42. Colleen Cutcliffe: Why Your Gut Holds the Key to Metabolic Health (And How to Fix It)

Have you ever wondered why gut health is at the root of everything, from metabolism and cravings to immunity and even mental clarity? Why do some people struggle with weight gain, energy crashes, and digestive issues despite eating well? And could the rise of GLP-1 medications like Ozempic be a sign that we've been ignoring a natural solution all along? In today's episode of Extend, I'm joined by Colleen Cutcliffe, a microbiome scientist and co-founder of Pendulum, a company leading the way in gut health research. She's here to break down why your microbiome isn't just about digestion, it plays a critical role in weight regulation, blood sugar balance, and even hormone production. We'll explore how your gut bacteria influence GLP-1, the hormone behind popular weight loss drugs, and why restoring your microbiome may be the key to naturally optimizing metabolism, reducing cravings, and improving long-term health. If you've ever dealt with stubborn weight, gut issues, or unexplained fatigue, this episode will give you science-backed strategies to rebuild your gut health, support natural GLP-1 production, and take control of your metabolism, without relying on injections. Colleen Cutcliffe, PhD, is a biochemist and microbiome researcher with over 20 years of experience in biotechnology and life sciences. She is the CEO and co-founder of Pendulum, a company pioneering next-generation probiotics to optimize metabolic and gut health. We Also Discuss: (00:00) What Is the Microbiome & Why It Matters (14:40) How Your Skin & Oral Microbiome Affect Overall Health (33:48) The Gut-GLP-1 Connection: How Your Microbiome Regulates Metabolism (44:24) How Menopause Transforms Your Gut Microbiome (51:05) The Gut-Brain Connection: How Your Microbiome Produces Neurotransmitters (58:02) How an Unhealthy Microbiome Leads to Disease (01:03:51) How to Improve Your Gut Health With Diet & Testing (01:14:32) The Future of Microbiome Science: Supplements & Targeted Probiotics 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 Colleen Cutcliffe: Website: https://pendulumlife.com/ Instagram: https://www.instagram.com/pendulumlifeco/ Instagram: https://www.instagram.com/drcolleencutcliffe/ Thank You to Our Sponsors: TruNiagen: Whether you are looking to stay sharp, feel more energized or simple age better, go to https://www.truniagen.com/ IFit: If you are looking to elevate your home gym fitness experience with the best in fitness tech, choose IFIT. Go to https://www.ifit.com/ Nexthealth: NextHealth: Your destination for cutting-edge health optimization—from IV therapy to hormone balancing. Explore at https://www.next-health.com/ Vitaboom: Vitaboom: For supplements you can trust and wellness solutions tailored to your health, visit https://vitaboom.com/

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.

• 0:51Dr. Darshan Shah?

  So have you been to a party lately and wondered why so many people are talking about gut health and gut microbiome? And why are probiotics a focus of so many conversations in the health and wellness world right now? Well, many people are struggling with weight, energy crashes, digestion issues, and they feel like they're eating all the right foods. And we're seeing a lot more people turn to medications like Ozempic and other GLP-1s to fix their metabolism and their obesity issues, while their body is not regulating their GLP-1s naturally. So what's going on here? In today's episode of Extend, I'm going to sit down with one of the world's experts in the microbiome, Colleen Cutcliffe. She's a microbiome scientist and co-founder of the company Pendulum. Pendulum makes probiotics that are specifically targeted

• 1:36Dr. Darshan Shah?

  to help your GLP-1 system. We're going to break down why your gut isn't just digesting, it's controlling everything from blood sugar and cravings to hormone inflammation, even your immune system. The science of GLP-1 is deep and is complicated, and Colleen Cutcliffe is going to break it down. She tells us it's a powerful hormone behind weight loss drugs and why your gut bacteria actually help produce it. The truth is, if your microbiome isn't in balance, your metabolism won't be either. There are ways to restore your microbiome production of GLP-1. GLP-1 naturally, and we're going to learn all about them. So if you're feeling stuck with stubborn weight, gut issues, or cravings, this episode is going to give you some tools that you can use to heal your microbiome,

• 2:20Dr. Darshan Shah?

  support natural GLP-1 production, and optimize your metabolism. Colleen Cutcliffe is my friend. She's a PhD. I love hanging out with her. She's so much fun to talk to. And she has over 20 years in biotech and life sciences experience. She's a CEO of the company Pendulum, as I mentioned, and she's pioneering next generation probiotics designed to restore gut health and metabolic balance. You're going to learn a lot from this episode about probiotics, about gut bacteria. So let's get into it.

• 2:53Dr. Darshan Shah?

  Colleen, thank you so much for flying down to join me today for the Extend Podcast.

• 2:57Speaker 01

  Thanks so much for having me.

• 2:58Dr. Darshan Shah?

  Yeah, I've really enjoyed our relationship, getting to know you, because I'm a huge believer in gut health and microbiome science. And so, meeting someone of your caliber, a true scientist that has studied this for a decade, over a decade now, right? Is that right?

• 3:15Speaker 01

  It has been over a decade now, yes.

• 3:18Dr. Darshan Shah?

  And, you know, just the depth of knowledge. And I particularly enjoy your viewpoint on the microbiome. So I can't wait to get into it. But before we get into that, Colleen, I would love to ask you, just big picture on microbiome, what do you think is the one thing that people get wrong when they think about the microbiome? Or they hear about the microbiome and they're trying to like, learn about it? What is the one misconception people have about the microbiome?

• 3:44Speaker 01

  I think historically, when people have thought about the microbiome, they thought about things like probiotics and yogurts and things like that that have been on the shelves. And when we think about those things, we tend to think about GI distress. So, oh gee, probiotics are good for my gut health, meaning they're good for diarrhea and constipation and gas and bloating. And I would say that's probably the biggest misconception, because actually, what we'll dig into here today is the microbiome is tied to every one of your body's systems, not just your GI. It affects your brain, your cardiovascular health, your metabolism. And so it really is a much bigger system in your body, impacting every aspect of your body. Your health. And so that's probably the biggest misconception is it's only doing this one thing when it's really changing everything about your health.

• 4:26Dr. Darshan Shah?

  That's so true. And that's why I really appreciate you coming on this podcast because I want to emphasize and double, really double click on the fact that the microbiome is connected to every system in our body. So it is monumentally important to our overall health as just as a biological being, right? And so, you know, the challenge is it's invisible, right? And we don't see it and we don't even really know it's there. But it's like this giant pharmaceutical factory in our intestines is constantly trying to make us healthy, right?

• 4:56Speaker 01

  Yes, it's constantly, well, it's evolved with us. And so it's interested in optimizing its host. It wants us to be in our optimal health so that all of those microbes can survive. So they're on the same motivation as us in wanting us to be as healthy as possible. So they are constantly evolving to adapt to all the things that we're doing to try to make our bodies better.

• 5:15Dr. Darshan Shah?

  Yeah, yeah. And constant is like, you know, minute to minute evolving, right? And so we'll get into that in a little while. But just big picture as well, what are two or three things people can do to positively affect their microbiome, whether it be nutritional dietary? What are your thoughts there?

• 5:32Speaker 01

  Yeah, so two of the biggest things that can modify your microbiome are antibiotics and diet. And so I am, just to be clear, I'm not an anti antibiotic-er. Antibiotics are incredibly important when you have a bacterial infection, but there does tend to be sometimes an overuse of antibiotics or people jump right to that and they really want to be on antibiotics and they don't have a bacterial infection. And so I'd say the first thing is that before you go on an antibiotic, before you feel like you should go on an antibiotic, have a conversation with your physician about whether it's a bona fide bacterial infection that you have and that you're trying to solve. Because if you go on an antibiotic, it is like a nuclear bomb to your microbiome. It is going to kill everything in there and you have to start back over. And one of the problems with that is

• 6:13Speaker 01

  that what we know is that the microbiome that eventually recolonizes after antibiotic treatment is not necessarily the same as what you started with. And so, and in fact, people who are on lots of antibiotics are more prone to obesity and it's something to do with this constant antibiotic treatment and then the replenishing of the microbes. Not quite the same. And so, so the first thing is just make sure you have to go on an antibiotic when you, when you have to go on it. And the second thing is try to incorporate high fibers and high polyphenols into your diet because that feeds the bacteria. That can have all these beneficial health outcomes for us. And when you think back to, you know, our caveman days, those are the kinds of things that we're eating. We're eating things that, you know, lots of vegetables, lots of berries. And so we, our bacteria are really evolved to feed off of those foods with us.

• 6:57Speaker 01

  And so avoid antibiotics if you can, eat high fiber, high polyphenol foods. And then the third thing is sort of a fun fact, which is that people who have dogs have more diverse microbiome than people who don't. So if you're thinking about getting a dog, you should get a dog and then you should hug it all the time.

• 7:13Dr. Darshan Shah?

  I love dogs.

• 7:14Speaker 01

  I love dogs too. We get two.

• 7:15Dr. Darshan Shah?

  I know. So they are actually beneficial to our microbiome. I love it. Talking about antibiotics, I would say that I see a lot of patients as a doctor and one of the number one requests I get is can I have some antibiotics?

• 7:26Speaker 01

  Right? Yeah.

• 7:27Dr. Darshan Shah?

  And I think it's such an important conversation now that I have this newfound kind of respect for the microbiome. Is that, like you said, you only want to take antibiotics if you really need them. How do you know if you really need them? Because your immune system should be able to fight off most infections, right? And most doctors, even most people know how to tell the difference between a virus and a bacterial infection. So that's step one is to make sure that you understand the difference between viral and bacterial infection. In which case an antibiotic will not help unless you have a super infection with a bacterial infection. Also, give your body a chance to just recover on its own, right? To treat itself. I think a lot of people think that I get sick all the times. I need antibiotics all the time.

• 8:09Dr. Darshan Shah?

  Really, it's because you're sick all the time and you're taking antibiotics all the time that you're getting sick all the time, right? And so it's like stopping that cycle somewhere and giving yourself kind of, giving your body what it needs to fight off the infection itself, I think is also very important.

• 8:24Speaker 01

  Absolutely. And fundamentally, your microbiome is there, as we said, we've co-evolved with it and it's there to boost your immune system in a variety of ways. And it can literally boost the levels of different interleukins when you're fighting off disease. So to your point, you take an antibiotic, you've gotten rid of half of your immune defense. System and then you've got a weakened immune system and then you get a, you know, sick again and then you take antibiotic again. And so you're kind of on this really bad cycle of, you know, getting in worse and worse situations. I'll tell you a funny thing. So I'm a scientist by training. My husband is a physician and our, we have children. And every time that our kids would get sick when they were younger, you know, we'd give them water and an orange. I mean, we, we really didn't have medications in the house. And at some point, they realized that this was weird, that all of their other friends

• 9:07Speaker 01

  were going on antibiotics, they were going on medication. And so we got disciplined by our children. How come that we never get any, you know, we never get to have better living through pharmaceuticals. We have to just drink more water. But I agree with you. You really, and it starts in childhood. That's when you start to train your immune system. You really do have all the pieces that you need to fight off kind of these small infections.

• 9:28Dr. Darshan Shah?

  Yeah. I would say the best pharmaceutical company in the world is the one that's in our gut.

• 9:33Speaker 01

  I would agree. I would agree.

