81. Dr. Zain Kassam: How Your Gut Bacteria Control Your Brain, Weight, and Longevity

What if I told you there's an organ in your body with more cells than the Milky Way has stars—and most doctors barely think about it? In this episode of Extend, I sit down with Dr. Zain Kassam, a gastroenterologist turned microbiome researcher who's pioneering how we understand the trillions of organisms living in and on us. We dive into why your gut bacteria aren't just bystanders—they're actively producing molecules that affect your mood, metabolism, immune system, and even longevity. We also explore the gut-brain connection, why not all probiotics are created equal, and how the microbiome influences everything from depression to skin health. Dr. Zain Kassam is a gastroenterologist, microbiome researcher, and Chief Medical Officer at Seed Health. He trained at McMaster University, Harvard, and MIT, where he pioneered clinical applications of microbiome science. He's led groundbreaking research on fecal transplants and develops evidence-based probiotic therapies. We Also Discuss: The Microbiome Revolution: From Forgotten to Life-Saving Why Your Gut Has More Cells Than the Milky Way Has Stars How Gut Bacteria Control Your Brain and Mood The Butyrate Connection: Your Microbiome's Master Molecule Why Most Probiotics Are Marketing Hype (And How to Choose Better) The 4D Framework: Diversity, Delivery, Do-Gooders, and Data Microbiome Testing: Crystal Ball or Expensive Guesswork? From C. Diff to Cancer: When Gut Health Becomes Life or Death The GLP-1 Secret: How Your Gut Makes Its Own Ozempic Post-Antibiotic Recovery: Rebuilding After the Nuclear Bomb Thank You for Our Sponsors: Pendulum: Use code DARSHAN or use the link https://pendulumlife.com/discount/DARSHAN to get 20% off IM8: Try IM8 today with a 30-day money back guarantee. You can get 20% off your first order with code DRSHAH at https://im8health.com/discount/DRSHAH. Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram: https://www.instagram.com/darshanshahmd/ Learn more about Dr. Zain Kassam: X: https://x.com/DrZainSays/ Instagram: https://www.instagram.com/seed/ Get 25% off DS-01 with code EXTEND25 at Seed.com https://seed.com/daily-synbiotic?utm_source=ambassador&utm_medium=podcast&utm_campaign=darshanshah&utm_term=25p&promo_code=EXTEND25

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:50Dr. Darshan Shah?

  Zane, thanks for joining me today on Extend. Really great having you here.

• 0:54Speaker 01

  It's a pleasure to be here. Excited to talk about the microbiome, gut health, longevity, and everything between.

• 0:58Dr. Darshan Shah?

  Yes, I love it. So I'm excited to talk about all of it. And you know, I love your unique perspective because you trained in gastroenterology as a physician, right? Where did you train at, by the way?

• 1:09Speaker 01

  Yeah, I did my clinical training in Canada. I did my internal medicine at McMaster University and my gastroenterology training at McMaster as well.

• 1:17Dr. Darshan Shah?

  Amazing.

• 1:17Speaker 01

  Before going down to Harvard to do my clinical trials training, and then to MIT for a postdoc in machine learning, before machine learning was really a thing a while ago. So yeah, a little bit of a tour through both Canada and the US.

• 1:30Dr. Darshan Shah?

  Yeah, and through medicine and also informatics and machine learning. I mean, you did a lot.

• 1:35Speaker 01

  It's, you know, I think one of the things that makes innovation happen is being a polyglot, being able to speak multiple languages in different ways and think laterally. And that's always been a bit of my passion. So hence the accoutrement of the different places.

• 1:48Dr. Darshan Shah?

  You know, and it's so helpful because I think that you have this unique perspective where you're not just in the science of microbiome, but you know, the data analytics part of it, and also the clinical aspects as well. And so, you know, I would love to hear from you a little bit about your experience. Because when did you train in gastroenterology? How long ago was it?

• 2:05Speaker 01

  So I did my training, I did my MPH in 2013, did my MIT postdoc in 2014. And then before that was all my clinical training.

• 2:14Dr. Darshan Shah?

  So relatively recently, right?

• 2:15Speaker 01

  Yeah, sure.

• 2:16Dr. Darshan Shah?

  Is there a lot of? And I say recently because I graduated 30 years ago. So you're a lot younger than I am. But the reason I ask this question is because is there a lot of talk in the Western clinical medicine world of the microbiome right now? Have you seen it kind of catch up to kind of like the educational process in traditional medical school, et cetera?

• 2:38Speaker 01

  I think it hasn't yet. It's starting to come. And so like when I first got introduced to the microbiome was well over a decade ago. You know, I had a patient as a GI fellow. She was 82. She was British. She loved her grandkids. She loved gardening. And I saw her in the emergency department with a terrible case of C. diff. She'd had a bladder infection, received antibiotics, and then C. diff came.

• 3:02Dr. Darshan Shah?

  Clusterton difficile.

• 3:03Speaker 01

  That's right. Tied to the toilet, like one of her colon removed, she was so sick. And the most potent antibiotics didn't work for her. And we had to turn to something that was from 5th century China, right? That's largely forgotten about called a fecal transplant. And she was gardening two days later. One messy enema, she was like cured. It was incredible. That's how I met the microbiome. That was a decade ago. And we still have not yet changed the way that we think about educating about the microbiome in clinical practice, fellows, medical students, and even before that.

• 3:34Dr. Darshan Shah?

  And that's what's so crazy because you know, like I trained in surgery and back then the microbiome was like an annoyance, right? It was something that you had to get rid of just to do surgery. Whenever someone came in with an emergency case, it was like the worst thing because that we had a microbiome because it would contaminate the field and you have to slam them with antibiotics and all of it. And so we almost grew up in a time of medicine, which is just now realizing this is not true, that I grew up that bacteria in our colon was just a bad thing. It's, you know, had no purpose really. And now it's incredible to hear the current thought process is exactly 180.

• 4:12Speaker 01

  Yeah, no, it's if you take a step back and just like, you know, think about the microbiome. You know, it's nearly 100 trillion organisms that live on and in you. There's, that's for the record, more stars than the Milky Way galaxy, right? It's massive biology. And when, you know, when I was at in Boston, when my colleagues were, you know, training monkeys to control robots, I was trying to figure out the microbiome, right? I was trying to unpack this invisible organ, this one that is massively important, and realized very quickly that it's not just a bystander, right? It's it's this invisible organ that has really important biology. It helps us digest, it modulates our immune system, it releases molecules that affect our mood, our metabolism, and even our longevity.

• 4:52Speaker 01

  Yet, exactly as you said, we've basically for decades thought of microbes or bacteria as the bad guy. We've waged a modern war on bacteria.

• 5:03Dr. Darshan Shah?

  Right.

• 5:03Speaker 01

  You know, nearly 100, two, over 200 million doses of antibiotics ever, right? Flowing like candy, hyper sterile environments for kids, ultra-processed foods. We're trying to get the microbes out of the way, like you said. And in this, like, we've basically used an atomic bomb when a scalpel has been needed, right? We've not only killed a bad bacteria, we've also killed these good bacteria, these critical organ, and the consequences are dire. We know that the research is very clear, as we disrupt our microbiome, especially early in life, there's been a rise in autoimmune conditions, metabolic conditions, allergic diseases, and I think that's a consequence of not having that scalpel, as opposed to taking the atomic bomb approach.

• 5:44Dr. Darshan Shah?

  Yeah, exactly. And I want to dive into all of those. I feel like they're all so important to connect on, connect the dots for people, right? Because I still believe that if you go to your traditional doctor, the microbiome is still almost thought of as an afterthought, and some people don't even believe in microbiome science still, right? And so it's really unfortunate, so it's really important for the listeners of this podcast to advocate for themselves and to kind of protect their own microbiome. Don't let your, you know, your emergency room visit nuclear bomb your microbiome away if you don't really need an antibiotic, because I think a lot of times there's a Almost a pressure for the people working at these urgent care centers or emergency rooms

• 6:27Dr. Darshan Shah?

  is giving antibiotic, get you out the door, right? And that's what's led to a lot of the problems today.

• 6:33Speaker 01

  I have empathy for both the patients and the clinicians, actually, both of them. It's a high-pressure environment. We want to do right by our patients. Having long conversations on the educational aspect is hard to do pragmatically, but also you go all the way to the emergency room to not walk away with something also feels like we're missing something. And so I have empathy on both sides of the house, but I think asking the questions to arm yourself, do I need an antibiotic? And if so, can it be more narrow? Does it have to be broad? How narrow can we get? And to be hyper vigilant about, you know, the consequences of that.

• 7:06Dr. Darshan Shah?

  Yep. Also, you know, in my field in surgery, if you were doing a surgery, it was part of the protocol to give everyone antibiotic beforehand, and now that protocol has gone away. Now there's big studies like the skip study that said that if it's a clean case, you don't need to give people antibiotics, you probably shouldn't, or even just only one dose, not narrow spectrum, not broad spectrum antibiotics.

• 7:28Speaker 01

  Exactly. I think that's the piece that sometimes clinicians forget is like, just really think about, is this the narrowest we can get? And can it be topical as opposed to systemic, right? To think about the route of delivery as well as the spectrum of the actually antibiotic as well.

• 7:41Dr. Darshan Shah?

  Exactly. And for people that don't know what we're talking about, explain narrow versus broad spectrum antibiotics, please.

• 7:47Speaker 01

  Absolutely. So, you know, antibiotics have a lot of different applications, mostly for, you know, dealing with infectious disease, obviously, but there's many types of infectious diseases that have very different types of bugs that are susceptible to different types of antibiotics. And so what you really want to do is instead of giving, you know, the set of antibiotics that works against every single type of bacteria which can breed resistance, you want to give an antibiotic that works very specifically against the bacteria that you have at that time or are likely to have based on the clinical picture.

• 8:17Dr. Darshan Shah?

  Right, right, exactly. So if you get prescribed an antibiotic, always ask, do I really need this and is this the right antibiotic for the bug that I'm, that I have? A lot of that involves getting a culture. So you, you know, you get a swab put in your throat or something and then Even antibiotic based on that, that's better. So I think your story about the elderly woman with a C. diff is very good. It's a very good place to start. And the reason I say that is because it illustrates why the microbiome is number one, important. But number two, also, this whole concept of transplanting the microbiome from one organism to another organism and the changes that can cause, right? So let's start with, why does C. diff develop in people? What happens there?

