The Tough Gut Playbook: Rebuilding Gut Resilience in IBS-Prone Patients

More and more in practice, we’re working with what I often think of as “tough guts,” patients arriving on increasingly restricted diets, afraid to expand foods because nearly everything seems to trigger symptoms. A big part of our work now is helping rebuild resilience: restoring dietary diversity, supporting the microbiome, and getting people back to eating, and living more fully again.

That’s one reason I was so glad to welcome Colleen Cutcliffe back to the podcast. I’ve long admired Pendulum’s philosophy of supporting the microbiome as an ecosystem rather than chasing quick fixes. This conversation really reflects the direction many of us are moving clinically, toward rebuilding function, flexibility, and long-term resilience for our patients. ~DrKF

The rising prevalence of IBS, metabolic dysfunction, and diet-related gut sensitivity has renewed clinical focus on the gut microbiome as a driver of systemic health. In this episode of New Frontiers in Functional Medicine, Dr. Kara Fitzgerald speaks with Colleen Cutcliffe, PhD, CEO and co-founder of Pendulum Therapeutics, about emerging microbiome science and the practical challenges clinicians face when working with patients experiencing microbial depletion and reduced gut resilience.

Together, they explore how targeted probiotic strains and complementary prebiotic fibers may support microbial balance, metabolic regulation, and dietary tolerance. Clinicians will gain insight into mechanisms linking fiber diversity, keystone microbes such as Akkermansia, and gut resilience, along with practical strategies to improve adherence, expand diet diversity, and support measurable outcomes in functional medicine practice.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi everybody, welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And of course, today is no exception. I am thrilled to be back with my long-time friend and frequent podcast guest, Dr. Colleen Cutliffe. Today we’re going to be talking about all things fiber, but creatively designed and likely essential for most of our patients in this era of tough guts. So say goodbye to the formulations of the past and listen to this conversation and especially how it synergizes with the greater family of Pendulum products. I am excited about the potential for this FODMAP friendly, creative, and important product to bring it to the toughest guts, but also just for those of us, including myself, who are just seeking good health.

Dr. Kara Fitzgerald: Colleen is a PhD, she is CEO and co-founder of Pendulum Therapeutics. She’s been at the forefront of translating microbiome science into real therapeutic applications for metabolic health and beyond. She’s worked hands on in everything from sequencing technologies to drug development. And now she takes her copious skills and brain and she’s brought them to Pendulum Therapeutics and they’re up to some amazing stuff. She understands the science deeply and she understands what it takes to move it into real world clinical tools. I hope you enjoy this podcast.

Dr. Kara Fitzgerald: It is always a super pleasure to get to hang out with Colleen Cutcliffe, the founder, CEO, wearer of many hats from Pendulum. I have quite a few podcasts with her and we’ll park all of them in the show notes if you want to go back. I just love to tell our backstory. I’m going to say it in five seconds. I started stalking Colleen and Pendulum because they were the people who figured out how to stabilize Akkermansia, a keystone strain in our gastrointestinal tract, an essential, essential player and healthy gut, and she and I have been conversing on this ever since.

Dr. Kara Fitzgerald: I’m a personal fan. I take my Pendulum Glucose Control every day and I prescribe it to the majority of my patients. I think the collection of probiotics that they’ve put a ton of energy in figuring out is very, very important and frankly, revolutionary. Colleen and team continue to put energy into expanding the Pendulum universe to optimize gut health. And so you’re with me again Dr. Cutcliffe, to talk to us about where you guys are at now. So tell me, tell me who’s coming to the Pendulum family.

Colleen Cutcliffe, PhD: Well, thanks so much for having me. And Kara, thanks for being ahead of the microbiome before we even existed. I think you were already interested in a lot of the products that we ended up building. I think it’s an exciting time, as people have started to learn a lot more about gut health, a lot more about the microbiome and bringing new tools to market. And we were just talking about how really good nutrition is such an important cornerstone to getting all your fibers and your polyphenols and all of this into your diet while also having a strong microbiome. But for those of us who can’t always get this amazing farm-to-table dinner in place, and all the veggies that we need, what we’re trying to do at Pendulum is to help people replenish the things that they’re not going to be able to get very easily.

Colleen Cutcliffe, PhD: And actually, some things we actually don’t even know how you can get back, but other things, it’s just about trying to help people be healthier in what is a relatively unhealthy time in human history. And so we’re very excited to help with this with the new product that we’re going to be releasing. We’re really excited to be helping with this challenge of trying to get all the dietary fibers and the diversity of fibers and polyphenols that are really going to be important for supporting next generation gut microbes. So, I’m excited to talk to you about that today and why the diversity of these different prebiotics is so important and why next-generation strains are so important as we talk about the Gut Fuel product.

Dr. Kara Fitzgerald: You know, just in preparation for this, thinking about Gut Fuel and the combination and using it in conjunction with your next generation strains, using it in conjunction with Akkermansia—and again, we’ll park our previous conversations in the show notes—But it’s just a key player in maintaining mucosal barrier integrity. Akkemansia, along with its sister probiotics, if you will, are essential, actually, in stimulating GLP-1 production. I mean, you’re figuring out this ecosystem for optimal gut health and I want you to walk us through Gut Fuel.

Dr. Kara Fitzgerald: But anyway, as I was preparing for this, I was thinking about the fact that, indeed, we are in a tough gut epidemic. And when we look at stats, it made me think about colon cancer. There’s just this meteoric rise in damaged, problematic, you know, all the way to colon cancer. Just in my clinic practice, it’s a world of really challenging guts, so we need these support products, and really, kind of, going back to the drawing board. Anyway, you put together Gut Fuel, so talk to me about what it is and how we as clinicians are going to think about it and use it.

