Episode 316: Microbiome, Metabolic Health & GLP-1 with Colleen Cutcliffe
Listen on Apple Podcasts | Listen on Spotify
Erin doesn't typically have brands come on the show to promote their products, but we're such a BIG fan of Pendulum at Team FN that we couldn't resist! Learn more about how GLP-1 works to increase satiety and curb cravings (and why it's labeled as such!). We're also discussing how probiotics help to support overall metabolic health. This episode is for you if you're interested in learning more about GLP-1, your metabolism or gut health. OR if you're a practitioner who utilizes probiotics — or works with metabolic health — in your practice.
Colleen Cutcliffe is the CEO and Co-Founder of Pendulum. She has over 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 received her Ph.D. in Biochemistry and Molecular Biology from Johns Hopkins University and her B.A. in Biochemistry from Wellesley College.
In this episode:
How the microbiome and metabolism are connected [8:06]
What is GLP-1 and how does it work? [13:27]
Insight behind the three specific probiotic strains in GLP-1 [23:27]
Benefits of Akkermansia and why you may have high levels [26:49]
Why inulin is included in GLP-1 probiotic and who should avoid it [40:04]
Reasons behind why Akkermansia levels may not increase on a stool test even after supplementation [46:55]
Resources mentioned:
Pendulum (Use code FUNK for 20% off of all membership first orders)
LMNT Electrolyte Replenishing powder (Use code FUNK get a free sample pack with any purchase!)
Ned Natural Remedies (get 20% off your order with code FUNK)
Qualia Senolytic (get up to 50% off and an extra 15% off your first purchase with link + code FUNKS)
Organifi supplement powder (save 20% on your order with code FUNK)
Learn more about Metabolic Health & Gut Health
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Erin Holt [00:00:02]:
I'm Erin Holt and this is the Funk'tional Nutrition Podcast where we lean into intuitive, functional medicine. We look at how diet, our environment, our emotions, and our beliefs all affect our physical health. This podcast is your full bodied, well rounded resource. I've got over a decade of clinical experience and because of that, I've got a major bone to pick with diet culture and the conventional healthcare model. They're both failing so many of us. But functional medicine isn't the panacea that it's made out to be either. We've got some work to do, and that's why creating a new model is my life's work. I believe in the ripple effect.
Erin Holt [00:00:39]:
So I founded the Funk'tional Nutrition Academy, a school and mentorship for practitioners who want to do the same. This show is for you if you're looking for new ways of thinking about your health and you're ready to be an active participant in your own healing. Please keep in mind this podcast is created for educational purposes only and should never be used as a replacement for medical diagnosis or treatment. I would love for you to follow the show, rate, review and share because you never know whose life you might change and of course, keep coming back for more. Hello friends. I've got an awesome show for you today. I sat down with Colleen Cutcliffe. She is the CEO and the co founder of Pendulum.
Erin Holt [00:01:22]:
If that sounds familiar, it's because I've talked about their probiotics here on the show before. Huge fan of the products and the work that they're doing over there. And we got to get into the nitty gritty of the microbiome, gut health, metabolic health, everything GLP-1 related. So it's a hot show. You're going to want to take notes. This is definitely for the average person who's just looking to get healthier or maybe interested in the GLP-1 discussion, but also great for practitioners. I hooked you guys up. I asked all the practitioner questions that were coming in and stuff that I know you guys are itching to learn about.
Erin Holt [00:01:59]:
So great show. Let me give you a little bit of background on Colleen. She kind of mentions it when I'm talking to her, but she's kind of a big deal. She has over 25 years of experience leading and managing biology teams in academia, pharmaceuticals and biotech. Prior to starting Pendulum, she was the senior manager of biology at Pacific Biosciences and a scientist at Elan Pharmaceuticals. She received her PhD in biochemistry in molecular biology from John Hopkins University and her BA in biochemistry from Wellesley College. So she knows a lot of this stuff. And she is really just a wealth of knowledge who's really cool to talk to as well.
Erin Holt [00:02:36]:
Pendulum was awesome because they hooked you guys up with a 20% off discount. So just use code funk, f u n k for all membership first orders, you'll get 20% off. And I was, you know, you'll, you'll hear me asking her about the GLP-1 because I just started taking them myself. I'm super, super curious to see my results. I'm brand new. I mean, and I've only been taking them for like four or five days, so I can't speak into results yet, but I promise to update you, update you on the show. So without much further ado, here's Colleen. Well, welcome, Colleen.
Erin Holt [00:03:15]:
I am thrilled to have you on the show and very excited to chat with you today.
Colleen Cutcliffe [00:03:19]:
Thank you so much for having me. I'm looking forward to our chat as well.
Erin Holt [00:03:22]:
So I just want to kind of debrief you on who you're chatting with today on the show. We've talked pretty extensively about the microbiome and why it's so important. We've talked about how to feed your microbiome. I've been singing Akkermansia's praises for literal years on the show. We've talked about short chain fatty acids, we've talked about butyrate. So you're coming into a warm audience and I really wanna highlight and feature your zone of genius here today. So just make sure you let her rip. Don't hold back.
Erin Holt [00:03:51]:
Anything you wanna say is fair game here. I definitely have some specific questions for you. And as a practitioner, and just kind of like a curious cat, I'm mostly interested in your new product, the GLP-1 probiotic. So I'm definitely going to ask some questions and kind of tuck into the nitty gritty of that with you today. So are you ready?
Colleen Cutcliffe [00:04:09]:
Great. Let's do it.
Erin Holt [00:04:11]:
Before, let's start with a general question because I'm curious a little bit about your background and kind of like, why probiotics? How did you get into this field of research? What was the gap in the marketplace that you saw? There's so many probiotics, blends, options. So what made you want to co found this company?
