Episode 100: Gut Microbiome testing and analysis using AI with Leo Grady and Jaclyn Kawwas

Adam Rinde, ND: [00:00:00] Hello, everybody. This is Dr. Adam Rinde. I'm the host of the one thing podcast. Welcome to episode number 100. We are so excited to make it to episode number 100. Thanks to all of you for being loyal listeners and helping support the podcast that launched in 2019. It's very exciting to be here. And this episode is especially interesting for me.

Adam Rinde, ND: And hopefully for you, we welcome on Leo Grady and Jaclyn Kawwas. Leo is the CEO of Jona and Jaclyn Kawwas heads up business development for Jona . And Jona is doing a very interesting thing. They're taking AI and applying it towards the study of the gut microbiome. They have a direct to consumer company that uses stool analysis and studying the microbiome within various stool samples and cross referencing it with the latest evidence through AI [00:01:00] technology and applying the research to recommendations to help with health issues.

Adam Rinde, ND: We dove deeply into this topic and understanding how AI interfaces with these gut microbiome applications. And we discussed some various factors that are involved with gut microbiome health. We studied the trajectory of stool analysis, where it started, where it is today and where it's headed. We looked at various components of stool testing, such as metabolomics and microbiome testing Really, it was fascinating to learn how deeply this company is applying evidence towards their work.

Adam Rinde, ND: They are not making any sweeping claims. They're really growing with the research. It's fascinating to know that over 2, 000 studies come out per month on the microbiome, and no one in their right mind could keep up with the research as it's being turned out. This technology really helps with making sure [00:02:00] that we're applying The latest evidence towards our interpretation of microbiome analytics and microbiome testing.

Adam Rinde, ND: So I think you'll enjoy this discussion as much as I did. And please share this with anybody who is really looking to. Understand how to study the microbiome and use microbiome data to improve their health. So without further ado, I welcome you to episode 100 of the One Thing podcast.

Adam Rinde, ND: This is The One Thing podcast, and I'm your host, Dr. Adam Rindi. The One Thing Podcast brings together leaders in functional and naturopathic medicine. To discuss actionable information that may unlock puzzles in the areas of gut health, brain health, metabolism, and longevity, please note these episodes do not replace the opinion of your doctor.

Adam Rinde, ND: They are not intended to diagnose or treat any condition. Please discuss this information with your [00:03:00] provider and discuss your own unique personal health history before adapting this information. Please subscribe to our episodes so that you can stay on top of the most current information in these areas of medicine.

Adam Rinde, ND: Jaclyn and Leo, welcome to the one thing podcast. It's great to have you on here today.

Leo Grady: Thanks Adam.

Jaclyn Kawwas: Thanks for having us.

Adam Rinde, ND: You're welcome. It's great getting to know you a little bit before we discuss today's topic and just getting into our conversation. And I think, it'd be great place to start is just to hear about Jona and the company's mission and kind of what you're out to accomplish with the people you're serving. And just hear a little bit background on Jona.

Leo Grady: Sure.

Leo Grady: So I'm Leo. I founded the company about 18 months ago. My background before Jona was in AI. So I did my PhD in AI 20 years ago, spent my career in more conventional medicine, building AI and radiology, cardiology and pathology was on the investor side for a bit and then founded Jona. And the reason [00:04:00] for founding Jona is because the microbiome is so integral to your health. The science has been really exciting showing that the microbiome has been connected to every GI disorder, autoimmune condition, metabolic disease, obesity, liver disease, but also cancer.

Leo Grady: And Parkinson's disease and Alzheimer's and depression, anxiety all have been linked with the microbiome. And yet it feels like there's so much science and there's so much complexity here that the only way we're really going to make sense of it all and, and really be able to take advantage of the microbiome is by using a technology like AI to decode what's going on in the microbiome and really chart a path for not only analyzing where you are today, but where you want to be and how to get you there. On a personal level, I've had a number of members of my family with a variety of different GI disorders. My ex wife has Crohn's disease. My sister's got colitis. My cousin has celiac, my [00:05:00] son has undefined GI issues, and so I've really seen their journey and their struggle with trying to understand what was going on in their health, and all these roads always point back to the microbiome as a missing piece and trying to understand it, and even though they've gotten great care over the years, it often takes a long time to get a diagnosis, and then even with a diagnosis, Trying to understand a personalized guidance on what you can eat, what choices you can make to help you manage your symptoms and feel better can be very difficult.

Adam Rinde, ND: Very interesting. Just hearing your background, it makes me think like the early days of radiology to where you took radiology. It seems like the study of the Microbiome or even study of the digestive tract, track through like stool samples may parallel a similar track that it's headed. Is that fair to say?

Leo Grady: Yeah, I think so. If you think about the early days of radiology, it was really x ray and x ray was phenomenal when it was developed, but it was limited in what you could see. You [00:06:00] couldn't see in three dimensions. You couldn't see soft tissue. You couldn't really understand what was going on in a person's body.

Leo Grady: And so it was only through the development of, computed tomography, CT, CAT scans, MRI, and then all the different forms of these with contrast agents and different pulse sequences that we're really able to interrogate. the body. And I think you're right about the parallel with radiology because people do talk about the microbiome and say it's a new organ, right?