Colleen Cutcliffe, PhD: Sure, and just to add on to what you were saying, this is one of the hardest times to have a healthy gut. And one of the things that we’ve learned is that even if at some point you had a healthy gut, you could eat or drink whatever you wanted to, you had a really resilient gut, things didn’t make you sick, over time, and through a lot of the things that we do, we start to lose the diversity of our gut microbiome.

Colleen Cutcliffe, PhD: We know that when we take antibiotics, that causes our microbiome to become depleted. We know when we change our diet, that can cause our microbiome to become depleted. We know simply as we age, our microbiome can become depleted. We know when we go through periods of stress, our microbiome becomes depleted. We know that when we travel, our circadian rhythm changes. The last time you traveled and you had to change your time zone, that caused your microbiome to become depleted. And we know for us women, when we go through menopause, our microbiome becomes depleted.

Colleen Cutcliffe, PhD: So, there are all these things that are causing our microbiome to become depleted. And the beauty of it is that now science has uncovered what are those depletions. And then what we are working on is, well, how do we replenish those to give people back those full functions? And one of the most important things that we become depleted in is these next-generation strains. Gut Fuel is a designer prebiotic formulation that has a diverse set of fibers and polyphenols that are there to feed your next-generation strains. We very specifically handpicked the five key ingredients in Gut Fuel.

Colleen Cutcliffe, PhD: They are resistant potato starch that is really helping you with your blood sugars and also is known to fuel Akkermansia growth. It has oat beta-glucan, which has a lot of really strong evidence around not only metabolic health, but also cardiovascular health. It has baobab, which feeds all of our butyrate producers in our gut, which are really important for your colonic health. We have grape seed extract, which is the polyphenols, which have actually documented and published data around supporting Akkermansia growth, in addition to all the antioxidant and beneficial impacts of polyphenols. And then the last one is Acacia, which is really one of these more gentle fibers that has good data supporting gut lining benefits. And so these five ingredients are really intentionally selected to help you with metabolic health, cardiovascular health, overall gut health, and the growth of Akkermansia and butyrate-producing strains.

Dr. Kara Fitzgerald: Awesome. You covered a lot of bases in one product. Why did you opt to go in this direction versus coming up with another probiotic?

Colleen Cutcliffe, PhD: We spend a lot of time talking about next-generation strains like Akkermansia, Clostridium butyricum, and I think it’s important to replenish those strains. But I spend just as much time talking to people about what are the foods that you can eat to really help feed these strains, and so let’s talk about the grocery store and where we should be shopping in all those different aisles. And it just occurred to me when I talk to people, a lot of times people are like, are you kidding me? I’m not going to be able to get all these lentils, and these vegetables, and these fruits, and these spices. I can’t do that at every meal. And so it just felt like there was a gap. I mean, there’s a gap in our lifestyles that we want to help fill.

Colleen Cutcliffe, PhD: So that was sort of the inspiration, is how do we give people the one-two punch? The one-two punch of the prebiotic and the probiotics to help them really improve gut health. And that was the inspiration. I think a lot of people are trying to do their best with eating well, but this is just helping you do even better.

Dr. Kara Fitzgerald: Yeah, and it’s a really nice selection, a compliment of variety, the whole map of fibers and we could go on. Each of them has quite a good body of science, I think, even beyond what you mentioned. So it’s going to be stoking locally. It’s going to be acting on the microbiome and supporting the maintenance of our keystone strains, including Akkermansia. And people always ask me, you know, do I need to stay on my Akkermansia forever? And the reality is maybe not. You know, when we track it and we measure it and certainly using interventions that you’ve demonstrated will support Akkermansia production is going to lead some of our people off of it.

Dr. Kara Fitzgerald: Personally, I have opted for keeping my A1C nice and dialed in to continue on Pendulum’s Glucose Control for the long haul. I haven’t stopped it, but I’m okay with taking a bunch of supplements every day. There’s plenty of us on the planet who would like to usher ourselves off of their little cocktail of supplements. This is also really well tolerated. I mean, you purposely designed it for the most sensitive gut. Speak about that.

Colleen Cutcliffe, PhD: Yeah, absolutely. There’s a growing population of people struggling with irritable bowel syndrome, IBS. Actually, about a third of Americans have IBS and most people don’t even know it. But if you find that when you eat certain foods, you get these digestive issues, and for a lot of people, those foods are actually good for them, so salads, for example. When people go to the produce section and just fill up on salads and you’re someone who’s like, hey, when I eat a lot of salad, it actually makes me feel sick. I get all these digestive issues, you probably have IBS. And it’s because your body’s not able to metabolize those fibers in the way that they’re being delivered to you.

Colleen Cutcliffe, PhD: This is a growing problem here in the United States as well as globally and so we wanted to solve for that. And actually, I would add to that, for a lot of people who are trying to do fiber supplements, they also find that those fiber supplements can really upset their stomachs and so we really wanted to solve for that. We wanted to help people who need to get more fiber into their diet, but your stomach is sensitive to those fibers. And that’s a growing number of us so we deliberately chose these ingredients that are what’s called low FODMAP. And if you know what low FODMAP is, you know what low FODMAP is and I’m sorry for you.

Colleen Cutcliffe, PhD: If you don’t know what low FODMAP is, that’s probably great. That means you don’t have all these GI issues. But I think we’re going to find that people are going to learn what low FODMAP means over time. It’s going to become more and more popularized, because what that does is it allows you to get the fibers that you need but without all that GI discomfort. And so this Gut Fuel formulation is low FODMAP. If you have a sensitive stomach to all these different vegetables and fruits, if you have a sensitive stomach to these other fiber supplements, then Gut Fuel is your solution because it’s a low FODMAP formulation.

