Kiran Krishnan on How to Build a Resilient Microbiome

This episode is brought to you by Nourish Me Organics, your Gut Health superstore. Are you looking for well researched probiotic supplements? Well, look no further. We have a range of clinically proven probiotic supplements including VSL3, Vivomix, Mutaflor, and recently the Microbiome Lab suite, including Megaspore biotic. Head to www.nourishmeorganics.com and use the code GUTHEALTHGURUS for 10% off. Hey guys. Crippen Govender from the Gut Health Gurus podcast. I've got a background in food science and I've got an amazing guest today. I've been trying to get this guy into the podcast for some time. He is an amazing smart speaker. He's making some serious waves around the world with his work around the microbiome and probiotics. Kiran Krishnan, welcome to the show.

Thank you so much for having me. It's such a pleasure to be on and thank you for connecting so far across the globe.

My pleasure, Kiran. I just wanted to make sure. Did I get your name right, Kiran Krishnan?

You did, yeah, absolutely. And you say it the way my mom would say it, so it's perfectly correct. I've heard many variations, but the one that's the most correct.

Awesome. Your background, Kieran. I've just got burning interest now that you mentioned about your mom.

Yeah, I grew up in India. I was born in India. I grew up in South India. I also lived in Malaysia. My dad actually grew up part of his life in Malaysia. His family's based out of there. We had a good mix of living between India and Malaysia, where I picked up a lot of good microbiome out there, as you can imagine, in India as well. And moved to the States just before high school and moved to a suburb outside of Chicago. Did all my schooling in Iowa and came back to Chicago, back to civilization after that. I've been here ever since. I'm based in Chicago right now.

Wonderful. I guess the pronunciation that I got right would lend itself to the fact that my ancestry is also South Indian.

But.

It'S in the linguistics with that kind of Tamil background. But my origin story is actually from South Africa, so third generation South African. And then we moved to Australia. And so what I typically like to do when I start my show is to introduce you to our audience. And you did introduce your parts of your story, but I want to go a bit deeper. So who is Kiran Krishnan?

Yeah. So, you know, I always joke, I'm a simple kid from the villages of India, just with a high degree of curiosity for the world around me. Right. So I was never one to take for granted how things worked. And that's one of the ways I describe the way my mind works. Right. I remember, for example, when I came to the States for the first time, there were so many things that people used and were commonplace that, to me, were completely foreign, like the microwave. We never heard of or used a microwave in India or Malaysia, and they came here, and I was always fascinated that you could put something in here in that machine, push a button or two, and it would get really hot in a short period of time. A lot of my friends, of course, knew how microwave worked, but they never understood what was happening. They knew how to work it, but they didn't know how it worked. That was the kind of curiosity I always had, is I never wanted to not understand the world around me. That lended the idea of adapting science, because science gives you somewhat of an understanding of the world around you. My mom's a doctor. She. She's a medical doctor. And in fact, I was always so curious about medicine and how the body works and all that, she actually named one of her clinics in Malaysia, Clinic Kirin. That was named after me because I would always be in there and looking at all her tools and looking at medication boxes and always asking her if I could watch when she's doing certain procedures like suturing people and so on. There were a few occasions that happened in that clinic that I think really drove me to wanting to study science. The big one that I remember was I was in my mom's clinic. We lived above the clinic, which occurred a lot in Malaysia and all that. In those kind of structures, people would have a shop and you would live above the shop. Or in this case, we had a clinic, and we'd live above the clinic. There was a guy that came hobbling into my mom's clinic, a worker who was working out in the field or the road or somewhere, and his big toe was massively swollen. He had dropped something really heavy on it. Basically, the nail was swollen, and the toe itself was just ballooned out. And he was in excruciating pain. I was actually in the front of the clinic when he came in, and I saw that thing throw, throbbing from 100ft away. And I was like, oh, my God, I've never seen such a thing. And he came in, and clearly he was in excruciating pain. And my mom took him in, and I was like, mom, can I come in? Can I see this she's like, sure, come on in. I came into the room to see what is she going to do to this insanely gnarly toe. She went in and she got a bunch of tools and all that. Then the first thing she did was she got these crazy looking tools and out his toenail. Right. And I was just baffled. That was not what I thought she would do. I thought she would rub some cream on it or put, this is an 8 year old me, right. And so I didn't really understand anything, but I thought she would put a bandage on it, rub some cream on it or do something. But she went in and ripped out his toenail and then put a hole in his nail bed and then squeezed out all of this blood, this dark blood that came oozing out. And that gave him absolute relief. Right. And it was so counterintuitive to what you would think you would do and that I remember being kind of a really important moment because I remember that so vividly, because it was so impressive to me that she had the knowledge base of how that toe functioned and what was happening in there, why it was swollen, what was causing the pain, that she was able to use her tools and her skill set to do this thing that seemed crazy, ripping out his toenail, which actually gave him immense relief. That kind of incident was a kind that really propelled me towards science to understand how the human body worked. Because it always bothered me that I could walk, I could talk, I could run, I could do all these things, but I didn't really know how all that was happening. Mmm.

And that led you onto a path of microbiology. So how did that eventuate?

Yeah, so that, that actually is all because of Hollywood, really. It comes down to the importance of watching movies.

You know.

And frankly, I was, you know, I knew I wanted to go into science. I actually thought I was wanted to go into medicine. And like every good Indian kid, I was pre med student. When I first joined university, I was enrolled as a pre med student and I wasn't sure which particular science I was going to study. In the first week in the dorms, just as kind of a social thing, they were playing movies in the lobby area. People would come down and sit and watch movies. One of the first movies they played was a movie called Outbreak, which I don't know if you remember, with Morgan Freeman and Dustin Hoffman. Right. So it was that simian virus that came in on this monkey and caused this massive outbreak of this really terrible disease in the small town. And the military was going to come and Bomb the whole town and all of this awesome drama. But underneath it all, there were these amazing scientists that were running around trying to chase this virus and figure out antidotes and all that. They were microbiologists and virologists. That's what really triggered me into saying, that's what I want to do. I want to chase. In my mind at that time, I wanted to chase Ebola and all the scariest diseases and find treatments to all of these things. Then the very next day, I went and I enrolled in the school of microbiology, and that's how that started.

