Episode 73: Life Finds a Way: The Genetic Map of Microbes

Robert Rountree:

This is the Thorne Podcast. The show that navigates the complex world of wellness, and explores the latest science behind diet, supplements and lifestyle approaches to good health. I'm Dr Robert Rountree Chief Medical Advisor at Thorne, and functional medicine doctor. As a reminder, the recommendations made in this podcast are the recommendations of the individuals who express them and not the recommendations of Thorne. Statements in this podcast have not been evaluated by the Food and Drug Administration. Any products mentioned are not intended to diagnose, treat, cure, or prevent any disease.

Robert Rountree:

Hi, everyone. And welcome to the Thorne Podcast. Joining me this week is a special guest, Dr Chris Mason, who's a professor of multiple disciplines. He can tell you about, at Weill Cornell Medicine. He's the Co-Founder of Onegevity, which was acquired by Thorne HealthTech last year, and a scientist and entrepreneur whose work focuses on understanding the human genome and microbiome, so we can better fight disease. So, Chris, welcome. And how about we start by telling our listeners exactly what you do and who you are. And I want to preface that by saying that I glanced again at your website for the Mason Lab, and there's a picture of you and a bunch of guys sitting in the New York City subway. And underneath that, it says, "Integrative, functional genomics." So what the heck? What does subways have to do with, and what is integrative functional genomics and who are you?

Chris Mason:

Yeah, well, thanks for having me here. It's a pleasure to be here. So yeah, again, I'm Chris Mason. So I wear a number of hats and one of them is really the great benefit of doing a lot of research at Thorne, in the Onegevity division. Again, we were acquired last year, but a lot of the work that's on testing out some of the Thorne products in clinical trials or developing new methods or new approaches to modeling how patients are responding to probiotics, prebiotics, supplements, medications. And seeing how their bodies respond and can we improve how we help patients along on their journey, is something I've a really great pleasure to do at Thorne, and previously at Onegevity.

Chris Mason:

So we do it all as a big team now, but also, we're ahead at Cornell, so have a lab there. The integrated, functional genomics lab is, to break that down, it's a lot of genomics. So we look at DNA and RNA and the barcodes of life, things that give you the recipe to make all your cells in your body. We try to see when it gets mutated or changed or damaged, which can lead to disease. But we also look at the microbiome and we go swab in subways, we swab patient samples. We do nasal swabs, throat swabs, rectal swabs, really, if we can swab it, we're looking at it.

Robert Rountree:

And astronauts too.

Chris Mason:

And astronauts, and in astronaut butt wipes, all kinds of things. Because every part of your body has its own ecosystem. And that includes on the outside of the body, things that are obvious, like your ear lobes and inside your ears is different from your feet, but also, you can see in your mouth or what's in your gut. There's all these other microbiome ecosystems that are key factors in human health and disease. So we want to have, what I'd like to say is, a kingdom agnostic view of the biology, because if you're sick, you don't care if it's a human cell, a bacterial cell or a virus, or whatever's making you ill, you just want to figure it out and get rid of it or change it. So we try to look in integrative functional genomics. We look across what is the function of each genome, whether it's human or otherwise, then integrate that data. And that what the lab does, but personally, I'm just a kid from Wisconsin. Now I live in a big bad, New York City.

Robert Rountree:

Well, that's a lot. It sounds like you've got a really fun job to be honest. You get to explore the unknown. We talk about Star Trek, exploring the unknown in space, but there's a lot of unknowns about the world we live in.

Chris Mason:

Yep. Actually, I have the best job really, quite possible because every day my job is to learn and discover, which we do literally every day in the best possible way, means we have the most data on any given day when I wake up. It is the best day to do my job as a geneticist. I have more data on every given day than the day before. So the capacity for discovery, the ability to leverage that data for new patients and for new clinical results, is literally, empirically better every day. So it's not even my opinion that it's the best day ever, to do my job. It's just a fact, it's just the state of the field. And so, I'm very fortunate.

Robert Rountree:

So every day there's a new question to be asked and resolved.

Chris Mason:

And more data to address it and to understand it. So it's wonderful.

Robert Rountree:

So I'd like to start by bringing up a fellow who, I'm sure you're familiar with, Dr Craig Venter, who is famous for asking a question that we didn't have an answer to. Which is, what's out there around the planet, in the oceans? And so, he got on his boat and sailed all over the planet and collected samples. Can you tell us a little bit about what that involved, what he found and what it meant? What were the implications?

