This GLP-1-Supporting Probiotic Is A Constant In Our Longevity Stack

Join me and Dr. Colleen Cutcliffe, a brilliant friend, scientist, and the powerhouse CEO of Pendulum, for our deepest dive yet into all things Akkermansia. This free-flowing conversation will take your understanding of this extraordinary probiotic strain to a whole new level. We’ll explore Akkermansia’s pivotal role in metabolic health—think cravings, GLP-1, weight regulation, A1C—and why we’re deficient in the first place. Plus, we’ll discuss its connection to stress, anxiety, and even neurodegenerative diseases. We’ll also dive into the hotly debated topic of Akkermansia’s impact on multiple sclerosis (MS), unpacking both sides of the controversy. And, we’ll touch on its promising influence on hormonal balance, from infertility to menopause.

As someone who’s deeply invested in science, I’m personally bullish on Akkermansia and trust Pendulum’s products as part of my own foundational health stack. With groundbreaking science and fresh insights, this episode will change the way you approach your practice. ~DrKF

Dr. Fitzgerald and Dr. Cutcliffe dive into the groundbreaking science of Akkermansia, exploring its role in metabolic health, gut integrity, and its impact on conditions like anxiety, stress, and neurodegenerative diseases. They also unpack the hotly debated topic of Akkermansia’s role in MS, offering new perspectives on both sides of the controversy and touch on the challenges of Akkermansia depletion, why we’re deficient, and whether we can recolonize it. They look towards the promise of how this unique strain influences hormonal balance, from infertility to menopause, and plays a key role in longevity. This episode offers vital insights into how this powerhouse strain can optimize health and improve clinical outcomes for your patients.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi everybody, welcome to new Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And of course today is no exception. I am once again sitting next to the amazing Dr. Colleen Cutcliffe. I love my time with her. It’s always a lot of fun and it’s brilliant and it’s game changing, so let me tell you who she is and we’ll jump right in. She’s the chief executive officer and co-founder at Pendulum and has more than 25 years of experience leading and managing biology teams in academia, pharmaceuticals, and biotechnology. Prior to starting Pendulum, Colleen was the senior manager of biology at Pacific Biosciences and she was a scientist at Elan Pharmaceuticals. She completed postdoc studies at Northwestern’s Children’s Memorial Hospital and she received her PhD in biochemistry and molecular biology from Johns Hopkins. Her BA in biochemistry comes from Wellesley College. Colleen, once again, welcome.

Dr. Colleen Cutcliffe: Thanks so much for having me. I always love our conversations.

Dr. Kara Fitzgerald: Yeah, it’s always great to be with you. So, one of the things that I was doing, sort of a little fun prepping for our conversation, was a tour of the state of the state of Akkermansia and just the meteoric kind of science that’s coming out around it. For anybody who doesn’t know– Actually, you know what I was going to tell you, Colleen? This is a total aside. We did a webinar together not long ago and we’ve done plenty of podcasts together and we’ll park all of those in the show notes and the literature that we reference, we’ll make sure it’s parked into the show notes. So definitely go there to access all of this. But the webinar that we did together looking at the GLP-1 benefit in Akkermansia, it was the best one in 2024. It was just massively performing. So thank you for that. It’s just how timely and important this information is, you know, and what your company’s doing.

Dr. Kara Fitzgerald: Let me actually remind folks listening, if you’re a healthcare provider, you can open up a wholesale account through Pendulum and can get $50 off if you use the code WSKARA50 at Pendulumlife.com/HCP.

Dr. Kara Fitzgerald: So with that, the data on Akkermansia, the probiotic that was recently termed ‘paradigm, next-generation, beneficial microorganism’, continues to rise. And I want your comments on that, but I want to layer that into this GLP-1 idea that I brought up and the exploration of some of your original research into Akkermansia and associated microbes. The benefit in metabolic syndrome– This is huge. This is huge. Stay with me– And then what you identified in the original science around cravings that got you thinking about GLP-1. So the floor is yours. Tell us what Akkermansia is and answer all that.

Dr. Colleen Cutcliffe: So, Akkermansia muciniphila is a strain that— Actually, I think you knew about Akkermansia before I knew about Akkermansia. So, you knew it was going to be important. I think that biologically speaking, there are these systems and sometimes proteins and enzymes and small molecules that have an outsized impact to our health and Akkermansia is one of those. It really is emerging as a keystone strain, a next generation beneficial microbe that does more than just one job and is really fundamental, I think, to our health. And one of the things that Akkermansia does is it plays a role in literally the structural lining of our gut. And the second thing that it does that’s really important is it is one of only two strains that’s ever been published to be able to directly stimulate GLP-1.

Dr. Colleen Cutcliffe: And so when you think about those two things, you’re fundamental to the structure of the gut lining and you stimulate GLP-1 and you’re only one of two microbes that does that, it starts to become really clear why Akkermansia is so important to the fundamentals of health around both gut health and metabolic health. And it all started with a bunch of correlative studies– thousands of correlative studies showing that in disease states, or as we age and as things are becoming depleted in terms of our functionality, there were big correlations between that and a lowering of our Akkermansia levels. And now we’re starting to uncover why that is and what it’s doing. At Pendulum, we’ve been really focused on the role of Akkermansia for gut health, but more importantly for metabolic health.

Dr. Colleen Cutcliffe: What we knew when we started working with this strain is that it had the potential to help with gut lining. What we didn’t know, what will become clearer later, is the important role that it has in stimulating GLP-1. So all of that has been uncovered, and we started to learn so much more about these GLP-1 analogs. But really, the GLP-1 analogs are mimicking our body’s natural GLP-1 hormone so we can learn a lot about how our body is supposed to naturally produce GLP-1 through the metabolism of food by our microbiome and what that production of GLP-1 looks like when it’s being done right in terms of metabolism of sugars and carbs, in terms of insulin and glucose response, in terms of food cravings. And so that’s all been really pretty interesting to uncover over time.

