What the Most Measured Human Can Teach Us About Health

What would it look like to see a health problem coming months before you felt a thing?

That's the thread running through this conversation with Dr. Michael Snyder, the Stanford scientist who has probably measured his own body more thoroughly than anyone alive. Momo and Guru dig into what all that data actually teaches us: that our biology is deeply individual, that the real signal often lives in the change from your own baseline rather than in a one-size-fits-all "normal" range, and that the most useful information usually isn't a snapshot of which microbes or molecules are present, but what they're actively doing.

Here's the full conversation.

The full conversation

Momo: Hey Guru.

Guru: So today we want to talk about measuring biology. When I talk to a random person in my circle, on the street and so forth, maybe I can expect them to know a few things about their biology. Of course you'll know your height and your weight. Maybe people know something about their HbA1c, or something because they've been wearing a CGM. And maybe they'll know something about their cholesterol. But most people don't know a lot about their biology, and they don't measure a lot about their biology.

Momo: That's true. And that's because the deeper biology isn't necessarily easily accessible. But today we have a guest who probably knows more about his biology than anyone else in the world. He probably knows so much that he knows his entire proteome as of about three o'clock yesterday afternoon.

Guru: Okay, proteome. So what is that? Most people don't even know what a proteome is. I know what proteins are, I know there are a lot of them, but what is the proteome?

Momo: Protein is the basis for the word proteome, and "-ome" just means a collection of. So the proteome is the collection of proteins found in our body, and it comes from human proteins as well as microbial proteins. Those are really the workhorses of our physiology — the actual molecules that perform the functions that keep us alive and functional and talking. We have tens of thousands of them. You just mentioned HbA1c. That's one of tens of thousands of proteins, and it's important for diabetes, but it's just one. So yes, I can go get my HbA1c tested, but our guest today goes and measures tens of thousands of proteins on a regular basis, which is pretty amazing.

Guru: So Momo, how do you even keep track of tens of thousands of anything? What does he make out of all of that data? Does he somehow aggregate it into higher-level things he can understand? In traditional drug discovery, it seems like you look for certain very specific proteins that have been studied, then target it — inhibit it or amplify it. But what do you do when you have that much data about your proteome?

Momo: Well, you know this better than anyone, but we're going to discuss all the details with our guest. We're going to be looking at patterns — how patterns change from a healthy state to a disease state, and how you can harness those datasets to predict disease and potentially reverse or prevent it. So that's pretty amazing.

Guru: I think our guest, Dr. Mike Snyder from Stanford — I cannot wait to talk to him.

Momo: He's probably the most measured person in the world, and we're going to dive deeper into all of that. I'm excited about today's episode. My name is Momo, I'm a biochemist.

Guru: My name is Guru, I'm an AI expert. So Momo, let me start with what's on my radar, and then you can go.

Momo: Let's go.
On the radar: epics, and the hormone estrogen
Guru: When I was growing up in India, we didn't study the Western epics, nor did we really study Western history. We studied Indian epics and Indian history — the Mahabharata, the Ramayana, the Vedas and the Upanishads and all that — but we did not study Homer. Now that I've lived in the Western world for a long time, there was a kind of gap in my head about the basics of Western culture. So when the movie The Odyssey came out a couple of weeks ago, I was super excited, because I wanted to catch up. I'm a bit of a history buff. And the movie is totally impactful on your brain and your mind, and the story is quite interesting, with all the magic and the scenes and his journey. However, I've got to say, it feels like one of the side stories of the Mahabharata. The Mahabharata is maybe a hundred times longer — it's a very long story, you can literally never finish it, and there are these tiny stories that happen on the side and then you come back to the main story. The Odyssey feels like one of those side stories. Not to put it down at all — that's just how it feels to me.

Momo: Well, given the ratio of the population of India versus Greece, I think a hundred times is perfectly fine.

Guru: Yeah, it is. It's a great story, I love the movie — but I get a lot more from the Mahabharata. Anyway, the other thing that's been on my radar the last few weeks is the hormone estrogen, which I personally didn't know much about. It's one of the three or so major hormones in reproductive health. Estrogen is such an important part of female reproductive health, and it turns out it also plays a significant role in male health, especially with bone and muscle. But it plays an outsized role in the cycle of reproductive activity in females — the 28- or 30-day cycle that follows menstruation. And then when menopause occurs and the estrogen level slows down and drops quite a lot, there are significant impacts on the physiology of women. I've been learning about this because we've discovered a lot of really interesting molecular patterns in the gut microbiome. If you're a female with these estrogen patterns, it impacts your health across many different systems — bone, muscle, heart health, mood, weight, metabolic activity. So I found it fascinating to understand the role of a hormone like estrogen for the first time. And just to finish the thought: for men there's testosterone, which is a very important reproductive hormone that also plays a role in women's health, and then there's progesterone. So those are the three major reproductive hormones, and I'm really enjoying learning about it.

Momo: I agree that we should do an episode just dedicated to testosterone and estrogen, because there are a lot of myths out there — especially with HRT — that have recently been debunked, and with testosterone too. There's a lot of conflicting information, and we now have quite a bit of data we can reveal, so that's going to be exciting. And as a little side note that people can read about — we'll post it in the show notes if I remember — a guy had chronic IBD that doctors couldn't do anything about. They scheduled him for a resection, meaning they were going to cut out part of his colon, which has a severe impact on your quality of life. In a moment of desperation, he read about fecal microbiota transplants, and he asked his mom if she would donate her stool for an FMT. She did. It turned out she was in menopause and she had hot flashes — and after the transplant, he developed hot flashes. It made the news, because it actually cured him of the IBD, but it brought on hot flashes. Now they can discuss hot flashes together, which is kind of a funny story. But it tells you how the microbiome plays an important role in estrogen metabolism and its effects on physiology.

Guru: Super interesting story. So Momo, what's on your radar?
On the radar: a Mediterranean spread and sprouted wheat
Momo: Too many things, but let's go quickly. Guru, if you can bring up the slides. I live to eat, so I'm always excited about food. This Mediterranean spread Guru is going to show you is one of my favorite meals — I just drool over it. We make it semi-regularly. There's a lot of competition from so many cuisines, but this spread is fairly easy to make at home, it's super tasty, and it's basically three dishes: Baba Ganoush, hummus, and tabbouleh salad. And if you also make whole wheat pita bread at home, which really isn't that difficult — you start in the morning, the dough rises over the course of the day, and you cook the pita in the evening — it's phenomenally healthy for a lot of people, and it creates a strong emotional connection with food. Highly recommend it.

Guru: My god, these pictures are mouth-watering, as usual. Is there any stuffing inside this pita, or is it just plain?

Momo: It's just plain pita. There's no stuffing — you use the pita to eat the food, because Baba Ganoush and hummus are basically finger foods. You cut a piece of pita bread and dig in. I hope some audience members will go find recipes, which are plentiful. There are infinite varieties depending on whether we're talking about Lebanon or Israel or Jordan or Syria — all slightly different, but kind of the same thing for us. So go get the ingredients on a weekend and make it from scratch. You'll likely love it. The next one I'm excited about is sprouted wheat. We actually had a specific request to talk about how to make it, so I'll outline it. Sprouting wheat is a completely natural process — there's nothing funky you need to do. It takes exactly 48 hours. You buy wheat groats or whole grain at your local store, from a bin, typically $1.50 or $2 a pound. You wash the wheat, spread it into a baking pan, then soak it — submerge it under water overnight. So you start one evening, and 48 hours later it'll be ready. Every morning and evening for the next day and a half, you drain the water and leave the groats wet. I cover them depending on the humidity where you are — if you're in New Mexico you'll need to cover them well; in the Pacific Northwest you can leave it more open. They'll start sprouting the next day. You rinse them again in the evening and leave them wet overnight, rinse the next morning, and 48 hours in you have sprouted wheat. Now, some influencers will claim magical nutritional benefits. There are mechanistic and molecular studies showing that some nutrients are more bioavailable from sprouted wheat and that it has a lower glycemic index, but clinical trials haven't really shown a convincing, strong preference — it's not convincingly better than whole wheat by itself. But it's fun to make. One dish I show is what I grew up with: sprouted wheat, a thin layer of sugar mixed in, and a very thick layer of ground walnuts. That's it. Adjust the ratios. It's one of my favorite desserts, and it's also healthy — walnuts are packed with nutrients, wheat is packed with nutrients. It's like taking a multivitamin and omega-3 supplements and a whole bunch of other things. I'll write the steps in the show notes so you don't have to worry about understanding what I just said, because I'm too excited to be very sophisticated here.

Guru: That's cool.

Momo: One more thing I want to highlight: how important it is that people understand the purpose of Viome, the company Guru and I co-run with Naveen, is to translate scientific discoveries into real life and actually give them to people. That's our focus every single day, including weekends and holidays. Here's another major breakthrough over the last six months — we worked in R&D mode to develop a new product, and our CLIA laboratory is fully set up.

Guru: We actually covered this in a previous episode — you went through the instruments and everything, left to right.

Momo: Exactly. So we provided more detail then. But the highlight today is that we're now going through clinical validations, and this October it's going to be released as a commercial product, which will be hugely advantageous. It's a food allergy and sensitivity test, but the cost is going to be remarkably reduced compared to the competing tests. That's really what we're about at Viome — not just bringing the most modern technology and putting it into people's hands, but making it affordable to as many demographics as we can.

Guru: I'm looking forward to doing this test, and to everyone else being able to access it at that price point, which is very low. And I'll emphasize the same point: if you don't translate the science, what's the point of the science? Knowledge is interesting and good, and sharing knowledge is good, but if you can't use it to make people's lives better, what's the point? That's what we believe in at Viome, and we translate all of the science. In fact, we do the science that we know we'll be able to translate — otherwise we don't even do that science.

Momo: Yep, exactly.

Guru: Time to talk about all of this measurement of biology with Dr. Mike Snyder. Very exciting to bring him on. Let's go get him.

Momo: Let's go.
Meet Dr. Michael Snyder
Momo: Today's guest is Dr. Michael Snyder, a Stanford professor and pioneer in using genomics and multi-omics for personalized health. His work explores how molecular data and wearables can detect changes in health before symptoms appear, and we're going to spend a lot of time on that. Mike, welcome to Two PhDs on a Pod.

Michael Snyder: Great to be here.

Guru: Welcome.

Momo: You've also founded several startups, so we may have time to touch on that too. Mike, we'd like to start with you giving an overview of what you think are the highlights of the last ten years of your career, where you've used these multi-omic tools to track people longitudinally to figure out what's wrong with their physiology before symptoms onset.

