If you’re a practitioner looking to level up your toolkit for regenerating the intestinal barrier and healing the gut, then this interview with Dr. Tom Fabian, PhD is exactly what you need. This fundamental piece of our functional medicine toolkit continues to progress, and today we’re zooming way out from just patching up the gut. Dr. Fabian and I dive into the dynamic nature of the barrier, including its circadian cycle, the role of prebiotics, polyphenols, probiotics, and postbiotics in epithelial regeneration and stem cell proliferation, and useful clinical pearls to assess barrier function using the GI-MAP stool test. So glad to have Tom back on New Frontiers, and I’m sure you will be too! Let me know what you think! ~DrKF
Today’s interview on the foundational topic of gut healing goes beyond the standard toolkit used to restore the intestinal barrier to discuss the latest research and clinical pearls on restoring the gut. We are joined by Dr. Tom Fabian, PhD, a translational scientist and leading expert on the role of microbiome health. Dr. Fabian focuses on the microbiome, immune function, chronic disease, and aging as a biomedical researcher, consultant, and science advisor for Diagnostic Solutions Lab. Join us to learn about a new paradigm in how practitioners assess and treat various conditions and support gut healing.
In this episode of New Frontiers, learn about:
- A systems biology-based approach to the intestinal barrier
- Key barrier components, including the microbiome, secreted factors, intestinal epithelium, and mucosal immune system
- The dynamic nature of the intestinal barrier
- The circadian cycle of the barrier
- Epithelial regeneration from intestinal stem cells
- The role of butyrate and Akkermansia in intestinal regeneration
- The influence of the microbiome and dietary factors on intestinal barrier function and epithelial regeneration
- The impact of fasting and ketones on stem cell proliferation and barrier regeneration
- The Four Ps: prebiotics, polyphenols, probiotics, postbiotics
- Assessment of the intestinal barrier with comprehensive stool testing using GI-MAP
- Clinical pearls for assessing barrier function
Dr. Kara Fitzgerald: Hi everybody. Welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And here I am, live in Baja, Mexico with my good friend and just all around, brilliant guy, Dr. Tom Fabian. And we’re going to be talking about all things leaky gut, and really importantly, the tools that you have at your disposal to do an accurate and useful assessment and treatment plan design. So, let me tell you about Dr. Fabian, and then we’ll jump right in. He is a leading expert on the role of microbiome health, immune function, chronic disease, and aging. As a translational scientist, his primary focus is on the clinical application of microbiome research in the integrative and functional medicine space. He received his PhD in molecular biology from the University of Colorado at Boulder, and he’s worked as a biomedical researcher in the biotechnology industry and more recently as a consultant in the microbiome testing field.
He currently serves as a consultant and science advisor with Diagnostic Solutions Laboratory. He’s also on the science advisory board at Designs for Health. In addition, he’s certified as a nutrition therapy practitioner by the Nutrition Therapy Institute in Denver. Dr. Fabian, Tom, always, always good to have you on New Frontiers.
Dr. Thomas Fabian: Likewise. Well, thanks so much for having me back, Kara. It’s great to be back.
Dr. Kara Fitzgerald: Yeah. We’ve got a lot to cover. So we’re going to jump right in. We’re talking about leaky gut. This is a perennially interesting topic in our field, actually from before we were able to assess zonulin. I mean, I remember actually, when I was a student, before I went to medical school, I worked in a naturopathic medical office. I was at the front desk. And I remember… And I would shadow. So, I was considering going to medical school and I would shadow one of the physicians there, Eugene Zampieron. He’s still in practice. And I remember vividly him writing the whole leaky gut figure, generating this for a patient as he taught. He was talking to the mom. The son had I think, ADHD and he was linking it to gastrointestinal disturbance and intestinal permeability. And this was in the nineties, and we were considered quacks actually.
So, it was a fundamental piece of our toolkit and something that we addressed routinely, but it was not accepted by the greater medical community at all, really not until Fasano a couple decades later discovered zonulin, and then we started to piece together the story that leaky gut is really associated with, I don’t know, kind of everything. And so give me just a basic thought on leaky gut, on what it is, on what it’s associated. So, just give us a leaky gut primer, maybe any comments on what I’ve just said, and just thinking about how we’re currently assessing and treating it. And then we’ll just go on, and I know you’re going to evolve our understanding in this conversation.
Dr. Thomas Fabian: Absolutely. Yeah. So, it really is a kind of a ever-progressing topic. So, I think the original concepts came out quite a while ago, as you alluded to. And it took quite a while, of course, for that to be accepted in conventional circles in research, but now you see hundreds of papers published every year addressing permeability, intestinal permeability issues. So essentially, I think the core of what it means is when you’re considering the intestinal lining, so of course we’re talking primarily about that one cell thick layer, the epithelial layer that covers the entire intestinal lining, entire mucosa from your mouth all the way down. And so in order for that to serve as a selective barrier… So we want the good things to come through nutrients of course, and then we want microbes in particular, toxins, just things that are really not good for our body, of course, we don’t want those to come through. So, our body has various mechanisms in place to regulate that and prevent that and to change it depending on the needs of what’s going on in the gut.
So, that really involves, kind of at its core, in terms of the classic definition of intestinal permeability is the spaces between those epithelial cells. And so those are regulated by several mechanisms, but the main one really is the tight junction complex. That’s a complex of proteins. It basically kind of sews the cells together. So basically, there’s this really tight, fairly impermeable barrier that only allows very small molecules to get through, but that can be regulated by the body through processes such as zonulin release. So, zonulin is sort of a product that our epithelial cells produce that basically increases the permeability. So, there are physiological scenarios where that may be needed for say fluid regulation, electrolyte regulation, those sorts of things, even circadian rhythms.
We know that permeability can increase just naturally during the day, and that’s part of the circadian rhythm regulation of intestinal permeability. So, that allows kind of facilitates nutrients getting through. So, there’s some physiological purposes to increasing permeability under fairly regulated conditions, but of course we know that can be dysregulated by infections, by toxins, even by stress, and that allows larger molecules to get through, even bacteria to get through. And then that can overstimulate the immune system, leading to a wide range of chronic conditions. I think there was a recent review article in, I believe it was Nature Reviews Gastroenterology, that basically reviewed all the evidence linking that to autoimmune conditions, chronic inflammatory conditions, and a wide range of allergic type conditions, so pretty much across the board, most of the conditions that we see in practice. So, very, very central.
Dr. Kara Fitzgerald: Yeah, it’s an extraordinary turnaround from when I was preparing to go to medical school. Yeah, it’s extraordinary, because really what isn’t pathological intestinal permeability associated with?
