Ep. 346 Gut Health: Unveiling the Science of the Microbiome with Dr. Colleen Cutcliffe 

I am delighted to have Dr. Colleen Cutcliffe, the CEO and Co-founder of Pendulum, joining me today. 

Dr. Cutcliffe is a proud alumnus of Johns Hopkins, with over 25 years of experience leading and managing biology teams in academia, pharmaceuticals, and biotech. Before starting Pendulum, she was the Senior Manager of Biology at Pacific Biosciences and a scientist at Elan Pharmaceuticals. 

In our discussion today, we dive into the emerging science of the gut microbiome, examining the effects of aging, antibiotics, nutrition, stress, travel, and menopause on gut health and discussing how vaginal and C-section deliveries differ in impact. We explore differentiators for various categories of bacteria and the roles of butyrate and fiber, looking at fecal transplants and the difference between probiotics, prebiotics, and post-biotics, and explaining why Akkermansia is an essential bacteria for regulating insulin satiety, fortifying the mucin layer, and facilitating targeted delivery of butyrate. Dr. Cutcliffe also shares her top tips for mitigating the effects of travel on the gut microbiome and offers a special discount for listeners. 

I am confident that you will find today’s discussion with Dr. Colleen Cutcliffe engaging and enlightening. Stay tuned to learn how to adjust your lifestyle for a healthier gut microbiome.

“If you could have a strong gut microbiome and strong gut health, it will impact all the other systems in your body.”

– Dr. Colleen Cutcliffe

IN THIS EPISODE YOU WILL LEARN

• The benefits of a vaginal delivery
• Various factors that disrupt the gut microbiome
• Why it is essential to get enough fiber in your diet
• What are the signs and symptoms of an unhealthy gut microbiome?
• The benefits of fecal transplants
• How the vagus nerve fosters communication between the gut and brain
• Why artificial sweeteners might not be as harmful to the gut microbiome as previously thought
• How prebiotics, probiotics, and postbiotics are interconnected and necessary for overall health
• The role of Akkermansia in the gut microbiome
• How to maintain a healthy gut microbiome while traveling

Bio: Dr. Colleen Cutcliffe:

Colleen Cutcliffe, PhD, 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. Before 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.

Connect with Cynthia Thurlow

• Follow on Twitter
• Instagram
• LinkedIn
• Check out Cynthia’s website
• Submit your questions to support@cynthiathurlow.com

Connect with Dr. Colleen Cutcliffe

• On the Pendulum Life website, use code THURLOW for 20% off a subscription of Akkermansia.

Transcript

Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I’m your host, Nurse Practitioner, Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. 

[00:00:29] Today, I connected with Dr. Colleen Cutcliffe. She is the CEO and co-founder of Pendulum. 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 at Biology at Pacific Biosciences and a Scientist at Elan Pharmaceuticals. She is also a proud alumni of Johns Hopkins. 

[00:00:54] Today, we spoke at great length about the emerging new science of the gut microbiome. The impact of vaginal versus C-section deliveries, the impact of aging, antibiotics, nutrition, stress, travel and menopause. Key differentiators for different categories of bacteria, the role of butyrate and fiber, the impact of fecal transplants. Differentiators between probiotics, prebiotics, and postbiotics. Why Akkermansia is such an important bacteria and why it’s a keystone bacteria that’s involved in stimulating insulin, satiety, regulating the mucin layer, and helping to deliver butyrate to the places it needs to be. And her top tips for limiting the impact of travel on the gut microbiome. I know you will enjoy this conversation as much as I did recording it. And Dr. Cutcliffe has a special discount for listeners. Use code THURLOW for 20% off your first order of their products. 

[00:02:00] Welcome, Dr. Cutcliffe. It’s such a pleasure to have you on. And I was sharing with you right before we jumped on that I have a family member that has really changed her life and her health with your products. So, it’s really an honor to connect with you. 

Dr. Colleen Cutcliffe: [00:02:13] Oh my gosh, I love that story. And thank you so much for having me excited for our chat today. 

Cynthia Thurlow: [00:02:18] Absolutely. I’d love to kind of start the conversation. I believe most of my listeners are familiarized with the gut microbiome, but perhaps not with how we start off when we’re born, that many of us are kind of inoculated as we’re going through a vaginal delivery. I know many people have had C-sections. I had too because I had two big breech kids. But understanding that this is usually the first time that we’re getting this swash of exposure to the human microbiome through our mother. 

Dr. Colleen Cutcliffe: [00:02:51] Yeah, absolutely. Well, I think it’s hard to turn anywhere these days and not hear something about gut health or the microbiome and how important it is for us. And we’re really realizing it’s at the core of all of these different systems in our bodies. And so, I sort of think about how in exercise and fitness, at some point, there was this aha-aha moment where people are like, “Your core. If you could just strengthen your core, you could do any exercise you wanted.” And I feel like we’re having that parallel now in the body, which is the gut is at your core. If you could have a strong gut microbiome and strong gut health, it will really impact all these other systems in your body. 

[00:03:25] And to your point, it’s not about necessarily just today, but also, where did we start and all the changes that are happening to our microbiome as we grow, as we age, and as we go through these different stages of biology. And so, it all starts actually in utero. So, we used to think that there were no gut microbes. The utero was completely, when you’re in the womb, there’s nothing in there except for no bacteria or anything like that. But what we’re realizing is that may not be true. There might be some things already starting to happen there. But certainly, your first real influx and exposure to the microbiome is in the vaginal birth canal. And so if you deliver a baby vaginally, it gets exposure to all of your vaginal microbes. And we know as women, that our vaginal microbiome and vaginal health is something that is really important. But it’s particularly important during pregnancy and during delivery, what are the microbes that are there and making sure that the baby gets those exposures. 

[00:04:20] And so, the baby is born via C-section. They don’t get that initial seeding of all these different microbes. And so there have been really extreme scientists who have had C-section babies and then immediately wanted a vaginal swab all over them to try to mimic what it would have been like to have a vaginal birth. I think that eventually we will get to a place where we can do something a little bit less dramatic than that, but that’s really where it starts. And then from there on, it’s all about increasing the diversity of your microbiome, from mother’s breast milk, to the first foods that we eat, to all of our lifestyle and exposure. It’s all about how do you diversify your microbiome to give it as many different functions as possible. 

