Podcast Episode 212: Food Choices & the Gut Microbiome: Managing Chronic Diseases Takes Guts – Dr. Orville Kolterman and Kristin Neusel

Melissa: Hello, and welcome to the sound bites podcast. Today’s episode is about the role of the gut microbiome and food choices in managing chronic diseases. So much research is being done and knowledge gained about the role of the gut microbiome and food choices in the management of several chronic disease states, including type two diabetes cardio-metabolic health, gastrointestinal disorders, and even mental health. This is truly a burgeoning area as we will discuss today.

I have two expert guests today, Dr. Orville Kolterman and Kristin Neusel. But before I introduce my guests, I want to let you know that this episode is sponsored by Pendulum Therapeutics, a company that applies evidence-based microbiome science and DNA sequencing to develop a new generation of probiotics.

And in addition to our robust conversation about the microbiome today, we’ll bring you up to date on some new products and services that Pendulum therapeutics now has available. Also, this episode is being submitted to the Commission on Dietetic Registration for continuing education for registered dietitian nutritionists, dietetic technicians, registered and certified diabetes care and education specialists.

You can check out my free CEU library @soundbitesrd.com/freeceus for updates. So I’m really happy to introduce you to my two expert guests today. And actually they’ve been on the show before, and we’ll talk briefly about that in a minute. My first guest is Dr. Orville Kolterman – he’s an endocrinologist. And after a long career of delivering diabetes care and working on glucose lowering medications that impact gut hormones, he now serves as chief medical officer at Pendulum Therapeutics and has done so since 2013.

Orville joined amylin pharmaceuticals in 1992, where he served in various capacities and led teams that developed and gained regulatory approval for 4 first in class therapies for type one and type two diabetes and partial lipodystrophy. He received his undergraduate degree from the university of Kansas followed by his medical degree and training as an endocrinologist at Stanford university.

My second guest is Kristin Neusel. She’s a registered dietitian, certified diabetes care and education specialist and certified personal trainer. She is Pendulum therapeutics director of nutrition programs, where she leads a team of incredible registered dietitians who help Pendulum’s customers through one-on-one coaching calls, group sessions, webinars, meal plans, and more.

Kristin has a master of science degree and bachelor of science degree in human nutrition and dietetics from Southern Illinois university Carbondale, where she also minored in Spanish. So welcome you both back to the show. I’m so happy to have you back on and excited about

Kristin: this topic. Happy to be here, Melissa.

Thank you so much for having us back.

Melissa: just briefly, the topic that we covered in the last episode, which was almost a year and a half ago, it was January of 2021. We talked about the gut microbiome and type two diabetes, and really focused on the role of some metabolic changes that we see occurring in the development and progression of prediabetes and type two diabetes and how that impacts the gut microbiome.

And today we’re going to go a little bit beyond diabetes, but I think the best place for us to start would be perhaps Kristin kind of set the stage with some of the definitions of some of the terms that we’re going to hear today, especially there’s a lot of different “biotics”. So could we start with that?

Kristin: Absolutely.

There’s a ton of new terms here that I wasn’t taught in my schooling and I might be dating myself because they might be teaching this nowadays, but there’s a lot of different Biotics I’m hearing all the time. And a lot of my friends who are dietitians don’t even know what some of these words mean. So the first thing we talk about is prebiotics and think of that as food for probiotics. All prebiotics are fibers, but not all fibers are prebiotics.

And we’ll get into that a little bit later, but that’s a key thing to remember. So I mentioned food for probiotics. Probiotics is another biotic that a lot of us as dietitians and healthcare professionals are relatively familiar with. And these are live microorganisms that are intended to have health benefits for the host.

And these can be applied to the body. These can be consumed they’re all over everything nowadays. I’ve seen them pop up in all sorts of things. Another key word that I’m hearing a lot about lately is something called a postbiotic. And to us as clinicians, we probably know this as different vitamins, different short chain fatty acids, but this is just a buzz word right now.

They called it something called post Biotics. And these are essentially bioactive compounds made when the friendly bacteria in your gut, the probiotic bacteria, I mentioned earlier, digest and break down those fibers, those prebiotics, what happens then is a post biotic and healthy postbiotics include nutrients, such as things like, oh, vitamin K, B, amino acids.