Dr. Kara Fitzgerald: And I would say, just going back to the tough gut paradigm that we exist in, the majority of my patients just struggle with gut issues. You know, small intestinal bacterial overgrowth, is sort of the original reason we were prescribing low-FODMAP diets, but SIBO intersects with IBS and we were just talking about, the uptick in colon cancer, but just the gamut of really damaged, very challenging guts is amongst us. When I first started practicing as a clinician, you pull somebody off a gluten and dairy, boom, home free. Boom, you’re done. We didn’t experience the kinds of guts that we’re experiencing now.

Dr. Kara Fitzgerald: So in less than two decades, there’s this massive transformation of guts. Back then, taking somebody off of gluten and dairy was a huge deal. Nobody thought of it. Now people come to me on these microdiets. They’re so sensitive and they’re terrified to expand the diet, but of course they have to. They can develop mild malnutrition just because they have these incredibly tough guts. So we’re always, always thinking in FODMAP terms for many of our patients, and to your point, ensuring that they have adequate and appropriate and tolerable fiber is a hard, hard lift. So the fact that you guys did it, that you pulled together this low FODMAP Gut Fuel product is awesome. It’s really cool.

Colleen Cutcliffe, PhD: Yeah, and it was hard too, because some of the fibers that have the most evidence behind them, the most clinical trials behind them, don’t fall in this category of low FODMAP. So, I think we’re seeing two things happening here. One is that it used to be that people got more sensitive guts as they age, but now people in their 20s, teenagers, are having gut sensitivities, and so we really do need to have solutions for that. So again, if you’re somebody who, when you eat a bunch of salad, it really upsets your stomach, when you’re eating a bunch of beans, it really upsets your stomach, you’re trying to get all these fibers in, but you’re afraid to eat, en masse, these different foods that actually create digestive issues. You should be looking into and looking up low FODMAP and you should be looking for low FODMAP fiber supplementation. That is really the goal. So one is, we’re seeing a lot younger people dealing with this issue. And number two, all the solutions that are out there, all the foods that are high in fiber, beans, lentils, salads, and then fiber supplements, are not helping any of these folks.

Dr. Kara Fitzgerald: Right, and so they just move away further and further to more and more processed foods, or the diet becomes really greatly curtailed. I mean, we do see malnutrition in practice more routinely among a population who is striving towards health just because they haven’t been able to get to the other side of their gut issues.

Colleen Cutcliffe, PhD: Yeah, yeah, that’s crazy. You’re right. It’s insane to think that here in the US, somebody with means would ever be dealing with malnutrition. But I think, to your point, it’s because you’re trying to steer clear of the things that are causing you gut issues. But then you’re creating another problem, which is you’re reducing the diversity of your microbiome.

Dr. Kara Fitzgerald: Yes, exactly. Right, and we just pick it up. I mean, most of us are doing functional medicine stool testing, or we might be doing SIBO breath test and kind of marrying that to the symptom picture. And it can be really challenging to turn around. And I think once dysbiosis kicks in and once you’re sort of contorting yourself to eat a diet that you can tolerate, it snowballs and things can get more and more challenging.

Colleen Cutcliffe, PhD: Yeah, it’s a really bad cycle. That’s exactly right. So all of a sudden you realize, my gut is sensitive to these foods, so then you start cutting out those foods. And now you’ve depleted your microbiome so you have less diversity of those microbes that could actually metabolize those foods. And you end up in this cycle of, now there’s fewer and fewer things that I can eat, and it’s frankly less and less enjoyable to cook, to eat, to be with friends, because all of sudden your diet becomes so limited and constrained. And the good news is that you can start to rebuild your microbiome to get that resilience back to these foods. And that’s really what we’re tackling here with Gut Fuel as well.

Dr. Kara Fitzgerald: Awesome. As you were talking about that I’m reminded of a lovely patient that I’ve been working with for years. And she’s really doing fabulously, but at her first visit to my office, her husband was crying. It was such an emotional meeting. They hadn’t been able to go out to eat in years because she was on this really, really restrictive diet. She couldn’t tolerate anything and it was heartbreaking for them, you know, the struggle. So bit by bit, we’ve rebuilt her and yeah, they’re back to experiencing a full life. She’s experiencing a full dietary pattern. And that’s something that we’re doing as clinicians more and more now. And, of course, we have to start out low FODMAP, but how do you see Gut Fuel… So, I’ve got this patient who I just described, how do we introduce Gut Fuel for these guys.

Colleen Cutcliffe, PhD: I think if you have a sensitive stomach and you’re not getting a lot of fiber into your diet, you can introduce Gut Fuel little by little. But really, we designed Gut Fuel to turn any of the foods that you’re eating into superfoods. Of course, there’s a daily dose that gets you your excellent source of fiber and all of that, but the idea is you just put some of this into the food that you’re eating, and bam, you’ve turned whatever you’re eating into something better— a food into a superfood. And so I think if it’s from your morning shake, to your afternoon yogurt parfait, to your dinner, to your desserts, all of this is intended to just give people that little edge. We’re just giving you a little edge so that everything you’re doing is just a little bit better. And that’s really what Gut Fuel is. Sprinkle a little bit on top of whatever you’re doing and you’ve turned what you’re doing now into something even better for you.

Colleen Cutcliffe, PhD: One of the other big targets we’ve gone after with this product is kids. If you’ve ever tried to feed a kid the appropriate amount of fiber, it is really hard. It’s really hard. They don’t like that. They like their sweet treats, they like gummies, they like all these things that are not really great fiber sources. Kids four and up can consume this formulation, and again, for parents, whatever your kid loves. When my kids were little, they could eat yogurt all day and all night and so mix some of this into the yogurt, and you’ve now got not only the benefits of yogurt, but also now you’ve gotten them some of their fiber in. Brownies, you know, but now you’re really able to get fiber in and so you can feel a little bit of relief in knowing that, okay, the things that they’re eating, I’m turning that into a better-for-them snack or treat, and now you can actually get that daily fiber into their bodies. And what you’re doing as a parent when you can get the fiber into your kids, is you’re setting them up not just for today, but for long-term health. And that is, I think, a huge gift that we can give to our kids, and this is just a hacky way to do it.