Cynthia Thurlow: [00:04:59] Yeah. And it’s so interesting to me because I have teenagers now. I’m now in this fun stage. I’ve loved every stage of being a parent, but helping them understand if they get a round of antibiotics, what the net impact can be on their gut microbiome. And right now, they think I know nothing. This is the teenage years where their parents know nothing, and helping them understand why it’s so important that lifestyle piece. So I’m certainly not suggesting there’s an appropriate utilization of antibiotic therapy, used judiciously and for the shortest duration as possible, but helping them understand that they’re at a stage in their lives where they’ve got a much more vibrant gut microbiome than perhaps the stage of life that I’m in, where our gut diversity starts to shift and change as we are getting older and perhaps talking about what are some of the kind of natural fluctuations that you will see when looking at the research throughout a woman’s lifetime. 

[00:05:54] Obviously, the younger we are, we have better diversity, we have sex hormones that can play a huge role, especially estradiol, in the gut microbiome. And how this starts to change as we’re getting older. And by this, I’m sharing this because I find this fascinating. This is not information I learned in undergrad or grad school. And so, I think the more that we understand, the better we can prepare and to ensure that we are making the adjustments in our lifestyle that will make a large impact on our gut microbiome. 

Dr. Colleen Cutcliffe: [00:06:24] Absolutely. And I really love that you are doing this podcast and getting everybody educated, because the fact is, none of us learned about it in school. And the reason is because this is actually a new science. Things like probiotics and yogurts have been on the shelves since the 70s, but actually microbiome science. If you look on PubMed at all the publications that have come out and you just type in the word microbiome, you’ll see that before 2005, it’s literally at zero. And then you see this really logarithmic exponential growth of all the papers being published. And it’s because actually DNA sequencing technologies are what’s enabled us to really survey the microbiome. And so now it’s really opened up this whole new part of health for us that we really didn’t have access to before. 

[00:07:05] So none of us who went to school earlier than 2010 were really even aware of this. And certainly, even now, there’s just more new information coming out. I also have teenage daughters, and so I think that or I also have teenagers, mine are both girls. I just laugh about how little we now know. There was a time when we knew everything now, we don’t know anything. And later, hopefully they will come back and realize that we might know a thing or two. But I think at the end of the day, it’s really hard for a teenager to be motivated to think about their health because we can all remember that time where we could eat or drink whatever we wanted to and we didn’t have to think about it or worry about it. And so, when you’re in that stage of life, you’re really not thinking about your future self. And gee how do I set myself up for future health? Because you can’t even fathom not being totally healthy. 

[00:07:53] And so I think, to your point, that’s kind of where you’re sort of at your most diverse, where you have the most functions in your microbiome. And what happens to us over time is that we do start to get depleted in that diversity. And it happens for a variety of reasons. One to your point is antibiotic treatment. That is one of the most potent ways to essentially kill all of the microbes in your body. And to be very clear, I’m not antibiotic or people should take them, they save millions of lives. But there is overuse of antibiotics that’s happening. And I think that it’s really important to know that it doesn’t come without a cost. When you take antibiotic, you really are killing off your entire microbiome. And we know that actually after antibiotics it takes a little while, but you will reconstitute a microbiome. But it’s becoming pretty well known that microbiome you get after the antibiotic treatment is oftentimes not the same microbiome that you had before. 

[00:08:47] And more importantly, it tends to be a microbiome that helps you hold calories. So, farmers have actually been using this tool for decades where they give their cattle antibiotics, not because they’re trying to disrupt their microbiome, but they noticed that they gained weight if they gave them antibiotics. And there have been studies shown in children where if you give kids a lot of antibiotics and infants a lot of antibiotics, they are more prone to type 2 diabetes, obesity, even things like allergies and asthma, ADHD, celiac disease. They’re more prone to all these diseases later on in life because that new microbiome is really not the same as the first one. We know that our diet is the second biggest way that you can change your microbiome. And so, the food that you eat is literally the food that you’re feeding to your microbiome. And so, you are selecting who lives and who doesn’t based on who you’re nourishing. 

[00:09:35] And then there are things that are outside of our control that really affect our gut microbiome. So, we know just simply as we age, we start to become depleted. We know that when we go through periods of intense stress, we start to become depleted. We know that when we travel and our circadian rhythm gets disrupted, day becomes night becomes day, we start to lose diversity in our microbiome. And for us women, when we go through menopause, we lose diversity in our microbiome. So, these are all just things that are part of living that can cause us to lose diversity. And that loss of diversity is super important because what it means is a loss of functions. So, all those things that your teenage body is able to do really easily, you now can’t do those anymore. And so that’s why as we age, we start to feel like everything’s sort of falling apart. Some of that is going to be the way it is, but some of it can actually be rectified by just giving yourself back these microbes. 

Cynthia Thurlow: [00:10:25] Yeah. And I think it’s so exciting because this is a conversation designed to be empowering and informational, not to be scary. Because let me be clear, and I agree with you 100%, when antibiotics are used judiciously for an appropriate duration, it can make a huge difference in many individuals lives. I always say with a ruptured appendix, it saved my life. But I had six weeks of antibiotics and antifungals, and I think even five years later, I’m still having to continue to work on replenishing that gut microbiome. And I love that you kind of tied in the nutrition and stress and understanding that when we get jet lag, which some of us do a better job with jet lag than others, I have a much easier time going east than I do west. And then also the changes that happen as we’re making that transition from perimenopause into menopause. 

[00:11:14] Let’s back up and talk a little bit about bacteria. I always say microbiology ruined my life in a good way, but it made me very aware of the fact there were a lot of species and microorganisms that were out there that I was just completely unaware of. Let’s talk a little bit about both anaerobic and aerobic bacteria. Because they play an important role in the gut microbiome, they play an important role in our digestive system. And there are certain areas where certain types of bacteria thrive and others do not. And sometimes when you get an overgrowth of non-beneficial bacteria. That’s where you can start seeing some problems. So kind of from a high level, talking about these basics, because I think it sets the stage for talking about specific organisms later in our conversation. 

