The Bile Acid Imbalance Accelerating Aging: How to Detect & Fix It

Have you ever struggled to understand why some patients just don’t respond as expected, even when you’re following all the usual gut protocols? In this episode, I sit down with Dr. Tom Fabian, who breaks down the latest insights from StoolOMX and GI-MAP testing and shows us how to put them into practice for our most complex cases.

We dive into how identifying specific types of inflammation, bile acid patterns, and microbial imbalances can guide more precise interventions, whether it’s introducing fiber, addressing biofilms, or supporting secondary bile acid production. Dr. Fabian makes the science practical, helping us see not just what’s happening in the gut, but what to do about it in real-world clinical settings. ~DrKF

P.S. Listeners, join me and Dr. Tom Fabian for a free LIVE webinar on October 23rd 2025 and get your questions answered on all things bile acids, pattern recognition on functional stool testing and precision-based interventions for optimal gut health and longevity. Register here.

Bile acids aren’t just for fat digestion. They’re powerful signaling molecules in the gut that influence inflammation, immune responses, and the balance of microbes. In this episode, Dr. Tom Fabian, translational science consultant and science advisor with Diagnostic Solutions Laboratory, breaks down the science behind dysbiosis, immunometabolism, and mitochondrial function in a way that’s practical for your practice. He also walks through how new tools like the StoolOMX test are helping us understand bile acid patterns and tailor treatments more precisely. Whether you’re looking to refine your approach to IBD, inflammatory gut conditions, or microbiome support, this conversation is packed with insights you can apply immediately.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: (00:00) Hi everybody, welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And of course today is no exception. I am here with my good friend Dr. Tom Fabian. He’s a translational science consultant and clinical educator at Diagnostics Solutions Laboratory. He specializes in the clinical application of microbiome research in integrative and functional medicine and has a doctorate in molecular biology from the University of Colorado.

Dr. Kara Fitzgerald: (00:01) As always, Dr. Fabian, it is great to have you with me today on New Frontiers in Functional Medicine.

Dr. Tom Fabian, PhD: (00:09) Thanks so much, Kara. As always, it’s great to be back, and I’m really excited about the topic today.

Dr. Kara Fitzgerald: (00:13) Yeah, I love talking to you because you’re cutting edge, you’re really current on the science, you’re bringing us forward in our thinking on all things gut. And we’re going to open this conversation with clarification of some terms and some evolution of definitions, if you will. So the first one, all of us know it, we use it all the time in practice, dysbiosis. As you and I were dialoguing a little bit off air, dysbiosis was not accepted in the medical and scientific establishment for many, many years. It was common parlance in the dark world of integrative and functional medicine but now it is mainstream and it’s evolving. So what is it? What’s dysbiosis and how has it evolved as a term?

Dr. Tom Fabian, PhD: (01:05) That is a great question. There is still some ongoing debate about that and I think it’s because there’s many manifestations of dysbiosis. The latest thinking about dysbiosis has to actually do with a redefinition of the term microbiome, which is, of course, what it’s based on. So I think it was maybe 2019 or 2020, there were some position papers that went out about considering the microbiome as not just the microbes themselves, a collection of microbes, but the environment that they’re in. So when we think of any sort of biome, the rainforest, et cetera, you’re not just thinking of the species there, you’re thinking of the reasons why you have a rainforest. So what environment. For example, a warm and humid environment.

Dr. Tom Fabian, PhD: (02:00) And the same is true in the gut. And we have different biomes, especially as you go through the gut and the mouth all the way down. Of course, the stomach is a very different environment from the large intestine. When you’re taking into account the microbes that normally live there, we know that they perform many functions that are, sort of, mutualistic with our physiology. They can actually support healthy physiology in numerous ways when it comes to mood, balance, et cetera. So dysbiosis is really synonymous with a change in the ecosystem, both in terms of the microbes, but that usually corresponds to changes in the environment.

