Episode 06:  How To Change Your Microbiome With Plants And Plant-Fed Animals

Episode 06: How To Change Your Microbiome With Plants And Plant-Fed Animals

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Summary

In this episode, Dr. Slavko Komarnytsky shares his expertise in pharmacogenomics (the study of how people respond to certain therapies based on their genetic makeup). He describes how we can use pharmacogenomics to our advantage, using polyphenols as an example of how we can change our own microbiome.

We discuss the complexities of plant microbiomes, natural antibiotics, soil, and why having even a small garden is highly beneficial to your physical and mental health. If you've ever wondered why eating plant-fed animals is important, Dr. Komarnytsky tells us why. Grab a vegetable, take off your shoes and go outside, and enjoy this episode!

To learn more about Slavko Komarnytsky click here.

Born in the remote wilderness of the Carpathian Mountains in Ukraine, Slavko Komarnytsky is an integrative biologist who combines expertise in botanical research and technological innovation with a commitment to reverse the worldwide trend of human metabolic and immune disorders. His scholarly work includes 70 papers that set trends in biodiscovery from natural sources, including phytochemicals such as phenolics and cannabinoids, and their interaction with bitter receptors and gut microbiome as related to health and disease. He is the Associate Professor of Pharmacogenomics at NC State University, and founder of the Mobile Discovery program that engages students and ethnic communities in global health research.

Highlights

What is Pharmacogenomics
  • The study of how people respond to certain therapies based on their genetic makeup
    • Seeing whether the body reacts as a state of threat, pleasure, aggression or defense
  • It looks at the individual and discovers - What about you is different in how you respond to the environment in comparison to everyone else?
Microbiome and Metabolic Disease
  • Consuming foods high in polyphenols is typically beneficial for you
  • How do polyphenols translate to pharmacogenetic changes in our bodies that are either better or worse health outcomes?
    • When the compounds enter our guts we do have an influence over their role UNTIL they meet regions where there is a high bacterial count
    • The translational effect of the microbiome is very important
    • Polyphenols, in a way, are like a prebiotic - you can preselect and promote the expansion of certain classes of bacteria within your gut effectively changing your microbiome profile by feeding the microbes, certain classes of compounds
Relationship Between Bacteria and Plants
  • Most plants get their water and nutrients from soil
  • All achieved by growing roots into the soil that give structure to the plant and need to be protected so the plant does not die
  • Plants selectively propagate certain classes of bacteria that are not pathogenic by feeding them something - they secrete certain classes of compounds out and this allows certain classes of bacteria to proliferate
  • Similar to intestinal epithelium
Gardening
  • Gardening, no matter how big or small is very beneficial to your physical and mental health
Secondary Metabolites in Plants
  • Plants make these to protect themselves, to communicate between themselves or with other organisms in the environment to try and survive
  • Natural antibiotics are chemical compounds which occupy certain chemical spaces and by chance fit into certain chemical spaces in the pathogens
    • I.e. bacteria that disrupts their membranes, inhibits enzymes and can stop their cell cycle
Plants In The Home
  • Having plants in your home is good for your families overall health
  • Plus you can use certain plants in the home to ward off pesky flies and ants like Heirloom tomatoes (the more hairs on the surface the better).
Consuming Plant-fed Animals vs. Conventional Farmed Animals
  • When animals eat a diversified diet they absorb and deposit those nutrients into their organs so we, as the consumer of animals, absorb those nutrients too
Mobile Discovery Program
  • Take a sample of saliva, and inoculate the medium with your own saliva
  • Anyone can participate and request a kit
Where to learn more about Dr.Slavko Komarnytsky...
Connect with Kiran Krishnan and Dr. Nicole Beurkens on...

Timestamps

spore based probiotics
  • 00:00:30 Episode Intro
  • 00:02:25 Dr. Komarnytsky's Story
  • 00:06:00 What is Pharmacogenomics
  • 00:10:00 Microbiome and Metabolic Disease
  • 00:18:16 Relationship Between Bacteria and Plants
  • 00:30:33 Secondary Metabolites in Plants
  • 00:36:35 Plants In The Home
  • 00:41:00 Mobile Discovery Program
  • 00:47:10 Episode Wrap Up

Transcript

Kiran Krishnan:

Hello and welcome to The Better Biome Podcast, where we explore the universe within. There is a complex and mysterious community of organisms that lives in, on and around us, that have an impact on every part of our health.

Dr. Nicole Beurkens:

These communities are called you biomes, and we're here to explore all the different biomes to help you and your family be the healthiest you can be. We're your hosts, Dr. Nicole Beurkens —

Kiran Krishnan:

And Kiran Krishnan.