Dr. Kara Fitzgerald: Yeah, there’s all sorts of ways. Isabella is really into sourdough toast right now, so sprinkling a little bit on that or doing it with pancakes. She’s pretty hip to pancakes as well. Easy.

Colleen Cutcliffe, PhD: Oh, pancakes, perfect. Yeah, they all love all the white foods.

Dr. Kara Fitzgerald: That’s right. That’s right. What about using this in combination with Glucose Control or Metabolic Daily?

Colleen Cutcliffe, PhD: Yeah, and I would actually recommend that. If you’re just starting on your gut health journey and you are trying to replenish these next generation strains, I would do sort of a 90-day challenge. I would take your Glucose Control or your Metabolic Daily, and I would pair it with Gut Fuel and do this for 90 days. Because Gut Fuel, it literally is, as the name suggests, it’s the fuel for your microbes and so that’s really a one-two punch. Now, to your point about colonization or about, gee, do you have to be on these things forever? In a lot of ways, we design Gut Fuel so that you don’t necessarily have to take the probiotics once you’ve gotten them colonized. The Gut Fuel then becomes the food. And so this is why adding it to any of your foods is the concept behind it. You’re already cooking anyway, you just have the Gut Fuel on your countertop and you add it to whatever you’re making, and now you have given yourself stuff that’s going to replenish these next generation strains.

Colleen Cutcliffe, PhD: Ideally, you take them together because you’ve got the food and the microbes. And I think about this like a high-performing car. If you have this amazing car, there’s two important parts to your car besides how it looks. It’s the engine that you’ve got and it’s the top of the line fuel that you put in the car. You don’t take a top notch engine and put in the lowest grade of fuel. And likewise, you can put in the best fuel, but you don’t have a great engine. That’s not going to help. So you really need both of these. And your microbiome, the probiotics, that’s the engine and the fuel is literally this Gut Fuel, the prebiotic. So if you’ve got the Gut Fuel prebiotics, plus the Pendulum Metabolic Daily probiotics, now you’ve got a high-performing body.

Dr. Kara Fitzgerald: And 90 days is the anticipated turnaround time?

Colleen Cutcliffe, PhD: I think 90 days is a good amount, but of course every person varies. Some people can feel a difference within days, and some people it takes longer than 90 days. But I always recommend 90 days to people to really get your gut health back in place and you ought to feel it showing up in a variety of ways. If you’re measuring your A1C, or you’re measuring your blood glucose spikes, or you’re measuring inflammatory markers, or you’re measuring your gut microbiome, you’ll see all of those come out of your measurements. But you will also start to feel things.

Colleen Cutcliffe, PhD: So if you’re just bringing some awareness to your body, you can start to feel improvements in digestion, you’re able to eat foods that you weren’t able to eat before. You have sustained energy, meaning you don’t get post-lunch slumps, you don’t get this brain fog that kicks in in the middle of the afternoon. And so you’ll start to feel all of these improvements to your gut and your overall health when you are giving your body the right prebiotics and probiotics and really amplifying your gut health.

Dr. Kara Fitzgerald: So you would anticipate combining Gut Fuel with Metabolic Daily, one of the probiotics that we’ll talk about, actually, because you’ve just reformulated it, or Glucose Control, the one that I’ve been using for years. Combining these, might we see a potentiation of the probiotics? As you know, I’ve been a huge fan of Glucose Control because I dropped my A1C considerably. Not quite to the same extent that Halle Berry did when she shared that with us, but pretty darn fabulous for me. It’s five and I mean, who’s going to argue with an A1C of five? But we might potentiate that. And we also know that the ingredients in both Glucose Control and Metabolic Daily help stimulate synthesis of GLP-1. So in concert, in that it’s going to support survival time of these organisms and the redevelopment of those endogenous players that we’ve got living in our gut, we could see some of the clinical benefits stoked by Gut Fuel.

Colleen Cutcliffe, PhD: Yeah, and what we know, not just through our work, but the work of lots of people, is that if you can increase someone’s dietary fiber, especially the diversity of their fibers and polyphenols, you do increase the presence of these strains. There’s literally thousands of publications showing that through diet alone, you can increase these strains. And so, absolutely, if you do the combination, it really is a one-two punch. You’re giving your body the best chance in the shortest amount of time to see the most impact. So I think doing them together makes the most sense. Now, do you have to stay on them together for the rest of your life? Hopefully not.

Colleen Cutcliffe, PhD: But in the case where you’ve got either genetic predispositions, or dietary predispositions, or lifestyle predispositions that are always pushing your microbiome to become depleted in these strains, it might just be easier to stay on all of them. And I’m like that, where I know that when I go off of these, even though I try to have a high-fiber, high-polyphenol diet, when I go off of the strains, there’s something about my body that’s just predisposed to depleting them. And I feel it. So I think if you’re that kind of person, there’s no shame in it, it just means that for whatever reason your body is your body and you need to keep replenishing them.

Dr. Kara Fitzgerald: That’s right. Yeah. Farm to capsule, as we were talking about earlier. Farm to capsule because it’s hard, and you know, we started the conversation talking about tough guts and you listed all of the reasons that all of us are experiencing… You know, we’re required to take some kind of medication or a cocktail of medications that have depleted our guts. We’re super stressed out, we’re traveling, we don’t have access to the kinds of foods that we need. Or you already have a sensitivity and so your diet has become just this micro dietary pattern that is inadequate. So there’s a lot of reasons why one might just opt to stay on it.