Colleen Cutcliffe [00:04:33]:
Well, my background is really in science, so I don't have a marketing background and so I really didn't come at it from, oh, how do we make a better probiotic? So my background is I have a PhD in biochemistry and molecular biology from Johns Hopkins. I did a pretty traditional postdoc at Northwestern. That kind of laid the foundation for me on basic science and the fundamentals of science. I then worked. My first job was in a pharma company. We were developing drugs for Parkinson's disease. And that's where I learned about, you know, what is the blueprint for pharmaceutical drug development? How do you meet the gold standard for demonstrating efficacy and really helping people with health? And then I joined a DNA sequencing company, and that's where I really learned about startup life. That company went through some really rapid growth.
Colleen Cutcliffe [00:05:15]:
We went public, and on the other side of that, I started this company, and there I really learned, what does it mean to build something from scratch, and what does it mean to be able to iterate quickly on that and to learn from your end users or your customers? So all of that kind of led me to this idea around Pendulum, me and my co founders, we're all very technical in our backgrounds, and there were two kind of missing things that we saw in the space. One was actually not about probiotics, but really the microbiome. So microbiome was sort of, this was eleven years ago. It was a relatively new science, frankly premised on DNA sequencing technologies. And we were like, oh, my gosh, all these probiotics and yogurts that are on the market today, they're not even using any of this knowledge that we're gaining around microbiome science. How do we start to translate the work that's happening into products that can actually have meaningful impact in people's lives? So that was the first gap, or the first kind of like, who can translate this stuff to help people right now? And then I think the second gap was, how do we think about helping as many people as possible? So we certainly could have followed what my training is in, which is go the pharmaceutical route. We use the science to develop products and then sell it to doctors who sell it to patients. But we thought there was a really big opportunity to expand the ability for people to get product by selling it directly to consumers.
Colleen Cutcliffe [00:06:40]:
And we're going to talk about metabolism here. And I think that's a place where, I mean, I don't know anybody who's not thinking about how to optimize their metabolism. And so should you make products that are limited to people who are all the way, you know, crossed over into having type two diabetes? Or can you make a product where you can have everybody who's trying to optimize their metabolism have access to it? So the big gaps were, how do you translate microbiome science? And the second one is how do you bring products that have real efficacy to the market and impact millions of people? And that's why we started pendulum.
Erin Holt [00:07:13]:
So cool. And it's just, you know. Preventative medicine really should be at the forefront of medicine. And so I, you know, I'm really resonating with what you said. We could wait until it gets to a point of a diagnosable disease, or we could manage the metabolism in all of the different ways that we can, like, long before it gets to that point. So, speaking of metabolism and metabolic health, including blood sugar regulation, insulin signaling, it's finally getting more time in the sun, I would say, with the rise of CGMs and just more chatter about it. I think it's on people's minds in a way that it hasn't always been. I think we've always talked about metabolism, but kind of like the Shape Magazine definition of metabolism, like calories in versus calories out, which is like, actually not what the metabolism is, but metabolic health.
Erin Holt [00:08:06]:
You know, blood sugar regulation is so important, and people are becoming more and more aware of that. I still think there's, like, a little bit of a gap in the knowledge base where I think people are kind of thinking about blood sugar regulation as how many carbs am I eating? And in order to regulate blood sugar, I have to restrict my carbs, which sometimes yes, totally, but that's not the whole picture. So I would love for you to start by explaining the connection between the microbiome and metabolic health.
Colleen Cutcliffe [00:08:38]:
Absolutely. So it's a little bit not intuitive when you first think about it. Most people think about the microbiome and probiotics as helping you with GI issues. But actually, all the food that you eat, once it gets through the stomach, is metabolized by your microbiome. And so your microbiome plays a super important role in metabolizing the foods that you eat. And moreover, we've evolved with these microbes so that there are certain foods that we eat that are really good for us, that we actually cannot metabolize. We need those microbes to metabolize them. And, you know, some of these fibers are a good example of that.
Colleen Cutcliffe [00:09:12]:
And so there is a really deep link between our gut and our metabolism just by virtue of these microbes metabolizing our food. But moreover, one of the things a lot of people don't realize is that our gut microbiome actually triggers GLP-1 release. And so GLP-1 is a hormone that our bodies naturally make when we eat food in order to tell our bodies that we're not hungry anymore. So it's sort of the unhunger hormone, and that is stimulated by very specific microbes that you have in your gut, including Akkermansia. And so these are some of the fundamental ways that our gut microbiome is almost like a major player in our metabolism.
Erin Holt [00:09:57]:
And so if these bacteria are not present, if they're not present in large amounts, then we're not producing this GLP-1 hormone. I've heard somebody refer to the gut as an endocrine organ. Kind of just like a little bit of a joke, right? Because it's obviously not, but it, like, it kind of is because it does produce hormones. So if we're, if we don't have this diverse, robust ecosystem in the microbiome or lots of beneficial bacteria, that we're not producing these compounds, these hormones, that can positively influence and impact our overall metabolism.
Colleen Cutcliffe [00:10:35]:
Exactly, exactly.
Erin Holt [00:10:37]:
And so the solution is, do we just replace those things, or are there, you know, can we take a multi pronged approach here?
Colleen Cutcliffe [00:10:46]:
I always think a multipronged approach is the right way to go. There may be certain things that are not feasible for people to be able to do just in their daily lives, but certainly, I think your body's ability to metabolize these foods. It's interesting. I often talk about how, like, we all remember a time where we could eat or drink whatever we wanted to, and we didn't have to worry about it at all. And you don't need a doctor or diagnostic test to tell you that as you age, you start to lose some of those key things. And what we know now is that you start to lose actually some of these specific microbes as you age, and they are performing these key functions, to your point. And so how can you get those microbes back? Well, one of the most powerful ways to change your microbiome is through the food that you eat. That is the diet that you have, that becomes then their diet.
Colleen Cutcliffe [00:11:38]:
And so you can almost control which microbes that you are allowing to colonize and divide by feeding them the foods that help them to divide. So I think food is an important one. Certainly, directly giving strains back to people that they're missing is another great way to tackle the problem. And then there are a variety of other lifestyle things that we know can negatively impact the diversity of your microbiome. So we know that stress, we actually know that your circadian rhythm. So when night turns a day, day turns at night. We even know that for women, when we go through menopause, our microbiome becomes depleted. So anyway, just another great aspect of menopause.
