How To TRULY Know What's Going On In Your Gut

But as we move through these other ones, just give us the big takeaways as far as what the major sexy parts of each of these different scores are. Because I think the next one after that, looking at it here is the resilience score. What's the resilience score?

So the resilience score, I think is unique to our test. Depending on the scoring thing, what we're finding, it may not be the most advantageous thing to start taking a particular probiotic to increase beneficial bacteria. May the first step is some elimination, some depopulation events to actually kind of bottleneck these pathogenic microorganisms to then allow ecological space, ecological niches for commensal microbes to then repopulate that.

I know everybody's favorite thing to do is poop and put it into a tube and send it off to some lab and Lord knows where to tell you what's in your gut or what isn't in your gut. And because of that, I want to do a podcast about it. I've. I've done podcasts on gut testing before. I think that it's super important. I think too many people just focus on maybe blood work or saliva or DNA and don't actually look at the gut. If you ask a lot of functional medicine doctors, that's kind of what makes or breaks your health. And a lot starts in your gut. So I decided that I would actually give you guys a full update on testing your gut. And Today I've got Dr. Alex Moore with me. He's the director of Micro Biomics at a company called Therium. And he essentially has been pretty instrumental in pioneering research on the gut microbiome. He knows a lot about using bioinformatics and what's called multi omic analyses to, to look into the relationship between your gut microbiota, you, the host, your metabolism, health outcomes. So he's a smart cookie when it comes to this stuff, but I don't know if he's as smart as the smart toilet Elon Musk will probably invent five years from now. But he's pretty smart. Alex, welcome to the show.

Pleasure to be here. Thanks for having me, Ben.

Yeah. Okay, so gut testing is confusing cause there's a whole bunch of different companies out there. Brad, Viome and Thorne and Vitrakt. You work with this company called Therium. Walk me through how we actually kind of like categorize different ways to test your gut. And if you could choose any one way to analyze your poop, what you would do.

Sure. Yeah. It's a Fairly saturated space. A lot of these companies do burn pretty bright. We know that for instance, ubiome is now defunct. Sun Genomics, recently, Flora, I don't know if you're aware of that company. They're, they're kind of going down right now. So there's a lot of different companies out there. There's a lot of confusion. I think people kind of have a vague sense of what the gut microbiome generally is and we can get into formal definitions for sure. But the profiling of the gut microbiome, you can kind of bin it in based on timeline. So you know, for a long time pre 2000s, we were really relying on culturing techniques. We were limited because a lot of microbes don't actually survive in oxygenated, oxygenated environments. So we weren't really accurately profiling what was in the, in the gut microbiome.

Is that, is that by the way, because when you send off your stool sample to a lab, it's getting exposed to oxygen.

Absolutely. And so that's a critical element of current sample collection techniques. You'll actually have to have special stabilizing chemistry in your collection sample. It's essentially to preserve the genetic contents and keep them stable. We advocate for our clients to get that sample back as quick as possible because there is obviously a timeline. DNA genotech, for instance, is kind of considered the gold standard in collection devices currently. They say that it's essentially room temperature stable for 60 days. But we do, through our own pilot studies, do see a loss in genetic content. So when someone is sending a sample, we want to have it ship priority to get the sample back quickly as possible.

Don't do, because I'm super anal about this stuff, haha. And I send off my kit right away and it drives me nuts because my wife, who's totally type B, there'll be some FedEx prepaid priority bag full of her crap in the refrigerator for like a week. And I always ask her, maybe you're going to send that off. So. So I'm right, you should send it off quick.

Yeah, you're absolutely correct. So anyway, going back to different profiling techniques, kind of the next really big advancement was amplicon sequencing. So here we were looking at a specific segment in the DNA encoding for ribosomal RNA. So this is typically called 16S sequencing. So we're looking at the encoding DNA that make that particular subunit within rna. That subunit has different variable region regions, essentially we call them hypervariable regions. There's nine. So because they're hypervariable we're actually, actually we're able to see what's stable and from that make an inference about which types of bugs are there. That technique is actually quite limited because with annotation we're only able to get down to the genus level. So if you think about the tree.

Of life, remind us of our high school biology.

I know I have to walk through some of these including yeah, we have to walk through some of these basics. So go down to the class, the order, family, genus and then species and then finally strain. Right. And that's, you know, strain people can think of. Like if you're taking a probiotic product, a company should be listing the specific type of strain that you're taking. For instance, lactobacillus, GG X, number of colony forming units or CFUs. So amplicon sequencing a lot of, in the research field, it's still widely used because it is fairly inexpensive and it's a really great way to kind of get a broad perspective of a community, particularly when you're doing a lot of these large cohort studies or population based studies where you're getting thousands of samples. For most investigators, it's just simply not feasible to use the more advanced techniques. However, if you're going to use a 16s approach, which I think generally for consumer products right now in terms of profiling the microbiome that's being phased out, I think there's a few companies that are still using it and I don't want to, you know, name them. And there's you know, on obviously this move towards what we call meta whole metagenomic sequencing. So if you think back 20 years ago or more than 20 years ago now, we had the Human Genome Project. So this was actually a private endeavor originally through Greg Venter. And obviously we were able to profile the human genome from that. After that project was finished in his, in his laboratory, he had all these different sequencing machines available and they're just kind of sitting. So he was like, okay, well I, you know, I just, I don't want to waste this resource. So he ended up taking his private yacht around the world and collecting all these water samples to profile. Essentially it's environmental samples, right. He was doing a more shallow approach in terms of the number of sequences from DNA he was getting. But that kind of pioneered this idea of shallow shotgun sequencing. So essentially we take in, you know, a DNA sample, you know, from human waste, human fecal matter. There's actually quite an involved process of essentially decontaminating the sample and removing all the other matrix that we're not interested, which is feel sorry for whoever has that job. Well, that was my, that was my thesis project. I had to, I had to do that with whole, whole stool samples of over 300 individuals.

Oh, man.