Dr. Kara Fitzgerald: If you don’t mind, I want to back up because you’ve obviously said a tremendous amount. So your original interest in Akkermansia was a massive database of correlation and you guys wanted to get in there and really uncover what was important about this strain. One of the huge dot connectors was its essential role in barrier patency and barrier function. And we know now that compromised barrier, damaged barrier, is basically associated with all systemic diseases, so from dementia on. Name the organ system, there’s some sort of bacterial dysregulation and there’s some sort of barrier compromise. So it makes sense too.

Dr. Kara Fitzgerald: So we see low Akkermansia as these disease states are present and continue. We see Akkermansia drop in the unhealthy aging journey, but we also see robust Akkermansia in people who are living well and long. So you have this information and then we can talk also about the fact that it’s an anaerobe and so you need to stabilize it and all of this. And so actually bringing it to production is a whole other, really extraordinary story that I’d love to talk about. But we have this idea of its involvement everywhere. And you guys decided to focus on the metabolic benefits of Akkermansia. Can you just briefly remind me of why you decided to take that focus?

Dr. Colleen Cutcliffe: I think first of all, yes, there’s a bunch of correlative studies out there. And probably the most important thing that we decided early on was that we wanted to know, is this correlation and these kind of underlying mechanisms that we think are leading to what Akkermansia’s role might be, is there any truth in them? And there’s only one real way to understand whether there is truth in them. And that is, is there a causation set of studies you can do? Can you replenish people in these strains, see that they’re performing the activities that you’re expecting, and then get the clinical outcomes that would lead you to understand that there’s actually a cause between this depletion and this disease, and then therefore there’s a cause between giving it back and actually improving a disease.

Dr. Kara Fitzgerald: Yeah.

Dr. Colleen Cutcliffe: And so, to be totally honest, when we started Akkermansia, it wasn’t Akkermansia by itself. It was in a formulation of strains that all work together in a consortium to not only work on the gut lining, but also work on the metabolism of fiber into short chain fatty acids, specifically butyrate, the stimulation of the GLP-1 pathway. But it’s a group of strains, a formulation. And the real question was, hey, if people are depleted in those activities and you just gave it back to them in the form of the strains themselves, could you see benefit? And I think for us, one of the most exciting things that unlocked this opportunity in metabolic health through the microbiome was in a placebo-controlled, double-blinded randomized trial in people with type 2 diabetes, compared to placebo, people who were on this formulation had a lowering of A1C by 0.6 and a lowering of their blood glucose spikes by 33%. That was the first indication that there’s causation, guys. It’s not just that you happen to be depleted. There’s something about that depletion that is causing disease, and you can undo that or you can reverse that by giving people back these strains.

Dr. Colleen Cutcliffe: So that’s been our big mandate, I think, is to continue to create data around what role does the microbiome play in metabolic health and how can we help people create tools around improving their metabolic health through the microbiome. I’m excited to talk to you about all the advances that have been made over time.

Dr. Kara Fitzgerald: Well, let me just come back to that because it’s a big deal that you discovered that and you went about doing this, you know, proof of principle. In fact, 0.6 in A1C is the difference between diabetes and not having diabetes. I mean, it’s huge. So this was a big, big, big deal. Extraordinary. And I also want to layer that just as big is the fact that you guys figured out how to stabilize Akkermansia. We’ve talked about that extensively, so we don’t necessarily need to go into that incredible story around how you figured it out and you patented the methodology and your whole journey and your persistence in figuring it out and bringing this now to us to market. And you’re right, I did know about this back in my postdoc. And really when Bob Roundtree told me about you, you know, we both started stalking you a little bit. We were like, who is this company that’s figured this impossible thing out? I remember we were very, very intrigued by what you’re up to and so it’s it’s just such a pleasure to really become your friend over the years that we’ve been collaborating together.

Dr. Kara Fitzgerald: So you figured this out, these two massive ahas. This works, you stabilize it and you bring it to market. But in this study you discover that, lo and behold, people drop cravings. There’s this whole other channel and this brings you to the GLP-1 story, so just talk to me about that.

Dr. Colleen Cutcliffe: Exactly, exactly. And I know we’ve talked about the manufacturing and I will say that ignorance is what drives the world. I think if we had known what you and Bob Roundtree knew, which is that these strict anaerobes are going to be really hard to grow, we wouldn’t have probably endeavored to do it. I think in our minds, we were like, this pathway makes a lot of sense. Let’s go build an intervention. And then we just tackled it as it came and I don’t think we really knew at all how big or hard that was really going to be so we just kind of trucked through it. I think people make children every day having no idea how hard that’s going to be. And we’re like that too. Like, we’ll have a baby. And then, you know, it’s 2am and you’re like, this is a lot more work than I thought it was going to be. And so it was not dissimilar from that.

Dr. Kara Fitzgerald: Yeah. That’s a good point. That’s a really good analogy.

Dr. Colleen Cutcliffe: But actually in that clinical trial, which was published in BMJ, we did not look at food cravings. We were really looking at clinical outcomes of metabolic syndrome– A1C, blood glucose spikes, all of those things, inflammatory markers. And what happened was after we launched the product into the world, and this is sort of the beauty of creating a non-pharmaceutical and going down non-pharmaceutical path is that you can make these products accessible to people in a much shorter amount of time because they’re sort of naturally occurring strains. So when we put this into the world, what we started to hear back was, man, my food cravings are really down. Or, gee, I walked by a whole plate of cookies at Christmas and I didn’t eat a single one. Usually I’m the guy who sits there and eats the whole plate. And so we started to get this feedback.