Wow, what an amazing origin story. I love that from the movies. And being inspired by Hollywood led you down this amazing field of microbiology. And the microbiome question for you. How would you describe your gut health and what does good gut health look like?

Yeah, so that's a really interesting question. In fact, I've done. I can't even count the number of interviews I've done, but that's the first time anyone's asked me about my gut health, which is really interesting. The way I would describe my gut health is with the word resilience. I think that should be the goal with most people in terms of where do you want to get to with regards to your gut health? We, as a species, humans, are omnivores. There are people out there that are vegan. There are people out there that. That are Paleo. There are people out there that are carnivore, that are on a carnivore diet. I mean, I've met people that all they eat is two steaks a day, and sometimes they'll throw an egg on it. But what's interesting when you look at the vast majority of human existence, we've existed as omnivores. We're lucky in that respect because we can eat many different things. We can eat all along the spectrum of biological abundance around the world. We can eat nuts and seeds and roots and tubers and insects and animals and plants and get through and survive that way. That's really important because if you look at the course of human evolution, there were many phases and even geographic locations in the evolution of both human history and animal history, where we were able to move up the evolutionary ladder, up the food chain. Number one, because of our intelligence. Number two, because of our resilience in our ability to eat a diverse diet. If you think about a lion, for example, a lion is an obligate carnivore. A lion cannot eat plants. It would get very sick. It would die. The lion Is heavily dependent on the population of wildebeests and other mammals that are walking around in the savanna. If there's a drought and their food source gets hampered because their food sources are obligate to herbivores. With the drought, the herbs go down or the plants go down, the herbivore population goes down and the lion suffers. With humans, if there's a drought, we could go eat termites, we could go eatwe could dig in the ground and find weird roots that we can eat. We can eat so many different things. The reason for that is we had gut resilience. Now we have so many people that are so sensitive to. To such big groupings of foods. I know so many people that can't eat eggs, can't eat dairy, can't eat wheat, of course, and can't eat certain types of grains, can't eat nightshades, they can't do soy, all of these different things, because they would have this negative adverse reaction to it. Also, their guts tend to be very sensitive to even minor changes in their work or their environment. So stress will create a significant amount of dysbiosis changes, geographic changes, traveling outside of the country, traveling to another city, all of these things create dysfunctions in their gut, which has a huge impact on their overall health. My focus has been to building resilience within my gut. I want to be able to eat anything. I don't want to be at a restaurant and quizzing the waiter on the chances that the dish I'm ordering has touched gluten somewhere in the kitchen. I don't want to be in the restaurant and having a hard time finding something to eat when the rest of my friends are socializing and just ordering off the menu. Too many people live with low resilience within their gut and are very sensitive to any sort of changes outside of a narrow range. That's how I describe my gut health. And I think that, to me is the most ancestral like way of existing. We should always make the right food choices. We shouldn't be eating, of course, crappy stuff out there. We shouldn't be eating burgers and fries all the time and all that. But you also shouldn't suffer for a week if you have some croutons and a salad, or if you eat a burger or if you go out for a night of drinking and have a few brandies or something, Throw you into a suffering fest. That's my goal for people, is to be able to build some resilience and be able to live. It really hampers quality of life when you have to be overtly vigilant on what you can put in your body.

Totally agree. I love that response to that question because it's so succinct and simple that just to have a resilient gut, I'm sure there'll be a raft of benefits to people across the planet because gut is such a huge area of dysfunction throughout the planet, and specifically the Western world. So, Kieran, how do we build a resilient gut?