And that was, that was a fun time in the lab. But anyway, so we extract the DNA out. There's several steps in this process where we essentially try to lyse this, the cell envelope of the microbe, whether it's bacteria, archaea or whatever, to get at the genetic material. We then fragment all that material and form these little short reads. And there's different ways that, you know, once we sequence that, we can reassemble them to essentially infer, based on alignment technologies, based on known fully sequenced microbes, what exactly those are. So that's who's there, which is defining taxonomy. So if you get a microbiome report, for instance, you'll see, you know, maybe they'll give a genus or species or a strain. That's all fine and good, but where the real wealth of data is when you do metagenomic sequencing is you can actually infer functionality. So not only who's there, but what they're actually doing. And this is really important when we're trying to understand the inter intricate connection with the gut microbiome and our own health, because just knowing who's there, really, we're just drawing kind of associations. We're not getting at the functional aspect of the microbiome.

Okay, give me an example. When you say who's there and what they're doing, give me an example of like a bacteria in terms of what it would be that you might commonly see in terms of who's there. And then give me an example of what it would be doing.

Yeah, so a good example of going back to Lactis lactobacillus. This is, you know, obviously considered. Many strains are considered probiotics. One of their key functions and why you can actually take them orally and have them go down to the colon and actually do something, is the fact that they express bile salt hydrogelase. So they're actually able to withstand the very harsh environment that it takes to get down to that region. Because bile can actually be actually fairly detrimental to these different microbes. A lot of them are quite fragile, so that would be a really key function for that particular microbe. So we can see.

Things like bio salt hydrogelase activity. We can see different things like carbohydrate metabolism. We can even look at antimicrobial resistance strain strains looking at lateral gene movement. Between different microbes. Which is another really important aspect to consider when you look at the microbiome. So if we're just looking at who's there. For instance, if I'm taking a 16s and amplicon based approach and I'm not inferring function, really you're reliant on literature to make. You're basically making an inference. You're making an inference.

Yeah, yeah, yeah. An inference. Or is the less scientific term would be a guess.

Yeah.

Okay, so with the whole genome sequencing, because I took the theriom test, but it's been like five months at least.

Yeah. And unfortunately the test has evolved since then. So you have probably taken an older version.

Okay. All right. Well, I don't remember what I did, but how much stool. And that's what I wondered because I get gut tests. It seems like once a month somebody wants to look at my poop. And sometimes it's like just like wipe your butt and take a little bit off the tissue paper. Sometimes it's like use this teeny tiny Q tip. And sometimes it's like yo, we want like seven tubes full of your crap. So why is there such variation? What do you guys do?

Yeah, that's a great question. So you. Some companies will take multiple samples to get a representation of if they're interested in for instance, stability. Seeing how your microbiome might shift over a brief time period. Some might include.

Different proteomic analyses or metabolomic analyses. That requires different stabilizing chemistry. So you can't aliquot on the same tube that you're going to be doing sequencing with. So might get multiple tubes. Again, not to name any companies, I am not a fan of swabs wipes. You really? Again, from our own pilot work, we're not able to get deeper sequencing with those samples and oftentimes we get very unreliable samples and then contamination. So we actually opt for. Again, going back to the device that I mentioned previously, DNA Genotext device, which is the gold standard currently for at home testing.

It is not the funnest. And you can maybe thinking back to five months ago, remember through the steps, essentially you have to defecate into this catch device and then literally take a scoop. Hopefully if you have like a Bristol stool scale poop of And I, I don't mean to be crass with my language, but we're gonna, we're talking about poop science.

I don't care, dude. Yeah, you can, you, you can, yeah, say whatever you.

If you have healthy bowel movements. So if you think about a clinically validated tool like the Bristol Stool Scale, where normally you're expecting like a sausage like bowel movement, you actually want to take the sample from the middle portion of that, of that bowel movement to get a more accurate representation. So at, you know, at the very least we're hoping to get a pea size piece of fecal material. Ideally we would take your whole bowel movement, But I think FedEx, UPS, whatever, I don't think they'd really appreciate that. And it would be, you know, fairly challenging to, to get that.

I strained my back on this giant sausage this guy gave me to mail off Ethereum. Yeah. And then hopefully you don't have like, you know, obviously some people would test because they don't feel that great, they have diarrhea, et cetera. I mean it's, you can't really get around the fact that it's not the funnest test to take. But you're saying that that method of like literally needing to go in there with a spoon and shove it into the tube is better than like the tiny little Q tip, you know, brown.

Spec based on our currently current technologies? That is correct. Yeah. So I again, I don't want to throw any company under the bus, but I would just be wary if you are going to use those types of collection devices.

Okay, tell me this. I'm a big fan of identifying whether there are certain foods that you might be allergic to or intolerant to. And so, you know, some of these blood spot tests, IgG, IGA, IGE sensitivity that tell you what, foods that you might have some type of a white blood cell reaction to seem pretty reasonable to me. What I need help wrapping my head around is how you could look at the bacteria in your gut and be told what you should or should not be eating. Because the way I think about it is wouldn't the bacteria in my gut be trained on what staples of my diet I'm currently consuming and therefore it's going to show me better able to digest those foods and maybe unable to digest other foods just because I haven't been eating those foods. And so I just don't really, or I haven't seen any really solid long term human clinical research on the idea behind, hey, this is what bacteria are in your gut, therefore this is what you should or should not eat. This is a perfect diet for you.

Oh, absolutely, yeah, I agree with you. And for instance, in our test we don't put in things like food intolerance.

Technology currently is not there to really make those statements. You're absolutely right. The microbiome, and coming from a nutritional microbiology background, the microbiome is really trained on what's coming in. Most people, unless you're fasting for instance, are consuming food every single day. That is a pervasive conditioner of the microbiome. And in many ways the microbiome, you can kind of consider it in the passenger seat, right of, of the host, the body. You're really kind of in control of it in many ways. So we know from really tightly controlled clinical work done over 10 years ago at this point that we can rapidly shift the microbiome in a matter of days based on what we're eating. Uh, this was work done.

Forgetting his name. It will come to me. But anyway, he, he essentially put these participants in a metabolic ward, even made them like a plant based vegan type diet or a high fat, I wouldn't call it carnivore necessarily, but more airing towards that side. And the microbiomes were completely different in, in the matter of a week. So you're absolutely right to make that statement. However, when we are profiling someone's microbiome and we are looking at functions, we can see, you know, what that person's microbiome is currently trained to do and what might be fueling for instance, pathogenic microorganisms and then that becomes a lever for us to modulate in terms of diet.