• 9:02Speaker 01

  Yeah, I know. So C. diff is like a really tricky bug. Many of us actually have, were colonized with cholesterol emphyseal. And it's kind of kept at bay because we have these healthy, good bacteria that keep it at bay. That what happened to, we'll call her Mrs. Smith, is that she took an antibiotic that cleared out her good bacteria, but didn't kill the C. diff. And the C. diff can go wild. They can basically produce a toxin that causes a terrible clinical impact to the gut. And it causes diarrhea and can even cause a hole in your bowel. So the problem is not with the bug itself. It's a factor in missing the good bugs. And that's kind of where fecal transplant, in that case, kind of stepped in.

• 9:37Dr. Darshan Shah?

  Exactly. And so as a surgeon, we used to, we used to remove colons on patients that had C. diff. And we probably never needed to. We just had to give them back the good bacteria to get the C. diff under control, right? Because the C. diff was probably there to start with.

• 9:51Speaker 01

  That's exactly right. In fact, it was a surgeon who, so I mentioned fifth century China when fecal transplant were first kind of described. But actually, it was a surgeon, Ben Eisman, who published the first Western literature for fecal transplants in 1952 in an American Journal of Surgery. So it's nice to talk to another surgeon who appreciates the microbiome. Not that I can talk to Ben Eisman, so yeah.

• 10:12Dr. Darshan Shah?

  I love it. And so from there, so you know, the first time Western medicine in any respect was after that fecal transplant for C. diff. And then I think it just kind of got compartmentalized into that one application. Was C. diff colitis considered fecal transplant? But I think that kind of started off this wave of research on animal models, on microbiome, right? And some, a lot of that research was done using fecal transplants. Could you tell us kind of how this whole science kind of got started?

• 10:42Speaker 01

  Yeah, I think there's a A couple of key experiments I think are really interesting and then they've actually gone into humans. So probably the one that's maybe the most famous and really kind of stark is that you have these mice and they're germ free. They've never seen bacteria before. And this really talented group at the University of Washington, Peter Turnbaugh and his colleagues, took twins, human twins, one was obese and one was lean, one was skinny. And they took that stool from the obese individual and the skinny individual and put it into these mice. And what happened next was kind of shocking. The mouse that got the obese stool became obese. The mouse that got the skinny stool became skinny. And this set off entire revolution in terms of thinking about the microbiome beyond just infectious diseases,

• 11:24Speaker 01

  but also into metabolic, immune and beyond allergic diseases. And there've been many mouse studies, but also been very many human studies. In fact, I was, I worked with Paul Moyeti and a group at McMaster did the first double-blind placebo-controlled trial for fecal transplants and ulcerative colitis, a condition that causes inflammation of the lower intestinal tract. My dad has it, it's an awful condition. And it worked. Now there've been five randomized placebo-controlled trials that are showing a positive impact in ulcerative colitis. And so we're just at the tip of the iceberg and unlocking kind of the microbiome as both a therapeutic, but also for everyday health.

• 12:02Dr. Darshan Shah?

  So just to double click on ulcerative colitis. I mean, that's another one of those surgical diseases that is so frustrating because there's nothing you can do. And then, you know, people come in with like ruptured colons and you have to take them to the operating room and do these terrible surgeries where you take a piece of their colon out through their skin and do a colostomy, right? And so you're saying that now fecal transplants can also be used for ulcerative colitis. Is that becoming more a mainstay of the?

• 12:26Speaker 01

  It's still taking time. So, you know, if you rewind to the C. diff era and I'll, you know, I, when I first published my poster or presented my poster at DDW, the big medical meeting for gastroenterologists, 30,000 GI doctors. I kind of got laughed at when I first presented it. But now, after the research has been kind of done, rigorously evaluated fecal transplants for C. diff, it's in clinical guidelines and they're new medicines, right? So it takes time to change clinical practice and hearts and minds. I think we're still there with ulcerative colitis where we're seeing that early data being very exciting, but it's more complicated than C. diff. Turned out, for example, the trial that we did, not any donor worked. One specific donor worked really well that drove the entire positive results of the trial. The other donors didn't work.

• 13:11Speaker 01

  For C. diff, it doesn't matter which donor, whether it's you, me, Wayne Gretzky, it doesn't make any difference. It all works. But for ulcerative colitis, we have to be much more thoughtful about the donor selection, and that's been kind of shown in a couple of studies.

• 13:22Dr. Darshan Shah?

  So on that, does that donor have a specific bacterium? Or what was so special about it?

• 13:28Speaker 01

  Exactly. Well, it did. Exactly. It had a very unique microbial signature, and you're able to use machine learning to see, when you look at the donor and you look at the recipient before and after who it worked for, and before and after who it didn't work for, you can triangulate which bugs are the ones that are driving the effect, pull those bugs out, and potentially use a new type of therapy.

• 13:47Dr. Darshan Shah?

  Oh, that's so interesting. This is where the machine learning application comes in. Because for, you know, for people who don't know, there are trillions of these. There are so many, and each one has its own unique genetic signature, right? And so that's what you're using the machine learning to extract the information.

• 14:00Speaker 01

  That's right. That was one of the previous companies that I started called Finch Therapeutics. That's the approach that we took and had a partnership with Takeda for developing AI-based new medicines for inflammatory bowel disease. And that's the approach we took.

• 14:12Dr. Darshan Shah?

  Wow. So can, I mean, do we have to do this testing on every patient? Or is it just one, one specific donor is like this, this person that we just got to get so many of their fecal transplant?

• 14:23Speaker 01

  It's a great question. I think we're not at the scalability stage for ulcerative colitis. There is some really key signatures for the microbes, we'll talk more about when we talk about longevity and other things, related to butyrate, a short-chain fatty acid which has significant health benefits. It's a master molecule. And one of the benefits that it has, which is really unique, is it has the ability to improve the barrier function. So not having a leaky barrier, which is really, really important, in addition to some inflammatory aspects, which we can talk more about as well.

• 14:54Dr. Darshan Shah?

  For sure. Okay. So yes, let me ask you more about the inflammatory aspect there.

• 14:58Speaker 01

  Sure.

• 14:58Dr. Darshan Shah?

  So, you know, we all know that most of our immune system lives in and around our gut, right? And so one of the biggest reasons people have inflammation, chronic inflammation, systemic chronic inflammation, is because of something going on in their gut. Could you describe that whole process for us?

• 15:15Speaker 01

  Absolutely. So, you know, I think that, you know, Aristotle once said that all disease begins in the gut.

• 15:20Dr. Darshan Shah?

  Yeah.

• 15:20Speaker 01

  Probably right, as kind of surgeons and gastroenterologists. And I think there is this huge ability to be able to modulate the immune system from your gut. And I think inflammation has an impact not just on active clinical conditions, but actually on longevity as well, which has become very, very clear. Maybe I'll take a detour into longevity to tell you a little bit about that.

• 15:40Dr. Darshan Shah?

  Sure, I would love to hear more about that.

• 15:41Speaker 01

  Because I think that's an important piece, and we can then double click on some of the clinical conditions around it. That's interesting. So, you know, I would say that the inflammation story and longevity has been now pretty well established. But I think the microbiome pieces have been a little bit less clear. So, you know, I always try to start with, what does the science say, right? And I always start with the epidemiology data, the population level data. And there's this beautiful study that was done relatively recently in Nature Medicine by a group in Seattle in 2022. A colleague of mine, Sean Gibson, who was at MIT with me, contributed. And they took 9,000 patients and they looked at their microbiome from eight, and they're from 18 years old to 101. So it's across the lifespan.

• 16:22Dr. Darshan Shah?

  Wow.

• 16:23Speaker 01

  And they had two really interesting observations. Number one, that diversity was highly linked to a healthy age, healthy lifespan. Number two, the individuals that had an unhealthy lifespan, had conditions that they picked up along the way in their age, had a depletion of these butyrate-producing organisms.

• 16:41Dr. Darshan Shah?

  Got it.

• 16:42Speaker 01

  Really interesting.

• 16:43Dr. Darshan Shah?

  Yeah.

• 16:43Speaker 01

  But to me, that question then says, well, that's cool. Is it chicken or the egg?

• 16:46Dr. Darshan Shah?

  Yes.

• 16:47Speaker 01

  I don't know. Is it a chicken or the egg? Well, that's where a couple, three other studies that were really interesting kind of come to play. So we talked a little bit about mice studies. And mice are a really good way of knowing whether it's chicken or the egg, because we can do a lot of manipulation with that.

• 16:59Dr. Darshan Shah?

  Right.

• 16:59Speaker 01

  Really elegant study that was done in the UK. They took young mice and old mice. And they took the old mice stool and they put it into the young mouse. And what happened? Something kind of wild happened. Three things. Number one, The inflammation in their brain went up and then activated actually overactive microglia, which is led inflammation in the brain plus overactive microglia can lead to neurodegenerative conditions, right? Things like Alzheimer's, dementia. Two, it actually showed an inflammation in the eyes, in the retina specifically, which through C3 and another pathway, and it also is associated with age-related retinal conditions.

• 17:40Speaker 01

  And the third thing, because all disease begins in the gut, is that it led to a dysfunction of the barrier in the gut. And so we saw this like barrier function disrupt. And that's great from a biology perspective, but what everyone wants to know is what happens if you did the other way around?

• 17:55Dr. Darshan Shah?

  Yes.

• 17:55Speaker 01

  What if you took the young stool, the young mouse stool, and put it into the old mouse? Well, it did the exact opposite.

• 18:01Dr. Darshan Shah?

  Wow.

• 18:02Speaker 01

  It decreased the inflammation in the brain, it decreased the inflammation in the eye, and decreased inflammation in the gut. And that's something that was incredible.

• 18:08Dr. Darshan Shah?

  Yeah.

• 18:09Speaker 01

  But I still don't know how it happened.

• 18:11Dr. Darshan Shah?

  Yes.

• 18:11Speaker 01

  Just that it happened. And so that's where, and this has been vetted by a couple of different groups, one in Sweden, where it was butyrate. They looked at this mouse study. It was butyrate that actually triggered a longevity pathway. And the longevity pathway, for those that are technical or fibroblast, growth factor 21, the ones that are really more interesting, most people might know is AMPK or decreasing mTOR, things that are more familiar in the longevity, space modulated.

• 18:41Dr. Darshan Shah?

  Yeah.

• 18:41Speaker 01

  So we're mopping up those dead cells, right? Like having autophagy, you're having this turnover, which I think is really, really interesting. So a couple of little pieces there on thinking through inflammation.