Dr. Nicole Beurkens:

And on today's show, we're talking with Dr. Slavko Komarnytsky about the connection between plants, the microbiome and human health. He is the Assistant Professor of Pharmacogenomics at the Plants for Human Health Institute, at North Carolina State University, and Director of the Life Habit Center for Biodiscovery. He has a B.S. in biology and M.S. in cell biology, and earned his Ph.D. in cell and molecular plant biology. He has held research appointments in metabolism and nutrition at Rutgers University prior to joining the food science faculty at N.C. State University in 2011. His primary scientific interests have been in how dietary bioactive components prevent chronic metabolic diseases and inflammation, with a specific emphasis on the pathological mechanisms of insulin resistance and muscle loss. His scholarly work has set trends in biodiscovery from natural sources and engagement of students and ethnic communities in global health research. He has authored over 40 major scientific publications and gained broad support from government agencies and industry sponsors. Such a pleasure to have you on the show today, welcome!

Dr. Slavko Komarnytsky:

Oh, thank you for your kind introduction, it's good to be here.

Dr. Nicole Beurkens:

When I first found out about you and the research that you were doing, I thought we have to have you on the show because this connection between plants and plant compounds and human health, particularly the microbiome, is not something that a lot of people are talking about, but I'd love to have you start by just talking about the journey of your career and how you came to be doing the work that you're doing today.

Dr. Slavko Komarnytsky:

Okay, so originally I come from Eastern Europe, Ukraine. It's a small, modest region in the western corner of the country. I belong to the Boyko people, a small, tiny ethnic group which has very deep connections to plants and human health. One of the reasons, obviously is because we are mountain communities, so we are connected to nature, we have to deal with nature everyday, and we use it to boost our benefits and improve our health. Our part of the country is extremely poor. Throughout history, people couldn't afford to travel to see a doctor, they couldn't afford medicine, so they had to find a way to deal with their health problems using the resources available in their surroundings. Growing up, I was constantly exposed to this idea of plants and human health in many aspects of the relationship. Deep, I would almost say spiritual relationships that people have with the local plants and how the knowledge about those benefits has been transduced from generation to generation.

When I started to grow up, I went to college and I joined the department of biology, I got my bachelor's in biology and chemistry, two related disciplines, but again working on the biological aspect: What kind of plants grew around us, and also the chemistry aspect: What plants manufactured. Plants are some of the most amazing biochemical factories out there. They beat most of our factories by a lot. Because in a tiny amount of space, with a tiny amount of resources, it can synthesize those compounds, which our organic chemists sometimes spend 10 years just making one. So with that, after I finished my undergrad degree, I went to continue with the Ph.D. at Rutgers University in the Plant Biology program, and slowly as I worked more and more with plants, I realized that my passion and interest is specifically the application of plants to human health. Then, when I joined NC State in 2011, I basically made this topic the core of my research program. And luckily, I'm a faculty at Plants for Human Health research institute, so it's basically a dream come true. It's one of those rare cases where you actually have a dream and you fulfill it and find the job that you like to do.

Kiran Krishnan:

That's wonderful. In the area that you grew up in, is there a traditional medicine that's based on plant medicine that has maybe hundreds or thousands of years of empirical evidence? In the like of, I'm thinking, Ayurvedic medicine in India. Is there some discipline like that?

Dr. Slavko Komarnytsky:

So you have to realize one thing, even though we are an isolated region, we are still a part of Europe, and in Europe, medicinal knowledge kind of goes across the borders, so a lot of our traditional knowledge is a mixture between the local plants and the ethnic knowledge of the people who live in the area, and also the influence from those famous plant schools in Padua, in Prague, in Krakow, in Paris. Those are all influences which basically transcribed odld greek and roman medicine and translated it to the Slavic people as the two civilizations collided. It's a very strange mixture. There are a lot of ethnic things, building pieces here and there, but then overall, it's still Galenic principle, it's still classical medicine, decoction, extraction, mixtures of different herbs.

Kiran Krishnan:

Yeah. Now you work in pharmacogenomics, right?

Dr. Slavko Komarnytsky:

That's right.

Kiran Krishnan:

So can you describe what pharmacogenomics is?

Dr. Slavko Komarnytsky:

Right. It's a fancy word, but basically what it means is a very simple thing. When we interact with plants, when we interact with our environment, this happens on a level, mostly, of biochemistry. Certain biochemical components come from the environment into our body, whether we ingest it, put it on our body, or walk through them. They cause certain changes in our bodies. We have to respond. And the first way that we respond is by detecting those chemicals and changing gene expression profiles, so changing the number, the amount, the allocation of proteins in our bodies to respond to either threat, pleasure, aggression, defense. That's exactly what pharmacogenomics is: It looks at the individual and says, what about you is different in how you respond to the environment, compared to everybody else?

Kiran Krishnan:

That's interesting. It brings up, to me, a bigger overview. A lot of people will believe, and it's likely true that a plant-based diet is a pretty healthy diet, right? But we think about it from a macromolecule standpoint, it's high in fiber, and it's lower in fat and so on, so we think about plant-based diets, the benefits that way. But I think from your work and the world that you live in, there are much deeper connections, right? There are epigenetic effects on us based on consuming these plants. There are compounds in plants that affect our gene expression in a significant way.