Chris Mason:

Yeah, happily. So actually, Craig Venter was the person who published the first sequenced genome. It was a virus and he looked at bacteria as well, back in the mid 1990s, but with the completion of the first human genome in 2001, and started looking at fruit flies and worms, he, I think caught a bug, which many people in the genomes field get is, okay. We can understand one genome, for example, the human genome. Even there, we barely understand all of it, but at least to have the very first map of the genetic book of life. Whereas before we didn't even know the letters, how they were placed in the book of life, we didn't know what were the constituent parts that made a human cell become human and how did encode all of its functions. But once you get that first map, you can start to tease it out.

Chris Mason:

And that's part of the functional genomics part of our lab, is we look at what are the functions of each of these bases. But invariably, once you have that first map you want say, "Well, could I make maps of other creatures and find out what's out there?" And it's even sometimes just a very fundamental question I think when we've all been kids, if you're wandering around a garden, you see 1, 2, 3 insects, you see different plants, you see you really different organisms all around you and you can't help but wonder, how many plants are there? How many kinds of bugs and worms and beetles? And you just Marvel at the complexity and diversity of life. And as Charles Darwin did, just wonder, well, where is it all? How does it change and how many kinds of them are there? And so, he went into the Sargasso Sea, Craig Venter did and said, "Okay, I want to go find anything that's in the oceans and just sequence everything that's there and start to build a genetic map of the planet."

Chris Mason:

And it was some of the first data sets of what's called metagenomics, meaning it's across all genomes, like you look at one level above a genome, it's metagenome, it's across all species. So it's human, bacteria, viruses. It could be plants, fungus, anything that's there when you sequence it, you'll see it and assemble it and start to understand it. And he did that in the Sargasso Sea and found thousands of new organisms. And we have done the same thing, actually going out to swabs cities, and particularly subways around the world, and also find it to be this bounty of new species, new functions, new life, quite literally under our fingertips.

Robert Rountree:

I seem to recall you saying in a lecture years ago, that when you began mapping all these species in different cities, I think you called it the Metropolome or something like that.

Chris Mason:

Yes. That was great.

Robert Rountree:

The Metropolome, that you said that this huge percentage of species you found were unknown. All you knew was that it's got to be some kind of bacteria or it's got to be a virus, but we don't know what it is or we don't really have a name for it. Is that still true?

Chris Mason:

Yeah, 100%. What I mean by that is, when you sequence a sample, you end up getting millions and millions of these short fragments of DNA, which are usually about a few hundred letters long. So you basically take that sequence and that'd be akin to say, walking into a library, say a large university library that has millions of books. And you want to take a snippet of text that you got from a shredder and say, "Okay, I want to know, where does this belong?" You want to map it to the appropriate text from which it came. So it's like trying to find just a source of a quote for example, or is it from Shakespeare? Is it from it Kim Stanley Robinson? Is it some other sci-fi writer? Figure out where a quote came from or a snippet of text.

Chris Mason:

And to do that with DNA, you basically align it, means you compare it computationally, you take each sequence and compare it to every other known sequence that's ever been seen. And when we do this, when we did it then, we saw there's about 49% of all the fragments out of those millions and millions of fragments of DNA matched no known species. And so, it doesn't mean that the New York city subways full of aliens, although sometimes it feels that way, but it just means that our databases are still incomplete. So our understanding of the totality and the diversity of life is still being created and accreted and expanded. We're nowhere near the saturation of understanding what life we can even look for. And so, every time we sequence a sample, we actually see lot times new species or new variants of species.

Robert Rountree:

So I know that this kind of genomic testing has gotten to the point where you can say, swab a room and then tell if an individual has been there. Can you do that with a city? Can you look at a series of samples and say, "This looks like Sydney, Australia." Or do cities have their own individual personalities, microbally?

Chris Mason:

Yeah, just like they have their own linguistics and accent. They have a microbial signature as well that we can pick up. And with about 93% accuracy, we could take a swab from a shoe or from a sample in a city and tell you where it came from. So it has this forensic application, which was unexpected to see how well it worked. And this is part of a global consortium, it's called meta-sub, which is the metagenomics of subways and urban biomes. It's actually over a hundred cities of people that we get together once a year, virtually. And we in unison, swab across the whole planet. So we create these planetary, microbial censuses on an annual basis. So it's this really fun group of collaborative, passionate swabs. And they just love to swab.

Robert Rountree:

Passionate swabbers.

Chris Mason:

Lot of vigorous wrist shaking. It's good.

Robert Rountree:

And what is all this telling you about the world that we live in? Seems like that's a two part question. One is, these microbes that are out there, they're interacting with us obviously, right? They're having an impact on our health in some way. And you mentioned earlier that most of the bugs you found on the subway, they're not harmful. They're not going to kill you, but do they interact with us? Do they exchange DNA with our own DNA?