• 18:51Dr. Darshan Shah?

  So this butyrate molecule is made by the bacteria, right?

• 18:55Speaker 01

  That's right.

• 18:55Dr. Darshan Shah?

  And if you don't have enough good bacteria, you can't make enough butyrate. And how does butyrate then, does it get absorbed into your bloodstream?

• 19:02Speaker 01

  It can, exactly.

• 19:03Dr. Darshan Shah?

  Okay. And then this turns on these pathways throughout all the cells in the body?

• 19:07Speaker 01

  Yeah, it happens. It acts at both the gut level itself for barrier function, but also acts systemically through a number of different inflammatory pathways, things like HDAC and et cetera. And they also trigger all those pathways on longevity as well.

• 19:19Dr. Darshan Shah?

  Yeah. And so are there exogenous forms of butyrate that people can take?

• 19:23Speaker 01

  People have tried those, but the challenge of butyrate is that it's a very volatile organic acid. So it's Quite pungent. I'll say quite. And so it's for me, I'd rather have the kind of the machinery, the bacteria factors always producing it versus trying to supplement it with the butyrate itself, both for a palatability reason, and they've done even butyrate enemas. Patients with inflammatory babbles couldn't really tolerate that. But I think it's better to get to the source, get to the root cause, and that's go to the bacteria.

• 19:53Dr. Darshan Shah?

  Yeah, because there's so many other side benefits as well as having a healthy gut bacteria. Yeah, I remember once buying a butyrate supplement. I just had to throw it away the minute I opened the bottle. It was so smelly and bad. But, okay, so we have this molecule called butyrate that has been shown to be lead to longevity, also potentially treat even conditions like ulcerative colitis, right? And so why isn't everyone just doing fecal transplants right now for longevity?

• 20:19Speaker 01

  I think that there, I think the research isn't there yet specifically for longevity. And like, and I'm someone that's helped kind of pioneer the fecal transplant space. And I'd say, it has to be done for the right condition, right? And so see if the data is there and it's very convincing. But I think to me, it's a tool to understand how the microbiome is working. It helps to tease apart chicken or the egg, right? And so I think it's not the panacea, but rather can we learn that the microbiome is causal? It can help change a condition as opposed to looking at the studies that say, well, these groups are different, but we don't know. So I always view as fecal transplant as a tool to get to a solution, not the solution itself.

• 21:00Dr. Darshan Shah?

  Right. Makes makes total sense. Although I will tell you, there are some companies out there that are taking fecal matter basically from athletes and turning them into supplements.

• 21:10Speaker 01

  That's right. Fit Biomic is one that I know. I know the CEO. We worked together back in Boston. And I think there's an interesting idea. That's not the fecal transplant itself, but is allowing him to get to the exact bug that he then you grow in pure culture to give as a as a product.

• 21:28Dr. Darshan Shah?

  As a product. And has that been shown to be helpful or beneficial?

• 21:31Speaker 01

  There's some data that shows that they just published some data for an athletes on performance. And so you can think about essentially lactic acid production, right? It turns out that lactic acid, when you're an athlete, can stop you from performing at your optimal state.

• 21:45Dr. Darshan Shah?

  Sure.

• 21:45Speaker 01

  They published a paper in Nature Medicine that showed that their bacteria was able to decrease the lactic acid.

• 21:51Dr. Darshan Shah?

  Interesting. And then there's also some fecal transplant studies in mice, I think, on immune modulation for like autoimmune disease.

• 21:59Speaker 01

  That's right.

• 22:00Dr. Darshan Shah?

  And can you talk about that a little bit?

• 22:01Speaker 01

  Absolutely. So similar to IBD, there is, you know, immunity can go into allergic space and go into autoimmunity, right? And so group in Boston Children's who showed essentially that fecal transplants in mouse models were able to decrease allergic diseases, which I think is really, really interesting. In addition to many studies, groups have shown that it improves in autoimmune conditions. But where I think that's most exciting for me actually is in the cancer space.

• 22:26Dr. Darshan Shah?

  Yes.

• 22:27Speaker 01

  And this is something that I think is just starting to hit. So using, thinking about fecal transplants again in, as a tool, there's two papers that were published in Science, a very good journal, that looked at patients that had metastatic melanoma, so a skin cancer in which they'd failed everything.

• 22:43Dr. Darshan Shah?

  Yeah.

• 22:44Speaker 01

  Included failing checkpoint inhibitors. These are immunotherapies that are really effective for treating many cancers, but they work through the immune system actually, and they work, and are modeled by the microbiome in terms of looking at some of the mouse studies. Well, they looked at patients that had failed the checkpoint inhibitors and they had nothing else. That's it. There was nothing else for them. So they gave another dose of the checkpoint inhibitors and a fecal transplant. And they saw 40% rescue of the effect.

• 23:13Dr. Darshan Shah?

  Oh, that's huge.

• 23:14Speaker 01

  For someone that was destined to unfortunately pass away, there was no other treatments, and that was replicated. One was a study was done in Pittsburgh, another was done in Israel. And so it's replicated in two studies. So just getting to the tip of the iceberg doesn't mean that we should be doing fecal transplants, but that means that likely something in that microbiome is working to drive an impact on the immune system to help support those checkpoint inhibitors to work better.

• 23:38Dr. Darshan Shah?

  Yes.

• 23:39Speaker 01

  Fascinating.

• 23:40Dr. Darshan Shah?

  Right. That is very, that's extremely fascinating. Is it just they're going from an unhealthy microbiome to a healthier microbiome? Are there specific strains that are causing this effect? Like, what is the?

• 23:50Speaker 01

  That's what we're figuring out now. And some of the preclinical data is looking at what specific microbes are working, in groups in Chicago and in Houston.

• 23:57Dr. Darshan Shah?

  Yeah.

• 23:58Speaker 01

  That are driving it. Some think it's beta-producing organisms, others think it's other organisms, on how exactly it interplays with the immune system. And so that's what's still an active area of kind of debate on mostly T-cell modulation specifically.

• 24:13Dr. Darshan Shah?

  Oh, okay. So that's, we know the microbiome ties to your immune system through modulating immune cells. And then we know also they create compounds called butyrate. We know that they also can keep bad bacteria at bay, like C. difficil.

• 24:28Speaker 01

  Yeah.

• 24:29Dr. Darshan Shah?

  Talk about the next aspect of microbiome that is being heavily researched right now, which is the brain micro gut connection, microbiome connection. Specifically, how your microbiome affects conditions like depression, anxiety, attention deficit. There's a lot going on in that field right now.

• 24:48Speaker 01

  So much work looking at the gut-brain axis. And in fact, I was very fortunate to work with Steve Collins at McMaster and Shemek Burchak, who did some of the first work in the gut-brain in 2011. And they started with a mouse. Again, I'll tell you a mouse story, then I'll tell you the human story. But they took, there's these two types of mice. One's a bulb-sea mouse. It's like quiet as a mouse. It's very docile. And they have a Swiss mouse, which is like a really aggressive mouse. It wants to bite your face. And it's like a super aggressive.

• 25:13Dr. Darshan Shah?

  Swiss mice.

• 25:14Speaker 01

  Exactly. The mice and the humans may be different. But they swapped the bacteria around. And it turns out, the Swiss mouse that was previously really aggressive became very calm.

• 25:26Dr. Darshan Shah?

  That's crazy.

• 25:27Speaker 01

  And oppositely, the bulb-sea mouse that was very calm became very aggressive. And it's set off an entire journey of thinking about what exactly in our gut is affecting our brain. And there's a number of studies that have looked at everything from autistic type mice, which is, the data looks really incredible, to all the way to human studies that are starting to happen. And I think the pathways that we're hitting are around inflammation in the brain, right? So we know that, for example, children that have autism have more inflammation in the brain on postmortems. It's around chemical toxins effectively that are crossing to the brain, things like peak cressel. If you have a leaky gut, then those things can kind of lead to your brain.

• 26:09Dr. Darshan Shah?

  I see.

• 26:10Speaker 01

  And also the vagus nerve. So it turns out, really elegant study that was done, that looked at if you give a certain bacteria out, you're able to increase oxytocin, the love hormone, the connection hormone, in the brain, something that's depleted in children with autism.

• 26:23Dr. Darshan Shah?

  Right.

• 26:23Speaker 01

  And that's through the vagus nerve. And so there's hormonal pathways, there's inflammatory pathways, and there's more mechanical systemic pathways, which really tie the gut and the brain together. But we sometimes forget, and you'll know this, there's more serotonin in our gut than there is in our brain.

• 26:38Dr. Darshan Shah?

  I was gonna say the next one, right.

• 26:39Speaker 01

  And so I think there's this huge opportunity for modulation in depression, anxiety, and even other conditions that's starting to kind of move our way there.

• 26:48Dr. Darshan Shah?

  Yeah. And it's amazing, because right now in psychology, all we have are psychoactive drugs, right? That's the only thing that's talked about. You diagnose depression, Prozac, right? And it just modulates the chemistry of your brain, which doesn't really treat the core root of the issue, whereas modulating the gut bacteria could potentially be curative.

• 27:09Speaker 01

  I think there's both. I think it certainly has the opportunity to do that. I also think the way that we think about psychiatry is going to evolve. The way our thinking has been, for example, with cancer therapy. Cancer therapy, we say, okay, gosh, this person's a little different. Can we put these two combinations of medicines together that will work really well for them? And right now, we're not doing a lot of great combination work with different mechanisms. We kept hitting the same pathway, the same approach. The way that we really make a stepwise incremental benefit is by taking two different approaches and putting it together, and then one plus one equals three, right? And I think that's where I think psychiatric care is going to go, maybe with psychedelics, maybe with microbiome therapies to pair with the standard therapies. And I think something that's near and dear

• 27:52Speaker 01

  to your heart, we'll get more personalized. We'll figure out, gosh, cancer's very different, but, you know, mental health is extremely heterogeneous, right? And so how do we get to more precision, or at least try to think about the protocols that we step through to get to the right kind of hopeful success?

• 28:08Dr. Darshan Shah?

