What follows is a transcript for the podcast Microbiome - Dr. Momo Vuyisich - Disease Prevention.
Naveen Jain: All right, Dr. Momo Vuyisich. It's a pleasure to have you here. So, Dr. Vuyisich, first of all, why don't you give us a little bit of your background on what have you done, just so that audience have a little bit of context to your tremendous background that you have?
Dr. Momo Vuyisich: Yeah, I'll be brief about my background. I was a scientist, biochemist, immunologist, microbiologist, all kinds of things. But really, I came very driven by the fact that we are in the dark ages when it comes to chronic diseases and cancers. So literally, in the 13th century, when the plague hit, we didn't know what caused it. And so we were completely blinded and we had no way to treat it. We didn't know what it was. And today, seven centuries later, when it comes to chronic diseases and cancers, we're in the same situation. We have no idea what causes them. A neighbor, or a family member, or a friend is diagnosed with cancer, and whoops, it's bad luck. Well, it's not bad luck. There's some underlying chemistry there that caused that disease. We just don't measure it, then we don't understand it.
So, that's really one of the driving forces behind my early development of the technology. And then the second driving force was a personal story that I was diagnosed with idiopathic rheumatoid arthritis and idiopathic sounds like a medical term, but it means we have no idea what causes it. So we're going to hit your immune system with immunosuppressants, and we're going to slow it down, but we have no idea what caused it and we can't cure it. And so you're just stuck with it. And bad luck, whoops. Well, as a scientist, I didn't take that as a final answer. So I searched for the truth, and what caused my disease. And I was able to cure myself completely with the diet change. And so, it was this sort of series of events that led me to completely shift my scientific career in 2010, and to understand what is it that we need to do in order to solve all these problems?
And so the first solution that we needed was a technological solution that can digitize the human body like it has never been done before. And so how can we collect multiple samples from every person over time, and create massive amounts of data, digitize all the physiological processes, both on the microbiome side and the human side, and understand what makes our body tick? What makes our body healthy and what makes it sick? And then we'll figure out how to reverse and prevent those molecular events that lead to illness. How's that for an intro?
Naveen Jain: That's very good. So, Dr. Vuyisich, you mentioned a little bit about these microorganisms. What are these microorganisms and what are they doing inside our body?
Decoding the Functions of Microorganisms in our Body
Dr. Momo Vuyisich: Yeah, so if you look at eukaryotic organisms... So we are eukaryotes, so all these higher organisms, we are all symbiotic organisms. We are an ecosystem that live in symbiosis with microorganisms, and there's a huge evolutionary advantage to living with microorganisms in that, those microorganisms protect us from pathogens, they help us digest food, and they provide chemical signals and nourishment for our health. And so we've basically co-evolved, like all other animals have, we have co-evolved to depend on these microorganisms. And they provide us, actually, with many benefits. They help us develop our immune system, and they help nourish us, and so on. So we have just as many microbial cells inside and on the surface of our body as we have our own cells.
Naveen Jain: Wow, that's amazing. And how about in terms of the number of genes? You know, I heard that they are more like human genes that we get from our mom and dad are 1%, and rest are all microbial. Is that true?
Dr. Momo Vuyisich: Yeah, that is very true. We inherit about 20,000 genes from our parents. So our genome codes for 20,000 genes, and these 20,000 genes encode functions that enable us to perform things, like kidneys use a certain subset of those genes to cleanse your body of byproducts and toxins. Your liver is using a subset of those genes to perform its functions. Your brain cells are using a different subset of those genes to perform its function. So these 20,000 genes allow all of our organs to perform the majority of their functions. And there are 20,000 of them. A typical gut microbiome of a typical human will encode four million genes, an average one.
Naveen Jain: Wow.
Dr. Momo Vuyisich: So four million genes versus 20,000 genes, a huge difference. Now, the majority of those microbial genes are, in fact, focused on microbial functions. And so the microbes are there because they're benefiting from it, but what they don't know, and obviously, microbes don't know anything. They don't have brains and consciousness, but what they don't realize, is that we have actually evolved and adopted many of the byproducts that microbes perform functions for. And we actually benefit from them. And so, I'll give you one particular example since we are trying to focus here on the immune system. Our immune system does not have a brain, it does not have consciousness, it does not have logical intelligence, right? It's basically trillions of immune cells, and they're listening for chemical signals. The only language that they understand is chemicals. If they sense certain chemicals, then they understand that our body's healthy, and they don't need to go and chew everything up inside the body.