Dr. Slavko Komarnytsky:

Right, and the best way of looking at it is realizing the fact that when we ingest food and we eat something, most of the food is being eaten, not by us — we basically feed a huge colony. We're talking about several pounds of bacteria which live inside of us, and they are very happy to receive that food. They consume most of it, or at least they metabolize most of it before we get to absorb it. So here you have a very interesting interaction between what happens on the outside: The way we prepare food, the way we treat food, the way we need food to survive, and what happens on the inside, because there is an intricate collision of our interest, what we want for our bodies, but also what bacteria want for themselves living within us.

Kiran Krishnan:

That's when you just look at the case of cellulose, right? Plants are made up of cellulose. We don't make cellulase as an enzyme endogenously. But our bacteria do. So there is a component to break down cellulose in our system that's outside of our own organs.

Dr. Slavko Komarnytsky:

We don't have a lot of it, right, as in you and me could depend just on cellulose to stay alive? Unfortunately, it's not very possible. But we do have bacteria which start to break up the cellulose fiber into more simple structures, and the energy which is being released is usually captured by bacteria, and then it's used to produce other things, for example B+ vitamins, which we then can absorb from the bacterial community and benefit our bodies. Or the energy is being passed to us, because if the complex molecules are breaking down into the simple sugars or short-chain fatty acids, now suddenly we can absorb them and use them to our benefit and we couldn't do it if bacteria wasn't there.

Dr. Nicole Beurkens:

Talking about how taking in the food, really it's the bacteria, all the microorganisms that really love that. You've done some interesting research on certain types of compounds and things that we eat and how that interacts with the microbiome, particularly related to issues of metabolic disease: Diabetes, obesity, those kinds of things. Can you talk a bit about that?

Dr. Slavko Komarnytsky:

Yeah, sure. So one of the biggest questions in Plants for Human Health area, if you talk about metabolic diseases, everybody knows that consuming foods which are high in polyphenols, whether it's cocoa, berries, grapes, red wine, it's beneficial for you. It's been a mainstream knowledge for about 20-30 years now, people swear by it, people do it, it works. As a scientist, you want to go one step deeper into the picture and say okay, polyphenols are very complex molecules, right? Usually you see some polymeric structures of many multiple units bound together. They're too big for us to absorb them and benefit from them directly. So then, how come if I just take polyphenols and put them in a human or an animal model, what happens? Most of it will be in the gut, and very little of it will cross all the membranes and go into the bloodstream and be transported to the tissues in the intact form. Then the question is: All these health benefits attached to benefits, how do they really translate to pharmacogenetic changes in our bodies which actually make better or worse health outcomes?

With that in mind, we worked on several animal models and several early phase human studies trying to answer just that question. And what we are trying to understand is: When these compounds enter our guts, most of the time, yeah, we start to digest the mix of food, but we really have no influence over their role. They just trek along the gut until they meet the regions which are high in bacterial count. And bacteria, as organisms which are capable of breaking them down into the small products, and one of them is basically the methoxycinnamic or hydroxycinnamic acids. These are smaller secondary metabolism breakdown products of polyphenols, they are much smaller. So now, we are looking at a small micro weight components, which can be crossing the cell membranes, travel through the blood system into the liver, getting metabolized again, getting into the rest of our bodies, eventually eliminated from our bodies, but these compounds enter our bodies in much higher quantities than the original polyphenols. And in order to prove this hypothesis in a way, we did a very interesting experiment where we took an animal model, where you have a diet induced obese mouse, you put them on a polyphenol diet, in this case it was blackcurrants, not very popular in America. They love them in Japan, they love them in New Zealand, they love them in Europe. The American palette for some reason rejects blackcurrants, right?

But when you add blackcurrants to the diet induced obese model, you improve their metabolism. They lost weight, they became better, their functions, glucose metabolism, insulin resistance normalizes. Great effects. I wanted to know how much of it is the polyphenols themselves, the compounds of the blackcurrants themselves and how much of it is the contribution of the bacteria. So what we did is take an antibiotic, and we fed it to this animal. Basically, we effectively eliminated 99.9% of bacteria in their gut. You can not ever be sure that you removed 100% of them, but you basically decreased bacteria counts to the point that you don't see them anymore. And the magic happens: All the benefits are gone. So the animals are still eating the same food, the animals are still getting exactly the same dose in, the polyphenols travel through their gut and exit on the other side.

Kiran Krishnan:

That's a really elegant experiment that shows how important the translational effect of the microbiome is. To really gain benefit from the foods that we eat, there is a really important conversion process that our microbes do for us. It benefits them, it's kind of symbiosis in that way, the metabolism of the polyphenols benefits them as well, but then they produce these byproducts that we then can use, Urolithins being one of them from polyphenols. So that's really quite amazing. Would you consider then a polyphenol more like a prebiotic?

Dr. Slavko Komarnytsky:

It is in a way, because when you feed polyphenols to the body, you actively preselect certain classes of bacteria which can utilize those polyphenols for their metabolism, for their purposes. They don't care about us for the major part, but you can preselect and promote expansion of certain classes of bacteria within your gut, so effectively, you change your microbiome profile by feeding the microbes certain classes of compounds.

Kiran Krishnan:

Microbes like [inaudible 0:14:35.8] bacteria probably do well with polyphenols, right?