Dr. Colleen Cutcliffe: And sometimes that kind of feedback is like a little dog nipping at your heel. And you have to know when you look down, you’re like, actually, that’s a massive dog. We should do something about this. And that was sort of what happened for us, that at some point we realized we should really look into this and that’s what led us to do an open label study. So this is not a placebo-controlled double-blinded, randomized trial, but an open label study where we used the food cravings inventory, which is a diagnostic test for your level of food cravings across the four major types: sugars, carbs, fast foods, and high-fat foods. What we found was that after being on these formulations with these microbiome interventions for 90 days– actually we found this happened in 45 days– 91% of people had lower food cravings. And I think that was huge because you can’t really feel when your A1C goes down.

Dr. Kara Fitzgerald: Right.

Dr. Colleen Cutcliffe: You don’t really know when your blood glucose spikes go down unless you’re wearing a monitor but you know when you have less cravings, so this was a moment to help explain to people, how do you know when your metabolic health is better? Well, you’re not craving all those crazy things that your body doesn’t really need as much. So for people who are wanting to know what can I expect to experience, this is something that you don’t need a measurement device, you kind of know it. So that was a big move for us.

Dr. Kara Fitzgerald: And I should actually just point out, I have been using Pendulum’s Glucose Control now for years, as have you. And then you mentioned when we were off recording with Halle Berry, who I’ve had the honor of chatting with about this, and Peter Attia, actually, but all of us using this and noticing this phenomenon. It’s really pretty extraordinary to experience it, but then just having measurable changes in A1C, just really seeing some of the outcome. I wanted to ask you, where in the journey did you start? When you did the food cravings research, was it after you knew that Akkermansia and Clostridium butyricum are essential to GLP? Did you already have that piece of information? I had thought that in your original study, you heard some anecdotal reports that cravings were dropped so you were thinking a little about that. And then–

Dr. Colleen Cutcliffe: Yeah. You’re right. We have always thought about it, and also our founding chief medical officer, Orville Kolterman, was the CMO who put out the first GLP-1 analog. So Amylin [Pharmaceuticals] put out their GLP-1s and he was the chief medical officer there and he had told us, hey, these GLP-1 analogs, one of the things we hear back is that they actually reduce food cravings. So that had been in our minds and then when these publications came out, really showing the direct demonstration that these two strains could directly stimulate GLP-1 secretion from the L-cells, we were like, well, there’s your mechanism. And then we know the GLP-1 analogs have this feature and we’re hearing this from customers, we decided we should just do a study. And so all these little data points all of a sudden converged on, well, we should just directly look at this measurement ourselves.

Dr. Kara Fitzgerald: Very exciting.

Dr. Colleen Cutcliffe: Yeah, and I think we know that GLP-1 analogs massively help people with cravings.

Dr. Kara Fitzgerald: Yeah, yeah. And one of the things that we’ve talked about though is why are we in this global GLP-1 deficiency state? Why is everybody requiring GLP injections? Obesity is epidemic and it continues to rise, as does diabetes. And for me, the massive aha is that GLP is fallout of another phenomenon and this is the extraordinary damage that we’ve sustained in our gut microbiome.

Dr. Colleen Cutcliffe: Absolutely, and I think that’s right. Why are so many people experiencing benefit from the GLP-1 analogs? It’s because so many people are depleted in the ability to make GLP-1. Why are they depleted in the ability to make GLP-1? They are deficient in these microbes that are there to stimulate your body’s GLP-1. Why are you deficient in those microbes? Well, there are variety of things that we don’t really have control over, like stress, travel, menopause, hormones. But one of the things we do have control over, and to some extent the government has control over, is the nutrition side of this. We know that the food that we eat is one of the most powerful ways to modify your microbiome. And if the food that we’re eating is actually not feeding these microbes, there’s a massive problem in the food system. And so I think it all links back to nutrition and the microbiome when we think about why these GLP-1 drugs are so powerful and successful broadly.

Dr. Kara Fitzgerald: Yeah, yeah, it’s all about an extraordinarily damaged gut second to, basically, a toxic food supply, you know, ultra-processed foods. There’s a lot of focus on it and the various toxins that they’re delivering and so on and so forth. But really, as important to that conversation is that we’ve all sustained these damaged guts and now we’ve got the intestinal permeability that goes with this damaged gut and insufficient Akkermansia and Clostridium butyricum, the insufficient butyrate to really supply and sustain a healthy gut. And then the fallout of all of these systemic issues and these are the diseases of aging. We’re interested in this longevity conversation now and this is so fundamental to it. And in fact, I’ll just pin the hallmarks of aging where dysbiosis is now one of them. And when you read the amazing publications coming out and really articulating why dysbiosis is there, it’s always coming back to a lack of Akkermansia and the response when Akkermansia is supplied.

Dr. Colleen Cutcliffe: Absolutely. And I would say, we just did a real rant. That’s a huge downer about all the things that are wrong. So just to put a light on this shit show, there is actually the ability to modify your microbiome and get back those functions that can get you into a healthier state. And that’s right where I think you and I have bonded over, which is the opportunity of the microbiome to help people improve health and it’s a totally new system and tool set that we didn’t have before.

Dr. Kara Fitzgerald: And what’s cool is that you guys actually figured out that there’s this real one-to-one relationship. Adding Akkermansia back in actually improves outcome. And your original work was in metabolic syndrome, but now we’re looking at cravings and GLP-1, and the research will continue and we’ll see bigger and bigger stories. That’s why the meteoric rise in publications. Yeah. So circling back to cool stuff, we know that polyphenols, we know that a healthy dietary patterns, the dietary pattern from which we really evolved to exchange this important information, the food is information. It’s exchanging data with our gut bugs and they’re taking that food and transforming it into other compounds that stimulate GLP-1 and myriad other things. We can add back in these polyphenols. We can restore our diet. We can choose not to eat a completely ultra-processed diet and actually support regeneration of Akkermansia and we can layer on the probiotic intervention as well.