Right, right. And that's what I want to talk about. By the way, the shownotes are at BenGreenfieldLife.com theriom T H E R I O M E I say that because you might want to check out the uploaded PDF of my results that I will put in the show notes or if you're listening to this, you might want to check out the video version. Unless you're really good at visualizing. Because I want you, Alex, if possible, to pull up my results so you can walk people through what you actually are able to tell from a test like this in terms of health recommendations or takeaways that aren't just like.

Apples are poison for you, you should eat liver, which makes you get from some of these tests. So are you game to just like pull up and, and share your screen and walk me through what you see on my tests? Use that for illustrative purposes as far as what you can find out.

Absolutely. So yeah, just going over the table of contents here, we have essentially 15 key analytical domains. Two of those are more for educational purposes and they're not actually informing the downstream analysis that I'll get to. And I think we're going to discuss things like digital twinning and artificial intelligence and how we use those tools in our testing platform. But just really quickly we do some broad strokes. We look at the overall microbiome.

Here's your overall score set. So this is, you know, obviously looking at the 13 domains that I alluded to. And we're, we're going to get more granular here and break each one of these down.

So yellow normative, green is optimized. So it looks like I do have work to do. It gives me a 70 out of 100. So I'm like a, like a C. Yeah.

So again, the reference ranges, this is something that we, we're, we're currently improving right now. And this is more better displayed in our metabolic test that we have. But for the Microbiome, anything from a 4 to a 7 is considered population normative. So it's not bad necessarily. But every, obviously everyone wants to be more optimized.

There's room for improvement, there's room for improvement.

But in terms of your score, you are in the top 5% of what we're seeing from. And again, most of our clients are in, in westernized populations, which we can certainly get into in terms of some, some problematic things that we see particularly, you know, from environmental exposures and diet, things of that nature. But overall you're doing, you're doing quite well in comparison to the number of clients and patients that we've profiled so far, particularly with community diversity. The Arkaim, which is another kingdom of microbes that we profile. It's not just bacteria that we're looking at. It's important.

Okay.

You're doing really well at controlling pathogen and parasites.

Great. All that sauerkraut is doing something. All right, so what can we see here? I think you got like 15 different things.

Yeah, our 13 there. So this is just an overview of our scores. So this is again just more looking at first glance, you know, why exactly you have this particular score condensed into one sentence. So for your overall microbiome, we're looking at the number of microbial species and you have a very high number of species for western males. So again, this is a really good finding for you. Very overall pre diverse microbiome. You do have, for instance, some viruses, which viruses are actually a healthy component of the gut microbiome, fungi and archaea, and then obviously dominated by bacteria when we look at a fecal sample. And again, I want to inject this point because this is really important when you're talking about testing. So a lot of, there's this contention in the space right now that if you're taking a fecal sample that really may not be representative of, of your overall gut microbiome. However, through different sectional work that's actually been done recently, it is actually a fairly accurate representation of what's going on in your colon. So that's where most of the biomass resides. Okay. So and that's where a lot of the biotransformation and creation of metabolites happen that come back into circulation. So for all intents and purposes, fecal sample is still really good. And it's, you're not gonna, unless you will, you know, get, go into a hospital or something, you're not gonna get biopsies. At different sections in your gut microbiome. There are new technologies emerging called lab on chip technologies. This is still developing, but essentially the idea is you swallow a pill that's ph activated. So as the pill goes down your gastrointestinal tract, your skin, there's different compartments that open up when activated at the particular th than to collect a, essentially a sub sample. So this is called spatial microbiome. So we can take a sample for instance from the stomach. Not that there's a ton of bacteria there, there's very few small intestines, for instance, upper portions and lower portions of your colon. So that's I think a new emerging area which I think would probably be a lot more valuable and feasible than, you know, the so called microbiome sequencer in your toilet. That's, I've been, I've heard that talked about for probably 15 years now. And it's, I've never seen anything come of it.

Yeah, like I was saying. Come on, Elon, hurry up. The lab on the chip, the swallowable thing, is there a name for that?

Not currently. This is work that's being done at a lab at Tufts.

So at this point somebody couldn't just like walk into a gastroenterologist and say, hey, I want this lab on chip swallow thing.

No, and I can email you after to the, the publications if you want to put those in the show notes.

Okay, cool. Yeah.

So then we go to the overall gut microbiome wellness index. So a lot of the work that we do in this so called omic space. And again there's, there's a lot of educational points that I'm going to have to kind of embed in, in this, in this, in this conversation. Omics is essentially referring to if we're viewing something through systems biology. You know, for instance, we have the gene ohm, we have the transcript ohm, the proteome. It's just a cute way of basically bringing all these different layers in systems biology together. So the microbiome obviously is. Is separate from the host, but obviously kind of dwells inside us. So really, to leverage all this data, we have to look at libraried and bank data, you know, to get a better understanding, particularly when we're talking about different phenotypes or different disease states. So what we're looking at here is each dot represents one person's gut microbiome. This was curated from over 8,000 individuals across the world, across countries, in different disease states, and through a really fancy way, through machine learning, essentially, we're able to essentially look at where you fall in a population reference range. Okay. So higher score obviously is going to be more optimal, what we would call eubiosis. And then anything below is zero. We're going, we're calling essentially dysbiosis.

So actually, so if you look at this screen, the more someone gets into the green, the lower the likelihood of them having something like a, like a clinically dysbiotic community.

Correct. And we're not just looking at phenotypes here, we're actually looking at contributing taxa and functions that would be pulling someone into that state, whether it's eubiosis or dysbiosis. So again, going back to what I was talking about, when you profile a microbiome, you're really looking for le levers of action. Okay. So, you know, you might have overpopulation of Clostridia or something, you know, know, whatever, that's something that we can address through intervention to actually pull that person out of that dysbiotic state. So we're not. Again, going back to your comment about food, we're not going to say, well, this is the perfect diet for you based on your microbiome. No, we're saying, here's the things that you can change to optimize the configuration of your gut microbiome, which I think is a lot more in line with what we know scientifically at the current moment.

Okay. And then I noticed underneath that you list some contributors that would shift it more towards the green in terms of certain species, et cetera, and then certain contributors or species that would shift it more towards the red. And those are, those are specific to me.