Dr. Thomas Fabian: Absolutely. Yeah. And so I think research has progressed not only in terms of understanding intestinal permeability in a bigger context, understanding the details, all the factors that are involved, how it’s regulated, factors that increase it, factors that help prevent that from happening. But in addition… So, that of course spawned some additional types of testing that are available for that. The one that we use with GI-MAP is fecal zonulin. So, that’s a great marker for kind of classic intestinal permeability. When you see elevated levels of zonulin, that could be related to even gluten exposure, stress. We see it frequently in autoimmune conditions, allergic conditions, even just extraintestinal symptoms. So, it’s common, for example, for patients to have skin issues, gut brain access issues, musculoskeletal types, symptoms. We see that all the time. Eczema.
Dr. Kara Fitzgerald: Yeah, it’s a fundamental investigation really for really any condition with some extent of chronicity, I think.
Dr. Thomas Fabian: Exactly.
Dr. Kara Fitzgerald: Maybe a little bit less concerned about acute, although we can see acute bit to something chronic when intestinal permeability isn’t sufficiently addressed, like say, food poisoning.
Dr. Thomas Fabian: Right. Yeah, I mean that is a point to know. There are some things that can raise it just sort of short term, may not be as much of an issue, but certainly chronic elevation. But beyond the concept of intestinal permeability in leaky gut, particularly involving tight junctions, really the idea of the intestinal barrier has expanded to include other components. So, now in terms of modern assessments with comprehensive stool testing, we have the ability to assess other contributors, other parts of this barrier. So really just to kind of zoom out a bit… We’re always focused, of course, to some extent in functional medicine on sort of the systems approach, systems biology. So zooming out a bit and looking at the intestinal barrier, even the gut microbiome, the normal microbiome is a key part of that barrier, and it really forms this sort of intimate relationship with the barrier where these microbes secrete various products that promote various aspects of the barrier, and then various components of the barrier actually also support the microbiome.
So, there’s all these different interactions. So, there’s the microbiome layer. So, we know if we have dysbiosis, that is one potential insight into the state of the barrier. Then the next layer down essentially would be the mucus layer, which includes not only….
Dr. Kara Fitzgerald: I want to just flag you. I actually want to ask you a couple questions. So my first question, I want to know the microbes. So I’m going to ask you about the microbes that are supportive and who we want to think about. And then I want to ask you, when you look at a… Actually I have one question before I ask you this one. Is the connection with the central nervous system permeability… If you see a significant gut permeability issue, are you thinking blood-brain barrier or would you be concerned about blood-brain barrier? Would you be less concerned, given what the person is presenting with or maybe the age and more concerned, obviously if they have some sort of a neurodegenerative condition? Can you just speak about that? And can there be insights on the GI-MAP that would make you think blood-brain barrier?
Dr. Thomas Fabian: That’s a good question. So, I’m not aware of something specific, other than the general fact that when patients do have increased gut intestinal permeability, that that’s been linked in research to sort of generally an increased risk for barrier dysfunction at other places. So, you can think of the gut-skin axis. We certainly know that there’s a two-way interaction there in terms of barrier dysfunction. That’s true for the lungs. There’s definitely a strong gut lung connection. And then of course the gut-brain axis, which does involve the blood-brain barrier to some extent. But I can’t say that there are specific factors that I’m aware of with GI-MAP that you would specifically identify as implicating blood-brain barrier issues.
Dr. Kara Fitzgerald: Okay. Okay, And I want to point gut genital urinary, chronic UTI’s, interstitial cystitis, so yeah, it’s important for us to just remember that likely, well, it’s influencing beyond just the local environment. Okay. So, let’s talk about good guys. When you glance at a report, what are you looking for in terms of protective factors, protective microbes, and microbes of concern?
Dr. Thomas Fabian: You can kind of roughly break that into, of course, the good guys, the bad guys. So on GI-MAP, it’s fairly easy to recognize. So, we have a full section on pathogens. Pathogens are well known to disrupt the barrier in many different ways. So, they all have kind of their own set of virulence factors in particular, some of which specifically target the barrier and disrupt the barrier in various ways. So, that is a key part of the assessment. Of course, you’re looking essentially at the balance, what are the factors that disrupt the barrier? What are the factors that promote a healthy barrier? So in terms of pathogens, I’ll just give a couple examples. So, C.diff is a really common one. We actually do see that. I think the stats are on average about three to 4% of the population has detectable C.diff.
A large proportion of that is asymptomatic. But if they are expressing those toxins, then we know from research that that’s really sort of how C.diff causes the main problems in the gut that lead to inflammation. And so these toxins A and B, and we have the genes for both of those toxins on GI-MAP. They can actually damage the intestinal barrier beyond just leaky gut. So, they can cause increase in those spaces between the cells, but they can actually damage the epithelial cells themselves, and that’s basically through this activity of the toxin. And then that can basically increase the exposure of the underlying lamina propria to these microbes, even just normal microbes. They don’t necessarily have to be opportunists that are producing LPS, just normal microbes that are in the wrong place. So, they’re getting too close or they’re getting even across the barrier, that can stimulate the immune system.
So, there are various ways in which they do this. There’s, for example, staphylococcus aureus and enterococcus produce enzymes that can actually disrupt the barriers directly. So, those enzymes act on barrier components, the tight junction components, and can directly cause leaky gut. So, there’s a sort of range of things that different pathogens will do. One of the things that we’ll get to a little bit later, because that’s going to be a significant focus here today, is talking about the regeneration of the epithelial layer, which when we’re talking about gut healing, so that really takes us beyond just this concept of leaky gut.
Dr. Kara Fitzgerald: Yes.
Dr. Thomas Fabian: First, we have the stem cells and the crypts. We also have the process of differentiation where those stem cells become the individual types of cells in the barrier, like in enterocytes in the enteroendocrine cells. And so the pathogens can influence that process. Basically they can interfere with the proper differentiation, so you don’t get these fully functional cells. They can increase cell death. So, you may have heard, for example, the term villous atrophy, which is common in a lot of infections. And in some cases, that can be due to the fact that pathogens can accelerate cell death, cause cell death in various ways, so that puts an extra burden on the regeneration process. Those same pathogens can interfere with that regeneration process. And obviously if you can’t regenerate the lost cells, then that’s another factor that contributes to barrier dysfunction.
Dr. Kara Fitzgerald: Wow. Okay. I want to make sure that we circle back. At the end of the talk, we can continue to lay it out to just give really key take home points in both using the GI-MAP, but also the interventions that we’re going to be leaning on as you kind of outline some of these new areas that we want to be thinking about. Let me see. What about the differences among the different parts of the gastrointestinal tract? Can you speak to that?