  Yeah. I had Chris Palmer on here, and he talks a lot about the metabolism now that relates to mental health, and how most mental health diseases are actually based in metabolic unhealthiness, you know? And so I think that's a big part of it as well. Okay, so let's take it to just my patients here at this clinic. So we see a lot of people in two camps, I would say. One that are just looking to optimize their longevity, optimize their overall health, how they feel, maybe their workouts at the gym, sleep better. And then we have patients that are struggling with gut health issues, right? And so let's talk about the optimization person first and kind of what they should be thinking about and what solutions we have for those people. And I don't want to touch on some specific gut health issues

• 28:53Dr. Darshan Shah?

  that I think the microbiome conversation is important because a lot of people struggle with gut health issues and they're just given a specific pill or something and the microbiome is not addressed at all. So I'd love to touch on both of those.

• 29:07Speaker 01

  Let's click into the optimization world first. And so let's kind of zone back up. You know, I have a lot of physician friends and colleagues and I have to ask them, like, how's your diet? And they're like, oh, Zane, it's really hard. Like, you know, 80/20 life, right? And they're looking for insurance policies, right? An insurance policy on the microbiome, whether it's multivitamin, right? Like, I don't eat right, or for your microbiome. It's not a replacement. I also think having a healthy diet is mission critical, increasing your fiber, fermented foods. These are important things. But I believe in dietary supplements to supplement because I'm a pragmatist on my day-to-day life. We know. And so one way to think about gut probiotics

• 29:51Speaker 01

  is how do you pick them and which one do you want to take? And I think it's really important to know that not all probiotics are the same.

• 29:57Dr. Darshan Shah?

  Absolutely.

• 29:58Speaker 01

  It's like saying the word medicine, right? Aspirin and Viagra, very different. Yet actually clinicians have a tough time understanding the differences between different probiotics. You know, gastroenterologists have a tough time delineating which one it is. In fact, they do these studies where they aggravate all probiotics together to see if it works for a condition. We would never do that for a medicine. Let's aggravate all medicines together to see if it works for a condition. And so really understanding which product you take matters a lot. And the question and framework that I suggest to patients that are trying to optimize their health is think about the four D framework, something that's practical and solution-oriented. First D, diversity. We talked a little bit about that before. But like a forest, diversity is a good thing.

• 30:43Dr. Darshan Shah?

  Absolutely.

• 30:44Speaker 01

  A very good thing for your gut. The more beneficial, healthy microbes you have in your gut, the better.

• 30:50Dr. Darshan Shah?

  Yeah.

• 30:50Speaker 01

  Yeah, we know that probiotics, most of them are one bacteria, maybe two, just a handful. DSO1, it's the product by seed.

• 30:58Dr. Darshan Shah?

  Yep.

• 30:58Speaker 01

  Is, is different. It has a wide variety.

• 31:02Dr. Darshan Shah?

  It's like 12 strains?

• 31:03Speaker 01

  Twenty-four.

• 31:03Dr. Darshan Shah?

  Twenty-four strains, wow.

• 31:05Speaker 01

  And it has, covers a wide genomic diversity, about 35,000 unique microbial genes. So it's giving you this diverse microbial package, which is different than most things. So number one, diversity. Number two, delivery. Just like a forest, if the sunshine doesn't get to the trees, it doesn't work.

• 31:20Dr. Darshan Shah?

  Yeah.

• 31:21Speaker 01

  It can't grow. Yet most probiotics kind of die in the stomach, from the stomach acid, right? DSO1's different. It has a targeted delivery technology, Viocap, to get to the colon, to allow for the optimal growth of these beneficial microbes.

• 31:35Dr. Darshan Shah?

  It's like a capsule within a capsule, right?

• 31:37Speaker 01

  That's right, capsule in capsule, almost like a Russian doll, right?

• 31:39Dr. Darshan Shah?

  Yeah, like a Russian doll.

• 31:41Speaker 01

  Exactly, exactly.

• 31:42Dr. Darshan Shah?

  And so the outer layer melts in the stomach, but then that allows the inner layer to make it to the colon.

• 31:46Speaker 01

  That's exactly right. And the outer layer actually links to the next D in the four D framework, which is do-gooders. So it turns out that, just like in a forest, you need fertile soil. No food, trees don't grow. Yet most probiotics don't include a prebiotic, the thing that the bacteria need to grow. And that's exactly what's in the outer capsule with DSO1. It's a prebiotic, a potent polyphenol prebiotic that helps the bacteria grow and thrive. And so a prebiotic and a probiotic equals symbiotic, which is what we pine for.

• 32:19Dr. Darshan Shah?

  Got it, got it. And what's the fourth D?

• 32:21Speaker 01

  The fourth D is data.

• 32:22Dr. Darshan Shah?

  Wow.

• 32:23Speaker 01

  Right? I think, I would say that typically, most groups don't complete studies on the full formulation of the product, and we can talk more about this, but taking a biotech approach to every D health. And where we really evaluate the science and the clinical trials to be able to make an impact on health, the ones we can talk more about. So think about those four Ds, diversity. Delivery do-gooders, those prebiotics, and then data. That's how I pick up my probiotic.

• 32:49Dr. Darshan Shah?

  Yeah, that's great. So just as, like you said, a probiotic is a supplement, but it's, if you're eating ultra-processed food, you have zero fiber in your diet, you have no polyphenols, you're just, you know, it's like you're putting out a city fire with a tiny little water hose, right? You gotta do both, I think. And I like to think of probiotics as my insurance policy for the days I don't have the chance to eat an optimal diet, right? And so I think it's really important to understand that the gut needs on a daily basis, polyphenols, it needs fiber. There's different kinds of fiber and fermented foods as well, if you can get them in as well. And so I would love to hear some of like your advice around fiber, polyphenols,

• 33:31Dr. Darshan Shah?

  and fermented foods, anything else you think is beneficial on a day-to-day basis of having your diet, so you have the healthiest micro, most diverse, healthy gut microbiome.

• 33:41Speaker 01

  Yeah, I really think fiber is like the holy grail. And I think we've forgotten that to some degree. If we look back into ancient times in history, we've had up to about 40 grams of fiber. Nobody, very few people these days are taking 40 grams of fiber.

• 33:57Dr. Darshan Shah?

  But that's because fiber's not in processed food. They take it out of processed food because it makes the food go bad.

• 34:02Speaker 01

  That's exactly right, exactly right. And I think we have to reintroduce fiber is really, really important. Do it gradually. I'm a big believer in doing it slowly and gradually because you can get, if you have too much too quickly, you can get bloating, you can get some GI distress. And so start with, you know, five grams in your diet. And if you need to supplement, supplement five grams. Go for a week if you're okay, increase another five grams. You're okay, another week. Keep going gradually to get to that target range. Don't have to get all the way to 40, but at least get to 30 grams all in is a really important part of helping your beneficial microbes. In fact, those are the necessary foods to help those butyrate-producing organisms.

• 34:42Dr. Darshan Shah?

  And what foods does this fiber come from?

• 34:45Speaker 01

  I come from grains and like psyllium is my go to choice. I really like psyllium fiber. I think it's excellent data and also healthy. Try to avoid things that are packed with sugar or dyes, et cetera. I don't have allegiances to brands or to types. Just look at what is available and what is as clean as possible.

• 35:05Dr. Darshan Shah?

  Right, yeah, I think clean as possible is key there because a lot of the fiber supplements, they found heavy metals in them and other contaminants. And if it comes in a plastic container, you might have microplastics. You've just got to be real careful.

• 35:16Speaker 01

  Yep.

• 35:17Dr. Darshan Shah?

  But I always advocate for getting it from natural food sources primarily. But like you said, that's hard for people. And so having a supplement available just in case you go a day and you don't get your fiber intake. It's good to have.

• 35:28Speaker 01

  Yeah, it's great. And it's not even just your microbes. You know, for colon cancer and heart health and many other reasons. It's like super, super important. So it's a good, it's a good approach to try to think about your fiber intake.

• 35:41Dr. Darshan Shah?

  Right, very well researched that. It prevents, normal fiber intake prevents cardiovascular disease. We know that also prevents colon cancer because it keeps gut mobile, right? And what about fermented foods?

• 35:52Speaker 01

  Great area of ongoing research and really powerful. I think diversity of fermented foods. There's a recent paper that came out of Stanford, I believe, that shows that's the key piece of it. Again, back to that diversity, right? It's the entire, it's kind of like the equilibrium of the world. So the more diverse you can from your fermented foods, the better you are.

• 36:12Dr. Darshan Shah?

  Okay, and then just to kind of wrap a bow around all this for optimal gut health. You know, one question that comes up a lot, and this can be controversial. You have these people that are on either a keto diet or a carnivore diet that have basically eliminated fiber from their diet completely, right? And so what do you think is the destiny of those people? And what should we think about? What should we counseling our patients on those types of diets?

• 36:38Speaker 01

  It's tricky. I know every, there's some really good data to show that there's a personalization to the way diet is how we metabolize. Right, I think that data has been really, really quite clear. It's about striking the right balance. I think you can do everything but all at the same time. And so I think my approach is that those are hard to do without getting those, that fiber. You just can't do it actually if you're being very restrictive. Do for keto might be different than than others, but can you have that 80 20? Can you get that fiber in? I just think it's an overwhelming amount of data to just the benefit. And so although controversial, my thesis is stick to your fiber. Get your fiber in there. I understand there's benefits for keto and and other kind of dietary changes.

• 37:20Speaker 01

  But I I think the benefit over time, when you're talking about the long scope of time, the fiber is going to win out.

• 37:26Dr. Darshan Shah?

  I agree. You know, I counsel my patients that are using keto. And I actually prescribe a keto diet and carnivore diet at some points to certain people that need a very restrictive elimination diet just to get a gut reset.

• 37:38Speaker 01

  Sure.

• 37:38Dr. Darshan Shah?

  But I always say it's an intervention, not a lifestyle.

• 37:41Speaker 01

  Yeah.

• 37:41Dr. Darshan Shah?

  I think humans have evolved for thousands of years to live positively with fiber and polyphenols. And I think eventually introducing those back into your diet is a good idea for most people.

• 37:55Speaker 01

  I think that's right. I think with the exception of some really like corner like medically cases, there's some data with like epilepsy and ketogenic diet that looks pretty interesting, actually. And so I think for an all comer population, I think your approach is like exactly right. It's a lifestyle. And so getting to the right right approach with fiber is the right goal.

• 38:13Dr. Darshan Shah?

  Yeah. And the Pareto principle is the 20% is going to move the needle 80% for you is just eliminate the ultra processed food.

• 38:19Speaker 01

  The creep.

• 38:20Dr. Darshan Shah?

  That's the key.

• 38:21Speaker 01

  Yeah.