Yes, absolutely. Yeah. Okay. So one thing, yeah, one thing that we do have throughout the test is because of how complex this data is, there has to be some translation, some digestion. And we do have what I, I'm calling scientist notes, which we're just putting in based. All this is unique to a report. So this is not just, you know, this is not just like fixed bullet points. These are changing for every report, giving you interpretation and, and hopefully to increase your understanding of the gut microbiome. Because, you know, as a scientist that is being super jazzed up on this, I really want to educate and, you know, get people more informed about the own health and, and taking control of their own health. And I think education and the translation is, is fundamental to that.

Yeah, okay, got it.

So moving on, we also have another kind of educational piece. This is not weighting any score. It's more there for you. This is just looking at what your core microbiome is. So this is the most prevalent, most abundant features that we detected in your sample. So you have again, going back to what we were seeing with your overall score, many.

Bacteria that would be deemed healthy. Prevotella, for instance, is more associated with a diverse diet generally seen not in western populations actually, but people like hunter gatherers, people that are eating more seasonally and are eating more vegetable products. You also have a good abundance of Akkermansia. And I haven't looked at your report in quite a while, actually probably five months, as you said. But I believe we can scroll down to the probiotic panel and look at this. I'm just going to skip ahead and we'll come back. I just want to make sure.

By the way, while you're skipping ahead, I do take a probiotic. I actually kind of go back and forth. I have this theory that it's good to kind of switch every now and again. So, so I typically the two I use most often are one called seed and one called just thrive. And then I have a pretty diverse diet. I mean, I kind of wasn't joking about the sauerkraut like we do sauerkraut kimchi, probably about, I would say up to 25 different varietals of herbs and spices and vegetables throughout the day. Then we got chickens, goats, dogs. You know, we're outside all the time, swimming in rivers and lakes and oceans and also traveling a ton. So for me, you know, my, my language is diversity when it comes to what I try to expose myself to environmentally.

Well, that is showing up in your test and is actually something that I encourage a lot of people to do. Even, you know, the, the kind of tired statement touch grass, like really actually go physically touch grass. You know, getting Outside getting different environmental exposures. That's actually very, very important for, for the overall diversity of your microbiome. You think about people in Western societies, we're essentially living in these built environments. So there's this evolutionary mismatch where it's really kind of a prime disruptor. And not to mention all the artificial things, whether, you know, this room, this, the paint that's on the wall, the plastics, all these things have an effect on your gut microbiome. So if you can get more back to, in many ways, you know, how our, our ancestors were living, not that that's going to be feasible, obviously, but that does go a long way for increasing diversity. So going back to the finding that we had with Akkermansia, you actually have a specific species in fairly high abundance that we call Akkermansia mucinophilia. And that is phenomenal. That's great, because this particular microbe is responsible for essentially helping produce mucus in the colon. So if you think about tries to, you know, do a cross section of your colon, most people think that, you know, just going in inside the tube that we have, you know, this biomass of microorganisms and then obviously all the digesta that's coming down from the small intestines that it's. It's kind of working on, and that, you know, those microorganisms are coming up against these cells that line that inner, inner luminal tube with which we call the brush border, or more scientifically accurate, enterocytes. That's actually not true or shouldn't be true. You should be producing mucus from your goblet cells that are also in, in that brush border to help push out a lot of these microorganisms, whether they're commensal or beneficial or pathogenic, they really shouldn't be coming into contact. There are some microbes that obviously reside in that mucus layer, like Akkermansia mucinophilia, that can be normal. Akkermansia mucinophilia helps, essentially. It feeds off the mucus, so you would think that you'd get reduction in mucus. However, what it does is it gets rid of old mucus so it doesn't overgrow, because overgrowing mucus can be problematic as well.

Well, almost like improving mucus turnover.

Right. I view it as kind of a lawnmower, essentially. Keeps things nice and healthy and trim. So. So this finding, again, is. Is tremendous. It's really good, shows that you likely have really good mucus turnover and you're not having a lot of Contact with, directly with the brush border. So if you think about those microorganisms in that inter luminal space, the lifetime of a microorganism is, you know, can be a few minutes, can be a few hours, perhaps a few days. They're currently, they're constantly dying off and lysing. A lot of those microorganisms, particularly what we term gram negative, just referring to a staining method that we use for bacteria have on their outer cell wall or their membrane these structures, signaling structures called lipi polysaccharides or LPS or abbreviated these are essentially endotoxins. Okay. So when you have this die off, this die off of biomass, those are constantly getting released. We have different protective mechanisms in order. Mucus is one of them. Obviously having strong proteins that are adhesing our enterocytes together is another one. These are called tight junction proteins. But effectively there's a leakage occurring to some extent in everyone's gut. I don't particularly like the term leaky gut. However, I guess it is kind of a simple way to think about this where those endotoxins can actually breach through the wall, come into circulation, they bind to a particular protein that actually is, is, can be a common marker that some labs are using now. It's called lipid polysaccharide binding protein. LPB interacts with that structure essentially once it goes to the liver, it causes a, a cascade of inflammation to occur. And LPS is tied to, I mean, you name a chronic disease, it has some association from diabetes to heart, heart disease to Alzheimer's. It's, it's something that you want to limit your exposure to essentially.

Especially true when you're eating high sugar, high fat diets, like the whole like average fast food meal. Especially if you throw like an ice cream, you know, what do you call it? Milkshake. I was gonna say ice cream smoothie. It's been so long since I've had a milkshake ice cream smoothie. If you throw one of those in there, yeah, it's bad news bears, especially for the lipopolysaccharides. Although you know, a lot of other things, you know, environmental stressors.

The milkshake is probably the worst because it's when you combine poor fat profiles with sugars. Because if you think about how fat is absorbed, actually LPS can form into those fat globules when you absorb them. So that again is another vector for absorbing these into your body. So it's probably the worst possible, one of the worst possible things you could to eat. Eating.

Yeah, yeah. You just ruined dipping your french fries in mayo and secret sauce for everybody. Okay. So I want to make sure, of course, that A, this isn't boring for people and B, we're able to make sure that in the time that we have actually cover the different things that you guys tested. We kind of got rabbit holed a little bit there with community diversity, but as we move through these other ones, just give us the big takeaways as far as what the major sexy parts of each of these different scores are. Because I think the next one after that, looking at it, here is the resilience score. What's the resilience score?