Yeah. So, you know, one of the analogies I always give people is we are a something called a holobiome. It's a word that I use a lot. It's defined as a superorganism. We are actually an organism that's made up of groupings of thousands of other organisms. They work together in concert in order to perpetuate the health of the entire ecology. We are essentially a walking, talking rainforest. We have all of these micro ecologies in all of these different parts of the body that have to communicate with each other, that have to support one another. Metabolites that are produced in the gut feed the bacteria in the vaginal canal, in the eyes, in the blood even. I mean, all of these areas that we thought were sterile, now we know, all colonized by viruses, bacteria, fungi. There's nothing sterile in the human body. We are a microbial construct. Then you take this microbial construct and you put it in an antimicrobial world. Everything around us kills bacteria. The stuff in our drinking water, the chlorine and the fluoride in our drinking water is killing bacteria. All of that Roundup and herbicides and pesticides on our food that are so prevalent, all of those kill bacteria. The antibiotics, of course, we use personal care products, preservatives and foods. All of these things are designed to kill microbes. And we are made up of microbes. Because of that, we really diminish our resilience because we bring down populations of really important, healthy bacteria that add to the resilience within our ecology. My focus is twofold. One is to minimize my exposure to things that I know harm the microbial ecology within the body. If you can choose organic food, eat organic food, because that's going to have less of the Roundup and the glyphosate and all of those herbicides and pesticides. If you can filter your drinking water through a carbon filter, remove some of the chlorine, do that. If you don't have to take a course of antibiotics, because more than likely that sinus infection you have or that cold that you have, is a viral cold, not a bacterial cold. Than forego that antibiotic I try to do. Oh, and then personal care products, that's a really important thing. Personal care products are full of crazy antimicrobials, most of which have never been tested on humans. I try to go as clean as I can with my personal care products to minimize my exposure to those things. Now, in this modern world, you can't eliminate exposure to all these things, but you minimize it so you have less impact on your inner ecology. That's one part. Then the second part is maximizing exposure. You want to maximize your exposure to microbes in the outside world. I'll give you a great example of that. There's something called the Finnish allergy study that was actually completed about a year and a half ago and published. It's a large scale long term study. There's a town in Finland that geographically is quite close in proximity to Russia, another town in Russia. So there's two towns, they're about 100 kilometers apart, which is not very big. So the geography in that region is very similar. The food sources in that region are pretty similar as well. But in the Finnish town, they have a really high prevalence rate of allergies and asthma. And in the Russian town, just 100 kilometers or so away, they have far less incidence rate of allergies and asthma. Then the question has been what is causing that significant difference? In Finland, allergies and asthma are becoming an epidemic. The government is spending a lot of time and money and effort trying to figure this out. This is one of the studies. Now, when they looked at hundreds and hundreds of people and families and homes and all that between these two towns, the one thing that they found that was the most prevalent and seemed to have the biggest impact was that in the Russian town they kept their doors and windows open more so outside microbes and all that would come in two. They did not sterilize their home. They did not clean their home with antibacterial cleaners and cleaners that say on the bottle kills 99.9% of microbes. They did not sterilize their home, which means that their home had a good abundance of bacteria that come in from the outside all the time. That exposure to bacteria curbs their development of allergies and asthma. In the Finnish town, they kept the windows and doors closed far more often, so they got less fresh air and bacteria coming in. Then they also cleaned their surfaces quite diligently with antimicrobial cleaners. The culture there in Finland is more that everything should Be very clean and sterile and has that smell of the cleaners and so on. That represents cleanliness, but in fact it represents illness. That lack of exposure to microbes causes that problem. I try to get as much exposure I can. I try to be outside as much as I can. If I go for a hike on a trail in a mountainside, if I'm going to pick up a sandwich and eat it after that, I'm not going to use hand sanitizer on my hands like a lot of people would, because you want some of that dirt, you want some of that environment on your system, in your system and so on. Minimizing exposure to antimicrobials and then increasing your exposure to microbes, just that simple change will allow you to develop a more resilient system. Then there's a third part, and that's the diet part of it. With the diet side, I try to eat as diverse of a diet as I possibly can. I don't follow any particular type of diet, I don't follow vegetarianism, veganism, paleo, carnivore, whatever it may be, all of these different diet types. Because our ancestors didn't follow any particular diet type. They ate what they could, they ate what they could find, they ate what they could gather, they ate what they could forage and what they could hunt and kill. Anthropological studies show that early humans consumed as many as 600 different types of foods annually. We, if you look at a westerner, consumes maybe 20 different types of foods annually. So trying to increase that diversity in my diet is a significant impact factor on the diversity in your microbiome and the resilience of your microbiome. And then of course I use a lot of the spore based bacteria as well, which does a lot of amazing things. The gut.

Wow, Kieran, what a start to the show. I mean, you've given some absolute nuggets spending more time outside increasing the diversity of the diet that we're consuming and potentially looking at products like your spore based product as well, which we will delve into shortly. But one topic I did want to cover with you was something I found fascinating. Metabolic endotoxemia.

Oh yeah.

So when I heard you speak about that, I was mind blown. So how about you explain to the audience what is metabolic endotoxemia and why is this such an issue?