A lot of what we’re going to talk about today are short chain fatty acids, which are also postbiotics and short chain fatty acids are so important for gut health. They improve gut health through a number of local effects. This can range from intestinal barrier integrity, mucus production, protection against inflammation to reducing the risk of colorectal cancer.

Synbiotics is another biotic we’re talking about and that’s a pre and probiotic together like I mentioned earlier in one form that are synergistic, they work together well. So for example, Pendulum glucose control has inulin. Gut microbiome and gut microbiota – I have a lot of people asking me, what’s the difference between these two terms?

So think of your gut microbiome as the entire collection of genes found in all of the microbial cells living in your gut. Gut microbiota on the other hand are microorganisms that inhabit the intestinal tract. So it’s the composition of this microbial community. And that’s really host specific. Everyone is going to be different.

Melissa: Kristin, thank you for those terms and definitions. With this topic, I always appreciate a review of these. So I’m guessing some of my listeners will as well. So that’s very helpful. So I want to build on the episode that we did back in January of 2021. And by the way, that was episode number 168, again, the gut microbiome and type two diabetes.

I want to briefly recap what we talked about since we’re going to build on that a little bit with this episode. We touched on the pathophysiologic changes that occur in the gut microbiome of people with type two diabetes, including the role of butyrate, which is a short chain fatty acid in the glucagon-like peptide one (GLP-1) physiologic pathway.

We also touched on the beneficial functions of the gut bacteria that may be missing in the gut microbiomes of people with or developing type two diabetes. And we touched on the food and nutrition changes people with early diagnosed type two diabetes can make to increase their intake of a broad spectrum of dietary fibers, particularly those containing or leading to the production of short chain fatty acids.

And we discussed the science and evidence for the use of a specific probiotic to assist with the dietary management of type two diabetes. And in that conversation, we also talked about Pendulum glucose control, which is the only medical probiotic specifically designed to address type two diabetes. So I really encourage people to check out that episode if you want the deeper dive on the gut microbiome and type two diabetes and Pendulum glucose control, but we’re going to touch on that as well today.

So my question to you Orville is since that episode is there any new research that Pendulum or other researchers have conducted that focus on the impact of metabolic changes in the onset of type two diabetes on the gut microbiome?

Orville: Thank you for that question. There has been a reasonable amount of additional knowledge gained since we last spoke. In terms of Pendulum Glucose Control, which contains five microbial strains that were selected to address the changes that have occurred in the microbiome of patients with type two diabetes where certain functions have either disappeared completely or severely diminished, we have been able to conduct some additional studies that confirm a key mechanism of action of our product (Pendulum Glucose Control). Mainly the stimulation of the secretion of GLP-1 by increasing butyrate. The data that I referenced the last time in our discussion regarding butyrate was largely drawn from studies in rodent models of type two diabetes because of the difficulties in assessing certain key samples in humans in a way that’s suitable to make the confirmatory observations. Since those discussions, we have been able to demonstrate that use of Pendulum glucose control in fact increases the content of butyrate in stool of subjects using the product. And more importantly, we’ve also been able to confirm an increase, significant increase, in circulating plasma butyrate. And what’s really reassuring is, is that the increase in plasma butyrate correlates indirectly with the reduction in hemoglobin A1C. That means that when plasma butyrate increases, hemoglobin A1C decreases in patients with type two diabetes using the product (Pendulum Glucose Control).

Now why that is so important is as that those observations confirmed that the exhaustive data that has been generated in the rodent models of type two diabetes in fact, have been demonstrated now to also be operative in human subjects. In those studies we also demonstrated that our strains result in an increase in circulating levels of a secondary bile acid called UDCA, which stands for ursodeoxycholic acid. And that’s a compound that has also been implicated based on rodent studies as being a signaling molecule that brings a metabolic benefit with it. Looking at the field in general, since we last spoke, there’s been a lot of focus on one of the strains in our formulation, namely Akkermansia muciniphila, which those studies just solidify the evidence that Akkermansia is a very important organism or microbe to replenish in patients with type two diabetes. Because in addition to playing a key role in maintaining the mucin layer and the intestinal barrier it now has been shown to by a unique mechanism to also contribute to the increase in secretion of GLP-1, which is a key regulatory hormone, as you alluded to in terms of maintaining metabolic control.