So the resilience score, I think is unique to our test. This is actually one of the hallmarks of our test and really important when you're profiling somebody over time. So again, through clinical work, we found that the microbiome, it can change. If we're really drastically changing, for instance, a diet or say we're having an experience extinction event through heavy antibiotic use, there is a, a potential rebound effect. So the microbiome, obviously it's a micro environment, it's alive. It's like any other ecosystem. It's going to have a rel. A level of resilience to it. Meaning if I push it, you know, to some degree, how quickly and you know, effectively is it going to kind of come back to the center? Homeostasis is another way to think about this. So if someone has a dysbiotic configuration and they're highly resilient, that's, that's actually pretty bad because that means it's going to be harder to pull them out of that configuration. So here we're looking at key elements. Essentially you think about a boat that is moored or whatever, it has, you know, an anchor to hold it down. We're looking at the anchoring elements that might be holding a microbiome configuration in its current current state. So if you're dysbiotic, we need to address, you know, these different pillars or these different anchoring elements before we can start, you know, providing more directed therapy. Everything kind of has to be staged with the microbiome because it is an environment, for instance, or a microenvironment. So, you know, getting this report back, depending on the scoring, taking what we're finding, it may not be the most advantageous thing to start taking a particular probiotic to increase beneficial bacteria. It may, the first step is some elimination, some depopulation events to actually kind of bottleneck these, these pathogenic microorganisms to then allow ecological space, ecological niches for commensal microbes to then repopulate that.

What are we talking about there, like an herbal eradication protocol? Coffee enema? I mean, when you say eradicate, well.

Maybe eradicate's too strong of a word. So I will be transparent with our test. We are currently not providing any pharmaceutical recommendations. These are all lifestyle, diet supplemental. So on that side we're looking at different antimicrobials. For instance, oregano, oil, you know, perhaps activated charcoal. It depends. Obviously it's going to depend. Even fasting, which can be, when used appropriately, can be a very, very powerful lever. And I've actually published on, on this through a clinical trial that we, we've done. But yeah, there's, there's many different ways to approach this. What I'm saying, it all has to be staged. Now, even structures in our gut that people thought were once inert. For instance, our appendix. So our appendix does actually serve quite an important role for reinoculating a devastated microbiome. It actually does hold kind of biofilms of our core microbiome. And if you're healthy, that structure should be kind of, say, I take a heavy course of antibiotics, that structure should be helping me repopulate my gut microbiome. So for instance, someone that had that structure removed, you know, there's some things to navigate around when we're forming recommendations, and that's all used in. We have an intake, a fairly detailed intake form to help us inform the navigation of our recommendations.

Right. The appendix is not a throwaway organ, it's a memory organ.

Correct. I'm going to go through these fairly quickly here. So we have the arkaom. So again, this is another kingdom of microorganisms that we have. It's at a very low percentage for a healthy individual, usually less than 1%. However, if someone is meth, methanogen dominant. So basically particular archaea that are producing methane, we can see that increased 5, sometimes even 10% of the overall abundance of the microbiome. That is not good because when we start producing a lot of methane, obviously there's going to be a level that we do want. But overproduction of methane can cause things like constipation.

We're going to have issues of transit time and this is heavily tied to constipation. Dominant ibs.

Yeah. Losing friends, burning through too many matches in the bathroom, all that.

Yep. Then we look at the microbiome. So fungus, we know, is also another.

Really important condition component, not microbiome microbiomes.

Correct.

Okay. Fungal community. Okay.

Yep. So you have a fairly diverse microbiome. You do have a small presence of Aspergillus, which I, we can go to the pathogen parasite panel, which I believe is subclinical, but we do look at it. You're doing really well not overproducing yeasts. So we look at yeast carbohydrate meta metabolism. Back to your point about, you know, sugar, because sugar really does love sugar. Fungal virulence.

So someone thought they might have like a yeast infection or a fungal infection present in their gut. This test would, based on the microbiome analysis, give them a decent idea whether or not that might be the case.

Absolutely. This is, you know, there's other testing available that are actually fairly cheap if you're really suspecting that, like the hydrogen breath test, things of that. Things of that ilk. But this is going to give you, you know, very specific at the feature level what might be driving that. And then obviously we have the function.

Okay. And there's a lot of companies doing like, urinary mycotoxin analyses. Based on what you're telling me about the, about the Myco. It's called the mycobiome. Could you do something instead using the stool? Like, would there be an advantage to doing the stool versus the urine if you're looking at mycotoxins?

So the urine would be more of a proxy for what you have in the host, obviously, because that is originally coming from, you know, filtration through the host. So the mic. The, the. In the microbiome, this is more of what's. I mean, the alimentary canal extending from the mouth to the anus is still considered an external environment. I know it's internalized, but it's still considered an external environment. That makes sense. So we, we're, you know, this is actually one component that we do have in the test in the microbiome is we look at your microbiome's ability to essentially bioremediate mycotoxins. So we're not directly assessing mycotoxins.

But you're, but you're looking at your ability to be able to get rid of them, correct?

Okay. Yeah. Yeah. So that is, you know, a fair point. That would be a nice thing to add to this test. But we'd have to, we'd have to have a separate collection tube and then, you know, that'd be another profiling. But that's a perfectly valid point and something that I hope that we can include in the future.

Yeah, yeah.

So, yeah, here we're looking at common mycotoxins and these key enzymes, these, you know, various, this panel of various enzymes that we have. Essentially how expressed are they? So your, your body's doing a fairly good job at.

At, you know, addressing those depending on your exposure. Right. And that's going to vary. Right.

You, you're basically testing the level of all the different enzymes that I have that could potentially help me fight against mycotoxins.

Correct. And for most people, that is going to be through a diet, actually, because a lot of agricultural commodities, unfortunately do have aflatoxins. Mycotoxins. I mean, coffee's perfect. Probably one of the main offenders, probably one of the most pervasive ones. But a lot of grain products, for instance. So that's something easy that someone can again, a lever address in their environment, in their diet.

Okay, all right, interesting. And by the way, if I show a weakness in a certain enzyme, like for example, I see on my report, when it comes to the type of things that could get rid of mycotoxins, I've got slightly low levels of peroxidase, monooxygenase, fumoniscin targeting enzymes. Do you guys include, like, recommendations on things like, well, here's the food you could eat to get more of those enzymes in your system or anything like that? Or is this more just data, not recommendations?