Chris Mason:

Well, the microbes do get transferred, say from your hands or the pole, or the seat to your elbow. There is a continual exchange of microbes that are either resident in the systems, or they just recently left there by your other fellow riders. And what's interesting is, as you noted, most of them are pretty innocuous or harmless. They look a lot just normal skin flora that you'd find, like some Acinetobacter or what's called staph. You might think of staph, staff infection, but staph epidermis is very commonly found on the skin. So it's just really, a normal resident microbe that represents actually a pretty healthy skin. So most of them just look like human skin, the species that we find there. But we have seen that they change really, on an hour by hour basis. Some places we swabbed in a continual sampling across every hour on the hour, and we can see continual movement and exchange. And so, it means you do sometimes bring it home with you and they could potentially change what's on your skin and potentially your health long term.

Robert Rountree:

And your wife wants to know who you brought home with you?

Chris Mason:

Really, yeah. You could be like, "I brought thousands of friends home with me", which might go over not that well, but it's true.

Robert Rountree:

If you go out and ride the subway every day, how much does that affect your intestinal microbiome? Does it have an impact?

Chris Mason:

So I don't think too much for intestinal microbiome. It really depends how much you bite your nails or put food in your mouth that you find in the subway. So it shouldn't impact your gut too much we don't think, but definitely your skin will get in exchange between the environment. I'd say, obviously it's your largest organ and has the first line of defense against anything that you might have, that could be bad. But the gut microbiome what's interesting though is, we can see, of course it has a lot of normal species. What are called firmicutes and bacteroidetes, which are these staple organisms that are present as this anchor to the ecosystem. And that we can actually see, sometimes though, we see that in waste water. We also look at waste water [inaudible 00:13:12]. And so, we can actually gauge the health of a city, based on what is left behind and also track COVID. So we even have multiple projects tracking the emergence of COVID variants in cities around the world, using what's left behind

Robert Rountree:

Well, now that we're not really tracking COVID cases that much with humans, it seems like this wastewater testing has become the major tool. We have to figure out what's going on globally.

Chris Mason:

That's right. And it's good because, everyone has to at some point, go to the bathroom. So it's pretty unbiased. There are some people taking camping trips and they're going out in the woods, but there's not that many. But otherwise, everyone flushes away their waste, but it is extraordinarily rich information about what, and not just COVID, but also, actually, this morning I was on a call. We just picked up monkeypox also, in the sewer. So we can pick up emerging pathogens, anything that's beginning to percolate through the population and emerge. We have this molecular view of the epidemiology of a metropolis, which is really interesting.

Robert Rountree:

So when I studied microbiology in college and I actually worked my way through college, working in a microlab and we were swabbing plates all day, we'd take samples. It was still swabs. You start with a swab, but you swab a blood plate or an auger plate. And then you see what grows and what inhibits it. But now, the testing that you're using, it is like Star Trek. It's way out in the future. I'm wondering, is there in a nutshell, can you explain to people what you're doing with metagenomics and how that's different than the ancient methods that we used when we plated things to look for bad bugs.

Chris Mason:

Yeah. So we still do some of that to confirm what we can detect, but now when you sequence the organism, meaning you look at all the DNA that's present. We can see the antimicrobial resistance markers. These antibiotic resistance molecules are made by the genes that the organisms have picked up and you can sequence them. You can see them. So we can actually quantify how much of resistance it can have before you see it phenotypically, meaning you see it on a plate and you can test it that way. And sometimes though, it's more complex because an organism might be potentially resistant, but doesn't really get activated to be resistant until it's challenged or until a later state. But you don't have to plate it to know what it could be resistant to, but you might still want to plate some organism to see what it's actively resistant to and really functional and able to resist to, and then validate that. So it's still useful tools. Those skills are still good to hanging on to, I'd say.

Robert Rountree:

They may come in handy, but we would never have had the ability to do what you're doing now, which is figure out in the subways and in the oceans and really, in our guts. And that's the parts that's really interesting is, where we've really progressed in terms of figuring out what's in a human intestine.

Chris Mason:

And also, what's exciting is for the Thorne, with the gut health test that we run for a lot of our patients and customers, you get this full catalog of what's in your gut, as well as essentially, what the implications are for your health, or you have need more or less diversity or different species to be added or removed. And we also, everyone does get this little pie graph of how many unknown microbes are in their guts. So we also include that and these methods are really cutting edge and just define the way the field works today. And in particular, they give you a lot of discovery for the future too. You can go back and look at the same dataset 20 years from now and find new things about it. So it has a lot of long term use too.