• 38:27Dr. Darshan Shah?

  Dr. Shah here, and I want to take a quick moment to talk to you about metabolism. So you've probably already heard, unfortunately, 88% of Americans are metabolically unhealthy. And it's not because of what they're eating. It's actually a lot about what's living in your gut. I'm talking about your microbiome. This is the community of bacteria that controls everything from how you process sugar to your energy levels to your mood. There's actually one specific strain in your microbiome called Akkermansia muciniphila. That's absolutely critical for metabolic health. This is a bacteria that strengthens your gut lining. It helps you metabolize carbs more efficiently and it increases GLP-1 production naturally.

• 39:10Dr. Darshan Shah?

  The problem is almost everybody is completely deficient in it. And until recently, there was no way to get this. But that's why I'm really excited about joining Pendulum. They're the first company in the US to bring live acromansia to the market. The company was founded by PhD scientists and doctors with the Mayo Clinic as their first investor. The metabolic daily formula that I take every single day doesn't just contain acromansia. It's formulated with multiple next generation strains. And these all work together to optimize your metabolism from the inside and out. So you can track every macron calorie if you want. But if your gut microbiome is out of balance, you're going to be fighting an uphill battle.

• 39:51Dr. Darshan Shah?

  Pendulum is going to give you the tools that you need to fix your gut at its source. Try Pendulum today. Head to my link below and use the discount code. You're going to feel the difference a healthy gut microbiome can make.

• 40:09Dr. Darshan Shah?

  Hi, Dr. Shaw here. I want to take a minute to talk to you about cellular health. So in my clinics, I've actually seen 30 year old people with cells that look like they're pushing retirement. And I've also seen 60 year olds with cells that look like they're 40 years old. So what's the difference? It's really about how fast their telomeres are breaking down. Your cells you see are like phones and they have limited cellphone battery. Poor sleep, stress, processed foods, all of these things can drain that battery way faster than it should. So this is the reason why I partnered with IMA. IMA powers that cellular battery. It's not just another multivitamin. It's a comprehensive 92 ingredient formula designed specifically for cellular health and longevity.

• 40:54Dr. Darshan Shah?

  I'm talking 900 milligrams of vitamin C. That's like 20 oranges worth of DNA protection. The clinical dose of CoQ10 that you need to power your cellular engine. You also get zinc, selenium, vitamin E, alpha lipoic acid. All of these work synergistically for cellular repair and protecting your telomeres. So instead of taking a handful of pills every day and all these supplements, IMA actually gives you everything that you need in one scientifically formulated system. And this isn't just a theory anymore. IMA had Partnered with Oxford University, the International Space Station, San Francisco Research Institute, and they've done studies and they've gotten this NSF certified to truly power your health. Most people are aging twice as fast as they should, unfortunately.

• 41:40Dr. Darshan Shah?

  You don't have to be one of them. Try IM-8. I actually have a discount secured for you if you go to drshah.com/ima or go to im8health.com/discount/drsah and you can get 20% off with my discount code, drshah. You can also find the link below.

• 42:00Dr. Darshan Shah?

  So, okay, so moving on from like the person trying, oh, no, I want to talk about also the longevity focused, the health optimization focused person. There's a lot of microbiome tests out there, direct to consumer, available at the doctor's office. What's your feeling about those? How often should people do them? What kind of data points you get from those?

• 42:21Speaker 01

  Yeah, great question. So I'd say again, similar to ProVox, not all microbiome gut tests are the same.

• 42:26Dr. Darshan Shah?

  Right.

• 42:26Speaker 01

  I think there's been a, be a bit of a bad rap around microbiome testing. I think people were ahead of the science a little bit about a decade ago. I think that's changing now. I think we now have almost a crystal ball that we can kind of look into the future to some degree. There is a resurgence of microbiome testing, but I think there's three things you have to really think, keep in the back of your mind. So number one, you really have to do deep sequencing. I think there's a lot of PCR tests which are not very effective or very helpful. So you have to think about kind of deep microbiome sequencing is being really, really important. Number two, you have to be able to have a tool that interlocks with the abundance of new data. I'm a big believer in standing on the shoulders of giants. There's so much data. In fact, there's

• 43:07Speaker 01

  2,000 microbiome papers published every month. So what can you do to be able to harness the microbiome literature that's out there to inform your health more actively? And then number three is something that is pragmatic to change something, to change your diet and or give advice. And there's one company that I, that I think does a good job of that called Jonah Health that has a tool that does that deep sequencing and is tied to the AI that allows you to actually get to recommendations that are transparent. So you can see why is that recommendation made? What's the paper that says that? And go click on it and get to the paper and, and read it. And being much more transparent and much more understandable to what the microbiome is. So that's how I think about the microbiome testing place.

• 43:51Dr. Darshan Shah?

  Yeah, that's, that's a great point. How often should someone test their microbiome?

• 43:55Speaker 01

  I think that like honestly, everyone has their own rhythm of of what makes sense for them. I think a yearly test is very reasonable, or every six months is very reasonable to be able to get general broad strokes. I consider the microbiome testing now not to be, um, you will test it and you will have IBD. No, it's more like a CRP. It's a guide towards where your health is and where you should be exploring more as opposed to a definitive diagnostic for a medical condition. And so if you frame it that way, how often are you doing your CRP? How often are you doing your other biomarker tests? I think just pair them at the same interval as your biomarker test. If you're someone that wants to have a very close eye, do it more frequently.

• 44:39Speaker 01

  If you're someone that wants to do it kind of with their general annual, I think that's okay too. I think everyone has their own, you know, playbook.

• 44:45Dr. Darshan Shah?

  I fully agreed with you on that point. I think it's a good indicator of overall health. I don't think it necessarily, for many conditions, doesn't necessarily point in one direction. Now, some of the testing does actually tell you if you have parasites, fungi, other things growing on that are potentially very harmful that need to be eliminated, but most of the consumer ones don't, I think. So, yeah, it's it's it's an interesting world out there with microbiome testing. This, I feel like there's a new one every few months that comes out. Can you double click on the on the deep sequencing? Because how does someone know if their test is offering deep sequencing or not? And what is deep sequencing?

• 45:20Speaker 01

  Great question. So there are different ways to interrogate the microbiome. You can kind of think of it, right now, most tests look like with the equivalent of like a microscope effectively, something called a PCR test, which is probably the most common way people look at the microbiome. On the other side of the house is sequencing, uh, which is looking at the genetic code of the bacteria themselves, or even beyond bacteria, other types of microbes. And this is where we use genomics, genomic analysis to understand, and this is like with the world's best microscope effectively. And so you have to look at the actual test itself specifically, and are they doing sequencing? And if so, how deep are they sequencing? And so that is kind of something that you have to look under the hood a little bit about

• 46:03Speaker 01

  and often buried in the frequently asked questions perhaps. But look for groups that are doing the genomics, not the PCR based testing.

• 46:10Dr. Darshan Shah?

  Got it, okay, those good, great advice on those. And then let's kind of zoom out a little bit more outside of the gut.

• 46:17Speaker 01

  Sure.

• 46:17Dr. Darshan Shah?

  Well, let's stay in the gut, but go up to your mouth. Your mouth also has a microbiome. That's very important. Can you talk about oral microbiome?

• 46:27Speaker 01

  Absolutely. So the microbiome in the mouth has got both direct consequences and indirect consequences, it turns out. So let's do direct first. So direct, it has a huge impact on even things like halitosis, right? Like bad breath, things that actually have significant quality of life factors. In fact, I remember reading a study that was done on a probiotic chewing gum to be able to outcompete the bad bacteria in your mouth that produce the odor, right? So I think there's a, there's a piece to that for sure, in addition to like cavity formation and some of the more common things. There's even oral microbiome as potentially a biomarker for more systemic health.

• 47:04Dr. Darshan Shah?

  Yeah.

• 47:05Speaker 01

  And so some of the microbial signatures, or even some of the biomarkers in the mouth that come from microbes have been associated with cardiovascular disease, rheumatological conditions, inflammation of the joints. And so that's something that I think is still emerging.

• 47:18Dr. Darshan Shah?

  So interesting that you can actually do a mouth swab, culture it, and have an indication if someone has rheumatologic disease. Yeah. So with the microbiome of your mouth, how does one keep your oral microbiome healthy? I know there's a lot of products out there they're selling now, oral microbiome, kind of chews and things like that. Does everyone need to do those? Or what are your thoughts on this?

• 47:40Speaker 01

  I think that, I think that place is where the research is still, hasn't quite caught up. I think it's still in its infancy. I would say, you know, brush your teeth. There's some controversial data about mouthwash and, and microbes, but it was a very small study in a very specific patient population. I think just general hygiene practices for now is probably where we should be. I think one place to just be mindful of ties back to our conversation related to overuse of antibiotics. Some dentists, not everyone, are really aggressive with, with antibiotics. And so just be cautious and careful there because the guidelines have changed related to dental work and antibiotic use. Just be an advocate for your health. Is this absolutely necessary? Do I really need this clindamycin? And I think that's one piece where I think it ties to more systemic than microbiome too.

• 48:25Dr. Darshan Shah?

  Yeah, that's great advice because you're right. A lot of dentists give antibiotics to everybody. I think most dentists now are using it for if you have like heart valve issues or something, something that's going to predispose you to getting a more systemic infection. So definitely a great conversation to have with the dentist if they're going to do a procedure. But just overall, I think oral health, we know poor oral health is tied to a higher risk of Alzheimer's disease, a higher risk of cardiovascular disease. And so maintaining good oral health is extremely important. Brush your teeth, floss your teeth, right? Twice a day, and then also see your dentist for a deeper cleaning twice a year.

• 49:00Speaker 01

  Absolutely.

• 49:00Dr. Darshan Shah?

  I think it's good baseline advice there. Okay, then let's talk about the skin after that. So we also have microbes on our skin.

• 49:07Speaker 01

  We have so many microbes on our skin.

• 49:08Dr. Darshan Shah?

  Should we be washing them off every day with antibacterial soap?

• 49:11Speaker 01

  We should absolutely not be doing that. The leading question you have there. I think the skin is really interesting, not only from a like, from a medical condition situation, but also from a cosmetic situation. So there's both, I think, pillars to this, and we can kind of talk about both.

• 49:25Dr. Darshan Shah?

  Please.

• 49:26Speaker 01

  I think the couple of really interesting ones related to on the medical side of the house, and you'll email me here, but there's a condition called alopecia, where you have an autoimmune condition where your hair is gone.