Leo Grady: And, but if it's a new organ, it's really not an organ like a kidney or a heart or something that you can image with an MRI. It's effectively an organ of data. And so one of the things that we talk about at Jona is how do we build the MRI of this new organ? to really be able to understand it from multiple different angles, understand what's wrong with it, and then ultimately how we can fix it.

Adam Rinde, ND: Yeah, I think one of the intimidating aspect of the microbiome versus, something like static, like a physical structure in the [00:07:00] body, say Looking at a shoulder joint or looking at a bone, it seems intimidating for even scientists about the fact that the microbiome is like a moving target in a lot of ways.

Adam Rinde, ND: Is that how you see it?

Leo Grady: I think you can look at it from the standpoint of being intimidated by the challenge of dealing with it. I think there's another way of looking at it too, which is there's an opportunity to change it. So the fact that it can change means that if we really understand how to change it, that there are real opportunities to fix it and to address somebody's health.

Leo Grady: I think that's one of the things that's so exciting about the microbiome for me. You look at fecal transplants and sometimes they can actually cure somebody's disease, like a chronic condition. Other times they don't have any effect. Other times they People have gotten really sick or even died through fecal transplants.

Leo Grady: And what that tells me is that this is very powerful stuff, but we don't understand it. And I think by really being able to analyze what's going on in the microbiome, [00:08:00] understand what's wrong, know where we want to bring it to, and then how to get it from here to there, from state A to state B, I think that's going to be extraordinarily powerful in helping address these issues disease in a way that's done safely.

Adam Rinde, ND: Yeah, so for people who, looking back at the origins of stool testing and to where we are today and where we're going, like comparing stool cultures to even the early days of microbiome testing can you walk us through that continuum and where that's headed?

Adam Rinde, ND: Is it the old days seem rather archaic, but yet still, there are still some applications of some of those old lab tests and cultures and those types of things. It's not like we can move on completely from some of those old studies, but can you just walk us through from where we were and where we're going?

Leo Grady: Yeah. So if you think about. The earliest descriptions of the microbiome, they were at the time that the microscope was invented, right? That was the first time someone could visually [00:09:00] see, rods and spheres and all the different types of bacteria and microorganisms. And through culturing and the germ theory and the development of a modern understanding of infectious disease, we started to realize how certain infections were really behind different diseases.

Leo Grady: And then through the invention of antibiotics and widespread application of those, then we were able to cure a lot of diseases that previously had plagued humanity. At the same time, there was a growing recognition that all germs weren't bad, all microbes weren't bad. And again, through the kind of culturing studies that you're talking about, we were able to culture some of these organisms and start to draw connections between these organisms and health.

Leo Grady: And, even whatever, 50 to a hundred years ago, we were People started talking about the clean hypothesis and probiotics and, overuse of antibiotics can actually cause problems. And, there've been a lot of studies on [00:10:00] this. And, but it was very difficult to actually study all these organisms through culturing because your colon is an anaerobic environment.

Leo Grady: And so once you actually pull these organisms out, trying to say them through culturing is very difficult. We don't even know what medium to grow them in. The conditions very different than your colon. So it wasn't really until genomic sequencing became widespread and possible that we could start to understand these organisms without having to keep them alive and feed them.

Leo Grady: And, the initial capability to do that was with the advent of 16S sequencing and bacteria, and that advanced the field quite a bit in the early 2000s, early in the late 2000s, early, 2010s. The challenge there. was that it was still expensive, and it was, limited in its resolution.

Leo Grady: So you could really see the bacteria down to a genus level, rarely a species level, and almost never a strain level. In addition, because 16S is a component of the bacterial DNA, you weren't able [00:11:00] to adequately measure fungus, or protists, or archaea, or viruses, or anything like that with this technique as well.

Leo Grady: Shotgun metagenomic sequencing was developed, around that time, or goes back even earlier, actually, but the costs were prohibitive, and with the continued decrease in cost for sequencing, it's become more and more capable to actually sequence these organisms at scale. We've had better and better databases to match the DNA against.

Leo Grady: And so we really have had a renaissance of our ability to measure all of these organisms, to match their DNA against databases, understand what species, genus, strain they're in, and then to be able to connect that to health outcomes. And, remember the amount of DNA in your microbiome is about a thousand times the DNA in your human cells.

Leo Grady: So there's a lot to sequence there. And so the fact that these costs have come down, the field has matured, we've seen this real flourishing. of studies where [00:12:00] today we have every month, about 2000 papers published on the microbiome and PubMed.

Adam Rinde, ND: 2000. Wow. And growing. No wonder I'm having troubles keeping up.

Adam Rinde, ND: That's amazing.

Jaclyn Kawwas: And you'll see too, Adam, that there's currently right now, there's kind of two sides of the coin for testing and stool testing. You have qPCR and the way I like to describe that is you're going in with a certain set list of organisms. But there's 20 or 30 pathogens that you're really looking for.

Jaclyn Kawwas: And you're saying, is it there, is it not there, and picking it up. With shotgun sequencing, you're going in blind and not having a, a biased list of what you're looking for. You can pick up to hundreds to thousands of different organisms based on what's there. So you get a lot more comprehensive view of what's going on in the gut.

Jaclyn Kawwas: But with that, now you have a longer list. Of organisms to work with and understand. So it adds a little level of complexity if you don't have the proper tools to interpret it.