• 9:34Dr. Darshan Shah?

  Right. Just gotta give it what it needs to make what it needs to help us and it'll take care of us without causing a side effects. On the drug, just real quick on the, on the drugs that affect the microbiome, is another category non-steroidal anti-inflammatory drugs as well? Do they affect the microbiome?

• 9:51Speaker 01

  Well, as far as we know, pretty much every study that's come out around do drugs impact the microbiome appears to be yes. But I'll also flip that on its head, which is to say that the microbiome can also influence these drugs. And so probably one of the earliest case studies of this was digoxin, which is, used to be a first line therapy for, I think, cardiovascular disease. But it has kind of this very narrow window of efficacy that seemed to be somewhat unpredictable for people. And so figuring out what is the dose to give someone was always a challenge. And if microbiome science had been more advanced at that time, we would have realized it actually comes down to the microbiome because what got discovered is that there are certain microbes that can metabolize digoxin. And so if you happen

• 10:33Speaker 01

  to have those in your gut, you need a higher dose because your microbiome is actually metabolizing these drugs. And so they're not as efficacious. Whereas if you didn't have these microbes, a low level of digoxin would work just great for you. And so it just shows how much our microbiome is evolving with our bodies and our Systems because they are actually evolving to be able to metabolize drugs themselves. And the drugs are impacting the microbiome negatively as well. And so every time we change something in our culture that is an evolution of science or medicine or things we put in our body, there's this whole other system that's then evolving with it, too.

• 11:07Dr. Darshan Shah?

  You just solved like one of my major mysteries from medical school. Because we would give people digoxin for cardiac arrhythmias. And we'd always have to check levels, right? And then you finally get them stabilized. You get the dose stabilized, the levels are fine. And they'd come in, you know, six months later. And all of a sudden their digoxin levels are like, are in the gutter or through the roof. And you're like, what did you do? You always blame the patient. Did you miss a dose? Are you not following the directions? You're being noncompliant. And it's not really that. It's probably a change in their microbiome that might have caused this, this change in the level of their digoxin.

• 11:44Speaker 01

  They probably had highly evolved microbiomes and you were disciplining them.

• 11:47Dr. Darshan Shah?

  Yes.

• 11:49Dr. Darshan Shah?

  I love it. Okay, great. So those are some great pieces of advice. Before we dive further into the microbiome itself, could you give us kind of a primer on what the microbiome is? Just from like a very basic level for people that don't really know. And just tie that into also gut health in general.

• 12:04Speaker 01

  Sure. Yeah, I think gut health is becoming a more and more popular phrase out there. And it's really referring to the microbiome, which is kind of definitionally, it's all the bacteria and viruses and fungi that live in us and on us. And so we have microbiomes all over our bodies. We have them in our guts, which is probably the thing that people are studying the most. But we also have them on our skin. We have them in our nasal passageways. We have them everywhere and they really have co-evolved with us. And so if we just take skin as an example, we are all supposed to have a layer of microbes on the outside of our skin. And what those, a lot of those microbes do is they are the barrier between the allergens in the outside world and our own immune system. And so you're supposed to have this layer that keeps you from having direct contact with these allergens.

• 12:49Speaker 01

  It first would hit those microbes. But because of, you know, we constantly, most people shower every day. Some people shower twice a day. Most people have, you know, regimens that are, that are cleaning their skins and trying to get Of all these microbes or they're inadvertently getting these microbes. So we essentially have stripped skin microbiomes. It's just us and all the allergens in the outside world. And this is one of the theories of why allergies have just skyrocketed. And then also, as you age, you sometimes people get allergies that they didn't have when they were younger. And it's literally because you're missing a whole line of defense. And now your body has to deal directly, your immune system, directly with the allergens in the outside world. And so the microbiome is incredibly important. And to your point, it's hidden. Who would know about that? But it's doing all this incredibly important work.

• 13:33Speaker 01

  And so we're now realizing that, you know, in medicine, I didn't go to medical school, but you have like the 11 systems of, you know, in the human body. The microbiome is tied to every one of those 11 systems.

• 13:43Dr. Darshan Shah?

  Yeah, so that's so interesting. Like in the gut, you know, I always talk to my patients about how your gut protects you from the outside environment. And there's multiple layers in the gut. You have the mucus membrane. I mean, you have the mucus layer, then you have the microbiome layer, and you have the actual enterocytes, which are the cells of the gut that protect you from the toxins that we basically ingest when we eat food. However, the skin is similar or the same. Like you have this microbiome layer protecting you from the outside environment as well. But aren't we constantly and consistently like removing that microbiome layer? When we're washing like with antibiotic soap or using all of these products that are out there with antibiotics in them?

• 14:21Speaker 01

  Absolutely. Antibacterial soaps, antiseptic wipes, where you use to wipe down your countertops. All of those are killing, we get so obsessed about killing the bad bacteria that we're basically killing also all the good bacteria in that process. And so, and actually, at some point, we decided in our house, we're not going to buy any more antibacterial soaps. We're just going to have soap, soap. It is incredibly hard to find soap that is not antibacterial soap. You almost have to go back to the old school, you know, bars of soap in order to find that. So, but it is constantly, we're depleting our microbiome. We think we're doing good things, but it's not actually necessarily good for us in the long run.

• 14:59Dr. Darshan Shah?

  Yeah, your microbiome is kind of like all of nature where you have, I would say, you know, in quotes, good bacteria and bad bacteria, but they're in a balance all the time. And when you eliminate all the bacteria, it actually Needs the environment for potentially bad bacteria to thrive and cause more damage than good. Is that kind of what you're saying?

• 15:15Speaker 01

  Absolutely. If you've ever had to tend to a garden and you see a weed in that garden, you're like, oh, my gosh, a weed. This would be like the equivalent of killing everything, you know, killing your whole lawn. Yes, you got rid of the weed, but now you don't have a lawn. And then not only that, but actually because weeds are different from regular grass, what you've done now is you've actually created an environment where the weeds have an easier time coming back. And so it really is just like having a lawn where you want to have things that specifically kill those weeds, but keep your grass alive. And so when you use these antibacterial soaps, or you're taking an antibiotic, I mean, you literally are just throwing bleach on your whole yard.

• 15:51Dr. Darshan Shah?

  Hmm. That's, that's a really good analogy, actually. And it gives me and hopefully the listeners a lot to think about to be more mindful of the products that we're using in our homes and on our skin, and obviously avoid antibiotics as well. You know, practically, just to kind of dive in even further into the skin part of, of microbiome, which I think is often like, is just getting talked about now, right? What are some practical changes people can make just today or in the next week to optimize how they're treating their skin bacteria?

• 16:24Speaker 01

  Well, I think the first thing is go out and try to find soaps that aren't antibacterial. And they're going to work just fine. And so that would be the first thing. The second thing, which is sort of interesting, there was a reporter, I want to say she was with the New York Times, but now I can't remember. She did this 30 day experiment where she didn't shampoo her hair. She would take showers, but she didn't use any shampoo for 30 days just to see what would happen to her hair and her skin microbiome on her scalp. Now, that's, that's pretty extreme, but I would say that for many people, if you, if you really do shampoo and condition every single day, to consider trying first, maybe every other day or every third day. I mean, you really don't need to be shampooing and conditioning every single day, most likely. And what you might find is that your hair looks a lot

• 17:09Speaker 01

  nicer because you're allowing your natural microbiome, your natural skin microbiome on your scalp to do its thing. And so those are two things that I have, I would say for sure, looking for soaps that aren't Antibacterial, but that shampoo thing, not doing it every day or doing it every few days. And eventually, some people will get down to like, once a week. And they feel like that's my optimal time for my hair to look the best. I've heard so many people say that that actually really works. And it's all coming down to allowing the microbes to actually flourish in your skin.

• 17:37Dr. Darshan Shah?

  Yeah, I'll tell you, I have personal experience with that. In my previous life as a surgeon, I would, one of the surgeries I'd do was hair transplant surgery. And a lot of guys that would come for this, and women too, were struggling with extensive hair loss and really bad condition of their scalp skin. Dandruff and, you know, red blotches everywhere and very thin hairs. And if you look at pictures of people from like, the 1920s and 30s, they had incredible hair late into life. And a lot of the damage comes from this marketing that's convinced us that we need to shampoo our hairs every day with these extremely like, harsh soaps in our scalp. And many of the men that would come to me for surgery for their scalp,

• 18:21Dr. Darshan Shah?

  I would tell them, I want you to go to shampooing your hair once a week. And it would have a massive change in the condition of their scalp. And I think that's, that's a point very well taken. It's because of, our microbiome, even in our scalp, is made, is keeping our scalp healthy, just like the rest of our skin. And yeah, definitely, I would recommend everybody do not wash your hair every day. It's, it's just marketing, it's just to get you to use more of these products.

• 18:46Speaker 01

  Oh my God, and literally shampoo is, you're stripping everything away. And then the conditioner is, you're putting those things back that were there anyway in the first place. So it is a lot of marketing effort. But, and, and it's interesting because what you start to see when you look at the microbiomes on the scalp of people as they, you know, kind of extend the period of time where they aren't shampooing, is you start to see it becomes more and more diverse. And what ends up happening is you can start to create a bio layer so that actually, if you were somebody who shampooed every day, you would have some diversity, it builds up over the day. And then it would all go away when you shampooed. If you shampoo, these people who did it every, you know, once a week or every few days, they start to get a layer so that when they shampoo, it doesn't go all the way to zero. So you actually are creating a sustainable, you know, biofilm on your scalp.

• 19:32Dr. Darshan Shah?

  I love that. Yeah. And you know, also with just showering in general, like I think most people would, you know, shower every day. Some people don't. And there's certain health benefits to that as well. But I shower every day, but I think it's very important to be very mindful of the soap you use in the shower as well, not just the hand soap. Shower soap is extremely, can be extremely damaging to your skin. And a lot of people with eczema out there, or flare ups of skin conditions, just by going to a less abrasive soap is a game changer. And a lot of that has to do with the microbiome.

• 20:01Speaker 01

  Yeah, eczema and atopic dermatitis and all of these skin diseases where the therapy is like these mild bleach treatments or these mild acid treatments, it's, it's, it's, it is literally like the killing your whole garden because you saw a weed. One of the, you know, the issue that they're trying to resolve with the bleach or the acid is if you have certain, you know, types of bacteria that are overgrown on your skin. But you're creating a system where now you've got no competition and those can come back pretty easily. And so some of the really interesting science that's coming out is what in the gut microbiome is interacting with your inflammatory and immune responses that could potentially help with eczema and atopic dermatitis. And I think of it at like, you know, if you have a car and the check engine light comes on, treating the skin is like you just put a

• 20:46Speaker 01

  piece of tape over that check engine light. And you're like, well, now it's solved. I don't see the check engine light anymore. But really, you have to check the engine and you have to fix what's happening underneath the hood in order to fix that check engine light. And so I am really excited about the research that's going on that's targeting the gut microbiome for skin diseases.

• 21:02Dr. Darshan Shah?

  Yeah, no, that's amazing. Colleen, I love all your analogies. Keep them coming. It really drives a point off, you know, like, yeah, I could see, I could see my mom just covering the check engine light with a piece of tape. It's fine.

• 21:14Speaker 01

  No problem. The car's great.

• 21:16Dr. Darshan Shah?