Yeah, it's funny, a lot of times when I speak about metabolic endotoxemia at functional medicine shows, often I take a survey right in the beginning of the talk and I ask the doctors and I say, okay, how many of you have brought a patient in and did a full analysis, a full history, blood work and all of that, and then written down the diagnosis of metabolic endotoxemia? I always get a little bit of a laugh because nobody has ever done that yet. When you look at the signs, it is likely the major driver of upwards of 90% of chronic illness. It's so prevalent. In fact, large institutions like the American Diabetic association, the American Heart association, the nih, they are all studying metabolic endotoxemia because it's such a prominent driver of chronic illness. Basically what it is, it's a really fancy term for leaky gut. And the most prevalent type of leaky gut. Let's break down the terminology first. Metabolic endotoxemia. Metabolic meaning it is associated with the process of digestion, breaking down food, converting food to energy, and so on. Everything involved in that, so just the process of eating. Then endotoxemia means an endotoxin, which is different than an exotoxin. An endotoxin is a toxin that's derived from within. It's not a toxin that we're getting exposed to from the outside. It's not like a mold toxin or something. It's a toxin that's derived from within our own body. And the EMIA ending means that it's in the blood. So the toxin is being generated through the metabolic process and now ends up in the blood. That's how you would define it and understand the terminology. Basically, what happens is when your gut is leaky and you have metabolic endotoxemia, every time you eat food, you get a massive influx of a particular type of toxin called LPS lipopolysaccharide. This is a toxin that is found on the cell membrane structures of gram negative bacteria. For your audience that doesn't know what in the world a gram negative bacteria is, basically every bacteria in the world can be categorized as either gram negative or gram positive. What that means is one way of studying bacteria is you take them and you stain them with this red gram stain. And then you look at them under a microscope. And if they are gram negative, it means that the stain doesn't take. If they're gram positive, it means that the stain did take and now the bacteria. Look, the reason for the stain taking is those bacteria have a cell wall structure. They have this additional cell wall that takes up the stain and that makes them gram positive. When they don't take up the stain, they don't have the cell wall and they're gram negative. That's microbiology 101 for your audience there. They can dazzle people at cocktail parties with nerdy gram staining talk. That's the difference what happens with gram negative bacteria, the ones that don't have the cell wall so the stain does not take. They have this compound in their cell membrane structure called LPS lipopolysaccharide. It's basically a fatty acid with sugar on top and it's a transmembrane compound, meaning it sticks inside the membrane of the bacteria. Now, the bacteria use it for many different things. They use it for signaling to other bacteria. It communicates with our own immune system. It can be used for binding to the mucus layer in the gut and so on. When it's in the bacteria, it doesn't cause any issue when it's out of the bacteria, meaning when the bacteria dies and the cell breaks and it releases this lps. When the LPS is free on its own, it becomes a really potent toxin, and especially potent to us, our immune system. When it sees this particular toxin floating around by itself, not in the context of being part of a bacteria, it freaks out. The reason for that is because it indicates to the immune system that there's a bacterial invasion coming into the body. Because the immune system is not supposed to see high levels of this endotoxin in the blood. Because if you see it in the blood, it means there's a whole bunch of this bacteria in your blood and they're actively multiplying and they're releasing toxins and that's what's going to make you sick. Everybody who's probably listening has heard of something called sepsis or bacteremia, right? And we know how dangerous that can be. You could go from being perfectly healthy looking, walking, talking, to being on death's doorstep in 24 to 48 hours if you have sepsis. Sepsis is the same thing as metabolic endotoxemia, but it's a far more pronounced version of it, that blood infection. That's when LPS gets propagated and produced at too high of a level in the blood. What's happening is there's LPS in the gut, in the lumen of the gut, which is the tube that goes through in the intestines, there's a whole bunch of this gram negative bacteria. In fact, probably 70% of the bacteria that live in your gut as your normal passengers that come along with you through the ride of life, they are gram negative bacteria. During the digestion process, when you eat food, the bacteria will die. And that's a normal process because of the acids released and digestive enzymes and bile and all this stuff that's going on. The digestive process is a violent process happening in the gut, and bacteria will die. When they die, they will release their lps. So when this LPS is released in the gut, it's perfectly fine. It doesn't cause us any harm. It's supposed to be neutralized in the gut. Certain bacteria will metabolize or break it down. Your immune system is supposed to send antibodies to neutralize it, and you're supposed to poop it out a few hours later and it doesn't cause any issues. But when your gut is leaky, the process of digestion releases LPS and causes the tight junctions, which is the space in between your intestinal cell line. Cell lining opens up and this LPS leaks through into your circulation. It leaks through at a really high level. LPS endotoxemia is defined as a five to six fold increase in the level of this endotoxin in your blood within five hours of eating a meal. The problem with that is it sets your body up for this really potent, long term chronic inflammation. Because every time you eat food, you're having a little blood poisoning or sepsis. It can concentrate in your knees, where it can develop into rheumatoid arthritis. It can end up in your brain, where it causes Alzheimer's and Parkinson's and senile dementia and chronic anxiety and depression. It has all of these impacts all over your body, and it happens when you eat. The problem is, if your gut is leaky in this way, the only way to prevent it, outside of the intervention that we've developed, is to not eat. That's not a solution. As a human, we have to eat. The most normal, common thing that we all do as a human becomes the most toxic thing we all do. It's far more toxic than all of the other behaviors that people may have because it sets you up for chronic disease.

And that's a huge issue with lps. And as you mentioned, once it gets into the blood, well, becomes an issue. And so with lps, are there specific types of bacteria that have more LPS than others?

Yeah, it's all the gram negative bacteria. So all classes of gram negative bacteria. Now, some gram negative bacteria will produce more toxigenic lps. So there are certain pathogens, like certain types of E. Coli that have more toxic lps. Those can induce more of a toxic response in the body than others. But in general, LPS in the gut, sorry, LPS in the Gut that's allowed to translocate into the circulatory system because of a leaky gut lining is going to cause significant chronic inflammation and which becomes then the foundation for most chronic illnesses. The American Diabetic association has published a dozen or so studies showing that LPS endotoxemia is the primary insult that leads to diabetes. For example, one of the studies they published last year, this is a study called the Cordial Prev study. They took 462 people that had high risk for developing type 2 diabetes. They had all of the risk factors. They were obese, they had family history of diabetes, they had high cholesterol, they had all of these markers and characteristics of developing diabetes. They did not have diabetes yet. Then they followed those individuals for 60 months. They were measuring all of these different markers to see which of the markers that they had were the best predictors of the development of diabetes. What they found was that there was only one marker. Of all of the things your doctor can test you for, there was only one that accurately predicted 100% of the time that the individual was going to develop diabetes, and that was the amount of LPS in their circulation. The more LPS you had in your circulation, the higher risk for diabetes is. In fact, the paper even suggested using LPS levels in the blood as a primary predictor of the development of type 2 diabetes. When you think about it, type 2 diabetes is said to be the biggest pandemic that we're going to face as a health issue. Right. Right now, it's something like 700 million people across the world are diabetic. And they estimate that four times that number are pre diabetic. And so at some point in the next couple of decades, we're going to have 3, 4, 5 billion people in the world that are diabetic. When you're diabetic, it quadruples your risk for many other chronic illnesses like cancers, heart disease, Alzheimer's, dementia, Parkinson's. All of these things are doubled to quadrupled. It becomes an underlying threat to humanity. As it turns out, this leaky gut, this lps, is the driver of this thing, and it comes from a dysfunctional gut.

Is there a particular mechanism that leads to LPS driving diabetes in the body?