Dr. Slavko Komarnytsky:

Right, orClostridium, which are known to produce all the short chain fatty acids, they love these types of compounds because they can metabolize them into their needs, and the byproduct, short chain fatty acids, benefits the gut lining or the enterocytes which cover our guts. They prefer short chain fatty acids rather than sugars to use for their energy.

Kiran Krishnan:

And then we also know that short chain fatty acids affect our metabolism in a big way, right? It up-regulates glucose control through all these proteins and peptides in the gut. So it's really this elegant system that if our microbes are compromised in some major way, the system doesn't work.

Dr. Slavko Komarnytsky:

You have to think of a human body as a vessel, in a way. I'm sure many of you have done beer or wine at home, right? Where you basically buy malt or you buy the berries. What do you do? You smash them together, you add sugar if you want a sweeter version of it. But then, you create an airlock, right? You put it in a bottle and you close it to make sure that the oxygen is not getting in there, and the fermentation begins. This is the magic, the 30 days that you have to wait patiently to get your wine or your beer, right? We're not that much different. It's exactly the same thing, we are big fermentation vessels. We put whatever substrate we want to put into our bodies, and we have to make sure that the airlock is tight because a lot of bacterial communities in our gut are very sensitive to oxygen. The most distant regions of our gut are pretty much depleted of oxygen, there is no oxygen there and that's why the fermentation can occur, it can occur in certain ways generating short chain fatty acids, it's beneficial for bacteria and beneficial for us. If you have any kind of disturbance in the gut, for example inflammatory disease, when you have increased perfusion of your gut walls, classical inflammation, it gets red, it swells, there is more blood in there. What happens? There is more oxygen entering the system. So immediately, those classes of bacteria which are sensitive to oxygen start to shrink. Obviously, they don't die overnight, but with each day you have a shrinking population of cells that were actually doing the fermentation. Your body can not survive without fermentation, so what happens next? You get an expansion of other types of bacteria that replace them. The process is very gradual. It can take days, it can take weeks, it can take years. But you end up with a shift of the microbiome, which pretty much depends on your diet and the amount of oxygen which reaches the fermentation.

Kiran Krishnan:

That throws the community structure out of balance and how your body reacts to food at the end of the day. Of course you do a lot of your work in plants. We talk a lot about our microbiome and the mutualistic relationship between us and our microbiome. Plants, obviously, are covered with microbes as well. They grow out of a soil that has microbes in the soil, or they should have microbes in the soil — that's something else we should talk about, the depletion of life in the soil. What is the relationship between bacteria and plants? Is there a mutualistic relationship there as well?

Dr. Slavko Komarnytsky:

There is. The relationship is not that different from ours. If you think about soil, this is where most plants get their water, nutrients and where they are rooted and have their physical structure or support. All of it is achieved by basically growing roots into the soil. Roots are structures which need to be protected, because if they malfunction, the plant dies. Plants are always charged with a very interesting situation, where they want to open themselves to be able to absorb the nutrients from the environment, but want to put a block on all the pathogens and all the unwanted interactions which are happening in real time, every single moment. In order to do that, they do pretty much the same things that we do with our gut bacteria. They selectively propagate certain classes of bacteria which are not pathogenic for them, by feeding them something. So roots are some of the best separatory factories known out there. A common person would think that roots, most of the time, what they do is absorb, right? They actually secrete a lot of things. This is where the feedback happens. So the plants secrete certain classes of compounds out, which are trapped and allow certain classes of bacteria to proliferate, and now suddenly, you have the root structure, which is engulfed with the beneficial or at least symbiotic bacteria. So on one hand, they protect the plant from other bacteria, on the other hand, they use certain compounds which are being secreted from the plants for their own metabolism.

Kiran Krishnan:

The analogy then is very similar to the intestinal epithelium.

Dr. Slavko Komarnytsky:

It's absolutely the same, if you ask me.

Kiran Krishnan:

That's fascinating, when you think about these two completely different systems in different parts of our world function in the same biological way, right? They are creating this mutualistic relationship with the microbes around it. The hosts, in this case, the plant and its roots are providing things in the microbes to try and select the right ones, and then the microbes prevent the wrong ones from the entry of the system, and the same thing is happening in our gut and it's at such a — the biology of that is just so elegant to me. What starts to happen, then, in our world of farming and all of that where we're spraying antimicrobials into the environment? Roundups, herbicides, pesticides, and of course antibiotic run off from the meat plant down the road or wherever it might be. As we're seeing, soil is dying. We're losing the microbial activity in the soil. Are you seeing that as an issue affecting the types of plants?