Dr. Colleen Cutcliffe: Yeah, and I think that we know that through high fiber, high polyphenol diet that you can stimulate Akkermansia growth. And I think, of course, that’s probably your most powerful tool. But when we think about the jump start, being able to replenish people through supplementation with Akkermansia paired with feeding them the prebiotics and the foods that help Akkermansia grow, you now are tackling the one-two punch of the pre- plus the probiotic. And I think that for Akkermansia in particular, one of the most interesting things about it is that it has never been found in any food or beverage. And people are looking. It has never been found in any food or beverage except one place: mother’s breast milk.

Dr. Kara Fitzgerald: Oh, interesting.

Dr. Colleen Cutcliffe: And so the theory now is you get it from mother’s breast milk and then you spend the rest of your life trying not to lose it. I think this is something about Akkermansia that makes it particularly amicable to supplementation, which is to say you can’t actually get it somewhere else. You can feed it through a high-fiber, high-polyphenol diet, but if you actually want to get the strain in there, the supplementation is sort of the most direct way to do that. We actually don’t know another way to do it besides that.

Dr. Colleen Cutcliffe: And then maybe I’ll just say, too, because I think Akkermansia has gotten a lot of press and attention, and people are now understanding how important it is, we have seen lots of products pop up in the space that are— And maybe I’ll just say this. The supplement space is a relatively unregulated arena and lots of junk shows up there and we are seeing that in Akkermansia. It’s really disappointing to see that there are bottles out there labeled Akkermansia and when you actually sequence them, there’s no Akkermansia in the bottle. There are manufacturing companies in China that are now selling Akkermansia to varying degrees of high quality or low quality and so I just think this is a moment for also our community of scientists and health care practitioners to come together and revisit where they’re getting the Akkermansia from and how can we maintain a high level of quality for the people who can really benefit from it. Yeah, it’s kind of gross to see that out there.

Dr. Kara Fitzgerald: There’s a lot of things that I want to talk about and I want to come back to that. I want to come back to the fake Akkermansia that’s out there. I want to talk about that, but before we do, I do want to say that there’s plenty of us that lose our Akkermansia. We have a damaged gut for whatever reason, maybe early antibiotic exposure, which is part of your backstory with your daughter. And again, we’ve talked about that previously and all of this will be in the show notes, folks. So there’s an absence of it, we can reintroduce it with this probiotic, and in some cases, combined with the polyphenol ingredients that can help stoke growth, some people will actually recolonize. Not all of us– some of us may need to take it for, I don’t know, maybe, I mean… Do some of us need to take it forever and we won’t be able to colonize it? Where are we at with that? I know you guys have evidence on colonization as something that could happen in a subset.

Dr. Colleen Cutcliffe: We do see colonization in a subset, a minority of people. And I think trying to understand what happens when someone stops supplementing but is able to sustain the strain is something that we’re very deeply interested in because I think that there will be periods where you’ll become depleted in the strain and it makes sense to supplement and get the strain back. But to the extent that you can use diet to maintain the strain and have it colonized, I think that makes sense. So you’re really improving your level of dietary fibers and polyphenols in your diet and that might be all you need to do. That kind of behavioral change can help people sustain the strains without having to keep taking the pills. We still don’t really understand why it works for some people and doesn’t work for other people.

Dr. Colleen Cutcliffe: But the microbiome is an ecosystem and like any other ecosystem, there is a dynamic and also complicated set of interactions that are creating pressures for some strains to be able to thrive and other strains to not. And so beyond just your diet and what you’re feeding these strains, there are probably things that are outside of our control, like hormones, and your own genetics, that could be creating pressures that will always make it hard for you as an individual to colonize. But we really don’t understand that. That’s really just a hypothesis for trying to explain why some people do and some people don’t colonize.

Dr. Kara Fitzgerald: Yeah, yeah, yeah, we don’t know. But fortunately, we can supplement. It’s a common question that we get that people want to be able to colonize and move off of supplementing and maybe you’ll be able to do that, and maybe you’ll need to supplement. And thank God we actually do have the supplement. I mean, I’ve opted to continue taking it. I’m quite bullish on it.

Dr. Colleen Cutcliffe: I never stopped taking it either.

Dr. Kara Fitzgerald: Yeah. You know, with a really clean diet for many, many years with a good exercise habit, you know, not terrible sleep and still having an A1C… Listen, no one’s going to argue with an A1C of 5.4 unless you’re in sort of the obsessed functional medicine space, but it was using Pendulum Glucose Control that brought mine down really for the first time to five. I come from a family just teetering on diabetes all the time. I’ve wondered about sort of the epigenetic inheritance pattern and some of the thrifty epigenetic… I’ve definitely speculated broadly on why, but that’s where the river’s flowing for me if I’m not really careful. And the only intervention that did it— And again, berberine, all of the myriad interventions we have that have some evidence around improving blood sugar and A1C and so forth, that it was just this that kind of took me that further step to an enviable A1C.

Dr. Colleen Cutcliffe: And I think that your story has always been particularly compelling to me, along with Halle Barry, and Peter Attia, people who are thoughtful and careful and conscientious about what they’re eating and putting in the body and educated on this front. To be honest, all three of you are amazing stories because if we were in Vegas, I would have put a dollar bet that you guys were not going to see improvement because you’re already doing all these great things that should be bolstering your Akkermansia through your diet. I mean, if you eat a meal like Peter Attia, with pounds of vegetables, you’d think, how could this person possibly benefit from supplementation with Akkermansia?