Yeah. In fact, there's two mechanisms. One is they've been able to show that lps, once it's in your blood, it'll go through your circulation. It can cross the blood brain barrier and enter your brain. It'll go into the hypothalamus and it will cause Inflammation in the hypothalamus, which makes your brain dysfunctional in terms of reading your blood sugar levels. Your brain is supposed to be able to tell what your blood sugar level is and release insulin and glucagon in response to it. And that is something called central insulin resistance. Most people know insulin resistance and diabetes as being an issue with your pancreas and your pancreatic isolate cells that produce insulin. That does happen, obviously, but that seems to be secondary to this formation of central insulin resistance in the brain. Part of the problem is that your brain no longer can communicate with the rest of your body to figure out what your blood sugar levels are effectively. Then your pancreas just starts producing lots of insulin all the time because of these crazy spikes in blood sugar levels. Because your body, your central command center, your brain can't control it. Then LPS actually also targets the islet cells in your pancreas, which are the cells that actually produce insulin, and starts killing off those cells through inflammation. It's a two prong approach to causing diabetes. In fact, in the us, and I don't know if this is the case in Australia, but in the US we're seeing more and more cases of young people showing up to doctor's offices. We're talking about 18 year olds, 17 year olds, 20 year olds who are not obese, who don't have classic metabolic syndrome, but they're showing up with a diagnosis of type 2 diabetes. That's what the most recent research on central insulin resistance, which is insulin resistance, starts in the brain. It's irrespective of body weight, you don't have to be obese, you can be lean, you can be what seems to be healthy and still develop type 2 diabetes because your gut is super leaky and that LPS is getting in and causing that central insulin resistance.

Wow. I have a burning question. Why is this impacting us at a younger age?

So more and more, what we're finding out is the mode of birth will have a major impact, right? So over the last 25, 30 years, or maybe even a little bit more, we've pushed more and more people towards cesarean section as almost an elective method of birth. Now, there are lots of people that end up having to do a cesarean section for medical reasons. But up to 33% of all births are now cesarean section, and a good number of those are elected for because it's easier, it's more convenient in many ways. You can predict and know exactly when you're giving birth. C section babies tend to have a highly dysfunctional microbiome compared to vaginal born babies because they're not getting that really important initial inoculum from mom's vaginal canal. Right off the bat, C section babies have an increased risk for immune dysfunctions, hormonal dysfunctions, metabolic dysfunctions and so on because they're not getting the full correct microbiome established that is supposed to happen during the birthing process. That's one driver of it. The second driver is the incessant use of antibiotics, especially with kids. The center for Disease control in the US even estimates that up to 50% of antibiotic prescriptions are unnecessary and they're used for things like viral infections. I've talked to lots of doctors about this, especially in places like urgent care centers where people are just going in acutely because they have a cold or flu or whatever the symptoms are. What's happening is doctors, patients are going in and they have some sort of illness. They're feverish, they're stuffy, all of this. And they're looking for a pillow to make them better because they don't want to miss work, they can't afford to miss more than a couple days of work and so on. And so they're pressuring doctors to give them something even though the doctor knows scientifically, intuitively that they have a viral cold and this antibiotic is not going to help them. But they are pressured to write a prescription because they know that the patient won't come back to that same urgent care center the next time they're not feeling well, because they will go to where they can get an antibiotic, and that's with adults. Now with kids, pediatricians feel pressured to write antibiotic prescriptions because parents push them towards it when their child is sick. I can understand that there's nothing worse than your kid being sick, especially if your baby's screaming because of an ear infection that's painful or throat infection or something like that, and you want to relieve their pain and their issue. So you want the doctor to give them something. They hate the idea of the doctor saying, oh, it's a viral thing. It'll work its course in four or five days. They can't take that. There's a lot of pressure on doctors to write antibiotic scripts. Those antibiotics can have a significant long term impact on the microbiome, the leakiness of the gut, and then all of the foundations for these other chronic illnesses. We're seeing kids at an earlier and earlier age having significant dysfunctions in their microbiome when you look at things like ulcerative colitis, prevalence rates in young kids, in young teens, or Crohn's. These things are allergies and asthma, which are a pandemic as well. All of these things are tied to that gut dysfunction.

It all comes down to the. The leaky gut issue or the metabolic endotoxemia, which seems driven by chronic overuse of antibiotics and things that disrupt the microbiome. So that's beautifully, beautifully summarized, Kiran. And now let's talk about. We're actually coming up to time, but I think this conversation is absolutely amazing. And if you wouldn't mind, I would love to talk about some probiotic stuff as well.

Yeah, absolutely, yeah.

So now you guys are involved in your particular company on development of probiotics to address a lot of these issues that we've spoken about and pretty much done in a clinical setting where you're running trials and whatnot. Firstly, let's start at the beginning. Firstly, what is a probiotic? Just very quickly.

Yeah. So the definition of the probiotics. Here's how the World Health Organization, the fao, basically every scientist accepts this particular definition. It is a live microorganism, when administered at adequate amounts, confers a health benefit to the host. There's a few different things that are really important in that definition. Number one is it has to be a live microorganism. It has to be something that's alive, that can get through the gastric system alive and enter into the digestive tract and function as a live bacteria. Then the second part is when administered in adequate amounts, confers a health benefit to the host, meaning there's a dose response to it, and then there is a known kinetic to the probiotic, meaning you dose it at this particular effective dose. It has this particular health outcome that encompasses what it is. But basically, in layperson term, it's a good bacteria that can give you a health benefit, but it has to be alive. And that's a really important part of it.

Correct definition. People might be wondering, it ends up in a little capsule, a little sachet. But how are these things actually made? Where are these bacteria actually derived from?

Yeah, a lot of them. A lot of the, what I call conventional probiotics. So when you look at your health food source store online, the vast majority of probiotics you see will fall into the category that I call conventional. When I say conventional, I mean they are predominantly made up of Lactobacillus and bifidobacteria. They are anywhere from five to 15, in some cases, 30 different strains in these products and the dosages get ever increasing. They go up to 3, 4, 500 billion. Those are kind of your conventional approach to probiotics. Now, the vast majority of those kind of probiotics are derived from dairy products, from fermented dairy. Some of them are derived from originally from healthy human volunteers, but all of them are actually produced by fermentation.

I have to pause you there for a sec. What do you mean when you say healthy human volunteers?