Colleen Cutcliffe, PhD: Yeah. It’s all those reasons we talked about before that cause you to become depleted. So yeah, if you ever have to go on an antibiotic, if you ever get stressed out, if you are aging, if you are traveling, these are all things where, yeah, you could hole up and not expose yourself to any of those things. But I think that’s awfully hard for a lot of us to do. And diet is another thing. Even though we try our best to eat as good of a diet as possible, food and community and love all go hand in hand with each other, and nobody wants to be that person at a party being like, well, I can eat that, I can’t eat that, I’m not touching that. Part of our community is sharing food with each other and so I think that also makes it kind of tricky sometimes for people.

Dr. Kara Fitzgerald: Yeah, and to get the collection of fibers that you guys put together would take some effort. Like, how much potato salad can you eat, really? Right? I mean, seriously.

Colleen Cutcliffe, PhD: Well, and with that comes all the mayo.

Dr. Kara Fitzgerald: You know, my mom is this exquisite fiber mixer and she has these concoctions in many, many, bags in her freezer of all sorts of stuff that she combines. And she uses Metabolic Daily too, but she puts a lot of energy into it. Way more than I will ever put into accessing a varied fiber-dense diet. I’m forever impressed with her. For me, having it done is way, way easier.

Colleen Cutcliffe, PhD: And I think that’s right. I think for many of us, we know that if you put in the effort, you could figure all this stuff out, but how can you just give yourself an edge? How can you just take the things that you’re doing and get more out of them every day?

Dr. Kara Fitzgerald: Yeah, yeah. What’s the protocol? Do we want to deliver this multiple times per day? Can we get away with once a day?

Colleen Cutcliffe, PhD: I would say you should use it in whatever way fits into your lifestyle. So if you’re like, hey, every morning I have a routine and I’m going to add this in a full dose to whatever my morning breakfast is, awesome, great. If you’re like me and you’re just like, all throughout the day I’m just going to figure out little ways to put this thing on. It’s like how many of us add salt or sugar, butter, whatever. There’s that old saying, butter makes it better. I think Gut Fuel makes it better. So I think there’s opportunity for that too. And we just had somebody do a kind of fun taste test here at Pendulum. She made banana bread, and one loaf was with Gut Fuel, and one was without Gut Fuel. And of course, she’s a scientist, so she made one batch of the bread and then just divided it in half before she went to bake it, and you really couldn’t tell the difference. You really couldn’t tell the difference. But you knew that sample number two was just a better-for-you banana bread.

Dr. Kara Fitzgerald: Yeah, that’s so cool. Well, I can tell from the list of of ingredients, none of them are harsh and you’re not going to be running to the bathroom in dire pain like you might if you had added psyllium. What are some of the players that you definitely stayed away from?

Colleen Cutcliffe, PhD: Well, the psyllium husk is a great one. I mean, that is an ingredient that’s been around for a long, long time and people have had wonderful clinical trial outcomes with psyllium husk and its ability to help improve both metabolic and cardiovascular health. But it’s one of the hardest things to actually consume in bulk and not be parked in the bathroom all day long. So I think psyllium husk is tricky that way for most people, but not for everybody. Inulin is another one. There’s so much data behind inulin and how wonderful it is for you. And actually, inulin also has this sidebar perk, which is that it’s got a little bit of a sweet taste to it, so when you add it to things it’s lovely. Unless you are sensitive to inulin and then it’s a nightmare for you. It’s a nightmare for your digestion. And a lot of people are sensitive to things like psyllium husk and inulin.

Dr. Kara Fitzgerald: Yes.

Colleen Cutcliffe, PhD: Even at very low amounts. Now try to imagine you’re actually trying to get your full dose of fiber in. That makes it really hard. So even though I love those ingredients from a scientific perspective, from a usability perspective, and we’re really trying to help people improve their health, there’s just too many people who can’t tolerate those ingredients, and so we steered clear of them for that reason.

Dr. Kara Fitzgerald: It makes sense. I don’t know if you remember, Starbucks came out with a bar for a while that was inulin sweetened. They did for about 20 minutes. I’m probably the only human who remembers this. They were really good, but they were intolerable and I’m sure that’s why they ended up getting rid of them.

Colleen Cutcliffe, PhD: Oh, I’m sure. That’s the last thing you want is that you’re trying to be healthy and then you feel sick all day. And that’s the thing too, Kara, is you might not know that you’re sensitive to these ingredients, but what we do know is that epidemiologically, more and more people are becoming sensitive. And so you’ve got to help people figure out, okay, well, how do I get my fiber if those things make me feel sick?

Dr. Kara Fitzgerald: The other piece, and we’ve addressed this, but I want to just underscore it a million times—and I know the the clinicians listening will be able to relate to it—is that our job, as often as not, is expanding people’s diets. It’s getting them back into a normal dietary pattern where, to your point, they can go out and eat what’s at the party and tolerate it and not be running to bathroom or not have to bring their own little stash of food, cetera, et cetera. This is something that’s very much a phenomenon: this limited ability to consume a varied diet is a real entity in our work in functional medicine.

Dr. Kara Fitzgerald: So starting with this and being able to dose it to tolerance and slowly expanding while we’re working on our gut-rebuild protocols, tracking with laboratory data as it’s indicated, and concurrently, or at a certain point in time, reintroducing previously untolerated foods. It just seems like this will be a good 90-day solution, as you say. Just a nice starting point given how cool the design is and the fact that you leaned on low FODMAP players and players with a nice body of science behind them for efficacy for things beyond gut health.

Colleen Cutcliffe, PhD: Yeah, I think that’s right. I get asked all the time, well, define a healthy gut. What’s a healthy gut? What am I trying to aim for? And I struggled with that a lot because there’s so many studies out there that compare, you know, what is health? Health is like absence of disease, as far as we define it in our current landscape. And so when you look at a healthy person’s gut versus a sick person’s gut, what are the functions and what are the things needed. And so I’d been struggling with trying to define what some of those functions are but I think I now really understand. My evolution of thinking is that a healthy gut is a resilient gut.