Michael Snyder: Well, one is the technology itself — the fact that we can now profile people incredibly deeply, with the genome, the microbiome, all kinds of measurements, and the wearables, so you get a much clearer picture of people's health. That's one of the biggest things. Some other highlights are things like showing you can use wearables for detecting disease. We're now subtyping diabetes — it's not simply type 1 and type 2. We think there are many subtypes of what people call type 2, but actually before they even get to type 2. And that subtyping is important for their food responses, the drugs they take, things like that. So in the big picture, we can profile health at a much different level than we're used to, and that's very powerful for treating people. It really is getting us close to the goal of precision health and precision medicine.

Guru: Let me build on that. The idea of individual variability in your molecular profile and your biology overall is a very big theme on this podcast. We've had many episodes where we talk about it, and hopefully our audience has heard us say it over and over — glycemic response is individual, inflammation is individual, all the biochemical pathways are individual. But you launched the field of personalized medicine in some way, and individual variability has been part of your career throughout. You even predicted your own type 2 diabetes. So let me ask: did knowing your molecular prediction change the outcome of what ended up happening in your own life, or did it just give you a head start on the behavioral interventions you wanted to do?

Michael Snyder: It totally changed the way things happened. As you said, we predicted my diabetes, and because I was aware of it from my genome, we caught it when it first struck. I became diabetic after a viral infection. It was first demonstrated for that in type 2 diabetes, was suspected for type 1 before that, and now it's actually very common for COVID. So I caught it quickly, got it corrected initially by lifestyle, and then it came back. I'm still struggling to get it as optimal as possible. But the genome predicted it, and then the tracking has helped me try to better manage it.

Guru: What type of lifestyle interventions did you make? And if you used pharmacology, I'd like to know that as well.

Michael Snyder: There's an interesting story there. Initially I got it under control just by lifestyle — running, cutting out carbs, cutting out all ultra-processed food, cakes, muffins, all that. That got it under control. Then it came back after I stopped running and got another viral infection. I got it partially under control but never really got all the way to normal, and gradually it kept getting worse. First I lifted weights and gained muscle mass — I gained 10 pounds of muscle, had a great trainer — but it actually failed to control my glucose. It turns out that's because of the particular kind of diabetic I am: I'm a beta-cell defect, meaning insulin doesn't get out of my pancreas. So once it kept creeping higher, I shifted to try metformin, and that failed miserably. It turns out I'm a metformin non-responder. Then I figured out I was a beta-cell defect — I didn't know that before — and I went on to try a drug called Repaglinide, which promotes insulin release from the pancreas, and that worked pretty well. These days, to be honest, I'm on the GLP-1s like a lot of other people, and that also works well. I'm also on the SGLT2 inhibitors. I switched to those two for a couple of reasons — one, they seem to work better. But I'll tell you, the GLP-1s, as great as they are, I'm a bit textbook: I do have a bit of stomach nausea. It's minor, but it's there. And the other unwanted side effect is they cause muscle-mass loss. So all that muscle I gained from weightlifting — I wouldn't say it all disappeared, but quite a bit went away.

Guru: I see.

Michael Snyder: And I really got very thin. I'm way thinner now, to the point where a lot of people look at me and say, "Are you okay? You look pretty thin." The answer is I'm actually quite healthy, except I'm on these GLP-1s, which have evaporated all my fat. I'm the coldest guy in the room. So I'm working on trying to gain some back — I take the lowest dose one-third of the time, and that's helping me balance my weight a little better. My glucose is a touch higher than I'd like, so I'm always adjusting.

Guru: The amount of muscle mass is important for diabetics, because the more muscle mass you have, the more surface area you have to absorb the sugar, the insulin, all of these things.

Michael Snyder: Yeah, it's lean muscle mass in general. Muscle is very important for glucose consumption, so it's that same concept you were saying.
The full multi-omics picture
Momo: I'd like to get back to all the data, because I've seen it from Michael's presentations, and it's fascinating how much data you've generated — a hundred or a thousand times more than a typical person in the longevity space. I'd like you to mention what data you're generating, and second, when normal people are going to have access. Today, if I want to measure my ApoB, that's very simple and easy to do, but the type of data you're measuring isn't really easily accessible to everyone, correct?

Michael Snyder: That's right. So we measure my genome — my collection of DNA. We measure my transcriptome — all the RNA generated from the genome. This is all out of blood, I should say. The proteome, the metabolome, the lipidome. In my case we've also measured my autoantibody profiles — what antibodies I have that might be reactive with human proteins.

Momo: Can we double-click on that? Your genome — where can people sequence their genome? Most genome services just provide SNPs or exomes, right?

Michael Snyder: These days you can get a whole genome. There are a few companies — I'm not conflicted on these — MyOme is one, Sophia Genetics is another. For about $500 they'll sequence the whole genome and give you a limited interpretation. They usually look for the Mendelian genes, as they're called — BRCA mutations, single-gene mutations that put people at high risk. BRCA is the prototype.

Momo: ApoE4, I'm sure? And ApoE3?

Michael Snyder: A lot of them don't give you the ApoE, because it's questionable in terms of actionability. You can ask for it, but because it puts you at high risk for Alzheimer's and it's controversial whether you can do a whole lot about that. I personally think you can, by lifestyle, a little bit — keep yourself mentally engaged. Some of them will tell you the ApoE status; it depends on the company. Boston Heart will give you this, but many don't. Some do, some don't. Things like high risk for cholesterol, a lot of cancer mutations, SDHB for example — these single-gene mutations you can get from a genome sequence. Depending on the company, they give anywhere from about 80 up to maybe 120 genes. It's not a fully comprehensive analysis, but it's probably the most actionable set out there. With BRCA, for example, you'll get screened more if you have a mutation. And then some of them do polygenic risk scores, some don't — that's a bit controversial in the genetics field, as you know. Polygenic risk scores work well if you're at the extreme end of the distribution — if you're in the top 2 to 4 percent, they'll work — but they don't work so well if you're in the middle. So some people say it's a good idea to present them, some say no.

Momo: Let's move on to transcriptomics, because that's super exciting.

Guru: Transcriptomics, yeah, I'm interested in that.

Momo: As you know, we're the only direct-to-consumer company that actually measures the metatranscriptome — not just the transcriptome in terms of human protein-coding transcripts, which is what's typically done, but a metatranscriptomic analysis, meaning we also measure the non-coding RNAs. So how would you say we could convert our metatranscriptomic analysis of blood into something more useful, beyond what we already provide?

Guru: Momo, can I add that I didn't hear Mike say microbiome yet? So you're going to get to that.

Michael Snyder: No, I was going to get to that.

Momo: We're going to get to that.

Guru: Let's put everything together in the metatranscriptomic question.

Michael Snyder: We can put it all together. I actually think the microbiome, we all know, is super important. It's been hard to get good and actionable information, though that's now emerging thanks to companies like yours and a few others, where we are now getting information from the microbiome we know how to act on. That was hard to get before — a number of companies entered this space and were not successful, because you have to turn it into actionable information. So I think your angle, the metatranscriptome, is quite unique, and there's value to all of it. On the transcriptome from the host — like out of the immune cells, the peripheral blood mononuclear cells — that has actually been harder to act on. Believe it or not, the proteome and the metabolome have been a little better when you're talking about the host. Now, the metatranscriptome, where you're looking for viruses or other things — there are certain specific markers that are valuable, but people are finding the proteome and the metabolome are better when you look at the host. That's a different scenario from the microbiome, where I think not only what's going on in the microbiome, but how the genes are acting, is a big deal. I do think it's important to collect information that becomes actionable, and that's where it's been hard for a lot of groups to figure out the business model. A good example was Arivale, which was collecting a lot of data for data's sake. They built these data clouds, but no physician knew what to do with it. The key is that yes, it's okay to build a data cloud, but it has to be one people can take action on. That's what you guys are doing. As the field has moved along, people have come to the realization that the information you get at the end has to be valuable. We're finding that in the area of proteins and metabolites — you can see that information and go on and use it. These days you use AI to pull together your information, the information from the literature, and the information from these tests to make very predictive, actionable models.

Momo: My comment on that, Mike, is that when it comes to proteomics, there are more data published tying specific proteins to specific diseases — but those are based on panels, not metaproteomic analyses. They're literally panels, which is fine, that's great. And the same with metabolomics — omega-3s and omega-6s and lipidomics. So we're going to bring up this metatranscriptomic association with diseases, which we already have. I think that's a really good discussion, Guru, to more robustly exploit our blood transcriptome dataset from the human side.

Michael Snyder: We can dig in on that, because I do think there's value to those datasets. You're right, traditionally they've been targeted panels, but now from a proteomics profile you can see how people are aging, for example — you can get their age type, which we think is very valuable, and the data are there in the scientific literature. But you're right, they haven't been traditionally measured. The transcriptome is much richer, and that's why people focus on it. I'd argue the metaproteome has almost not been studied at all, nor the metametabolome. So it's a very unknown space.

Momo: It's hard, yeah.
Activity, not presence: making the data actionable
Guru: And it's very complex. The way we manage the complexity, Mike, is to look at the domain-understood pathways coming from the metatranscriptomics. A classic example is short-chain fatty acids. We know a lot about short-chain fatty acids in the gut and how they impact physiology. So if you can see the activity of the metatranscriptome with respect to short-chain fatty acids, and then make actionable recommendations based on that activity, we think that's a more concrete way of moving forward with the kind of data we have today. At the right price point.

Michael Snyder: A hundred percent agreeing. You're hitting on two important concepts, in my opinion. One is this pathway-level analysis — that's how you get understanding. Short-chain fatty acids, super important. The other is you're in the gut, looking at the microbiome and the metatranscriptome, and that is its own beast and a very important window into health. Very understudied, in my opinion, and I think that's where you guys are pushing the boundaries. You're able to take that information and use it in an actionable form. We don't yet know if the metaproteome would give the same information, or the metametabolome — that's a lot trickier, especially the metabolome when you're getting it out of the gut. So there are technical issues there. The proteome may have value too, I don't know — it just hasn't been explored the way you guys are diving in. And what's going on is very logical. People started with the genome — the metagenome — and saw what bacteria are there, and that gave some information with some value. You've taken it to the next level with the metatranscriptome, which says what genes are there, which ones are active, and what pathways are going on. I think that's super important. Whether the metaproteome adds onto that, I'd say, is an unanswered question.

Momo: Right. Guru, do you have a next one?

Guru: Let me take the next question. The pathways can be associated very strongly with specific diseases — for example, inflammatory bowel disease. We've noticed there are about eight or nine pathways that are highly involved in IBD, and we now have a large enough dataset of people with and without IBD to be able to say that these specific pathways are active in the IBD, or let's say Crohn's, for example. There's a pretty big difference between Crohn's versus colitis. So we can say in Crohn's there are these types of pathways that are active. In your analysis of all the omics you've studied, I was wondering how you ignore the transient noise and isolate the relevant signals for specific diseases.