You know, so basically scientists look for what looks like healthy people walking down the street and they kidnap them and they throw them in the back of a van and poke and prod them for bacteria and they get a bunch of bacteria and they put them back on the street. But that's kind of what it sounds like, right? Although the volunteer part means that they opted to do it themselves. No. A few decades ago, when we were starting to understand that there are beneficial bacteria, there are some that have interesting functions. A lot of universities, a lot of labs and scientists were sampling different body sites of people. They were sampling fecal matter of volunteers coming in and they were looking for microbes that lived naturally and organically in different parts of the body. In some cases, they found certain microbes having really unique effects within that particular person. The whole idea was then trying to take that same microbe, grow it in fermentation, and then administer it to other people to see if it had similar effect. There was a lot of isolation. The spores we work with were isolated from healthy human volunteers a decade ago. We work with Royal Holloway London University on these particular spores and they were looking for native Bacillus spores that were natural colonizers of the human gut. They got a lot of healthy volunteers to come in and donate fecal samples. And they basically tried to isolate these bacteria from the fecal samples. Looking for human derived functional bacteria. A lot of times when people hear some companies will market their products as human derived, that means that the bacteria was isolated from some human specimen at some point. If it's not human derived, then it could be lacto derived, which means it comes from some sort of dairy fermentation process.

Gotcha. Gotcha. You mentioned the word spores. Some people might be wondering what is a spore based probiotic?

Yeah, they are a unique set of bacteria. They're typically in the genus Bacillus. That's what they're called. As opposed to Lactobacillus. Lactobacillus is different than Bacillus. It's a different group or type of bacteria. These bacteria are really Unique. They are ubiquitous in the outside environment. So you find them in the dirt, you find them in dust and vegetation and rivers and streams and all that. They're very ubiquitous in the outside environment, but they're also fairly ubiquitous in the human gut. They are both colonizers in the gut and also live in the outside world. When you look at a bacteria that does that, it really speaks to a very unique feature and function of that bacteria. Because the inside of your body, the inside part of your intestines, is a very, very, very different environment than the outside world. Many people don't even realize that it'd be equivalent to a human that could live on land and could also live 5,000ft below the ocean surface. We know how different 5,000ft below the ocean surface is. There's no light, there's a little bit of oxygen, there's high pressure, it's super cold, all of these things. Yet if you can live in both of those places, you'd be considered a superhuman. These are essentially super bacteria because they can live in the outside world where there's UV radiation, there's desiccation, it's oxygen rich environment, all of these things that bacteria have to adapt to, then they can also live inside the gut where there's no light, there's no UV radiation, there's no oxygen in most of your digestive tract. It's an anaerobic environment. There's no oxygen, there's liquid and food and all of this stuff constantly moving through. There's an immune system and there's about 100 trillion other bacteria in there. And then also their ability to pass through the gastric system. The gastric system is like a gauntlet for bacteria because there's so many steps in the process of swallowing something that is designed to kill microbes. Number one, the stomach acid. Stomach acid is super strong. If you have normal stomach acid, you've got a PH of hydrochloric acid of around 1.3, 1.4. To understand what that means, if you had hydrochloric acid in a cup and it was at the PH that's in your stomach, if you stuck your finger in it, it would burn off your skin. That's how strong it is. If you poured it on metal, it would eat through metal. That's how strong that acid is. That's in your stomach. That is called the gastric barrier because it kills the vast majority of bacteria that's trying to enter your system. Then the second step, if a bacteria makes it past that, there's something called bile Salts, bile salts, which are released in the small bowel. Those are strong antimicrobials. Those kill bacteria as well. Then you have pancreatic enzymes that are released in the small bottle to break up food. They also can kill bacteria. There's a bunch of things on the way to making it to the intestines that the bacteria has to survive through in order to get to the intestines alive and fit the definition of a probiotic. What we were looking for was a probiotic or bacteria that had a natural capability of surviving through this amazing gauntlet and making it to the intestines alive. That's where the spores come in. They're called spores because when they are outside of the body or they're under any sort of stress condition, they cover themselves in a thick, protein, calcified armor. That armor allows them to survive through the stomach acid, through the bile salts, and through the pancreatic enzymes and actually get to the intestines completely alive, where they can then go function to as a live probiotic cell. We started testing conventional probiotics, remember the conventional lactobifero stuff I talked about? And we found that the vast majority of them that we tested was not surviving through this gauntlet. We were looking for natural bacteria that had the capability of surviving through. And that's where we identified the spores.

Wonderful. In terms of the applications and the benefits. Talk about short chain fatty acids and metformin. What do those two words mean to you?

Yeah, so really, really interesting and a very exciting area of study, actually. So short chain fatty acids are something called postbiotics, not that people need another term because it's prebiotic, there's probiotic, and then there's something called postbiotics. And I'm sure there'll be something new in a year. Or most biotics are actually compounds or nutrients or metabolites of some sort that are made by the microbiome that are essential to our health. The microbiome makes literally thousands of proteins and compounds that we need to function as a human. We can't get these from anywhere else. Short chain fatty acids are a great example of that, especially butyrate. Butyrate is one of the main ones that has an impact on metabolism. There are certain types of bacteria within your large bowel. If you have adequate amounts of these healthy bacteria, they will take incoming carbohydrates and convert them to these short chain fatty acids, like butyrate. Butyrate, for example. One of the things it does is it significantly improves insulin sensitivity. Your body can now Detect your insulin levels with a much higher degree of accuracy. It also stimulates all of these cells in your gut and outside of your gut, all the rest of your body, to use fat for fuel and to burn off and store away sugar as glycogen. It's an important orchestrator and controller of your metabolism. There's this compound called metformin, which is the number one used prescription drug for people who are diabetic. Just a couple years ago, it was discovered that the way metformin actually works is it increases butyrate production in the gut, that it's the butyrate that's produced by your microbiome that's actually resolving the insulin issue. The problem with the drug metformin is there are side effects to it, and then of course, the effectiveness of it decreases over time. Typically, people have to keep increasing their dose of the product. One of the things that we've looked at is can you increase butyrate production significantly by just a probiotic or maybe a probiotic and a prebiotic combination? We've got a couple studies that we published this year on that. In one case, using the combination of our spore probiotic and a prebiotic, we were able to increase butyrate production by over 150% in three weeks. That has a huge impact on, on your overall metabolic health. Inflammation in the body, the leakiness in the gut. Butyrate is one of the most potent things to heal. Leakiness in the gut. Also in our most recent study, seems to have a significant impact on your skin. We just completed an acne study. A significant reduction in acne lesions when you take the probiotic. One of the mechanisms is the increase in short chain fatty acids. Because we were able to see that in people with acne, they had low levels of certain short chain fatty acids, and people with no acne, they had high levels of those particular short chain fatty acids. When we added in the probiotic, that level of short chain fatty acid went up and that corresponded to a reduction in acne lesions in general.