Dr. Colleen Cutcliffe: I think what that tells me, that all three of you saw real outcomes and benefits– and me too. I mean, admittedly, I have dietary issues. I’m not the best person. I don’t have diabetes or pre-diabetes, but I wore a continuous glucose monitor and for me, also on Pendulum Glucose Control, I saw all of my area under the curve go down. I think what that tells us is that you can be doing all the right things, you can be going through and picking the right foods and doing the right exercise and doing the right mental health exercises to reduce stress, but there just might be this extra tool that’s the boost that you need that you would never know if you hadn’t really explored the microbiome.

Dr. Kara Fitzgerald: Yeah, I think that’s absolutely right. And if you’re going to continue to sort of live in the real world with this modern stress, I just think some of our modern experience drives us towards damaged GI, imbalanced microbiome, even as we’re putting a lot of intention and effort into keeping it strong. And we need extra effort. You know, I’m not retiring right now to Sardinia or Okinawa. I’m going to be living here, living a relatively involved, busy, kind of stressful existence and I need this extra support. Maybe that’s a piece of it.

Dr. Colleen Cutcliffe: I think that’s right. That’s why I think it’s been so awesome to have the clinical trial results on Pendulum Glucose Control for people with type 2 diabetes. But then to also realize that as we go through, as you’re saying, ‘life’, and as we are enjoying some parts of that life but also damaging our bodies in unexpected and maybe unpredictable ways, that the microbiome and that this formulation in Pendulum Glucose Control can really create benefit for a wide variety of people. That’s huge. And it also speaks to why metabolic health, I think, is in the zeitgeist and people are starting to realize how important and fundamental that is to overall health.

Dr. Kara Fitzgerald: Yeah, that’s exactly right. And longevity. If you’re coming at it from that space, thinking about the hallmarks again, just fundamental. I’ve been taking Pendulum’s Glucose Control and I have a lot of my patients on it, but of course, we can’t deny there’s a high price point. You know, there’s definitely a commitment. There’s an investment. There has been an investment to taking this. It is part of my fundamental supplement stack. As you and I’ve talked about, I pack it on ice and take it with me when I travel, it’s that important to me. I can probably afford to miss it, but it is just a fundamental important piece of what I do and I do prescribe it in my clinical practice a lot. But it’s had an expensive price point.

Dr. Kara Fitzgerald: And I understand and respect that because I know the backstory on how you guys figured this out. You invested in clinical research and you’ve patented the technology to actually stabilize it. This is a huge deal and it’s a big, big, big financial investment. So I understand why you ended up at a price point that gets some pushback to put it mildly. But as we were talking off camera, you’ve got an amazing announcement. So do tell what’s up with access.

Dr. Colleen Cutcliffe: I do, I’m super excited to share that we’ve had some massive advances in our manufacturing and really just economies of scale that have enabled us to now significantly lower that price. And I will just tell you that we’ve been manufacturing these strains from day one and it has been really hard and challenging to figure out how to manufacture them, but also really expensive to manufacture them. These are strict anaerobes, so that means end to end, you have to keep oxygen out of the system. No plant existed that could do that, and so we had to build our own plant to be able to figure that out.

Dr. Colleen Cutcliffe: These strains grow in different nutrient arenas. Akkermansia is literally embedded in the mucin layer and feeds off of mucin, so how do you replicate that in a manufacturing setting? You’re trying to replicate what’s happening in the deep recesses of the gut microbiome and the distal colon. When we first started selling Pendulum Glucose Control at $165 a bottle, we were losing money on every bottle we sold. That’s how expensive it was to make it. And so at some point we were like, well, you should probably try to break even on these things and so we’ve been living in that world. It’s not like we’ve been fleecing anybody and we were actually losing money in the beginning.

Dr. Colleen Cutcliffe: But through all these advances in manufacturing and economies of scale, we are now able to reduce from $165 a month to $99 a month. And I know that’s still expensive, but it is one of those situations where we are actively working to try to lower the cost so that we can get more and more accessibility to people. It’s the reason we are not selling these as drugs, which we could actually really jack up the price. It’s the reason why we are passing the savings that we figure out directly to the customer, so I am really excited to be able to bring it to $99. And then for practitioners like you, we’re going to have this conversation with your patients to be able to, with a straight face, say, well, this feels like a reasonable investment given how much we all spend on Starbucks every month.

Dr. Kara Fitzgerald: Yeah, easy. That’s easy. Right, right. That’s a good draw. Yay! Congratulations. That’s awesome. So that is happy news for many, many people. And we were also talking about this, that it’s possible that some of us can drop to a half dose, and so there would be an additional savings. So if you’ve been taking it for a while, one could go down to a half dose. But, you know, my hat’s off to you.

Dr. Colleen Cutcliffe: That’s right. Literally, if you’re going to maintain– So the dosing from the trial is two pills a day and if you’re going to kind of a maintain dosing or you don’t really have diabetes, but want to keep these strains sustained, and you went to one pill a day, now you’re at like 49 bucks a month. So, hopefully it will enable a lot more people to be able to get access to Pendulum Glucose Control.

Dr. Kara Fitzgerald: Yeah. And I do want to say, healthcare providers can actually access a discount, a wholesale price and a layered on discount on top of that. If you go to Pendulumlife.com/HCP and use the code WSKARA50, and I’ll layer this in elsewhere.

Dr. Kara Fitzgerald: So what else do we want to talk about here? I want to talk about a little fun bit. I mentioned to you the meteoric rise in literature and I spent a little time exploring, and you and I ping each other with papers that come out that excite us all the time, and the mental health piece, you know, the gut-brain axis. There’s definitely been some exploration in the beneficial possibility of a robust gut with adequate Akkermansia and it reminds me of the fun story just kind of linking it to the broths that you create these guys in. The amount of GABA that’s produced… Is it okay that I bring it in? You knew where I was going.