• 49:37Dr. Darshan Shah?

  I have that. Okay. I used to have alopecia areata.

• 49:39Speaker 01

  Okay, so alopecia areata. Tricky condition, right? Some people have immune modulators, there's other approaches.

• 49:46Dr. Darshan Shah?

  I was given steroids for it.

• 49:47Speaker 01

  That's right, exactly. There's a couple of really interesting reports, so early data. I'll go back to the fecal transplant world for a second outside. I mentioned too that that the microbiome drives, the GI microbiome drives the immune system, but even beyond the gut. And case study was done where, or two at least now, out of Brown University called Colleen Kelly, and she gave a fecal transplant to a patient that had alopecia for CEDF. But something really interesting happened six months later. Person went from having no hair to growing all back.

• 50:17Dr. Darshan Shah?

  Crazy.

• 50:17Speaker 01

  Wild. And that's been replicated a couple of times, likely to the immune system approach, right? So there's something about the way that our gut and our skin also interact, it's got skin access that I think is really clear. There's also skin skin, which is what your skin microbes themselves. And there's been really interesting studies that do skin microbiome. For acne and they've seen wonderful data to out compete the acne bacteria with microbes that have it's actually a different strain of C. acnes that doesn't cause the clinical consequences of like acne on your face. And so that's been kind of early work that's been starting to show a little bit of interesting data on the skin to skin, which is which is really interesting.

• 50:58Dr. Darshan Shah?

  Acne is a massive problem. I mean, everyone's using Accutane or some other, you know, sometimes dermatologists give antibiotics orally for bad acne.

• 51:07Speaker 01

  That's right.

• 51:08Dr. Darshan Shah?

  So this could be a potential.

• 51:09Speaker 01

  Potential down the road kind of solution. And even with, you know, I would say on the cosmetic side, we know that hydration barrier inflammation, we think that and we know that inflammation back to our initial thesis is the driver of wrinkles. And if you can decrease the systemic inflammation, great, so beauty from within, but also topically, skin microbes have the ability to decrease inflammatory cascades that can lead to wrinkles and also the barrier being disrupted. So that's kind of something where I think the field is going.

• 51:36Dr. Darshan Shah?

  Is that the next seed product, a skin?

• 51:39Speaker 01

  Our pipeline is very, very under top, top secret. So we'll keep you posted, but it's a it's an area that I think is really, really exciting.

• 51:45Dr. Darshan Shah?

  I want to test it when it comes out. Okay, so we've covered the skin, we've covered the gut. Let's talk about women's health and vaginal microbiome. That's extremely important as well. Tell me a little bit about the thought process. I know you guys have a product for a suppository, right? For the vaginal microbiome?

• 52:02Speaker 01

  I think the vaginal microbiome, I think is like the next frontier in some ways of the microbiome. I think it's what I felt about with C. diff like a decade ago, I think I can see happening in the vaginal microbiome space. It's a sector where, you know, 40 million women have vaginal conditions and it's really hard. There's not a lot of good solutions. There's been a lack of innovation. But the vaginal microbiome is very different than the gut microbiome. We talked about diversity being a good thing in the gut. It's the opposite in the vagina. Yeah, you only really want to have one specific microbe and one very specific type. You really want to have lactobacillus crispatus. People that have more diverse microbiome in the vagina is associated with in epidemiological studies, many women's health conditions, everything from.

• 52:45Speaker 01

  Dieteral vaginosis, recurrent urinary tract infections, even fertility challenges.

• 52:50Dr. Darshan Shah?

  So interesting.

• 52:50Speaker 01

  It's a totally different world where you want to go to the opposite. And when you have this lactobacillus crispatus, it allows you a decrease in inflammation, increase in the barrier function, and increase in the acid in the vagina, which is very protective. And so that's a really important part of thinking through the biology that's different than the GI system. And so we partnered with one of the world experts in the vaginal microbiome, Jacques Rival, who looked at a cohort of women and deeply sequenced them very carefully and realized that it's not just any lactobacillus crispatus. It's three very specific types that he put together. And then we actually worked with him to develop a product that includes both prebiotics and a targeted delivery, kind of all together, to create VS01,

• 53:34Speaker 01

  which is a vaginal symbiotic for women. And I think it's been really, really amazing to see the response from women that are having a huge benefit. And I've been working with a number of clinicians in the OB-GYN space and the gynecologists, who are now like 30 to 50% of all their patients are putting onto this because they're seeing the benefit. And that's something we're really excited about.

• 53:55Dr. Darshan Shah?

  Is this something you take proactively? Or do they take it if they're having a condition?

• 53:59Speaker 01

  You can do either. So nine in 10 women have some disruption in the vaginal microbiome. I think right now, most people are taking it with something just feels off, right? And or they're going to their women's health clinician, and something's just not quite right. And it's you take a kind of an induction period. So you hit them hard to reset for the first month. And then you can kind of take it as a maintenance thereafter to protect a little bit more.

• 54:21Dr. Darshan Shah?

  Got it, got it. Those fantastic science that you guys are doing out there.

• 54:25Speaker 01

  Yeah.

• 54:26Dr. Darshan Shah?

  Okay, let's move on. I know we talked a lot about just optimizing microbiome health. Let me just touch base on that one more time, too. So you have this product, OS1, right?

• 54:35Speaker 01

  DS01, yeah.

• 54:36Dr. Darshan Shah?

  DS01. And would someone just take that once a day, twice a day? What do you recommend with food, without food?

• 54:42Speaker 01

  Two capsules, once a day.

• 54:44Dr. Darshan Shah?

  Okay. Doesn't matter.

• 54:45Speaker 01

  Doesn't really matter. Like whatever it's going to do, that you're going to remember to take it. So habit stacking is really important. You're brushing your teeth and you're stacking your habits. It's the most important is you get it in, not the timing when you get it in.

• 54:57Dr. Darshan Shah?

  Great. And then this particular pill does not need to be refrigerated, right? But they're still alive in there.

• 55:03Speaker 01

  Correct.

• 55:04Dr. Darshan Shah?

  Because they're in this.

• 55:05Speaker 01

  Live off alive. So they're like put into hibernation mode, kind of freeze dried. And that's actually a really, this is something I think some people don't quite know, but it's like really important is that the freeze dry conditions, it's really easy when it's one bacteria. But when you're trying to freeze dries many different bacteria that have very different freeze dry parameters. It's actually a really complicated problem to solve and we've been able to solve that. And the way that we do our quality control is to make sure that those bacteria are alive as well. We use something called flow cytometry, which is like the gold standard of ways to make sure the bacteria is there and alive.

• 55:38Dr. Darshan Shah?

  Got it, got it. Okay. You just, once a day, it doesn't matter what time of day you take it. Got it. Great. Fantastic. And now let's talk about certain conditions that I think that I've used probiotics for with my patients. And I'd love to hear your take on these. So one is metabolic health, right? So I have a lot of patients that have poor metabolic health. They, you know, hemoglobin A1C is high. They have trouble losing weight and we have a long talk around GLP-1s, obviously. And so a lot of patients are on GLP-1 injectables now as kind of a bridge to help them lose weight. But my talk tack with them is that while you're on this exogenous GLP-1, we need to work on getting you to make your own GLP-1 again.

• 56:20Dr. Darshan Shah?

  And a large part of that equation is your microbiome. So tell that you take it from there.

• 56:26Speaker 01

  Yeah, absolutely. So I want to go back to that master molecule that we talked about before called butyrate. And butyrate is this like superpower molecule because it does something really interesting with respect to metabolic health. It actually interfaces and increases intestinal GLP-1. And intestinal GLP-1 is not the same thing as Ozempic, right? We know that's a systemic administration to your brain effectively. But intestinal GLP-1 has been shown in some studies to actually also affect your vagus nerve and then actually affects the tide in your brain through a slightly different pathway. And so you're seeing this like a duality of, of your, your natural GLP-1 actually is spawned by actually your microbes. Or has the ability to be kind of triggered by your microbes.

• 57:10Speaker 01

  And so that's an area we think that's really, really important. So microbes that increase butyrate have a very powerful impact on, on, on even your metabolic health.

• 57:19Dr. Darshan Shah?

  Are there specific microbes that do that?

• 57:21Speaker 01

  There are, and in fact, actually, you know, some, we have some really interesting data that we'll be sharing at our next major medical meeting. So like spoiler alert, but DS one is able to increase butyrate, uh, which I think is really, really powerful to show in humans, which has been something I'm really, really proud about.

• 57:35Dr. Darshan Shah?

  Yeah, no, that's huge. Okay. And so metabolic health. So once again, I, you know, I put people on a probiotic every time they're going through this GLP one journey. And I think it's extremely important for all the listeners of this podcast, if you're on Ozempic,

• 57:48Speaker 01

  Yep.

• 57:48Dr. Darshan Shah?

  to use the time you're on this to number one, reframe your relationship with food, but also to rebuild your gut, rebuild a healthy gut.

• 57:56Speaker 01

  I think that's really important. I think the thing to also add on to that is that one of the most common consequences of systemic GLP one therapy is constipation, nausea, vomiting. The GI manifestations that are really, really tough. In fact, most people stop or can't increase the dose because of the constipation. And so being able to optimize your gut health for the constipation as an adjunct is also really, really important.

• 58:20Dr. Darshan Shah?

  Yep. We can help on that side effect as well. Yeah, for sure. Let's talk about reflux disease and just gastric ulcer disease. Okay. So, you know, you being gastroenterologist, you've dealt with a lot with this.

• 58:31Speaker 01

  Yeah.

• 58:32Dr. Darshan Shah?

  Me being a surgeon, we had to have a lot with this. We used to do a surgery, which just seems so barbaric right now. We used to cut the vagus nerve for this. Terrible, right? And then, you know, that surgery went away because of the advent of PPIs, proton pump inhibitors. And it turns out that's not necessarily a good thing either, or even the right treatment, right?

• 58:54Speaker 01

  It's interesting to think about peptic ulcer disease because if you go back actually historically, we used to think about stress, right? Remember back, you know, that was like the thesis and then Barry Marshall from Australia is like a maverick of a scientist clinician worked with, uh, you know, was, was at DDW and also was kind of laughed at and said, no, no, I think it's a bacteria, guys. I think it's a bacteria that's causing this. They're like, no, no, no, get out of here, Barry. You're like, what are you talking about? And he kind of proved them all wrong because he, and the famous experiment where he took a vat of Alcoobacter pylori and got peptic ulcer disease and then won a Nobel prize.