Colleen Cutcliffe [00:12:19]:
Add it to the list. But you know, I think that when you think about all the tools to kind of manage through those different things and particularly stress, you know, there's a lot of stuff that goes beyond just prebiotics and probiotics and into things like, you know, mental health, exercise, meditation. These are all things that can also help you just kind of slow down that depletion in microbes.
Erin Holt [00:12:45]:
I mean, I don't think that that's being discussed as much. And we know, like stress is bad, right? Stress is bad for the body. But to like really zoom out. An overall healthy lifestyle, low stress, supporting circadian rhythm, eating good foods is going to positively influence your microbiome, which is going to positively influence your overall metabolism. So all of these things are all interconnected. And I appreciate, and you know, this is a co founder of a probiotic company saying that food lifestyle matters matters majorly. So let's drill in a little bit to GLP-1 because it's a bit of a hot topic. GLP-1 is now like a household name, whereas, you know, a year, two years ago it absolutely wasn't. So let's talk specifically more specifics about what does GLP-1 actually do.
Colleen Cutcliffe [00:13:44]:
Absolutely. Well, we've been working on GLP-1 for a decade and so I thought it was a super important hormone for a long, long time. And so I'm really excited that it's kind of making its way into the world because it is a really, really important hormone. So the reason why GLP-1 has become so popular is because of these drugs that are out in the world. And these drugs are synthetic mimics of a hormone that your body naturally makes called GLP-1. So that's why things like ozempic and wagovia are called GLP-1 analogs. They're trying to mimic your body's natural GLP-1 hormone. We've been very interested in the body's natural GLP-1 hormone because it plays a couple of really important roles.
Colleen Cutcliffe [00:14:30]:
One is that maybe we'll talk a little bit of, like, we'll geek out a little bit on the mechanism here, but when you eat, food gets metabolized by your gut microbiome. It stimulates GLP-1 to be released from your l cells. And what GLP-1 does is, number one, it helps to stimulate insulin release so that it helps your body metabolize the sugars in the food that you just ate. But second of all, it gives your brain and your stomach a sense of fullness. And so it's been called kind of the unhunger hormone in that it tells you, hey, we've eaten enough, we're done. It's sort of like when you add gas to your car, you know, you stick the nozzle in, you set that little thing, and then you just kind of space out and you don't have to worry about that fuel kind of leaking out of your car because you know that when the tank is full, there's going to be a click. And therefore the thing is done adding fuel because it knows it's done. GLP-1 is that click in our bodies.
Colleen Cutcliffe [00:15:26]:
And so if you have the right GLP-1 production, you get that click. You eat food, you're full, you're not hungry again until the next time that your body actually needs the fuel. But if your GLP-1 is misregulated, you're not producing enough of it, or you're producing it at weird times. That's when what you start to experience is these food cravings, and especially for foods that are not really good for your body. And so your GLP-1 hormone and that whole pathway has been misregulated and you're not getting GLP-1 at the right times and the right amounts. And so that's why GLP-1 is so important. It helps you metabolize the sugars in your body, but it also helps your body to know, I'm not hungry anymore.
Erin Holt [00:16:05]:
And you had said, especially for foods not good for your body. Is there like actual research to say, like, if your GLP-1 signaling is mismanaged? I don't know if I'm using like real good, good tech, tech terms here, but hopefully you're following me. If that those systems are off, then you're more likely to have cravings for foods that are perhaps not ideal for human health.
Colleen Cutcliffe [00:16:34]:
Yes, and even more compelling, if you can fix a person's GLP-1 response, so it is backed the way it's supposed to be, you can significantly reduce those cravings. So it's both ways. And probably the most important thing is that if you are not producing enough GLP-1 or you're producing it at not the right levels, it's sort of misregulated. That if you are able to get that GLP-1 back into place, and a lot of people are doing it through these GLP-1 analogs, it gets rid of all of your cravings.
Erin Holt [00:17:02]:
And so with this class of drugs, the GLP-1 agonist, we are seeing pretty significant and sometimes even rapid weight loss, because there is a reduction in hunger and so people are eating less, for better or for worse. That is not part for us to determine. And it's not the conversation we're having today. Your product, GLP-1 probiotics, total different mechanism of action. It's not going in. And replacing our own GLP-1 hormone, it is stimulating our own innate production of it.
Colleen Cutcliffe [00:17:40]:
That's exactly right. So what the drugs are doing is you're injecting into your bloodstream a chemical mimic of your body's natural GLP-1 hormone. What our GLP-1 probiotic is doing is it's taking advantage of your body's natural abilities. And the science that we've learned around how to your body stimulates GLP-1. And we're saying, okay, we're giving you back that function. So now your body can make its own GLP-1. And the result of that is that you don't have kind of this massive high levels of GLP-1 signaling happening all the time. You have it in the time that your body's supposed to have it.
Colleen Cutcliffe [00:18:14]:
And so we know that people who are on this GLP-1 probiotic who are delivering back these strains after being on that for six weeks, 91% of them had reductions in food cravings across all the four major types of food cravings. So everybody usually knows what category they fall into when I list these. But there's sugars, carbs, high fat foods and fast foods, and those are the primary types of food cravings. And 91% of people had reduction in those cravings after giving themselves back these probiotics for six weeks. And that's because the way your body is supposed to work is you're supposed to have a lot of these strains, and we've lost them for a variety of reasons. And so giving them back can enable people to stimulate their own GLP-1. Teaching your body sort of the fish instead of just giving it the fish.
Erin Holt [00:19:01]:
Yeah. We have a saying where we try to regulate or self regulate before replace. So, you know, think of something like a hormone like progesterone. Like, let's try to get your body to produce its own progesterone before we swoop in and give you bioidenticals. Not that we would do that, me personally, but just the general we. So it sounds like it's pretty similar. And we're in a, you know, not casting judgment on somebody who is taking bio identical progesterone, to stick with this analogy. But it's like, let's try to get the body to do what the body is supposed to do first before we swoop in and try to replace it.