Michael Snyder: We're keen on individualized profiling, as you know, so we track individuals over time and get a sense of what their personal baseline is like. That's very important, and it's all different — your baseline heart rate, blood oxygen, skin temperature, they're all different from mine and from Momo's. That's step one. Then, in our case, we're trying to catch disease early, so we look for shifts from those baselines. That's turned out to be very powerful. When I caught my Lyme disease, it was because my blood oxygen went down and my heart rate went up, all in advance of symptoms. So you can see these things for early disease detection — but it only works if you know your healthy baseline, because we're all different. Now, on the issue of disease-versus-healthy signals, that's valuable too. There are clearly markers, but they tend to come a little bit later if that's all you're doing, because then you're using population-average measurements — you look for things like CRP, or inflammatory markers for IBD. That's valuable, but I'd love to hear more from you: how are you able to use that information for treatment subtyping? Can you subtype IBD and treat accordingly? We do that for diabetes — we can now subtype diabetes based, of all things, on the shape of a glucose curve, and your subtype determines what foods you should eat and what drugs you should take.

Guru: Mike, in our case, to put it on the table — if you take IBS, there are so many subtypes: a constipation subtype, a diarrhea subtype, a mixed subtype, and so on. We're able to isolate the specific pathways — for example, sulfide production pathways, methane production pathways, or serotonin pathways — and we have gastroenterologists looking at the pathway activities to determine what kinds of treatment or care to recommend. That's exactly what we're doing.

Michael Snyder: That's perfect. Based on their subtypes, you can recommend specific treatments. I think that's huge. Another area I know something about is ME/CFS, chronic fatigue syndrome, where it's the same thing — a very heterogeneous disease. So you want to break it down and, based on people's tests, decide how to treat them. One of my companies, Rhythm, does that. I'm totally keen on the subtyping. And that comes back to your earlier question, Guru — to what extent can you tell disease signal from normal? I think you can use some markers for that. I'd love to be able to tell, just on the person, disease signal from normal. IBS is a good example, IBD too — they have periods where they're perfectly normal, and then they shift away from that. But I like where this conversation went: to be able to subtype people based on these big-data profiles and then treat them accordingly, because most of these complex diseases aren't just one thing, they're multiple things. Knowing that is critical for the course of action.

Guru: Momo, back to you.
The ME/CFS mystery, and measuring mental health
Momo: I have tons of questions, but ME/CFS is such a big mystery, and it completely degrades the quality of life of the people who suffer from it. Can we spend a couple of minutes on it? What have you seen in that disease, and what should people know who are suffering from it — in terms of what tests are available that may not have been available in the last few years, or what's coming up soon?

Michael Snyder: First, I'll say I'm not a physician, so you should go see your doctor for these sorts of things. ME/CFS is a real mystery. It's very heterogeneous. The one common thing they have is the fatigue, which manifests after people overexert. But it's very different from one person to the next. Some people have heart issues associated with it. For some it's fairly mild; other people are bedridden and literally can't get out of bed, their case is so extreme. And there's everything in between — some people have gastrointestinal problems. It's all over the map. In this case I probably won't venture far beyond where I'm at, but I really think you do need to see specialists, the ones who know what they're doing, because they'll order the right tests. They look at your cytokines and a variety of markers, and based on those they'll start some treatments — but they monitor those pretty carefully to see which ones are working and how the markers shift. That's another important part of the measurement space: not only diagnostics, but monitoring treatments. A good example is the mental health space, where we don't have good markers. It's very hard to see how people are responding to treatments — you have to wait three months, six months to see if anything's working. A fraction respond, most don't, to most of these treatments. It's a real mess. I am a measurement guy — we're keen on making lots of deep measurements on people to better figure this out. I think that's an area really lacking in the mental health space, and I'd argue ME/CFS has more markers and would probably benefit from more omics profiles.
What wearables can catch
Guru: In terms of measurement, Mike, I know you're very big on wearables. At a strategy level, do you see wearables as deep enough and high-fidelity enough to get to the broad range of chronic diseases, or not? With infectious disease it's relatively easy — I've actually had my Oura ring warn me one morning that I shouldn't go running that day. I ignored it and went running, and later I collapsed somewhere, came back home twelve kilometers later, and I had COVID that night. My Oura ring caught it. So I believe wearables can give us information about dramatic changes in your physiology, especially with infectious diseases, which happen quite suddenly and intensely. But chronic disease is a very different beast — it's very slow, long-range. Even if you get so much data every day, I'm not sure how much noise versus signal there is in wearable data for long-term tracking of chronic disease. What's your view?

Michael Snyder: A couple of comments. First, I'm a big fan of wearables — I have six of these: four watches, two rings. I left my hearing aids upstairs, they're also sensors, and I have several others. And here's my continuous glucose monitor. So I'm a big fan. And not to toot my own horn, but we were the first to show you can detect infectious disease from a simple smartwatch. But they go way beyond that. Let me break down what you brought up. I think they can detect many diseases — we showed that with machine learning and AI; now you'd use deep learning. We can predict things like red blood cell count and hematocrit, which is sort of a blood marker, even fasting glucose and hemoglobin A1c, from a smartwatch. They're not clinical-grade measurements, but they're plenty good to see a shift from baseline. And that was done with the 2016 watch, so I know we can do even better. Others have shown you can pick up AFib now. We had a case we're trying to get published — it's a bit of a sad story. There's an individual, a super-fit guy in the lab, 76 years old — you'd look at him and think this guy's great, and he was great. He's doing well, and then suddenly he dies one day, right after running on a Peloton. His wife shares his aura ring and smartwatch data, and we look at it, and sure enough there's a step-function change that occurred four and a half months prior to his catastrophic event. His heart rate went up, his heart rate variability dropped, his gait shifted, his sleep shifted, his step count shifted — all these things were there. That hits the point you're raising: the information was there, but it was not relayed back. There was no system for taking it and relaying it back to say, "Hey, something's off here, maybe you should go get checked out, or maybe you shouldn't run." He ran one of his hardest times ever on the Peloton. So we need a mechanism for taking this information and feeding it back to people. And I predict it's going to be valuable for IBS and IBD too — maybe preceding some of these events we'll be able to pick that up.
The future checkup — done at home
Michael Snyder: I do think a lot of the medical exam in the future — not a hundred percent, but a lot — will be digital data: smartwatch, facial recognition, other data. And then you'll add biochemical data on top of it, and probably microbiome data, but you'd do a lot of it at home. People would get measured a lot more, too. We've set up something called micro-sampling, where you do little drops of blood and mail it in — one of my companies does this. You get measurements on 650 metabolites that cover all these 20 wellness areas: inflammation, oxidative stress, heart health, kidney health, all these things. And you can combine that with microbiome, which you could also measure at home. Suddenly you've got both a biochemical picture of people and a microbial picture, as well as the digital ones, and I think you could deduce a heck of a lot from that. Then we can measure people at home much more frequently, so we can track people's health and not wait every two years until they come to a doctor when they're already ill. That shifts the whole paradigm. We've got to keep people healthy, or we're going to keep operating in this broken healthcare system we're in now.

Momo: This is amazing — we could discuss it for hours. We only have a few minutes left, so let's touch on a couple of points. Even though wearables aren't necessarily very precise — they don't have clinical-level precision for individual markers — if you have enough longitudinal data points and establish that baseline, when the baseline changes relative to your own baseline, you can deduce that something is wrong and go get it checked out with more precise markers. I really like that. Blood pressure would be one — smart devices aren't super accurate, but if your blood pressure keeps creeping up, something's wrong and you should get it checked. That's obviously a super important metric.

Guru: By the way, Momo, I do have a blood pressure monitor from one of these companies, and I take it every week. It's not every day, but every week I think is reasonable.

Momo: It's reasonable, yeah.
How many subtypes of type 2 diabetes?
Momo: So Mike, let's touch on type 2 diabetes, because it's obviously a huge topic. Are you saying there are two subtypes of type 2 diabetes? If we focus just on type 2, there are two: one is the reduced ability to produce or release insulin into the bloodstream, and the other is what's classically known as insulin resistance, where your cells aren't responding to insulin. Is that the two, or are there others?

Michael Snyder: There are more than that, believe it or not. Even insulin resistance you can break into subtypes. There's muscle insulin resistance, which is the major form, but there's hepatic insulin resistance — your liver — and there's also adipose insulin resistance. On top of that, there's a beta-cell defect. And on top of that, there's also the incretins, these GLPs — they're actually natural hormones in the body — and there are people who have defects in that pathway as well. So you can be defective in any of these areas, or combinations thereof. Now, it is true that muscle insulin resistance and beta-cell defect are the most common ones, but these others are out there too — they're not zero. And just from the shape of a glucose curve, we can predict muscle insulin resistance versus beta-cell defect. So you can now get your subtype. We haven't fully released this, but we will soon — you can get your subtype just from a simple at-home test, and we think that's very powerful.

Momo: So when you release this, are you saying you have a company that will offer it as a product?

Michael Snyder: Believe it or not, no — of all the companies we have, this is one that isn't doing it. Although there's a company in India called Iora that I'm an advisor on that will incorporate it there. I've been trying to get some of the companies here to incorporate it. In the end, if nobody picks it up, we'll just toss it up there as a free at-home test that anybody can do. In fact, we did that for the infectious disease detection.

Momo: So in other words, someone would collect CGM data and then apply some method you'd release publicly to determine their subtype?

Michael Snyder: You'd just upload it onto a website, if we put it there. To be honest, that's the most likely plan that'll emerge — we'll upload it and then you'll see what your subtype is. I want to point out that we're very predictive for muscle insulin resistance and beta-cell defect. We're not so predictive for the others yet, meaning we'll probably have to add other information or improve our algorithm.

Momo: But those two are the most common ones, and your approach to fixing or preventing them is very different, so those basically cover most people.

Michael Snyder: It is, yeah. We think it's very powerful.

Momo: So Mike, we'd love to have you back on the podcast when you provide that website — maybe all three of us could wear CGMs before the podcast, upload our data, and do it live on the show.

Michael Snyder: That'd be a lot of fun. Sure.
The moonshot
Guru: That sounds great. Before we let you go, Mike, I have one last, big-picture question. If you had a blank check today and zero regulatory red tape, what is the single biggest moonshot experiment you'd like to run on the human population?