Dr. Thomas Fabian: Yeah. Yeah. I think before we kind of fully dive into that though, I wanted to… So, we talked about the microbiome being a key part of the barrier, and then there’s the mucus layer, which has secreted factors, like secretory IgA is a part of the mucus barrier, these antimicrobial proteins and peptides. So, it’s like alpha defensin, proteins like that that also have antimicrobial function produced by what are called paneth cells. That’s a type of epithelial cell. So, that’s a big part of the barrier. Then, of course, the epithelial cells themselves, and then there’s the immune system. So, you essentially have kind of four main components to the barrier. So, understanding that, then you can see from research that those components can change as you go through the GI tract. So for example, one of the big differences is in the mucus layer between the small intestine and the large intestine.
So, we know that the small intestine typically has, especially the upper small intestine, which is involved primarily in absorption… So, we know the mucus layer is much thinner there. And the thinking is that it’s thinner to allow those nutrients, more easy access to get through and be absorbed. Further down as you get towards the ileum, when that microbial concentration increases, then you need a thicker mucus layer to start to provide more protection and distance between those microbes. So, you get a thicker mucus layer a little bit to some extent, in the ileum. And then in the colon, that really changes a lot. So in the colon, you have two mucus layers. So, the deeper layer that’s right next to the epithelium is this very kind of thick, impenetrable layer. And then there’s the outer mucus layer, which in the colon is where a lot of these mucus dwelling microbes, like akkermansia, tend to thrive.
And those same microbes actually help promote the production of mucus. They actually can influence the whole process of regeneration of these cells so that… For example, akkermansia can skew the development of cells more towards these mucus producing cells, which are the goblet cells. So, lots of really interesting interactions coming out of the research and how microbes are involved at every level of this barrier sort of renewal process. One of the kind of stats I just want to throw out as far as the barrier, just to I think set the stage for this sort of focus on the regeneration aspect of it, is essentially I think we’re all aware that the intestinal lining turns over every three to five days or so. So, that amounts to… I mean, they basically have done estimates of the number of cells involved, and that’s up to 50 billion cells are shed every day in the intestine.
So, of course, they have to be renewed. They have to be replaced. And that’s really a very fine- tuned process. Lots of studies now show that diet and the microbiome can actually influence that process. So, there’s a lot of ways in which we can influence the barrier, again, beyond just the original concept of leaky gut.
Dr. Kara Fitzgerald: It’s really fascinating, and I appreciate you bringing this to our attention. I know a lot of us are aware of akkermansia. I happen to be a big fan of it. We’ve talked about it many times. And we know that it’s a mucin degrader, but what you’re saying is that it’s actually… It seems like it degrades in order to allow for renewal. It sets the stage for the recycling journey and keeping that barrier really intact and functioning. Would you say that’s true?
Dr. Thomas Fabian: Absolutely. Yeah. So, studies indicate that it doesn’t necessarily, under most circumstances, kind of over consume or break down the barrier excessively, but at the same time that it’s consuming the mucus, it’s producing factors that stimulate the renewal of mucus, and that’s actually a really dynamic process. So, I think most practitioners may not be aware that the entire mucus layer is replaced on average every one to two hours.
Dr. Kara Fitzgerald: Incredible.
Dr. Thomas Fabian: So, it’s a highly dynamic process.
Dr. Kara Fitzgerald: Incredible.
Dr. Thomas Fabian: Yeah. Yeah. And I think… So, let me draw the distinction though, between commensals like akkermansia that promote sort of this homeostatic balance versus pathogens. So, another set of virulence factors secreted by certain pathogens are enzymes that basically break down the mucus, and they can break it down completely. So, they’re essentially kind of-
Dr. Kara Fitzgerald: Like toxins A and B from C.diff? I mean, those guys-
Dr. Thomas Fabian: That one isn’t of the ones that necessarily digest mucus, but there are others, I believe from say salmonella and other pathogens. And pathogens, they have a whole kind of tool belt of things that they can use to kind of access the barrier because that’s really how they do their damage and how they can replicate and how they can re-engineer the whole gut environment to their favor. And so that’s really a big difference there, is that pathogens tend to really damage the barrier. They can over degrade the mucus, they can dissolve the tight junctions, they can kill off the epithelial cells, et cetera, et cetera. So, there’s lots of things pathogens can do. But as far as the good guys, probably another one we would want to talk about is butyrate.
Dr. Kara Fitzgerald: Yes.
Dr. Thomas Fabian: Butyrate producers. So, there’s a lot of details here and we certainly can’t cover it all in the podcast. So, if you kind of get a little bit lost in some of the details, we can kind of come back and summarize. But really, the bottom line for a lot of this is ultimately you want to make sure you’re working towards balance. Because regardless of some of these details, ultimately it comes down to balance. You want enough of the good guys. So with GI-MAP, we have that commensal section and we have a really great representation of some of these key organisms that play a role in supporting the barrier. So when we’re talking about expanding our view of assessing the barrier, assessing the commensals is a really important part of that.
Dr. Kara Fitzgerald: Let me just ask you a question on this topic. You and I have talked about this before. We’ve had a lot of discussions in our clinic, in our clinic rounds about akkermansia and the fact that it shows up at higher levels in certain conditions, like MS comes to mind. And my thought, so I’ve pushed back on whether or not… I don’t know that it’s a pathogen. I don’t know that there’s any evidence for it being pathological, but it strikes me because we know intestinal permeability, is certainly present in all of the conditions that I’m aware of associated with higher akkermansia. There’s just a couple maybe papers that it’s shown up.
Could it be evidence, could it be a surrogate marker of excessive mucin degradation, pathological mucin degradation. So, akkermansia is showing up at higher amounts in the fecal bolus. I just want to get your input. I’ll bring it back to my clinician rounds. And I know people here are listening or thinking about it. What are your thoughts there?
Dr. Thomas Fabian: So, there was some original research that sort of suggested that maybe the case when there were these original observations, that akkermansia was higher in certain kind of neurodegenerative neurological type conditions like MS, Parkinson’s, et cetera.
Dr. Kara Fitzgerald: Yeah.
Dr. Thomas Fabian: Since then, it’s really not clear if it’s playing a role. So, it could be just sort of a downstream effect of some of the changes that happen as part of these neurological conditions, neurodegenerative conditions. So, we know that a lot of them, of course, when you start to get neurodegeneration, that can have a negative effect on the gut-brain axis obviously.
Dr. Kara Fitzgerald: Sure.