Erin Holt [00:19:35]:
It's a pretty good strategy. So I like that. You know, the six week study that you're referencing, is that something that your company put on?
Colleen Cutcliffe [00:19:43]:
Yeah, I mean, these strains. So there's only ever been two strains, two probiotic strains that have ever been published to show that they can directly stimulate GLP-1. And so we have been able to manufacture those two strains, and then we added a third strain that we actually know works with those two strains. And so this is a three strain formulation. And we ran the study in several hundred people. So the caveats are, we ran the study so you can take that all with a grain of salt. And the second caveat is it was an open label study, so people knew that they were taking a probiotic. It's not a placebo controlled, double blinded, randomized trial.
Colleen Cutcliffe [00:20:22]:
And so that will hopefully come out in time. But this was an open label study. It was in several hundred people. And we used the food cravings inventory, which is the diagnostic test for food cravings. And so that's the kind of study design.
Erin Holt [00:20:38]:
Did you see increase in GLP-1 production? Did you measure this in this study?
Colleen Cutcliffe [00:20:43]:
No, in this study, we didn't do microbiome analyses or GLP-1 analyses. We were really just, you know, when you're in product development, the first thing you want to know is, like, does it do anything? And then if it does something, let's go spend the resources to go figure out, like, okay, well, how is it working the way we thought it was going to work? So this was sort of the first of a long lineup of studies that just says, like, does it do anything for people? And I think the fact that we saw such a compelling improvement in food cravings has us now investing a lot. And we're doing this also as collaborations with a lot of academics to look at, you know, okay, well, is it working the way we think it's working?
Erin Holt [00:21:19]:
So cool. This is so fascinating to me as somebody who does not conduct my own studies. It's very cool. And that's why, you know, the label, the actual label that I'm holding in my hand here, it says, naturally curbs cravings. And it's because that is the primary result that you were able to see in the six week study.
Erin Holt [00:22:52]:
So you had mentioned that there's specific strains that is in this GLP-1 probiotic. Can we talk about those strains and why they're there?
Colleen Cutcliffe [00:23:34]:
Sure. So the three strains that are in the formulation are Akkermansia mucinophila, bifidobacterium infantis, and clostridium butyricum. These are three different strains that usually, if you're used to reading labels of probiotics, you're used to seeing things like lactobacillus and bifidobacterium. And so clostridium butyrichum and Akkermansia mucinophila certainly fall outside of that. And these three strains play an important role in helping our body to metabolize fibers into butyrate. And butyrate is quite well known for its role in being able to help with metabolic syndrome. But clostridium butyricum and Akkermansia mucinophila specifically have been able to show that on their own, they can stimulate the release of GLP-1. And so that's super exciting.
Colleen Cutcliffe [00:24:30]:
And I think that the mechanism for Clostridium butyricum is the butyrate that it produces is able to bind to these g protein coupled receptors that are in the l cells. And that tells them, okay, release the GLP-1, and then Akkermansia, which plays a variety of different super important roles. It's starting to emerge as a keystone strain in our microbiome. It can stimulate GLP-1 production in a few different ways. The first and probably least effective way that it does it is it produces another short chain fatty acid called propionate. And propionate can be converted into butyrate, and then it follows this g protein coupled receptor pathway.
Erin Holt [00:25:09]:
Wait, why do you say that's the least effective?
Colleen Cutcliffe [00:25:12]:
Well, because I'm about to tell you the other two, which are way more direct. So. Because essentially, secreting propionate means you need the other player in there to convert that propionate into butyrate. So it's like a two step as opposed to a one step. So the other things that it does that are the one step is it has a surface protein called amuc_1100, and it secretes a protein called P9, and those directly bind to receptors on the l cells and stimulate GLP-1 production. So Akkermansia has three different ways that it helps our body release GLP-1. Two of them are direct, one of them is indirect.
Colleen Cutcliffe [00:25:48]:
And, of course, these strains are both relatively novel. And so there's a lot of publications coming out, and we're learning more and more every day. But, you know, as of 2024, this is what we know about Akkermansia.
Erin Holt [00:26:03]:
Because wasn't Akkermansia discovered in, like, in the two thousands? It's, like, new to us. I mean, it's not new to our bodies, but new to our minds. Like, we're just aware of it more so now.
Colleen Cutcliffe [00:26:13]:
Exactly. And you're right. The early two thousands feels like a long time ago, but in the context of science and our knowledge about things is super short. It was discovered in the early two thousands by a physician at Mass General Hospital who is actually a bariatric surgeon and was trying to understand, okay, after bariatric surgery, what are all the metabolic changes that are happening? And discovered Akkermansia as a key player.
Erin Holt [00:26:39]:
So cool. And do you want to just highlight, I mean, like I said, we've talked about Akkermansia, but other things other benefits of acromansia outside of just GLP-1 production?
Colleen Cutcliffe [00:26:49]:
Yes. So Ackermansia has this important role in GLP-1 production, but it also has this other incredibly important role in the structure of our gut lining and maintaining the structure of our gut lining. So your gut lining is sort of like a fence. So if you imagine a wooden fence that has all these planks and it has glue that holds those planks together, you really need to have strong planks, but you also really need that strong glue. Your gut lining is the same way. You have these epithelial cells that are lined up next to each other and they have glue that holds them together. It's called mucin. And Akkermansia is the only strain that has been discovered to date that lives in that mucin layer and can both strip away the mucin or the glue when it gets old and stimulate new glue at the same time.
Colleen Cutcliffe [00:27:37]:
So it's basically the master regulator of your glue. So it can strip away the old glue, put up the new glue, and therefore it becomes like one of maybe the most important strain for maintaining the integrity of your gut lining. And so when you're low in Akkermansia, that has been associated with a wide variety of diseases that people typically think of when they think about, you know, so called leaky gut. So you have GI issues, you have inflammatory issues, you have weird immune responses. So all these things that are kind of supposed to be housed inside your microbiome, they now the glue is missing. You've got these gaps between your cells and things are leaking out into your bloodstream and causing havoc. And so Akkermansia not only helps stimulate GLP-1 to help you with metabolism, it also makes sure that your gut lining is intact.