  I love that. Before we go and get into the gut, where the majority of our discussion is going to go, I want to talk about one other area that I feel is very often ignored as far as micro, talking about microbiome goes. And it's actually part of the gut. It's our mouth, right? And so there's a lot of oral care habits, I feel that have once again been marketed to us as being healthy, that are absolutely not healthy for our oral microbiome. Could you talk to that a little bit?

• 21:42Speaker 01

  Well, I would say the jury is still out for me on really discerning which of these products and which of these regimens is good for what person. So I do think there is likely somewhat of a personalized nature to this, depending on your diet and depending on, you know, kind of your routines. And so, but the, you know, very, very fundamentally and at a very high level, we're probably doing too much. And so the need to constantly eradicate everything in your oral microbiome, again, it comes back to this same theme. You are trying to kill the bacteria that are going to feed off the sugars that you're eating and create cavities, yes. But, you know, is there a more sophisticated way that we can go after this problem other than just getting rid of everything that's in there? And some of the interesting stuff that's coming out around the link

• 22:27Speaker 01

  between the oral microbiome and the gut microbiome is showcasing, for example, there's a series of small molecules that your gut microbiome makes. They're called short chain fatty acids. And they're very volatile, meaning that they go, they turn into gas, you know, pretty easily. And you could actually measure in somebody's breath how much short chain fatty acid is in their gut. So the levels of butyrate and things like that. And then moreover, the levels of those gases are an indicator of oral health. How all those things are tied together, I think is not totally clear. So these are all correlative studies. But I think there's something really interesting about probably the diet that you have, your oral care, and then your gut microbiome that is all kind of new learnings that are being uncovered.

• 23:09Dr. Darshan Shah?

  Yeah, yeah. You know, when you mentioned the butyrate that comes from our mouth, is there a world where we would have like a, maybe a device that measures that? And then we can kind of assess our gut microbiome health by measuring the gas levels?

• 23:22Speaker 01

  There are several companies that are so close to figuring out how to do this. I'm dying for that tool because it's such a great tool for, I mean, short chain fatty acids are such an important part of what our microbiome does. And being able to have a breath test without having to go to a stool test would be a lovely way to measure.

• 23:38Dr. Darshan Shah?

  Yeah, exactly.

• 23:40Speaker 01

  Yeah.

• 23:40Dr. Darshan Shah?

  Wow, that's, that's, that would be incredible. I want to put a pin on the short chain fatty acids as well because I want to talk about that and supplements that have short chain fatty acids. And then we'll talk about that later. But just to Kind of wrapped the bow on the oral health thing. I think there's a couple of things that everyone should consider is that is number one, you have to have a regular visit with your dentist at least once every six months and get your teeth cleanings done and get your oral health fixed. Because if you have any oral health care issues, there is a long-term relationship between your oral health and your cardiovascular health with Alzheimer's risk, with metabolic disease. And it's some of that has to do with the microbiome. Some of it just has to do with constant inflammation in people's mouths

• 24:23Dr. Darshan Shah?

  from having poor dentition, poor oral care, poor gum health. And so it's so important to see your dentist, get your oral health in order and maintain it. I think also another thing that a lot of people kind of forget too is tongue cleaning. The, you know, I think because you can't make a lot of money off of tongue cleaners. It's not marketed that very, very often, but go on Amazon, buy a good metal tongue, tongue cleaning device. I think that's very helpful. And finally, obviously flossing two or a couple, three times a day is very important as well. Brushing your teeth with a, with a toothpaste that does not have an antibiotic in it or something that's going to kill your microbiome as well. Would you agree with those pieces of advice?

• 25:02Speaker 01

  I think those all make sense. And some of the things that people do in addition to that, that have some kind of controversial data coming out are they'll do like a Listerine treatment afterwards. And so this daily use of Listerine to really kill all that bacteria. I think that's where some of the data is coming out that's showing like, maybe that's not so great for you.

• 25:18Dr. Darshan Shah?

  No. If you're worried about your breath was going to work much better than Listerine and be so much better for your long-term health is tongue cleaning. I would get rid of all the harsh Listerine type of, you know, type of mouthwashes, unless you have a situation where you have an active infection going on in your gums or something like that potentially, working with a dentist. Do you think that's right?

• 25:38Speaker 01

  Totally. And with bad breath, I mean, I know that there are regimens where you're changing your diet can actually impact that. And so, um, you know, that's a, I think, probably a much better way to go about it.

• 25:48Dr. Darshan Shah?

  Yeah, exactly.

• 25:55Dr. Darshan Shah?

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• 26:35Dr. Darshan Shah?

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• 27:14Dr. Darshan Shah?

  All right, now let's get into the gut.

• 27:17Speaker 01

  Get to the guts.

• 27:17Dr. Darshan Shah?

  Where does your microbiome live in your gut?

• 27:21Speaker 01

  So you eat food and the food goes to your stomach and gets digested there through the acids in your stomach. And then after that...

• 27:29Dr. Darshan Shah?

  Is there bacteria in your... Is the microbiome in your stomach as well?

• 27:33Speaker 01

  I don't think that that's really been very well studied. I think, generally speaking, we think of the digestion in the stomach mostly coming from the acids there, not really the microbes.

• 27:41Dr. Darshan Shah?

  And the mechanical.

• 27:42Speaker 01

  Yeah, and the mechanical, exactly. Go ahead.

• 27:44Dr. Darshan Shah?

  I was just gonna say, just real quick on that, too. If there is a bacteria in your gut, there's one that can be potentially very harmful called H. pylori that can cause ulcers and things like that. So in general, I think that the microbiome doesn't like the harsh environment of the stomach, and it kind of starts later on in your gut, right?

• 28:00Speaker 01

  Exactly. All the actions happening after. The stomach. So the stomach's got its job to do and it's kind of like the, you know, brute force. We're gonna, you know, the mechanical and the acid. And then you've got your more refined microbiome on the other side of that, which is much more targeted and thinks about what am I metabolizing, you know, these things into. And so actually starting the small intestine, you know, just on the other side of the stomach, you start to see the appearance of certain types of microbes there. So lactobacillus and bifidobacterium, you know, they, some of them reside there. But you keep traveling all the way down and you get to the distal colon. That's where all the real action is happening. So when we talk about the gut microbiome, it's the distal colon. So all the way down at the end there. And, you know, one of the unique things about that environment is first of all, it's this very busy ecosystem, these trillions of microorganisms that are all piled up

• 28:45Speaker 01

  on top of each other in this ecosystem, working in conjunction and sometimes against each other. And it is a strictly anaerobic environment, meaning that by the time you get to the distal colon, there's no oxygen there. So it's like a really unique, different environment than what we experience in the air around us. And so there's always this, you know, interesting question of how do those microbes get there in the first place? And how do we sustain the good ones? And what happens when they go away? And how do the bad ones get in there? And there was an interesting study that just came out that showed that only like 3 to 5% of your gut microbiome can be found, is related to the microbes on the food you're eating. And you would think it would be, because your food can change your microbiome so dramatically, you'd think, maybe I'm getting some of the

• 29:26Speaker 01

  microbes from the food, but not really. That food is really serving as food for the microorganisms. So anyway, it's all happening, it's in the distal colon.

• 29:34Dr. Darshan Shah?

  So where does it come from? If only 3 to 5% comes from your, comes from the food, where is the rest of it coming from?

• 29:39Speaker 01

  I know. It's, it's, I think that's a mystery that's still being unraveled.

• 29:43Dr. Darshan Shah?

  Interesting.

• 29:43Speaker 01

  We know that, you know, mother's breast milk is one of the first places that you start to seed these early microbes. And we know that you get a fair amount in the early days from food. So in this study, I think they were really looking at adults. And so the, you know, kids, as you start to get exposed to, most parents, we have a kid, you give them one food and you kind of like, watch how it goes. And then you add on food. And so as you're exposing your kid to more and more foods, they're getting exposed to different microbes. But you have such a diverse microbiome that it's not clear, kind of, And this is why I think the depletion of the microbiome becomes so important and why you start to think about supplementing because if it's really hard to figure out where these microbes can come from, then it's all about you get what you get in the beginning and then you've got to take care of that, you know, with a lot of care and feeding.

• 30:27Dr. Darshan Shah?

  Yeah. Isn't there a big problem with babies born by C-section not getting seeded with an appropriate microbiome?

• 30:33Speaker 01

  Yeah, there's a whole system between mother and baby that is all about seeding that first microbiome. And so, you know, we used to think that it was an entirely sterile environment, you know, in the fetus, but we now know like, no, no, there's a little bit of microbiome action, action happening there. But that the first real seeding of your microbiome is when you go through the vaginal canal and there are a ton of microbes there that become the really important foundation for building your immune system and your digestive system. And so for babies who are born via C-section, they don't get to have that vaginal birth and get that initial seeding of the microbiome. So they're just starting out in a depleted state.

• 31:11Dr. Darshan Shah?

  Right. And I think now a lot of OB-GYNs that are delivering babies by C-section will actually do a vaginal wipe and then seed the microbiome of the baby after the...

• 31:21Speaker 01

  Are a lot of people doing that? I didn't know how many people were actually figuring that part out.

• 31:25Dr. Darshan Shah?

  I think it's becoming more and more commonplace now in my tracking. You know, when we had our children, we did not do that because it was not well-known. And now it seems like there's more talk around it. But definitely, if you're planning on having a baby, whether you're having a natural birth or a C-section birth, because we know sometimes a natural birth can turn into an emergency C-section, have the conversation with the OB-GYN about seeding the microbiome using something like a vaginal wipe. I think that's an extremely important conversation for mothers to have with their OB-GYNs before going through birth, even if they're planning a vaginal delivery.

• 31:59Speaker 01

  Absolutely. The baby's microbiome, that infant microbiome, literally is your start to life. And you're supposed to be getting all this stuff from mom, you know, that nature has, is first the vaginal, you know, delivery, then mother's breast milk. And, and so if you're not doing those things, you got to figure out, okay, well, how am I going to then get these into my baby if I'm not, don't have a vaginal, you know, birth, or if I'm not able to, you know, breastfeed in the way that I would like. And then the third part... That is, you know, my first daughter was born prematurely and for preemies, she was almost two months premature. For preemies, they give you multiple doses of antibiotics in the hospital, not because you have an infection, but because you're so fragile, they don't want you to get an infection. So this would be a case where you have to ask yourself, the baby doesn't have an infection. They're already weak and fragile because they're born prematurely.

• 32:43Speaker 01

  Is an antibiotic treatment the right thing for my newborn baby? And I'll tell you, my daughter got multiple doses of antibiotics. She was born prematurely. My co-founder, who had his baby after we'd like learned all this research and all these studies have been done, added the luxury of data. He had, his first son was born prematurely and he essentially told UCSF, no antibiotics. And so I think we are evolving, we're learning. But the early start to life, if you're not doing a vaginal delivery, if you're not breastfeeding, if you're being told the baby has to have antibiotics, these are all things that can really alter the future of your, your kid's microbiome.

• 33:18Dr. Darshan Shah?

  And just so everyone gets the end of the story there, did your friend's baby do okay without any antibiotics?

• 33:24Speaker 01

  He's just fine.

• 33:25Dr. Darshan Shah?