Michael Snyder: I can answer that in several ways. The most obvious is I'd like to put a smartwatch on everybody on the planet, because then there'd be some level of health tracking for most of the world. Most of the world has a smartphone, believe it or not, so all you have to do is put a watch or a ring on and pair it, and suddenly you've got some level of health monitoring. I predict that by itself would lead to people improving their health. Now, it'd be good to incentivize people, and this is where the answer gets a little more convoluted. The biggest problem we have with healthcare today is there's no incentive for keeping people healthy. So I think we should have plans that give you points for wearing a smartwatch — points meaning a reduction, maybe your payments are less — points for getting your genome sequenced, points for getting your microbiome done. Do these things that are useful for keeping you healthy. That, I think, is what would change the way medicine is done today.

Guru: That's amazing. I agree with you completely — we should incentivize people by reducing their insurance premium if they do all these things, just like in the car industry, where if you drive safely and use a device that tracks your driving, they reduce your premium every month. We should do the same in health.

Michael Snyder: We should have the same for health. It's crazy.

Momo: Amazing. I might get a smartwatch just based on this conversation. Thank you.

Michael Snyder: I hope so. You don't need all four — just one will do the trick for everyone.

Momo: Just one. I'll get one. Dr. Snyder, it's a huge pleasure to have you as a guest. We're looking forward to the next episode, when we can discuss these subtypes of type 2 diabetes and more. Thank you very much.

Guru: Thank you so much, Mike.

Michael Snyder: Thanks for having me.

Guru: Awesome. Bye now. We could continue talking to him for hours, because there are so many great topics, and he's got so many results over such a long, distinguished career, and so many common topics of interest with us that we could just keep going.

Momo: We will. We'll have more episodes with him — we've already scheduled the next one, and we'll have more over the years.
Audience questions: skin vs. gut microbiome
Guru: The next part of today's episode is questions from the audience. One audience member asked: are there any microbiome areas you might extend into in the future, like skin or vaginal? Momo, go for it.

Momo: We're always looking at what kind of tests we can bring to market to make the biggest impact for our customers and for people in general. When it comes to skin microbiome, we actually had a very serious R&D effort and we locked in the test. But by the time we did that and were considering the go-to-market strategy, we realized — both from the literature and from our own data and our customer feedback — that the skin microbiome actually plays a minor role in skin health. It's really the gut microbiome that plays a major role in skin health. So we took that off the table. I'm not sure if or when we'd bring a skin microbiome test to market, because it's not showing much relevance, and we don't want to offer another product for no reason. Now, the vaginal microbiome is very, very important — that's well known. But here's the thing: our CEO's daughter, Priyanka Jain, founded a company focused specifically on the vaginal microbiome. We're friends with them, and I'm one of the earliest advisors of the company. Look up EVVY — they have the most advanced vaginal microbiome test, both in terms of the molecular test and, most importantly, the interpretation of the test. So we have no reason to offer a vaginal microbiome test at Viome, because EVVY's got it. Look into that.

Guru: I spoke to her this morning, actually. The clinical studies they're doing are really great — they're looking at the impact of different types of issues with the vaginal microbiome related to female health, and other procedures people may go through. They've got solid science, and they're doing a great job giving the market a product.

Momo: They're on the cutting edge of both the science and the clinical interpretation, which is what women need. They don't just need data, because if they take that data to normal doctors, they're not going to know what to do with it — it's such cutting-edge science. So EVVY is really doing the translational science piece very well, and I'm very proud of them.

Guru: Momo, there was another important point I wanted to highlight: our metatranscriptomics assay that you built is applicable to literally any type of sample.

Momo: Any type of biological system — it can be deep ocean vents, air filters, tissue biopsies, soil, it doesn't matter.

Guru: Exactly. So whether it's a human sample, an environmental sample, or an animal sample, whatever it is, if we can get those samples into the lab in a preserved way, we can do the same metatranscriptomic assay. There are a lot of possibilities in the future, because we don't have to build a new assay — it's a comprehensive assay and it's generalizable to any type of sample. That's important for people to know.

Momo: On that topic, I want to mention that we've fully developed and validated an environmental test that includes molds, and molds are a huge medical concern. I think we have the most advanced mold test in the world, for two reasons. One is that it's completely unbiased — we're not testing for specific molds we're looking for, we're looking for all of them at the same time. And second, our fungal database of medically relevant fungi is the most advanced in the world, because we made a significant investment in it. The combination of those two would make it very useful for a lot of people. Unfortunately, we don't have the bandwidth to go to market with that test, so if there are entrepreneurs out there who want to white-label our test and market it in a big way — and we're only looking for a big way, not a small way — contact us and let's go. We've also dabbled in animal microbiome, like cats and dogs and horses, but we really need to focus on what's most important at the time.

Guru: Which is human disease, human chronic disease.

Momo: Yes, human chronic disease and cancers.
In the news: the ZEUS trial and the limits of one target
Guru: Speaking of which, we're starting another interesting segment of our podcast that we'll probably repeat in many episodes, called "In the News." What is a major, exciting piece of news out there for everybody to consume — and what's underneath it? Not just the headlines, but what's underneath, and a view on the reality of the situation, the science, and the impact on health. I'll start with a piece of news that came out in the New York Times, I think yesterday. This was a major study run by the pharma company Novo Nordisk. They called it ZEUS — speaking of the Odyssey, it comes right back to Greek mythology. The ZEUS study had a hypothesis that inflammation is the underlying root cause of cardiovascular disease, and in particular they went after the IL-6 cytokine, and some potentially related things. They developed a molecule that would suppress IL-6 and other proteins like CRP. Their hypothesis was that this would lead to an improvement in cardiovascular disease, specifically atherosclerosis. So they recruited a lot of people — I think 6,000-plus with the disease — gave them the medication for a period, and measured it just last week, apparently. They published that they did not impact their primary endpoint, which was the disease itself. Even though the IL-6 and CRP and other inflammatory markers they were targeting did reduce, the disease did not. So Momo, I'm going to turn it around to you, the molecular scientist: what is going on here with this inflammation hypothesis?

Momo: I think traditional drug design goes after one target, and that's worked for decades. However, the complexity of human biology is such that when we talk about inflammation, we're not talking about one or two molecules — we're talking about hundreds of molecules. It's very unlikely that one molecule is going to be such an important factor in a disease that if you knock it down, you'll prevent the disease. Now, it has happened in the past. TNF-alpha is the first such target — another cytokine that's a central player in the immune system. The most lucrative drug type on the market since the early 2000s are these monoclonal antibodies, or biologics, against TNF-alpha, and that's worked fairly well. It works really well in some people, not so well in others. So Novo Nordisk, who people will probably know brought us the GLP-1 receptor agonists, went after this IL-6 target, which very strongly associates with cardiovascular disease, and they thought it was going to be the next TNF-alpha. Unfortunately, that didn't turn out to be the case. What that tells us is either they didn't dose it properly — they didn't knock it down enough to see results — or, much more likely, there are many redundant inflammatory pathways contributing to cardiovascular disease, and knocking down one of them just isn't going to have a significant impact. That's sort of the core of what we do at Viome. We're not targeting one thing — we're looking at hundreds of pathways in the gut microbiome and oral microbiome and human blood, and modulating hundreds of them at the same time with thousands of micronutrients, to shift the balance toward less inflammatory. When you shift that whole balance, you're impacting many different pathways, not just one molecule. So I'm not super surprised. I feel bad, obviously — on average it costs $3.2 billion to bring a drug to market, so they spent a lot of time and money, and it failed. That's unfortunate.

Guru: Very interesting and important result, in the sense that you can't reduce everything to one thing. There's a reductionist view that you reduce everything to one thing, and that's not likely to work a lot — there's a lot of multifactorial stuff going on, and that's kind of what we do. So Momo, what else is in the news?
In the news: food allergies and the gut microbiome
Momo: I want to bring up a paper — I'll list it in the show notes — that I found fascinating. The rate of food allergies and sensitivities has been increasing for decades. These things used to be super rare, like 50 years ago, and now they're super common. We've normalized the fact that people are allergic to different foods, and what's not known is the root cause. We've had good evidence that it's the gut microbiome that determines these things. I want to point out two papers. One specifically shows — and it was demonstrated mechanistically in mice — that the gut microbiome determines the fate of specific immune cells called T cells in the lining of the gut. If they convert to a specific type of cell, they release cytokines that tell B cells to switch to making IgEs, and these IgEs are antibodies that facilitate allergy responses. But the other effect of the microbiome can be that these T cells convert to so-called T-helper cells that actually recognize food as food and develop tolerance. So the very first signal for whether we're going to be allergic to or tolerate a food starts with the gut microbiome. That's really nice. And this second paper, which just came out literally yesterday, shows a mechanistic view that has to do with bile acids. Bile acids are complex molecules our liver produces and our pancreas releases that solubilize fats in our food. Some of those bile acids make it to the colon, where the microbiome processes them, and they're showing that when these bile acids are processed by specific microbial members in the colon, we do not develop allergies. But if there's a lack of that biochemical function, then the person — and the mouse — develop food allergies. This is really exciting to us, because we're going to be offering a food allergy product soon, combined with our deep microbial understanding. For me, the most exciting thing is that maybe in a year or two or three or five, we're going to be able to modulate the microbiome in a very deterministic way to prevent allergies. That's really where we want to be.

Guru: That would be amazing, Momo.
The monthly challenge winner — and how often to retest
Guru: So it sounds like we have a monthly challenge winner.

Momo: We do — go ahead, Guru.

Guru: It's Chris Brink9272, who made the comment. Remember, the challenge was for you to make a really good comment — interesting and relevant to a lot of people — or ask a question. He says: "Knowing that DNA is static and RNA is dynamic, I'm curious about your thoughts on how frequently the average consumer would need to test their molecular data." Awesome question. And it turns out we just published a paper on this topic a few months ago. We took a number of customers on Viome — more than 6,000 of them — and looked at the rate of change of their microbiome, and the significance of the change from time zero to month one to month two and so on, all the way to month twelve. We found that around the six-month mark is when the microbiome changed significantly — statistically significantly — when you compare each time point to the previous one. The takeaway is that yes, your microbiome changes a little bit based on your actions on any given day or week, but it takes an entire half a year, two quarters, for the microbiome to change enough to settle into a new steady state. Because of that, we recommend that all consumers retest their Viome molecular test every six months. That's our recommendation, because if you take our supplements or any of our recommendations seriously and actually make the changes we recommend, it will take about six months to get to that new steady state. I'll put a caveat in: if you have some dramatic event in your life — a surgery, an antibiotic regimen, or you move somewhere and dramatically change your diet — that could have a bigger impact. In that paper, we studied one interesting thing: after a colonoscopy, your microbiome actually bounces back within a couple of weeks. But if you had something really dramatic, maybe it'll be a little faster. On average, though, I'd say about six months.

Momo: Awesome. Congratulations. So what we need is for Chris Brink9272 to please email us at podcast@viome.com and show yourself to us, and we'll provide you with a free Full Body Intelligence kit. So please email us and we'll go from there. Congratulations.