But if they get chemical signals that says, whoa, there's a pathogen here, then they're going to get activated. And that's what we call inflammation or activation of the immune system. And so now, the immune system is going to say, there must be a pathogen here somewhere. I'm going to start destroying everything around. And this is where these inflammatory and autoimmune diseases kick in, where the immune system is hyperactive all the time. Where, in fact, the immune system should receive a signal from a pathogen, it should become active, it should clear out that pathogen, and then it should shut down. That's the normal sequence. It should be very inactive, very rapid activation, clearance of the pathogen, very rapid inactivation, and it goes back to the normal state. Now, the challenge today, and one of the biggest problems is that the signals from the microbiome that normally regulate this immune system activity, 70% of the immune system is in the intestines listening for the chemical signals coming from our food and our gut microbiome.
So that's the majority of the immune system, of course. So our microbes actually control the activity of the immune system. And so when our microbes are either, of a wrong composition, or more commonly, when they're fed the wrong diet, they actually send the wrong chemical signals to our immune system, and our immune system becomes chronically inflamed. And that leads to obesity, and diabetes, and autoimmune diseases. And all of these degenerative diseases like rheumatoid arthritis, and ankylosing spondylitis, most of these diseases are actually related to inflammation. Even Alzheimer's disease is related to inflammation, and so on. And so, we really have to focus on the communication between the gut microbiome, and our immune system. And the microbiome, again, doesn't have a language, doesn't have a brain, doesn't have intelligence, its chemical signals are produced in response to what foods we feed it.
And so, the most simplified example I can give you is, you put yeast together with some barley, and what's the yeast going to do? The yeast is not going to make gold. It's not going to make some other exotic compound, or chemical. It's going to simply eat or consume that barley. And the byproduct of that is ethanol. And that's how we make beer, right? So beer is made by employing one microorganism and giving it one ingredient, which is the polysaccharides in barley. Well, in our gut microbiome, we have a thousand different microorganisms, and we're providing them with something on the order of 20,000 ingredients in our foods that we consume. And so these 20,000 ingredients flood the intestine, 4 million genes that the microbes code for process these into byproducts. And these byproducts can either, feed our cells like butyrate, or it can signal to our immune system, wait a minute, something's wrong here, get activated. They control, basically, almost every part of our physiology.
Naveen Jain. Wow. So is it true then, are you saying that these microbes are really the master and we are simply the puppets here? And they actually train us somehow, that if you feed them the wrong thing, they're going to do a bad thing for us. And if you feed them the good thing, they're more or less training us as human hosts, what do they want?
How the Microbiome Impacts Neurotransmitters
Dr. Momo Vuyisich: Well, that's one way to look at it. I would look at it as, it's a true symbiosis. We benefit from them, they benefit from us. For example, a fascinating example for me is serotonin. So people know that serotonin is one of the major neurotransmitters, but it turns out that the majority of the serotonin in the body's produced in the intestine, by the intestinal cells. And, in fact, if you have an animal that does not have the gut microbiome, these are called germ-free mice, their intestinal cells do not produce serotonin. So they have evolved to not produce serotonin on their own. However, what stimulates serotonin production in the gut? It's the microbiome. Now, why would the microbiome stimulate production of serotonin, a very important neurotransmitter in humans? Well, it turns out that, many of the microbial members, many of the bacteria that live in our intestines, they can also live in soil. And so, they have a certain number of genes that enable them to live in soil and the intestines.