Dr. Thomas Fabian: So, we see similar changes. For example, in Parkinson’s, one of the early signs is constipation. And with constipation we often, whether it’s related to Parkinson’s or not, we often see elevated, sometimes decreased, but sometimes elevated akkermansia. And I was really curious about that because in a general pattern of poor digestion, that’s one of our most common patterns, you see a lot of overgrowth. You may see course low elastase, high H. Pylori, which can suppress stomach acid. We’ll often see high akkermansia. So, I looked into the research to see what’s there as far as that possible link. There wasn’t much initially. Then eventually a study came out showing that high sugar consumption is one of the factors that can lead to increased akkermansia. And since then, there’s a little bit more research kind of adding to that picture. So, this is mostly a clinical observation, but what we think is in patients that have degenerative conditions, that’s possible that the reduced digestion component is an early part of the effects of reduced nerve function, and that can lead to reduced digestion.
When you have increased substrates getting into the colon, we know that can stimulate overgrowth of a number of microbes. And we just see that pattern a lot, so it kind of makes sense based on the pattern. We’re sort of waiting to see the research catches up with that. But the story of akkermansia being a cause of these conditions, so far, there’s not enough research to really implicate it.
Dr. Kara Fitzgerald: Right. Right. I had a thought earlier when you were giving us some of the extraordinary turnover rates of the cells and the mucin, et cetera, is that it’s just a massively energy consuming organ.
Dr. Thomas Fabian: Yeah, right.
Dr. Kara Fitzgerald: And we know that deterioration of energetics are involved in neurodegenerative conditions as well. We can see mitochondrial defects, people who have mitochondrial variants, mitochondriopathies , genetic mitochondriopathies, actually even acquired mitochondriopathies, of course, they show up first in the gut. So, that was a thought that I was flagged on earlier when you were sharing about this, just the change to energetics. It’s not surprising that neurodegenerative conditions would show up in the gut first.
Dr. Thomas Fabian: Right, absolutely.
Dr. Kara Fitzgerald: You know for this reason.
Dr. Thomas Fabian: Yeah. And there’s actually a growing amount of research on that, that very topic, that because there’s such a high energetic demand obviously if you’re turning over this many cells, and these cells are performing so many functions, I mean, that’s such a critical set of functions that they have to carry out to manage that interface between the environment and are internal physiology, very energetically demanding. And I think it’s second only to the brain in terms of consuming overall energy. So, of course you need a lot of substrates for that. And when there are local conditions in the gut that restrict some of these nutrients, then that can certainly be part of the problem. So, I think that that can be an issue with, for example, inflammatory bowel disease and conditions where you have a lack of the butyrate producers.
Dr. Kara Fitzgerald: Yes.
Dr. Thomas Fabian: So especially in the colon, when you have a lack of butyrate. That makes up I think 70, 80% of the substrate for energy generation for healthy colon cells. And so they think that actually one of the problems with regeneration and healing the gut and IBD is when you have a lack of butyrate, because typically butyrate producers are low in patients with IBD.
Dr. Thomas Fabian: So, it’s interesting that you call attention to the energetics just because there is such a high energy demand. Again, when we are thinking about the intestinal epithelium and the energy demands for the turnover for all the functions that they are performing, it’s really second only to the brain in terms of its energy demands. So just an example, in the colon, we know that the normal microbes, especially the butyrate producers, provide a lot of energy substrate for the colon cells, so particularly butyrate. So, we know butyrate makes up 70 to 80%.
Dr. Kara Fitzgerald: And just remind me again on the GI-MAP, the top butyrate producers, what we’re looking at.
Dr. Thomas Fabian: The top butyrate producers on GI-MAP would be the Faecalibacterium prausnitzii, so that’s really kind of the top butyrate producer, the widely recognized keystone species. And then we also added recently Roseburia. Roseburia is another prolific butyrate producer. And then you can get some indirect insights into butyrate, for example, from secretory IgA because one of the key stimulants for that is butyrate. So, you see low butyrate or low butyrate producers, and then of course low secretory IgA. That can be part of the sort of this picture overall suggesting insufficient butyrate. But again, you’re always putting this whole picture together. But if you have a lack of butyrate in a scenario of, say for example, of inflammatory bowel disease… So, we know that typically in a Crohn’s disease, the normal microbes can be reduced by somewhere from 10 to 50-fold, so you’re getting a much lower production of butyrate, which is really kind of starving those cells of the key fuel that they use.
So when you have damage that’s happening from the inflammation in IBD, then you’re not able to repair that barrier so well when you don’t have sufficient energy. So, that’s kind of one of the key processes that’s thought to be involved. And actually, the normal microbes produce several other factors as well. I’ll just mention a couple just to help everybody understand. These beneficial microbes produce a lot more than just, of course, butyrate and some of the short chain fatty acids. One of the ones that’s becoming more and more recognized, it’s not really talked about, is called purines. And so these are precursors to nucleic acids that are needed for cell division. They’re needed for ATP itself, for example. So, we know that those can be decreased in various conditions, IBS, IBD, et cetera. And even a recent study showed that Faecalibacterium prausnitzii, which is on GI-MAP. Of course, not only produces butyrate, but it does break down fiber, and the fructose that it generates from fiber.
So, fructose at a low level actually is supportive for the intestinal barrier. So, the kind of bottom line is that these microbes are producing a pretty wide range of factors that are all supporting the healthy intestinal lining, in particularly this regeneration process. And when you have inflammation and pathogens and infections, a scenario that is causing an increased demand for regeneration, then you can really get into a situation where it’s difficult to repair the barrier.
Dr. Kara Fitzgerald: Yeah, it’s interesting, just if you’re talking through this. The term that has is being bandied about a lot these days is postbiotics, all of these extraordinary postbiotic layers that are regenerating the epithelial barrier and all of that amazing information on mucin and so forth. So, it requires a ton of energy and it requires a really robust, healthy microbiome. And of course, we all have gut issues. I mean, when you think about what we’re eating in the United States and elsewhere and how we’re living and stress, to circle back to that point you brought up earlier, of course, pathological leaky gut is everywhere and we all have dysbiosis. We’ve been giving our microbiome and our intestinal lining just horrible information in terms of our diet.
Dr. Thomas Fabian: Absolutely.
Dr. Kara Fitzgerald: That’s really no surprise. So, let’s-
Dr. Thomas Fabian: Yeah. Yeah. I was just going to say that’s certainly part of the barrier assessment, so we definitely advocate kind of a bigger picture view beyond just leaky gut, as I mentioned. And to really boil it down to most simple approach, assessing those same factors, whether it’s diet, whether it’s pathogens, opportunistic overgrowth, et cetera. You, of course, want to recognize what are the things that are interfering with barrier function, and then emphasize the things, of course, remove those, if possible, or address them, and then at the same time, emphasize the microbes and the diet factors, et cetera, that are promoting a healthy intestinal lining. So along those lines, I would kind of come back to akkermansia and a few others as well. So when it comes to this whole concept of regenerating the epithelial barrier, we know there’s the normal sort of homeostatic process, which again, we’re turning over 50 billion of these a day, so your body just needs to keep doing this. Your normal commensal microbes are promoting that process in several ways.