Dr. Tom Fabian, PhD: And there’s also new research, and we’ll get into some of that today, that indicates that a lot of these environmental factors might actually be what’s responsible for the dysbiosis or driving the dysbiosis, versus say, the bad guys being the main actors. They certainly do play a role. LPS (Lipopolysaccharide) plays a role, et cetera, in stimulating inflammation, but we have to really consider it in the context of the gut environment. And that’s why with comprehensive stool testing, which we’ll also talk about, we do have markers that tell us about the environment in the gut.

Dr. Kara Fitzgerald: (03:14) Yeah. When we think about the term dysbiosis, is there any specific econiche down the line or… Yeah, talk about that. Dysbiosis could be anywhere, as you said in the beginning, from oral to anal.

Dr. Tom Fabian, PhD: (03:36) Exactly. Yeah, it’s really going to be in the context of what you’re looking at. Typically, of course, we’re looking at health versus disease and usually specific diseases. So the dysbiosis that you see in Crohn’s disease could be significantly different, of course, from the dysbiosis that you see in irritable bowel syndrome, or in celiac or in food allergies. And then there’s oral dysbiosis, and that sometimes can seed dysbiosis downstream. And so that will often involve different microbes, but there are some commonalities so we can actually identify common types of dysbiosis. Probably one of the most important ones, which is of course our key topic for today, is the inflammatory-type dysbiosis. And that typically is characterized in the gut by a set of bacteria that have common characteristics. One common example would be LPS production.

Dr. Kara Fitzgerald: (04:40) I want you to define inflammation, because again, as we were talking off air, that term has evolved in the literature as well. But before you do that I want to let everybody know, please head over to the show notes, if you’re able to, and grab the PDF of the GI-MAP as well as the StoolOMX. And we’ll have a host of other downloads and all of the references that Tom gets into. So with that Tom, just as the definition of dysbiosis has evolved over the years, inflammation has as well. So talk to me about that.

Dr. Tom Fabian, PhD: (05:41) Yeah. There’s a few dimensions to trying to answer that question, but I would actually start off with, and this is sounds a little evasive, but there’s a really excellent review article and we will include that as well. The title is The Spectrum of Inflammatory Responses and it’s authored by one of the leading researchers in the field of immunology, his name is Ruslan Medzhitov. So again, you’ll have that reference. But he starts off, his first sentence in this article is, “Inflammation is a biological phenomenon that defies simple definition.” Right?

Dr. Kara Fitzgerald: (06:20) Yeah. Fair.

Dr. Tom Fabian, PhD: (06:26) So it’s not something that can be easily defined. He goes on to talk about how it’s sort of context dependent. It really depends again, just as with dysbiosis, what it is that you’re looking at. But all that said, we know that inflammation is often referred to in terms of the context of the specifics of the immune cells that are involved. In general, inflammation can probably be defined or at least characterized as a state where you have some sort of trigger. Whether it’s an infection, whether it’s damage from an injury, for example, that can basically stimulate the immune system into action. So it’s basically the state of immune activation.

Dr. Tom Fabian, PhD: Now there are different states, and we’re finding out more and more over time that there’s a whole spectrum of different states of immune activation. Many of those are referred to as inflammation. Not necessarily all types of immune activation are really inflammation but they’re often broken down based on the types of immune cells that are involved. Traditionally that’s been centered around T cells, which is a subset of the adaptive immune system. I know early on, probably a couple of decades ago if not longer, the focus really was on what were called the Th1 cells and the Th2 cells. With Th1 being kind of your classic inflammatory type scenarios, such as inflammatory bowel disease or immune conditions. And then you had your Th2 cells and those are the ones involved in allergic responses.

Dr. Tom Fabian, PhD: So that’s all still, of course, pretty valid, it’s expanded from there. Since then they’ve discovered different types of T cells beyond those, Th1 and Th2, including something called Th17, and these regulatory T cells or Treg cells that are super important for making sure that the other arms of the immune system don’t overreact. They’re not overactive. So those are kind of the four pillars. Certainly it goes beyond that, but I would say now a large part of how it’s categorized are based on those different types of T cells. Nowadays we actually refer to those instead of Th1-type inflammation, it’s Type 1 immunity or Type 1 inflammation, Type 2, and then Type 3, with Type 3 being the Th17 based cells.