Colleen Cutcliffe, PhD: If you have resilience—meaning you can eat all these different foods and you don’t have gut issues; meaning you can experience periods of stress and that doesn’t cause all kinds of GI issues; meaning that as we age, our metabolism and our gut health can maintain their highest ability—you are resilient to all of these things that are going to be happening to you. That’s a great gut. That’s a resilient gut. And so to your point, if you are unable to eat a whole bunch of foods, you don’t have a resilient gut. So how do we help you build the building blocks of your microbiome so that now your body can tolerate those foods, it can digest those foods? And that really is what all these tools are designed to do, is to help you build towards a resilient gut. You don’t have a resilient gut if there’s a bunch of foods you can’t eat. You don’t have a resilient gut if the little bit of stress causes you all kinds of GI issues. You don’t have a resilient gut if as you age, your GI and your metabolism and everything feels like it’s all falling apart. So you can get back that gut resilience, but it starts with those building blocks of the microbiome.

Dr. Kara Fitzgerald: Yes, yes, yes, yes. And we know, of course, centenarians have resilient guts. They’ve got loads of Akkermansia and other keystone players.

Colleen Cutcliffe, PhD: That was one of the craziest studies, is looking at these people over 100-years-old and what is different about their microbiome? They have these levels of Akkermansia that mimic people who are 16, just these incredibly healthy, high levels of Akkermansia. And I don’t know if I’m going to live to be 100, but I think Akkermansia is definitely a link.

Dr. Kara Fitzgerald: Yeah, for sure, and it’s been added as a hallmark, right? Thinking about the hallmarks of aging, the importance of the gut is just really being recognized.

Colleen Cutcliffe, PhD: One other thing maybe that we can talk about is, people who are on GLP-1 medications that significantly curb your appetite. And, we talk about malnutrition, that is one of the places that we’re seeing this pop up and it’s becoming more more prevalent because basically you’re not hungry. And when you’re not hungry that causes weight loss, which is all great, but when you’re not hungry to the point that you’re not getting proper nourishment, this becomes a problem. So this is another place where Gut Fuel can come play a role, which is, okay, you’re not hungry enough to eat all the— And by the way, high-fiber foods are incredibly filling and so if you’ve eaten lentils, that fills you up really quickly. So if you are not hungry and you’re already walking around full all the time, how do you get those fibers into your diet? Gut Fuel is a great way to do that as well. And so I think, again, that’s another use case for improving people’s gut health.

Dr. Kara Fitzgerald: Yes, that’s a really, really good point actually, and improving your own ability to make GLP-1. I think that it’s exquisitely important that when we’re using GLPs or when we’re supporting our patients on their journey using GLPs that we’re super, super careful with that small amount of food that we’re going to be taking in, that it’s just really exquisitely well designed. We need to have sufficient protein in there, obviously. But yeah, using Gut Fuel to lean on the fiber component and to get that nice broad sweep of good quality fibers makes total, total sense. The thing that I was thinking about was going back to the idea of resilient guts. I mean, sometimes we need an antibiotic, you know, sometimes we need medication. We might need an antiparasitic depending on what’s going on and where we are and what we’re experiencing.

Dr. Kara Fitzgerald: I mean, sometimes we need these really hard-core, gut-damaging medications. In fact, most of us will at some point in our lives have some sort of a need for something that’s going to damage our microbiome. Can we rebound from that? Back in the day, I think we did. Back in the day, I think we could be exposed to some of these things. Now, these medications can tip somebody into inflammatory bowel disease, like permanent IBS, maldigestion, heartburn, et cetera, SIBO and on.

Colleen Cutcliffe, PhD: Yeah, we’re fighting against so many things in our current food system, to be frank. I think that is a huge source of problem for many of us. And we’re fighting that battle in a way today that we weren’t fighting even 20 years ago. When you think about all the additives that are put into all the foods we are eating, even when you don’t know and you’re trying to be good and these things aren’t on the label. There’s so many things that are attacking our gut all the time right now that it’s not surprising that we’re less resilient.

Dr. Kara Fitzgerald: Yes. It’s not. And we just need to put the intention into rebuilding or maintaining what we have.

Colleen Cutcliffe, PhD: And not to seem like a total lazy piece of shit, but basically, I mean, we know that if you can have a good diet and you can read all the labels and you can exercise, you can do all that good stuff all the time, like, those are great solutions. But I think if I can get those supplements in a pill format or in a powder format, for me that’s just easier. And I’ll be honest, there’s a certain amount of laziness to it. Or how can I get this thing faster? How can I get this to fit into my lifestyle? But I also think I’m not alone there. So we’ve really tried to think about how can you replenish those strains and those prebiotics in just easy ways? Just how do you take a pill? How do you sprinkle this stuff in the food you’re already eating? Like, just make it easy for people.

Dr. Kara Fitzgerald: I’m with you on that. I am. I mean, I’m visualizing my mom in her freezer with her 27 little brown bags that she got at her local health food store, where you package up all that stuff. And that’s not me. It’s not me. But she’s in her 80s and she’s ridiculously healthy. So I want the outcome, but I don’t want the effort that she goes through. And then she texts me or she’ll call me, “And I added a little list of this for my breakfast and this…” and she’ll could just go through her whole list. And it’s really impressive. I’m like, I’m impressed, mom. And you know, I’ll take my little silicone baggie here of my capsules.

Colleen Cutcliffe, PhD: I love it. If you want the outcomes without all the work, come to Kara.

Dr. Kara Fitzgerald: It’s true, it’s true. Although I do have like a big container down there of salad and some steak and stuff as well. But yeah, a lot of capsules. All right, speaking of capsules, let’s move on to the Metabolic Daily reformulation. I want to say again, we’ve chatted for a long time, and for many years I’ve been a hardcore, committed Glucose Control person. Way more than you even because I’m the one who’s willing to pack it on ice and take it when I travel. So I’ve been super committed and I never thought that I would jump to Metabolic Daily.