Robert Rountree:

So one thing I would point out, and maybe you can explain this more, is that the kind of technology that you have worked with, with Onegevity, and now Thorne looks at all the DNA in the sample, which is really different than the first generation stool DNA testing, which use, they use probes so that they could say, "Well, we're going to look for this bacteria. We're going to look and see if you've got bifidobacteria or lactobacilli." So you have to look for something, to know if it's there. Whereas this is exactly the opposite as, I think the word you used earlier is, it's agnostic. You look at everything that's there. Can you say something about that?

Chris Mason:

Yeah. So most, even other tests on the market and even diagnostic testing, if you go to Quest or Labcorp or go to a lab and say, "Okay, I want to get tested for strep or I think I might have COVID." A lot of these tests are very particular. They are focused on one or two pathogens, maybe five or 10. And they have potentially a chemical assay, often, which is PCR based, polymerase chain reaction, which just tries to amplify a targeted region of one specific part of one particular organism. Or if it's what's called multiplex, meaning you do more than one at a time. It does it maybe for five or 10 species or a few more. But what's interesting about being unbiased and agnostic is, we sequence every molecule that's in that sample. So if it's monkeypox, if it's COVID, if it's staphorsius, if it's MRSA, if it's something that's any variation of any species, as long as it has DNA or RNA, we can sequence it and see what it is.

Chris Mason:

So it is the most thorough and broad view of the biology of a sample, because you get this really, almost completely unbiased view of all the molecules. There are some caveats. So if something is really abundant in a sample, you'll see more of that species than a different one. So if something is really rare, you had just a very beginning of an infection. You might sometimes miss low abundance species. It's the only caveat, but otherwise, it's something we do more than any other assay, because it has the greatest potential for discovery and use.

Robert Rountree:

I'm sure you know Dr Martin Blaser, who wrote a famous book called The Missing Microbes. And he says that what's happening in the human gut is that, we actually have fewer and fewer overall microbes than we used to have. And that impacts our health. When you do this metogenomic testing, is that something that shows up? Can you see that?

Chris Mason:

Yeah, we can see. So the diversity is falling. So actually in our guts, in our skin, even just in the subway, we can see this, because during the pandemic, we can see the diversity of species found on the subway system drop down because there were less people riding it. So we can see, even in cases of really sharp perturbations, like a pandemic, where it changes the environment. But in our own bodies, comparing our guts versus those of samples banked from 20 or 30 years ago, he called the book The Missing Microbes because we're really frankly, missing microbes. So we know this, just relative to past samples, and relative to other tribes that have been sampled that are still say, in the Amazon or other Aboriginal samples. They do seem to have a greater number of species, different types of species.

Chris Mason:

They have this more robust and diverse ecosystem, which like all ecosystems, you want to have that because it's more resilient if you kill one or two species, but you only have five that are really abundant, that'll be really destructive. But if you have dozens of species, you can tolerate more loss of one or two species. And so, that is what we're seeing, unfortunately, in the guts. But the good thing is, we don't have to sit by, we can actually add probiotics. We can monitor these changes. We can help people in theory, tweak and improve basically, their entire gut ecosystem.

Robert Rountree:

Well, I know that it's pretty clear when you sample gut microbiome of people in the ICU, that have had trauma or something bad has happened. They're really sick. And those people do get down to just a handful of species. So it's clear that's bad. Has it been established that these Amazonian tribes that have a lot more microbes in their gut, are they healthier as a result of that?

Chris Mason:

It seems to be. Some of these studies are small, having only a few dozen people or maybe 100. And interesting data, but it's too early to say definitively, I would say, but they definitely are distinct where markers of inflammation seem to be much lower, and even stories I've heard from Larry Weiss, who's the founder of Persona Biome and other companies. He was at AO Biome before that. He's been there to visit some of the tribes and they don't really have any acne or they seem to be missing some of these other, more modern ailments that we have. So it really is this intriguing thought of, what if we could find the species we've lost and then put them back into our diet, put them back into our life and back into our bodies? So it's an intriguing question. It's early days, but it's definitely some evidence that, that's the case.

Robert Rountree:

And does it look like we're on some clues about how to enhance that diversity? Not just guesses, but things that we know will do that?

Chris Mason:

Yeah. At least in terms of what are these called Keystone species, which really hold the ecosystem together. There are at least now candidates being tried that will help that. And one of the most notable ones for gut health, is Akkermansia muciniphila, which really seems to be a great driver for maintaining gut health, and also reducing risk of even diabetes. So it's not just about maintaining the ecosystem, it's also processing your food and when you take medications, it processes your medication. So if you're looking for the nearest pharmacy, you just got to look at your gut. And so, it's important for almost all aspects of your health and disease for humans.