• 59:27Dr. Darshan Shah?

  Yep.

• 59:28Speaker 01

  Shows that. Bacteria have a huge impact in peptic ulcer disease. I think that's really, really important. Certainly, I think for individuals that have halicobacter pylori confirmed diagnosis, antibiotics plus PPIs have been shown to be very effective in clearing. So that's really important. I think your thesis around PPIs and your question around PPIs, I think they can be right in the right populations, as all things, right? I think there's no panacea in life. And so, thinking about what's the underlying cause? Can you get there first with non-therapeutics first? Things like dietary changes have been very effective, actually, for peptic ulcer disease, or, sorry, GERD, I should say, or reflux, I mean. So I think thinking about that, had a bad test, those are really important. PPIs themselves, I think, sometimes get a bit of a bad rap.

• 1:00:11Speaker 01

  And we can talk more about where they get the bad rap from. Probably three areas people worry about. So we can talk about three of them. One is C. diff. The second is kind of bones, essentially, osteoporosis. Those are, and the third is kidney disease, but pretty rare. And so we can talk-

• 1:00:26Dr. Darshan Shah?

  Aren't there some vitamin deficiencies associated with the two?

• 1:00:28Speaker 01

  There's some that have been reported. I think the challenge with those studies are all large epidemiological studies. They have large confounding variables because so many people are on PPI and typically they're elderly and not eating well. And so that's kind of one of the challenges where, same with C. diff. C. diff affects elderly individuals more than young individuals. So a lot of the, like, I would say, strong GI epidemiologists say, always worthwhile thinking about, measure your vitamins if needed and make sure you get your DEXA scans and your BMDs appropriately. But probably they're generally safe.

• 1:00:59Dr. Darshan Shah?

  Yeah. But do you think PPIs, I feel like, you know, they're given out just like antibiotics. They're like candy now. And I feel like people stay on them for years and decades. And they don't use the time that they're on. I feel like PPIs mask the symptoms of something that needs to be corrected in an underlying basis.

• 1:01:17Speaker 01

  I think you're absolutely right there. That's one thing where, if you have a course of it, it's good to take a holiday.

• 1:01:22Dr. Darshan Shah?

  Yeah.

• 1:01:23Speaker 01

  See, are your symptoms gone? Are they, are they good? I'm a big believer in trying something. If it's effective, but it's not a life-threatening condition, that's important, right? You don't want to stop your chemotherapy or your, you know, your really important medicines. But have a conversation with your clinician and say, hey, is there any hard- Me stopping this and trying to take a couple of months off. And if it comes back, then you know, then maybe you have to go back on it. But I think having that kind of conversation with your clinician is really important. Because we get into this world of polypharmacy.

• 1:01:51Dr. Darshan Shah?

  Yes.

• 1:01:51Speaker 01

  Kim, you know this and I know this. I see patients with these lists, like thirty medicines, like, why did you put on this? I don't know. How long have you been on it? I don't know. I'm like, oh, we need to do some like housekeeping, right? And so I think that part of it is really very, very true.

• 1:02:04Dr. Darshan Shah?

  That's so true. Yeah. And I think also with PPIs in particular, you know, I think that with the advent of GLP-1s, most people that are on PPIs, in my experience, are very overweight. The minute we get their weight down, they can come off of PPIs and then hopefully off GLP-1s as well. So okay, let's move on down the GI tract from the stomach to the intestine. So sometimes people with, that are on PPI, sometimes the people that have taken antibiotics or even have heavy metal toxicities, get a condition called SIBO, right? Small intestinal bacterial overgrowth. I'll let you take that one from there too.

• 1:02:39Speaker 01

  You know, SIBO or small intestinal bacterial overgrowth is a really tricky condition. It's actually really, really common. A lot of people have this. They get terrible bloating, a lot of gas, abdominal discomfort. I've seen patients that like show pictures before and after on how much they've like distended. And it's a really like very difficult situation and it's likely probably driven in part by bacteria or actually even other microbes, not bacteria, but archaea, which are other microbes that can produce gas. Right now, the treatments are often antibiotics, right, to try to clear out those bacteria. There's some rifaximin, yeah, exactly, or other ones that are cycled through. The treatments are okay, right? And I think you'll probably have patients like this that are just suffering over and over.

• 1:03:24Speaker 01

  I think it goes back to the first principles about, okay, it's okay to clear out the bacteria, but you're not done. That's only one step. You gotta follow it up with replacing it with a healthy nutritional diet that's diverse in fiber, prebiotics.

• 1:03:40Dr. Darshan Shah?

  What caused it in the first place? There's a reason those bacteria overgrowth.

• 1:03:43Speaker 01

  That's right. That's right. Exactly. So what's the source of that? Right? What's coming from the overall microbial environment? So how can you get your overall health and lifestyle factors better?

• 1:03:53Dr. Darshan Shah?

  Yeah, yeah. A lot of my patients with SIBO, you know, we sometimes send people for the breath test because there's for people who don't know if you're struggling with abdominal distension, bloating, some of these symptoms of also alternating diarrhea, constipation sometimes, get the breath test done. It's really easy to do and that'll tell you if your stomach bacteria are fermenting a special kind of sugar, right? And that's how they measure it. And then if it's positive, it's time to start looking for the reasons you might have SIBO.

• 1:04:22Speaker 01

  That's right.

• 1:04:22Dr. Darshan Shah?

  And so I found people with heavy metal toxicity, even mold toxicity sometimes affects your gut as well. And so I think it's a common problem and there are solutions, but step one is to get, figure out that you have it.

• 1:04:33Speaker 01

  That's right. That's right. I think it's not always thought about by clinicians.

• 1:04:36Dr. Darshan Shah?

  Exactly.

• 1:04:37Speaker 01

  So I think it's an underdiagnosed problem and I think gets you on a journey towards optimizing your gut health.

• 1:04:42Dr. Darshan Shah?

  Yeah, exactly. Yeah. And the treatment is optimizing your health overall, actually. And sometimes antibiotics or for CFO, small intestinal fungal overgrowth, there's also antifungals you can take, but like you said, just a bridge to fixing the root cause in the first place.

• 1:04:57Speaker 01

  Exactly.

• 1:04:57Dr. Darshan Shah?

  Got it. So back to specific conditions. Are there any other specific conditions that you can, oh, I know another one that I wanted to quiz you on, but I'll quiz you on, ask you about is post antibiotics. Okay. So say you absolutely have to take an antibiotic. Your doctor's like, if you don't take this, you're going to end up in the hospital. Gives you Cipro. That's like a nuclear bomb to your gut bacteria, like you said. What can you do?

• 1:05:21Speaker 01

  No, so I think this is a really important question. It's a question I get at the gastroenterology and every dinner table conversation. Saying I took a bunch of antibiotics, which probiotics should take to kind of supplement and give back my good bacteria? Or if you had SIBO, right? You could have had antibiotics. So I think there's a lot of questions about what to do in that context. And I think what we're really excited about, we talked about data being really important is not all probiotics are the same. And in fact, there's a study done in this prestigious journal called Cell saying, oh, probiotics don't work.

• 1:05:49Dr. Darshan Shah?

  Yeah, I remember that study.

• 1:05:51Speaker 01

  For individuals that have taken antibiotics. And that to me is like, cool, medicine doesn't work? Like, what are we talking about? That specific probiotic doesn't work in that context.

• 1:06:00Dr. Darshan Shah?

  I think they tested like a single strain or two strains only.

• 1:06:02Speaker 01

  That's right. I was thinking it was 11, but it was still a narrow, generally narrow probiotic. Didn't have targeted delivery, didn't have the right microbes. And so all the details in those four D approach don't come to bear. And so when we, so we said, okay, great. Let's take that as a challenge. The study said probiotics don't work. We're going to say DSO1 is different. Let's go and evaluate specifically the impact of antibiotics on individuals that have with DSO1. So we did a double-blind placebo-controlled trial where one arm got broad-spectrum antibiotics, they got Cipro and Flagyl, and they got DSO1 during the antibiotic course and after. And then the other arm got antibiotics and a placebo

• 1:06:43Speaker 01

  during antibiotic course and after. And we looked very deeply into their microbiome and actually the barrier function, which is a big driver of the biology of what the antibiotics are disrupting. So antibiotics disrupt your barrier function, that leads to inflammation, leads to all the consequences of health.

• 1:07:00Dr. Darshan Shah?

  How did you evaluate the barrier function? Serum's onulin?

• 1:07:03Speaker 01

  We did not use onulin. We used a lactulose-based test, which is the gold standard. Yeah. So that's the kind of the key thing. That's a great point because there's been a recent systematic view in med analysis, about eight trials, over 500 participants, and I was the only one that was able to show a positive benefit with the lactulose-based test, which is the gold standard. You want to look at the right biomarker, right? And so that kind of already spoiled the answer, but we showed an improvement in the diversity, showed an improvement in the beneficial bacteria compared to placebo 175-fold, and we showed an improvement about 50% better in the barrier function compared to placebo. And that was something we're really proud about. So when my dad unfortunately had to test antibiotics, guess what he got? He got an antibiotic that I feel comfortable and confident knowing is going to optimize the barrier function.

• 1:07:46Dr. Darshan Shah?

  Got it. And so this is a published research that you have out there, and it showed to take DSO1 during and after the treatment of antibiotic.

• 1:07:55Speaker 01

  So we presented it at Digestive Disease Week, and it's been published in the gastroenterology, which is a journal that kind of ties to that, and the full paper is under review, which we're really excited to share. And essentially, it's taken, so there's a, we have a pack called the DSO1 Gut Reset Pack. Which is at Target and elsewhere where you take it for the course of the antibiotics. Typically, the antibiotics are about seven days and seven days after. But what we're realizing is that people take the 14 days, feel a lot better just from their bowel habits. And so they're continuing on. So you can kind of flip from that to the DSO1.

• 1:08:27Dr. Darshan Shah?

  And it's the same dose? It's the same? Okay, great. Yeah. So those are available at CVS and drugstores?

• 1:08:32Speaker 01

  At Target.

• 1:08:32Dr. Darshan Shah?

  Target, okay, great.

• 1:08:33Speaker 01

  So we're Target nationwide. And then our overall products are available online at seed.com as well as Amazon. And also with from a clinician perspective from Full Script as well.