  Exactly. That's what I figured the end was gonna be. Okay, so I want to really emphasize again, you know, like we're talking about protecting the microbiome and we're talking about making sure you get seeded with the microbiome. And we're having all these conversations because it is an incredibly important part of our system, of our biological system. It's almost like, you know, we need to actually have a category as this being one of the systems of our body. Right? It has so many important functions. I keep saying it's like a pharmaceutical company in your colon, you know? But I would love for you to talk about why it is so important and the interconnectedness of the microbiome with the other systems of our body.

• 34:05Speaker 01

  Sure. Yeah, I was saying that I think that eventually microbiome is going to be a chapter in your biology book. Because we are learning so much about it and how it impacts the other systems and how those systems impact it as well. So I think, you know, people probably think a lot about the microbiome and gut health, GI health. So, you know, diarrhea and constipation, things like that. But maybe we can dig into a maybe not so obvious place, which is your metabolism. And so I think that, you know, knowing that your stomach does a lot of metabolism. Metabolism of your food, but then also knowing that your gut microbiome does actually a huge amount of that metabolism starts to tell you that you have all these microbes that are there to metabolize your food. And if you're lower missing some of those, your metabolism is actually impacted by that. And one of the things that, you know,

• 34:49Speaker 01

  we've been studying and many people around the world have been studying is, okay, well, what are those functions and what are those microbes? And one of the most important functions is actually the stimulation of GLP-1. GLP-1 has has become very famous over the last couple of years. I don't know if you want to weigh in on its infamy or fame?

• 35:06Dr. Darshan Shah?

  Yeah. I mean, basically, for the listeners don't know what GLP-1 is, is basically that entire category of drugs that got popularized by Ozempic. And there's more Jarno, there's other ones. It's basically semaglutide and its cousins that are, they're peptide hormones that cut off your sense of hunger, basically. And there's a lot of positives to it and some negatives that, you know, unfortunately, people are using it for vanity's sake. And so now we have this whole kind of backlash against GLP-1s. But all that being said, it's a very powerful molecule. But the key knowledge about this molecule, GLP-1, is your gut makes it anyway for you, right? And so that's where I think we need to dive into the science of where is it

• 35:50Dr. Darshan Shah?

  made? And what is affecting it just in our population? Like, people are obese now. People are hungry all the time. What happened? Why is there like a GLP-1 deficiency in our population that now needs to be looked at? And, you know, people are needing to treat it with these injectable medications now? What's going on?

• 36:09Speaker 01

  Exactly. And it does come back to the microbiome is actually the thing that generates GLP-1. So to your, your point about these GLP-1 drugs, so Ozempic and Magovi, these are drugs that are meant to mimic your body's natural GLP-1 hormone. And so what's supposed to happen when you eat food is it gets metabolized by these, this factory of trillions of microbes. And there's, in that factory, there's one department whose job it is to say, okay, we just ate food. Now we got to stimulate GLP-1 release. And so when you eat food, that factory, that department says, let's stimulate GLP-1. GLP-1 gets released. Into your bloodstream. So you'll see after you eat your GLP one levels would go up in your bloodstream. And there's two important things that it does. One is that it metabolizes the sugars in the foods that you were just eating. So, you know, it's part of this insulin response system.

• 36:54Speaker 01

  And the second that you alluded to is that it tells your body, we just ate, we don't need to eat again for a while. And then after a while, that GLP one in your bloodstream will go back down again. And so, and then you'll get hungry again, and then you'll need to eat, and then it'll go back up again. So you're supposed to be on this cycle of GLP one hormone in your body. And the issue is that if you don't have those strains, you're missing that department. There's actually nobody who can sub in for that department at the moment. You are not getting that GLP one produced. And then moreover, it's even more, a little bit more complicated than that because you can actually have misfirings where then you're getting weird amounts of GLP one at different times. And so you end up with these like food cravings at weird times of day and cravings for foods that you don't really actually need.

• 37:36Speaker 01

  And so that's kind of what we all feel. That's the outcome of not having a tightly regulated GLP one system where the GLP one gets to the levels it's supposed to get to. And so the difference between what is supposed to happen in your body and the GLP one drugs is that your microbiome, these specific microbes will stimulate GLP one and you'll be on a cycle. And what the drugs do is they, you know, you're injecting a chemical entity that looks like that hormone. And it just sort of stays at really high levels all the time. And so they're incredibly impactful because you basically have this signaling molecule all the time saying metabolize sugars and we're not hungry. And metabolize sugars and we're not hungry. And so you get this immediate impact. But the downside to that is that you haven't really taught your body how to do it on its own. So when you stop taking that, your GLP one levels drop again.

• 38:19Speaker 01

  You get this immediate rebound of being super hungry again and your ability to metabolize sugars has gone down. So the advantage of going after the gut microbiome, either in conjunction with, you know, or instead of those is that you can teach your body to fish if you can get those microbes to colonize. And now you're going to generate your own GLP one hormone. The downside is you're not going to see that immediate impact that you see with the drugs.

• 38:42Dr. Darshan Shah?

  Right, right. And in my practice, I mean, when I have to use them, they work together. And the way they work together is that when someone goes on an injectable medication for metabolic health for Massive obesity, we also start them on an Akkermansia type of probiotic. The department that you're referring to is Akkermansia, right? Is that the?

• 39:01Speaker 01

  There's actually two strains that have been shown to be able to stimulate GLP-1. Yeah, one is Akkermansia muciniphila and the other is Clostridium butyricum. And we know that they actually work because it is all an ecosystem. They actually work in conjunction with a third player called Bifidobacterium infantis, which is just upstream of them. And together, they're they're kind of the players we know that are in that department.

• 39:21Dr. Darshan Shah?

  Yeah, so it's pretty complicated, but our body's got this figure this figure this out through evolution. And I think it's like this vicious cycle, right? What happens is really what's killing our gut guts ability to produce GLP-1 is ultra-processed food, alcohol, toxins in our food that come from toxins toxins in our environment. And this is what's truly damaged modern society's ability to produce its own GLP-1. But the good news is is that we can rehabilitate this by either changing our diet completely. And, you know, that's the first thing you want to try to do is just have a complete dietary change away from ultra-processed food so that your gut has a chance to regenerate these beneficial bacteria.

• 40:03Dr. Darshan Shah?

  However, I think the GLP-1 medications for people that have have unfortunately succumbed to the hyper-palatability and the hunger of having ultra-processed food all the time, they just need a little break, right? And so I look at the GLP's medications, the injectables, as giving people a break so their gut has a chance to catch up and they can retrain themselves on how to eat again. Right?

• 40:26Speaker 01

  Yep.

• 40:26Dr. Darshan Shah?

  And so I think that's super helpful. And then tying it in with a probiotic that can help them regenerate these three beneficial species that work together to to produce GLP-1.

• 40:37Speaker 01

  Absolutely, and I think in conjunction, you know, makes a ton of sense. And I also think that, you know, one of the things that we don't fully understand about people's gut microbiome is why does some people's microbiomes appear to be really diverse and healthy? I mean, we know some things about that, but other things are kind of a mystery. And why does some people's tend to always, you know, rejigger back to an unhealthy state? And so it could be that you are the kind of person and you're something about your microbiome ecosystem. System that, you know, we really don't understand causes makes you more likely to get depleted in that department of strains. And if you are more likely to get depleted in those, then you're always going to be fighting a different battle than somebody who doesn't have that. And so we think a lot about like, well, gee, how come two people can go on the same diet? And one person has all these great outcomes and the other person's really struggling with it. Oh, you probably weren't on the diet. You weren't following it.

• 41:22Speaker 01

  And we point a finger at that person. But what we're now realizing is that actually your microbiome can impact how well you respond to that diet. And in fact, there was a study that was done where they Did exactly that. They took a several hundred obese patients. They put them all on the same calorie restricted diet. And they found that the people who had higher starting levels of acromansia actually performed better on that diet in terms of their waist to hip ratio, their triglyceride levels and their weight. And so there is something there about you just started out with having more guys in that department. And so I think there's, you know, not that I'm trying to remove blame and we all do have a role to play in our own health, but there are things that are outside of our control and it really is these microbes. And the great, and the great news that you were saying, which is that let's not be all

• 42:07Speaker 01

  downer about this, but the great news is that you can give these microbes back. You can modify your diet to feed these microbes. And we know that if you give those three, you know, guys that are in that department, if you replenish people's microbiome with those, after just six weeks, 91% of people have reduced food cravings. So you can change all of these things that feel like maybe, oh, this is just me.

• 42:29Dr. Darshan Shah?

  Right, exactly. So, you know, I think the reason this is so important is that your metabolic health is kind of the cornerstone of all other diseases, cardiovascular disease, Alzheimer's, neurodegenerative disease, cancer as well. And so it's so important to get your metabolic health right. You mentioned some biomarkers like triglycerides, HDL, waist hip ratio, which is a measure of visceral fat. Those are all actually measurements of metabolic disease or metabolic syndrome. And so everyone should know what those biomarkers are for themselves so that they can know if they're headed towards a metabolic syndrome, which has as root in the gut and the gut health of our, these three species, correct?

• 43:10Speaker 01

  Absolutely. And, and one of the things that we know is that While there are things that we can do to control our microbes, so our nutrition and exercise and all these things, there are a lot of things that are outside of our control that can cause us to become depleted in these microbes. So you may have to actually take an antibiotic at some point. That will cause you to become depleted. We know that as we age, we actually become depleted in microbes. We know that when we go through periods of intense stress, that can cause these microbes to become depleted. And we know that for us women, when we go through menopause, there's a major shift in our microbiome, including depletion of these strains. So there are things about you that you're just doing that are just part of life that can cause you to become depleted in these strains. And so there could be a simple period of replenishment and then a focus on the diet that keeps these guys colonized that could really totally change your outcomes and your health

• 43:55Speaker 01

  and your overall sense of well-being.

• 43:58Dr. Darshan Shah?

  I can tell you see it over and over again. You know, I think that microbiome and probiotic science has advanced so much in the last like five years, in fact. You know, and you've been a huge part of that advancement. Where before it was just like, you know, take a probiotic and see what happens. Now like really honing in on the strains and why they work and what they're doing has totally changed the landscape of probiotics.

• 44:20Speaker 01

  Absolutely. I mean, these next generation probiotics are really, this is when we're talking about the distal colon, like where all that action is. All of that science is getting uncovered. And there are a handful of companies that are now translating that science into products, both on the pharmaceutical side and on the consumer side. And you know, it's funny because probably about 15 years ago, somebody asked me if I would come be an advisor for one of these supplements companies that was selling primarily probiotics. And you know, I have my, my background is in biochemistry and molecular biology. And I basically said, that whole thing is bullshit. I mean, I didn't, I was like, no, like I have a reputation to uphold. I don't want to be a part of any of that stuff. And boy, I got to tell you, over the last 10 years, all of the data that's been uncovered around the microbiome, it is a real science now.

• 45:03Dr. Darshan Shah?

  Yeah, it really is. You know, you mentioned menopause and your gut bacteria. And I think this is an area that's just being elucidated now too. Like the connection of your gut microbiome and your hormones. Can you speak about that connection and menopause? And how this, they interrelate with each other?