Melissa: Okay. Thank you for bringing us up to speed on some of the research developments there and for our conversation today, I want to know a little bit more about, I mean, we know that the gut microbiome needs to be healthy for us to be healthy overall.

But I’d like to hear more about what other chronic diseases that I mentioned earlier – Cardio-metabolic, gastrointestinal, even mental health. What is the research showing regarding the role of the gut microbiome and also about food choices? So Orville, perhaps you could start off with what the research is showing with regard to the gut microbiome.

And perhaps Kristin can talk more about the food choices.

Orville: Sure when you have the advent of the DNA sequencing that allowed  characterization of the bacteria present within the gut microbiome of individuals, but what evolved next was the demonstration that these various chronic diseases. And in fact, yeah.

I think there’s hardly a chronic disease that you could name, now that hasn’t been demonstrated to have some alterations in the gut microbiome associated with it. But up until just recently, those associations are sort of guilt- You knew it was the implication that those alterations in the microbiome played a role in the disease itself – it was sort of guilt by association. Since we last spoke there has been – there just continues to be a constant stream of studies that are now getting into demonstrating what the mechanisms are for that underlie those associations and therefore enhancing our understanding of how the changes in the microbiome are contributing to neurodegenerative diseases.

Even changes in mental status, depression, anxiety, along with the other metabolic diseases, atherosclerotic cardiovascular disease. Yeah, osteoporosis, autoimmune diseases and the list goes on and on.

Melissa: Yeah. So it sounds like the more we understand the mechanisms, that can help us develop better treatments or interventions.

Orville: That’s absolutely correct. And how

Melissa: much of a role does inflammation play in that relationship between gut health and chronic disease, does it depend on the type of chronic disease or in what’s going on? I know we touched on inflammation in the last episode, but if you could enlighten us a little bit because I feel like this is an important

Orville: point.

I agree that it’s an important point. It’s an area we’re going to see a fairly rapid increase in our understanding of how this all works or how this all fits together. It’s really clear, and I think undeniable, that the inflammation that’s engendered by reducing the integrity of the gut barrier plays a major role in metabolic diseases, pre diabetes, type two diabetes. cardiovascular disease, it’s associated with type two diabetes. But it’s also becoming clear that because of the widespread inflammation in the body, that there’s an effect on a function on the central nervous system on mood on so-called fatty liver disease as well as probably the neuro degenerative diseases such as Parkinson’s diseases. And it’s interesting, intriguing data emerging around inflammation in Alzheimer’s disease. Just to name a few.

Melissa: Thank you. And before we hear from Kristin about some of the food choices and that role that food choices play, which we know is very important.

Orville, why do you think it’s taken so long to zero in on recognizing the importance of the gut microbiome and chronic diseases?

Orville: So I think there are two components to it. One is that the high throughput DNA sequencing that was affordable needed to be available. And that didn’t arrive until sometime between 2000 – 2005.

And once it was present, investigators began to observe the associations between changes in the microbiome and different disease states. But as I alluded to earlier, those associations were just sort of guilt by associations that raise questions about how are these changes related to the disease that they’re associated with, are they causative or are they a result or a consequence of the disease developing? So that then requiring going into animal models of their respective diseases and looking to identify potential mechanism that could understand, or that could explain the connections and that’s where we are right now is that those explorations in the animal models have identified mechanisms associated with various chronic diseases.

And the focus is now turned on, so impact on this mechanism in say, fatty liver disease is strong. And the mechanism that we see here to clearly play a role in fatty liver disease, but how does it work with the microbiome impacting that? How exactly, what’s the next step down the line to get to a full understanding that it’s required to then attack things in terms of designing a fair, leveraging those observations to create a therapeutic modality for the disease that we’re talking about.

Melissa: Okay. And just to be clear, so the animal models and that research can help determine what might need to be studied in humans, correct?

Orville: Correct. And the reason is the animal models are so important. It’s now well-known that the microbiome is producing many different substances, neurotransmitters, the short chain fatty acids, other metabolically active compounds that are produced within the gut.

And then they enter the Hepatic circulation going to liver. Then in turn the peripheral circulation. In animal models, you can be invasive – more invasive than you can in humans – and do studies where you can sample directly and quantitate what’s coming out of the gut as a result of changes in the microbiome where that’s more difficult to do in humans.

