right. So, our simple fix to all of this is really to increase the production of short chain fatty acids. And we’ll talk about how you do that. To increase the conversion of polyphenols, ellagitannins in particular, from certain berries, and fruits and nuts, into urolithins and urolithin A in particular. And then of course, production of lactic acid in the gut, which is directly correlated with certain types of lactic acid bacteria. These three things themselves will have a huge impact on your overall health, and wellness, and of course, the function and production of your mitochondria. 

And these three dysfunctions, low biogenesis, mitophagy, and redox imbalance drives all of these conditions, right. So, the way we look at it is the simple fact of increasing butyrate, increasing diversity, converting polyphenols to urolithins, and then, of course, improving the overall function of your microbiome by stopping leaky gut and so on. So, let’s talk about things. So, we’ve put together systems in place to help this. And I’ll talk about some real practical solutions as well. 

First, we started working with spore-based probiotics. Now, the reason we started working with spore-based probiotics is because spore based probiotics were shown in pharmaceutical use since the 1950s to be able to do something called quorum sensing. They can go into the system, read the microbial environment, and identify pathogenic overgrown organisms, sit next to them and actually bring down the growth of pathogenic and overgrown organisms. 

Now, that’s fascinating. Step one, that the fact that they can even read the rest of the microbial environment and know who’s there, right. So, our hypothesis was if they can do that with pathogenic and overgrown organisms, can they also then increase the growth of underrepresented organisms, or ones that are struggling in that gut ecosystem and bring back balance to the microbiome and thereby increasing diversity and so on? 

So, we published a couple of studies on this showing that, sure enough, just adding in the spore-based probiotics alone dramatically increases the diversity of the microbiome. In one such study, we saw a 30 percent increase in three weeks of taking the spore-based probiotics. That’s a massive increase in the number of functional bacteria doing work for you within your microbiome. And then they also significantly increase something important called keystone strains. 

In particular, akkermansia, faecalibacterium, ruminococcus. Now these strings are called keystone strains because they are really important players in maintaining the rest of the microbiome and maintaining diversity within the microbiome. And a number of these Keystone strains, especially faecalibacterium, prausnitzii and ruminococcus, are also major producers of short chain fatty acids. 

So, not only are they helping with the diversity in the microbiome, which is critical for overall health, they’re also kicking up butyrate production in a significant way. With the probiotic, we saw a 50 percent increase in butyrate and short chain fatty acid production in three weeks. Just adding the spore based probiotic in. 

Then we said, okay, can we enhance all these effects if we utilize a, what we call precision prebiotic, one that has oligosaccharides in it that specifically make it to the large intestine and feed certain keystone strains. And sure enough, this Mega Pre product that we formulated, when we combine it with the probiotic all of those effects double. So, the increase in diversity almost doubles. The increase in short chain fatty acid production goes from 50 percent to as high as 140 percent in some individuals, especially those that started off with really low levels of short chain fatty acid production. 

And so, just those changes alone will play a significant role in mitigating the mitophagy, in putting back the balance in the redox state imbalance, and also generating, improving the biogenesis of mitochondria. And then the Mega Mucosa is a product that we created that has a specific polyphenol mix that is high in the polyphenol compounds that can be converted into urolithins. And then it also has things like immunoglobulins to help bring down inflammation in the gut as well. 

Most importantly, it’s a probiotic and a prebiotic, that combination resolving the diversity issue within the microbiome and increasing the presence of bacteria that make short chain fatty acids. Just those two components alone will help you significantly mitigate the mitochondrial dysfunctions that occur over time. Now, other things that you can do that really help diversity. One is intermittent fasting.  Doing kind of a 16-8 fast or whatever suits your schedule but doing some form of semi-regular intermittent fasting will increase the diversity in the microbiome. As you stated earlier, increasing the diversity in diet is really critical in increasing the diversity in the microbiome as human… 

Ari: On that subject, I’ve heard you give an interesting tip. You’ve said something in one interview I listened to of yours, you mentioned, shop in Chinese and Korean grocery stores. I’ve never heard that tip, but it’s such a great tip, right. Because you just, we’re limited in the variety of foods that we encounter in our normal grocery store. So, go to an entirely different type of grocery store with different cuisine and you get different kinds of foods. 

Kiran: Totally. And then especially in the produce aisle, right. Because you’ll see fruits in a Middle Eastern, or a Chinese, or Korean grocery store that you won’t see in your Whole Foods and Trader Joe’s. You’ll see things like star fruits and things that have different compositions that feed different bacteria, even within families of food. So, within cabbage itself or within tubers and roots that you’re used to, you’ll see cousins of those versions of food in these other types of grocery stores. 

And because they are slightly different, they will feed different types of bacteria. And so, the easiest way to do it is I tell people just each week, go to one of these ethnic grocery stores and pick one or maybe two fruits, or foods, that you’re going to add into your diet that week. You don’t have to make a whole Korean meal. You don’t have to make a whole Chinese meal. You don’t have to complicate it. Just adding in small amounts of different foods each week can really play a role in increasing diversity. 

Another great way of doing it is by getting a dog, right. And we know that I showed you earlier data that shows that maintaining diversity actually increases your longevity. And it’s a big measure of both your biological and chronological age. Just two weeks ago, a study published showing that households that brought a dog into the household actually increased the longevity of members of the household. 