• 45:21Speaker 01

  Yeah, so. You know, for, for women, we, we kind of go through most of our fertile life with kind of these high levels of estrogen and progesterone. And one of the things that happens, one of the hallmarks of going through menopause is that as you're going through menopause, there's sort of this precipitous drop in, in both of those hormones, and then you kind of level out at this low level of estrogen and progesterone. And what's been found is that your gut microbiome, literally, if you were to trace it, also goes through this incredible transformation during menopause. And it's, it's, some of it is that menopause is changing your microbiome, but some of it is that your microbiome is changing kind of your menopausal state. And one of the kind of, I don't know how people will feel about this, but one of the most dramatic things that happens to your microbiome is that women's microbiomes start to look like men.

• 46:06Speaker 01

  Oh. So if you are in kind of before menopause, you could take a microbiome of a man or a woman, and you could almost immediately tell like, oh, this is a microbiome from a woman, because we have microbes that help metabolize these hormones. And I'll get into that in a second. But if you look at a woman after menopause, you basically cannot distinguish between a man and a woman. We essentially look like a male microbiome, because we don't have all these microbes that are there to work with our hormones, these high levels of estrogen. I don't know how people feel, if they feel good about that, or that's depressing, but that is what it is. But one of the key families that distinguishes women before menopause and after menopause are these strains that have the ability to produce what's called beta-glucuronidase.

• 46:48Speaker 01

  So just to really take one step back here, and you know, I'm not a medical doctor, but essentially, you know, your body makes estrogen primarily through your ovaries, but there are other parts of your body that can make estrogen. And when your ovaries release estrogen into the bloodstream, there's kind of one of two routes. And one of those routes is that it can, you know, one is that it stays circulating in the bloodstream, and the other route is that it can go to your gut microbiome. And, sorry, I should say, before that, you know, one is that it can be circulating, go to your gut microbiome, the other is that it goes to, does it go to the liver?

• 47:20Dr. Darshan Shah?

  Estrogen, yes.

• 47:21Speaker 01

  Yeah, goes to the liver, thanks. This is where I have to give all the caveats, like I'm not a medical doctor. It goes to one of your other organs. It goes, this is not the gut. It goes to your liver, and it can get conjugated with these, basically, attachments of glucuronide? I guess is what it is.

• 47:35Dr. Darshan Shah?

  I think it's glucuronide, yeah.

• 47:36Speaker 01

  I think it's glucuronide, yeah. And it doesn't matter, actually, what the conjugation is unless you're deeply interested in biochemistry. But basically, what happens is when that gets conjugated, that tells your body that you should get rid of that estrogen. So it goes out in your stool and your urine and things like that. But when that kind of estrogen that has an attachment to it goes to your gut microbiome, for women before menopause, you have a whole series of strains, and their whole job is to actually do the de-conjugation. So they produce beta-glucuronidase, which will take that glucuronide off, and then that estrogen becomes free circulating estrogen. So in other words, if you have more of these strains, you will have more free circulating estrogen. And if you have less of these strains, you'll have less free circulating estrogen because of this attachment signal.

• 48:20Speaker 01

  And what happens after menopause is you basically don't have any of those strains anymore. They're not doing that job. And it's very much correlated with having very depleted levels of estrogen. So one of the ideas is that in order to mitigate all of the nasty symptoms that are associated with going through menopause, is that you could replenish these strains that will not be a, completely change you, but will slightly increase the amount of circulating estrogen so that it's less of a precipitous fall and maybe more of a leveling out. So this is all super new science and really interesting, but it's definitely this handful of proteins, a handful of enzymes that can generate beta-glucuronidase that are associated with pre and post-menopause.

• 49:01Dr. Darshan Shah?

  That is so interesting. What are the strains that modify your estrogen? What are those strains?

• 49:06Speaker 01

  Oh, man, now you're really testing my knowledge. There's a couple that we're in deep investigations on. And one of them that people can read about out there is called F. praznutzi. F. praznutzi. And it's a very interesting strain that appears to play a role both in your immune response, but it also encodes for beta-glucuronidase. And so the question is, is it doing that activity? And it's one of those strains that also becomes depleted as we age. And so that's, you know, that you can't buy that on the market right now anywhere. But it is a next generation strain that I think is super interesting.

• 49:40Dr. Darshan Shah?

  Yeah, that is really interesting because, you know, there's this whole giant industry around helping women with menopause symptoms, right? And so if it's a microbiome type of solution and replenishing certain bacteria that can help us like deconjugate estrogen, then you can have, like you said, a symptom reduction that is not a pharmaceutical agent.

• 50:01Speaker 01

  Exactly. I mean, that's basically what hormone replacement therapy is. You're just giving exogenous, you know, estrogen. And so if you have a body, your body has a natural way to do that, that could be a really interesting tactic. And, you know, I think one of, and I'll just give this plug that is not going to be any new news to anybody. But there's a incredible paucity of studies and research around menopause, including with the microbiome. And so we're going off very little information here. So the more that's invested in researching these and understanding the microbiome and its relationship to hormones and menopause, the better we're going to be able to come up with new therapies and interventions.

• 50:36Dr. Darshan Shah?

  Absolutely. I love this kind of shift from making chemicals that are pharmaceuticals to actually using natural systems that are already part of our body. And I'll refer to the microbiome as a system because I want people to think of it that way to give us what we need. Things like GLP-1, estrogen and menopause. Let's move on to the next kind of system that I think our microbiome is severely underappreciated in, is the connection between our brain health and our gut health. And you were mentioning to me earlier about the incredible amount of neurotransmitters that are made in the microbiome. Can you talk about that connection?

• 51:11Speaker 01

  Yeah, I think one of the most fascinating things that's been discovered about the microbiome is that it makes more dopamine, serotonin and GABA than your, that is produced in your brain. So your gut is producing more of these neurotransmitters than are being produced in your brain. And the question is, why? What the hell is going on here?

• 51:28Dr. Darshan Shah?

  Yeah, why?

• 51:29Speaker 01

  And, and so kind of the second really interesting discovery on the, on the heels of that is that you have neurons in your gut. And so we all kind of know we have neurons in our brain and that moreover, the neurons in your brain, you kind of get what you get. And as they die, they don't come back, right? That's why like heavy drinking and, you know, brain damage, like it's hard to recover back because those neurons never come back.

• 51:50Dr. Darshan Shah?

  The neurons are the only cells in our body that last our lifetime. Everything else is replenished.

• 51:54Speaker 01

  Everything else is replenished. Except now I'm gonna change you on that, which is that you, the neurons in your gut, they do get replenished. They turn over and you're constantly making new ones. And so, this is, then this becomes like a really interesting part of the story. So you've got neurons in your gut and you've got neurons in your brain. The neurons in your gut are generating all these neurotransmitters. And there's actually a direct path from the gut to the brain called the vagus nerve. So these neurotransmitters have a way to then make their way to the brain to then have the, you know, receptors and the activity that are normally happening in the brain.

• 52:26Dr. Darshan Shah?

  So these, I'm sorry to interrupt you, but those neurotransmitters travel through the vagus nerve to the brain, not to the circulatory system, or is it both?

• 52:33Speaker 01

  Well, that's actually, I should say, that's probably still too early to say it's only through the vagus nerve, but we know that that's one of the ways in which it can get to, those transmitters can get to the brain.

• 52:42Dr. Darshan Shah?

  Good, that concerns me because one of the surgeries I was done a lot in the past, you know, I, I, and I did this surgery many times, is a vagotomy. For ulcer surgery, like cutting off that, that highway of neurotransmitters, potentially could be a massive problem. So I'm so glad that surgery's not done anymore, or rarely done. But yeah, the vagus nerve is so important too, that connection between the gut and the brain.

• 53:05Speaker 01

  It is, it's one of those classic things where like, we don't know what this thing is doing here, take it out, you know? Um, but it turns out it is, it does have a role to play, didn't get there by accident.

• 53:14Dr. Darshan Shah?

  Right.

• 53:15Speaker 01

  And so, so, right, so the first thing is your gut is making all these neurotransmitters en masse. You have neurons in your gut. And then the third, probably craziest piece of data that's come out is that, um, when you think about these diseases like Parkinson's and Alzheimer's, and I actually started my career going after Parkinson's disease in, in drug discovery. And we were very focused on the plaques in the brain and, oh my gosh, how do you get rid of these plaques? That's gonna be the secret to stopping Parkinson's or even reversing it. Well, it turns out that these plaques first show up in your gut neurons. And then they show up in your brain neurons. So the current hypothesis is, there's actually some dysfunction that happens in your gut neurons. These plaques start to form, then because they can communicate directly with your brain, they're actually misfiring to

• 53:59Speaker 01

  The brain and then somehow this is getting translated to the brain. But probably the most important thing about this is that if that's true, you could intervene at the gut and it is way easier to intervene in the gut than it is to intervene in the brain. And so rather than focusing all your time and energy on the brain, it could be that if you got to the gut, you would get there earlier and actually be able to impact a change. And so it's just a really fascinating set of science coming out.

• 54:26Dr. Darshan Shah?

  This is mind blowing for me because I have a few patients that are showing the beginning signs of Parkinson's. And it is so concerning because there's no good therapy for this. And so I know it's super early science, but do you have any kind of advice for some of these patients or people out there that are potentially seeing signs of Parkinson's? Is there something that they can do now modifying their gut bacteria to help?

• 54:50Speaker 01

  Well, again, I think it's really, really early. And so I don't know that I can point you to a clinical trial that shows changes in the gut microbiome that could help ameliorate Parkinson's. I know I can't, that's not out there yet. But I do think that there have been some reports of, you know, if you can increase your dietary fiber and polyphenols and things like that, that that, you know, might be beneficial. But I mean, really, we're on the cusp of being able to say something more useful than what I just said to you. And so I'm, I mean, not we, but as a community. And so I think it's going to be an exciting time. You know, I don't know that there's anything really actionable out there quite yet. That's, that's got science behind it.

• 55:26Dr. Darshan Shah?

  Yeah, but I do think, you know, you touched on something there, which is big picture. We know what we need to do. We need to get our guts healthy again, right? I mean, that's the big picture. And I think the things that I always harp on is eliminate ultra processed food from your diet, minimize alcohol, minimize the toxins in your food by choosing organic food that's been raised responsibly, close to where you live. All of these things are going to be massively beneficial to your microbiome. And so just a general, getting your microbiome healthy is going to help your GLP-1 production, is going to help protect your brain from some of these diseases, is going to help all these different factors that we're talking about, right?

• 56:02Speaker 01

  Absolutely. And so hopefully the question you asked me in the beginning about the biggest, you know, misconception about the microbiome is that it's only here for, you know, constipation. And diarrhea. Hopefully, what we've gotten to here at the end is like how many other systems is involved in and how your body has these natural things it's producing through the microbiome, GLP-1, serotonin, dopamine, circulating estrogen, and that really we're just at the beginnings of understanding, how can you now modify a person's microbiome to increase its ability to do all these functions? And knowing that your microbiome becomes depleted as you age, means that you know that you start to lose some of these functions. And so how can we give those back to people becomes a huge opportunity for change.

• 56:43Dr. Darshan Shah?

  Right, and more targeted probiotics that are really working, not just for general gut health, on the big ones that we know of, which you can just basically get from yogurt, I think, right? It's just having some of these more targeted probiotics. One important aspect of the microbiome that we haven't touched on yet, is its connection to the immune system, inflammation, and by proxy, cancer. And I'd love for you to talk about how having a depleted microbiome or unhealthy microbiome can potentially lead to immune disturbances, which then lead to cancer.