That's amazing. If you could take a step back, what was the specific prebiotic that was used in that particular study that you ran?

Yeah, so we use a combination of oligosaccharides. I'm a big fan of oligosaccharides. Oligosaccharides are a type of prebiotic. They are very complex carbon structures, they're very complex carbohydrate structures. They're heavily branched, they're very resistant to digestion. In the upper part of the gi, so we don't break them down for caloric benefit. We don't get an insulin spike from having them. But they go into the large bowel and they feed certain types of really important bacteria, especially the high butyrate producing bacteria. The most common oligosaccharides that people have probably heard of are fos, which are fructooligosaccharides gos, which is galactooligosaccharides. We used a combination of two foss, which both come from Kiwi actually in New Zealand nearby. You? Yeah, they come from the pulp of the kiwi, both green and golden Kiwi. Then we use a galactooligosaccharide which comes from milk actually. And then we used a xylosaccharide, which is a unique oligosaccharide that comes from the cob of the corn. We did a combination of those four and we saw all types of amazing benefits, including significant increase in diversity in the microbiome, which is probably one of the most important measures of how resilient and healthy your microbiome is is the diversity in the microbiome. We saw about a 40% increase in diversity. And we saw a significant increase in these keystone bacteria that exist in the large bowel that are highly protective against chronic illness, all in the combination of the probiotic and that 4 oligosaccharide prebiotic mix.

Wonderful keystone bacteria. What would be those particular keystone bacteria that the combination of this prebiotic and probiotic have an impact on?

There's a number of them, but the most important one is, or the most important few are active Akkermansia muciniphila. Akkermansia is so important, it is inversely correlated with everything under the metabolic syndrome spectrum, which is almost 60 different diseases. You can actually reverse type 2 diabetes by increasing Akkermansia. It has so many important protective functions in our gut. So that's one of them. We saw 100 to 1000 fold increase in Akkermansia in the microbiome in three weeks of adding in this combination of probiotic and prebiotic. In fact, that study I think might have just gotten published because I saw something on ResearchGate, because they send me links to studies if I'm an author on it, so they'll send me a link or your study is published. I think I just saw it today. Then the other one is Faecalum bacteria prosnitzi F. Prosnitzi typically abbreviated very important bacteria in terms of protecting against inflammatory conditions in the bowel. So ibd, so Crohn's colitis, even colorectal cancer. It has other benefits in terms of inflammatory responses systemically as well. Another one called Bifidobacterium longum, then Rheumnococcus is another one. Rheumnococcus actually turns out to be inversely correlated with inflammation in the skin, including acne. Some of these are really important. You'll never find most of them in any probiotic product because most of these are what we call obligate anaerobes. These are microbes that have to live in the gut and only live in the gut. The moment they're exposed to oxygen, they die. So you can't grow them outside of the gut in a factory and reintroduce them and so on. We have to find natural ways of increasing them. What we've been able to show is through the probiotic and prebiotic, we get a huge increase in these really important bacteria. Great.

That's a great summary of the keystone bacteria. And I've got to ask you this question. What's your thoughts on dead bacteria? Being one, as being a therapeutic off, therapeutic use. And secondly, what's your thoughts on Akkermansia, which is also being looked at as a potential probiotic in dead form?