Dr. Colleen Cutcliffe: I knew you were going go there. You want your shot.

Dr. Kara Fitzgerald: Yeah, I want my GABA shot. So talk about that discovery that you guys have had and any thoughts you have around the gut-brain axis and Akkermansia’s involvement.

Dr. Colleen Cutcliffe: Yeah, I think, as you know, the gut-brain axis is a really ripe territory for new interventions in the gut microbiome. One of the things that we discovered about Akkermansia is when you look at the genetic code, it encodes for genes that are in the GABA pathway, like precursors of GABA and all this stuff. And so we were like, why is it encoding for all this GABA stuff? So we just asked the question, does it make GABA? And so when we grow our strains, if you’ve ever done bacterial or yeast culturing, you know that you have your strains, and they’re growing in this rich broth media and then you want to take the strain itself and essentially spin down the cells, and you throw away the media, and you take those cells, and that’s what the product is. So there’s a media that we were just dumping down the drain. We just took some of that and tested it for metabolites and found just shit tons of GABA in it.

Dr. Kara Fitzgerald: Incredible.

Dr. Colleen Cutcliffe: So much GABA. And so, and the precursors of GABA and all the parts of the GABA pathway. And so we were like, my God, it’s making GABA literally in this media that we’re dumping down the drain. So then, of course I shared that with you, Kara, and I was like, we should do GABA shots.

Dr. Kara Fitzgerald: GABA shots, yeah.

Dr. Colleen Cutcliffe: Just take this media and do shots. And so before I went on stage with you to go do our shots together, our team got together and said, well, let’s actually taste it and see how it tastes and you know, it tastes pretty awful. It’s media and if you’ve ever smelled a bacterial growth, you’ll know it’s not pleasant and your nose plays a big role in your taste and it’s terrible. And then they tried to add aromatics and all this stuff and I was like, I can’t. Kara is my friend, I can’t make her do it. Maybe there’ll be an unlock at some point where we can do that but beyond that kind of fun story about GABA being produced by Akkermansia, I think that there are a variety of correlate papers that have shown that when you’re depleted in Akkermansia, it’s associated with a wide variety of diseases that we’ve traditionally thought of as neurodegenerative diseases.

Dr. Colleen Cutcliffe: So Alzheimer’s, Parkinson’s, autism, all of these things that we were always looking at the brain, it now it looks like there might actually also be a gut-brain connection. In particular around stress and anxiety— I have to think if I’m doing that thing I do with you, which is overshare. There is a study— I believe it’s been presented at conferences, but it hasn’t been published yet— This group in Asia that showed that by supplementing– This is a pre-clinical study, so it’s an animal model. But it’s an animal model for stress and anxiety, where they showed that by supplementing with Akkermansia, they were able to reduce these symptoms of stress and anxiety. In these animal models, much like in human models, the signs of stress and anxiety are, for example, the animals that are stressed and anxious literally don’t move around as much. When you track their movement in their cage they move around a lot less than the ones that are not stressed and anxious.

Dr. Colleen Cutcliffe: And I think for us as humans, at least I’ll say for myself, when I’m feeling an enormous amount of pressure and stress and anxiety, I’m not really motivated to go work out. In fact, it’s a big lift to go do that. I’m naturally a little bit more sedentary. What they found was that when they took these stressed animals and they supplemented with Akkermansia, all of a sudden they were as active as the healthy counterparts and there’s a few of these different things. There’s even exploration. You put something new in front of them. How interested are they in exploring it? They become more interested when they give them Akkermansia.

Dr. Colleen Cutcliffe: I think I’ve been clear about my feelings about preclinical studies and how they may or may not translate to humans, but that’s interesting. And so we are actually running a series of clinical trials in actual humans to understand is there benefit to stress and anxiety by supplementation with Akkermansia. And I can’t wait to share those with you as soon as we get them, but it’s a big opportunity, I think.

Dr. Kara Fitzgerald: Yeah. Big opportunity, gosh that’s very exciting. And I appreciate you qualifying and not just stating it as translated science. And I also appreciate you stepping up to the plate and doing some actual clinical studies. So bravo you. I’m very excited about it given the GABA broth. I think that’s quite compelling. And GABA is an inhibitory neurotransmitter and it stands for gamma aminobutyric acid for anybody who’s not familiar with GABA. You can ChatGTP it, and maybe get a little… But just clarify the chat’s citations.

Dr. Colleen Cutcliffe: Basically, GABA has been on the market and available for a long, time as something that helps you counter stress and anxiety.

Dr. Kara Fitzgerald: That’s right. Yeah, that’s right. That’s right. It’s pretty routinely prescribed for that indication. So I think it’s really exciting to pull this thread. And we can also just track sort of the metabolic disease depression data. There’s plenty of that. So we know metabolic imbalance will drive the inflammatory phenomena that will deplete serotonin, et cetera, et cetera. That mechanism has been–

Dr. Colleen Cutcliffe: Absolutely. But then also Kara, I’d be curious to hear— One of the things that surprised me that I didn’t know is that when people are experiencing stress and anxiety, they also have a higher propensity to have GI issues like IBS. Is that something that you’ve…

Dr. Kara Fitzgerald: Yeah, yeah, absolutely. Sure.

Dr. Colleen Cutcliffe: So that’s another tie-in to what’s the underlying foundational thing that’s wrong that would then show up as stress and anxiety and as IBS. And I think that this could be an interesting unlock to that link.