Guru: Congratulations, Chris Brink — you're the lucky person.

Momo: Lucky, and pretty in tune with what's going on with human biology and RNA versus DNA. So that's all we have for today's episode. Thank you so much for listening. I'm Momo, a biochemist.

Guru: And I'm Guru, a data and AI expert. All right, see you next time. Bye-bye.

Momo: See you next time.

Guru: All right, I have a question for you. If you took your car to a mechanic because you feel that your engine is sputtering, and then he kind of looks around outside and checks some things and then says, "Oh, you know what? There are no dents on this car, you don't need anything," and gives you back your keys and says, "Hey, you don't have a problem," what would you do?

Momo: Well, first of all, I would find a new mechanic, and then I would probably tell him to check himself, because something's not right with his expertise.

Guru: Exactly. I mean, that's what's going on with a lot of doctors, especially when you look at gastroenterologists, who are essentially intended to look across all types of maladies of the gut. Traditional gastroenterology will look for structural issues. They look for a polyp or a blockage or something like that, but they don't focus on any functional issues like IBS, like bloating. These are 60% or more of the issues that GI doctors face. So when they're faced with a functional issue, they end up just doing trial and error. They don't have a prescribed way of going about it.

Momo: Well, that's because they lack molecular tests to actually figure out what the molecular features or what molecular processes are causing those symptoms. Lack of tools.

Guru: Yeah, they're flying blind. We need to help them out. So our Gut Health Pro test can make a huge difference. And that's what we're going to talk about today with our special guest, Dr. Michael Bass, a gastroenterologist. Hopefully everyone will stay around and listen to all the great points about how to improve your gut health, and if you're a doctor, how to improve the gut health of all of your patients.

Momo: Yeah, this is a great analogy, Guru, that a mechanic without the tools to actually open up the engine and examine all the parts and understand why the engine is broken, just being able to look around the car and take pictures of it and say, "Hey, the car looks good," that is not very helpful for a lot of people. Of course, if you were in a car wreck and you dented the outside, then yeah, that's helpful, but that's not all of the cases. And I laughed when you said an engine, because I've not had a car with an engine in five and a half years. Speaking of cars, electric motors are the new thing.

Guru: I know. And in my case, I have not had a car for about 10 years now, so I'm not a car guy. Maybe we'll talk about that some other day. I decided that public transportation and using Uber and other services are much more efficient for my life compared to owning a car and living with the overhead of that in New York City. It's just not worth it for me.

Momo: Of course. Very smart. So in summary, what we're going to talk about today is all of the molecular data, what Guru calls molecular software, that now empowers physicians, gastroenterologists, to actually look under the hood, so to speak, and see all of the molecular details of what's going on in the intestine that are responsible for more than 60% of gastrointestinal symptoms. That's amazing. We're entering a whole new world today. So welcome to the episode. I am Momo, a biochemist.

Guru: And I'm Guru, an AI expert. We're two PhDs on a pod. All right, who's going to go first?

Momo: All right, I'll tell you what I'm excited about. I'm always excited about more things than we have time to share, but let's go with this one. So if you don't mind sharing the slides, I put together four photographs of the Pacific Northwest. I've lived in Seattle now for six years. Let me tell you, it is really difficult to plan any trips to go outside of the Pacific Northwest. I used to be excited about so many places in the world, but wow, this is like a world-class area for so many different things except tropical beaches. We don't have those, but we have a whole bunch of other things here. The summer here is crazy because our sun rises sometime around five o'clock in the morning and sets after 9:00 PM, so we have these absolutely beautiful, gorgeous, sunny skies all day long for months. It's insane. So we take advantage of it and we go out and explore. Here's Mount Rainier. This is one of the most famous parks in the Pacific Northwest, Mount Rainier National Park. Let's go to the next.

Guru: Beautiful, beautiful picture, man. Amazing picture.

Momo: Yeah, this is my son and I. We woke up at four in the morning and hiked up, and oh man, it's amazing. Let's go to the next one. This is actually crazy because this is literally like a 45-minute drive from Seattle, and then it's a bit of a hike. It's 3,000 vertical feet, so it's a bit of a huffer and buffer. But look at this. It's crazy that you get to see this.

Guru: What's the name of this mountain range?

Momo: So this is the Cascades, or North Cascades. This lake is called Lake Serene, and it's literally the very first part of the Cascades as you drive from Seattle, so right there on the edge of the city. Pretty amazing. Next slide, please. And then in the Puget Sound, you can go sailing, boating, kayaking, all kinds of things. Just recently we went whale watching. We have local resident pods of orca whales, and they're here year-round, and the local tour operators can take you to view them and watch their behavior. It's pretty cool because you can get fairly close to them, within a nice distance. Next slide. This is another crazy thing. This is literally the closest part of the Cascades to Seattle. This is on Snoqualmie Pass, the major pass east of Seattle on I-90. You just park on the pass by the road, and this is called Snow Lake. It's about an hour-and-a-half hike. It's crazy that we have this. This is just a few of hundreds of places that are super, super beautiful around here. So I'm excited about this.

Guru: I want to visit a few of these places next time I'm up there.

Momo: Guru, let's go.

Guru: I told you. And now my brother's going to be there too.

Momo: And now some nature as well. Awesome. So I'll take you to all these cool places. And then I promised in the last episode, I talked about mole and I promised that I would show pictures. This is the recipe from about the 1550s based on historical records. It's basically a combination of the New World foods and Old World foods, a modified version of mole as it was developed in the pre-Columbian era, but it's still delicious. This one is made with cocoa, the black mole. I'm just showing here the ingredients and some steps in cooking. You've got to roast your vegetables to extract the most flavor from them, and roast the nuts with the spices, and soak the chile. We're going to actually post a recipe for this in the show notes so that others can reproduce it, because black mole has a very unique flavor. No matter how many different cuisines and meals you've tried, you have never tried black mole unless you've tried it. It's a very unique flavor.

Guru: Very cool. I'm definitely going to try this.

Momo: Amazing. All right, Guru, now what's on your radar?

Guru: Okay, so you showed a lot of things from nature. I'm going to do the contrast to that, which is city life.

Momo: City life, the big city, Big Apple, right?

Guru: In the Big Apple. And I love the city energy, the kinds of activities that you can do. A couple of things happened in the recent past. I just want to show you one, which was a tall ships parade that happened in the New York Harbor for the 250th year, July 4th Independence Day celebrations.

Momo: Oh, I love that.

Guru: There were, I think, 50 different ships from different countries that showed up, and all of them were very fancy tall ships, all sail ships, by the way. I was just mesmerized by them. There were planes going around from different countries, from their militaries, but there were also these tall ships. I took a couple of pictures. One is from India. This is the INS Sudarshini, which is a 177-foot boat and it's 113 feet tall. These guys have sailed for approximately 15,000 miles all the way from Kochi, India, which is the hometown of this boat. They've sailed all the way to the New York Harbor just by using wind energy. Whenever I think about that, it's always fascinating to me. It took them a couple of months to get here, but you see all the people on the masts, you see the people standing up, that's the crew. They've been on this ship for that long and they got here. It was just amazing to see them. We all not just waved, but we kind of sang and shouted and all of that good stuff. The other ship I want to show you, right next to the Statue of Liberty, was a ship from the US. This is the 1877 tall ship called Elissa. It's a historic ship, built at the Galveston historic seaport in Texas, apparently. It's 152 feet long, 100 feet high. Very, very beautiful ships. You just see these things and they're beauties. It's manmade, but some of the most exquisite manmade objects, in my opinion.

Momo: No, absolutely. Love the sail layout.

Guru: Yeah, and it's amazing to me that the technology and the engineering allows you to harvest essentially the wind energy and navigate this wherever you want to go, with the speed and the direction, and even with storms and big waves and everything else, they manage the whole thing. It was an amazing thing for me. So that was one thing. The other thing I want to show you guys is that I'm always fascinated with the street musicians of New York. I'm a musician myself and I love to hear people who spontaneously create music. The street musicians of New York are some of the best. I keep teasing people in other cities that our street musicians are better than their concert musicians, and I actually believe that. I go to other cities and I go to these massive, high-priced ticket concerts, and then I say the street musicians in New York are way better than this stuff. So I want to show you an example of a street musician that I fell in love with in New York City. Somebody made a great short video of that, so I'm just going to play that. Let's enjoy it for a minute and a half.

Momo: For those who don't know, Guru, how do you find these street musicians? Are they always at the same place, or is it random?

Guru: It's totally random. So actually it's both, to be honest. When I get out of Grand Central Terminal every day when I go to the office and I'm walking by, I do see some musicians in some standard places, but they're all different musicians. So it's random in the sense that you don't know what to expect on any given day.

Momo: Got it.

Guru: But many times you're just walking somewhere, literally on the street next to a park, next to some kind of monument, and just in the street corner there are a couple of street musicians who are doing something that blows your mind. Sometimes I just stop there and I forget about the rest of the world because it's so good.

Momo: So for people who want to experience this, who are visiting New York City, are there any particular areas of the city they should go, or any particular time of the week or time of the year?

Guru: It's all around the year. If you're here in the summer and you want to experience this, anywhere that tourists hang out you will see street musicians. There's no question in my mind.

Momo: So you really don't have to look for it. You just walk around and you'll see it.

Guru: Yeah, you just walk around the city and you'll see them, next to monuments, next to historical places, next to parks. Wherever you go to eat, to see, to hang out, you'll see these guys on the street. I'll show you an example. This is a sophisticated type of music that's created by just two random strangers who came together on the street and just decided to create. And this guy Ari that I'm going to show you does this all the time. He just walks down the street and creates music with random strangers he meets. I'm so fascinated with that lifestyle for him. He just creates videos, and I'm going to show you one of them.

(video plays)

Momo: Wow.

Guru: What do you think of that?

Momo: What a show. What a show. No fireworks like the big concerts, but super unique.

Guru: I know, man. I get mesmerized by these things. I just stop and I forget about the rest of the world and I just stay there. And then, of course, I give them a nice tip and everything. That's why I love New York City.

Momo: That's amazing. Super unique. And the dancing dude, wow, what the heck?

Guru: That guy who was dancing came up and rapped on top of this music for a few minutes, just made up lyrics and rapped on top of that. And then some woman came and sang on top. The whole thing went on for a whole hour. It was ridiculous.

Momo: That is super unique. You cannot possibly prepare for that or recreate that. It's just a moment in time and you've got to be there. It's crazy. So unique. Super cool, Guru. Thanks for sharing that. All right, are you ready for Mike Bass?

Guru: For Mike Bass?

Momo: We are ready for Dr. Bass.