So akkermansia, as I mentioned, in particular, can actually produce factors that help to promote the proliferation of stem cells so that you get the cells then to replace the ones that are lost. But akkermansia does more than that. It actually produces factors that then help these cells assume their proper functions in cell type.
Dr. Kara Fitzgerald: Wow.
Dr. Thomas Fabian: And in particular, it helps promote those mucus producing cells, the goblet cells. And that’s been shown to decrease with age. So, hopefully we’ll touch on that.
Dr. Kara Fitzgerald: That’s so interesting.
Dr. Thomas Fabian: Yeah. And so you see these correlations where akkermansia goes down with age for a lot of people. But centenarians, one of their stand-out features is they, so they may have a healthier intestinal barrier overall because they have better akkermansia. And then so far, we only have animal studies, but animal studies do show that you can give akkermansia as a probiotic and that can help these goblet cells that produce mucus recover. And that’s a big, big deal because the mucus layer can decrease three to six-fold in thickness with age, and akkermansia was able to increase that up almost back to normal. So, you’re talking about sort of reversing some of these aging changes that happen in the intestinal barrier just by applying these microbes strategically.
Dr. Kara Fitzgerald: That’s so interesting. And again, just going back to the fact that we turn it over within hours, we need to be competent at doing this. And I would imagine many of us just simply aren’t, and then we lose it over time. And the other piece that’s really extraordinary, I want to underline the point that you made, is that akkermansia and other players, you can speak to, the other factors are involved in not just stem cell production, which is amazing because that’s something that really drops off with age, but differentiation of stem cells and helping them get into their jobs, differentiate into the various somatic cells that we need to be functioning and thriving. I think another phenomena that happens with aging is that there may be these stem cells, but they’re sort of almost ghost cells. They’re subpar. They’re monoclonal, but not differentiating and not functioning.
Dr. Thomas Fabian: Yeah.
Dr. Kara Fitzgerald: It’s fascinating to me the role that the microbiome plays probably locally, and I want you to keep talking about that, but I wouldn’t be surprised if it has extra intestinal influence as well.
Dr. Thomas Fabian: Absolutely. Yeah, I mean, that’s actually referred to in the big picture… In science, they refer as the stem cell niche or niche, however you like to pronounce that. I say niche. And so that’s really where the cells surrounding the stem cells, the diet factors, the microbes in that vicinity all have an influence on the health of the stem cells. So, that’s part of the picture. You can break it down into all kinds of details now based on the studies that are out there, but there’s evidence that these stem cells themselves lose some of their functionality as they get older. They can undergo senescence. They can just not proliferate as much as they should, particularly when really needed to repair damage. Some of those cells in the surrounding area, such as the connective tissue cells, the immune cells, they all undergo cell senescence as well, epigenetic changes. So, lots of things going on during aging that can affect that sort of process. So again, from dietary standpoints, there’s ways to potentially help to improve that. And actually, there’s really good research now on fasting-
Dr. Kara Fitzgerald: I was going to-
Dr. Thomas Fabian: … various types of fasting. So there’s unrestricted fasting, caloric restriction, ketogenic approaches. We know that ketones in particular, which are generated during fasting, help to regenerate and sort of essentially almost rejuvenate these stem cells so that they’re better able to carry out their functions as we get older.
Dr. Kara Fitzgerald: I think. So, I want to underscore what you’re talking about here by shifting your focus onto supporting stem cells, stem cell regenerations, stem cell functionality, et cetera, and that we need this full microbiome. We’re thinking about diet. You’ve just brought in fasting, and not just fasting, but production of ketone bodies as being key players in helping with barrier regeneration through stem cell proliferation. And that’s just a game changing concept Tom, you’ve brought a few game changers to this podcast. We had a great conversation not too long ago on hydrogen sulfide. And by the way, folks, we will link to Tom’s previous conversations with me so that you can access them. And you have a knack for really being in the front of the science, and we need to be considering this and all of the variables that are going to influence not just barrier repairs. So, we’re moving way beyond glutamine. Glutamine might be indicated way beyond zinc carnosine, again indicated in a smart intervention, but thinking more broadly.
Dr. Thomas Fabian: Well, I think that’s where the… Yeah, I mean, I know we’re moving more and more over time as the field to incorporating sort of precision medicine, personalized medicine approaches. And at the other end of the spectrum, also incorporating the system’s biology, sort of big picture interconnectedness. Both of those come into play. We have a lot more research now to inform both sides of that. And that’s really where this all comes into play, is when we’re thinking about gut healing it really is way more than just glutamine and zinc carnosine and a few other things that. Those are standbys. There’s good research. Those are still, of course, helpful, but they’re not the full picture. And that’s especially good to know when you’re working with patients and you’re not getting those results that you’re hoping for. You may want to dig a little bit deeper, you may want to look at the microbiome more depth. And if they have low akkermansia, there are ways to increase akkermansia. Lactobacillus is another one that…
There’s quite a few studies now showing that that also helps promote repair of the epithelial lining, can both help stimulate regeneration and also promote differentiation. From a diet standpoint, one of the ones I want to mention is… So, these compounds called indoles, which are present in cruciferous vegetables, various types of indoles, particularly something called I3C for short, indole-3-carbinol.
Dr. Kara Fitzgerald: Which we think about for estrogen metabolism.
Dr. Thomas Fabian: Right. But it plays a crucial role in this whole sort of barrier differentiation process. And so there’s certain things like fasting, ketogenesis, microbes like akkermansia, lactobacillus, even E. coli that promote this sort of stem cell proliferation. But at the same time, you don’t want that to be sort of excessive or out of control. You want that to be balanced. And research shows that one of the main balancing factors are these indole products. And there are two ways you can get them. One is from cruciferous vegetables. So again, this indole-3-carbinol gets converted to DIM, diindolylmethane. That’s facilitated by stomach acid. So, this is where you’re connecting the dots that if you don’t have good levels of stomach acid, you may not be doing that conversion very well. But they act through something called… And I brought this up I think in probably one of the previous pod podcasts.
It’s got a complicated name, but it’s called the aryl hydrocarbon receptor. It plays an absolutely critical role in this whole mediation of environmental and bacterial signals and barrier functions. And actually, I do have a review paper here I just want to read a couple of the lines from to kind of underscore this. This one we can put in the show notes potentially.