• 57:14Speaker 01

  Yeah, so there's been quite a bit of research on the relationship between the gut microbiome and our immune system. Now, immunology is one of the classes I hated, because it's so complicated. And I don't think we really, you always wonder like, should this number, should this IL be high? Or should it be low? And oh, it should be high in certain circumstances, but low in others. And so it's like one of the most complicated systems in the body, in my opinion. And so, but what we do know is that your microbiome can influence, and there are certain strains that can actually influence the levels of interleukins in your body. And that's really, I think, interesting. And then moreover, there have been immuno-oncologists, some of them really sophisticated in thinking about the role of the gut microbiome in conjunction with chemotherapy.

• 57:56Speaker 01

  And there's actually a book written, I think Dr. Williams, I'm blanking on his first name now, but he wrote a book, I think, called The Immunotherapy Revolution, or something like that. And in that book, he talks about immunotherapy, and he talks about the role of the gut microbiome, and he calls out specific strains that he believes are important in terms of their role with the immune system and immuno-oncology. And I learned about Dr. Williams because In his book, he wrote about four really important strains. And three of those are strains that we had identified as being important for glucose control. So Pendulum Glucose Control has five strains in it. Three of them, he wrote about in his book, is being really important for enhancing immunotherapy.

• 58:36Speaker 01

  And I met him because he was using our products alongside patients that were on immunotherapy and shared with us some just amazing stories about patients who are supposed to be on, you know, let's say, eight weeks of chemo. And when he paired the gut microbiome intervention with their chemo, they were done after four weeks. Or, you know, gee, I thought that you were going to have to come back, you know, four weeks from now for your second go at it. And they didn't have to. They could actually extend the period of time between the treatments. And so really, really interesting and, you know, opportunities out there.

• 59:11Dr. Darshan Shah?

  Yeah, I mean, you know, when a patient is undergoing chemotherapy, a lot of what you're going through seems very, it's very hard. Let me just say that. Anything that you can do to make it better for people, extend time period between chemo sessions. I mean, that's incredible. I love it that people are looking into this.

• 59:28Speaker 01

  Yeah, and I would say like what's been amazing for us as a company is that by releasing our products, you know, and making them available to everybody and not just going through the kind of traditional medical system where they have to be prescribed for certain disease. What we've done kind of is to enable all of these healthcare practitioners who have had theories about the gut microbiome and who've been doing all this research to now have a new tool in their toolbox for their patients. And for me, one of the most rewarding things has been watching other people. I mean, I didn't have that idea at all. So like, I'm not going to take credit for it, but we have a handful of immun oncologists that did have that idea. And the fact that they understand the importance of the gut microbiome alongside their treatment

• 1:00:11Speaker 01

  and they understand their patients deeply and where there might be opportunity is just an incredibly rewarding thing to see and also shows us that there's so much opportunity out there when we think about improving the microbiome.

• 1:00:22Dr. Darshan Shah?

  Yeah, absolutely. I mean, I think the statistic is about 80 to 90% of your immune system actually lives in your gut. And what's happened- There, one of the, one of the things that I see a lot in my practice is that people have unhealthy gut microbiomes. And they also have high markers of inflammation, HSCR P, homocysteine. And the minute they fix their microbiome, the minute they get their diet in order and they take some probiotics, their inflammation goes away. And that inflammation is one of the other root causes of all disease next to, next to having a poor metabolism. So we've touched on, you know, the microbiome, preventing disease through metabolic effects, through reducing inflammation, through, you know, hormones that go for our,

• 1:01:05Dr. Darshan Shah?

  from hormones that go into our brain and also throughout our body. Like it has so many different effects. And the correlate to that for me is having an unhealthy gut microbiome through these various biological pathways is what's actually led to this massive, massive increase in disease in the last 50 to 80 years, right? And so I think there's something very pivotable, pivotal about the microbiome in that regard.

• 1:01:31Speaker 01

  Absolutely. And, you know, there's something, you know, also that I want to make sure that is, is really clear, which is that the microbiome is very much tied to your nutrition. And so I think about it like a high performing car. You got to put the great fuel in that car, but it has to have an amazing engine. If you want to have a high performing car. And so your body is the same way. It's about the fuel that you put into your body, the food that you eat, and then having a high performing engine, which is your microbiome. And if you've got both of those going well, you've got a high performing body. And you don't need to be a doctor or scientist to know that almost everybody has experienced a time in their life where you just kind of ate shitty food. And then you felt shitty and then you ate more shitty food. And you can end up being on this cycle where, and it's not just like, oh, I, I don't feel good.

• 1:02:13Speaker 01

  But it's, you know, like mentally or emotionally, but all of your other systems are, you know, you're tired. You've got less energy. And so you can be in this really bad system where the food in your microbiome, because they're so tied, you can get into a bad cycle. And for some people, it's really just changing one or the other of that, that can have put you immediately on a totally different, bouncing from this treadmill to this treadmill, where all of a sudden, you know, everything is much more operational, your metabolism is. Working better, you've got therefore better energy. You're not kind of going through this, you know, crazy spikes and crashes throughout the day. Your hormones are much more regulated. Your levels of serotonin and dopamine and GABA and all these things are much more regulated and in tune with a healthy body.

• 1:02:55Speaker 01

  And so it's just to say that a small change could really have long lasting and large effects across all the systems in your body.

• 1:03:03Dr. Darshan Shah?

  Absolutely, and we know that things like exercise, sleep, having good sleep affect your microbiome as well. But I think, like you've mentioned, the biggest change that you can make is in your diets.

• 1:03:19Dr. Darshan Shah?

  This episode was brought to you by Next Health, a health optimization and longevity clinic located in Los Angeles, Manhattan, and soon to be opening in Montecito, Nashville, Miami, and many other cities in the United States and Canada. Next Health is the Apple Store of wellness, where you can optimize your health span and lifespan using cutting edge technology. I actually founded Next Health eight years ago to give my patients a place to go get extensive biomarker testing done and provide them with all the tools that I use to get my health in order. The longevity circuit in Next Health using hyperbaric oxygen, sauna, cryotherapy, and LED light is a game changer. In addition, the doctors at Next Health measure thousands of biomarkers and put into place

• 1:04:03Dr. Darshan Shah?

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• 1:04:18Dr. Darshan Shah?

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• 1:04:59Dr. Darshan Shah?

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• 1:05:12Dr. Darshan Shah?

  Let's give people some practical tools that they can use right now to improve their gut microbiome. Well, first of all, before we even do that, let's talk about testing because how do people know if their gut microbiome is off? And so there's all these stool tests, you can buy them online now and you can send them in and somehow they figure out you should eat radishes and not celery. Is any of that worth it?

• 1:05:38Speaker 01

  Well, let me start by saying that I do believe there's going to be a day where gut microbiome testing will be tied to what you should be, some kind of like action you should take on the other side of that. As a regular person, we are not there yet. There are some practitioners who are using those gut tests in conjunction with other tests and information they have about their patients and they're able to tie together a story that helps guide them on dietary changes or treatments. And that I do believe in. I believe in that. But it's definitely not codified and it's definitely not out there in any kind of protocol that is scalable at the moment. So I think all of that is going to happen. I have a lot of skepticism around the consumer gut microbiome tests because many of those companies especially,

• 1:06:23Speaker 01

  they actually, their business is they're selling supplements. And so if someone is giving you a test and then their conclusion is you need to buy more things from them, there's just a kind of a natural skepticism you ought to have and probably just have by instinct. I do think that there are a couple of good tests out there. So I would say Genova Diagnostics has a good test and DSL does a great test, especially for measuring acromancy or their GI map. Those you can't actually get as a consumer. So that maybe tells you something about the level of quality of those tests. So that being said, the most important thing about testing your microbiome is to not just do one test and then think that that's the result that you've got. You should take multiple tests and get yourself a baseline piece of data because the time of day that you create the stool, the meal you just had

• 1:07:05Speaker 01

  right beforehand, like all these things can change the way that readout happens. But there will be some stable things about your microbiome that you'll be able to see once you have longitudinal data. So the thing for sure you shouldn't do is take one test, look at that result and be like, aha, you should definitely. Take multiple and you should probably mostly do it through your healthcare practitioner.

• 1:07:23Dr. Darshan Shah?

  Yeah, that's why those tests are only sold to healthcare practitioners because they are very complicated to read. And you don't want to make jump, you don't want to jump to conclusions based on one test. Like we were mentioning, we had dinner last night, even just all of us hugging each other and eating the same food. That changes our microbiome. Your microbiome is constantly changing hour to hour. Depending on kind of what you're eating and what you're doing, how you slept, all these things. And so I think stool testing is very complicated and you're right, the science is not there yet. But there are certain things that we can elucidate from stool tests. And you mentioned one of them is diversity, right? So can you talk a little bit about diversity and how to create more diversity in your microbiome?

• 1:08:02Speaker 01

  Yeah, I think at a really kind of, you know, high level metric that we look at is diversity. And it's, it's not, it's not great because it's just basically saying like more diverse is better. But that's probably not totally true in general, but it's, it's good enough for now. Because we don't know what are all the very specific functions that you need to get replenished. But the whole concept is like more diverse means you have more functions and then therefore that must be better. So I think it's a fine metric to use for now, but it'll get better over time.

• 1:08:30Dr. Darshan Shah?

  It'll get better over time.

• 1:08:31Speaker 01

  So when we think about increasing the diversity of specific functions in your microbiome. I think a lot about these short chain fatty acids. There's a whole family of strains that are responsible for increasing short chain fatty acids. And specifically butyrate is one of the ones that's been probably the most well studied for its role in not only colon health, but also actually also in metabolic health. So the kinds of foods that you can eat that bolster these strains are, if you imagine walking into a grocery store, you either veer right or you veer left for where all the produce is. So you're walking to that produce section, anything, any of your leafy greens, any of your berries, things that are, you know, your asparagus, your, so all of these things that are high in fiber and high in polyphenols. And again, it really does go back to caveman days.

• 1:09:16Speaker 01

  What were we eating when we didn't have access to Frito Lay? We were eating, you know, these vegetables and these berries. And so that's the section where you're really going to be replenishing these butyrate producing microbes.

• 1:09:28Dr. Darshan Shah?

  Right, right. So, yeah. Cavemen, we were foraging and that's when our microbiome basically started to live synergistically.

• 1:09:35Speaker 01

  Yes.

• 1:09:35Dr. Darshan Shah?

  With us. And so it's so important to have produce in your diet that's well sourced, that's organic and does not covered with pesticides, right?

• 1:09:44Speaker 01

  Exactly, exactly. And then particularly this strain that we've talked a little bit about, acromancia is, we know that it flourishes when you have increased high fiber, but particularly polyphenols. And so that's where you're starting to think about your berries. So pomegranates, they're actually a great source of polyphenols, but even getting outside of that. So green tea is also a great source of polyphenols. And then even though I know we're not supposed to drink a lot of alcohol, red wine does actually have good polyphenols in it and dark chocolate. So if you gotta have a vice, at least get some polyphenols in.

• 1:10:13Dr. Darshan Shah?

  Exactly, exactly. The short chain fatty acids supplements that you see out there, are they beneficial? Could they be also be helpful in helping us kind of produce bacteria that can create more short chain fatty acids? Or what are your thoughts there?