And they have to turn on certain genes in soil, in order to survive there. And they have to turn on certain, totally different genes in the intestines, in order to survive there. So, because they don't have eyes, they don't have ears, they don't know, they can't see where they are, they again, have to use this chemical communication. So these bacteria will produce small molecules that, basically, are released in their environment. And those small molecules stimulate serotonin production in humans. When serotonin is produced by the human, it's also released inside the gut. And now, the bacterium senses that serotonin and says, aha! I must be in the intestine, because nothing in the soil can produce serotonin. So the bacteria is using our serotonin production pathway as sort of a pinging system, like a echo locator that says, whenever I produce this small molecule, if the return signal is serotonin, I know I'm in the gut. And therefore, I'm going to be producing these genes. And that's how I'm going to survive. If I don't get serotonin back, that means I'm in soil, and I'm going to live in soil. How cool is that?
Naveen Jain: Well, that's very cool. That's like a GPS locator. So they actually are using the human body, is trying to figure out from the satellite, where they are.
Dr. Momo Vuyisich: Exactly.
Naveen Jain: The human body is their satellite.
Dr. Momo Vuyisich: Exactly.
Naveen Jain: Okay. Would you say that even aging is a chronic disease, and we don't really have to age, because we both know people, when they are even 60 or 70, they still perform as if they're still in their thirties or forties, right?
Dr. Momo Vuyisich: Yeah.
Naveen Jain: So how is it that happens?
Dr. Momo Vuyisich: I know. I mean, look at you, you're in your sixties chronologically, but you're like a 25 year old mentally and physically. Amazing. So yes, definitely, as a byproduct of what we do, aging is definitely like a disease. Meaning, there are physiological changes that human body undergoes, and these physiological changes actually reduce our cognitive abilities, reduce our physical fitness, reduce our mental fitness, and that's what we call aging. But also, aging is actually the number one risk factor for chronic diseases and cancers. Also, aging turns out to be the number one risk factor for infectious diseases, such as COVID, such as flu, right? So the number one risk factor for COVID deaths is the age. But [crosstalk 00:15:13].
Naveen Jain: You would argue that even death... I mean, dying, in fact, aging is a very good predictor of death also, right?
Dr. Momo Vuyisich: Yes, it is. But if we consider aging to be just like any other disease, meaning there are molecular changes that the human body goes through as time goes on, and that's what causes all these things that we observe, such as reduced fitness and increased disease burden. All we have to do is understand, what are those changes that take people from their twenties to their seventies, and how can we now prevent them? So again, there's nothing magical about it. It's just chemistry and mathematics, and that's what Viome is built upon. It's built upon chemistry and mathematics. We're measuring chemistry, using our fancy tests, and we're overlaying on top of that, mathematical equations that we obtain from data science and machine learning so that we can understand these changes. And we already have built those models, so now the next phase really is, how can we use those data to develop interventions that slow down and reverse aging, and then perform randomized control trials to actually test those ideas? And we're actually moving forward in all those, and we are scheduled to start a clinical trial for antiaging this year.
So, over the last few decades, we've had nutritional sciences that have basically used epidemiological data, where you're looking at, oh, some ingredient, on average, is harmful to humanity. And therefore, you should avoid it. And some ingredients are beneficial overall, to the whole of humanity. And therefore, we should consume it. But that's really the average, but no one is average. Everyone responds to different foods differently, and that's because their microbiome is different. And so really, unless we measure exactly what the microbiome activities are, we cannot make any personalized recommendations. And this is exactly why, if you go today with some kind of a set of symptoms, if you go to three different nutritionists, and present to them, exactly the same story, you're going to get three different recommendations.
And that's because nutritional sciences actually don't do any measurements. And if they do, they're limited to deficiency in certain nutrients. They take your blood and they measure, "Oh, you have low vitamin D. Let's supplement vitamin D." But really, nutrition is so much more complex, because like I said, we're providing about 20,000 different ingredients in our diet to a gut microbiome that has 4 million genes. And they're processing these 20,000 ingredients at a flood of chemicals. And these chemicals can be harmful or beneficial to us, and the combination of foods and microbiome in each person will determine that. And so the only way you can actually make these recommendations is by measuring.