Colleen Cutcliffe, PhD: I feel like you’re going to out me about that.

Dr. Kara Fitzgerald: I do a better job than you at taking your product. So the thing is, I would prescribe Glucose Control to my patients and some would get it, they would do a good job, they’ll keep it in the fridge, they’ll remember to take it out, they’ll remember to take it. I have a timer on my phone, so I remember. It’s part of my little morning routine. I’ll hit snooze on it maybe sometimes 80 times before I finally get to the refrigerator. But anyway, I’ve been committed to doing this, but I would see some of my patients would succeed at this and some of them wouldn’t, in which case I would put them on Metabolic Daily because it’s shelf stable. But I always had the bias that Glucose Control was what we wanted to do. However, you’re going to talk to me about the reformulation, which is kind of a big deal. So go ahead.

Colleen Cutcliffe, PhD: Yes, I would just say I remember you standing in front of thousands of professional HCPs, healthcare practitioners, and just saying like, I love Glucose Control, but I’m not sure about Metabolic Daily. It doesn’t work as good.

Dr. Kara Fitzgerald: That’s right. I’m sorry. That’s really funny.

Colleen Cutcliffe, PhD: Okay, but let me just say this. You you can do clinical trials and testing and all of that stuff, but it’s not until things get out into the real world that you really learn what’s working and what’s not working. And, you know, that was hurtful to hear, but also super important. And I think as scientists, we can’t have an emotional attachment to a product. We need to do what the evidence is telling us. And you were not alone in that.

Colleen Cutcliffe, PhD: We got a lot of feedback from a lot of HCPs. And you know, we talk to HCPs all the time. We’re really into like, how do we fit into protocol? How can we be beneficial? And so this was a very consistent piece of feedback we got. Number one, I don’t think that that formulation is as potent as Glucose Control. I’m literally seeing lab outcomes showing me that it doesn’t work for everybody, right? Some people it’s fine for, but most people, if I put them on Glucose Control, I know I’m going to see an outcome and I don’t know with Metabolic Daily. So that was one thing. We don’t know if we’re seeing the same outcomes.

Colleen Cutcliffe, PhD: But the second thing was, as you said, people were saying, well, Glucose Control is too expensive for my patients. Also, dealing with the cold chain is too difficult. They just travel a lot, or they just can’t remember because their whole other routine is not sitting in the fridge. And so we really listened to that and as you know, we’ve been constantly trying to improve the viability of our products in manufacturing. These novel strains aren’t things that just any old manufacturer in China and India can make, especially to make sure that they’re to potency and work. So we’ve been working in R &D on solving this pain point. And so I’m really, really excited to be able to say that we quietly improved Metabolic Daily’s formulation.

Colleen Cutcliffe, PhD: We took the three key strains that are in there, Akkermansia mucinophila, Clostridium butyricum, and Bifidobacterium infantis, and we increased the concentration so that it’s really almost to the level of Pendulum Glucose Control. These are the key strains that are really doing all the hard work in there. And we didn’t change the price and we have not changed any of the things that we’re saying about the product except that now you should start to see more of a difference. And you can still keep this thing at room temperature.

Dr. Kara Fitzgerald: That’s amazing. That’s amazing. So we decided that I’m going to do the Metabolic Daily N-of-1 challenge. It’s funny. Oh my God, I can’t believe I said that in front of many, many, many people. I think Halle Berry was like amongst us as well. And she was like, I use Glucose Control too. Anyway, I’m going to do it. I’m going to jump ship. Even though I have my routine, it might be a little contorted when I have to hit the snooze button 87 times before I get it out of the fridge. And certainly plenty of my patients just don’t even do that. I’m going to switch to Metabolic Daily and I’m going to get my A1C at baseline and then I’m going to track it and just make sure it’s there where it needs to be. I will.

Dr. Kara Fitzgerald: So I’m excited about that because indeed it will make my life a little bit easier. I won’t be rolling my bags down the hallway at the hotel, trying to remember to stop at the ice machine and fill up my larger silicone bag for ice so I can take it home. But yeah, I’m going to do it. I’m doing it. I’m stoked that you figured it out. You figured out how to make it shelf stable at this higher dosage and I know that you were talking to me about that a while ago. That was your puzzler that you began working on, so the fact that it’s here, you’ve done it, you’ve released it, and you’re not changing the price points–

Colleen Cutcliffe, PhD: We’re not changing the price point. We’ve been working on this for probably about a year and a half trying to figure out how to make this new formulation, this improved formulation doable because we are also running a business. So what you don’t want to do is to make it a better formulation and then push it out of the price point that people can actually afford. And so I’m just really proud of our team for figuring out all of that and really bringing out this improved formulation. I cannot wait to see how your test comes out because if it works for you, we’re going to see you back on that stage with your new-and-improved story.

Dr. Kara Fitzgerald: Yeah, I’m psyched. I did not anticipate making this change, but actually, I’m in. I’m all in. I’m thrilled. You guys just laid it on me when we were preparing for this podcast. You’re like, by the way…

Colleen Cutcliffe, PhD: I know, and I think we’ve been doing it quietly, that’s true. Because look, what really matters for people is feeling and seeing the outcomes, and so I think if you can do a new and improved and more people are feeling the outcome, then you’ve won. And maybe this is just because we’re a bunch of scientists, but I think there’s a lot of marketing frenzy that can go into like, “new and improved” and all, and so I think we just haven’t done that. We just know that if more people are feeling benefit from it, people will tell other people about it.