Adam Rinde, ND: Yeah, that's a great point. Having been on the other end of getting this volume of really cool data and trying to make sense of it.

Adam Rinde, ND: Is a daunting task, especially since, like you said, like 2000 [00:13:00] studies coming out, on a blink of an eye, it's like you could be well behind the eight ball, like within days. So that's a really good point, Jaclyn. So I'd love to hear how you entered this world too. It is really.

Adam Rinde, ND: Fascinating to me to help people get into this profession of, this world of solving complex chronic illness.

Jaclyn Kawwas: Yeah, definitely. So my, I've always been interested in healthcare and preventing and treating disease. It's just been a general interest of mine. I started off my career in biomedical engineering.

Jaclyn Kawwas: So coming at it from the technology approach, I was working at Medtronic for a while, designing cardiovascular devices. So really treating and creating devices for people that have. Heart attacks, hypertension, the whole gamut and really love the building and creating, but wanted to understand, help decide what we build next and get closer to the patient and consumer as well as a provider.

Jaclyn Kawwas: So I pivoted and went to the business route, went to grad school for business and focusing a lot on healthcare as well as software. I felt like software was the future to be able to commercialize quicker, be able to reach a lot more [00:14:00] people faster and make a difference. And so I dabbled in a lot of different health tech and AI startups with the lens of preventing and treating disease.

Jaclyn Kawwas: I joined Jona back in the early days, back in the fall of 22, when Leo was announcing that he was starting his own stealth company and it was provider and consumer facing was health tech AI. And it was centered around like prevention of disease. This is the combination of everything that I was super interested in.

Jaclyn Kawwas: So essentially I reached out to him and said, if he's looking for kind of a MBA intern at the time and Went from there. And since then we really hired a lot more people, full time built the technology, built the product and launched last year. So it's been a lot saying from zero to one, but it's impressive to see how quickly everything came together.

Adam Rinde, ND: That's very cool. Yeah. It's interesting because my early interface with AI in health care really was from this website called Scite.ai and I started uploading sort of notebooks of papers that I don't didn't have time to read and chatting with those papers, basically asking [00:15:00] questions like I'm talking to the author and, I'd say gave me here.

Adam Rinde, ND: This felt like a superpower all of a sudden, knowing, oh, wow, I'm extracting data that's really applicable, but also this uneasiness of I should really be sitting down and reading these papers word for word and struggling through them like I have, throughout my career.

Adam Rinde, ND: And I realized there was like this checks and balances of that approach. And then I learned about you guys and what you're doing. And I was like, wow, hearing about the AI component, because obviously there's been companies that have been looking at the microbiome and giving us these interpretive guides and, trying to make sense of the data, but you're taking it to a different level.

Adam Rinde, ND: And I'd love to discuss the AI component and how that works within this setting.

Leo Grady: Yeah, I'd love to. As we talked about shotgun, my genomics sequencing is great. As Jaclyn mentioned, it's an unbiased look at what's in your gut. So it's not a PCR test. It's not a fixed panel.

Leo Grady: It's really looking at all the bacteria, the fungus, the viruses, everything in your gut down to a strain level. [00:16:00] The challenge is these 2000 papers every month, right? And When you read one of these papers, for example, you look at a paper on obesity. It's not like there's one organism when it's too high or too low is linked with obesity.

Leo Grady: It's a whole ecosystem that's linked with obesity and it's not just obesity. If you look at Parkinson's or cancer or Crohn's disease or colitis or any of these things, IBS, they're all different ecosystem shifts. And so the study is, even the results are complex. And then if you are trying to look for these signatures in somebody's microbiome, it's very difficult to take advantage of all these papers, or different cohorts, different sizes.

Leo Grady: You have to put them all together. And then, as we talked about before, you can actually change the microbiome through diet, lifestyle, supplements, drugs, medications. And as a result, it's You know, each of those interventions is also complex. You go vegan, it shifts your microbiome in a totally different way than if you go keto, or you're carnivore, or you cut out gluten, [00:17:00] or whatever it is.

Leo Grady: And it's not just a simple change. And It's one thing to get the shotgun metagenomics and get all this rich information about a person's microbiome, but how do you leverage all of that science to really understand it, to analyze it, and then to also figure out what to do about it, right? So here's what we built at Jona.

Leo Grady: We built a dedicated AI system that reads all of that literature, matches the patterns in your microbiome to every study that's ever been published, so that we can say for you, your microbiome fits the profile of you. diabetes or depression or cancer or maybe just bloating and fatigue, brain fog, whatever it is.

Leo Grady: And then the AI will cite the studies, tell you how much evidence there is, link you to the studies so you can go read them yourself. But then the AI also reads all the interventional literature, diet, lifestyle, supplements, medications, and applies each one of those changes ecosystem shifts to your microbiome.

Leo Grady: So we basically make a virtual vegan you like a digital twin of your microbiome going [00:18:00] vegan. And then we make another virtual keto you and another gluten free you and a you on metformin or on rapamycin or whatever it is. And based on all of these virtual yous, we can see the different shifts that would happen in your microbiome based on the studies.

Leo Grady: We're not inventing anything, we're just reflecting the literature. We ask you what your health goals are, the health goals of your patient are, and based on those goals, whether it's to reduce bloating or abdominal pain or maybe to lose weight or whatever it is. We help select those, microbiome shifts, those virtual use that are going to help achieve that goal.