Dr. Kara Fitzgerald: Okay, good.
Dr. Thomas Fabian: So, the title of the article is “Cell Intrinsic Aryl Hydrocarbon Receptor Signaling is Required For the Resolution of Injury Induced Colonic Stem Cells”. And so the lines I wanted to quote here, just cause I think they’re so impactful, is “the aryl hydrocarbon receptor is an environmental sensor that integrates microbial and dietary cues to influence physiological processes within the intestinal environment”. So, it plays a major role in interpreting what’s going on, and then adjusting processes. And then the last line says, “AHR has had a pivotal position in the delicate balance between controlled regeneration and malignant transformation”.
Dr. Kara Fitzgerald: Fascinating.
Dr. Thomas Fabian: And so it’s actually thought of as… There’s a review paper that said that this HR receptor is now thought to be considered a tumor suppressor for colon cancer.
Dr. Kara Fitzgerald: Fascinating.
Dr. Thomas Fabian: So, this is really gets into this whole sort of barrier regeneration, but it’s a delicate balance. You don’t want to have too much proliferation because that may set the stage for some sort of malignancy tumor, for example, colon cancer.
Dr. Kara Fitzgerald: Well, what would excessively stimulate in our toolkit. When you caution us, what are you thinking about specifically?
Dr. Thomas Fabian: So, there’s good research now suggesting that chronic infections…
Dr. Kara Fitzgerald: Okay. Okay.
Dr. Thomas Fabian: So, basically it’s sort of a built-in response that when you have gut infections, that proliferation increases because you’re trying to basically prevent or reduce the damage that the pathogens can cause. Some of them are actually inside the cells. They infect the cells, so it’s a way to get rid of those infected cells. So, it’s going to accelerate that process. Inflammation, chronic inflammation is also known to accelerate that process. Long term, chronic inflammation could be a major contributor to stem cell exhaustion so that you’re no longer able to sort of regenerate if you have too much inflammation. But kind of getting back to the hydrocarbon receptor and these indoles is they really help to promote that differentiation process so that you get that proliferation is managed, it’s regulated, not excessive. And this is just an example of all these factors that come into play in the barrier from diet and from the microbes that help to balance this process so that you can ensure healthy outcomes.
Dr. Kara Fitzgerald: So, I3C and DIM, so after it’s converted to DIM. And we can prescribe DIM as a standalone, which in addition to cruciferous obviously in the diet, will stimulate these receptors.
Dr. Thomas Fabian: Right.
Dr. Kara Fitzgerald: And thereby promoting balance.
Dr. Thomas Fabian: Cruciferous vegetables are a key source, and then also products from the microbiome, especially lactobacillus and other species. Those are probably the best studied that can convert tryptophan into these indol metabolites. So, there’s several ways to get these right products. And research also shows that the expression of that receptor is primarily sort of upregulated, just normally in the upper small intestine also plays a really key role in oral tolerance. So, there’s just lots of benefits to-
Dr. Kara Fitzgerald: Interesting.
Dr. Thomas Fabian: Yeah. Yeah. So, I think it’s just sort of overwhelming how much of this research has been coming out in recent years, but I think the bottom line is it leads to potentially new ways in which we can assess the barrier and also essentially approach treatment and improve barrier function.
Dr. Kara Fitzgerald: So fascinating. It’s just really cool. I think about allergic disease. I mean, I teach on it at IFM. And of course we see… I think one, there was a recent statistic, one in four people have allergic sensitization. It’s probably even higher than that, but I’m thinking about oral tolerance a lot, and we see adult-onset loss of oral tolerance and establishment of allergies, even anaphylaxis. And this is interesting. It’s just potentially another tool we can think about. And probably approaching it… I mean, would we use DIM, I’m just sort of thinking out loud, I3C or DIM to help promote tolerance through these receptors, or would we be using the various probiotics and prebiotics and maybe both? Just fascinating.
Dr. Thomas Fabian: Yeah, I mean, it would be good to see more human studies at this point, particularly on that. So, of course, what’s done so far is animal studies. So, I’d have to go back and look at my research to see-
Dr. Kara Fitzgerald: How you might translate that?
Dr. Thomas Fabian: Yeah, there’ll probably be more clinical evidence on the probiotic side than there would be on DIM, for example. The DIM is mostly based on studies in animals at this point.
Dr. Kara Fitzgerald: It’s still cool. It’s interesting, and it’s always fun to think way outside the box, which we can do in this medicine. So with chronic infections… And this would be anything that’s going to stimulate proliferation, so just the whole chronic… Plenty of our patients come to us with these smoldering… I mean, dysbiosis could fit into the category of being a chronic low-grade infection, and thus stimulating proliferation, increasing risk for colorectal cancers, which are on the rise. Thoughts on that?
Dr. Thomas Fabian: Yeah. Yeah, I mean definitely, it’s going to be a little bit microbe specific. So, I wouldn’t want to necessarily extrapolate and say all pathogens, all opportunists have that effect. And in fact, there are a few examples of pathogens like Shigella, which actually is on GI-MAP. We don’t see it very often, but Shigella actually has the opposite effect. So, that one in particular produces virulence factors that basically reduce regeneration. And for particular reasons, that’s an advantage for that particular pathogen. So, not necessarily a feature of all pathogens, at least during the infection, but the general idea of chronic inflammation promoting excessive inappropriate proliferation, I think is out there. That’s generally-
Dr. Kara Fitzgerald: Established, yeah.
Dr. Thomas Fabian: Yeah, that’s one of the sort of generally accepted risk factors, I think for increased, not just cancer, but of course virtually any chronic disease.
Dr. Kara Fitzgerald: Right.
Dr. Thomas Fabian: But there will be some nuance though.
Dr. Kara Fitzgerald: Yeah, I agree with you, but I think any weight on the web is potentially a problem. I want to just circle back to you talking about ketones and the benefit of ketones and ask your thoughts on a ketogenic diet. So, you talked about fasting stimulating stem cells and gut regeneration and being an important tool in our toolkit, or time restricted eating. But ketogenic diet certainly in animal models have had some negative outcomes. We haven’t seen the same outcome translated to humans. Ketogenic diets are generally beneficial, although we can see that it can sort of lead to almost a compromised microbiota. So, I want to ask you on using a ketogenic diet for stem cell regeneration and your thoughts. And we can always consider pulsing. It shouldn’t be a long-term intervention, unless you’re doing something working with somebody with epilepsy, or maybe certain type of diabetes. But the other question that I want to ask you after that is using ketone esters. And would that be something in your toolkit for thinking about stem cells?