Robert Rountree:

Now, one last thing before we take a break that I wanted to bring up is that, these new discoveries about DNA alterations, et cetera, have also extended to screening the body for cancer. We're looking at DNA floating around in our bloodstream. And I wonder if you could just speak to that in a sentence or two about what's the potential of this genomics frontier for cancer screening?

Chris Mason:

Yeah, it is really also fundamentally changed how we do cancer screening and also prenatal screening. So there's fragments of DNA in our bloodstream that are always being shed, because cells are dying and being born all the time. But as they die, they give information about where they came from in your body, because DNA, of course the DNA is the same in every cell in your body. But what has turned on or turned off is a control called epigenetics. And that can be controlled by little chemical marks called methylation. Which what that means is, if you take all the fragments of DNA floating around your bloodstream, if you look at these epigenetic signatures or methylation, you can see which tissues are dying more than others. And you can even see, if it's a cancer cell, they have distinct epigenetic signatures, and you can look for those in the blood. So you can look for mutations as well as epigenetic differences. And this has fundamentally changed how we screen for newborns, or not newborns, but prenatally, you can look for fetal abnormalities.

Robert Rountree:

Down syndrome, things like that.

Chris Mason:

Yeah, it's fundamentally changed how, 10 years ago was all amniocentesis and CVS with a pretty high risk of miscarriage. But today, for cancer's now undergoing the same transformation where basically, you can screen for early stage cancer, but also as you're undergoing therapy, you can see the mutations go away if the therapy's working and you can quantify how many molecules of the cancer cells are showing up on your blood. Because it's like having a whole body molecular scan just with one blood draw, because your blood is this liquid organ that captures basically, molecules from all of your body. So when you sequence them and look at all those fragments, you can tell where they came from, if they're mutated and if they're cancerous. And so, it's really a hope that you could start to detect cancer maybe really early, before it starts to spread.

Robert Rountree:

So this is really just a variation on the same technology you're using to look at the gut microbiome. Now we're doing liquid biopsies, so-called liquid biopsies, where we look at the DNA circulating in your bloodstream.

Chris Mason:

Yep, exactly. So you just basically take all those fragments, prep them and sequence them, and then characterize where they came from. So it's like what we do for subways and see what city did your fragment come from? You can do the same thing inside your body and see what tissue did it come from? Does the tissue look normal? Does it look like it has cancer? And so, it really is this powerful tool. The sequencing tools really reveal this really vast area of biology you can use for diagnosing cancer and then seeing treatment efficacy. But then, you can maybe catch it early as well.

Robert Rountree:

Things have definitely changed since I went to school. It's a whole new world out there. And I think it comes in handy to know how to use a computer.

Chris Mason:

A lot of it becoming more a competition. It's just lots and lots of data, you got no choice.

Robert Rountree:

Let's take a short break and then we'll come back to answer some questions from our listeners.

Robert Rountree:

Although getting older is inevitable, you can control how well you age, and Thorne offers a variety of solutions to help you do just that. Thorne's Biological Age Test utilizes a blood panel that analyzes the rate of aging for your entire body and its various organs, and provides specific recommendations to help you slow or improve the aging process. Thorne also offers several science backed formulas that promote healthy aging from nutrient rich, NAD+ boosters, to collagen powders, so you can age better inside and out. Find the right formula for you by taking Thorne's Healthy Aging Quiz and get real recommendation from Thorne's medical team. Learn more by visiting thorne.com/healthyaging, that's T H O R N E.com/healthy aging. And we're back. So now it's time to answer some questions that have come in from the community. The first question this week comes from a listener who asks, what is the planetary microbiome? So we touched on that, Chris, I'm just wondering if you could give us a holistic view of what we're talking about when we use that phrase.

Chris Mason:

So the planetary microbiome is a view of the planet. Even though they're very small, it's microbes, but about the broad range of diversity of those microbes that really define our whole planet. And we actually now can map at a planetary scale, changes in these ecosystems, including say, coral reefs because they also have their own microbiome. The oceans do. We can see changes in livestock. We can see this really continual movement of microbes now that we have enough technology to do sequencing and have people out collaborating and sampling and characterizing these different environments. So it really is a view of biology at a planetary scale, which is I think, how it always functions.

Chris Mason:

So we're just now being able to see the way the world has always been, which is, even microbes been moving through the atmosphere, being moved in streams and rivers, and also more modern ways like through trucks and through ships and through Ballast containers, and more recently COVID. We also have people travel and they bring viruses with them and infect others. So we've all gotten a real keen sense of this more recently, but we can now think about it, model it, map it, and actually respond to it at a planetary scale, which is pretty cool.