Erin Holt [00:28:28]:
Question for you, because we do run stool tests in our practice, and we have a lot of practitioners who listen to the show that also do that. And there's a lot of issues with stool tests. I am not going to sit here and pretend that they are perfect. The filter that myself and my other clinician run ourselves through is, are they guiding treatment plans that get people feeling better? And if the answer is yes, we're going to continue to use them as a tool. Not the only tool, but a tool. And so the one that we run does measure Akkermansia. And so it's not uncommon to see this low. It's actually quite common, and once in a while we'll also see it high.
Erin Holt [00:29:10]:
And I'm curious if you could speak into that. What we've noticed is that we'll see it elevated sometimes. If there is a lot of inflammation in the gut and it's like, you know, inflammation, what do we do? You know, we can tend to drive more of that mucin production. Right. And so it kind of makes sense that maybe we would see Akkermansia levels being a little bit high with inflammation. But from your side of things, the research side of things, could you speak into reasons for high levels of Akkermansia? And is this, is this a problem?
Colleen Cutcliffe [00:29:38]:
Yeah, it is a area under a lot of investigation, and I think it's super interesting to think about, you know, why would one have high levels of Akkermansia? You know, I'll start by saying there are thousands of studies around on Akkermansia from around the world. The vast majority of them are around low levels of Akkermansia. So our knowledge around high levels of Akkermansia and what is happening here is pretty limited, but I think it's growing every day. So I'll caveat what I'm saying now with, we're really on the steep part of the learning curve here and trying to understand it. I think that when, and also I will say that as I talk to practitioners about what do you do when you see high levels of Akkermansia? I get totally disparate answers on how they're managing through this. So I think what the data tells us is that there are certain even diseases that appear to be associated with high levels of Akkermansia. And some of the ones that have some, one of the ones that I think has pretty strong studies around it is multiple sclerosis. So people with multiple sclerosis tend to higher levels of Akkermansia than people who do not.
Colleen Cutcliffe [00:30:39]:
Then, you know, there are a variety of studies on. Okay, well, is that causative or correlative or what's happening here? And there have been a multitude of animal studies, mouse studies, which have their own caveats. I hate mouse studies, but these are the studies that people are able to.
Erin Holt [00:30:59]:
I'm taking you off piste here. I'm sorry.
Colleen Cutcliffe [00:31:02]:
The reason why I really don't like mouse studies is because they are not small humans. And if you've ever worked in drug development, you know that if you're a mouse and you have cancer, you are made. There are so many drugs that are going to help you, but they don't translate to humans. And so there it's. And then when it comes to the microbiome, it's an even bigger gap because they don't eat the same foods that we eat. And since your diet is one of the major things that shapes your microbiome, you have to then go into these very, like, fake mouse models. So there's a fake mouse model of the disease and a fake mouse model of the microbiome. And now you're saying, like, oh, now I want to learn something about how it works in humans.
Colleen Cutcliffe [00:31:37]:
It's just not like, a good proxy. However, in these MS studies, there are two kind of, I think, well orchestrated studies that were done that give the exact opposite results. So, in one study, these investigators took a mouse model of multiple sclerosis, and they gave directly these mice Akkermansia, and they showed that the MS symptoms got worse. So you're like, oh, man, Akkermansia is bad for MS. The other study, which was also very well conducted, took a mouse model of MS, and they directly gave them Akkermansia, and the mice got better. So you're like, okay, the body's upregulating Akkermansia in order to fight this disease. And those are the two schools of thought right now that are out there.
Colleen Cutcliffe [00:32:17]:
And I think it's TBD whether your body has a compensatory mechanism that is allowing you to upregulate Akkermansia in order to fight these inflammatory diseases. And we are really interested in that research. And so, hopefully, what we'll start to see come out are studies in humans trying to understand, is higher Akkermansia actually beneficial? And one of the other pieces of information I think is really interesting on this front is that there have been multiple clinical studies showing that polyphenols or increasing your polyphenol intake can help with multiple sclerosis. And we also know that polyphenols help foster Akkermansia growth. And so it is possible that it's really the second train of thought, which is, okay, your body is trying to fight this disease, and that's why you see up regulated amounts of it. Pretty similar to, like, why you see increased inflammatory markers and things like that. But the data is still TBD.
Erin Holt [00:33:18]:
Thank you for taking the time to answer that, because it's honestly, I would say one of the top ten questions that I get from practitioners is like, what's up with high akkermancia? And people get frustrated when I say we don't know yet.
Colleen Cutcliffe [00:33:31]:
I feel like I gave you a lot of information, which this conclusion is, we don't know yet.
Erin Holt [00:33:37]:
You talk about this a lot, and I so appreciate the candor is that, listen, microbiome science is in its infancy. You know, we think we know so much and it's like we are just barely scratching the surface. And even, you know, an expert like yourself, whose career has been in researching the microbiome, you're still like, look, there's a lot of gaps in knowledge here and we're still figuring it out. So I just appreciate that.
Colleen Cutcliffe [00:34:02]:
Totally. We're like teenagers. We know just enough to be obnoxious and we think we know everything totally, 100%.
Erin Holt [00:34:10]:
I love that. Okay, so back to the GLP-1 and how these three specific strains can really help to generate GLP-1, either on their own, the probiotic themselves, or through short chain fatty acid production. What would, you know, what about just taking butyrate? Would that help to just stimulate our own production of GLP-1? And would you do kind of like a combo platter of, like, we take some of these probiotic strains, we take some exogenous butyrate in the form of the supplement, and bingo bango. Now we've got heaps of GLP-1.
Colleen Cutcliffe [00:34:47]:
Butyrate is such an interesting small molecule to me because there have been so many amazing studies showing the benefits of butyrate in metabolic syndrome, as well as a variety of other diseases. The biggest issue with butyrate supplementation is that while there's all this great lab data and there's all this great mouse data, there is actually not great clinical data or data in humans. And it appears that for some people it can be beneficial. For a lot of people it's not. And you don't get these statistically significant results like you do in these other models. And so the question is why? Why isn't it translating? And I think it really has to do with delivery. Our body is a very tight system of things get delivered here, and that's important for their ability to have efficacy. And so the butyrate receptors, these g protein coupled receptors, are embedded in the gut lining and so require the butyrate to be right there in order to hit at that receptor.