Dr. Slavko Komarnytsky:

It's definitely an issue, and it becomes a bigger and bigger issue as we expand the amount of arable land, because in the past, when people used to live in small, tiny communities, what they did, they would just move to a new area, cut the trees, burn them down without affecting the soil, basically improving the soil with the minerals coming from the trees, and then use that small piece of land for 10-15 years until exhaustion. It was pretty much destroyed. If you tried to grow another crop there in 10 or 15 years, you couldn't. But because it was done on a small scale, it wasn't that detrimental. After 10-15 years, the family moves somewhere, or if another family comes back there in 30 years, the soil is restored. Well, it's what, 6-7 billion of us today? We have to make sure everybody has food. It's probably more important sometimes than the health of the soil, unfortunately or fortunately, that's what it is. That's the reality. Therefore, we start to struggle with the modern agricultural practices, because as we expand, we can not sustain anymore. We are reaching those points where we start using the soils, and even with the crop rotations, even with the change in seasons, even with the change in strategy, even with the change in minerals that we put back into the soil, we can not restore the soils to the same levels as they used to be. It's a sliding scale. It's not a drastic sliding scale, it's not like we can look five years into the future saying we will not be able to grow a crop, that's not exact. But it's a problem that if not addressed now, will hit us 30 years down the road.

Kiran Krishnan:

Right. I think the World Health Organization said there is a certain limited number of crop cycles that we theoretically have left on earth.

Dr. Slavko Komarnytsky:

Right. If you really know your soil, I'm not a soil scientist, so I can not really speak deeply on the topic, but if you really know your soil, there are certain strategies, whether it's fertilization strategies, crop rotation strategies, but most importantly letting the soil rest. So basically taking some plots off-cycle for a year or two to let the bacterial communities re-establish themselves before you put them back into the rotation, which can lead to an improvement. The question is: If you're a farmer and you work in a very small profit margin — because farming is a fun thing to do but it's extremely low profit. You have a big farm, you have a big profit, but your margin is very, very small. So try to ask that farmer to change his routines to implement new strategies to preserve soil. They'll say yeah, we'd be happy to do it, but we cannot afford it. So something needs to change.

Kiran Krishnan:

Right. Do you see an importance in people growing any of their own food, even small gardens and things?

Dr. Slavko Komarnytsky:

Now you're hiring a chord with me because I'm an Eastern European. I was born in the former Soviet Union, witnessed the collapse of the country and the birth of the independent countries, including Ukraine, where I'm from. Throughout our whole history, every single person has a garden. A part of it is always a flower garden. Ukrainian people love flowers. The house has to be pretty and surrounded by flowers. But the significant part of it is boring: It's potatoes, it's tomatoes, it's cucumbers, it's cabbage. Nothing fancy. We're not talking about fancy and exotic fruits. People really use them to supplement their incomes. Some people really need that. Maybe not so much now as 20 years ago, but still, right? But also supplement their diet, because they believe when they grow their own food, they are in control when the food is ripened and when it is collected, and how fast it hits your table. Nowadays, we live in a world of abundance of food. Even though there are some hungry people in this world, theoretically, there is no shortage of food. There are just problems with distribution…

Kiran Krishnan:

We throw out most of the food we make.

Dr. Slavko Komarnytsky:

I lost my train of thought, but…

Kiran Krishnan:

Well, back to the gardens. I love that, because to me, if you're looking at a 30,000 ft view at a city or neighborhood and there were all of these little gardens in everyone's homes, the community, that creates a unique ecosystem in itself, even though these gardens are physically not connected, there is still an impact on the ecosystem surrounding it, right?

Dr. Slavko Komarnytsky:

It has a lot of additional benefits. It creates a green ecosystem. It creates these little patches which allow certain birds to return to the urban neighborhoods, certain insects to return to the neighborhoods. It allows a flow of genetic information, so suddenly these communities can cross-pollinate themselves so they don't become bottlenecked unto a single kind everybody is growing. So it does a lot of good things. It does a lot of emotional good. Because of the stressed environment we are in, a lot of people find gardening as their way to relax and connect back to nature, even if they cannot leave the city.

Kiran Krishnan:

And there are certain microbes that have been shown in the soil like Mycobacterium vaccae that actually increase the serotonin in humans, as you're playing around in the dirt, in human exposure, right?

Dr. Slavko Komarnytsky:

Right. A lot of people don't realize but there is more serotonin in our gut than there is in our brain. A lot of it is being produced and secreted in response to the bacteria in our gut. And I'm just thinking about my childhood, when I was growing up. Obviously there was always a garden full of vegetables, but there was one thing which is kind of interesting. As a kid, about five to eight years old, if you live in that part of the world, your mom and your grandma really believe in goat milk. So goat milk is a panacea for everything, and when the kid is growing up, you have to drink goat milk. It's a rough taste, it's a strong smell. But the best part of it, people believe that you have to drink it fresh. So what you do in the morning, you wake up — or they wake you up because you don't want to. They give you a cup. 8 Oz, I guess, if you're talking American standards. You take that cup and you go across the garden, you jump the fence to your neighbor who usually has a goat. It's usually an older woman, and you would give them the cup, and they would milk the goat right into your cup. It's basically cappuccino. It's warm, it's foamy, it has some hairs on top. It's a different story. You drink that milk and then you go back. While doing it, you have to cross the garden twice. As a kid, what do you do? "Oh, there is a carrot!" You pull it, you rub it on your pants and you eat it. There are peas. There is sorel, you just pick and eat it all the time, and I think it really benefits your microbiome.