Dr. Kara Fitzgerald: (08:38) Yeah. It makes sense that the phenotypic expression of inflammation would have many different flavors, many different presentation potential, depending on the dysbiosis. And going back to your definition, thinking about it as changes to the environment. I like the rainforest analogy that you used because maybe the trees are cut down, or maybe the rain is now polluted, or maybe there’s fire nearby. All sorts of shifts can go to drive imbalances forward, the creation of the dysbiosis, and then the subsequent inflammation that arises. Another term that we want to fold into the conversation, again we’re thinking gut here and we’re going to bring in the GI-MAP and the StoolOMX so that we can all analyze this in our patients, is immunometabolism. And this is a term that we’re using more and more in functional medicine, thanks to Dr. Jeff Bland and others. But talk to me about immunometabolism and where it fits in the dysbiosis-inflammation picture.

Dr. Tom Fabian, PhD: (10:03) Immunometabolism largely comes from, of course, studies. Now that we have these omics type technologies available in research, some of these are now even being used clinically. But there’s the field of metabolomics where we’re looking at a big picture, a whole set of metabolites, that characterize all aspects of metabolism. And through studies such as this they’ve combined with some other advances in methodology, like single-cell transcriptomics, et cetera. They’re able to look at different types of cells in a very granular way. For example, with immune cells, how they change as they go from prior to activation. Those are, for example, the naive T cells and then those can become activated, say, into a Th1 cell or Th2 cell.

Dr. Tom Fabian, PhD: (10:51) Those are characterized not only by the different cytokines that they produce, but also the specifics of their metabolism. So the idea here is that metabolism actually can undergo different changes and that process is referred to as metabolic reprogramming. And that’s actually mostly an epigenetic phenomenon. So basically, with these signals that are coming in saying we need to activate and we need to activate towards the Th1 type cell based on the types of microbes that are detected, that can activate a specific metabolic program.

Dr. Tom Fabian, PhD: And that’s really important because there’s evidence that it’s the metabolism, to some extent, that drives the rest of the activation and supports the activation. So you need to switch metabolism to be able to ramp up energy, to crank out all these cytokines, to be able to begin to divide and proliferate so you have a lot more T cells around to deal with whatever the challenge is. So it’s really a critical aspect of how do these immune cells actually achieve their functions by changing their metabolism.

Dr. Kara Fitzgerald: (12:08) Interesting.

Dr. Tom Fabian, PhD: At a cellular level, that’s really what’s meant by immunometabolism. And then of course, there’s sort of a systemic level to this as well that can influence that cellular process.

Dr. Kara Fitzgerald: How do you think about it in the gut? Is it the same kind of thing, depending on the assaults or the response to whatever is happening? Metabolism will shift locally with the immune cells.

Dr. Tom Fabian, PhD: (12:36) Actually, there’s a really well-defined process now. You can think of metabolic programming as occurring in not just immune cells, but also other cell types, including the epithelium. So basically the cells that line the intestine. And then that can also occur in certain microbes. I’m going to illustrate a scenario here where metabolic reprogramming and immunometabolism are known to be key factors in the dysbiosis that’s related to inflammation in the gut. And this is mostly characterized in the large intestine, and probably best characterized in the context of inflammatory bowel disease. So that’s kind of our reference here. So when we’re talking about or visualizing this process, you can start with some sort of insult.

Dr. Tom Fabian, PhD: It may start with an infection that basically then changes the environment in the colon. So that infection basically can stimulate inflammation. If you think of your typical pathogens like salmonella, they can stimulate inflammation and then that inflammation can change the environment in a way that makes the colon less anaerobic. So then that’s favorable to all of these inflammatory type microbes, these opportunists, which could be organisms like Klebsiella, Proteus, E. coli. You see a lot of these overgrown in inflammation in the colon. But it turns out that part of that process, at the same time, is the loss of butyrate producing bacteria because they thrive in an anaerobic environment. So when you don’t have that, they start to produce less butyrate.