Dr. Colleen Cutcliffe: [00:12:00] When we think about kind of just the biology of our bodies, you start to learn and understand that there’s different parts to the system that are environmentally really different. It’s like going for a hike through different terrains. You’re really in totally different landscapes from the beginning to the end. So, it starts kind of with the air around us, which has a ton of oxygen in it. And when we eat food, there’s certainly oxygen in our system, oxygen in our stomachs. But after our stomach starts to digest that food and we start to talk about the intestines and where these microbes are residing, your food kind of starts to go down the intestinal tract. And so right on the other side of the stomach, there is still some oxygen there. But actually, as you traverse down this intestinal tract, you start to get more and more of an oxygen-free environment. And by the time you get to the distal colon, which is where the gut microbiome is, there’s actually no oxygen there. And so, what happens is that you have these microbes that are sort of on the other side of the stomach that are doing a lot of your work for you. 

[00:12:57] A lot of the lactobacillus and bifidobacterium strains that we see on the market today, they are kind of all along the tract there. And so, they can be grown in the absence of oxygen. They’re not so sensitive. But when you get to the gut microbiome, where there’s no oxygen, most of those strains there are strict anaerobes, which means that they actually not only do they not like oxygen, they can’t even survive in the presence of oxygen. And so, these next generation probiotics that are going to come out are all going to have this different kind of a feature, which is that they’re used to living in an environment with no oxygen. And so, if you want to be able to manufacture them, take them outside the body and really grow them up and deliver them back to people, you have to figure out how to recapitulate that environment where there’s no oxygen. And so that’s one of kind of the new discoveries I think, that’s going to differentiate the current probiotics that are on the shelves from the next generation of probiotics. They can’t have any oxygen when they’re being grown.

Cynthia Thurlow: [00:13:48] Yeah. And it’s interesting, during the course of preparation for our discussion, there’s one specific anaerobic organism that I knew a little bit about, and I say this openly, I knew a little bit about it. But understanding how challenging it can be to create probiotics or to create these organisms outside of our body and do it in a way with integrity, because it is so challenging to grow anaerobic organisms outside of our bodies, it really is incredibly challenging. And so perhaps explaining the degree to which you and your colleagues have gone to to be able to create Akkermansia as an example, to be able to create that outside the body and have it be a high potency product that actually is effective and efficacious. 

Dr. Colleen Cutcliffe: [00:14:38] Absolutely. And hopefully we’ll dig a little bit into Akkermansia muciniphila, the most important strain you’ve never heard of. [laughs] And really, that is the challenge. Like I said, probiotics and yogurts have been on the shelves for decades. When we first started this company, we said, “Okay, we’ll need R&D for innovation, and then we’ll just outsource. Once we know which strains we want to grow, we’ll just outsource to these manufacturing companies to make the strains for us.” And when we did that, and went all around the globe looking for manufacturers, everybody sent us back dead strains because all of the manufacturing out there right now doesn’t have this. Okay, no oxygen can enter the system, kind of a requirement. And so, they were growing them in their normal ways of growing them, and all these guys were dying. And so, what we ended up realizing is that if we really want to get this company kicked off, and we’re an early-stage startup, every day matters. 

[00:15:32] And so, we had to figure out how to manufacture them ourselves. And so, we ended up having to build our own manufacturing plant and an entirely new innovative system for how to grow these microbes, where you are trying to mimic their environment. And remember, they not only– it needs to be oxygen free, but these guys are used to being in an ecosystem with a bunch of other things. And so, it’s like when you have a garden or you’re taking something out of a rainforest and you’re saying, “Now I want it to grow by itself in my kitchen, that is a whole new set of environmental factors that you have to take into consideration.” So, we ended up building our own manufacturing plant. And even just keeping these things alive through manufacturing is really important. But on the other side of that, the most important thing is that you can deliver these to people, they have to get back to that distal colon, they have to revitalize, and they have to perform activities that you want them to perform. 

[00:16:22] So you’re taking something out of a system, you’re growing it in this artificial system, you’re putting it back in and you’re saying, “Do what you normally do.” And so, I think every one of those steps we didn’t realize was going to be a challenge. But every one of them you have to do perfectly if you actually want to be able to deliver people these microbes that give them back these functions. And so, it ended up being almost eight years of R&D work that we were not anticipating. [laughs] 

Cynthia Thurlow: [00:16:46] That’s really an incredible process. And I think for a lot of people, they just assume that when they purchase, let’s say, a probiotic off the shelf, that everything in there is still alive and beneficial and helping people navigate, making good choices, whether it’s probiotic rich food as an example. But I would really love to talk about something that I think is poorly understood. I mean, there are polarizing, dogmatic people on social media that will say fiber isn’t important or you can get by without fiber. And I think both of us would agree that there’s some degree of bio-individuality. But let’s talk a little bit about what fiber, what is its role in the body? Why is it important? And how can we, I guess, capitalize on ensuring we are not only consuming the right types of foods that can facilitate the feeding the strains of bacteria in our body that are necessary to be able to have a healthy gut microbiome? And what are the things we need to be looking out for? 

Dr. Colleen Cutcliffe: [00:17:46] Sure. Well, I think it all kind of starts in our caveman cavewoman days, which is to remember that these microbes have coevolved with us over time. And so in those days, it was fruits and vegetables, berries and vegetables that we had the most access to. And so, the vast majority of microbes that are beneficial for our health that we’ve coevolved with, that’s their food, that’s what they rely on. They’re not used to seeing processed foods and fake sugars and all of these things that we’ve created in the last decade or last two decades. But that’s not the timeline of evolution for these microbes. And so these high-fiber foods are really important because they are feeding these strains that then metabolize that fiber and convert them into things that are actually integrated with our own signaling system. 

[00:18:33] And in fact, there are certain fibers that our bodies, we actually can’t metabolize on our own. So, we entirely rely on having these microbes to do that metabolism. And some of the important things that get produced on the other side of this metabolism are things that help us. These are called postbiotics, but things that really help us in our signaling of our gut lining. So, butyrate is a really important small molecule. We know that it’s really important for colonic health. And actually, there have been a lot of studies around its role to help prevent colon cancer. We know that these short chain fatty acids that get produced by the microbiome are really important for our gut lining, and we can get a little bit more into that and what it means to have a healthy gut lining and how you know when you don’t have one. But then probably something that people have started to really learn about lately is that your gut microbiome also produces these things that stimulate your body’s natural ability to produce GLP-1.