Kiran Krishnan:

Absolutely. And you're running across the garden, maybe barefoot, and you're bringing that dirt into the house and it's…

Dr. Slavko Komarnytsky:

That's another thing, a layer of bacteria on our skin. It's another microbiome that people don't realize is there.

Dr. Nicole Beurkens:

That level of interaction with the earth and the world around us in a way that most people, certainly most kids don't experience now.

Dr. Slavko Komarnytsky:

It's very true. That's one of the reasons, probably, why our immune systems start to flare up, because as a kid, it matures. There is a critical period of time between 0 and 5 when our immune system is building up it's capacity, but it's born with a capacity to respond to the diseases, which can be addressed with vaccination, but it's also the capacity to recognize things in the environment and not react. It has to be trained. In order to be trained, it has to be exposed. If you miss that window, you can try doing it later, but it's the same thing as with languages. It's the same thing with many other things. If you miss that window, you will spend three times more energy and time in order to do the same thing.

Dr. Nicole Beurkens:

You were talking about, it's really fascinating, the root structure of plants and how they sort of secrete things which select — which gets me thinking about the idea of antibiotics. We know we have antibiotics that we can take if we have an illness or an infection and it kills that off, but it strikes me that these plants have these antibiotic compounds. That would be a way of thinking about that. You're doing some interesting research into those antibiotic compounds in plants and how they work and how they may be useful to human health.

Dr. Slavko Komarnytsky:

You have to realize one thing: When you are a plant, you're rooted in the environment where you come from. They can not change the environment and go to a different country and start a new life. If somebody does it for them, they can do it. Dig up the plant and move it across the world, sure. But if not, they have to address the issues right there on the same spot. There is an environment, today it's raining, tomorrow it's shining, then the frost comes, there are diseases and other kinds of pests and bacteria. It's the rainy season, you get a flare up of fungi, it's very dry, you have bacterial diseases but no fungi around. There are insects that come to you and want to feed off of you. There are a lot of challenges which plants have to deal with every day, and they cannot move. They cannot even twitch. I mean some can, but most of them can not even turn away from the sun if it's too much sun. So what they do or learned to do throughout history is to respond to every single assault with a chemical clue. They have these large groups of enzymes which have only one rule, to synthesize secondary compounds and secondary metabolites. We call them secondary because if you put the plant into the ideal conditions and you remove those compounds from the plants, nothing happens. They are not sugars, not fats, not proteins, they are not required for metabolism, they are not required for the wellbeing of the plant. But plants make them either to protect themselves or to communicate between themselves or with other organisms in the environment basically trying to survive. One of the ways to prevent the expansion of pathogens is to release a chemical which will interfere with the pathogen metabolism in one way or another. That's what we call a natural antibiotic. Now you have to realize, during the evolution, it's hit and miss. A lot of people who believe in evolution try to treat evolution as God. Why is that? Evolution is very smart, look at all these fancy things which evolved through the millions and millions of years, can you believe all the complexity. It's true. The complexity is there, but very few people really understand the process getting to that complexity. It's extremely random. So every time you make a little change, most of the time, that change means nothing, and you fail miserably, and sometimes you succeed. So natural antibiotics are exactly that. These are chemical compounds which occupy certain chemical spaces, which by chance fit into certain chemical spaces in the pathogens, for example in the bacteria, which means disrupting their membranes, inhibiting their enzymes, stopping their cell cycle, doing something. But all this happens by chance, and because of the millions millions of years of evolution, you see the end product. You see the compound which is effective in controlling a bacteria.

Kiran Krishnan:

Yeah, and it's powerful then to be able to take advantage of that time, the millions of years of evolution rather than a bunch of scientists sitting in a lab and trying to evolve molecules from scratch themselves, right?

Dr. Slavko Komarnytsky:

Here, it's an interesting dilemma, because in one point of view, yes, it's true. We have all these molecules which were developed throughout these years, but you have to realize that pathogens and plants always interact. So one year it's there, another year it's not, it depends on the seasons. So most of these molecules are not developed to their perfection. If you compare a natural antibiotic to a second or third generation of pharmaceutical drugs which kill bacteria, drugs will be more effective, and there is a reason for it, because we put our minds and specifically morphed them into the point of being effective on a very particular target. Nature doesn't care about that. Nature wants a general defense which it can modify every single minute depending on what challenge comes. So if you are really sick, if you really need an antibiotic, take a drug. It will be more effective. But if you are on the borderline, or if you are trying to change your lifestyle, if you are trying to support your body, take a natural antibiotic. It's much milder. The topological profile is much better. It's not as effective, but it's not as toxic. Slowly, over time — because you are not sick, you've got time, right? Slowly over time, you can shift the microbial communities in your body based on the natural therapy. You can do it. But if you have high fever.

Kiran Krishnan:

Yeah, I mean if you're septic.

Dr. Slavko Komarnytsky::

If you're septic, please! Take the pharmaceutical — you don't have time for this.