Colleen Cutcliffe [00:35:47]:
And moreover, your colon cells are the only cells in your body that use butyrate as their primary source of energy. Every other cell in your body uses glucose, your colon uses butyrate. And so effectively, when you take a butyrate supplement orally, all of those cells, as it's trying to make its way to those g protein coupled receptors, are grabbing that butyrate as their source of energy. And I've likened it to like you. If I was going to give you, Erin, a million dollars would you rather I put it in a suitcase, knocked on your door, and handed it to you? Or would you rather I called you up, was like, hey, I just spread it all over highway 101. You can go pick it up there. And, you know, you don't want option number two, because what's happening right now on highway 101 is people are pulling over and they're grabbing all your money. By the time you get there, you get a dollar.
Colleen Cutcliffe [00:36:31]:
And so that's really what these butyrate supplements are facing the challenge of. As the supplement, as the butyrate is making its way down the GI tract, every colon cell is grabbing those dollars. And by the time the butyrate gets to the g protein coupled receptors, which is where all the action has to happen, there's very little of it to hand off to that receptor. And so that's why butyrate supplementation, on its own hasn't had the kind of super strong data behind it that the lab data has shown.
Erin Holt [00:36:56]:
Oh, that's so interesting. And so maybe, perhaps it, you know, it's. It's. Has some efficacy as just fuel for the cells, but it's not, you know, landing in those like that lock and key dock or that receptor site. Oh, that's. That makes a lot of sense when you. When you spell it out like that.
Erin Holt [00:40:04]:
I'm curious. So we've got the GLP-1 probiotic, which is your new feature piece, and it makes a lot of sense as to why you created this. There is one thing we didn't talk about, is the little itty bitty, little bit of inulin that's in that. That sometimes can freak people out, particularly if they do have, you know, like SIBO. They have a tendency for a lot of, like, bloating gas, that kind of stuff. And, you know, when I look at this, it's 200.
Erin Holt [00:40:45]:
I don't have my glasses on. It's like 200 milligrams. You know, when we're giving people inulin fos and different types of soluble fibers, it's like, sometimes up to, like 5 grams a day. So comparatively speaking, this is just like a, this is a pinch, right? Have you found that that exacerbates Gi issues, that small little amount of inulin? And also, why did you include it?
Colleen Cutcliffe [00:41:14]:
Maybe I'll start with why we included and then what we're observing. So we included it at that particular dose because that like physiologically, that's not a clinically relevant dose. To your point, you need like grams and grams of inulin in order to actually have a physiological response. That inulin is not there for you, that inulin is there for those microbes that are sitting in that capsule together. And so the whole point is to have the probiotics and their prebiotics together in the same capsule. It's like I told people, like, if you're going to drop me off on a deserted island, I love if you drop me off also with a cooler full of sandwiches and beers, like, so we're basically giving them the food so that when they get to the distal colon and that capsule dissolves, you've got now the strains plus the food that they eat in close proximity. So that can help them to get a jump start in colonization. That's why the inulin is in there.
Colleen Cutcliffe [00:42:06]:
And we know from our own studies that having it in there does actually improve the efficacy of those strains as opposed to having just the strains by themselves. That being said, I do think there are a population of people who are extremely sensitive to inulin, so even that amount can be problematic for them. And I think that for us, as we developed this GLP-1 probiotic, of course, there's no such thing as a one product fits everybody. We really took into consideration what is a product that can maybe help the majority of people. But I think there's a big opportunity for us to create products that potentially don't have that inulin in there, but can try to serve up the population that's super sensitive to it. But the reason the inulin is there is to help jumpstart these strains. And if you're incredibly sensitive to, like even milligrams of inulin because of, you know, some other condition, you know, it could potentially be problematic. We haven't gotten reports of that.
Colleen Cutcliffe [00:43:07]:
Most people, when they start on this probiotic, they actually have improved digestion and improved Gi, and that's because of Akkermansia's role in the gut lining. But there are some people that, you know, I don't think that that discounts the idea that some people really will, might have issues with it, it, and.
Erin Holt [00:43:22]:
I would also say just kind of like, you know, anecdotally speaking, clinically speaking, what I've seen, if you do have a,, you know, trial one of these probiotics and you notice a little bit of, like, funky guts for a day or two or even like, you know, up to a week, that's pretty typical of starting a new probiotic. It can just take the body a little bit of time to adjust. It's like you're throwing, like, like, new stuff and you're like, good luck down there. And it's a little bit of a party. And so I wouldn't just say, oh, it's because of the inulin like, right out of the gate. It might be just an adjustment period. I am taking the GLP-1 probiotic right now.
Erin Holt [00:44:03]:
I've only been on it for just under a week. The first day, like, for 2 hours after I took it, I was like, oh, I feel funky. And then it went away and then I didn't experience it again. So my adjustment period was super short. Some people, you know, don't even notice anything, but I just feel like it warrants saying that in this discussion.
Colleen Cutcliffe [00:44:22]:
Absolutely. And it could also be, to your point, the strains or the production of butyrate. Butyrate is a volatile. You know, it can produce gas. And so, you know, there are a lot of reasons why if you're depleted in these strains, taking them can, at the onset, sort of feel, like, disruptive. And I would say that if you feel something when you take the probiotic, that means it's changing something. So if you take it and nothing happens, you know, maybe it's not really doing so much. But I do think that for some people, kind of dosing down, like, especially if you were incredibly low in these strains, it can feel like a jolt to all of a sudden give them to your body.