Dr. Kara Fitzgerald: When you’re in a stressed state, you’re sympathetic dominant. You can’t rest and digest. So whatever you’re eating, which is probably not going to be as good when you’re stressed out, the quality, you’re not going to be able to break it down. It’s going to putrefy… All sorts of mischief is going to happen in that phenomena. Those of us clinicians practicing in the functional medicine space definitely know you want to move into as calm, as relaxed, as parasympathetic dominant a space [as possible], when you introduce food, again, when you introduce this information in the body so that we can appropriately metabolize it and ready it for our microbiome. So that would be another piece of the IBS picture, the gut changes, the microbiome changes in a stressed individual.

Dr. Colleen Cutcliffe: Absolutely, absolutely. And getting back to this conversation, this diet is linked to increasing your Akkermansia levels. I think that’s super interesting because essentially, if you’re depleted in Akkermansia, your gut lining will be compromised so that could lead to all these GI issues. But then if you’re not producing as much GABA as you should be in your microbiome, that could lead to this heightened stress and anxiety. So those two things are really feeding each other from the same underlying cause.

Dr. Kara Fitzgerald: Yeah, yeah, that’s right. That’s right. So lots of research remains to be conducted, lots of exploration. We’re going to continue to tease out why it has the title of being a keystone strain, which is a big deal. There’s a lot of bugs hanging out in the gut and there’s not many that have been given that lofty title. So it plays a fundamental role in many, many different processes. What else do I want to talk about with you?

Dr. Kara Fitzgerald: So, a perennial question that comes up in our space, in this functional medicine space, is the handful of papers that talk about high Akkermansia and it being associated with, you know, MS is one of them, Parkinson is another. There’s not a lot of papers, but there’s a handful and boy, did they get a lot of attention in my space. And providers tend to kind of think linearly. If it’s high, you know, therefore we need to eradicate it and that will address the Parkinson, that will address the MS. Or in individuals with MS, Akkermansia is contraindicated. And I think that that’s a massive miss and not an appropriate direction to go, but talk about it. Talk about your thoughts on those papers.

Dr. Colleen Cutcliffe: Yeah, so first of all, we are early in microbiome science and microbiome research. Whatever we know today in 2025, we’ll know massive amounts more by the end of 2025 and in 2026. So let me start with that. We are still learning a ton. But I do think that in general, things that create fear have a tendency to spread faster than anything else. And these correlative studies that have come out have definitely tapped into that fear and showing that there’s a correlation between MS and high Akkermansia levels is not the same as causation. It is not the same. And that is incredibly important to differentiate correlation from causation. It’s actually the thing to be able to differentiate.

Dr. Colleen Cutcliffe: So for example, we’ve talked about this before, you could have heightened markers for inflammation that’s telling you that there’s something wrong with your body that your body’s fighting off, you don’t want to get rid of those markers. You really want to know what’s causing that heightened inflammation and it’s actually your body’s response to that problem and its attempt to resolve that problem. What we don’t know about this correlation is, do high levels of Akkermansia cause MS or is it that MS is causing your body to respond by increasing Akkermansia levels?

Dr. Colleen Cutcliffe: That’s the meat of the whole thing. And until you have that answer, you don’t know what this correlation means. So I think it is important to keep track of the literature. I have been kind of disappointed that because it has so much buzz and people are so fired up about it, why haven’t there been further studies in humans? But I will tell you about studies that have happened preclinically and they’re going to just make everything even more confusing. There is a group out here at UCSF that has an animal model for MS, and they did a microbiome transplant where they showed that if you put Akkermansia into this model of MS, the animals get worse. So from their data, that would actually suggest that supplementation of Akkermansia made MS worse.

Dr. Colleen Cutcliffe: But there’s a group at Harvard that also has an animal model for MS, and they did a similar experiment where they supplemented those animals with Akkermansia, and they showed that these animals had resolution of MS. So in that study, you would say, well, Akkermansia cures MS, and your body’s increasing it in order to fight whatever it can on this MS response. So I think what we know is that we don’t know and that animal models, as we all know, mice are not humans and so you can make a model that is actually not a proxy for what’s happening to a human. But we must see, we have to be able to see what is happening in a human.

Dr. Colleen Cutcliffe: That really requires someone to go out there and say, if I supplement with this can I see a difference in the disease state? And I think maybe in all fairness, the reason it hasn’t been done is because it’s scary. Who wants to participate in the study of something that could make things worse. But that’s the only way we’re going to know causation versus correlation.

Dr. Kara Fitzgerald: And when we understand the underlying mechanisms, when we understand how Akkermansia influences systemically, in my mind, the association is only correlation and not causation. I mean, that’s what I’m bullish on. You mentioned these two mouse studies, and we know that mouse models are very different. So the first and obvious question is what was the mouse model in California and what was the mouse model in Harvard? Because they’re just raised, they’re fed, they’re genetically very different. And so that would be an obvious first place to look for me.

Dr. Colleen Cutcliffe: Yeah, I agree.

Dr. Kara Fitzgerald: Then the other piece, and I’ve thrown this out when we’ve conversed before, is okay, is the body actually making more Akkermansia and that’s why we’re seeing it as a protective response to the MS, to the Parkinson’s? Which could be possible, because both of these have intestinal permeability associated with them. So it would be a logical attempt that the body’s going to help try to recycle, rejuvenate, keep that mucin layer. Or is the mucin layer just really sloughing off? Is there an active damage process going on that’s liberating the Akkermansia from the mucin layer eco-niche into the fecal bolus and that’s why you’re seeing a ton.

Dr. Colleen Cutcliffe: Yeah, and I’m glad you brought that up. I forgot about that theory, that hypothesis.

Dr. Kara Fitzgerald: My theory. Yeah.