Leo Grady: And by doing so, we can not only analyze what's going on today, but then build a custom action plan to help you leverage all of these studies. to take actions that are going to move your microbiome in the right direction.

Adam Rinde, ND: That's great. So you're not just telling people to eat fiber?

Leo Grady: No. And eating fiber is great.

Leo Grady: And don't get me wrong. I think, certainly, studies show that [00:19:00] people don't eat enough fiber. But the fact is, it's not one size fits all. Your microbiome and my microbiome, On average, we only share about 10%. And so the fact is that fiber is going to do something different for you than it is for me, because we're starting from a different place.

Leo Grady: I think the only way that we're going to actually understand where you are and where I am is by looking and then. Whether it's a lot of fiber or fiber plus something else, or maybe something else entirely to help you and me get to where we need to get to, it's not going to be a one size fits all solution.

Adam Rinde, ND: Yeah. I think that's where, what really is missing in this space is those granular customized suggestions. Cause I think, for the last five to seven years, it's just, defaulted that, fiber, and lower saturated fat and avoid all these things. And it's I just spent all this effort to get that information where it's been like the default message, but it's really great to hear that you're creating, these different [00:20:00] models of individualized recommendations.

Adam Rinde, ND: Yeah. I imagine that's only going to get deeper and deeper.

Leo Grady: Yeah, that's right. And I think there's something also that A lot of people, there's a misconception out there, which is that, they're good guys and bad guys and that you always, you want more good guys and you want to get rid of bad guys.

Leo Grady: And, unfortunately it's more complicated than that, right? It's like blood pressure, right? Blood pressure is not good or bad. You don't want it too high. You don't want it too low. You want a certain level. And you wouldn't say everyone should take blood pressure medication to lower their blood pressure.

Leo Grady: without checking what it is in the first place. And Akkermansia muciniphila:

I think is a really good example. Yeah, Akkermansia is being sold as a probiotic. It's certainly the case that there are a number of studies that have linked low Akkermansia to a variety of health problems. At the same time, there are other studies that have linked really high Akkermansia to Parkinson's disease and other issues.

Leo Grady: And so to say that everybody should be getting Akkermansia without knowing where you're starting from is like saying everyone should get Akkermansia be getting blood pressure medication without [00:21:00] measuring somebody's blood pressure.

Jaclyn Kawwas: And to Leo's point, and he mentioned that you and I only overlap a certain, a small percentage of our microbiome.

Jaclyn Kawwas: You've seen a lot of reports now. I've reviewed a lot of reports with different clients and some people might have the same exact symptom. They're both struggling with bloating, but because they have a different microbiome signature or kind of match to that, their recommendations are completely different.

Jaclyn Kawwas: Somebody might be recommended to take a certain vitamin and somebody might be recommended to. Stop being lactose. And it's very dependent on what that person is. We also consider part of your diet right now as well. So for example, we ask if you're eating lactose and take that in consideration just to make it a little bit more personalized as well in the report.

Adam Rinde, ND: Yeah, that's really helpful. And when the machine learning aspect goes out and pulls down. data from referencing studies. So there's a lot in this profession, as far as the microbiome profession, there's been a lot of like inferences and associative data. And do you have a way of going into like ranking of the evidence to causative, causative correlations at this point?

Adam Rinde, ND: Or are [00:22:00] we still in the associative inference stage? For example, saying like this particular population of microbes was abundant in your stool sample and it's been linked to potentially causing this pathology or what have you or linked to is a causative factor. Are we there yet? Or are we still predating that?

Jaclyn Kawwas: Yeah, I think from the papers that we read, a lot of them are associated, right? They're not. necessarily causal. Some of them are causal, so that comes into the model as well. But I like to think about it in a couple ways. There's a lot of tests that we do where we find signatures of certain disease.

Jaclyn Kawwas: If you think about Occult blood, like the fecal occult blood tests, that's an association or a kind of an instance or reference that it might be related to colon cancer. There are other elements or examples like that are linked to certain diseases and you get a lot of valuable information from it. It's not necessarily causal.

Jaclyn Kawwas: So I think a lot of it has value and association and we use both for our model.

Leo Grady: Yeah, and I think that example, Jaclyn, is a really good one because fecal blood, occult blood is a [00:23:00] great test for colon cancer But fecal blood is not causing colon cancer and the treatment for colon cancer isn't to treat the bleed And yet at the same time when you see that test positive, it's still really helpful to going out and getting an actual diagnosis and treatment, even though the treatment has nothing to do with the bleeding itself, per se.

Leo Grady: Even associative studies with the microbiome can be extraordinarily helpful in trying to understand, what's really going on at the root cause. And Ultimately, we don't have a diagnostic, a clinical diagnostic right now based on the microbiome. But if you're seeing signatures that have been linked with Hashimoto's disease, for example, throughout a lot of different studies then maybe you should go and test this person for Hashimoto's, right?

Leo Grady: Now, as far as how the AI Works and deals with all of this. We have a two tier ranking system within the AI. So we have an inclusion criteria. You can think of it as like a meta analysis. We have an inclusion criteria where we only include papers that are peer reviewed, reputable journals. [00:24:00] human subjects, stool samples, sequencing, no culturing, subjects age five and older, et cetera, et cetera.