So currently we do make broad recommendations for this. We are currently refining our library to get a lot more specific because here we're actually looking at, um, again, these, this goes back to what the micro, the microbe possesses that. It's the microbe that is expressing these enzymes. So it's not just increasing these enzymes specifically, it's increasing the microbes that are expressing these enzymes, if that makes sense. Yep, yep.

All right, so we got the mycotoxins and then what?

Then we have the virum. So we're looking at viruses. And viruses, again, are a small fraction of the overall abundance of the gut microbiome, but also extremely important because they're doing a lot of the, I would maybe kind of call it shepherding of the microbiome. There's bacteriophages, for instance, that can induce lateral gene transfer events. So this is a healthy, you know, can be a healthy component of the microbiome. A lot of people might freak all virus. That's not, not the case at all. You do want healthy populations and a good diversity and obviously functionality. We want to make sure that you're replicating these. Well, you know, you're not you're not overdoing interactions with the host. And then there is a balance with horizontal or lateral gene transfer. The problematic thing with lateral gene transfer. So again, not to get too technical here, if we think about like a vertical gene transfer event is when, for instance, a mother has a child and she's transferring a lot of her microbiome to that child. Lateral or horizontal means that it's happening after that event occurred. Where microbes, you know, they, they're sending information or, or viruses are sending information to bacteria. Where this becomes problematic is with antibiotic exposure. So here's where we can get what's called a resistome. So these are antimicrobial resistance genes that can embed themselves in the genomes of these microbes. And we actually have a panel for that. You know, again, based on the populations that we're profiling, a lot of people may have had 40 courses of antibiotics in their life. And that unfortunately reflects in their antimicrobial resistance panel where they're going to keep, essentially keep these genes in many cases, throughout the course of their life. That's going to make them more resistant to different antibiotic therapies. And, you know, antibiotics themselves are not the only vector for these things to increase. It's heavy metals can actually increase these. Different environmental microbes can increase these. So this is another really key aspect of our test that we have that's directly related to the virome.

Yeah, probiotic panel. We talked about that. You could look at different probiotics. I know we, we kind of briefly covered that, but then. Then after that you got a pathogen and parasite. That is something I was wondering, like you. You can actually look at parasites, huh?

You can, I will say. So there's pathogens, like bacterial pathogens, fungal pathogens like Candida albicans, viral pathogens, protists, multicellular organisms like, say more commonly known as, like roundworm, pin worm, liver flukes, tapeworms, whipworm, things of that nature. You know, probably if someone is really thinking that they have this, I probably direct them more towards something like microscopy, which is going to be a more definite way of assessing these. We do include this because we can. Because of how deep we're sequencing with our runs, we can pick up potentially DNA. I won't say, and I believe we have a disclaimer. I won't say that this is, you know, diet. This is. This is not. This particular panel is not diagnostic. So if you are suspecting a multicellular organism, you're probably gonna wanna do some additional testing beyond ours, just Being fully transparent.

Okay. How concerned should I be that it detected enterotoxigenic bacteria? They look pretty clean, but there's no one that's hot.

Well, you're pretty low. I would consider this subclinical. And oftentimes you might have some transient microorganisms, particularly for someone like you. It sounds like you're interacting with animals. You're outside. This is. This is. You're going to have passengers. That doesn't mean that they're going to take up residence and be there for the long term. So I wouldn't be. I wouldn't be super concerned. However, this, you know, because it is over the reference range, this is something that we can easily, you know, address.

Okay. All right. Okay. And then we got what? Antimicrobial resistance?

Yes, antimicrobial resistance. So this is what I was talking about previously. So here we're looking at specific genes that are conferring resistance to antibiotics. And actually, again, you've had it. You have an older report here, so we expanded this library out quite a bit. So currently we were profiling in this particular test, 478 different resistance genes. We've now extended this to over 1500.

Like, if my doctor wants to put me on antibiotics. That's incredible. You expanded that much in five months. And I. I'm showing. Let's see here. What does it show? I maybe have macrolids.

Tetra. Tetra. Tetracyclines. Yeah. So essentially what this is telling you is for those particular drug classes in terms of, you know, if you are addressing something in the gastrointestinal tract, it's likely that these are going to be less effective.

So the ones that are, like, colored red would be less effective antibiotics for me, if I had. That is super interesting.

Yeah. Correct.

Okay.

And again, I mean, you live a really clean life, you know, I assume your exposure to, you know, these drugs is low. However, I. When you're a child, for instance, there's things that are sometimes out of your control. Right. A lot of people have early life exposure that persists throughout the course of life. Like I was mentioning with horizontal gene transfer, particularly if you have an environment for those. Those microorganisms that harbor those genes to proliferate, which normally they're going to be more pathogenic.

Okay. But this is useful. Interesting. Okay. And then digestion looks like the next one.

Yeah. So digestion, we're looking at, again, key functions that are important for the digestive process. So we're looking at fiber degradation capacity. You're doing awesome. Protein fermentation Great. Your gas production is, is lower again. There's a balance.

I don't ask my wife about that. No, I'm just kidding. I actually am. I used to fart a ton when I raced triathlon, but I was eating like 80% carb diet for much of that period of time. Once I went like keto low carb got rid of a lot of that. I mean occasionally I'll let one rip, but it's, it's really not bad compared to when I was eating a lot of carbohydrates.

Sure makes sense. You have a lower ability for lactose and simple sugar digestion, which seems to.

Kind of, which, which I know. Like I'm always like where's the, where's the dairy free section when we go to the ice cream store. And my, my, my kids are always impressed at my self control to pass by the, you know, banana cream and pistachio flavored gelato and go for the dairy free. I take one for the team sometimes. But yes, this backs up my own knowledge that I'm a little lactose intolerant.

Fat metabolism is normative, phytate metabolism is normative and you're doing well with overall enzymatic function. So again, looking at each one of these dots, this represents a, a reference microbiome essentially. So these are, it's, it's kind of clumped, but that's, that's 8,000 metagenomes. So you're just seeing where you're falling within reference range.

But like when you get a DNA test, you know, like 20, well maybe not 23andMe, but I don't know. You know, there's a whole bunch of em out there. You know, 10x and self decode like that will tell you that you have a high propensity toward lactose intolerance. This, this says that also. But because kind of like we were talking about with food earlier, the bacteria in the gut are largely changeable based on what you eat or the probiotics you might take. You could technically shift this in a direction that might be favorable to lactose digestion, right?