Dr. Colleen Cutcliffe: I do think that is another interesting point to make, which is that there are no gut microbiome tests right now that people are using that are literally biopsies of the gut microbiome. This is all what’s measured in the stool, which is a proxy for what’s happening in the gut. But to your point exactly this, which is that you could have a higher level showing up in the stool, which is actually a counter indicator of what’s happening in the gut. That is important to recognize.

Dr. Colleen Cutcliffe: And I will say that one other experiment that would be interesting if a set of practitioners were up for doing this, would be to get longitudinal data on people that are high risk for MS. And so you could get to see the timing of when the Akkermansia levels went up versus the timing of when the symptoms of MS started to show up. That could be an interesting piece of— Again, it be correlative data, but it would be more interesting than just like these single time points after somebody’s already got MS. So I think there’s a bunch of interesting stuff to try to dig into. But we haven’t made any further advancements as a field beyond really those correlative studies in our understanding.

Dr. Kara Fitzgerald: You know what we could do actually? We’re kind of just waxing theoretical here at this point, but Terry Wahls, you know, the Wahls Protocol, I mean, she’s always conducting research in her protocol. We know that it’s polyphenol dense. So when people who are colonizing Akkermansia, they’re probably stoking growth with the transition from whatever standard diet they’re on into this extraordinary Wahls Protocol that would absolutely have some influence. It has favorable influence on the microbiome. I mean, it would be interesting to look in her cohort if they’re collecting stool samples, which I think that at least some of the studies she’s done have stool samples, have banked data. I mean, let’s look and see. We could actually begin to see. She might be able to answer this question now, data that she has or will have. Boom.

Dr. Colleen Cutcliffe: My gosh, Terry Wahls, if you’re listening, me and Kara are calling you now. Yeah, I love it. I love that. She’s already got it. That is a brilliant idea. I love it.

Dr. Kara Fitzgerald: I’m super psyched. We’ve got to do it this month. Listen, we’re really kind of wrapping up here. Is there anything else, any new research, anything coming down the pipeline we want to be thinking about, anything that we didn’t cover in this really wide ranging conversation?

Dr. Colleen Cutcliffe: One topic we didn’t cover that could be interesting is thinking about the microbiome and hormones. And we’re not going to have time to get into it here, but maybe I’ll just plant a little seed, which is to say that we know that there are microbes that play an important role in the amount of circulating hormones that you have, including estrogen and progesterone. And I think that it is of great interest to us at Pendulum to understand what are those strains doing? How do they change over time during different phases of a woman’s life, particularly? And are there ways in which we can help at different stages of life where free-circulating hormone becomes important?

Dr. Colleen Cutcliffe: And I think there are some key moments where that matters. One is, of course, when people are trying to get pregnant. Second is during pregnancy. But then maybe a third very big one in this moment is menopause. And so I think there’s a big opportunity to think about the microbiome and menopause or the microbiome and hormones. And we’ve talked a lot about gut-brain, but I think that’s an interesting one as well.

Dr. Kara Fitzgerald: Super interesting. Yeah, there is some conversation out there around the microbiome and infertility. God, I’m glad you guys are thinking about that and chasing it. Well, Colleen, let me actually remind folks listening, if you’re a healthcare provider, you can open up a wholesale account through Pendulum and get $50 off if you use the code WSKARA50 at Pendulumlife.com/HCP. All right. It was great to be with you. I’m so glad we had a chance to catch up.

Dr. Colleen Cutcliffe: Great to catch up with you too. And for anybody who’s listening, if you go to PendulumLife.com, we also have a ton of resources there, including some protocols I think that have been authored by you, Kara, on how you’re using these in clinical practice. So some real practical how-tos there. And if you have any other questions, please, please reach out to us. We’re excited to engage in conversation and learning together.

Dr. Kara Fitzgerald: Yeah, absolutely. Yes, you’ve always been open and into that. All right. Thanks, everybody.

Dr. Colleen Cutcliffe: Thank you.

Colleen Cutcliffe is the Chief Executive Officer and co-founder of Pendulum. She has more than 25 years of experience leading and managing biology teams in academia, pharmaceuticals, and biotechnology. Prior to starting Pendulum, Colleen was the senior manager of biology at Pacific Biosciences and a scientist at Elan Pharmaceuticals. Colleen completed her postdoctoral studies at Northwestern’s Children’s Memorial Hospital. Colleen received her Ph.D. in Biochemistry and Molecular Biology from Johns Hopkins University and her B.A. in Biochemistry from Wellesley College.

Dr. Colleen Cutcliffe

Pendulum Clinical Trials

Pendulum Practitioner Resources and Protocols

Pendulum: The Science Behind GLP-1 Probiotic

Pendulum Protocol: Support GLP-1 Production Developed in collaboration with Dr. Kara Fitzgerald, ND, IFMCP

Study: Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation

Robert Rountree, MD

Halle Berry

Orville Kolterman

Research from UCSF: Gut Microbes May Influence Multiple Sclerosis Progression

Research from Harvard Medical School: A Probiotic to Treat Multiple Sclerosis?

Dr. Terry Wahls and The Wahls Protocol

Study: Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1^−/Δ7 mice

Study: Microbe Profile: Akkermansia muciniphila: a conserved intestinal symbiont that acts as the gatekeeper of our mucosa

Study: Possible application of Akkermansia muciniphila in stress management

Podcast: Latest Evidence and Clinical Applications of Akkermansia with Dr. Colleen Cutcliffe

Podcast: Polyphenols, Novel Probiotic Strains & Metabolic Health: The Latest in Microbiome Science

Podcast: A 360-Degree View of the Microbiome: Practical Strategies for Clinicians

DrKF Clinic: Patient consults with DrKF physicians including Younger You Concierge

Bio Age Lab Test

Bio Age Self Assessment Quiz

Younger You Group Program

Younger You book

Better Broths and Healing Tonics book