And so the animal work sort of provides an important bridge from an observed mechanism, understanding how the mechanism sort of fits together and works, and then allows you to identify downstream consequences of those changes that you can actually monitor in humans to confirm whether what you’re seeing in the animal models translates to humans.

Melissa: Thank you. So, Kristin, is there any research that you’ve seen on these topics that you’d like to share and then also bringing in the food aspect? Because first we need to understand the mechanism and for the average person, they’re not going to want to maybe be interested in understanding the mechanism, but we all can appreciate, okay, what types of foods can nourish the gut health? And then the next question is, okay, what can we do with foods and what might we need supplements for? And that’s where Pendulum comes in. So I know I just threw a lot out there, but if there’s any research and information you wanted to share, I’d love to hear it.

Kristin: Absolutely such a great question. Everyone’s always wondering, well, how can I nurture my gut? Because when we think about disease and conditions, what we’re learning is that it all starts in the gut. I mean, 70% of our immunity is found in our gut. So everyone’s asking what can I do to sort of nurture this part of my body that I hadn’t thought about before.

And we always educate on increasing your fiber, your prebiotics and your probiotics, but another thing, another buzz word I’m hearing a lot about a lot of research that’s being conducted as on something called a polyphenol and polyphenols – they are naturally occurring compounds found largely in fruits, vegetables, seasonings, cereals, beverages, keyword here, red wine. So now that I have your attention, red wine is a polyphenol and there are more than 8,000 types of polyphenols that have been identified and they can be further categorized into four main groups, such as flavonoids, phenolic acids. Polyphenolic amides and other polyphenols.

So taking you back to your organic chemistry courses but basically what we want to take away from this is that polyphenols have been shown in mice studies to actually increase the abundance of Akkermansia, which is one of the products we at Pendulum have. We’re the only producers of this key strain that a lot of people are super excited about.

Regularly consuming polyphenols is thought to really boost digestion, brain health, as well as protect against things like heart disease, type two diabetes, and even certain cancers has been found in the research. So when you think of polyphenols, think of, like I mentioned, the red wine, dark chocolate, tea, berries, just some of the best known sources.

And I like to think of them like antioxidants. So as I mentioned, there’s over 8,000 types of which makes it really really hard from a clinician standpoint to differentiate between, okay, well, which polyphenols do I pick? So I recommend really focusing on just trying to get a variety of those fruits and vegetables, different seasonings to incorporate into a healthy eating plan.

Melissa: Excellent. And you talk about something that really catches my attention. You talk about diversity versus density with different food groups. We know that a variety of foods is important because that’s how you get a variety of nutrients. But I would love to hear your take on this diversity and density.

Kristin: Absolutely. When we think about what we’re feeding our gut microbiome what we’re feeding our bodies. Think about density and diversity. So fiber, those foods like whole grains, apples, fruits and vegetables, all of those things really impacts the density. So when we’re getting a lot of fiber, we’re impacting the density of the strains that we already have.

Now how we increase the diversity of your strains in your microbiome is through things like probiotics, kefir, yogurt, supplementation, and both are necessary for a healthy microbiome. And you can eat super healthy, workout regularly and still have gut dysbiosis, meaning an imbalance in your gut microbiome because you’re lacking the foods or supplements to nurture that gut microbiome.

For example, we recently had a client who had been following a very strict keto diet for the past nine years and suddenly had a pre-diabetes diagnosis. They were at a healthy weight, no family history of diabetes at all. And I immediately thought of the microbiome dysbiosis she could be having due to lack of fiber and probiotic foods.

So she had purchased Pendulum glucose control to try and correct that. And that’s just an example of sometimes supplementation with probiotics might be necessary and over time we can really negatively impact our microbiomes and we think we’re doing the right

Melissa: thing.

Yes. And I recall from last episode where it was really impressed upon me that wow you could be eating a lot of great fiber rich foods, but if you don’t have the right bugs in your gut to take that fiber and turn it into butyrate, hopefully I got that right. Then it’s not going to work your, your body just – the fiber is not going to have that function that you want it to. And that’s where the Pendulum glucose control came in. Did I get that right?

Kristin: Yes, you did. It all works synergistically. So over time, our gut microbiomes can change to where we’re missing or lacking functionality of the strains that perhaps were once there.