Dr. Thomas Fabian: That’s a good question. So, it’s hard to extrapolate from the research the long term. We don’t really know enough at this point, I think, to really say what the effects would be long term. Short term, the research does suggest, and again, I don’t know if there’s enough yet for us to say, yes, this is a well-established clinical tool, but enough research to suggest that a ketogenic diet, increased availability of ketones in the stem cell niche should help to promote regeneration. There’s an accumulating amount of studies for that. But I would say that probably the majority of studies I’ve seen have to do more with fasting, and fasting will upregulate ketogenesis in the stem cells. So, so far, it seems that the best evidence is based on fasting.
Dr. Kara Fitzgerald: And what kind of fasting structure?
Dr. Thomas Fabian: So, I’ve come across studies both for time restricted feeding diet, long term kind of longer-term dietary restriction, and then there was one study on the fasting mimicking diet.
Dr. Kara Fitzgerald: Oh, interesting.
Dr. Thomas Fabian: Yeah. So, there seems to be a growing amount of evidence that different types of fasting type diets do tend to stimulate ketogenesis, which then promotes this regeneration process. There’s actually a fair amount of research also on high fat diets, not necessarily ketogenic diets, but those actually can lead to excessive proliferation. So like anything, I think it’s a balance. Whether the standard ketogenic diet amounts to “excessive”, I think remains to be determined. But my guess is that sort of short term for promoting healing, that there’s probably a relatively low risk, probably significant benefit for patients that may be older or compromised in some way where they’re not able to heal the barrier well.
Dr. Kara Fitzgerald: And there’s a huge continuum in implementing a ketogenic diet. One can do so in a balanced way and one can do so with bacon and cheese.
Dr. Thomas Fabian: Right.
Dr. Kara Fitzgerald: So, it’s going to be a far-reaching effect on the microbiome depending on your choice of implementing a keto diet.
Dr. Thomas Fabian: Right, and it does kind of suggest, again, looking at beyond just sort of one or two factors at a time.
Dr. Kara Fitzgerald: Yes.
Dr. Thomas Fabian: And we just talked about that whole AHR receptor, the cruciferous vegetable derived indoles that promote differentiation. So, it’s possible that if you have a balanced diet that includes cruciferous vegetables, for example, while you’re on that healing ketogenic diet, that may result in better outcomes. Again, we don’t have direct studies demonstrating that that combination will do that, but we have individual studies that suggest that could be the case.
Dr. Kara Fitzgerald: And we have studies looking at certain dietary patterns just being beneficial over the long haul. We’ve got blue zone data, those centenarians. We’ve got an idea of the snapshot of a healthy centenarian’s gut, we have our study showing an eating pattern with a balanced high vegetable, some animal protein, et cetera, resulted in bio-age reversal. There’s plenty of studies on the Mediterranean diet as beneficial, and also showing biological age reversal. So, I think we have some indirect evidence that it’s likely really beneficial.
Dr. Thomas Fabian: Exactly. Yeah.
Dr. Kara Fitzgerald: All right. So, what else do we want to talk about here? Intestinal, do you want to run through some of the key markers? So, let’s summarize interventions. Let’s run through key markers on the GI-MAP. And before we get there, is there any of the other background, any important points for us to be aware of?
Dr. Thomas Fabian: I think we covered most of the sort of main concepts when it comes to… I mean, the main points I think overall here is to, in terms of barrier components, again, kind of expand your view beyond just the tight junctions leaky gut that we’re looking at the microbiome, we’re looking at secretory IgA, we’re looking at mostly indirect markers for mucus like akkermansia, we’re looking at immune health. So, there’s this sort of combination of markers that help you understand holistically what’s going on with the barrier. And then in terms of that sort of introducing or just sort of emphasizing this developing area of epithelial regeneration as being a… That’s sort of the essence of gut healing. We used to think of gut healing as sort of healing those tight junctions, sort of improving intestinal permeability.
That is actually part of that process because that’s one of the features of the epithelial cell functions, but there’s much more to it than that. And really kind of looking at it more from this regenerative process and just appreciating that certain microbes play a role in that process, certain dietary factors play a big role, and that we may be able to influence that. So, that’s kind of the leading edge of where things are at now. But taking it back to looking at GI-MAP and how would you more comprehensively assess the barrier, again, it comes down to just looking at… If you see course pathogens, opportunists, overgrowth, we know that most of those will disrupt the barrier one way or another. So, you already know that likely the barrier is compromised just by pathogens and opportunists for the most part. And there will be some details there. And then also looking at the normal microbes, and if those are especially deficient, particularly these key ones like akkermansia, the butyrate producers, faecalibacterium, lactobacillus. We didn’t talk much about escherichia, but that one also plays an essential role in this whole intestinal barrier regeneration process.
That’s a common pattern that we see. If you see low escherichia, low akkermansia, and also low bacteroidetes, that is one of the common patterns that we see that suggests poor barrier function, especially in the colon. We actually know that those are all mucus dwelling. So, a lot of the bacteroidetes are certainly akkermansia is, and then escherichia is one of the key mucus dwelling. So again, some indirect ways of looking at the barrier there. And when you see those are deficient, especially for some of them, we have good tried and true ways to increase them. So with faecalibacterium, we’d want to look at fiber, polyphenols, postbiotics, as you mentioned, butyrate of course being kind of the best known, and of course, probiotics. We call those the four Ps, just to easily remember them. So, that’s prebiotics, polyphenols, probiotics, and then postbiotics. And then when you look beyond that to…
I mean, there are some sort of additional details like parasites can disrupt the barrier in different ways, especially giardia. And then there’s the intestinal health markers. So probably the, of course the best known as zonulin. That’s the most direct marker for leaky gut itself. But low secretory IgA, that almost always tracks with lack of normal bacteria, especially akkermansia. So if you see both of those low, akkermansia and secretory IgA, likely there’s a significant barrier issue. And again, we have lots of tools that we can use now and including probiotics to help to increase akkermansia.
Dr. Kara Fitzgerald: Good. Good. And we’re thinking now, everybody about intermittent fasting and the benefits on stimulating intestinal stem cell production and differentiation. And again, the really cool pearl you gave us about akkermansia being a player in stem cell differentiation, specifically to goblet cells, to make that mucin turns over every few hours, extraordinarily enough. And into that environment, we can only think about bringing a robust nutrient dense whole foods diet to make sure we have all of the ingredients for this incredible complex array of compounds to be made. However, on certain occasions, as you also brought up using a ketogenic diet or that, well, I brought up the idea of ketone esters, maybe some of these more radical interventions in the short term to help stimulate barrier repair, but some questions we both had around long-term.