Absolutely. It's not static like profiling the human genome, which makes this very valuable for longitudinal tracking. Just like metabolomics or metabolites.

Yeah, yeah. How often would you get a therium test if you could just like wave a magic wand?

Um, you know, the microbiome is, is interesting because as I said, it's fairly stable. And you know, I'm probably not as healthy as you, Ben, but I'd like to think I'm fairly healthy for someone like myself, that'd probably be every six months. But when you're talking about someone that's really dysbiotic and doesn't have a resilient microbiome that may be within three months, we do recommend a retest window. We're kind of careful with that, obviously, you know, through a feasibility, you know, feasibility lens. But we are very transparent in saying, like, the microbiome is, is not going to be like the metabolites in your blood that are shifting constantly. This is these, you know, if you are going to want to make a change, you're looking at a longer time horizon, you know, so we make that forecast in the report.

Okay. All right, folks, hang on here. We got three more. And then, and then you got take time to fill us down on this digital twinning thing.

Sure, sure, sure.

Alex, don't let me forget before you go to get into that. Okay, what's next?

So next we're looking at nutrient generation. So obviously this is fairly connected to digestion. We're really interested. And this is actually a hallmark with a lot of good microbiome tests. And I, you know, I'm gonna obviously say we have a good one, but there's plenty of really good offerings out on the market. And usually to see that you have a good one is you want to see the profiling of what's called short chain fatty acids. So short chain fatty acids are, you know, a lot of them are products of microbial fermentation and have a very beneficial effect on the host because these are metabolites that can cross over the gut wall, whether they're like butyrate, for instance, which is the key fuel substrate for the brush border cells. So it keeps them nice and healthy. Make sure that they're heating well. Tight junction proteins are strong. We're not going to have things like leaky gut acetate, which can actually help with fat metabolism and, you know, maintaining a healthy liver. Things of that nature propanate also from digestion of fat. I mean, these, these are all really fundamental metabolic processes that are occurring in the gut that we want to make sure are, are, are healthy. For your particular test, you're showing fairly normative butyrate production. Acetate is, is a little bit low.

This might be, again, a reflection of, of, of your diet.

Propionate is nice. Lactate is a little bit low. This can also be affected by things like exercise, which interesting, interesting enough when you exercise very vigorously. You know, I know lactic acid used to be Viewed as like a waste product. We know that that's actually not the case. It can actually go to the liver.

Yeah. Metabolize back into glucose via the core.

Yep. Correct. It can actually also cross over into the gut lumen and interact with bacteria which then can repackage it as a fuel substrate. So now you kind of have a second. It's not terminate Corey cycle, but you have a second mechanism to repurpose that so called waste product to make it usable again. So that's really cool work that's being done.

Right. And just, just out of curiosity, when you're looking at stuff like this again, I know you guys don't necessarily say well here's the diet switch you should take or the supplements you should take, but you know, I really. This might be outside your wheelhouse, so we're just spitballing here, but could you theoretically take something like this, upload it to GPT or GROK or whatever and say, hey, I'm showing low lactate production. What lifestyle, dietary or supplementation changes would be recommended based on that?

You absolutely could. I would obviously warrant some caution with that. You know, this is the whole discussion right now in healthcare, when are.

But if you ask it to act as Dr. Alex Moore, you know, or the world's top gas rent.

Sure, sure.

Might be a little better.

Yeah, yeah. I mean this is where I think medicine, the real fear is with practitioners that they're eventually just going to become prompters for, for a chatbot, which I don't know.

I think that's fine because it doesn't necessarily put people on a job as much as it allows you to help more people, in my opinion.

Right. But you're going to always have some Luddites and you know, some protective, you know, elements. But yeah, you're absolutely there. You can absolutely do that. I would just be, you know, make sure that your prompts are good. I would just say that, yeah, that, that's true.

I think, I think prompt engineering is going to be increasingly one of the best things to teach your kids. And you know what, you can ask GPT how to prompt more effectively. There you have it. As long as that prompt is good. Okay, so then we got gut barrier integrity.

Yep. So again, going back to what I was mentioning about, you know, trying to make sure that we're essentially kind of encapsulating that environment. We're not getting a lot of crossover. Um, here we're looking at key subdomains that are gonna make sure that that barrier is nice and strong. Again, butyrate as I mentioned is, is a really important cell sub or fuel substrate for kerasites mucus degradation. So you are showing a little bit on the lower side. I think that's a, an artifact of the elevated Akkermansia that we saw in your sample. You're doing excellent with LPS production so you're obviously not producing too much. We want to balance there. Tight junction regulation is great. Then overall gut barrier balance or gut barrier related metabolism is a little bit lower, but it's still kind of in that normative range.

Still not too bad. Yep. And then inflammation. Pro inflammatory and anti inflammatory microorganisms. Yeah, that's interesting.

Okay, so one of the main things that we look at here is actually bile acid metabolism. So a small percentage, if you're healthy, a small percentage of bile will create cross over from the small intestines into the large intestines. And you know, these are referred to as primary bile acids. We can actually have bacteria, as I alluded to before with Lactobacillus that can actually cleave those and or deconjugate them really and create these secondary bile acids that can act as essentially cellular communicators. They can affect things like glucose metabolism, lipid metabolism. Now some of that's okay, but we have too much of that occurring. These can actually start acting as protein pro inflammatory signals. So you're doing well here. You're doing really well. If not overproducing hydrogen sulfide, which is another big issue that we see with a lot of.

GI diseases. Tryptophan metabolism, you are a little bit low here. So tryptophan is very interesting because through the kyurenine pathway we can actually produce beneficial metabolites that not only affect health, health locally, but also can cross over structures. It like can go across the blood brain barrier and go into the brain. And this is actually one of the main mechanisms for the, the so called gut brain axis. So we're not directly assessing that obviously, but we're looking at the metabolism. Tryptophan sometimes, for instance, if you're a little bit lower here, you may have, I mean this could be an artifact of your diet. For instance, if it's, you know, maybe you have had lower protein or something for a course of time or if you're having really efficient digestion in your small intestines, we may not see as much coming into the colon.