• 1:10:26Speaker 01

  For the most part, those supplements have not had the kind of clinical data that one would expect or hope based on kind of animal studies and things like that. And so like if you do an animal, if you look at the animal study literature, it's amazing. You could just give these animals butyrate and then all of a sudden they're cured of like a quite a variety of diseases, including metabolic syndrome. But what you have to know about the way that those are delivered to those animal models is they're literally gavage feeding them. And so they're getting the those short chain fatty acids right directly into the gut microbiome. And the supplements, when we take them, we're not gavaging them, we're taking a pill. And so the, so I think the issue with why

• 1:11:05Speaker 01

  we haven't seen that kind of efficacy with the supplements of butyrate is because it's a, it's a, it's a delivery problem. So I'll do another analogy, just because that's how my brain thinks.

• 1:11:16Dr. Darshan Shah?

  Yeah, I love it.

• 1:11:17Speaker 01

  You know, if I were, if I said, Darshan, I'm going to give you a million dollars, would you rather I put it in suitcase, knocked on your door and handed you the suitcase, or would you rather I called you and I said, hey, I just scattered it all over PCH? You would much rather get that suitcase delivered directly to you because you know you're going to get that suitcase of money. And if I scattered it all over PCH highway, everybody's pulling over their cars and they're taking your dollars. And that's sort of the same thing with these short chain fatty acids. So butyrate is a small molecule that is used by all of your colon cells. So your colon cells are different from every other cell in your body, because every other cell in your body uses glucose as its energy source. Your colon cells use butyrate as its energy source. So every colon cell would love to get as much butyrate as possible. That's the dollar bills. So when you take this butyrate supplement, it has to make its way past all those colon cells who are

• 1:12:02Speaker 01

  basically all the drivers on PCH grabbing all your butyrate. By the time it gets to the receptor that it needs to get to, these G protein coupled receptors, it's basically gone. And so if it doesn't get to that receptor, if I don't hand it directly to you, the recipient, then you've got a problem with delivery. And I think that's actually why they haven't worked. Butyrate is super important. You've just got to get it to that receptor.

• 1:12:22Dr. Darshan Shah?

  You know, I've always wondered why those supplements did not work. And I agree with you. Like, the research shows that it's not as anywhere near the effect that you see in some of these animal models. And that's the reason why. They're not getting where they need to be to the bacteria that need them. And so, once again, it's very important to keep the bacteria healthy, so they can make the butyrate.

• 1:12:42Speaker 01

  And they literally sit right there. I mean, so acromancy is one of these things that can help, you know, produce these short chain fatty acids. It's literally sitting right next to the receptor. So it is doing that handoff. It's making it and the receptor's sitting right there.

• 1:12:53Dr. Darshan Shah?

  Right, right. Wow. Amazing. So what about fermented foods? I think those are also very helpful in your diet as well?

• 1:12:59Speaker 01

  Yeah, those are chock full of, you know, kind of these, there's a category of probiotics out there that fermented foods and yogurts and all of those do carry. And they're primarily in the lactobacillus and bifidobacterium families. And so, yeah, I mean, those are important also.

• 1:13:14Dr. Darshan Shah?

  Probiotic yogurts?

• 1:13:15Speaker 01

  Yes, yeah.

• 1:13:16Dr. Darshan Shah?

  I think also, a lot of people talk about ingesting things like bone broth, which has collagen in it as well for your gut health. You know, I talk a lot about how to rebuild your gut, because it's crazy. Almost 80% of people have some level of leaky gut, and they have some level of microbiome dysregulation. And so I think it's really important for people to know, what are the kind of the tools in the toolbox? And a lot of it is just a natural diet, right?

• 1:13:41Speaker 01

  Yeah, I, I, I think the, the natural whole foods, you know, are, are really, like I said, it's that produce section. It's hanging out there and the more of those that can go in your meal, the better. And then also, you know, things like lentils, those are also really important for your gut microbiome.

• 1:13:57Dr. Darshan Shah?

  We had lentils last night.

• 1:13:58Speaker 01

  We had lentils last night. Yeah, yeah. And so all of those high fiber foods.

• 1:14:03Dr. Darshan Shah?

  Right, exactly.

• 1:14:03Speaker 01

  Those legumes.

• 1:14:04Dr. Darshan Shah?

  Right, right. Okay, so we've touched on food as very helpful, of course, for your microbiome. Let's talk about the advancement that you and your company have made in microbiome science and what you found to be helpful. What are some of the products that you have created from the science? Which I love the depth of science that you've, that you've put out there. Let's talk about some of those products and why they're helpful.

• 1:14:28Speaker 01

  Sure. So, you know, our company spent almost a decade doing R and D before we came out with the product. And the premise was we wanted to really go after the gut metabolism axis. And we wanted to go after things that we knew had an underlying mechanism of action would, would lead to positive outcomes. And we wanted to have measurable positive outcomes. And so our flagship product, our first product we put out there is Pendulum Glucose Control. And it's a formulation of five strains that generate butyrate, work on the regulation of the gut lining, and also stimulate GLP-1 production. And all three of those are known to be important for metabolic syndrome. And one of the things that was very important to us is that we don't just hypothesize that that's going to happen, but we have actual data to support it.

• 1:15:13Speaker 01

  And so we did a placebo-controlled, double-blinded randomized trial that was published in BMJ that showed that compared to placebo, people with diabetes who were on this formulation for 12 weeks had a lowering of their A1C by 0.6 points and a lowering of their blood glucose spikes by 33%. And that means that you can have effectively the efficacy of a drug, but the safety of a probiotic, all in this formulation. That was massive for us. I mean, super exciting because you can have a lot of theories about how mother nature works, but to actually be able to change it and have that kind of outcome, I think is really. Um, it was just really exciting. And so pendulum glucose control is something that you can buy if you have type 2 diabetes and you're trying to lower your A1C and

• 1:15:56Speaker 01

  blood glucose spikes. We also sell the single strain of acromancia if people are just trying to replenish that strain. And then we just launched a new product, our GLP-1 probiotic last quarter, and it's basically a subset of the pendulum glucose control formulation. It's just the subset that helps stimulate GLP-1 production. So there's three strains that are in that department. That's what's in that, those pills. And I think one of the exciting things about what we've put out into the world is that these are strains that you can't get anywhere else. These are strains that are really being clinically studied for the first time and they're novel. And so you're really tackling your microbiome in ways that you can't, you haven't been doing with all those other kind of supplements that are out there. And so it's just giving people another tool to be able to use and

• 1:16:39Speaker 01

  practitioners another tool to be able to use against metabolic syndrome. And it's been a very exciting. And we do also offer a polyphenol booster. And so we specifically studied a panel of polyphenols and how they interacted with our acromancia strain. And so the idea there is that you can take this polyphenol to, as the food to help also boost your levels of acromancia in these different formulations.

• 1:17:01Dr. Darshan Shah?

  Wow.

• 1:17:02Speaker 01

  Yeah.

• 1:17:03Dr. Darshan Shah?

  Amazing stuff. It's, it's just such a massive step forward in the science. And I think, I mean, I think you'd agree, we're still at the infancy of all of this, right?

• 1:17:12Speaker 01

  Oh, man, we are definitely at the infancy of it. And I would, I couldn't stress that enough, which is to say that, you know, this is all we know right now. I think there's massive opportunity, but, you know, we also have to point out that there's also risk and potential downside. Because this is a new science, because we don't fully understand the ecosystem or what all these strains do in the context of different, you know, microbes, it is important to stay on top of the literature and it is important to fuel more and more research so that we know it's probably not going to be a case where everything is good all the time and no matter what the circumstance is. And so we need to get a lot smarter about that. We need to get a lot more sophisticated than diversity is important. Like, well, diversity of what? And so I think all of that is, you know, we're really just at the beginnings of. And I mean, in your practice, when you think about supplementation and these next

• 1:17:57Speaker 01

  generation probiotics, I'd be curious How do you think about them?

• 1:18:00Dr. Darshan Shah?

  Yeah, you know, I'm very careful with supplements with my patients because I always want to meet the patient where they're at. Right. And it's kind of like a bell shaped curve of people. There's people that a bell shaped curve, meaning that, you know, people fall into generally like a few different categories of people with most people falling somewhere either to the right or left or the middle. Right. You can see that in politics. You also see that in supplements.

• 1:18:22Speaker 01

  Yes.

• 1:18:22Dr. Darshan Shah?

  And so you have people on one side of the spectrum that want absolutely nothing. They're like, I will never take a supplement, no matter what you tell me. I don't believe in them. And then you have people on the other side of the spectrum that are like, I want everything that Brian Johnson, Mark Hyman, and Andrew Heberman take. I want all of it. And so it's like, you know, you have to find people, um, meet people where they're at. Right. And so I think most people have kind of a measured approach, um, either right or left of the middle of this. And I consider my kind of middle ground approach for most people to get them started is there's certain foundational supplements that I think are extremely important for most people to consider. Those are certain vitamins, such as vitamin D in the form vitamin D three K two.

• 1:19:04Dr. Darshan Shah?

  Those are methylated B vitamins, especially if you have a genetic deficiency called MTHFR. Things like also omega threes, I think we don't get enough of those in our diet. And, and then I've added to that certain core supplements that are more recent in the literature. Things like nicotinamide riboside, which helps to boost our mitochondria. I've also added the pendulum.

• 1:19:31Dr. Darshan Shah?

  I, I use a metabolic health for people that, for most people, especially if they have some degree of metabolic syndrome, which I find to be almost 90% of people. If they don't have any degree of that, like, you know, I have a few patients that are very tightly controlled on their diet and they do extremely well with their diet, then we use maybe one of the other ones as a, as a core supplement. And then lastly, you know, we didn't talk about this yet, but urolithin A is also something that's becoming, I think, very well studied to help boost our mitochondria, mitogenesis, et cetera. And I've, and I'm strongly considering that being part of my core stack. And then, you know, if people want more, there's more, but we, we start there. But I think this gut health problem is so pervasive in our modern society. Even if you're eating the most healthy diet possible,

• 1:20:16Dr. Darshan Shah?

  the problem is, is we are exposed to the most toxic environment that humans have ever been exposed to. So your gut is having a very hard time keeping up. And I think that, you know, I think that microbiome support is going to be one of those core foundational things that we need to do. Now, I do think I love the evolution that we've gone through where we've gone from away from shotgunning, you know, how many CFUs of lactobacillus is the supplement have to a really targeted approach to things that work? And I think that's where we needed to be before I added this to the core stack.

• 1:20:47Speaker 01

  Yeah, yeah, I think that makes a lot of sense. I mean, it really is a systems biology approach that you're taking in your practice. And I love to hear from, you know, people that are actually practicing medicine with different patients to try to understand, you know, in what circumstances are different things being used and working. And so, but I agree with you, having gut microbiome as one of the core things in your stack just makes good sense.

• 1:21:09Dr. Darshan Shah?

  Yeah, I think so. And I think even if you don't, if even if you're not a supplement person, I think having this focus and this realization that the microbiome is another system in our body, almost, or I would say just as important as our cardiovascular system, as our liver, as our metabolic system. Like having that level of respect for the microbiome changes your perspective into bringing something that's invisible to the forefront so that you do change your habits around your diet and your sleep and your exercise and your stress management to really respect this. And it can be a massive and dramatic shift to your health in a very short period of time, actually. You mentioned six to eight weeks, you can change your microbiome, right?