[00:19:24] And GLP-1 is a little bit of a hot topic. Now, although we’ve known about this small molecule for a long time, we haven’t really known all of its benefits. But one of the things that people don’t necessarily know is that GLP-1 is actually produced at your gut microbiome. And so, if you don’t have these gut microbes, your body is not producing GLP-1. And you’re getting all these downstream problems of heightened food cravings, you’re not getting good metabolism of sugars in your body. And so, it turns out that the fibers that you eat are all super important for feeding these microbes that then help you with your metabolism, help you with your gut lining, which helps you with your inflammation, your immune response, even your gut-brain connection. So, all of these other systems are dependent on you feeding those microbes. And I’ll just say this, which is that I think a lot of the reasons why people start to try to shy away from fibers or try to look for other things is that their bodies are sensitive to this. 

[00:20:16] Because one of the things that we’ve done also to ourselves is we don’t eat as many fibers as we probably should be eating. Most of us don’t. And so, because you’re not feeding those microbes, they now don’t exist in your microbiome. So now the fiber that you’re eating, there’s nobody in there to metabolize those. And so, then you end up getting GI distress, or you feel like you’re really sensitive to fibers. And the fact is that you then end up in this really bad negative loop where then you think, “Okay, I shouldn’t eat fibers.” So, then you’re really not feeding those strains, and then just continue to get more and more depleted. And there’s a step-in way to start to get access to these strains so that you can start consuming fibers, so that you can really feed these microbes and feed all these other systems. And so, I’ll just give that in terms of why people may be shy away from fibers, but that they really are helpful for these microbes. 

Cynthia Thurlow: [00:21:02] And I think that’s such an important point. And I like to use myself as the example because it makes it a little more tangible. When I had six weeks of antibiotics and antifungals, you better believe for at least 18 months, I loved vegetables, couldn’t eat vegetables, was full carnivore for nine months. And I used to tell my functional medicine doc, I know that the reason why I cannot tolerate this is my entire gut microbiome was obliterated appropriately given my circumstances. But I think many people will say, “Well, I have to be carnivore for the rest of my life because I get bloated, I have digestive distress, I don’t feel good when I eat vegetables, fruit, etc.” And I think it really speaks to the fact that there’s something going on that is making it harder for you tolerate these things. But it’s a sign that something is off. And to your point, you’re talking about how many things are impacted by an unhealthy gut microbiome. And from your perspective, what have been some of the signs or clues or complaints or concerns people will express when they are struggling with their gut microbiome not being fully optimized? 

Dr. Colleen Cutcliffe: [00:22:12] Well, it’s interesting because I think we often think about our gut microbiome as playing a role in our GI health. And so, one of the most common things where, you know, your microbiome has been disrupted are these GI symptoms. So, things like, gee I get diarrhea all the time, or I’m constipated all the time, or I have a lot of gas, or I feel bloated, my belly feels distended all of the time. And so, there’s all these kind of GI symptoms that are signals to you that your gut microbiome might be not optimal. But there’s other things too that we don’t necessarily connect to the microbiome. So, we know that there’s this gut metabolism axis. Your microbes are metabolizing your food. They are a really important part of a healthy metabolism. And so, you might find that, gee I started to gain weight more easily than I used to, or I have these food cravings that I didn’t used to have before, or maybe my food cravings are escalating and just getting worse over time. And then even we know that there’s this really important gut-brain connection. Your gut actually produces massive amounts of serotonin, GABA, dopamine, and these all go directly to the brain. There’s this vagus nerve that literally connects your gut to your brain. And so, as you start to feel things like, gee I feel more tired, I have brain fog, I have this post lunch slump, and it seems to be getting worse. These are all things that are also kind of indicators that your gut microbiome might be not optimal. 

Cynthia Thurlow: [00:23:35] Yeah. And I think these are important because I think for many individuals, they may have chronic digestive issues that they’re like, “Oh, I have a sensitive stomach, and it could be much larger than that. Or I’m middle aged, I’m not getting good sleep, this is why I have brain fog, or I’m going through perimenopause and menopause. This is why I’m having these symptoms. And it can be so much larger than that.” What are your thoughts on– because I had some questions that came in around greens powders, polyphenol powders. Are you a fan of these products? Do you think that they’re helpful if someone is struggling to get enough? And I’m not saying brands, I’m just going to say greens powders, polyphenol powders. Do you think that they can be helpful if someone is working diligently on gut health? Or do you think it’s more important that we’re actually consuming the food, chewing it up, swallowing it, and going through the whole digestive process, as opposed to a powder that’s mixed in liquids?

Dr. Colleen Cutcliffe: [00:24:28] Sure. Well, I think the goal is to get as many fibers into your system as you can. And of course, as we’ve talked about, the natural way for your body to get those is actually through the whole foods. So that produce section of the grocery store where you’ve got your fruits and your vegetables, that’s the best way. Now, not everybody can prep those foods in a way that is enjoyable to them, and not everybody has time to do that. And so, there are a lot of reasons why that might be really hard to do. So in that case, rather than just throwing our hands up, there are these supplements and these green powders and a variety of actually, these different mixes that you can mix with your water. I mean, Metamucil is probably, we’re not going to name brands, but that’s the oldest version of this. And now people started to add other things into those mixes, but all of those are beneficial for getting those prebiotics, those fiber parts into your body and help you boost those microbes. 

[00:25:22] And there have been studies showing that supplementing things like inulin and supplementing polyphenols can have a beneficial impact to your microbiome and feeding those bugs. So, I would say that whatever tools you need in your toolbox to get those fiber components in is great, starting with the fruits and vegetables straight from the grocery store and then going to those powders if that’s easier for you to get them in. All of that is better than kind of doing nothing. 