Well as usual, you just brought a compelling conversation to New Frontiers. I’m always grateful for that. Folks will have links to the various papers that Tom has referenced in the show notes and will link to your other podcasts. I encourage people to listen to them, particularly the most recent one we had on hydrogen sulfide. It was another game changer. Maybe we’re overtreating what we infer is hydrogen sulfide, small intestinal bacterial overgrowth, and maybe we’re overtreating it to the detriment of where hydrogen sulfide is essential elsewhere in the body. So, that was a fun, cool, practice changing podcast. Anything else you want to leave our listeners with today?
Dr. Thomas Fabian: I guess maybe just a couple things. Maybe two of the factors that I would add, just to give a couple more pearls on things that may help with regeneration, there’s growing amount of research now on, of course, NAD precursors.
Dr. Kara Fitzgerald: Oh yes. Right.
Dr. Thomas Fabian: And nicotinamide riboside, and others that are out there. So, research is starting to show that those also can help promote the regeneration process, and essentially sort of in their opinion, potentially rejuvenate the intestinal lining with aging. So, kind of TBD on that one, but again, there’s a growing amount of research that that may be one of the additional benefits when patients are taking those. And even just some of the simple day-to-day nutrients like biotin. Biotin is essential for regeneration of the epithelium. And actually certain microbes, so I mentioned escherichia, which is E. coli, can stimulate proliferation of stem cells in various ways. One of them is by producing biotin. So again, there’s lots of factors that they can produce, and we don’t necessarily need to remember all of them, but the key is if you see them low on GI-MAP, you may want to consider ways to improve them. But other than that, I think the take homes would be just to remember and maybe encourage practitioners to seek out some of those research. And I will put hopefully some of those papers in the show notes.
But research has progressed tremendously to the point where I think we have more to work with now than sort of was typically noted 10 or 20 years ago for gut healing. But kind of coming back to our original point, glutamine is still quite useful, but we have more options now, I think.
Dr. Kara Fitzgerald: We’re zooming way out from just patching up the gut. Way out.
Dr. Thomas Fabian: Absolutely. And it’s sort of also realizing that a lot of what we’re already doing just has these additional beneficial effects that we didn’t know about.
Dr. Kara Fitzgerald: Yes. Yeah.
Dr. Thomas Fabian: So, it’s not totally changing everything we’re doing, of course. It’s just sort of adding weight to why are we recommending cruciferous vegetables, for example.
Dr. Kara Fitzgerald: Going back to nicotinamide riboside, which is supporting the production of nicotinamide adenine dinucleotide, NAD, which drops as we age. I mean, that’s a fundamental player in our energetics, again, going back to mitochondria. And it just occurs to me that when we’re looking at acquired and genetic mitochondriopathies, they first show up in the gut. And some of the key interventions are our go-to mitochondrial nutrients like CoQ10, alpha-lipoic acid. I wonder if there’s a place for those here in what you’re talking about.
Dr. Thomas Fabian: Absolutely. And that actually would be a connection back in part to what we talked about in the last podcast on hydrogen sulfide. So, there’s so much concern about now that there’s these breath tests out there that detect hydrogen sulfide, even though research actually shows it likely mostly comes from the oral microbiome. So, I’m kind of questioning whether and how much that would reflect. But certainly there isn’t enough research to suggest that really high levels of hydrogen sulfide in the gut can have negative impacts on the barrier. But normal physiological hydrogen sulfide is thought to improve barrier function in several ways. And one of those main ways is actually through your normal healthy colon cells, they’re getting enough butyrate, mitochondria are healthy, they have CoQ10. That’s essential to convert hydrogen sulfide into these detoxified products like just sulfate, but also to these antioxidants we talked about that have potent antioxidant activity.
And that’s thought to now support systemic antioxidant activity just part from the products produced by the microbiome that go through this process. And you need CoQ10 in these colon cells to do that. So, I think it kind of, again, speaks to how these things are all interconnected. And if you’re deficient in CoQ10 and not only you have just sort of the direct effects of CoQ10 deficiency, but then you won’t be able to detoxify hydrogen sulfide very well.
Dr. Kara Fitzgerald: Interesting.
Dr. Thomas Fabian: And that’s part of the equation that’s not focused on so much is maybe not so much avoid your cruciferous vegetables because those are healthy, that benefits, but make sure you can detoxify hydrogen sulfide well so that you can really gain the benefits from it.
Dr. Kara Fitzgerald: Fascinating. So, you might use CoQ10… I know we’re at the end here, but you might use CoQ10 if you suspect pathological hydrogen sulfide overgrowth?
Dr. Thomas Fabian: Absolutely. CoQ10, polyphenols, and fiber, because most hydrogen sulfide comes from the process of protein fermentation. So, excess protein getting into the colon leads to high ammonia, high hydrogen sulfide, et cetera. Lots and lots of research studies show that polyphenols and fiber actually help to reduce that process, and polyphenols may also directly help to detoxify hydrogen sulfide.
Dr. Kara Fitzgerald: And which ones? Which would be your top ones?
Dr. Thomas Fabian: For polyphenols? That’s a great question. So, I think the best studied would be extracts from berries, especially the anthocyanins or anthocyanidin. I always get them mixed up. One of my favorites is rosmarinic acid from rosemary.
Dr. Kara Fitzgerald: Yeah, mine too.
Dr. Thomas Fabian: CoQ10, for sure. Green tea extract has been studied and basically does that as well. Resveratrol, quercetin. So, they’re a growing list of these polyphenols that have been shown to detoxify hydrogen sulfide.
Dr. Kara Fitzgerald: Fascinating. They’re also, all of them are epinutrients, so I’ve been thinking about them in my work. That’s pretty cool.
Dr. Thomas Fabian: Absolutely. Yep.
Dr. Kara Fitzgerald: All right. Well, we’re at the end. Thank you for that little divergence, those handful of pearls for everybody. I know they will appreciate them. So again, Tom, thanks. Really good conversation.
Dr. Thomas Fabian: My pleasure.
Dr. Fabian is a leading expert on the role of the microbiome in health, immune function, chronic disease, and aging. As a translational scientist, his primary focus is on the clinical application of microbiome research in the integrative and functional medicine space. He received his PhD in molecular biology from the University of Colorado, Boulder, and has worked as a biomedical researcher in the biotechnology industry, and more recently, as a consultant in the microbiome testing field. Currently, Dr. Fabian serves as a consultant and science advisor with Diagnostic Solutions Laboratory and is also a Science Advisory Board member with Designs for Health. In addition, he is certified as a Nutrition Therapy Practitioner by the Nutrition Therapy Institute in Denver.