Leo Grady: And so we ignore, the AI ignores every paper that's not meeting these criteria. And then within the studies that do meet that criteria, we give each one a quality score, which is a function of the cohort size, the size of the study and the quality of the journal it was published in. And so when we're microbiome to these different studies, we can

Leo Grady: basically give a weighted average across all of these different studies where the weighting is defined by the quality of the study. That's

Adam Rinde, ND: excellent.

Jaclyn Kawwas: Having those signatures are super helpful because a lot of providers, a lot of your clients and patients will come in saying you have abdominal pain, fatigue, and maybe bloating, that can be a lot of different conditions and whether it's celiac or IBS or Crohn's, quite frankly, and so having this kind of snapshot of what they potentially look like, you can help maybe think about the next steps and what that treatment could look like.

Adam Rinde, ND: To your point, we've longed for a [00:25:00] signature and enterotype to explain this world of digestive patterns or this link to these disease processes or pathology processes. And so the fact. of those enterotypes have not been solidified yet, right? So I'm sure they are going to start to emerge with this kind of work.

Leo Grady: And we don't know, we really don't know. It's possible that these signatures are something like a liquid biopsy where, ultimately you'll be able to diagnose somebody with enough work by looking at a microbiome signature. It's possible that these signatures are more like a BRCA gene, the breast cancer gene where no matter how many studies you do...you're not going to diagnose somebody with breast cancer by looking at a BRCA gene, right? But if somebody has an alteration in their BRCA gene, you just know that their risk profile is a lot higher for developing breast cancer. It's more likely to be aggressive. And so it'll never be a diagnosis, but it may still be useful clinical information.

Leo Grady: And I think with the microbiome, we don't know. How ultimately [00:26:00] we're going to, this information is actually indicative of a current diagnosis, the current disease state, or whether it's more predictive and correlative with, a higher risk factor. And I think, my own personal suspicion is that it's not going to be one answer.

Leo Grady: I think there'll probably be some diseases we'll be able to find a signature and ultimately diagnose somebody with that disease in the future. And for some signatures, we'll just say, Hey, your risk factor is higher. Your odds ratio is higher developing this disease, but we don't know that you have it yet.

Adam Rinde, ND: Makes sense. Were you going to add something else, Jaclyn?

Jaclyn Kawwas: Yeah, I was just going to say like for all the symptoms, we test many different symptoms and we tell you, we break it down. These are the ones you've self reported, but the ones that you care about, these are the ones that we found that stronger signature, like that strongest match.

Jaclyn Kawwas: And then these are all the other ones. We give you the full list, whether it's a lower signature match as well as medium to high. And so if you go to the, to your doctor and you're not really presenting with certain symptoms, But then two months from now, you start having severe anxiety. I think it's really cool and interesting to be able to go back to your report and [00:27:00] say, did I have the signature for one of these symptoms that are now popping up later?

Jaclyn Kawwas: It's a time capsule of what you have. And so because we have really detailed layers of information for each symptom and condition, you get this whole comprehensive view of yourself, whether you're experiencing it in that moment or not, and you can refer back to it a month or two later, if something kind of manifests later on.

Adam Rinde, ND: That's a good point. Yeah, I like the term PRODROMAL |

. Like when you can see a pattern before it fully manifests into the phenotype or like above the surface symptoms. So that's a really good point that you make just to be able to see what's coming or where your body's shifting, especially if it's following, like a long period of being ill or, some major changes in your life or travel or.

Adam Rinde, ND: . So I want to circle back on some of the shifts that we might be able to see in the microbiome. But. The other layer of data out there that I can't help but think would marry well with what you're doing is the metabolomics. Metabolomics - a primer - PMC - National Center for Biotechnology ...

 And can you explain for people who don't know what that is, what it is, [00:28:00] and just your take on it for now?

Leo Grady: As when these microorganisms are presented with different nutrients, they process these nutrients and they create metabolites out of the back end. And these metabolites, some of these metabolites have been shown to be really important for health. Things like short chain fatty acids, butyrate, acetate, so on.

Leo Grady: And there's a question within the scientific community, Is it the organism that matters or is it the metabolites that they produce that matter? And so some people have advocated for just measuring the metabolites and saying let's forget measuring the organisms at all let's only measure the metabolites.

Leo Grady: And you can do these metabolomics through targeted panels or you can do untargeted panels. And, certainly it seems to be the case that some metabolites have an important role in health. I think the way that we look at it. is that it's not that one, piece of information is more important than the other.

Leo Grady: They're really two sides of the same coin, right? You're not going to produce these [00:29:00] metabolites unless you know what, if you don't have the right organisms. And if you have the right organisms, you're not feeding them the right way, they're not going to produce the metabolites either.

Leo Grady: But if you know the nutrients that are going in, the organisms that are there, you should have a pretty good handle on the metabolites that are being produced and vice versa. If the organisms that are there, the metabolites, you should have some idea of what nutrients are coming in. This is a continuous chain and it's all part of, similar, it's all part of one chain, right?

Leo Grady: So our view is that today. If we're trying to leverage the existing science is really connecting the ecosystem in your microbiome to a variety of different diseases or shifts based on different actions, much less is known about the metabolites. And I think that there's certainly important science to be done there, but if we're really trying to take advantage of the science that we know today to understand root causes in a person's body and what we can do to shift them, there's just a lot more that we know about the gut microbiome.