Naveen Jain: So one thing, interestingly, you keep mentioning gene and this diet. There are lots of companies who claim that based on your genes or DNA, we can tell you what foods are good for you or not. And it has always puzzled me. And I wanted to get your thoughts on it, because I have always thought that, if you do my DNA today, and a year later, I gain 200 pounds, my DNA hasn't changed. And if I get heart disease, my diabetes, my depression, my anxiety, or I even die... Even after I die, my DNA hasn't changed. So DNA can't even differentiate between you are dead or alive, let alone you're healthy or sick. So when someone tells you, based on your genes, they can give you a diet. Is the diet going to be the same when I've gained 500 pounds, and I'm diabetic, and heart disease? Because my DNA hasn't changed, so how is it, all these company making this claim of personalized diet based on your DNA? What am I missing here?
Dr. Momo Vuyisich: Let's talk about DNA versus RNA, and why is it that we only looked at RNA at this point in time. So you gave some good examples, I want to give some more. So I would like everyone to understand that, every cell in the human body has the same 20,000 genes. And so, if you sequence your liver cells, and your kidney cells, and your brain cells, the DNA is going to be the same.
But look at the differences between a kidney, and a brain, and a liver. I mean, they are completely different. They look different and they perform completely different functions. That's because only a subset of those genes is activated in each one of those organs. And that's what makes those organs what they are. It's not the DNA, it's the RNA. So when a gene gets activated, it makes copies into RNA. And that RNA gets converted into proteins that actually perform the functions. So RNA's really executive version of the genes. And if there is no RNA, then the fact that the gene is there, doesn't make any difference.
Let's now go to the next example, which is even more powerful. Someone today has a perfectly functioning kidney, but three years later, they now develop some kind of a chronic kidney disease. If you look at their DNA of that kidney when it was healthy, versus when it's sick, it's the same thing. If you look at the intestine of a human, who has IBD, when they're in remission and that intestine looks perfectly healthy, and their life is good, the same person goes through a flare now, and they're sick. They're in pain every day. They're in pain every minute of every day. They can't function, and their intestine is completely inflamed. If you sequence the DNA of those cells, it's identical because it's their same DNA a month apart. What's very, very different, black and white different, is the RNA. So the genes that are activated during health, enable that intestine to be healthy and function and absorb nutrients, and not provide you with pain, whereas, when you go into a flare, that IBD person is now going to express totally different genes. And this is all caused by the microbiome and food.
And now the human genes are differently expressed, and now the person is sick. And so the difference between health and disease has nothing to do with DNA. It has only to do with RNA, in which genes are actually active. And now, let's shift to the microbial world and give one more example. So people have heard of E. coli. People have heard of Clostridium difficile, for example. And what I want everyone to understand is that these microorganisms are sometimes portrayed, or most of the time, are portrayed as evil and bad. But in fact, they can be very, very important friends. So clostridia are microorganisms that produce butyrate in very large amounts. And that's one of the most important beneficial metabolite, or chemical produced in the gut. And so 40% of Viome customers have Clostridium difficile in their gut microbiome, and that's natural.
That's not a problem. It's a very beneficial bacterium. But when a person consumes lots of antibiotics, and they probably have some other kind of a dysbiosis, this Clostridium difficile can take over the community, become pathogenic, and actually can kill the person. So if you sequence its DNA, when it's beneficial, versus when it's killing a person, it's the same DNA. The DNA cannot distinguish. That same DNA has the potential to be beneficial, it has the potential to be harmful, but if you sequence RNA like we do, then the difference between the same organism that's being friendly versus foe, is very, very different. So that's why we focus on RNA. It's the behavior, it's the actions of a microorganism or a gene, not the potential.
Differentiating Inflammation vs. Chronic Inflammation
Naveen Jain: I'm going to switch a little bit here. So let's focus on inflammation and a chronic inflammation. I think there's a reasonably good understanding, where I think most scientists now believe that chronic inflammation is a root cause of chronic diseases, including cancer and aging. Now, what causes the chronic inflammation, and when there is a chronic inflammation, what can one do about it, and how does it relate to cancer, aging, and other things? And also, how microbes relate to the immune system and also cancer.