Cynthia Thurlow: [00:25:07] Yeah. And I think when we reflect on the standard American diet and how devoid it is of fiber, for some individuals, maybe having those polyphenol powders or a greens powder might be a stepping stone to eating more vegetables or finding things that they like and can add into their diet. Now, a concept that was new to me 10,12 years ago, but has now become much more mainstream for those who are dealing with extremes are fecal transplants. And I had several questions that came in around this in particular, and certainly when I was rounding in the hospital, I saw a lot of C. diff infection. So people that come in, especially the older population, people that are immunocompromised, they get put on antibiotics and they end up developing an overgrowth of a bacteria that actually does actually reside in the microbiome. And so, what has been your kind of evolution on the success rates and the importance for some individuals of having an actual fecal transplant, which has tremendous success rate, despite the fact there’s a strong ick factor for a lot of people? 

Dr. Colleen Cutcliffe: [00:26:50] Yes. So, the fecal transplants are exactly as they sound. It’s basically getting stool from one person into another person. And there have been a variety of ways in which people have tried to do that. And you’re right, the first really big, I think, indicator that this was going to be useful was for these C. diff infections. Clostridium difficile is a strain that, as you said, many of us have at low levels, and it’s no big deal. But you take antibiotic, you kill everybody off, except for, for some people, there’s some of this Clostridium difficile strain that doesn’t get killed off by the antibiotic. And then because there’s no competitors around all the food you’re eating, it’s basically growing and replicating and dividing and taking over your whole gut microbiome. And when that happens, it causes you to be really sick. Ultimately, actually, it’s fatal. And so, you really need to treat it. 

[00:27:38] And ironically, actually, the treatment for this, which you get from taking antibiotic, is actually more antibiotics to try to kill the strain. And so, there was this whole nother theory that came out, which is, “Okay, look, if the problem is that you’ve killed everybody off and now the guy has no competitors, what if we just inundate you with a whole new microbiome?” And that was really the theory behind the fecal transplant. And it turns out it is highly effective. And when you’re talking about ineffective is death on the other side, highly effective going from 70% success to 99% success is something where you don’t worry about the ick factor anymore. And so, I think that what that opened up for people and a scientist is this idea of, “Okay, well, can I use this fecal transplant concept in these other disease states, and can I actually help them?” So, getting outside of that case of Clostridium difficile infection, can I use it to treat all these other diseases?

[00:28:31] And so, these fecal microbiome transplants have been used for IBS, irritable bowel syndrome, for IBD, which Crohn’s disease, ulcerative colitis, they’ve been used for type 2 diabetes, they’ve been used for obesity, they’ve been used for even things like autism, people are starting to use them for. And so, what you see in there is that if this fecal transplant can actually help with resolution of symptoms and resolution of those diseases, then, you know, there’s something in there that’s conferring that benefit. So for us, the evolution of thought was there’s going to be safety concerns around giving people stool. I mean, that’s a legitimate safety concern. And as scientists, can we figure out, rather than giving someone the kitchen sink, what are the components in there that are really helping them, and then actually make a manufacturable product out of that? But these fecal transplants were the first indicator that there’s something in your microbiome that can cure you. 

Cynthia Thurlow: [00:29:24] I think it’s really fascinating. And from my understanding, it’s actually the enemas have the highest success rate, because, of course, the ick factor is high. And people were trying to create, I guess, oral capsules, which I can’t even fathom that, but for individuals who need that level of care or have that level of illness, I can imagine it could be life shifting for them. 

Dr. Colleen Cutcliffe: [00:29:45] Absolutely. And I mean, it’s funny because for a long time, the only FDA-approved microbiome intervention was stool transplants. [chuckles] And all the jokes can come in like, “Oh, I can’t believe we’re giving people that shit.” Surely, we can do better than this shit. [Cynthia laughs] And so, I think that really sparked a lot of people’s interest in how do we deduce what actually is helpful? 

Cynthia Thurlow: [00:30:07] Yeah, I think that’s really important. I would love to talk a little bit about the role of the vagus nerve and how it’s one of the longest nerves, if not the longest nerve in the body, communication between the gut-brain, because it’s only now that we’re really starting to speak up about this enteric second brain, how we have the bulk of our neurotransmitters that are produced in the gut microbiome, why it makes so much sense that we literally are what we eat, but how much it influences mood, depression, anxiety, as you mentioned, ADHD, and all these other factors. 

Dr. Colleen Cutcliffe: [00:30:39] Yeah. This vagus nerve and this relationship between our gut and our brain is still an emerging science, but a lot of really cool things have been discovered. So, first of all, as you mentioned, we produce things like dopamine, GABA, serotonin, all these important neurotransmitters that, in massive amounts, much more than the brain. Moreover, and I didn’t know this before we started looking into it, you have neurons in your brain, we all know that. And we also, many of us know that you kind of get what you get as they die, they don’t replenish. And so that’s sort of when they die, the end of that life. But you also have neurons in your gut. And the neurons in your gut, unlike the neurons in your brain, they’re constantly turning over and replenishing. And one of the most fascinating discoveries was that these things like Parkinson’s and Alzheimer’s disease, where the hallmark is you start to see these plaques show up in the brain and in these neuronal cells, these are sort of these black plaques that show up. And for a long time, I started my career developing drugs for Parkinson’s disease, and we focused, really on those plaques in the brain, and how can you get rid of them? Because they’re what’s kind of causing your brain neurons to not be able to signal to each other. And so, you got to get rid of these plaques. 

[00:31:43] One of the most fascinating discoveries was that people discovered that those plaques show up in your gut neurons before they show up in your brain neurons. And so, the new leading hypothesis is, okay, if you have these gut neurons and they start to develop these plaques, they’re then misfiring signals to the brain and really mobilizing those misfirings to the brain. And so, the gut becomes a really huge opportunity to even go after those diseases. And because your gut is constantly turning over these gut neurons, you can actually have a chance at fixing them. And so, it’s just a really, really exciting field. And then going from Parkinson’s and Alzheimer’s, which are really diseases of aging, all the way down to autism, which is really many people think of as a neurological disease that’s sort of genetic. 

[00:32:30] One of the most interesting things about autism is that many people will talk about how, when they change the diet or they find the optimal diet for their child, they’re actually able to reduce the symptoms of autism. And that really points to a gut microbiome role. It may not be for everybody, it may not be for all kids with autism, but there is an opportunity here to think about if the dietary change is causing a change in symptoms. It is almost certainly going through the microbiome. And so, what are these bugs that are actually doing that function that is. And a lot of these studies, they look at siblings, where if you have one sibling that is healthy and one sibling that has autism, what do their microbiomes look like? And what you can see is that even though they’re genetically very similar to each other, their microbiomes actually look really different. And so that’s another, I think, really fascinating area of science. 