Robert Rountree:

That's very cool. If the next question was, if the planet has a microbiome, are we the viruses? I'm not exactly sure what they mean, but are we the interlopers? Certainly the bacteria were here first and we came second. So how do humans fit in to that microbiome?

Chris Mason:

So we're a more recent addition to the planet, but that's for sure, but we, I think bring something really unique. And I wouldn't characterize we humans as a virus, although commonly discussed in movies and in philosophy, are we doing more harm than good? Because we definitely do some harm and have done harm to, not just our own species by killing each other and murder and mayhem and crime. But also, we have created, genocide has happen. We've created extinction for different species. So humans are not perfect, but I really argue that they're really unique and essential, because they're the only species, we are the only species with the awareness of extinction. So really, only we have the capacity to address it because we're the only ones that know it's even possible.

Chris Mason:

And so, this gives us a unique responsibility as well as awareness of extinction, and I think a duty to protect life against it. Not just our own for selfish reasons, but all life as we know, otherwise it will eventually be burned to a crisp by the sun when it engulfs the planet. So if you look at a long enough timeframe, as far as we know, we are the only organisms in the universe that can protect ourselves or others against imminent extinction. So I think it gives us unique place and duty, and that means we're not the virus, we might even be the savers.

Robert Rountree:

It's the savers. And is it fair to use the term supra organism, which I've seen in some articles saying that humans are really, we are really an amalgamation of the microbes that make us up?

Chris Mason:

Yeah. There's some terms for this. The holobiont is one idea or some people call it omniGenic, meaning all genes in a human genome contribute to a phenotype or also other genes. Some people just call it ecosystem or even a metaspecies. There's a number of terms for it. But empirically, also another one is just called systems biology. We look at all systems together, but really, that's what you should be doing anyway, if you want to understand a system, you want to have included all the components that may mediate changes in any given system. Whether it's an engine for a car, where you're trying to figure out if something's wrong with the car, you look at all the components, not just something say, only in the front of the hood or you look at the front or the bottom, anything it's connecting all the wires, all the plumbing, where the gas is coming from.

Chris Mason:

So same thing's true with our bodies and our ecosystems. We want to look at them holistically. And I think whatever you might call it, is not as material as the fact that you have to do that to have a better model of what's happening. And so, I think the modeling has to be done, but then also, you want to predict what will happen. That's the best test of understanding is, can I make a model and guess how well you'll do for say, for a therapy for a cancer or a probiotic for a gut problem, or even for an ecosystem. You can make these things called gene drives, which are self replicating entities that move through an ecosystem and copy themselves and fundamentally change what species are even present in an ecosystem. So we have these really awesome new powers genetically, but we've just begun to roll them out, but we might need all of them to survive long term, I think.

Robert Rountree:

So how connected are our genomes to each other? If you've got a dog that licks your face, and you and your partner, your wife, spouse, et cetera, sleep together every night. How much of an exchange is going on that impacts the mutual microbiome?

Chris Mason:

Yeah. The old saying is that, we're all about 99.9% similar to each other at the human genetic level, your human DNA. But on a microbial level, you could be anywhere from 95% the same as someone say, you live with, to only five or 10% the same from someone far away with a very different diet and a very different background and different lifestyle. So the microbiome diversity can be vastly divergent between people. And that means also how you eat, how you process food, how you have gut inflammation, how you actually maintain homeostasis in your gut and your body. It depends a lot on where you came from, where you grew up. And that's actually another thing you can do is that, everyone does have what's called a gut print, like a fingerprint. And you have a gut print which tells that it's you.

Chris Mason:

So if we set up a little DNA sequencer on every toilet around New York City, I could tell you where you're probably going to the bathroom if I had enough of your samples before. Which we've not done yet, but I would love to do that. It'd be interesting. So that's one thing. And also, there's actually this really great website called the iTOL, it's the Interactive Tree of Life, where you can put in any two species and see how convergent or divergent they are. Are they 1 million years apart or 1 billion years apart? So that's a fun tool that you can use as well.

Robert Rountree:

So the next person asks, how do I heal my microbiome? So that's interesting, because embedded in the question is the assumption that our microbiome needs to be healed, that something is "Wrong", as Dr Blaser would've said, "Things are missing." So do our microbiomes need healing? And if so, what's the best way to do that?