And in that case, we don’t have those strains to break down that fiber and the short chain fatty acids, like you mentioned, butyrate, is not produced to help with a multitude of different functions in our body. So it’s important to get a really good mix of those pre and probiotic foods or supplements.

Melissa: Okay. Yeah. So for me, the takeaway is of course we want a healthy diet and a varied diet, and there are limitations just – access to food or just the realities of busy lives or whatever, but then there’s the fact that you could be doing a really great job in getting a lot of great nutrients in and still need a little bit of help from a supplement.

And so I’d love to hear a little bit more from you about how do we know which kinds of supplements we need. How do we know that they are quality? What do we look for? That’s

Kristin: a really great question. A lot of people don’t know what to look for on the probiotic bottle. And for example, I have a friend who she called me one day, pretty frantically saying my son, he’s having some GI issues and I gave him a probiotic and it didn’t work.

So we’re not going to use any probiotics. And that’s just not the case. There are trillions, there are so many different probiotics and what you really want to look for and what I recommend all clinicians educate their clients on, is looking for the genus, the species and the strains, that’s going to really provide a lot of credibility.

For example, when you look at a bottle of Pendulum glucose control, you’ll notice [27:10] I’m going to say one that I’m not going to butcher the whole word on Akkermansia is going to be the genus. And mucinophila is going to be the species. And then we have WB-S T R – 0 0 0 1. That’s going to be the strain.

So those are really important to be listed on a bottle that you’re looking at when you’re looking at the store. Another really good resource for clinicians I like to recommend is AEProbio.com. And you’ll notice that Pendulum is listed on this website. So that’s another good, reliable resource to educate your clients on when looking for a credible source of a probiotic.

Melissa: Okay. Yeah. And it’s a lot of science, so it’s always helpful if you could have this conversation with your healthcare practitioner and hopefully they are educated about probiotics and prebiotics and supplements, but of course we’ll have some resources to share at the end where people can get more information.

So since you and your team of registered dietitians at Pendulum are working to apply this research that we’ve been talking about to help consumers and patients improve their health and clinical outcomes, can you talk a little bit about how your team translates this research? I’m just curious.

Kristin: Yeah, definitely.

Our team works really hard to constantly be up to date with the latest microbiome science. And again, I’ll reiterate this isn’t something that’s taught in school. So it’s really good to make sure that our team is up to date and we’re in the Renaissance period of microbiome science. And these things are unfortunately, like I mentioned, not taught in school.

It’s important for us to be able to translate that evidence-based research to our customers in a way that is – pun intended – digestible. And we do this through different things like conducting one-on-one nutrition coaching calls for each of our Pendulum probiotics. Okay,

Melissa: great. And Orville, I should ask you as well.

Is there any other new or ongoing research that Pendulum is involved with that you’d like to tell us about?

Orville: Sure. Thank you for that question. We are having increase in requests from academic investigators to participate in their research. Two examples of that are: We are in the early stages of enrolling patients in a post-menopausal osteoporosis study in Australia because of a connection again, through our friend butyrate between the gut microbiome and the mineralization of bone. Equally important is an emerging collaboration with an investigator who has formulated a very exciting hypothesis about the role that the microbiome can be playing in bipolar disorder. So those are two examples of how things are branching out beyond the metabolic focus that we’ve had. And we also are working to explore whether we can leverage some of our strains to benefit people with irritable bowel syndrome.

There’s a lot of problems in that area.

Melissa: Yes, there are. Okay. So that leads me to this question that I have. I know that your product line has expanded and you also have some new services. So do you want to briefly just explain some of the new products and probably a recap of Pendulum glucose control as well?

Orville: Yeah. Our initial product was designed to specifically address the abnormalities in the microbiome of patients with type two diabetes. And that’s the product that we spoke about the last time we were together Pendulum glucose control. Our second product is just a single strain Akkermansia strain marketed as a separate product. We remain the only entity that can manufacture Akkermansia in large quantities. And there’s a just a huge emerging interest in Akkermansia for a wide range of indications, including some very important potential interaction between Akkermansia and various chemotherapy agents used to treat various cancers.

And then the third is an initial product of what we think will be a family of products to address the burdens of irritable bowel syndrome. And also there’s probably some application in inflammatory bowel disease.