Dr. Momo Vuyisich: Yeah, so obviously, the primary function of the immune system is to keep microbes outside of our body. That is it. And so it has to distinguish, what is something that's going to harm us and kill us versus everything else. And everything else includes our own protein. So it has to recognize self. And so, when someone develops an autoimmune disease, that means that their immune system has now shifted from attacking the pathogens to attacking self. Let's talk about inflammation. So inflammation is very, very important because inflammation in the gums and in the gut can lead to leaky gums and leaky gut, which now enables the microbiome from oral cavity, and from the intestines to leak inside the blood. And then the inflammation of the blood brain barrier can now allow microorganisms to actually go into the central nervous system. And then, inflammation, systemically speaking, for example, CRP is a great marker of systemic inflammation, leads to basically destruction of all organ systems.
So for example, when we talk about cardiovascular disease, we're talking about the inflammation at the artery walls. When we talk about IBD, we're talking about inflammation at the intestinal walls, and so on. When we talk about rheumatoid arthritis, or any kind of a joint problem, that's inflammation in the joints, and that's either autoimmune or it's actually due to some other activities. And so for example, my rheumatoid arthritis and ankylosing spondylitis came from immune system reacting to food ingredients. Many other people develop these reactive inflammatory diseases due to molecular mimicry. And a molecular mimicry is where a microorganism that's present inside of them, provides some kind of a protein, expresses a protein, or activates a gene that's very similar to our own gene. And now the immune system gets confused. And then most importantly, the microbiome can activate inflammation simply by producing lipopolysaccharide.
So lipopolysaccharides are molecules that are produced by certain members of the gut microbiome in response to feeding them certain foods that activate the immune system and cause this chronic inflammation. And so what we have figured out at Viome is, how do we actually prevent that LPS production, and how do we actually lower inflammation? So that's extremely important, but there's actually an important component there because LPS, lipopolysaccharide, is not all pro-inflammatory. Meaning it's a variety of molecules. It's hundreds of different kinds of types of lipopolysaccharide. And majority of them, in fact, activate the immune system and cause unnecessary inflammation. But there are some of them that deactivate our immune system, meaning they slow it down. And so by measuring which exactly types of lipopolysaccharides are produced in each person's body, and how do we control the production of those lipopolysaccharide by feeding certain people foods, we can actually modulate the functions of the microbiome and modulate the inflammation of the human body, which is really phenomenal.
Naveen Jain: I want to spend the last couple of minutes here, on aging and cancer. So if you look at aging, at least from all the things we have seen, analyzing over 300,000 people that as people are aging, they always seem to be that inflammatory markers are the cytokines that are pro inflammatory cytokines are going up. And is that what causes aging?
The Link Between Inflammation, Cancer, and Aging
Dr. Momo Vuyisich: Well, there are many things that cause aging. So inflammation is certainly a huge contributor. Also, reduction in T cells is a huge contributor. And that makes it-
Naveen Jain: But what causes the reduction in T cells? Is it inflammation or something else?
Dr. Momo Vuyisich: It's something else. It's basically the reduction in the size of thymus, and gene expression pathways in the thymus. So thymus is an organ where special antigen presenting cells are activating T cells, and they're teaching the T cells what is self and what is not self. And so it is inflammation that's destroying the thymus. And so we have to reduce that, but there are other regulators of aging via T cell activation that we can also modulate via the microbiome and nutrition. So we'll address that inflammation, like you said. And then there's a process called senescence. So senescence is a process where, due to inflammation, due to reactive oxygen species, due to random mutations that are not repaired, basically, a flood of harmful chemicals coming from the environment and coming from the gut microbiome is causing errors in our physiology. And these errors cause an increasing number of cells to stop functioning.
So we all assume that when we have a kidney, that a hundred percent of the cells inside of a kidney are performing the function of filtering out the bad chemicals from blood. But as we age, the percentage of kidney cells that are senescent, or they stop functioning, increases and eventually the kidney fails and the person dies. That's one of the reasons that a person's died. So when we talk about the immune system issues, such as reduction in T cells and inflammation, we're talking about the senescence of the immune system. So as we age, there are more and more errors introduced in the immune system. And so, one of our big efforts at Viome is to actually, because we're doing the blood test, we're understanding how the senescence of the immune system affects aging, and how it affects all other organ systems. And therefore, our first efforts will be at reducing the senescence of the immune system to slow down and prevent aging.