Leo Grady: And this information is going to be highly. [00:30:00] related to the metabolites, especially if we understand the nutrients that are coming in.

Adam Rinde, ND: Great. Yeah. So I'd like to take one common clinical scenario maybe and just see your thoughts on what you've learned because it's, it pops up a lot and some people think it's over touted.

Adam Rinde, ND: Other people think it's like the panacea. So this is like intestinal permeability and Is that something that you dive into with your tests?

Leo Grady: There's certainly been studies linking microbiome shifts to intestinal permeability or leaky gut and that those studies are being, read by our AI and incorporated into the analysis.

Leo Grady: The mechanisms behind which this permeability is happening. Again, a lot of the signs point back to the short chain fatty acids that we just discussed. We don't fully understand everything that's going on that's ultimately leading to this permeability. What we can say is that certain changes in your microbial ecosystem have been linked with intestinal permeability, and that's what we report those.

Leo Grady: [00:31:00] And as intestinal permeability has been linked with a whole variety of different health challenges, inflammation, infection, et cetera. So it certainly can be a serious condition, I think, and you would know better than I do. The science is still evolving on how we understand it and treat it, but it definitely seems to be important.

Leo Grady: And insofar as we can see it through changes in the microbiome, we're able to detect that and provide it to the provider.

Adam Rinde, ND: Yeah, I think there's a medication that's like in stage three trials right now from University of Massachusetts, I believe it was Dr. Fasano was behind it that is touted to treat a portion of intestinal permeability called the zonulin receptor, zonulin function. Fasano Laboratory: Alessio Fasano, MD - Massachusetts General Hospital

Adam Rinde, ND: So yeah, I think it's definitely something that people are looking to find out and see if they have it. And sometimes it's implied that they have it based on a subset of symptoms or conditions they're dealing with, but Yeah, it's definitely comes up in practice, with all my GI cases, at least.

Adam Rinde, ND: So it's [00:32:00] interesting that I love how you're sitting in a really good, responsible place. I really like that because I think, with technology, it could easily be, packaged in a way that we know more than we actually do. And to sit in that pocket of like responsibility and checks and balances is really comforting.

Adam Rinde, ND: For me to hear sounds like that's a core value of what you're doing.

Leo Grady: Yeah, core value is exactly how we talk about it internally. The fact is that unfortunately there's a history within the microbiome world of sensationalism and likely snake oil salesmanship. And that's unfortunate because the science is really there and really growing and is really meaningful.

Leo Grady: And we certainly don't know everything. There's certainly quite a bit left to uncover. At the same time, the literature is growing rapidly. The studies are growing rapidly, and there's a lot that we can say. And we view our job, as sticking very close to [00:33:00] what's known to providing all of that evidence to telling you, whether this is more established or whether this is much more preliminary, but really to be able to operationalize the complete literature in a way that is both comprehensive and systematic.

Adam Rinde, ND: Wonderful. Yeah. A couple more questions. Cause this is just my thing. So bear with me on this. I want to go deeper a little bit with other discoveries that you're finding. So we had Dr. Ghanoum on the podcast, who's a big. fungome researcher out of the Cleveland area, and, I can really talk about, we know so much about bacteria and there's this whole other world that we need to dive into.

The Mycobiome with Dr. Mahmoud Ghannoum

Adam Rinde, ND: Are you going into levels of virome and fungome and the archaea? And is that part of the reference system?

Leo Grady: A hundred percent. This is one of our motivations for doing shotgun metagenomics is because you see beyond bacteria. ...fungus, virus, protists, and archaea. , And all of that is clearly important in your gut.

Leo Grady: Now, again, the science is more [00:34:00] established in the bacterial realm. I think largely because 16S has been more accessible for longer. So more people have studied it. More and more studies are happening on fungus and yeast, and even there's work being done on viruses, the virome and protists and archaea as well.

Leo Grady: At the end of the day, there's a lot to discover here. And we want to be not only where things are today, but where the puck is moving to in the future. So yes, we do take advantage of all of that literature. There's just less of it than there is in the bacterial world.

Adam Rinde, ND: So Jaclyn, you're interfacing with clinicians and some of the public here.

Adam Rinde, ND: Any early insights on some cases you've heard or anything that you've heard back from folks about, how they're doing with the test?

Jaclyn Kawwas: Yeah, I think one thing that surprises me is how many people, quite frankly, are suffering with some of the similar symptoms. I think if you look at some of our demographics, 30 to 40 percent of them have.

Jaclyn Kawwas: bloating or gas or mental health challenges. So that was something that surprised me. [00:35:00] I always knew that I had a sense of that, but just seeing the actual, the data there of who we're reaching out to, there's clearly a need in a lot of people are suffering. I've also been like had people that I know that have been tested and it's validating for me to see that a condition that they're struggling with or talked about anecdotally shows up in their report or like it has a signature to it.

Jaclyn Kawwas: So I'm like, I knew it. That's very validating for me to see, but yeah, I know people that said that they've. like I've lost weight on it. I know Leo has experiences as well with people and is close to him and his family that took the test and saw a lot of relief from there. I think everyone is different in their own way.

Jaclyn Kawwas: We've been live since the fall, so we're newer to the scene I would say in terms of that, but we've gotten a lot of strong testimonials on the impact that it's making both for the provider and the patient side and making their lives easier and better quality of life.