Dr. Kara Fitzgerald: Yeah, very much on the down low you did it. I mean, I knew you were puzzling on it and working on it. You gave me that little bit a while ago and now you’ve actually done it. That’s awesome. And I mean, the other thing is, that you’ve consistently worked at trying to figure out how to make it more affordable. A lot goes into R &D and you guys had to figure out how to stabilize an anaerobic microbe, which is no joke. You couldn’t just, like you said, go to India or China and and hire a manufacturer. You had to figure it out. It took endless amounts of development, engaging in human research and clinical research is a massive expense. So there’s a lot that goes into figuring out something and making sure it’s efficacious. But I appreciate that and then I also appreciate you being mindful around price point.

Colleen Cutcliffe, PhD: And thank you for saying that. There is so much that goes into trying to create a quality product for people. And there’s so many supplements on the shelves that it can be hard to know what’s good and what’s not good. And a lot of these things are, you know, your triple click, quadruple click into development, but I think we’ve been very focused on seeing efficacy in people. So clinical trials, looking at efficacy in people, we’ve been focused on these innovative strains and how do you have them consistently have the right viability and the right activity that you’re looking for. We’ve consistently invested in the right capsule, which gets it all the way to your distal colon, which is where your microbiome is. So these capsules that can get through the stomach acid, these capsules that have time delayed release. Not everything is encapsulated like that. It just opens up in your stomach and you’re done.

Colleen Cutcliffe, PhD: So it’s really the human testing, the strain viability that’s consistent, the encapsulation, and then even the bottles. Even as we have tried to improve the packaging and all of that, we’ve really made sure that the bottles themselves are maintaining the viability of the product. And so, all of that is investment in your health, and so hopefully people feel that.

Dr. Kara Fitzgerald: Yeah, that’s a lot. It is a lot. I know that they’re dark, the bottles actually. I have my Polyphenol Booster here. The redesign is really gorgeous.

Colleen Cutcliffe, PhD: That’s the redesign we did with Halle, yes.

Dr. Kara Fitzgerald: Yeah, that’s right. The Halle Berry redesign. They’re gorgeous. But I think that is also a decent point to make. It’s the whole entire journey, being mindful around that so that the end product actually works, actually does what it says, gets to where it needs to be in the gastrointestinal tract. Many, many, probiotics don’t do a heck of a lot. I’m sure we’re just killing them when they hit stomach acid, you know, when the capsule breaks open. I’m sure that that’s correct.

Colleen Cutcliffe, PhD: Yeah, and that’s where I think for us, we’re not just a consumer brand that’s out there on TikTok. We’ve really invested a lot in education of HCPs. And I love doing these with you because you have an audience that is discerning and is trying to learn and trying to figure out what are the differences between all these different things that are on the shelves. We just got number one GI doctor recommended brand and I think that that’s not because consumers are learning about this. It’s really you guys, it’s the HCPs who are helping the public discern what’s good and what’s bad and those kinds of accolades are just really awesome for us because it’s hard in this sea of supplements.

Dr. Kara Fitzgerald: Yeah, yeah, no doubt. Especially when you want to do the right thing and there’s a vertical investment curve there. Well, my dear, it was awesome to have our conversation once again and talk about what you guys are up to over at Pendulum. And I’m going to start my Metabolic Daily challenge so you’ll hear from me in a handful of weeks. I guess I’ll probably retest in three months. I’ll be consistent and then retest in three months. Let’s see where I’m at.

Colleen Cutcliffe, PhD: I can’t wait for you to do that challenge.

Dr. Kara Fitzgerald: Yeah, I’m going to get my baseline test in a couple of weeks and then jump on and I’ll share it with you for sure.

Colleen Cutcliffe, PhD: Awesome.

Dr. Kara Fitzgerald: Thanks so much.

Colleen Cutcliffe, PhD: Thanks for having me.

Dr. Kara Fitzgerald: As always, that was such a fun conversation with Dr. Colleen Cutliffe. I think that they’ve made a good argument for the essentiality of a well-tolerated fiber product. I mean, we are in the era of tough guts. Of course, you know that most of your patients are struggling with some degree of dysbiosis. And of course, some of our patients are on highly, highly restricted diets because of these problems. So if this is a step that we can take which will ultimately allow us to support our patients in reintroducing a full dietary pattern I’ll take it. I’ll take it.

Dr. Kara Fitzgerald: As always, you will find all the links and the resources in our show notes. And if you found this podcast to be helpful, please share it with a colleague. It really helps us to reach more listeners. Thanks for joining me and we’ll see you soon on New Frontiers in Functional Medicine.

Colleen Cutcliffe, PhD, is the CEO and Co-Founder of Pendulum Therapeutics, a category-defining leader in microbiome innovation focused on transforming metabolic health. With over 25 years of experience spanning academia, pharmaceuticals, and biotechnology, Colleen brings deep expertise in translating complex science into scalable, market-ready solutions. Prior to starting Pendulum, Colleen was the Senior Manager of Biology at Pacific Biosciences and a Scientist at Elan Pharmaceuticals where she worked on neurodegenerative disease therapies. Colleen holds a PhD in Biochemistry and Molecular Biology from Johns Hopkins University and has been instrumental in unlocking the commercial potential of next-generation probiotics and microbiome-based therapeutics, positioning Pendulum at the forefront of a rapidly expanding market.

PENDULUM Resources / Links to Publications

Research Mentioned In This Episode

Achieving healthy aging through gut microbiota-directed dietary intervention: Focusing on microbial biomarkers and host mechanisms

Comparative analysis of the gut microbiota in centenarians and young adults shows a common signature across genotypically non-related populations

People Mentioned In This Episode

Halle Berry

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

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

Blog: From Promise to Paradox: GLP-1 Agonists May Offset Their Own Benefits Through Gut Microbiome Dysbiosis

Bio Age Self Assessment Quiz

Younger You book

Better Broths and Healing Tonics book