Guru: Dr. Bass. Okay, get into the different mindset now. Let's go. Hi everybody. I'm so happy to welcome Dr. Michael Bass, MD, to our show today. Mike is a really good friend of ours. He has been very active in the gastroenterology world for a number of years. He was actually the founding medical director of Oshi Health, and he's had a private GI practice for 14 years. He's now a Global Medical Director here at Viome. And one more thing that's super interesting about Mike is that he is a top voice on LinkedIn, so you might actually see a whole bunch of things from him on LinkedIn about all the latest news and analysis of various things in the gastroenterology community on a regular basis. I actually follow him and learn a lot from everything he says. So Mike, welcome again. I would love to start with a perspective from you about a modern gastroenterologist as we know it. There's so many good things about gastroenterology, but there's also so many limitations. People are still practicing what they've been taught from maybe decades ago. And there's a lot of functional aspects of GI conditions that are pretty difficult to diagnose and pretty difficult to treat. So give us a little introduction to how you see the world of gastroenterology today, please.

Dr. Michael Bass: Of course. Guru, Momo, thank you. Thank you for having me on. I'm a huge, huge fan of this podcast. It's the best healthcare podcast out there. And I might be slightly biased, but definitely is the case. So I've been a private-practice GI doctor for the last 14 years, and what I've seen is that we are great at telling you if there's a structural problem. So if somebody has cancer or a polyp or a blockage, we can do all types of tests and we can tell you about that. But what we're not great at is managing the everyday issues that, frankly, most people have that come into our office. These are classified as functional gastro issues, where we've done all the testing and we don't see an actual structural problem, but there's some issue in how the bowel functions. This is irritable bowel syndrome. These are things like SIBO, even visceral abdominal wall pain. So these functional gastro issues make up close to about 50 to 60% of all outpatient GI visits, and frankly, we don't have adequate tools to manage these issues. And then second is personalized care. Diet is a big, big thing in GI. As of now, we have standard dietary protocols like the low-FODMAP diet. But what we know, and this is something I've learned from your podcast, is not every food is good for every person. So we need personalized dietary recommendations, and in the world of GI now, that's an area that's extremely lacking.

Momo: Also, Mike, I've heard that the low-FODMAP diet is not really sustainable. What do you have to say about that?

Dr. Michael Bass: That's 100% correct. I think the standard practice is to basically print out a four- or five-page handout for a patient, giving them a list of all these foods that are low in FODMAP, and then have them try to follow it themselves. But that diet is so exclusionary that nobody can follow it. And in general, there's a lot of misconceptions in how to utilize the low-FODMAP diet. Some people think that they have to stay on the low-FODMAP diet for the rest of their life, and that's not really protocol. But to answer your question, Momo, it's extremely difficult to follow the low-FODMAP diet.

Guru: Yeah. And also, Mike, you've told us on various occasions that the treatment protocols are quite, I would call it, hit or miss. You take a guess as to what might be going on and you try a few protocols, and then if it doesn't work, you switch, and sometimes it may take multiple tries before you can get it right. So how did we end up over there?

Dr. Michael Bass: Yeah. Well, it really goes back to the fact that there's no really objective test as of now that tells us, with these functional gastro issues like IBS-D. As of now, there's no standard test that indicates whether you have IBS-D. So it's more based on clinical symptoms, history, and then basic tests that rule out structural issues if indicated. But even if we come to the conclusion that a patient truly does have a functional issue, there's no test that actually breaks it down and says what the actual pathway is. What's the issue with somebody who has IBS-C? And so if we don't know what the actual pathway issue is, then there's not a lot of guidance in terms of what medication we start first. So often it is trial and error. For a patient who has IBS-C, we might start them on Linzess first line, but there's no guidance, there's no rationale as to why you would start somebody on this medicine, Linzess, versus Amitiza. It's all trial and error. And so if we start somebody on Linzess and it doesn't work, or they have side-effect profiles, they follow up and see us in three to six months and they say that med's not working, so then we'll give them something else and basically pray that it works. But there's no objective data points right now in GI that help tailor personalized treatment.

Guru: Yeah, Mike, speaking of objective tests, that's the whole central point about this episode, that we now actually do have an objective test in the market, and that's called the Viome Gut Health Pro. In one of the previous episodes, we had just mentioned that it was launched just a few weeks ago. But I would like to dive into the details of this test and have you explain to us what this test can do for gastroenterologists, how it's useful, how it can be incorporated into standard clinical workflows, what the utility is at each step, different kinds of scenarios, so we can actually make this test available to most patients out there through their doctors. So let me just share with you this picture that I'd previously shown to our audience about our Gut Health Pro test. It's something that is considered today a very advanced gut health test. In fact, it is the most advanced gut health test that I know of, because first of all, it has the most advanced underlying molecular technology, which is RNA technology, which we'll talk about in just a minute. And it has a number of molecular AI algorithms that are working for it. But even more importantly, I think this is looking at a very comprehensive view of your gut. It is looking across many different diseases. It's looking across many, many pathways. It's looking at multiple different activities of the gut microbiome, and it is surfacing only those that should give a lot of clues to a doctor and to the patient about what to do. So this test, which we are going to go into in detail, is based on a technology that we've talked about quite a lot, Momo and I, which is metatranscriptomics. So Momo, do you want to explain and refresh people on what this is, and then we'll get back to Mike?

Momo: Yeah, let's refresh people on DNA versus RNA. The vast majority of tests out there are looking at DNA, some analysis of DNA. And DNA, I want everyone to think about as: what is your risk at birth for a disease? So this person here, this is a Crohn's patient, this is their small intestine, and their risk at birth may have been high or low. It doesn't really matter. What is happening today can vary from month to month. On the left side, what we're showing is the small intestine of the patient in remission. So they're healthy and they have a normal life, they can do anything they want, they basically have no symptoms. But just a few weeks later they enter a flare, and the result of that is the inflammation that you can see on the right in the middle picture. So now their life is turned upside down. They basically cannot do the things that they want to do, and they're in pain 24 hours a day. There's a structural change here, but there really isn't any molecular change that anyone can observe with DNA, because if you analyze the DNA of this intestine one month apart, you're going to get the exact same sequence back. It's the DNA of the person that they were born with. But if you look at the RNA of that intestine a month apart, you can see a black-and-white difference, in this case a blue-and-red difference, that's shown on the right graph. So this is not something that we have discovered. This is known to the world, that the gene expression profile is the one that determines whether a tissue is going to be diseased or healthy. It's not really the DNA. DNA plays a very minor role. So this is basically the explanation of why RNA analysis is so much more relevant to a disease state than DNA analysis.

Guru: Yeah. And the other interesting and super important point here is that it can be modulated. It can be modulated through diet and lifestyle. The gut microbiome, which is a big part of what happens in your overall health and disease state in your gut, is modifiable. You can actually improve the expression levels by feeding it the right stuff, or you can even populate it with more probiotics and other forms through food, so that you can increase the population of healthy commensal, useful bacteria. Over time, you can actually convert a potentially inflamed or not-so-healthy gut into a healthy gut if you have the right diet and lifestyle.

Momo: Yeah. I really want to elaborate on that a little bit, because people may not be familiar with how you can modulate the microbiome. The microbiome basically is alive because you feed it. It doesn't really survive on thin air or nitrogen from the atmosphere. It literally feeds on the foods that you consume. Depending on what you consume, you're going to feed certain members of the microbiome, and they're going to be producing certain chemicals or metabolites that are going to then affect our own tissues. And the example that I think everyone gets is, when you're making beer, you're actually doing this. You're modulating the microbiome. In this case, you have only one species. It's Saccharomyces cerevisiae, the brewer's yeast, and you're supplying it with food, which is malted barley, and it produces ethanol for you and some other flavors. The more barley you add, the more ethanol it will make. So if you want to modulate how much ethanol your yeast makes, you modulate the amount of material you feed it. That's exactly the principle of our approach, except that the complexity here is such that an average person will have about 1,200 species of microbes, and each species has many, many metabolic possibilities. Which ones are actually active and which ones are associated with disease is what we're going to now discuss.

Guru: Exactly. And so this DNA versus RNA difference, I think, is very, very critical in deciding why a test can be objective. And it's not just us saying it. It turns out that there was an international panel that got together and came up with a guidance statement. When you look at all of the points they make in that guidance statement, this is, by the way, in The Lancet Gastroenterology & Hepatology, you'll see that all of those statements are prohibiting or discouraging the use of DNA-based tests like metagenomics tests for microbiome analysis. So when somebody comes in and says, "Hey, we use shotgun metagenomics," it sort of sounds fancy, but at the end of the day it's doing DNA analysis of your microbiome. That is only telling you what is the static content, potentially, of your microbiome, but it's not telling you what's actually going on in there. Whereas what we need to do is a functional assessment. And the functional assessment can only happen when you know what the current activity of your microbiome is. So one of the major points that this consortium made is that it should be a validated functional measurement in order for it to be useful. And then it says, over and over, like statement 20 over here, function should be prioritized over just inference. Measurement of the function should be prioritized over the inference of function. It also says you need to have functional reference ranges, you need to have disease-specific evidence, and you need to have high quality and reporting from your laboratory processes. All of the statements and the criteria that they put forward in this particular consensus statement, I would say, have been met by Viome. In fact, the Viome test is the only one that meets all these criteria. There's no other commercially available test that meets all these criteria. Mike, do you take this Gastroenterology & Hepatology statement seriously, and how widespread is this in the gastro community?

Dr. Michael Bass: Definitely. Just to start it off, most GI doctors now currently do not use stool microbiome testing, because most of the prior tests are based on metagenomics, which tells you the presence of certain strains but doesn't tell you actual function. And the big, big point there is that different bacteria can have different functions in different people. So there's not one universal, and Guru, tell me if I'm wrong, but there's not one universal bad gut bacteria. That same bacteria in one person can be good; that bacteria in somebody else could be bad.

Momo: Oh, and Mike, the same bacterium in the same person with different micronutrients can turn from bad to good or good to bad.

Dr. Michael Bass: Right. Okay. So it's about the environment that that bacteria's in. It's not necessarily about the bacteria.

Momo: Exactly. Going back to the example of yeast and ethanol, if we establish that there is just the right amount of ethanol to keep a person healthy, you want to feed that yeast just the right amount of barley, let's say an Enjoy food. If you feed too much barley to the yeast, it'll overproduce ethanol, and now that's harmful. If you underfeed it, it'll produce too little, and that's not healthy because it's needed. And that's how you modulate basically what is the metabolic output of your microbiome using micronutrients. So that's basically the whole platform of Viome: we can make most people's microbiome healthy by tuning their functions.