Okay, okay, got it, got it. All right, so this is super interesting. But then this next page, this is where we get to, you know, maybe you don't need to feed stuff into GPT because you, you guys have this digital twin and I actually have recommendations here that are pretty sound based on everything that we just went through. So now I've got just two pages that say, hey, take this, do this. Which is great, but what's that mean that you generated this using a digital twin?

Sure. So digital twinning.

It'S not a new concept. I think people are going to be hearing about it a lot more. This was something that was actually from aerospace. The engineers were very interested in looking at ways to have different simulations on, on different, essentially parts in the manufacturing processes because it's very expensive in aerospace to actually put those through formal experiments because of the different types of conditions that you're going to be having at different atmospheric levels, temperature, things of that nature. So basically what they did is they set all these different parameters for a particular aerospace part and essentially stress test it to see, you know, what is its, what is its optimal operating parameters going to be. So essentially it's a form of prediction. So we can do the same thing with biology when we're dealing with really high dimensional data sets like something with the microbiome where we could in your sample bend we had 1600 features or something like that. That's not including all the functional features that we profiled. The human brain is just simply not going to, I mean maybe you could, but it would take you a very, very long time to digest all that information. Obviously we've done some of that heavy lifting with condensing things into these health modules or these health domains that we just reviewed. However, even with that condensed information of 27 pages, there's still a lot to interpret to your point. You could feed it through a large language model. You know, I think you're going to, might get some, some decent recommendations, but what you, you know, want to do to make it scientifically sound is benchmark it against a curated library designed specific specifically for this data set. And that's what we've done essentially. So we formed a library of published interventions, also some unpublished interventions, some more new type interventions that may not have as much scientific validation currently by showing promise.

Yeah, yeah. But I learned a ton of stuff on here though. This is very, it's very interesting how, how you're able to basically.

You know, create another biological me and test simulate all these various health scenarios. But some of the stuff on here are just like mild tweaks. Like I told you, I'll rotate between just thrive and seed. But this says take just thrive in the morning and then take the seed in the evening. So kind of like stacking them in one day, which I just never thought of. Or take 500 milligrams of Berberine to address the ETBF activity that I mentioned to, you know, might be concerning on the, on the, the Bad Guys panel. I don't remember which one that was. But you know what was super interesting? This would be cool for a lot of people to know, or at least perhaps disruptive to their life. Chronic nicotine exposure has been shown to decrease overall microbial diversity, which is critical for a resilient gut ecosystem. Limit to 2 milligrams per day. Tucker Carlson is not going to like that.

Yeah, it's very popular. I know. The pouches, for instance. People think that they don't have an even. Peter Attia, I think, has talked about this. Oh, yeah, they do have an effect on our health. And I think they're probably overused for the most part.

I think so, too. I probably got into them four years ago. I haven't had nicotine now in about two months. I didn't really intentionally. What stopped me from using it is I saw the report come out on microplastics and gum base, and I was chewing that Lucy nicotine gum, and I don't like the pouches that much.

I guess you could do a patch, but I just. I feel like an addict when I put those things on. So I just kind of quit using nicotine. And it was tough for maybe like three days. I don't use it anymore. But that's good to know about what it does to the overall microbial diversity. Very interesting. So basically, if I could do nothing, I could just like print page 28, 29 and 30 and start to do that stuff and then just, it says here, retest in six months and see what happens.

Correct. So the, the very important point that I want to make here is we transpose all of the microbial data and obviously our library with, or contextualize it with your, what we term metadata. So you take a survey before this. So here we're able to understand what your current diet is, you know, what your current supplement regimen is. That way, you know, if there are things that you're doing that are working well, for instance, the probiotics we're taking, you can make some tweaks to optimize it, or maybe there's some things that you're doing that are going to be deleterious to you. We can again make tweaks. So we're not trying to reinvent the wheel we're trying to, you know, work within your operating system, which is very important when it comes to compliance. So we present all these recommendations and sometimes these will extend. Yours is going, you know, roughly two pages. Sometimes this will extend three pages. Compliance. I can give you the most perfect protocol in the world. The question is, are you going to follow it? So for, I mean, a couple pages. Sounds trivial. However, there's a lot of recommendations here. You know, what we're doing here is providing an impact score.

Oh yeah. Rank, prioritize them. Okay. Yeah.

So how much is this going to move the needle for a particular domain that we have listed in this column? And then how much scientific evidence do we have to support that? So it's a, it's, it's kind of a conglomerate score. So what people can do, and I'm not advocating use this as a la carte menu, but you can kind of select, you know, things that are going to work best. I would obviously advocate for, you know, waiting more on the high impact scores, but then that this way people don't feel, you know, that they have to do everything. If they can just make, you know, select say the fives or some of the fours, they're gonna go a long way in improving some of these scores and getting a more optimized gut microbiome versus, you know, nothing. Cause they just get overwhelmed. But the entire list.

Right. Cause like a five for me is bear brain, but then a two is incorporating dietary zinc for tight junction regulation. So yeah, I had totally missed that on the score. And interesting, I guess. No, nicotine is also a two, but that's still something I've never talked about on the podcast before, about its effect on the gut ecosystem. Alcohol, of course, although polyphenol intake is high. So I bet you I have my organic glass of wine at night. But I'm very careful. I don't do any more than that. Well, this is really interesting. Again, I know this was probably for those of you listening, somewhat useless for the last half hour because you couldn't see what we were talking about. However, if you're watching the video or if you even just listening, you download the PDF to review it afterwards. I'll put my results. I don't care. You can make fun of my gut. I'll put my results@BenGreenfieldLife.com Theriom I know we've got links. We have some kind of a discount on your test if people also want to poop and dig around with a spoon and send it off. Alex I know we're about out of time, but this is just absolutely fascinating, man. I really appreciate you walking me through all this.

Well, it was a pleasure and it was a great conversation. And I know we could, we could dig into this a lot more. But looking forward to the future if, if, you know, we can have another conversation.

Oh, yeah, for sure. I mean, I think I'm going to do another test, so I'll, I'll get a hold of you. But in the meantime, folks, go to BenGreenfieldLife.com Theriom you're gonna learn a ton. Check it out. Until next time, I'm Ben Greenfield along with Dr. Alex Moore signing out from Ben Greenfield lifestyle.

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