Dr. Tom Fabian, PhD: Butyrate is the key metabolic fuel for the cells that line the colon. And so it turns out that by essentially metabolizing butyrate, these colon cells use up a lot of the local oxygen. And that’s a key factor that helps, basically, maintain the colon as an anaerobic environment. All these studies show that you need that process. You need the butyrates to be used and available by the colon cells. In order to help maintain that anaerobic process, you need to have an anti-inflammatory or non-inflammatory scenario. Both of those together can promote these inflammatory microbes because they tend to respire. There’s respiration. They do that when there’s more oxygen available. But they can’t do that if it’s an anaerobic environment, so that’s really kind of the genius of this system.

Dr. Kara Fitzgerald: (15:29) That’s really very interesting. I mean, we’re thinking about butyrate all the time. And of course we’ve got Akkermansia on our radar for gut mucosal patency and now we’re thinking about it in GLP-1. But keeping a lockdown on the anaerobic environment, having it be fundamental to maintaining that anaerobic environment is very compelling. It’s really interesting to me that that could get thrown off with a local infection. Oxygen is just allowed in or these are oxygen users? I mean, how does that happen?

Dr. Tom Fabian, PhD: (16:09) It’s kind of a multifactorial process, but one of the key mechanisms is there are virulence factors, for example, produced by certain pathogens like salmonella that stimulate inflammation. Basically what happens when you have inflammation, they’re also using oxygen to generate reactive oxygen species to combat the pathogens. So they’re using up some of the oxygen there, but also those reactive oxygen species then kind of– I don’t want to get in too much detail here– but they end up getting converted through local processes to molecules that then these pathogens and opportunists can use for respiration. And so that’s really what fuels the growth of these opportunists and pathogens. And that’s largely what contributes to this whole inflammatory and infection process.

Dr. Kara Fitzgerald: (17:00) Interesting. Well then with that in background, let’s talk about some the microbial metabolites that we might be able to actually analyze and begin to think about this phenomenon occurring in our patients. And again folks, grab the PDF so you can look at the StoolOMX and the GI-MAP along with us.

Dr. Tom Fabian, PhD: (18:10) Exactly. Yeah. So because a lot of these studies have linked key microbial metabolites to this whole scenario of what’s going on with the metabolic changes in the gut that then can fuel inflammation, on the one side of the equation we know from lots of studies that when you have a decrease in these butyrate producers. And that’s certainly part of the process. Sometimes it’s a consequence of the inflammation that’s already beginning. Sometimes it can precede the inflammation, for example, when you have antibiotics that are knocking out these butyrate producers.

Dr. Tom Fabian, PhD: Regardless though, if you have insufficient butyrate production, then of course you don’t have the fuel for those colon cells. So you do want to be looking at those levels and also the butyrate producers, which is why we have both the microbes as part of GI-MAP and also this new add-on to GI-MAP where we’re looking at their main metabolic products, which are the short-chain fatty acids and the bile acids. We know that the short-chain fatty acids, especially butyrate, are really important for that process, so you can see the levels there. The trick with interpreting the short-chain fatty acids, though, is you also have to factor in transit time. Because when you’re looking at what’s in stool, you’re looking at the end result of production plus absorption. So for example, we know with fast transit, that’s going to decrease the absorption time. So you factor that in as well.

Dr. Kara Fitzgerald: (19:40) Yeah. So you might have a false normal, basically, because transit time is so fast that the colonocytes aren’t able to actually use it. Is that correct? Or you might even see it high?

Dr. Tom Fabian, PhD: (19:49) Exactly. In some cases, yeah. So the old way of interpreting it was that it was just sort of directly interpreted as production, kind of an indicator of fermentation. And certainly that’s part of the picture. But the problem is in these specific scenarios where you have fast transit, especially in diarrhea. So for a patient with Crohn’s disease or IBS-D that has diarrhea, if they have a lower number, but it’s still an okay number of butyrate producers, but they have really fast transit where they’re not really absorbing them, that can look normal or even a little bit high and you can misinterpret that as looking okay.