Colleen Cutcliffe [00:44:57]:
So taking one pill every other day, kind of stepping your way into it, it could be an important thing. And then, you know, for Akkermansia, we definitely know that there are practitioners who want to start with, with a really high dose of Akkermansia to jumpstart and replenish Akermansia levels and then move their patients to a lower dose to kind of maintain. And then conversely, there are some practitioners who have certain patients where they're like, well, I want to start in a low amount of Akkermansia and then dose people up to a higher amount. And so for practitioners specifically, we have an Akkermansia 100 and an akkermancia 500 to address that, those exact different case needs.
Erin Holt [00:45:35]:
Oh, that's so interesting. I actually didn't realize that you had mentioned colonization and because you just brought up akkermancia. Again, I don't want to jump around too much, but I'm like, you said it, so I'm going for it. Another big question that we get on Instagram is I'm taking the Akkermansia, and my levels on my stool test are not increasing. So when I think about this, when I'm working with a client, and we are recommending an Akkermansia probiotic because we see low Akkermansia, we're also doing other food polyphenols. We're probably doing some fibers, if they can tolerate it as well, in addition to. But I really want to. If a practitioner is listening, listen up.
Erin Holt [00:46:21]:
Because I want to discourage us from treating the lab. We always have to treat the human being behind the lab. So, yes, we'll be looking at, okay, our levels coming up if we rerun that stool test. But I'm also looking for metabolic changes. We're doing blood work. We're saying, okay, if you had high fasting glucose, did that come down? Your symptoms of high blood sugar and low blood sugar and those swings in between, is that mellowing out? So we also have to look at the symptoms. You know, like you said, people will start Akkermansia and then their digestive issues get better because we're essentially helping to make the gut healthy and strong as well. So I, you know, I'll let you take it from there, but I want to just throw that in, into the mix where it's like, just because the levels are not coming up on a GI map does not mean that you're not receiving some benefit.
Erin Holt [00:47:07]:
But are there some suggestions you could make that could help with the colonization piece?
Colleen Cutcliffe [00:47:12]:
Yeah. Well, thank you so much for saying that, because I think that as practitioners, you guys are trying to think about what are people's diseases, their symptoms, the root causes of all these things in the microbiome is one of the tools. And these microbiome tests are one way to know whether the microbiome is changing or not. But, you know, we kind of to the point earlier that you were making about how much do we really know this, like, healthy range. I don't think that we have enough information to know what that means, especially on an individual level. Some people might be able to get away with very little of Akkermansia, and that's good enough for what their body needs and other people might need a ton of it. And so unlike a lot of the blood tests where, you know, we have so much data behind what is, like, normal and what's associated with disease, we really don't have that kind of data. And moreover, a lot of these microbiome testing companies do the testing in different ways.
Colleen Cutcliffe [00:48:05]:
It's not regulated, and they're collecting their own data, and so that's all they really have to go off of. And so there's some, you know, some of the reasons why the Akkermansia levels might not change are really related to the test that you're using and not really knowing, like, is this amount, what is the right amount for a person? So I love that you're pointing to. Well, I'm pointing to the gut because the person having this issue is the issue actually getting better. And so some of the things that might be the reason why the Akkermansia levels aren't getting higher are, one, the test is maybe not accurate enough for what that person needs. They might not need that much and they're fine. The second is actually the source of your Akkermansia supplementation. One of the things that we have observed is that there are lots of people right now out there selling what they're calling Akkermansia. And what is in the bottle is not actually Akkermansia.
Colleen Cutcliffe [00:48:58]:
And one of, one of the professors at Cornell, which hopefully he will publish this data, literally bought a bunch of akkermancia off Amazon and tested all of them, and none of them had actually Akkermansia in it except for Pendulums. So I think the second thing is just to be really careful about the source of the Akkermansia, because maybe you're not even giving them Akkermansia. In that case, you would not expect the akkermancia levels to increase. But the third one is that it might not be good enough to give somebody just the straight up strain. The microbiome is an ecosystem that has already these thriving strains in it and all these things that are happening. And basically it's like you're going into some huge garden, you're like, I'm going to plant one seed and oh, I can't believe it didn't grow. I think that for a lot of people, that's really hard to plant one seed and actually see it grow within the existing ecosystem. So some of the things that you can do to really help that are what you were mentioning, which is, is on the prebiotic side.
Colleen Cutcliffe [00:49:57]:
So really increasing the amount of high fiber foods, especially soluble fibers, that's been clinically shown to be able to increase Akkermansia levels on its own. Increasing polyphenol levels can increase Akkermansia on its own. And so it's possible that you need to pair the fibers and the polyphenols with Akkermansia, or hopefully none of my investors are listening. You might be able to get away with just those foods, and you don't really need to have the Akkermansia strain itself. So there's lots of ways you can boost Akkermansia. Obviously, directly giving it and pairing it with these prebiotic foods is probably the best one to punch for increasing levels.
Erin Holt [00:50:35]:
You know, there are some people that don't have access to a stool test that might be listening to this or practitioners who don't use functional labs. And, you know, we can still leverage the use of Akkermansia probiotics without having the data to say, maybe you're high, maybe you're low, maybe we don't really know. But remember that it has a lot of metabolic effects as well. And so I would love for you, I know we're coming up on the hour and I want to be respectful of your time, but there are three different products. There's Akkermansia, there's your metabolic daily, and then there's your GLP-1 probiotic. So how can consumers or even practitioners discern which one is right for who?
Colleen Cutcliffe [00:51:16]:
Great question. And I'll add there's a fourth one in there to talk about as well. So there's Pendulum Glucose Control. There's Pendulum Glucose Control. That's if you have somebody with type two diabetes and you're trying to lower their A one C and blood glucose spikes that has publications in BMJ and really is the kind of heavy hitting powerhouse for people with type two diabetes. Metabolic daily.
Erin Holt [00:51:38]:
Is it just probiotics or is there anything else in addition to it?
Colleen Cutcliffe [00:51:42]:
It also has some inulin in it. So it's a symbiotic.
Erin Holt [00:51:45]:
Yeah, got it.
