Imagine taking your car in because the engine is sputtering, and the mechanic walks around the outside, tells you there are no dents, and hands back your keys.
That's the picture Guru opens with this week, and it's a surprisingly accurate one for how a lot of gut care still works. Traditional testing is very good at spotting the structural stuff, a polyp or a blockage, but the everyday bloating, pain, and irregularity that send most people to a GI office in the first place don't leave a dent anyone can see. In this conversation with gastroenterologist Dr. Michael Bass, Momo and Guru get into what actually changes when you can look under the hood, meaning the microbial activity in your gut, not just a static list of which bacteria are living there. The through-line worth holding onto: the same microbe can behave one way in one person and another way in someone else, depending on what you feed it, so wellness is less about hunting for a "bad" bug and more about tuning what the microbes you already have are producing. That's the whole reason your food list looks the way it does, and it's why the science of pathways, gene expression, and metabolites keeps coming back to something you can actually do at the dinner table.
Here's the full conversation.
The full conversation
Guru: Let's get started. Hey, Momo.
Momo: Hey, Guru.
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.