Dr. Tom Fabian, PhD: So you definitely, as always, want to look at the context. Look at their butyrate producers and if those are low and you know their transit is fast, then you want to take that into account for sure.

Dr. Kara Fitzgerald: It’s a big deal.

Dr. Tom Fabian, PhD: But overall, you definitely want to look at the butyrate producers. And we definitely see in many cases, not only is the total short-chain fatty acid content decreased, but we also break it down by the composition, the percentage of each of the main short-chain fatty acids. And in many cases, we’ll see relatively low butyrate. And I’ve seen cases where the butyrate was almost non-existent And then frequently in those cases, you’ll see either high acetate or high propionate. High propionate can give you some additional information about which microbes are likely imbalanced. Mostly that would be coming from the Bacteroidites phylum, which is thought to be often high in patients with fast transit or diarrhea. So we’re really piecing the picture together based on what we’re seeing and what we know from research.

Dr. Kara Fitzgerald: (21:36) And what might the end clinical presentation be with a really high propionate or any of the other short-chains, and a low butyrate? It’s going to be biased towards more inflammation, I would say fundamentally, but the microbial patterns will differ.

Dr. Tom Fabian, PhD: (21:59) Yeah, and we’ve seen this scenario quite a bit already with inflammatory bowel disease, especially Crohn’s. In fact, I had one case, I think it was pretty textbook based on what I’ve come across in the research, where in this scenario where a patient has Crohn’s disease, you can see that they have a decrease in their key butyrate producers typically. Especially Faecalibacterium prausnitzii. And then you’ll often see an overgrowth of these inflammatory microbes. On GI-MAP that’s on page three under the opportunists. We will often see organisms like Klebsiella, E. coli, Fusobacterium, all very elevated. And a new piece of this puzzle here, which happens to be a really interesting dovetailing here where new research has come out to help us better understand the role of bile acids, and bile acids are part of this picture.

Dr. Tom Fabian, PhD: (22:58) A brand new study that just came out, I think earlier this year, showed that in Crohn’s disease, it’s frequently a scenario where there’s bile acid malabsorption. So you get an increase in bile acids getting into the colon and they’re normally supposed to be reabsorbed efficiently in the ilium in healthy individuals. But in a subset of patients that have these disorders they can be malabsorbed and they showed specifically in this study that the excess bile acids actually damage the mitochondria. So it’s kind of like a two-hit scenario where if you have lack of butyrate, which also negatively affects the mitochondria, and you have an excess of primary bile acids.

Dr. Tom Fabian, PhD: (23:40) Those are the ones that are not being converted by the microbiome into secondary bile acids. That’s a scenario that’s been characterized as at the very least, irritating to the colon. It can irritate the lining and maybe contribute to leaky gut. But in this scenario, it can actually promote inflammatory type dysbiosis. And likely through this whole process of just suppressing the function of the mitochondria.

Dr. Kara Fitzgerald: (23:55) I want to know specifically what we need to look at. Just give me the names of the primary bile acids that are going to be showing up in elevation and then the secondary bile acids as well. Mention those and let me also say to the audience that we will link to a previous conversation we had where we did a deep drill down into this area as well. So people who want to really understand and access what great utility these two clinical laboratory tools have, they can listen to both podcasts. So go ahead, educate us on bile acids.

Dr. Tom Fabian, PhD: (24:53) Yeah, I think that’s really important because bile acids do take a little bit of understanding in terms of how to interpret them and what they mean. Because there’s sort of that part upstream where they’re course coming from the liver, they’re part of digestion. In a normal situation, they’re getting absorbed by the ilium. At that point they’re referred to as primary because they’re produced by the liver. In humans, the two main primary bile acids are cholic acid and something called chenodeoxycholic acid, or CDCA for short. Those are usually released by the liver conjugated to an amino acid. That helps them really do their functions in the small intestine more effectively and also protects the epithelial lining because they do have detergent activity, particularly when they’re not conjugated. So they can actually damage the lining of the intestine.