• 1:21:49Speaker 01

  Yeah, yeah, it's pretty incredible.

• 1:21:51Dr. Darshan Shah?

  Yeah, I'll tell you one more thing, just real quick. Like I have a patient that, you know, just by fixing their gut health, this is a very well-known person was suffering with depression, months and months of depression on two different medications. One medication to boost the effect of the antidepressive medication that actually gave him suicidal tendencies. And when he saw me, I was, you know, we did our standard battery of tests and we saw that he had massive amounts of inflammation. And then, you know, going through a history, we found that a lot of this was due to Just eating ultra-processed food all the time, actually eating fast food all the time. Massive gut microbiome dysregulation. So through a combination of fixing his diet and microbiome support, in eight weeks, he was able to get off his antidepressant medication, both of them.

• 1:22:33Speaker 01

  Wow.

• 1:22:34Dr. Darshan Shah?

  Right.

• 1:22:34Speaker 01

  Wow.

• 1:22:35Dr. Darshan Shah?

  And it's just, you know, it's like this pharmaceutical approach to treating all diseases, especially mental health disease, by masking the symptoms, which has a ton of other effects. Just going to the root cause, which is the microbiome, is so effective. So I really applaud what you're doing with your company and really helping humans address this issue.

• 1:22:56Speaker 01

  Thank you, thank you. Yeah, and just as an add-on to that, you know, thinking about mental health, we think a lot about food cravings as part of that. And so I'll just tell you, you know, the story about an individual who came to us and said, like, I've always been the guy who, if there's a cake after, like, I'm eating that cake. And if there's a plate of cookies at the holiday party, I'm eating that whole plate of cookies. And I just have always been a sweet tooth. That's always been me and who I am, and I can't really do anything about that. And he went on this GLP-1 probiotic for two months. And he said, it has been an amazing transformation because, he said, I actually don't even really crave dessert anymore, or I can take a bite of dessert and then I feel satiated.

• 1:23:37Speaker 01

  And that weakness, that I used to joke about, like, oh, I just have a sweet tooth, that's actually not me. I now realize that was a deficiency in my microbiome, that I had defined myself as a sweet tooth, and that was always going to be who I was. And now he had broken this pattern and viewed himself in a totally different light. And so felt like he was a much more healthy person, able to make good choices. And so I think we end up in this catch-22 where you tell people like, oh, you shouldn't be eating all those sugars and all those cookies. And they can't do it because they're actually missing the right signaling pathways, the GLP-1 production. But once they have that, all of a sudden, you feel stronger, you feel more in control, you feel like you can make these good choices. And those are the stories that I think feel very relatable

• 1:24:20Speaker 01

  and also can get you out of the kind of trap of thinking, this is me, this is who I am, and I'll always be like this.

• 1:24:27Dr. Darshan Shah?

  Absolutely. And you know, like you mentioned, when you first started telling the story about mental health, because that is a mental health issue. When you feel like you're out of control, when you have no ability to regulate yourself, whether it be with diet or other addictions or other cravings. And you know, this is a whole other topic, but there's a lot of research going on now with GLP-1 and reducing cravings for things like alcohol, for things like, you know, even sex cravings, so sex addiction. And so I think there's a massive amount of research to be done there, but it just emphasizes the point of your gut is so intimately connected to your brain and your emotional health and your neurologic health. And it's definitely something that people need to consider if they're struggling with

• 1:25:12Dr. Darshan Shah?

  mental health issues or addiction.

• 1:25:14Speaker 01

  Absolutely, absolutely.

• 1:25:16Dr. Darshan Shah?

  Wow, what a great conversation, Colleen. I love it. I think people will really gain a new understanding and get some really practical tools to help with this issue that all of us are facing. Colleen, you know, you're such an interesting person. What I love about you is you're a scientist, but you can, through your storytelling and through your analogies, you're able to tell an incredible story about your science. And so

• 1:25:39Speaker 01

  Thank you.

• 1:25:39Dr. Darshan Shah?

  I really love that. And I also want to hear kind of where this is going because you're on the forefront. I want to keep in touch with you and make sure people hear what you're doing all the time. Tell us, what are you excited about? What's coming up in the future for you?

• 1:25:51Speaker 01

  Well, I think, you know, I'm really excited about, let me all start with, we've developed these products that I think could be real game changers for metabolic syndrome as well as for gut microbiome. And most people haven't heard of Pendulum. And so what I'm really excited about is getting the opportunity to talk with people like you and others to kind of get the information out there and into people's hands so that more people can benefit from these products. You know, our mission is to help millions of people improve their health through the microbiome. And we can't do that without awareness. And so I'm really excited about the opportunity to share out what's been built. And you know, these products, I'm, you know, I don't want to say like they're for everybody, but I do think fundamentally they're for most people because we are living in a world with depleted gut microbiomes.

• 1:26:35Speaker 01

  And so I'm really excited to see these products. Kind of make their way into more households and help benefit more and more people. And then I'm very excited. We covered a wide breadth of different opportunities in the microbiome. I'm so excited to see other people who are working on those different arenas to really come out with the next products. And for me personally, I'm very interested in this gut-brain connection. Because I started my career looking at the brain and things that we traditionally thought of as neurological deficiencies like Parkinson's. And to realize that we might be able to target them through the gut, which is a way easier target to change. I just think that is a game changer for neurological diseases. And that ranges from autism to stress and anxiety to Alzheimer's and Parkinson's.

• 1:27:20Speaker 01

  So just massive opportunity there.

• 1:27:23Dr. Darshan Shah?

  Yeah, we wasted a generation chasing therapeutics that work directly in the brain against things like plaques. And just drug after drug that has failed over and over again. And to have this new perspective, just to hit the reset button, start over and have some hope. Because as we know, all neurodegenerative disease, Alzheimer's, Parkinson's, is on such a massive upswing right now. And to be able to prevent it early, I think the early is the key, right? Is just massive. And so I'm so excited to see what you come up with there. And it's going to be a game changer for the world.

• 1:28:00Speaker 01

  It is. It is. It's an exciting time to be in the microbiome.

• 1:28:03Dr. Darshan Shah?

  It is. Thank you so much for joining us today, Colleen. I look forward to having you on again and telling us some more stories and giving us more analogies.

• 1:28:12Speaker 01

  Thanks so much for having me.

• 1:28:14Dr. Darshan Shah?

  Thank you, Colleen. We'll see you next time.

• 1:28:16Speaker 01

  Thanks.

• 1:28:20Dr. Darshan Shah?

  That was an incredibly insightful conversation with Colleen. I'm so glad she joined me at this podcast. Every time we talk, I learn so much. She's a true expert and she explains it so well. So here are the top 10 things that I learned talking to Colleen. Number one is that your gut controls much more than just your digestion. Your microbiome isn't just helping you digest food, it's actually regulating your metabolism through secreting compounds like GLP-1. It's also regulating blood Trigger hormones and even mood. So if your gut health is off, it usually means that your gut microbiome is off. And that's what's throwing off some of these other factors. Number two is GLP ones. We've heard a lot about them as drugs. Well, they're not just drugs.

• 1:29:02Dr. Darshan Shah?

  It's actually a natural substance and a hormone that your gut makes. It's the same hormone behind weight loss drugs like Ozempic. And we produce it naturally by our gut bacteria, specifically Akkermansia. If you have a depleted microbiome and specifically depleted Akkermansia, it means that you're going to have lower GLP one levels, which leads to weight gain and blood sugar issues. Learning number three is that a damaged microbiome drives food cravings. So if you're craving sugar or carbs, I think it's a good idea to understand that it's not just your willpower that's at fault here. Your gut bacteria are influencing your hunger hormones. So the wrong balance of microbiomes and especially not having Akkermansia

• 1:29:43Dr. Darshan Shah?

  can keep you in a cycle of overeating due to unregulated cravings. Number four, I like to say this a lot. Antibiotics are like a nuclear bomb for your gut. So while they're sometimes necessary, antibiotics do wipe out both good and bad bacteria in your gut. And rebuilding your microbiome after a round of antibiotics can take months or even years. So this is why it's really important to only take antibiotics when you need them. And then after you're done with the antibiotics or even during antibiotic therapy, you want to have fermented foods, lots of fiber, and even some targeted probiotics to help rebuild those gut bacteria. Number five, your gut is talking to your brain using your microbiome.

• 1:30:24Dr. Darshan Shah?

  So the gut is producing dopamine, serotonin, and GABA more than even the brain produces. So if your gut is unhealthy, it can contribute to anxiety, depression, and brain fog by dysregulated levels of these neurotransmitters. Number six, low microbiome diversity equals a slow metabolism. So a healthy gut is a diverse gut, meaning you have many different strains of bacteria, viruses, and fungi living there. People with low microbiome diversity have slower metabolisms, higher body fat, and more difficulty managing their blood sugar. So when you're doing gut bacteria testing, the diversity score. Matters. Learning number seven is your skin microbiome matters too. Oversanitizing with antibacterial soaps, harsh cleansers can strip away beneficial microbes,

• 1:31:07Dr. Darshan Shah?

  leading to skin issues like eczema, acne, and increased sensitivities. Number eight, C-section babies miss a critical microbiome boost. Vaginal birth provides newborns with essential bacteria that build their immune system and digestion. Babies born via C-section often start life with a depleted microbiome. And I could tell you from delivering babies in the hospital that this was not something that is commonly known, that when you're doing a C-section delivery for any reason, you do want to do a microbiome wipe to the baby. And you should talk to your OB GYN about that if you're delivering a baby in the near future, or know someone that is. Number nine, ultra-processed foods are starving your gut. So this is how ultra-processed foods are really affecting our health.

• 1:31:48Dr. Darshan Shah?

  Your gut bacteria thrive on fiber, polyphenols, and nutrients from real food. Processed foods don't have a lot of fiber. They don't have a lot of polyphenols. They don't have a lot of nutrients. What they do have is a lot of sugar, sometimes artificial sweeteners, and empty calories. And these starve your gut bacteria for the nutrients that they need to make beneficial compounds for you. So this is how ultra-processed food and a diet high in ultra-processed food can lead to your gut bacteria being unhealthy, leading to more symptoms. And finally, number 10, if you work hard at it, you can rebuild your gut in just six weeks. Research shows that by eating fiber-rich foods, reducing toxin exposure,

• 1:32:29Dr. Darshan Shah?

  specifically ultra-processed foods, and supplementing with targeted probiotics like Akkermansia, you can restore some key bacteria in your gut. And this will lead to improved metabolism, better mood, weight loss, decreased bloating, lots of great benefits. So you can rebuild your gut. It takes some time, six weeks, but you should get started now. What a great episode. I'm so glad that you stuck around to the end to hear my 10 takeaways. I think they're incredibly impactful. And it's also really important to make your gut health a priority in your life. So if you know someone that's struggling with gut health issues, or even issues such as anxiety and depression, this could be a really good episode for them to listen to. Please forward it along and thank you once again for listening to the Extend Podcast

• 1:33:13Dr. Darshan Shah?

  with Colleen Cutcliffe as my guest this time. Thank you.

• 1:33:18Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked 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.