Kiran Krishnan:

One of the things we talk about a lot on our podcast is creating a healthier environment around you. There is a good amount of information out there that having plants in your home actually improves the health-providing benefits of the home itself. There are plants that will detoxify the air, will filter the air and so on. You're an expert in plants in many different ways, in the more finite area on the molecular structure, but are there plants that you think people should be having in their homes that can actually impact their health outcomes?

Dr. Slavko Komarnytsky:

If you're living in warmer climates, you have to learn from other animals. If you look at the sparrows, for example or other types of birds, if they get a chance, they bring tomatoes. But not the fruit. They bring the branches of tomato plants with leaves and stems to their nests. One of the major reasons for it? It repels insects. Any kind of pathogens that bother them, that live under their feathers, you can mimic their behavior. You can bring tomato plants to your house. And if you are in a warmer climate where you have a problem with ants, with mosquitos, a lot of flies entering your house, you can actually use real life simple heirloom tomato plants. The more hairs on the surface, the better they are because they secrete more active products. Just crush them a little bit if you want the real effect right now, if you are infest with swarms. Or just put it in the corner of your house and you will see the amount of flies in your house will decrease dramatically. And it's a simple tomato. So I'm pretty sure there are plenty of examples like this. You can do exactly the same thing.

Kiran Krishnan:

Bringing things full circle, obviously, us eating plants is good for us, there are lots of connections to phytochemistry involved in plants and our health benefits. We also eat animals. Now, I would assume then, animals who are herbivores, eating plants is better for them than eating corn feed or whatever it is. Nowadays we are looking at an increase, or in some cases a diminishing amount of animal protein that's being consumed, but there's got to be an impact on our health if we're eating animals that aren't eating plants versus animals that are eating plants, so the whole free range grazing animals versus the ones being fed cornmeal and so on.

Dr. Slavko Komarnytsky:

That's absolutely true and there is no way to argue with that. Animals, whether they are farmed or wild, when they are provided a diversified diet, our bodies — by "our", I mean mammalian bodies, so whether you are a human or an animal, are very smart. They know exactly what they want, they know exactly how much of it they want, whether it's minerals or other beneficial things from our diet. So, as long as you provide a diversified diet to the animal or to the human, unless you're sick, your body will sort it out. It will take whatever it needs and it will deposit it into proper tissues. So then, the livers will have the proper amount of the B vitamins, our fat tissues will have the proper amounts of carotenoids, and we will store these things and use them as we need. Exactly the same thing is happening in animals. If they are offered a diversified diet, open pastures, not just stuck to corn or one source of carbohydrates, they absorb, metabolize these components and deposit into their organs. And then we, as consumers, when we eat animal protein, we benefit from it because we can take it up and our body will make exactly the same decisions: Do I need more carotenoids? If I do, I have them to absorb, transport and deposit them somewhere else. But if you don't, what do you do? You still get your sugars, you still get your proteins, you still get your fats. But you don't get all the other secondary metabolizing or get all the other beneficial biochemical components which have the capacity to improve or at least sustain your health.

Dr. Nicole Beurkens:

We were talking before the show started about the work that you're doing in the university setting with students and how passionate you are about helping students studying plant biology to really embrace these things and understand the real life applications of them. What are some of the things that you have going with students right now that you think are really interesting?

Dr. Slavko Komarnytsky:

One of the best examples for this approach would be the Mobile Discovery Program which we run out of the lab. I have a small unit within the lab which is dedicated to antimicrobial research. Basically, as any other scientist out there, we look for new sources of compounds with antimicrobial properties. So I have 10 people in the lab, we have only 20 hands, we can do a certain amount of work and research trying to discover something. For a long time, it was bothering me because I feel very limited. I say okay, I'm here, for example, located in North Carolina. Great state, we have exposure to the ocean, we have mountains on the other side of the state. The biodiversity is huge. People don't realize but mountains in North Carolina are the number two hotspot for biodiversity in the entire United States. People don't really know, go to Smoky, you will see it by yourself. Sitting in that biodiversity spot, my question was: How do I utilize these resources? I can't just send 10 people on collection trips day after day. So what do I do? Then we came up with a very simple idea: If we create a tool, instead of doing it ourselves. IF we can create a tool that enables other people to do the primary screening, the primary research, the primary moment of discovery where you take something out of the environment and you confirm whether it has antimicrobial activity or not — and if anybody can do it, doesn't matter how old, how young, doesn't matter what their education is. You don't even need to read, it's that simple, then suddenly, I have an expansion of the network of people who go outside to the environments which I don't have access to for reason of time, cost or any other reason - and they can screen these environmental samples for the presence of antimicrobial properties and report it back to us. One of the biggest challenges that we have during this exercise: In order to screen for microbes, you need to have microbes. The problem is microbes are biological pathogens. There are safety rules which say you can not bring in microbes to school, you can not take microbes outside of the lab, you can not put them in a park, you can not put it in your car and drive across state borders or worse, you can not even travel internationally with microbes in your bag. So how do I do screening if I can not bring microbes? I think that was the break point, because once we figured out where to take the microbes from, it was all solved. And do you know where we take them from?

Kiran Krishnan:

The human body?