Chris Mason:

Yeah. So it depends on the person and your microbiome. So it doesn't necessarily need healing. Sometimes you just might need a different diet and your microbiome will respond. So that in a sense, you've healed your microbiome, but you really just changed what you're giving to your microbiome. But there are places where you can have really a deli belly, they call it, you can get parasites, you can have really sharp disruptions of your microbiome in your gut, which leads to persistent diarrhea or IBS or IBD. And we've shown with clinical trials that we've done at Thorne, a paper we just published a little bit over a year ago was ways where you have a guided intervention for what probiotics and prebiotics are used. And some of which I know you prescribed clinically for your patients. This can help heal the microbiome and make it so it's more robust. It actually helps you process food.

Chris Mason:

It leads to lower inflammation and it generally makes you healthier. So I think if it is deeply perturbed, some patients are harder than others, and some of the patients we've healed. I've gotten some of these emails and I know you have as well, where patients who hadn't had a normal bowel movement, sometimes for five or six years, suddenly can feel like they can go to the bathroom. And so, it's really quality of life. It's the ability to live without suffering that can really be healed if it's done right.

Robert Rountree:

It's interesting, because I often see in the mainstream medical journals that comment, probiotics don't work, probiotics are waste of time. And I think, "Well that's discordant with the published research. It's discordant with the literature." I assume you agree with that statement, that it doesn't jive with what we know that probiotics can work. It's just that different probiotics work differently for different people.

Chris Mason:

Right. It really just depends. Yeah, exactly. So it is. And it's like most medicine, we think of precision medicine as if it was this big revelation, but we should always have been doing precision medicine. You give the right drug to the right person at the right dose or the right treatment to the right, essentially paradigm for someone to be treated in, to match that patient as best you can. Otherwise, you're doing a disservice to that patient. And so, that's what is finally happened I think, that we've reached that stage.

Robert Rountree:

Now we're getting to the point where we can do this gut microbiome testing and say, "You are more likely to respond to lactobacillus or bifidobacteria or bacillus coagulans or something like that.

Chris Mason:

Yeah, exactly.

Robert Rountree:

So here's an interesting question. If our bodies are tuned to a planetary microbiome, I assume they mean our bodies are tuned to Earth's microbiome. What's going to happen if we bring back a sample from the Mars Rover and there's a microbe in that Mars Rover in a rock. What's going to happen? Is it possible that would be bad for us or good for us or unpredictable? What's your take on that? Is there going to be a war of the worlds, somebody says, a microbial war of the worlds?

Chris Mason:

Yeah, no it's possible. I think what happened when we brought smallpox over to North America from Europe, that was of course not so good for the native population, amongst other atrocities that happened. So we know that there that, or even Black Death and bubonic plague was used as war in the 12th century and people would actually launch stool over the gates of different city states. So pretty gross and pretty devastating, but effective. So I think the worry is that we might have an Andromeda strain, is what Michael Craig called that, someone would come back to earth and we'd all be doomed. It would kill everyone on the earth. So that's probably unlikely, just because microbes are really attuned to where they come from and would probably wouldn't even replicate that well in humans or in other terrestrial creatures, probably. But unless we share a common ancestor for all of our DNA, which might be three or 4 billion years in the past, then maybe they would.

Chris Mason:

So we don't know yet, but there is a Mars sample return mission slated for 2032, where NASA and ESA will be bringing back samples from Mars to characterize them, to examine them and see if they have life and then potentially try and grow it here, or at least characterize it. And they're going to do it very carefully. It's like equivalent of a BSL-4 laboratory, like you see Ebola being studied in or Marburg or really contagious viruses. And then it'll be built containment around that as well. So it should be pretty contained and hopefully it'll be okay, but maybe it's not a risk. What if something comes back that is a magical probiotic that gives you nutrients and vitamins and you just have to take the pill once and it's the Martian super probiotic. We don't know what we'll find. It could be good. It could be bad, it could be neutral, but I want to keep all options on the table until we get it.

Robert Rountree:

So I know that you have published some studies based on swabs you've done on the International Space Station. And I'm wondering, have you found microbes growing there that nobody had ever seen before? And if so, where do those microbes come from?

Chris Mason:

We have. So what's interesting is, we have several papers showing that these species continue to adapt and evolve in space, just like they do everywhere else. And they evolve so much that, eventually they have enough of a genetic difference. They're technically a new species, but almost all of them came from the crews that brought them up. So they really-

Robert Rountree:

Oh, okay.

Chris Mason:

Some acinetobacter, some staph, normal... Some acetobacter, some types of species you find in skin that just have evolved while they're in space. And so, we don't think they're coming from outer space, into the space station colonizing and being brought back down. It's just that they're terrestrial organisms that have become so divergent and evolved, that they actually are technically a new species.