Adam Rinde, ND: Excellent. And so the take home from the reports are not only dietary changes, lifestyle changes, but also probiotic, nutraceutical, vitamins, is that how deep do you go in your recommendations?

Jaclyn Kawwas: Yeah, so we focused on food first, food and [00:36:00] diet. And we do a lot of supplements. But again, we don't make supplements, we don't make these products. We're not identifying like brands right now. We're not saying try this brand. We're saying certain probiotic strains or certain vitamins and letting the provider or the consumer kind of make those decisions.

Jaclyn Kawwas: But yeah, there's also a lot of studies on lifestyle, even like certain exercise. I've seen a lot of papers on acupuncture as well. Seems to be a big impact on the microbiome. So that's one of the kind of lifestyle incorporations. Yeah. Intermittent fasting also comes through a lot. So that's the realm that we are operating right now with food, lifestyle,

Leo Grady: supplement changes.

Leo Grady: Although there is a literature also on medication and not only in terms of how medication can impact your microbiome, whether it's aspirin or, metformin or whatnot, but also that certain microbial states are predictive of how effective a drug is going to be, particularly in immuno-oncology drugs, and biologics. and GLP-1's.

Leo Grady: So there's actually a fair bit of literature on this to not only associate [00:37:00] somebody's microbiome with drug response, but also how drugs are going to affect somebody's microbiome. Today, we're not providing that information, even though there's studies on it, because we want to be very careful about doing anything that might cause any kind of, concern, and we want to, Just be careful in releasing that information.

Leo Grady: I think we will eventually provide that information to doctors and providers so that they'll have it as they go about, figuring out how to manage to the patients.

Adam Rinde, ND: Yeah, that's great. It's been really helpful just to even hear that when people are non responders to certain medications that, to look at the microbiome for clues for why, and just to even see what's going on.

Adam Rinde, ND: To even know that's a link has been really helpful. It'll be great to see where that grows for helping people with medication selection.

Jaclyn Kawwas: And a lot of people have symptoms when they're taking a GLP 1. So a lot of people stop because they're nauseous, they're having abdominal pain, all these types of issues.

Jaclyn Kawwas: And so if you can get ahead of that or reign those symptoms in either before or during medication. You potentially can last longer on that [00:38:00] medication. It could have potential better outcomes and have more retention for the individual.

Adam Rinde, ND: No wonder they don't feel like eating. It's not very pleasant, but yeah, those medications have been amazingly helpful for so many people.

Adam Rinde, ND: And it's nice when People can take them and tolerate them better. And, so it's not coming with such a big cost of side effects. So that's, it's really good to know that's a other link. And, so I think I'd love to close out a little bit with a few practical aspects, just Some quick hitter questions, and then talking more about how to order the test and go from there.

Adam Rinde, ND: But personally, and just your own take on the microbiome from a big picture perspective, what are some of the top disruptors? Like how do people get into a place where their microbiome looks dysbiotic? Or, it doesn't look as balanced. Yeah. What are some of the factors and, I think, I'll throw one in there. That's just well known is like overuse of antibiotics can play a role, but beyond that, anything else you've learned and you're saying like, wow, this has some pretty good evidence to be a [00:39:00] factor that we should really screen for.

Jaclyn Kawwas: One thing that comes to mind is just the Westernized diet, honestly, in terms of the food that we have in this country, in the U S.

Jaclyn Kawwas: A lot of it is processed, a lot of different oils, different chemicals that are in it. So the food that we have now is a lot different than we used to have 20, 30, 40 years ago. So I think that this is a change of what that looks like also is disrupting a lot of people's microbiome as well as they're not getting like a diversity of different vegetables and fruits and other food groups because they're eating in a certain concentrated area that's higher sugar, higher fat and more processed.

Jaclyn Kawwas: That's just my general take. I'm curious, Leo, if you have any other ones to add. Antibiotics, obviously, for sure, that one as well. And I think people traveling and globalization, eating different things and potentially getting food poisoning probably does not help the microbiome as well.

Leo Grady: Yeah, I think the ones that you both raised are certainly important.

Leo Grady: Processed foods, more and more evidence is showing that they just disrupt some of the nutrients that the microbiome needs. and can really, cause shifts there that you don't want. Some of the surprising studies have also looked at emulsifiers and [00:40:00] preservatives too, and the effects of those on the microbiome, artificial sweeteners, and all of that.

Leo Grady: But there are a lot of ways that things can go wrong. It's not just antibiotics. A lot of times people come off chemo and cancer therapy and they beat the cancer, but then they ultimately end up with GI issues because the chemo has really affected their gut. People who are on serious drug addiction, opioid addiction, many times, even though they can get off of these drugs, their microbiome has been destroyed through the use of them, certain infections can cause disruptions in your microbiome.

Leo Grady: Everything from a salmonella, food poisoning. type infection, but we know that there's post infection IBS and, we're seeing people with long COVID, you have these situations with like pandas and pans where someone will get an infection and it can dramatically change not only their microbiome, but the rest of their health.

Leo Grady: So there are those sorts of examples as well. There's some really interesting studies that have looked at the proximity of humans to [00:41:00] animals over time and shown that as people have had less connection with animals and been living in a more, cleaner, bubble fied world, that it actually seems to have a negative effect on their microbiome as well.