Melissa: Is that the GI repair?

Orville: That’s the GI repair

Melissa: Thank you. And then of course, the services Kristin, I know that you’ve been expanding the number of dietitians on your team.

That’s just great news. Can you give us a summary of some of the programs and services that you and your team offer at this point?

Kristin: We at Pendulum truly care about our clients and don’t just want to give them a bottle of pills. We give them support along the way from true professionals like registered dietitians because we want our customers to be successful.

And in addition, Pendulum’s probiotic line has really expanded. And with that has the need for dietitians to educate these customers on each product. We do have a growing team of now five dietitians. We call them nutrition educators, comma, registered dietitians. So the acronym is nerd. It’s kind of fun.

And in addition to myself, and so they conduct one-on-one nutrition coaching calls, educational webinars. We create microbiome focused meal plans and group nutrition education classes as well. So lots of fun stuff. And in addition to the six of us, we have Pendulum has an awesome team of two other dietitians who focus specifically on HCP focused education and work with healthcare professionals.

So if you’re listening to this and you’re interested in learning more, feel free to email them. It’s Cindy and Natalie. So their email is HCPinfo@Pendulumlife.com.

Melissa: Okay, great. Thank you. And I’m guessing that the education that you and your team does is primarily virtual.

Kristin: Yes, it is. We live in a virtual world, so that makes it a lot easier to reach so many different people.

That’s

Melissa: what I thought. Yes. We definitely live in a virtual world. So in wrapping up, I would love for each of you to sort of share kind of the most important thing that people need to know that that’s a really tangible takeaway from our conversation today and from where things are in your world about the gut microbiome and chronic diseases and food choices, and also kind of take a look into the future and tell us what you think about five, 10 years from now –

What we’ll be talking about with the role of the gut microbiome and the food choices and their impact on managing chronic diseases. So Orville, let’s start with you.

Orville: Near term, I would just encourage the listeners to really watch this space because the microbiome area is just in its infancy. And some of the things that we’ve talked about today in terms of the mechanism of action, our understanding of those will continue to grow over the coming years. And as that understanding grows because of the unique safety advantage that these forms of therapy have, there will be more and more targeted therapies becoming available directed at different disease states. And I think that they’re going to be really significant developments and really better understanding some aspects of those disease states that aren’t that well understood today. The last thing that I would end with is that over the next 10 years, there are what I call medical observations of interest that we’ve had for decades.

And we thought that mapping the human genome was going to provide the answers but that hasn’t proven to be the case, but there are these observations that are just proven time and time and time again, but we don’t know why they happen. Going forward. I think the microbiome is going to provide the insights that lead us to really understand what’s going on in those situations.

Okay,

Melissa: thank you. And Kristin,

Kristin: I will echo what Orville said. I couldn’t have said it better myself Orville. So really just take away from this to pay attention to this space, like Orville said, I would recommend everybody really start putting an ear out for more information, signing up for Google notifications.

That’s an easy way to get the latest research and my crystal ball. Oh my goodness. I’m a big dreamer and I’m very hopeful and optimistic that one day we will continue to find – we’ll have more conditions and disease focused treatments, such as Pendulum glucose control that can assist in the management of different conditions and diseases by simply adding a strain specific probiotic and altering the diet and lifestyle.

And I think that there will continue to be a huge, necessary role of the dietitian in this field. It’s truly fascinating what we’re learning each and every day about the trillions of strains in our system. So I’m excited to see where we go from here. Excellent.

Melissa: Thank you. And as I promised, people can find more information – the website is Pendulumlife.com and there’s a lot of great information on there. Kristin writes a blog series and all the science and research is accessible there. And I will also have links to that and any other pieces that you want me to include in the show notes, Kristin and Orville, but they’re also on Instagram at Pendulumlifeco and I also have a couple of related episodes to digestive health and postbiotics that I’ll put links to in the show notes as well at soundbitesrd.com.

So thank you both so much for coming back on the show and giving us an update on everything in the gut microbiome space right now, with regard to chronic diseases.

Kristin: Thank you so much for having us. This was wonderful.

Orville: This has been great.

Melissa: Thank you. My pleasure. And for everybody listening as always enjoy your food with health in mind. Till next time.