Yeah. So it's interesting. Dead bacteria in general can have. They don't fit the scientific definition of a probiotic because remember, the probiotic has to be a live microorganism. They are called something else in the research and science world. They're called metabolic response modifiers or biological response modifiers. There are some that are very well studied, like Lactobacillus rhamnosus gg. They found that that particular strain actually works better in terms of modulating immune response in the body when it is dead. So when it's heat treated and killed and then administered another one, there's a massive company called ABM just has released a probiotic, bifidobacteria, called BLP1. And it improves metabolic response in the body, which can be useful for weight control and so on. But that one is heat killed as well. They don't call it or sell it as a probiotic. They know that it doesn't fit that definition, but it has that really important benefit. Now, if people want to know how can a dead bacteria actually have any benefit, there's a couple of theories behind it, some of which has strong data behind it. One of them is that there's some confirmation on the outer cell membrane or cell wall structure of the bacteria that binds to immune receptors. And Stimulates a certain immune response. Neurons within the body. That's one of the theories. The other one, which I think is actually far more interesting and likely the one that holds the most water is something called Microrna or excretory vesicles. Bacteria have these tiny little nanocapsules that they can put peptides in it, they can put neurotransmitters, all kinds of stuff that they release into the environment. Those nanoparticles actually have affinity for different parts of the body. These particular strains of bacteria that seem to have an impact when they're dead, and even more so of an impact when they're dead compared to when they're alive likely contain these types of vesicles and, or something called microrna. Microrna are these little tiny fragments of RNA that can actually enter your cells and change your gene expression. That's a really fascinating area study because that's also one of the ways in which plants can actually impact our health. It's not just the fact that the plant is healthy, but the plant may contain numerous types of micro RNA that actually changes some of our own gene expressions. It's considered to be intra kingdom communication. If you remember your classification system for all living things, it starts with the kingdom and it goes to phylum, order, all of that. It goes family order, and then genus and species, all the way down to the bottom. But the kingdom part separates all of the living organisms into the largest groups. We've got mammals and we've got plants and all that are completely different biological entities. But as it turns out, Microrna is a way for these very different biological entities to actually communicate and influence one another. That's a really interesting area of study. But the limitation on the dead bacteria thing is a couple fold. One is it's really strain specific. The RHAMnosis GG variant has this effect. But if you use wild type or normal rhamnosis, that's not the GG variant. It's not going to have the same effect. It's very, very strain specific. A lot of times what companies do, because they don't really do their own research, they will put a generic Lactobacillus rhamnosus in a product and use the studies from the GG product to market their products. It becomes really important to be very specific in looking at the species level identification. Then the other limitation is that it only has an effect as the bacteria and those components are passing through your system. It's called a metabolic response because it only exists through the metabolic process and it is temporary. The Moment you stop taking the probiotic, the effect completely goes away, typically, although it has a place, it's really interesting. I think a lot of pharma companies are looking at that, because what they're looking at is, why administer the whole bacteria when we can just break up the bacteria, find the effective compound and then administer that, or recreate that effective compound synthetically and then administer it? There's a lot of work going on in that area. Now, Akkermansia in dead form is interesting because a lot of the metabolic studies show that you need live Akkermansia. The dead form doesn't give you the same benefit, I think, in my view. Why do you need dead Akkermansia when you can grow your own endogenous Akkermansia by 100 to 1000 fold by taking the right prebiotic and probiotic?

What's AMOC? Is that a compound Akkermansia produces, or is that the dead cell?

That's a compound that would be one of those postbiotics in the pharma world. And the pharma is heavily invested in the microbiome side, but their focus is on these specific compounds that bacteria produce, like faecala. And bacteria produces a whole number of compounds that reduce inflammation and risk for all of these inflammatory conditions. They're trying to figure out what those compounds are, what their mechanism of action are. How can they synthesize it and recreate it in a different way and mimic the natural effect in the body?

Kiran, you've been so generous with your time, so appreciative. So we better start wrapping up so you can get on to the rest of your day. And I'm sure it's going to be dinner time pretty soon for you.

It is, yes. And hopefully you'll be eating a very diverse dinner with a variety of things.

Absolutely. And the final question I have for all my guests, and I think you've covered this in spades during the podcast, but if anything comes to mind, if there was one thing you would do for your gut health, what would it be?

That's a really, really great question. Okay, so one thing. I would take the spores. I mean, we did a study on people with leaky gut, for example, with a really inflammatory form of leaky gut. They didn't do anything else. They didn't change their diet. We didn't give them any other therapies. They didn't change any of their behaviors. Just taking the spores for 30 days completely resolved the leaky gut and all of the inflammatory effects on it that came along with it we did a triglyceride study where people with really elevated triglycerides, which we'll also be publishing this year. We saw that in 90 days of taking the sports without doing anything else, triglyceride levels fell far more than you can with any fish oil, any prescription product. We see all of these impacts. The acne study we're talking about, we're doing a gingivitis study. I don't want it to sound like a hokey miracle product. It's not what it is. It's something that seems to affect the diversity and the production of certain postbiotics within the microbiome. And it speaks to the power of the microbiome to afford healing and wellness. Because if the microbiome is diverse, if the microbiome is resilient, if it's producing the things that it's supposed to be producing for human health and wellness, then you're going to be fine. If your microbiome is hurt, which most people's microbiome are, because of the toxic world we live in, then we're going to have this high risk for disease. Right now, the simplest thing would be get some spores into your system because they seem to do a lot of beneficial things. Then of course, there's all these other things I talked about that I tend to do and I always recommend that people are doing, but that would be the simplest thing.

Wonderful. Thank you, Kieran. And just so people are totally clear the name of your brand and I guess where can they find these products?

Sure, yeah. Our company is called Microbiome Labs. The main probiotic we've been talking about is our spore based probiotic called megasporebiotic. If you come to microbiomelabs.com, you'll find a whole bunch of resources. If you are a doctor or practitioner of some sort, you can register for an account and you can get access to the products wholesale and then provide them to your clients and patients. If you are a consumer and a client, you can go on there and you can actually put in your zip code and, and look for a doctor or practitioner somewhere in your area that's selling it, or a few of them do sell it online as well. So you can access it online. But if you want to hear more interviews by me and other topics within the microbiome, if you just put my first and last name in YouTube, you'll find a whole bunch of videos and interviews that people have very kindly uploaded that I've been privileged to do. So thank you so much for this opportunity. I always, as you can probably tell, I could talk forever on this. It's sometimes too long. But this is the most important thing for me in what we do is this ability to empower people with information and knowledge so that they can take control of their own health, take control of their own wellness. Because nobody's going to advocate for yourself better than you. And your doctor doesn't have all the answers. Your health practitioner doesn't have all the answers. You have to have a lot of those answers for yourself. These kind of programs are so important. So I always am very happy and excited to be able to participate.

Wonderful. Kiran. Kiran Krishan. It's been a long time in the making, but we got there and the man did not disappoint. So thank you so much, Kieran Krishan.

Thank you. It's my pleasure.

Hey guys. We hope you enjoyed this episode of the Gut Health Gurus podcast with Kieran Krishnan. If you enjoyed what Kieran had to say and you want to try out Megaspore biotic, head to www.nourishbeorganics.com and use the code gut healthgurus for 10% off. Now your your support means the world to us. Please leave a kind review Apollo Podcasts and also if you want to access the show notes, head to podcast www.nourishmeorganics.com au I hope you have a great week. Until next.