• 1:08:43Dr. Darshan Shah?

  Yeah, seed.com.

• 1:08:45Speaker 01

  Seed.com. That's where to go.

• 1:08:46Dr. Darshan Shah?

  Yeah. Are there any other conditions that we haven't hit upon where probiotics could be useful?

• 1:08:51Speaker 01

  I think IBS, so very common condition, you know, affects about one in four people. Not a lot of great tools overall. We did a study that we presented again at Digestive Disease Week with Tony Lumbo, who is one of the world experts in irritable bowel syndrome at Harvard. And so we ran a trial at Beth Israel at Harvard Medical School and showed that DSO1 had a significant impact on individuals with IBS compared to controls and also an improvement in their microbiome. And actually, we know why it worked. We saw an increase in serotonin, which is really, really interesting. And so the number needed to treat, which is our fancy medical terms around how we think about that, was about five, which is really, really quite exceptional. And so we were really excited to see the results of that in that study.

• 1:09:32Dr. Darshan Shah?

  What was the endpoint of that study? Was it symptoms?

• 1:09:34Speaker 01

  The endpoint was abdominal pain based on the FDA threshold. The FDA says 30% improvement in abdominal pain for responder versus non-responder. We said the bar is 40%. We wanted to make sure the bar was even higher. And so we saw about 25% versus 5% because we had a run-in period that excluded individuals that had placebo effect. And so we saw roughly about a 20% delta.

• 1:09:56Dr. Darshan Shah?

  Oh, wow. So for IBS as well?

• 1:09:58Speaker 01

  We're seeing some benefits there.

• 1:10:00Dr. Darshan Shah?

  Well, let's go back to the vaginal microbiome as it relates to child delivery. So we had our child by C-section and unfortunately, this was before all the talk about the microbiome. And, you know, the C-section is of course a pretty sterile procedure, right? And now we know that that exposure to the vaginal microbiome. Microbiome is extremely important, right?

• 1:10:22Speaker 01

  That's exactly right. So if you think about the way that most humans come into this world through the the mother's birth passage, you get caused by gut bacteria. You're born technically sterile, but it's that passage through the vaginal wall, vaginal cavity, as well as the stool that's around there that's happening, that makes your, that colonizes on day zero of your, of your birth.

• 1:10:43Dr. Darshan Shah?

  That's your first microbiome.

• 1:10:45Speaker 01

  That's exactly. It's like a microbiome transplant, literally right there. The one at step zero. And that's the microbe that train your immune system. And they have a huge impact on your, on your overall health. When you come through the world through the skin, you actually get colonies with skin bacteria, not gut and vaginal microbes. And that we see with epidemiology studies that individuals that have been committed to the role with a C-section or get antibiotics very early in life, between zero and three, they have a higher chance, exactly. They have a higher chance of having allergic diseases, autoimmune conditions and metabolic conditions over time. And so that's something that people are starting to explore. In fact, there's a study that was done in Scandinavia that looked at C-section babies

• 1:11:28Speaker 01

  that were randomized to get a swab of the vaginal secretions at the time of delivery versus not. And there's studies that have shown, actually one in China, that showed some benefits in neurodevelopmental testing. And individuals that got the swab versus the not swabbed. So that's still early, I would say, but interesting early data to show that, A, it's important, and B, we might be able to do something about it, which I think is really exciting.

• 1:11:51Dr. Darshan Shah?

  So for anyone who's pregnant now and they're, they're planning to undergo a C-section, or there's, of course, always the potential of an emergency C-section, what would you recommend?

• 1:12:03Speaker 01

  So I think it's having a conversation with your OB-GYN about this. Ask them, be an advocate for your health, about this process and procedure. Saying, is it possible to be able to take a swab of my own secretions? I'm like, and give them to babies? Is that possible? And if not, what can we do to find some kind of solution? I think that's, it never, there's zero harm in asking and having that conversation. And also, it's not a very technical procedure, right? And so, you know, some folks take it in their own hands.

• 1:12:32Dr. Darshan Shah?

  Yeah, yeah, exactly. Great. And then there's a pediatric product that you guys also have, right? What was the impetus of that one? And what does it do?

• 1:12:40Speaker 01

  Yeah, so PDS-08 is a great product as well. It's for individuals between 3 and 18 effectively. It's a slightly different formulation in which, again, follows the same 4D principles, but targeted specifically for the pediatric population. It actually has more fiber. It's in a sachet as opposed to a capsule. It's in a sachet that gets mixed into whatever your applesauce or your yogurt or whatever you're having. And we did a study, it was published in Nature Family Journal of Pediatrics, that showed an improvement in constipation, which we thought was really, really important as well. So targeting the right product with the right data for the right population.

• 1:13:16Dr. Darshan Shah?

  And pediatric, what age groups does that cover?

• 1:13:18Speaker 01

  3 to 18.

• 1:13:19Dr. Darshan Shah?

  3 to 18, okay. And prior to that, breast milk is where you get your bacterial exposure food?

• 1:13:26Speaker 01

  That's right, HMOs as well as kind of more HMOs than bacteria per se, but it definitely helps kind of optimize the bacteria for sure. It's like a prebiotic.

• 1:13:35Dr. Darshan Shah?

  I see, I see. Amazing. Great. Is there any conditions we did not cover?

• 1:13:40Speaker 01

  I think we've done a lot of ground.

• 1:13:41Dr. Darshan Shah?

  Yeah, exactly. So it sounds like, you know, like there's, you go to the pharmacy, there's at least 100 different varieties and variations of probiotics. And I think a really important takeaway for me is not all probiotics are created equal. It's like saying aspirin versus Viagra versus Cipro, like they're all different. They're all, they're all, you know, the bacteria are different, so there's different probiotics out there. Most of the probiotics I see, they are competing on lactobacillus and bifidobacterium and then the number of colony-forming units of each one. But I feel like that's kind of tricking people, right? Into thinking like, oh, the more CFUs I have of these two bacteria, the better off I am. Can you talk a little bit about that as well?

• 1:14:24Speaker 01

  Yeah, absolutely. So I think the more is not necessarily better. As I was mentioning before, it's like getting it to the right place. The reason why people put more is because some of it's dying in the stomach and they have to kind of get it all the way there. But what's better is a targeted delivery piece. I think it's like number one to think about dosing. The second piece is really important, lacto and bifido. Lacto and bifido are like... Massive biology differences within the lacto. And so what I'll also leave with you is that not all lactobacilli are the same.

• 1:14:53Dr. Darshan Shah?

  Yeah.

• 1:14:53Speaker 01

  In fact, it's like saying, um, you know, a Chihuahua and a Great Dane. I mean, they're both dogs, but they're pretty darn different.

• 1:14:59Dr. Darshan Shah?

  Yeah.

• 1:14:59Speaker 01

  Right. And so understanding that next layer. So I mentioned lactobacillus crispatus.

• 1:15:04Dr. Darshan Shah?

  Yes.

• 1:15:05Speaker 01

  That is a microbe that has the ability to have a huge impact in the vagina.

• 1:15:09Dr. Darshan Shah?

  Right.

• 1:15:09Speaker 01

  It's not the same as other lactobacilli, right? And so understanding, you don't have to understand this are in great detail, but starting to understand that not all lactobacilli are the same, not all probiotics are the same. And the key to get to diversity, right? Get to that diversity.

• 1:15:22Dr. Darshan Shah?

  Yeah. I think people go make that jump from they get a stool test done and the stool test tells them, oh, you're low in lactobacillus. And then go out and buy a lactobacillus.

• 1:15:30Speaker 01

  Sure.

• 1:15:31Dr. Darshan Shah?

  Probiotic, but really that's not the path to follow, right?

• 1:15:35Speaker 01

  Yeah.

• 1:15:36Dr. Darshan Shah?

  It's more about just creating more diversity, finding the right strains. And so I guess the question there is regardless of what your, your microbiome test might show you.

• 1:15:48Speaker 01

  Yeah.

• 1:15:48Dr. Darshan Shah?

  You still want to get the most diverse.

• 1:15:51Speaker 01

  Yes.

• 1:15:51Dr. Darshan Shah?

  Product with the best delivery.

• 1:15:52Speaker 01

  That's exactly right. I think the way that I think about it is like in an emergency situation, when you have a patient that comes in to the emergency department with floored infection, they're really, really sick with sepsis. Do we sit there and think about microbiome testing? Not necessarily. You want to give them broad spectrum antibiotics in that moment.

• 1:16:09Dr. Darshan Shah?

  Right.

• 1:16:09Speaker 01

  We don't do that with antibiotics and nor should we because we can build resistance.

• 1:16:13Dr. Darshan Shah?

  Sure.

• 1:16:14Speaker 01

  Probiotics are different. We're allowed to have a broad spectrum probiotic because sometimes the hole in the ship is going to change.

• 1:16:20Dr. Darshan Shah?

  Yeah.

• 1:16:20Speaker 01

  You're going to plug the hole in different days of the time. And so I do think that microbiome testing is important, right? We talked a little bit about that from a biomarker perspective to directionally see where you are. But I think the approach, the solution typically is a broader microbiome probiotic.

• 1:16:34Dr. Darshan Shah?

  Got it. Got it. Well, fantastic. Well, what's next for Seed and for you?

• 1:16:38Speaker 01

  We're really excited about, we have some, some new products that are coming in 25 that I'll, people will come back and then talk more about.

• 1:16:45Dr. Darshan Shah?

  Yes, you will.

• 1:16:45Speaker 01

  But we're really excited about kind of where we're going with respect to kind of some of our new products. And also just making sure we get on stage to tell people not all probiotics are the same, right? And really focusing on their gut health and kind of taking the autonomy of their health in control. So we're really excited about that.

• 1:16:59Dr. Darshan Shah?

  That's awesome. Fantastic. Well, it was so great to have you. I know we can find you on seed.com. Great domain name, by the way. Where can we find more from you?

• 1:17:09Speaker 01

  So feel free to kind of check me out on LinkedIn, Zane Kassam. That's kind of my place. I'm also on at Dr. Zane Says on Twitter. And just, just see.com is a good place to go.

• 1:17:20Dr. Darshan Shah?

  All right, well, thank you so much for educating us on gut health and can't wait to have you back on again.

• 1:17:25Speaker 01

  My pleasure.

• 1:17:26Dr. Darshan Shah?

  Thanks.

• 1:17:26Speaker 01

  Cheers.

• 1:17:29Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you like this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best and it's always important to seek their guidance.