Colleen Cutcliffe [00:51:47]:
And then there's Metabolic Daily, which is if you're just trying to maintain metabolic health, it has actually all those same strains that are in that heavy hitting one but at a lower dose. So anybody who's really just trying to maintain their microbiome and their gut metabolism axis to be strong. GLP-1 probiotic is if you're specifically trying to increase your GLP-1 levels, you are really interested in battling your food cravings. You're really interested in the point that you made earlier, trying to do everything that you can to naturally increase your GLP-1. And then Akkermansia interestingly, it's almost kind of like if you're in the know, so, like, you've taken a test and you, like, just want Akkermansia. It always surprises me how many people are into, you know, the single strain, because I tend to think these formulations are like, oh, you know, they're telling you what, you know, they're lowering your blood glucose, they're reducing your cravings. But Akkermansia as a strain itself, I think, are for the people who are in the know about what Akkermansia by itself can really do as a keystone strain, and they're just trying to supplement Akkermansia for themselves. And so if you're trying to solve the problem of a one c or you're trying to solve a problem of food cravings, you would go for Pendulum Glucose Control or the GLP-1 probiotic.
Erin Holt [00:53:01]:
Got it. Okay. And for those who are interested in the GLP-1 probiotic, is this something that you take long term? And somebody else also asked, is there benefits of increased dose? So it's like, I really want to increase that GLP-11 bad. Should I just take four to five probiotic pills at a time?
Colleen Cutcliffe [00:53:26]:
Oh, my God, it's so funny. I just met with one of our investors yesterday, and he's like, well, I'm up to four pills a day. And I had another investor say, well, I've been taking eight pills a day. And I was like, we should get you all together and have, like, a showdown of, like, who's taking the most, you know? But, you know, I think it kind of depends on how low you are and whether kind of taking more of those is really helping you to have those strains colonized. So there might be things in your life that are actually working against you, either genetically or environmentally in terms of these strains being able to take a foothold. And for those individuals, they might find that, okay, if I double the dose or I triple the dose, I actually feel more benefit from it. And to your point about what are the symptoms, or what is the thing you're trying to solve? If that works for you, great, go to town. And I think that's the thing that people need to be really sensitive about for their own bodies and really kind of like, being, I think, thoughtful about and measuring.
Colleen Cutcliffe [00:54:21]:
Am I seeing an improvement? Do I need to be taking more or less? And so that's kind of how I would address that question. To the question of, do you have to take these pills for the rest of your life? The answer is probably not, frankly. So if you're low in these strains through whatever variety of things that are and aren't in your control, simply taking the strains and taking the foods that can help feed those strains could help you to jumpstart the colonization in your gut. And once you have these strains colonized in your gut through the right diet, you can keep feeding them and keep them colonized and growing. So it is possible that you can take the strains, you modify your diet so that you're eating high fiber, high polyphenol foods on a regular basis, and that keeps these strains alive. There are these things that are kind of outside of your control that can cause you to become depleted in the strain. So let's say you had an incredibly stressful period. Let's say you took an amazing trip somewhere that was a twelve hour difference from where you live now. Let's say you go through menopause.
Colleen Cutcliffe [00:55:23]:
I mean, these things that are not in your control, you might need to reintroduce at some point. So it might be like, you go on it, you taper off, you go on, you taper off. And for me, that's probably the more realistic situation. Now, I take Pendulum Glucose Control every day because I wore a continuous glucose monitor, I saw that all of my spikes and crashes were actually minimized on the product compared to placebo. So I did a placebo controlled trial on myself. I don't have pre diabetes or diabetes, but I am aging and I don't really eat that great. And so I take it every day because I like to be able to, I do try to eat high fiber, high polyphenol foods, but I also have my weaknesses and like to be able to keep doing those. And so I know I'm fighting, you know, these microbes in terms of what I'm feeding them.
Erin Holt [00:56:09]:
The sandwiches and beer that you want on that desert island.
Colleen Cutcliffe [00:56:12]:
Yeah, those aren't really, you know, feeding these, these microbes very well.
Erin Holt [00:56:18]:
All right, well, this is so informative and so helpful. Thank you so much. I think we got all of the questions, the listener questions answered. So that is wonderful. And I just appreciate your insight into all of this. It's really good stuff. I'm such a mega fan. It is rare that I have, you know, have somebody come on to the show to just talk about their product, but I'm such a fan of it that I'm like, I would, I would love to have her.
Erin Holt [00:56:43]:
So thank you. So, so much. You're, you're just such a great, great gift to the show.
Colleen Cutcliffe [00:56:48]:
Thank you so much for having me. And I, I did want to ask you about your experience as a practitioner with the products, because we get to have all the science and all the theory behind it, but you get to really tell us, like, okay, well, what's happening in real life? What can you share out? Yeah.
Erin Holt [00:57:02]:
And I would say that we are the, definitely the ones using that single strain Akkermansia. That's us. I was not familiar with the Glucose Control, so that is something that I'm going to be looking into for sure, especially for those folks who we know have those really elevated A1Cs or even just a little bit elevated A1C. So I'm curious to tinker around with that. With Akkermansia. The Pendulum Akkermansia is our go to when we do see low Akkermansia on a stool test, but we're also doing the fibers. Like I said, if somebody can tolerate that, we're doing the polyphenols, but we like to throw them a bone, too.
Erin Holt [00:57:46]:
And especially if there are signs of intestinal permeability. And we could, you know, like, let's get all hands on deck, all resources on deck. And we have seen akkermancia levels come up on stool test sometimes and sometimes not. But again, I'm looking for those other biomarkers as well and how people are feeling. That's really my primary focus. How are you feeling? Cool. The lab says this. How are you feeling? And so, we continue to use that product because we continue to see pretty favorable results.
Colleen Cutcliffe [00:58:20]:
Amazing. Well, thank you for sharing that. I do appreciate that.
Erin Holt [00:58:23]:
Yes, you're so welcome. And thank you so much for your time. I super appreciate it.
Colleen Cutcliffe [00:58:28]:
All right, great. Thank you.
Erin Holt [00:58:35]:
Thanks for joining me for this episode of the Funk'tional Nutrition Podcast. If you got something from today's show, don't forget to subscribe, leave a review, share with a friend, and keep coming back. Back for more. Take care of you.