Dr. Michael Bass: Yeah. And that makes perfect sense to me, because with a lot of the standard tests that have been used, and I'm not going to name names, basically we'll have patients come in with a laundry list of different bacteria that are 15 pages long, and honestly, we don't know what to do. Just because something's positive, there's no management change, so it's not actionable. So one of the reasons why I love Viome's test is that it just doesn't give you this laundry list of different bugs. It tells you this is the problem, this is the function, and this is what you do about that function. So this tracks definitely with what I'm seeing in practice.

Momo: Guru, you have some slides on what GH Pro... Yeah, there we go.

Guru: So that was actually a perfect segue into the slide, what Mike said. When you take the Gut Health Pro test, it assesses many areas of functional health, and specifically seven areas that I've mentioned over here. We could dive into the details of this, but each of these areas is clearly important to your health and potentially to illness in your gut. Any given functional health area, for example, I'm just going to pick one, gas production. It could have multiple pathways that impact gas production. You can have methane gas, you can have sulfide gas, you can have ammonia gas. We talked about this in an entire episode. If you've listened to one of our earlier episodes, we talked about what those pathways really mean, and how our lab process, which Momo explained in yet another episode, leads into the assessment of specific pathways. So if you're interested in exactly how we do that, please go back and look at our previous episode on the topic of gas production. But that set of pathways is then aggregated into a gas production functional health score that can then be used for assessment of what we should do. Is it nutritional interventions? Is it potentially pharmacological intervention in some cases? Is it some lifestyle changes? It could be various sets of things that we can recommend. Besides gas production, I also want to pick gut lining health as another super important thing, as we have talked about in some episodes. You have a barrier between your gut, which is an anaerobic environment, and your blood. You don't want any kinds of molecules going back and forth between those two environments. If something like that happens, for example if TMA, which is a trimethylamine molecule, moves from your gut to the blood, that's not good, because it can get converted into TMAO, and that can lead to atherosclerosis. And the other way around is also true. If things come from the blood into the gut, that can lead to oxidative stress, because as I said before, the gut is an anaerobic environment. You don't want oxygen coming into the gut either. So you want to first assess gut lining health and then decide whether there are ways in which you can actually control that. It turns out there are many ways of handling that, both through nutrition, through supplements, and so forth. So each one of these areas can give us insights into how to manage it. I want to go to the next slide, where we have a little more information. Actually, I'm going to go to this slide first.

Momo: Hold on just a second. Hey Guru, I want to say something here. I think that many gastroenterologists have maybe heard from their colleagues saying, "Oh, they're talking about leaky gut, this sort of mythical phenomenon that doesn't exist." That used to be the case 10 years ago. Now there are absolutely premier scientific publications showing not only that leaky gut is a real thing, but that it's actually involved in many, many different pathologies and many different diseases. So don't just dismiss gut lining health as, "Oh, that's leaky gut." There's now a very solid publication literature on that. So please take it seriously, because it is very important for your patients.

Guru: Yeah. And also, Momo, along the same lines, there are quite a few good studies now that are showing the impact of food and supplements on leaky gut as well. So we can start to look at what kinds of interventions are possible and how to use that in daily life. The point I wanted to make was that these pathways we are talking about all are associated with various disease states. We've talked about IBS constipation and IBS diarrhea. Those are disease states, and there are specific pathways for gas production, for example methane. We know that methane contributes to IBS constipation. Gut lining health: there are pathways underneath gut lining health, for inflammatory pathways, for mucin degradation, and so forth. Those kinds of pathways are associated with non-alcoholic fatty liver disease, type 2 diabetes, multiple such diseases. So it turns out that this Gut Health Pro test focuses on six diseases and gives you a specific disease risk score for these common GI-related diseases: IBS constipation, IBS diarrhea, inflammatory bowel disease (which we showed a picture of earlier), non-alcoholic fatty liver disease, type 2 diabetes, and depression. So Mike, I want to go back to you and first ask you: is this set of diseases what you would consider to be common GI-related diseases, and what you would normally look for in your patients, and how you want to go ahead and treat those?

Dr. Michael Bass: Definitely. So these six, the reason why we chose these six is because they reflect several domains that frequently overlap in clinical practice. The way I view it, there's basically five different areas. One is functional and motility issues. Two is inflammatory processes. Three is the gut-liver biology. Four is metabolic health. And five is that gut-brain axis. So all six of these fall within those five broader subtypes. It's common patterns that we see in clinical practice, and all of them are linked.

Guru: Yeah. And so in this picture, what you see is a clinician report on the right-hand side, which says that this particular patient has a high risk for IBS type C, that's constipation, and fatty liver disease. And there's an expanded view of IBS type C where it says, you can see that this risk is 6.04. That's on a scale of zero to 10. Anything that is more than five is flagged as a high risk. And that is essentially the cumulative odds for a person to have that disease, IBS type C, given that the pathways associated with that disease are not in an optimal state relative to a reference population.

Momo: Can I put that in the perspective of, for example, Alzheimer's? People say if you're homozygous, so you carry two genes for APOE4, you have the highest risk of Alzheimer's. That's about an eightfold higher chance of Alzheimer's. And here we have a range of five to 10, so that's a ballpark very high risk, right?

Guru: Yep, exactly. We actually published the data behind all this risk assessment and showed exactly how the odds ratios are calculated and how it is aggregated for a given disease. And we did that analysis in an independent validation cohort of more than 15,000 people. So this is a very large cohort and we validated this data in this very large cohort. This is not just from a small study or a low-powered study. This is a really large population compared to a reference population of more than 20,000 people. So it should definitely be taken very seriously. So Mike, I would ask you, how would you look at the pathways, the clinical notes next to it, and the nutritional recommendations that come right next to that?

Dr. Michael Bass: Yeah. So for IBS-C, this is a common patient that we see in practice. Basically the patient's going to have difficulty going to the bathroom, bloating, abdominal pain, and they've had all of the standard tests, standard workup, that rule out structural problems like cancer. So now we have this patient that's labeled as IBS-C based on clinical history and other tests that have ruled out other structural processes. So what do you do with that IBS-C patient? If we don't have this info, it really is a trial-and-error process. Maybe we tell them to increase fiber, tell them to increase fluids, maybe start them on some stimulant laxatives. But without this detailed pathway info, we don't know if any of that's going to actually work. So what this test does, just looking at this pathway breakdown, as you see on the very bottom, that methane gas pathway is off. So what that tells me is there's either two things. One, there's some issue with gut transit. If stool sits inside the colon for an extended period of time, all the bacteria inside the colon act upon that stool and increase the amount of methane gas. Or you can have by itself an overgrowth of just methanogenic bacteria. So it's kind of like the chicken-or-egg problem. But based on this pathway, I would focus on the methane aspect of it. So I would want to work on transit, either starting them on medications that actually help transit, like MiraLAX, Linzess, Amitiza, and then use those dietary recommendations there to formulate a more tailored dietary approach. In your standard patient who has constipation, you might tell them to increase the amount of fiber. The problem with this case is that if you increase the amount of fiber, you might actually make it worse, because fiber creates more methane. So many patients, when we tell them to just increase the amount of fiber, they actually get worse, but we don't really know that mechanism, why. So with a breakdown like this, I would see that that methane pathway was off, I would not tell them to have more fiber, I would follow those dietary recommendations, and I would start them on a medication that helped the gut move.

Guru: Exactly. So what is interesting to me over here is that somebody might think that IBS constipation is one monolithic thing, but it's actually potentially multiple pathways that could be wrong with it. It's like the same symptom, constipation, but you might end up having multiple potential root causes. It could be the methane that you were talking about, Mike, or it could be sulfide production going the wrong direction. It could be bile acid, secondary bile acids. It could be short-chain fatty acid, could be serotonin, it could be any one of these pathways. And depending on which pathways are not going in the right direction for a given individual, we can take the right actions, as Mike was describing.

Momo: Have we talked about pathways yet? Have we defined those?

Guru: Well, we had a whole episode on pathways, but we should probably take a moment to reintroduce those. So Momo, go ahead.

Momo: Oh, well, the example I gave earlier with brewer's yeast making ethanol from malted barley, that's basically a pathway. What it is, is a series of biochemical reactions that converts a micronutrient from our food into a chemical or metabolite that may have a physiological function in humans, such as lipopolysaccharide, TMA that you mentioned earlier, butyrate, hundreds of these compounds. So that's basically a pathway.

Guru: Exactly. And you see over here in this particular picture, we are showing these five specific pathways that are associated with constipation, and any one or more of those pathways can be out of balance. That may be the reason why you have constipation. And when you know which of these pathways are not doing well, you can focus your intervention and your treatment plan on those pathways specifically.

Momo: And to make things more complicated, even within each one of those pathways, the intervention in different people will be different.

Guru: Oh boy. Okay.

Momo: So basically the level of data and the level of complexity of this biology cannot be just tuned down to a protocol that traditional physicians think of, if A then B. There's just too many inputs, too many combinations, that the only way to really interpret this is to take this kind of a test and really follow the guidelines as computed, and not as interpreted by a human.

Guru: That brings me to the AI point that I was going to make, which is that the number of data points we have here, it's in the tens of thousands, to say the least, for the recommendations. The actual number of data points that we look for in the Viome test is in the millions. And so we whittle that down to clusters of molecular functions that are relevant to biology, specific pathway biologies, and we bring it down to the point where it can be understood, interpreted, and then you can take an action on it. That's why we have pathways in the order of more like a hundred, instead of just giving you the millions of data points straight out of the lab. So Viome's AI, which we are showing here on the right-hand side, takes the thousands and thousands of biological functions and maps them against the micronutrients and hundreds of different health conditions and comes up with a precise nutritional plan. The way it does it, and we've talked about this in one of the previous episodes, but just to recap: we have a food database already in Viome right now, so we know the specific macro- and micronutrients for each one of the foods in our food database. The macronutrients first go through a glycemic response prediction step, which we also talked about in a previous episode, all the details behind it, the paper, the science, the study, the population. If you're interested in that, please listen to that episode with an endocrinologist, Dr. Damon Tanton. That was the previous episode. And based on the glycemic response prediction, each food goes into either an Enjoy bucket or a Minimize bucket. Then, based on the micronutrients, we look at all of these pathways we were talking about earlier, whether it's a methane pathway, the butyrate pathway, the oxalate pathway, and so on. We then fine-tune the Enjoy and Minimize foods. We could potentially take an Enjoy food and promote it, if it's going to help your pathway, to a Superfood, or we can demote it to an Avoid food if it does not help your microbiome. So in this case, I'm showing the example of someone whose spinach was in the Enjoy food category after coming out of the glycemic response prediction. But if their oxalate elimination pathway is not very good, meaning that elimination is low, then that can drop down to an Avoid food like you see on the right-hand side over here. And if it's good, meaning the elimination is high, it is in the Superfood category. The reason why oxalate is important, and we've mentioned this in some other episodes, is that it can lead to kidney stones. So if you eat too much spinach when your oxalate is not being eliminated in your pathway, that could lead to kidney stones. That's the reason why this logic works this way. But every pathway has a similar logic for different micronutrients in the many foods that are in our database. We go through that analysis one by one and we decide to put each food either in your Superfoods, Avoid foods, Enjoy foods, or Minimize foods. That's what you see in the Viome app. And that's kind of the starting point. You can also turn some of those into supplements, into probiotics, into prebiotics, and that can augment your basic food and nutritional habits. So that's how we end up with the food recommendations in the Viome app. And finally, you may ask the question, "Okay, that's great that you're doing all that stuff. Does it really work?" So we've done a bunch of randomized, placebo-controlled trials, and Momo, you should probably explain each one of these things, please.