Cynthia Thurlow: [00:33:20] No, absolutely. And for me, it’s really just reinforcing a lot of these lifestyle measures that things that we think, certainly as a traditional allopathic-trained provider, nutrition was, you know, just follow the USDA guide, food pyramid and close the door. That’s as much as you have to think or talk about nutrition. And yet it is so critically important. Thoughts on artificial sugars. I know there was that article in Nature that was comparing oral glucose tolerance testing and sucralose and aspartame and saccharine, and some of these kind of frequently utilized artificial sugars. What are your thoughts about the health of our gut microbiome and utilizing fake or lab-derived sugars? 

Dr. Colleen Cutcliffe: [00:34:02] Well, it’s funny, because since I have gotten to know Peter Attia, and he’s definitely a fan of these alternative sugars that don’t cause these significant blood glucose spikes, we’ve sort of been discussing back and forth kind of the pros and cons. I think, at a fundamental level, because our microbes have co-evolved with us, they’re not used to seeing these sugars. And so, their ability to metabolize them the same way that they can metabolize naturally occurring sugars, is depleted. And so, then the question becomes, well, so what? Is that really a problem? And I think that my understanding from Peter is that the way that people think about these artificial sugars is maybe too broad. So, people kind of bucket them altogether, but they’re actually quite different from each other. And so there may be kind of gold in those hills where a lot of these studies sort of show that artificial sweeteners are really bad for your microbiome. They cause your microbiome to become depleted. But I think what we need to be doing is looking at them at a more granular level, because there might be certain ones that are actually beneficial for us. So, I would say the jury is still out on artificial sweeteners. And if they kind of help you reduce the overload of sugar that you would otherwise be getting into your diet, they might have real benefit for your glucose system. So, the publications so far have shown that these nutritive sweeteners will– these artificial sweeteners will reduce the diversity of your gut microbiome. But I’m not sure that they’ve been run in maybe the most diligent way. 

Cynthia Thurlow: [00:35:25] Yeah. And I think if I recall from that Nature article, when it came out, I guess it was September of 2022, it was looking at a mouse model, at least initially. And so, you obviously, being the scientist, sometimes we love to extrapolate rodent data to humans, and sometimes I always remind people, “Yes, mouse models or rat models, they are mammals, but we are not equivalent.” And so, I think it’s one of those things where the jury is still out. I think that most, if not all, people have a palate exquisitely attuned to sugar. And so, finding ways to reduce the amount of sugar in your life, whether it be artificial or otherwise, is usually my best recommendation. Now, I would love to help differentiate, because I think there’s a lot of confusion about prebiotics, probiotics, postbiotics, and helping the Everyday Wellness community to understand how they work together, why they are all equally important, and how we can think about them from a systems level. 

Dr. Colleen Cutcliffe: [00:36:23] Sure. So, what we’ve been talking about here, these bacterial strains, these are the probiotics. And so, the probiotics are the strains themselves that perform all these functions. The prebiotics are the food that feed those strains. And so, examples of prebiotics are fibers, polyphenols and things like that that feed the bacterial strains and help them to grow. And then what these probiotics do, the reason why we think they’re interesting and why they’re important for our health is they manufacture and they produce and they secrete all these small molecules and proteins. And those are the postbiotics, and those postbiotics, those small molecules and those proteins integrate with our signaling system and are involved in things like our metabolism, our ability to metabolize sugars, our inflammatory response, our immune response. And so, the prebiotics are the food, the probiotics are the live strains themselves, and the postbiotics are what they generate. And so, at the end of the day, one might argue the postbiotics are the only thing that I really care about. But just taking those on their own are not as effective, actually, as these other two, the pre and the probiotics. 

Cynthia Thurlow: [00:37:24] And I think it’s important for people to realize that because there are a lot of what I believe are well-meaning supplement companies that are out there that are creating a lot of these postbiotics. And so probably the one that I think is most well-known is butyrate. And so perhaps helping people understand why is butyrate so significant, especially when we’re talking about short-chain fatty acids, what do they do in the body that makes them so significant, and why should we be focused on them? 

Dr. Colleen Cutcliffe: [00:37:48] Sure. So, butyrate is an incredibly, maybe one of the most important small molecules that your microbiome generates. And the first thing to know about your colon cells is that they’re the only cells in your body that use butyrate as their source of energy. Every other cell in your body uses glucose. Your colon cells use butyrate. And so that means that if you’re not getting enough butyrate, your colon cells aren’t getting enough energy essentially, and you’re not fueling them. And so, you start to have issues with colon health. And then, as I said, there have been a lot of studies linking a lack of butyrate to colon cancer. And so, they’re really important for your colonic cells. The other important thing about butyrate is that it stimulates your L-cells to produce GLP-1. And so GLP-1 is an important small molecule that tells your body to metabolize sugars and also tells your body that you’re full and you don’t need to eat any more food. 

[00:38:39] And so, butyrate is an important molecule. So, when you eat food you have these microbes that produce butyrate, and then butyrate stimulates your body to release this GLP-1 molecule, and then it starts to metabolize the sugars that you just ate and tells your body, “Okay, we’re full.” And then GLP-1 kind of goes away in the bloodstream until you eat again, and that system repeats itself. And so, butyrate is important for your metabolism, it’s important for your colon health, it’s important for your gut lining. The issue with taking a butyrate supplement is really tied to that thing that I said earlier about all the colon cells loving butyrate and I tell people, “Would you rather, if I were going to give you a million dollars, put it into a suitcase, deliver it to your front door and hand it to you?” Or would you rather I called you and said, “I just scattered your million dollars all over Highway 101?” You would much rather I deliver it to you, because you know what’s going to happen if I scattered all over 101? Everyone’s going to pull their cars over, they’re going to grab all your money. By the time you show up, it’s going to be gone. 