Naveen Jain: What is the microbiome’s role in cancer?
Dr. Momo Vuyisich: Wow, that's a huge topic, but let me summarize it. So what we've realized now in the last few years, is that the microbiome readily crosses into the bloodstream, and then gains access to all the organs via leaky gut and leaky gums. What we have also now realized, is that the microbiome is actually an integral part of every solid tumor in the body. So every time a solid tumor is biopsied, there's microbial components in there. And someone would ask, "Well, why is that?" Well, microbes, bacteria, fungi, and so on, they want to survive. So if they find a way into a tissue, the immune system will come chase after them, and try to kill them. So it is in microbiomes interest to find a place, a safe place, which happens to be inside certain stem cells or certain cancer cells that are starting to form cancer, that normally the immune system recognizes and cleans them out.
So there's something called immune surveillance where billions of our cells are turned into cancer every day, but the immune system comes and kills them. But if a microbe comes inside of a cancer cell and says, hey, I want to survive her, they can express certain signals on the surface of those cells, that say to the immune system, hey, there is nothing here. Don't worry about it. And so now, they can actually create an immuno protective area where the immune surveillance no longer works. And that's what stimulates the onset of cancer, and later, progression of cancer, and spread of cancer to other sites. And so the microbiome can actually actively promote carcinogenesis and can actively protect cancer from the immune system and also immunotherapy. And so the microbiome plays, now, a critical role in the onset of progression of cancer, and spread of cancer.
But not only that, the microbiome... Remember the gut microbiome, even without actually entering the human body, because it regulates our immune system, it can weaken our immune system and not really enable it to do immuno surveillance and kill cancers, or it can actually stimulate our immune system to be very healthy and very strong, and to perform immune surveillance and kill all the cancers. And so now, we have two reports where people who are undergoing immunotherapy for melanoma, if they do not respond to immunotherapy, but another person from that clinical trial responds, all the doctors did is, they swapped poop from the responders into non-responders. And now they turned non-responders to immunotherapy into responders. So they're the same person. They're eating the same food, they're doing the same thing. All they did is they received poop from a person who responded, and now they become responders. That's unbelievable, basically, that the entire function of the immune system is so regulated by just the gut microbiome that's found in the intestines.
Naveen Jain: Wow, wow. Unbelievable. Now, in the last two minutes here, Dr. Vuyisich, what will be your prediction for the next decade or so, if you were to look in 10 years from now. Where do you see... As a big picture, from the humanity perspective, and for Viome, both?
Dr. Momo Vuyisich: Just the reminder that our mission is to eradicate all chronic diseases and cancers, and that will happen over a period of a few decades. So we are attacking now, what we call the low hanging fruit. And so within the next decade, we are going to focus heavily on gastrointestinal diseases. So we're talking about IBS, IBD, SIBO, gastrointestinal cancers, GERD, and so on. And we're going to focus on metabolic diseases. So this is obesity, type 2 diabetes, fatty liver disease, and so on. And then, we're going to focus on cognitive diseases, specifically on Alzheimer's and mild cognitive impairment. And so those three big groups of diseases, I think that in 10 years, for the most part, we will understand exactly what causes them. And we will be able to prevent those events from taking place. Which means that we will have very, very good preventative strategies for that whole spectrum of diseases. And we will already start working on the others. It's not like we're going to ignore the others, we're working on all of them. But after that, the rest of the dominoes will start falling.
Naveen Jain: Well, here's my prediction, Dr. Vuyisich, that I think within a decade, we, as humanity, would get rid of cancer. That means we'll be able to prevent the cancer from happening, or early diagnose them while they're still curable. And to me, that will be a great day for humanity. And let that be the last word here, so that one day we can hope that no one will ever get sick. And the billions of people on planet earth can live a disease-free life. And we can all, essentially, be proud of it, what we have done at Viome, and what we together, as humanity can achieve. And I'm so glad that you and I are part of that mission. And one day, we're going to look back and see what we have created. So, Dr. Vuyisich, thank you very much for being part of this series here. And looking forward to continuing to work on that mission.
Dr. Momo Vuyisich: Thank you, Naveen. Thank you.
Naveen Jain: Thank you.