Dr. Slavko Komarnytsky:

We take them from the human body. And even better off, we take it from saliva. So our saliva, each of us, every single one of us has plenty of bacterial populations in there. Basically, what you need to do is collect the sample and sorry to say it on the air, you spit on them. You take a sample of your saliva, and you inoculate the media with your saliva. Suddenly, I have a tool. I have a kit that I can give to you or anybody else. It's a piece of plastic, which costs very little, enables the discovery, and I don't run into any security issues. I can go now to a high school, I can bring undergrads, I can go to an international trip and enable bio discovery happening right there. But that possibility developed. We brought a lot of students — for example, I have an active research class with Catawba College, which is a small private school not far from our institution where we teach a class in antibiotic resistance and drug discovery. We bring these kids to the lab, we teach them how to make the kits, we teach them how to make the screen and then we tell them it's time for their individual project: You go out there, collect the samples, look for the activity, and the best part: If you find something, it's yours. Because the way that intellectual property laws work, whoever makes a discovery owns the discovery. So there is no biopiracy involved. I can take the kit and give it to people in Australia, they can use the kit to make a discovery, the intellectual property, the rights to the discovery belong to them. With that, we probably manufacture somewhere between 2000-3000 kits every year, which we distribute to different local schools, organizations, university students, basically any person who wants, they can write to us and we will provide a kit for them to do the screening.

Kiran Krishnan:

It also speaks to how many bacteria we have in our mouths.

Dr. Slavko Komarnytsky:

Right. It's very interesting because usually as a part of the class, I also teach them some microbiology techniques, so they always use their saliva to profile the bacteria, then the fun part comes because they start to compare their profiles to each other! And sometimes you can figure out very unusual things, for example, if somebody has a secret relationship, their profiles match!

Dr. Nicole Beurkens:

That's right! So if people are interested in connecting with you about that, that information is on your website, right?

Dr. Slavko Komarnytsky:

Yes, there is a separate section called Mobile Discovery, and people can just reach out to us.

Yeah, and we'll make sure that people have the link to that in the show notes, because I think there are lots of people listening who might be really fascinated about participating in that, it's really brilliant. As we start to wrap up, what do you think are some of the most interesting things on the horizon, as far as thinking about plants, plant compounds and human health? What are one or two of the things that you think are most interesting?

Dr. Slavko Komarnytsky:

If you ask me, I think it's the horizon itself which is very interesting, because right now, microbiome research is still in its infancy. We obviously knew that the fact that there are bacterial communities everywhere, we've known it for a very long time. It's only recently that we got the capacity to explore them in the detail that we could have never done before. The cost was just too prohibitive. Now you can sequence your microbiome, you can get your profile, you can generate 10,000 data points from a single person, now think about the population studies, think about ethnic studies, think about country studies. The question is: What do you do with all that data. You're asking what's interesting on the horizon, I think we are one step before. What's interesting is what do we do with the data that we generate? It's too many data points. I'm not a bioinformatician, obviously, so there will be a lot of people critiquing me, but I basically feel like the amount of knowledge, the primary knowledge that we can generate about the microbiome is huge, and whoever figures out what to do with that knowledge and how to come out to reasonable conclusions-base will be one step ahead of everybody else and still not there yet.

Kiran Krishnan:

Yeah, it's like we have these massive blueprints, but we don't know what they build. Whoever knows how to read the blueprint and put something together…

Dr. Slavko Komarnytsky:

Give it some time! As any kind of area of science, it has its birth time and it has its development time, and we are just getting the first glimpse of what's really out there. So obviously, we don't often understand very well what the signature means. If #5, #10 and #16 are up, what's the response? We are still identifying the signatures. We can take people with different diseases, look at their microbiomes and say it's most likely that this type of microbiotic signature is responsible for this condition. We don't know whether it causes it, we don't know whether it fixes it, we don't know whether it is our body's natural defense towards the disease by modifying the microbiome, we're just not there yet.

Kiran Krishnan:

I guess one thing we can feel pretty comfortable about is our connection with the natural environment is clearly important, right?

Dr. Slavko Komarnytsky:

It is. And considering that there are several billions of those bacteria in and around our tissues, and each of them has a little tiny connection, a little arm reaching out towards us, those connections are very strong. You can see it. You put animals into septic environments and they grow up? They grow up, they develop, but their immune system is a mess, their metabolic system is a mess. So there is a very deep network. It happened by chance, it happened by evolution together with bacteria. Every single cell in us has a bacteria, mitochondria, inside of us, but that core evolution was too close. If you hate it, if you don't like bacteria, if you try to remove it from your environment, you can't. Your body and your health crucially depends on it.

Dr Nicole Beurkens:

Thank you so much for being here, this has been a really fascinating conversation, for sharing things about your life and your story and the research you're doing. Really fascinating stuff, thank you for being here.

Kiran Krishnan:

Thank you for joining us.

Dr. Slavko Komarnytsky:

Oh, thank you so much. It was a pleasure to be here.

Dr. Nicole Beurkens:

Awesome. And thanks to all of you for joining us for today's episode of The Better Biome Podcast. Tune in next week to continue with us as we journey through the universe within.

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