[00:39:29] And that’s literally what happens with these butyrate supplements. You take them while the butyrate is making its way to the receptor. That’s actually going to do all this awesome signaling for you. Every colon cell is grabbing that butyrate. And so, you have this problem, which is a delivery one that the butyrate never makes it to the receptor. And that’s why the efficacy of those supplements is never as good as what we see in the lab and never as good as what you see in animals where you can do that direct delivery. And so, it’s because everybody’s taking that butyrate and doesn’t get to the receptor. And that’s why the probiotics become really effective, because the probiotics will colonize literally right next to that receptor. So, when they produce the butyrate, it is that direct handoff, that suitcase is going right to the receptor and delivering the goods of the butyrate to it in the right location.

Cynthia Thurlow: [00:40:11] Yeah. And to me, it’s so interesting. I mean, obviously, GLP-1, the exogenous options are now all the rage. I mean, between interviewing multiple people here on the podcast, talking to clinicians that are prescribing them, it’s really having a moment. And my concern is always, what is the net impact on our endogenous GLP-1 secretion if we are taking these powerful drugs that are designed to hit us really quickly, as opposed to what I would imagine that when we’re talking about this GLP-1 pathway, it’s probably a more slow delivery and certainly very personalized depending on the individual. Now, what I find really interesting is the role of Akkermansia with this process as it pertains to butyrate and GLP-1 secretion. And so perhaps we can talk a little bit about that, because as I stated at the very beginning of our conversation, I just thought about Akkermansia as this mucus-loving, mucus-producing bacteria. And there’s so much more to it. 

Dr. Colleen Cutcliffe: [00:41:09] Absolutely. Well, I think maybe there’s three things to talk about with Akkermansia. The first is that it was just discovered in the early 2000s by Dr. Lee Kaplan at Harvard MGH. He’s a bariatric surgeon. And so, he was looking at why do people– what are the cause of all these weight loss? And really discovered Akkermansia as this important strain. So, since that discovery, the number of publications on Akkermansia has really been skyrocketing. And so, the first thing to know is that healthy people appear to have a lot of Akkermansia. And when you’re lower depleted with Akkermansia, it’s correlated to a wide variety of diseases, ranging from IBD and IBS, to type 2 diabetes, to Parkinson’s. And so, what has started to emerge is that Akkermansia is maybe a keystone strain. It maybe has an outsized function in the microbiome. 

[00:41:58] So, first of all, Akkermansia is a keystone strain. The second thing is that Akkermansia has this mucin-loving component to it. And I think we shouldn’t gloss over that. That’s actually super important, because the way that your gut lining works is almost like a wooden fence, where you have these planks, the planks are held together by glue. And what can happen over time is that glue can start to weaken, those planks can start to fall, and that really destroys your fence. Your gut lining is literally the exact same way. You have these epithelial cells, these are the planks, and they’re held together by glue, which is called mucin. And Akkermansia’ s job, it is the only strain that has ever been discovered whose job it is to regulate that glue. So it takes down the old glue when it gets old, and it actually stimulates new glue production. So, it can not only consume mucin, it also stimulates new mucin production. And so, its job is to keep that glue strong, because what happens is when that glue starts too thin or you have a thinning mucin layer, is these planks can start to fall and you lose these so-called tight junctions between your cells. And then you get what a lot of people call leaky gut. 

[00:42:56] But really the effective is that you don’t have tight junctions. You do have sort of these holes between the cells. And all the things that your gut microbiome is making can now leak across that lining into your bloodstream, causing heightened inflammatory responses, weird immune responses, and all these other problems. And so that gut lining, the core of the gut lining, the only strain that’s ever been discovered that regulates the glue is Akkermansia. So that’s the second thing about Akkermansia. 

[00:43:22] And then the third thing about Akkermansia. So it’s a keystone strain, it regulates your gut lining. And the third thing is that everyone has sort of known that butyrate can help stimulate GLP-1 production. But there have been recent studies that have shown that Akkermansia can directly stimulate GLP-1production because it secretes this protein called P9. This is one of those postbiotics. It secretes this protein called P9 which binds directly to your L-cells and stimulates GLP-1 production. Akkermansia also produces a short-chain fatty acid called propionate, which can be converted into butyrate, which also binds to your L-cells and stimulates GLP-1 production. So, it has two different ways in which it can directly stimulate GLP-1 production. And I think the important thing for people to know is that you have these L-cells, they’re just holding GLP-1 in them. And so, without Akkermansia, they’re going to keep holding them. But with Akkermansia, we know that it can now tell those cells to release GLP-1 into your bloodstream. And then you get all these benefits of satiety and blood glucose metabolism. And so that’s the third thing is Akkermansia plays an important role in stimulating GLP-1 and in our metabolism.

[00:44:24] So, it is quickly becoming in the scientific community, one of the most important strains. And it’s really hard to grow because not only does it have this no oxygen component, but it also has to consume mucin and live in this weird environment where it’s with the glue and all of its role there. And so there have been people trying to market dead Akkermansia. There are people who are selling Akkermansia on Amazon that aren’t even Akkermansia at all. And so unfortunately, in the supplements business, you don’t have the same type of tight regulation that you do in drugs. And so for the consumer, when you go into Amazon, I get asked this question all the time. They’re like, “What about all these other people selling Akkermansia?” We literally have sequenced these things and look into them, and most of them don’t even have any traces of Akkermansia. And the other ones have dead Akkermansia in them. And so it’s really hard for people who are trying to do the right thing to actually find the right product. And so, I’ll just give that warning out there to everybody who’s going to listen to this and then go onto Amazon and just be like, “Which one should I buy?” [chuckles] 

Cynthia Thurlow: [00:45:23] Right, exactly. And it’s interesting. I think one of the things I heard you say is, what is fakerrmansia or fake Akkermansia? Meaning to your point that there are always people out there that want to capitalize on the advances that are going on with the gut microbiome. And so, I think that this is where let the buyer beware. And certainly, your company which is Pendulum Therapeutics, and I can now share with the community that one of my cousins has been taking your product. And we were having a conversation yesterday and she said, “This is the first thing that’s helped my gut in 15 years of being on antibiotics.” And so, I don’t take that lightly because she’s a physician. And so, if people are interested in purchasing Akkermansia, is it most efficacious to take the supplement? Are there foods that can help with that process? I mean, that’s the other thing is that I think what I know of things like Concord grape juice and pomegranate juice, there are some properties, but you probably would have to consume quite a bit of it. And it’s also juice, which is not necessarily the healthiest thing to consume. 