So, that is significant because other studies have shown that if you have a dog in your household, it increases the diversity because they’re bringing stuff from the outside and they’re exposing you to it. So, in addition to reducing the amount of sanitizing we are doing in our household products, I mean, it’s important to note that a clean house is not a house that smells like chlorine, and chemicals, and is sterile, right. That is a programing we all have in the Western world that this sterility is associated with cleanliness, when, in fact, the more microbes we have in our ecosystem, the healthier the ecosystem is. 

A Finnish allergy study showed that in households that had kept doors and windows open more often and did not sanitize the surfaces, had lower levels of allergies, asthma, and viral infections in kids. And so, these type of aspects become really important getting out in nature. Of course, there’s a whole grounding idea with getting that grounded with the with electron flux from the earth. Besides that, just getting out in nature, there are lots of bacteria in nature that actually enhance diversity within your microbiome and can enhance mood by stimulating serotonin production and so on. 

So, exposure is really important. I recently posted something on social media that showed that people that have bigger social circles and spend a little bit more time with those social circles in person, actually had better health outcomes overall. And again, that is appeasing our evolutionary need of being social creatures and animals. So, all those things matter quite a bit. Taking the right probiotic and prebiotic can have a huge impact. All of those lifestyle things are going to be really, really prevalent in improving your overall outcomes. 

And then one more thing I want to mention is, a vitamin that people really don’t talk about when it comes to energy, and that’s vitamin K2-7. Vitamin K2-7 is something that I kind of fell in nerd love with a couple of decades ago because it’s produced by bacteria, right. So, the bacillus bacteria, the spores that we work with, produce high levels of vitamin K2 and it’s fermenting certain substrates like the natto bean, in the nattokinase, the Japanese food, and it produces a very high level of this vitamin called vitamin K2-7. 

Now, it’s been extremely well studied in bone health, and heart health, and neurological health, and so on. But we started asking the question, why do bacteria produce vitamin K2-7? And because they don’t have bones, they don’t have hearts, so they’re not using it for that. What do they use it for? As it

turns out, bacteria use vitamin K2-7 as the main receptor in in their electron transport system. 

So, remember the Krebs cycle that then feeds into the electron transport system. The electron transport system has compounds like ubiquinols that shuttle the transport mechanism to produce ATP. In humans, we use Co-Q10 or ubiquinols, but as it turns out, we also use vitamin K2-7. And in some studies, vitamin K2-7 is shown as a better transducer of the electron transport chain then ubiquinols. And in fact, we started studying that at University of Texas and we found about a thirty percent increase in ATP production when you add vitamin K2-7 into the system. 

Ari: Wow. 

Kiran: Thirty percent. So, that’s the ability, the bioenergetics of the mitochondria to produce energy and fix that energy, the redox imbalance that’s going on. And in fact, vitamin K2-7 has been shown in both an Alzheimer’s and Parkinson’s model to be able to reverse damaged mitochondria and increase the energetics of a damaged mitochondria. So, aside from all of the things that you do for the microbiome that we talk about, one thing that becomes really important as a nutrient for your mitochondria, is going to be vitamin K2-7. 

Ari: Kiran, this has been phenomenal. You are just a wealth of wisdom and brilliance here, as it pertains to, of course, gut health, and mitochondria, and the link between them. Just phenomenal the way you’ve put the pieces together. I love it. I want to quickly just wrap up with just a list of everything you just said, because there’s so much gold here.  

So, you mentioned lifestyle tips, intermittent fasting, daily feeding and fasting windows. Keep the windows open, get out in nature, let the dirt in, don’t over sanitize, get a dog. 

Kiran: Yeah. 

Ari: Just got a puppy four weeks ago myself. So… 

Kiran: Awesome. You’re going to live longer now. 

Ari: Yeah. 

Kiran: Because the studies show you actually live longer when you bring a dog into the household. 

Ari: Yes, it’s all about me. That’s why I got him, it’s all about my selfish interests in longevity. And then, of course, your products that you mentioned. So, Mega Spore Biotic, Mega Prebiotic, Mega Mucosa, Mega Quinone or Quinone. And we’ll have links to all of those products on this page so people can get them. People can download them, in the links below this interview. So, Kiran, and please, if I forgot anything in that list, did I forget…? 

Kiran: No, nothing at all. Just, maybe just a diverse diet. That’s a really important part. The tip of adding in other types of foods from ethnic stores. And one other message I would put forth to people is, what’s the beauty of this body, and the system is its ability to repair itself, right. 

We have all of these systems in place to regenerate tissue, regenerate mitochondria, and repair damage that’s being done. And it doesn’t matter if you’re 30 or you’re 65 years old, you can still repair your system. It’s about putting your system in the right context to allow that repair to occur. So, it’s never too late to improve. It’s never too late to regenerate. It’s never too late to get healthier and live longer. 

Ari: Beautiful. Kiran, this is honestly one of my favorite interviews that I’ve ever done. This is just brilliant, phenomenal stuff. Thank you so much for it for sharing your wisdom with my audience. I really appreciate it. And I look forward to connecting again. I feel like I want to talk to you for the next five hours. 

Kiran: Same here. 

Ari: I have loads of questions I want to ask you and not enough time to do it. So, we’ll have to do another one of these. 

Kiran: I look forward to it. Thank you, Ari. 

Ari: Yeah. Thank you so much. 

Show Notes

The mitochondria microbiome axis (01:15)
The link between mitochondria and health (07:19)
How the gut bacteria affect our mitochondria and energy production (30:24)
How to heal your mitochondria and your microbiome (44:00)


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