Robert Rountree:

So there's no space invaders that are sneaking on board.

Chris Mason:

No, not to our knowledge. We're going to keep looking for them though, I think. We'll see.

Robert Rountree:

Yeah. And I know you have found some very strange things on that though. We say the toilet on the International Space Station seems like a particularly fertile place to swab.

Chris Mason:

Like all toilets. It's a little mini rainforest of diversity. So we found, there's some strains of pseudomonas putida it's called, where it actually, it became more resistant to antibiotics than the ground controls over time. So some things do give us a moment of pause, where we want to keep an eye on the station, keep an eye on the environment, make sure it doesn't get too bad, but we have seen some interesting changes for those space station microbes.

Robert Rountree:

So we need to be careful what we're bringing back.

Chris Mason:

Absolutely.

Robert Rountree:

With those rocks. So next question, civilization, uncouples us from living naturally with our planetary microbiome. How do we get back to embracing the planet microbiome, instead of fighting against it? Which that's a very interesting question.

Chris Mason:

Well, you can't manage something until you measure it and you can't modify something until you've got a model of it. So I think we are doing both those things now, as we're measuring and modeling. We can begin to at least know what would happen if we change something and know what's there. So even if something goes wrong, we can get back to it. But I think we can, instead of just chopping down rainforests and starting to build farmland, we can study them first or at least know what was there, but then also repopulate. So we can bring back ecosystems back to how they were before.

Chris Mason:

There's even species being brought back. There's the woolly mammoth, been working with Colossal, with their team to resurrect the woolly mammoth, bring it back from extinction. And there too, there's a lot of discussion about, should we resurrect the other ecosystem that came with it? That's also something that we're working on right now, is to bring back the micro [inaudible 00:39:43] plants. So it's not just about even embracing the microbiome, but even reconstructing what was the ancestral microbiome and even the ancestral ecosystem for us, and maybe for some woolly mammoths in the near future.

Robert Rountree:

So that begs the question, Jurassic Park. Is that even remotely possible, what they did in that movie?

Chris Mason:

There, the DNA's too degraded. And they admit as much in the movie, in it's very short snippets, but there's no good DNA sample that's been ever found from a dinosaur.

Robert Rountree:

You have to find an egg.

Chris Mason:

Not yet. So if you can get a really good intact piece of DNA, you could theory, give it a shot, but it would likely fail.

Robert Rountree:

Oh, how disappointing. Yeah. So one last question. How have humans changed the planet's microbiome for good or for bad? So we've alluded to that. We've talked about that a little bit. We've talked about how the human gut microbiome is less diverse. Is the overall, the microbiome of the planet less diverse? Has that really changed or has it just moved around?

Chris Mason:

It is, coral reefs for sure it is. And in other ecosystems we've measured, it does seem to be decreasing. And this is an ongoing debate amongst naturalists, ecologists, modelers is, how many species have we lost? How many are we losing? How many are left? And these are ongoing debates, but the trend is definitely in the downward trajectory, which is not good as that we're murdering whole species relatively quickly and we're hoping not to murder any of them. So we really do need to, I think, prevent that from having more in the future.

Robert Rountree:

And there are things that we can do to, as you said, bring back, if not woolly mammoth, at least the ecosystem, the microbes that accompanied the wooly mammoth.

Chris Mason:

Which is odd to think about, but the technology for the sequencing and the synthesis and the building of species is in our hands. So it's really an extraordinary time.

Robert Rountree:

All right, folks, that's all the time we have this week. Chris, thank you so much for coming on.

Chris Mason:

Thank you, my pleasure. Pleasure to be here. Thank you.

Robert Rountree:

So if people want to follow your work and find out what you're up to, what's the best place to keep track of you?

Chris Mason:

Couple places. There's on Twitter. I'm @mason_lab, as in Mason Lab. So that's one place. Then also in Instagram, I'm christopher.e.mason. And also, on our labs website is masonlab.net, is where a lot of the material is. And yeah, also do feel free to email me if you have any specific questions. My email's on the website.

Robert Rountree:

Great. Excellent. As always, thank you everyone for listening and hopefully you'll tune in again for another interesting podcast. Thanks for listening to the Thorne Podcast. Make sure to never miss an episode by subscribing to the show on your podcast app of choice. If you've got a health or wellness question you'd like answered, simply follow our Instagram and shoot a message to @thornehealth. You can also learn more about the topics we discussed by visiting thorne.com and checking out the latest news videos and stories on Thorne's Take 5 Daily blog. Once again, thanks for tuning in and don't forget to join us next time for another episode of the Thorne Podcast.