Dr. Colleen Cutcliffe: [00:46:24] Yes. So, there have been a lot of studies showing that you can boost your Akkermansia levels with soluble fibers. So specifically, inulin and so you can find inulin in Jerusalem artichokes, also known as sunchokes, they have really high content of inulin, but also things like asparagus, kind of any of your leafy greens that you’re seeing in the produce section. So, all of those greens, those vegetables can be a good source of inulin that help bolster Akkermansia production. The other type of foods that can help bolster Akkermansia are things that contain polyphenols. And so, this is a lot of your berries. So, pomegranates, cranberries, all of those have good polyphenol counts, but also red wine, dark chocolates, these also have high polyphenol counts. And so, you can get your polyphenols in some more enjoyable ways. [chuckles] And then there are polyphenol supplements. So, if it’s hard to get those fruits and vegetables into your diet again, you can use this other tool, which is to take the powder form. 

[00:47:18] We actually did a study across all these different polyphenol powders to look at which ones work best with our Akkermansia, and we found three of them work really well. So, we created actually a customized blend of polyphenols to help bolster this strain of Akkermansia. And so, you can take the Akkermansia probiotic. And then if you also supplement with foods that are high in fibers and high in polyphenols, that can help basically feed the Akkermansia so that it can really start to colonize and grow and flourish. 

Cynthia Thurlow: [00:47:44] And that’s really looking at it as a synergistic effect. And how long does it typically take when you’re taking this Akkermansia product to see improvements, like if someone’s having digestive issues, bloating, gas, diarrhea, constipation, is it fairly quick or is it over time that builds back up? 

Dr. Colleen Cutcliffe: [00:48:01] Well, I’m going to give the annoying answer-

Dr. Colleen Cutcliffe: [00:48:03] -which is that it depends. It really varies from person to person. It depends on what your starting microbiome looks like. It depends on what your diet looks like. And it depends on kind of how far along the illness that you are and how far back you’re trying to get your system. And so, for some people with GI distress, we’ve heard people report within days things are better for them in terms of these GI symptoms. And then for other people, it’s five to six months. And so, it really does depend on what your starting point is. And it also depends on whether you’re doing this kind of one, two punch of increasing these things in your nutrition and in your diet while also taking the pills, that can really accelerate the efficacy over just taking the probiotic by itself. And so I think, generally speaking though, I tell people give it 90 days to feel an impact. And the reason I say 90 days is because we know that if you change your diet, like you go from being an omnivore to a vegetarian, it takes about eight weeks before you see your new microbiome is really kind of established. 

[00:49:01] And so that’s kind of doing this really big whole hog change. We’re trying to introduce a specific strain or a specific formulation of strains into an existing ecosystem. So, give it another 30% of time. So, give it 90 days. And the other reason 90 days is sort of a key number is because your hemoglobin A1c cells, which is your measure of diabetes, they turn over every 90 days. And so that gives you a chance to actually see an A1c change. So, I say give it at least 90 days. Many people feel it much sooner than that. 

Cynthia Thurlow: [00:49:28] Well, it’s such an exciting and emerging field. One last question for you. So, for those of us that do quite a bit of travel, as I’m sure you probably do as well, what are some of the things that you do personally to help offset the net impact on your gut microbiome while you’re traveling? 

Dr. Colleen Cutcliffe: [00:49:42] Well, I think, again, it comes to nutrition. It’s really easy when you travel to slip and slide on that. And I think frankly, one of the most enjoyable things about travel is the food and the culinary experience of things that you’re not used to. But so, to the extent that you can try to be exploring new cuisines and new ways of cooking things that have fibers in them and have polyphenols in them, I think that’s helpful without kind of taking away from the enjoyment of the trip itself. So, I think trying to keep those things in your diet that are high in fibers and high in polyphenols is really important. I think the other thing is taking these probiotics with you and so that you are continuing– because we know that you can lose diversity, you can lose these strains when you’re traveling. 

[00:50:22] And so if you’re supplementing and giving them back to your body while you’re traveling, that’s going to help you kind of stabilize the changes that you’re going to be experiencing. And so, I think those are really important. And then probably one of the most important factors that really disrupts your ability to make good choices is sleep. And so, to the extent that you can try to get sleep even though there’s time changes, I think that’s really important. We all experience this. You don’t have to have a doctor tell you this, but when you don’t get enough sleep, you start to have different food cravings, and then you start down this cycle of, and those different food cravings don’t tend to be good ones. And so, trying to get good sleep is an important part of having the strength to be able to make good choices in food. 

Cynthia Thurlow: [00:50:58] Well, and I think those are certainly items that people can lean into that are certainly very accessible. Thank you so much for this conversation. I’ve learned so much preparing for this podcast. Please let listeners know how to connect with you, how to purchase your products and learn more about your company. 

Dr. Colleen Cutcliffe: [00:51:15] Absolutely. So, the number one place to get more information and to learn about the products is on our website, pendulumlife.com. And there you can learn about all these different strains. And I will say if there’s any healthcare providers on the call, we actually have a section specifically for you, which goes a little bit deeper into the science, which also goes into the clinical trials that we’re running and calling for. And if you are not a healthcare practitioner, but you’re like me, you love science, please go to that part of the website as well. And you can purchase all of our different products on the website. And actually, I think we have a code for your listeners today, which is THURLOW which gives people 20% off the first bottle of membership. But you can also purchase these products on Amazon, on walmart.com, and if you are a practitioner, we also sell them on Fullscript, which is a platform for practitioners. But our website, pendulumlife.com, is where you’re going to get the most information. We really welcome feedback and questions. The microbiome is a new science. We want to learn from you too what you’re experiencing. And so really excited to have this podcast come out and have more people come to the site and learn about the microbiome. 

Cynthia Thurlow: [00:52:16] No, like I said, I learned a lot while preparing for this, and I think that this is one of those opportunities for people to really better understand why diversity in our diet is so very important. Thank you again. 

Dr. Colleen Cutcliffe: [00:52:28] Thank you for having me. 

Cynthia Thurlow: [00:52:31] If you love this podcast episode, please leave a rating and review, subscribe and tell a friend.