Momo: Yeah. I'll just highlight, these are all decentralized, randomized, placebo-controlled clinical trials run in the United States, mostly in adults. We have three boxes here for three separate trials. The one on the left, we enrolled patients with IBS. And you can see here, in the subgroup analysis of patients who had IBS constipation at baseline, 67% of them transitioned from constipation to healthy in three months with our personalized nutrition, and only 9% transitioned from constipation to healthy in the placebo group. And that's very statistically and clinically significant. In the middle box, we're talking about reducing anxiety. We ran a mental health trial in adults, again, and we were able to transition 50% of the people who had anxiety at baseline back to healthy in three months, versus 28% in the placebo group, and that's a statistically significant result. Last but not least, we were also able to reduce HbA1c, the major biomarker of prediabetes and diabetes, using our intervention. This is obviously based on this glycemic model that Guru just described, where we were able to reduce HbA1c in a clinically meaningful amount and statistically significantly in three months, by 0.28%, in mostly pre-diabetic people, so early onset.

Guru: And that's harder to do compared to diabetic people.

Momo: Much harder. Yeah.

Dr. Michael Bass: Yeah, Momo, these numbers to me, definitely with the IBS group, it's shocking, because I can tell you, in private practice we do not make 70% of the people better with the things we do.

Momo: Yeah, we are about to publish this paper, so it'll be really important to publish this and share it with the gastroenterology community.

Guru: Awesome.

Momo: I have a question for Dr. Bass.

Guru: Go for it.

Momo: So given what we just discussed, and speaking directly to another gastroenterologist, how would you recommend that a gastroenterologist uses the GH Pro: the timing, the conditions, the management of nutrition, follow-up, things like that? Can you paint a realistic picture?

Dr. Michael Bass: We have to look at the use case. If there's a patient that's coming into a GI practice office, that patient isn't coming in here for prevention or to optimize health. They have a specific clinical question or a clinical issue that they want answered. So the first thing is to just identify what is the actual clinical problem. Is it constipation? Is it bloating? Is it pain? Is it IBS-D? So that's problem number one. But then two, in a standard GI practice, we're seeing maybe 15, 17 patients per day, so we only have a limited amount of time. And that's the one thing I actually love about GH Pro, because there's six things. It's lean, and it basically covers the vast majority of things we will see in a standard GI practice. So the first step is to just find what is that clinical problem that you're trying to treat. Order the test, you'll get insights, you'll find these pathway breakdowns, and based on those pathway breakdowns, that's going to help guide treatment for you, likely. Or it might move you into ordering further tests that would give you the standard confirmation that a patient has a certain issue or not. Say, for type 2 diabetes: if that DRS score is high, it's not that as the GI doctor we don't manage that, but we would recommend following up with their primary care doctor, just getting a standard hemoglobin A1C. We can even order that, but it just helps triage patients into that right bucket. So it's treatment management tailored to the actual right choice of treatment, as opposed to this trial-and-error process where we just throw everything at the wall and see what sticks, and figure out where do we triage the patient after that.

Momo: Okay. But I'm also thinking, Dr. Bass, that there's an opportunity here, because a lot of people come for screening colonoscopies starting at the age of 45, and they may not present with any symptoms, but I think it's an opportunity for them to do the gut test and see what they're at risk for, whether they have polyps or not. What do you think?

Dr. Michael Bass: No, I 100% agree with you. In a perfect world, frankly, I think everybody should be getting Gut Health Pro, or even pH Pro. In a perfect world, it's great to have a baseline. We're seeing more and more data right now about how changes in the gut microbiome can increase your risk of having polyps. So I would definitely, if that's possible, recommend that just as a standard baseline. But if you look in the typical GI practice, again, volume of patients is extremely high, time is limited. It might not necessarily be the best setting to get a standard practice test.

Momo: But let's think about the actual logistics. Let's say, through the process of a patient scheduling a screening colonoscopy until they get the results, where would the physician have the opportunity to encourage the patient to order the GH Pro, or to request it so that the physician can order it?

Dr. Michael Bass: Yeah. Well, it depends. Because if it's just a standard screening colonoscopy, a lot of the cases are actually booked straight to the surgical center, so the doctor might not necessarily meet the patient until the day of the actual test. So I think that seems to be a relatively easy prompt to solve: when that patient's calling in just to make a standard screening colonoscopy, then they would just automatically be set up for a GH Pro test. That test would then just be mailed to them, they would give the sample at home, and then they would mail it in. The other option is that if the patient's seeing the doctor prior to that screening colonoscopy, then the doctor would just order that GH Pro at the time of that visit, and then they would do the test at home and mail it in. Frankly, I think in a screening colonoscopy there's plenty of opportunities to actually obtain stool samples. It's very, very rare that when we're doing this screening colonoscopy there's no stool. So if the patient's sleeping, and if there's stool there and they can send that, I mean, is there an opportunity to get stool at that point?

Momo: No. Unfortunately, no, because the microbiome is going to be severely disturbed with the colon prep. However, the good news is that what you described is everything prior to the colon prep. The patient can receive the kit and collect a sample, or all they have to do is wait one week post-colonoscopy. We just published one of the latest Viome papers. We show that the microbiome completely restores after a week post-colonoscopy. So the GH Pro can actually be ordered while delivering the results of the colonoscopy, and by the time the patient receives it, it's going to be basically a week.

Dr. Michael Bass: Wow, that's great. That's awesome.

Guru: Yeah. And I want to mention that we keep adding more and more disease screening capabilities into GH Pro over time, as we collect more data, analyze more data, and are able to get the right type of validation evidence for each disease area. Like Momo mentioned, colon polyps would be an addition to Gut Health Pro in the near future, so you can get an indication of whether you have colon polyps, what level it is, and so on and so forth. And over time, I can see us getting into colon cancer, early detection of colon cancer as well, which we know that the signal already exists in the stool, because we've done multiple internal studies in which we've already seen the signal. There's also very significant evidence of connection of all the systemic different processes in your body to the gut. So people talk about the gut-brain axis, which means we already talked about depression and anxiety, but we could also go a step further. We could go into dementia, we can go into mild cognitive impairment, into all of these other areas over time. We can also talk about the liver, the gut-liver connection. We can talk about the gut-heart connection. So the entire systemic health profile of an individual, from the gut as the central body that interacts with and in many cases regulates the disease and health processes, can become part of the Gut Health Pro test. That's one of the things that we are working towards at Viome. We call it the multi-disease early detection test. That's kind of the concept for having a range of different diseases that we can detect through a gut test.

Momo: Yeah, that's a really... oh, go ahead, Mike.

Dr. Michael Bass: Well, I just wanted to double-click on the entire colon polyp aspect of it. As of now, we prevent colon cancer by doing a scope and then removing that polyp. But what if we can shift it upstream, before that polyp forms in the first place? That's where I see the power of, eventually, at some point, the power of Gut Health Pro. If we start seeing shifts in that microbiome that might indicate the patient's at risk for forming polyps, we can make dietary recommendations and we could possibly decrease that chance of them forming polyps in the first place. To me, that's an incredibly exciting pathway for GI.

Momo: Yeah. I want to highlight and summarize what Guru said, which is: treat this test as a dynamic test. It's not like it's done and it will always be static, like most other tests are. It's going to evolve as the science evolves, and physicians can actually influence what direction it's going to move into. Because if there's a physician that presents a very solid case as to why the condition they're interested in is important and tied to the microbiome, we may study it, and even physicians can work with us to actually create a study so that we can learn from it and then incorporate it into the product. So this is really a platform. It's not really like a fixed test for one marker and that's all you'll ever get. It's really a platform to serve the gastroenterology community for basically years and decades. So think of it that way.

Guru: That's a great way to end the episode, Momo. It's kind of an invitation to work with us, both at the practice level day-to-day, as well as at the research level, strategically, over time. So thank you very much, Mike, for joining us for this conversation. I'm sure we'll have you back here to talk about things that we are learning from the Gut Health Pro in the field in the future. But thank you so much for joining us for the last hour.

Dr. Michael Bass: Thank you. Awesome.

Momo: Thank you, Dr. Bass.

Dr. Michael Bass: Thank you, Momo.

Guru: Yeah, that was great to have Mike on the pod. I think we learned a lot of things about how gastroenterologists behave. I think we hope to change the practice of gastroenterology by focusing more on the functional elements, not just on the structural elements, like we've been talking about. And of course, in a few months we will get somebody from the gastroenterology community back on our show, so we can talk about how things have changed in that community, because we are going to be implementing the Gut Health Pro test in multiple gastroenterology practices.

Momo: Yep. Amazing. I love the episode, and really, the next quantum leap in gastroenterology, enabling physicians to really look under the hood and identify all the molecular reasons, and then, as we discussed, actually modulate the microbial functions and human physiology using micronutrients. That's really the holy grail, that you can prescribe people diet and change their physiology. Okay, so Guru, the bimonthly challenge. Let's remind the audience that all they have to do is post questions on any one of our episodes, and we will consider those questions, answer them, of course, and we'll consider them for our monthly challenge, for which the reward is the Full Body Intelligence kit. So what's in the next episodes, Guru?

Guru: Yeah. Well, first of all, for our audience members, I want to say, don't be shy. If you have a question in your head, just go ahead and post it in the YouTube channel and we will definitely take a look. We will answer you, perhaps on one of the next episodes. And if your question is really great and will help a lot of people, then you might end up getting a free Full Body Intelligence, as Momo said. So looking ahead, I mentioned last time that we have a number of really great leaders in the community joining us as guests. We had an investment leader, Vinod Khosla. We just had a gastroenterology leader. We are going to continue to have biology leaders, scientific leaders, business leaders who are very much in the field of longevity and preventive medicine. And we are going to try and get interesting conversations going that will engage and educate everybody in this audience. So that's what is coming up in the summer.

Momo: So excited. All right, thank you, Guru, so much. I am Momo, a biochemist.

Guru: And I'm Guru, an AI scientist, and we're two PhDs on a pod.