Leo Grady: There's a really interesting study in Ireland about the travelers the tinkers, and how, despite poor diets and so on, the hypothesis seemed to be that they had pretty decent health because of their proximity to animals. And we know that dogs can affect your microbiome in a good way and cats to a lesser degree.

Leo Grady: But certainly like the introduction of pets. So there are a lot of factors that go into it. And even if you're eating healthy and not getting cancer and not addicted to opioids, you can still have shifts that happen due to environmental changes or travel or whatnot. And so ultimately this is a core pillar of your health.

Adam Rinde, ND: That's awesome. I own a tortoise. I don't know if that's helping me though. Oh, that's interesting.

Leo Grady: I don't, I haven't seen any studies on that.

Jaclyn Kawwas: Yeah.

Adam Rinde, ND: Yeah. I [00:42:00] don't know. They eat a lot of lettuce. So I'm sure there's something good going on there. Cool. And yeah, I'd say that it's going to be fascinating to see, when fecal transplant really comes on the scene, what level of criteria we're looking for donors and screening for healthy donors and how many boxes they check of things that we mentioned.

Adam Rinde, ND: Cause it's. All these disruptors and to get a good donor is so essential.

Leo Grady: I think ultimately we're going to get to a point where we understand the microbiome enough that we'll be able to engineer it into a desired state without having to pass through a fecal transplant. I don't know how long that's going to take.

Leo Grady: Certainly in the meantime. There are banks and all that are doing good work and trying to screen donors and make that kind of material available. And certainly now we have an FDA approved therapeutic in the form of fecal transplant for Recurrent C. Diff Management of recurrent Clostridioides difficile ... - Mayo Clinic

Adam Rinde, ND: great. So we've covered a lot and I really appreciate you being on here and just to wrap up, what's the process of ordering Jona and what's the next steps if someone's listening to this and they're really interested in [00:43:00] pursuing it, what would they do?

Jaclyn Kawwas: Yeah, so there's kind of two sides. So if you're a consumer, you can go to our website, Jona, and go to the product page and order directly on that. So it's pretty simple. And then once you do, you'll get an email about your confirmation and emails along the way. And then once you, and you'll be sent a kit next business day, it was shipped out a kit to your home, the address that you put in.

Jaclyn Kawwas: And I'll ask you to register your barcode and activate and create your account and fill out that health survey or that intake. send the sample back to us, and then once we get it into the lab, it takes about three weeks, I would say, for the report to be generated. From the provider side, we have a provider's page in our website.

Jaclyn Kawwas: You can fill out the form if you're interested in partnering with us. We have a separate provider product and a portal that you can access. You can invite your clients, you can manage your different clients and the different reports, be able to look at the report first and understand the complexities of it.

Jaclyn Kawwas: So there's a different sides of the coin. So if you're interested in both sides, you could either go to the provider page. If you want to work with us from that side of the coin, or if you're a consumer and want to try it out yourself, you can go to Jona. health.

Leo Grady: You could also [00:44:00] always email us at hello at Jona dot health.

Adam Rinde, ND: And then there's a partnership in place with Emerson ecologics, so for providers that are already linked up with Emerson, I think they're going to be able to order tests through there. Is that correct?

Jaclyn Kawwas: Yeah. If you're excited to announce a partnership with Emerson and full script. So our product, our microbiome profiling kit and AI interpretation is on Emerson platform right now, and it's under the lab test catalog.

Jaclyn Kawwas: So super excited to be able to offer that to all their different providers and

Adam Rinde, ND: practitioners. Great. Yeah, those things that people are already using is always helpful because that's one less process to learn. So it's good. Yeah. Thank you for being here. This has really been very interesting and educational.

Adam Rinde, ND: And thank you for taking such a responsible approach to this world. It's refreshing for me, for someone who's been ordering the stool test for nearly 20 years now. So it's just really refreshing. I'm looking forward. I signed up, so I'm looking forward to getting started with helping patients through this.

Jaclyn Kawwas: And I know, Adam, you mentioned this is your hundredth episode. So

Adam Rinde, ND: yes,

Jaclyn Kawwas: in honor of [00:45:00] that, we have a promo code for all the listeners. So it's ONETHING100 you can put that into the product page on the coupon code and it should reduce it by a hundred dollars.

Adam Rinde, ND: Oh, we appreciate that. Thank you so much.

Adam Rinde, ND: All right. I love to connect with you down the road when we're further along and learn more things together.

Leo Grady: Wonderful. Thank you so much, Adam. You're welcome. A lot of fun. Thank you.

Adam Rinde, ND: Thank you.

Adam Rinde, ND: Thank you so much for tuning into this week's episode of the one thing podcast. Please share these episodes with your friends, loved ones, colleagues, patients, healthcare providers, anyone who you feel might benefit from hearing these informative interviews. We tend to learn best from people sharing things with us.

Adam Rinde, ND: That's often the first time it's introduced. So don't hesitate. If the content of these episodes reminded you of someone that might benefit from that for the episode to them and to you. I'm sure they'll either appreciate it or be appreciative that you've thought of them. So once again, we'll look forward to seeing you next episode on the [00:46:00] one thing podcast.

Adam Rinde, ND: And again, much appreciation for you being here with me.