Dr. Tom Fabian, PhD: (26:10) There are a couple things to consider when they’re getting into the colon. We know that normally about 95% are absorbed in the ileum. When they get into the colon they’re usually rapidly deconjugated, meaning the amino acid component is removed. That’s actually not a great state for them to be in. If you have an excess of deconjugated, which you can actually have when you have high Bacteroidetes phylum, that’s been shown in some studies, then that can be damaging or irritating to the lining of the colon. It might contribute to leaky gut, it might even contribute to some inflammation. But fortunately in a healthy gut we have a whole range of bacteria, we have good diversity. Many of those bacteria actually can convert those primary bile acids quickly into secondary bile acids.

Dr. Tom Fabian, PhD: Far and away the two best known and most abundant secondary bile acids are lithocholic acid, (LCA), and deoxycholic acid, (DCA). But since the early days when we knew about those basic bile acids, we know that there’s a whole list now. I think the last count was probably upped even into the hundreds now so there’s quite a few. A lot of these are minor and not characterized yet so we don’t know much about them. But there are a core set of secondary bile acids that we now know have very interesting and important functions. They can reinforce the intestinal barrier, they can have anti-inflammatory activity, they can have metabolic functions. For example, we know they can bind to the receptors on L cells that stimulate GLP-1 production, which contributes to metabolic health. So that’s why there’s so much excitement about these bile acids, especially secondary bile acids, because of these physiological effects, far beyond just helping to digest with fats.

Dr. Kara Fitzgerald: (27:58) Why would somebody have an accumulation of the primaries?

Dr. Tom Fabian, PhD: (28:01) That’s a good question. Generally the main reason is if you have a high level of bile acids getting into the colon, that starts with bile acid malabsorption, which happens in the ileum. A really interesting recent study showed that in patients with inflammatory bowel disease and IBS, particularly IBS-D, they had an overgrowth of biofilm-forming opportunists in the ileum, particularly dominated by E. coli, in many cases. So the E. coli biofilm can overgrow in certain scenarios, possibly after an infection, possibly after antibiotics, for example. And then that may actually interfere with this absorption process. They’re still researching exactly what the effect of that is, but in that study it was associated with an increase in primary bile acids getting into the colon. So it could start there where there’s some pathology in the ileum.

Dr. Tom Fabian, PhD: (29:02) Once they get into the colon, as I mentioned, they’re usually deconjugated and then at that point they’re ready to be converted to secondary bile acids. So looking at your secondary bile acids with StoolOMX is a really good comprehensive way to gauge the diversity of your microbiome. Because you have to have a good level and diverse amount of bacteria that can carry out these specialized functions to create the secondary bile acids. If you don’t have those microbes, so if you just have dysbiosis, you just have lack of diversity, if you have inflammation, then that can lead to a scenario where you have a predominance of primary bile acids in the colon.

Dr. Kara Fitzgerald: (29:49) Our last conversation on this was quite fun, you know, connecting the dots around GLP, and needing those secondary bile acids, and also longevity. You were linking this back to, I think… Was there a study identifying it in healthy centenarians? What was the longevity connection?

Dr. Tom Fabian, PhD: (30:09) Yeah, they did find that in centenarians there generally tended to be higher levels of specific secondary bile acids that are both LCA itself, that’s one of the main secondary bile acids, again that’s lithocholic acid. But also some of the lithocholic acid derivatives that additional bacteria can make. One was called, I believe, iso-allo-lithocholic acid (isoalloLCA). They have these really long, confusing names, but they found that one in seem to be elevated in centenarians. We now know that has all these metabolic benefits and benefits for the intestinal barrier. But also in that article, they linked it to potentially better protection against pathogens and opportunists. So you can imagine as people are getting older, their immune system is aging, you have certain levels of senescence. Older people are generally not as able to fight off infections as well, but that’s where their gut microbiome can come into play and actually help to kind of boost that up a level so that they may be less susceptible to infections, especially gut infections.

Dr. Kara Fitzgerald: (31:02) Yeah. It’s so interesting. It seems like this panel is indicated for all of us. We should all get a snapshot of what’s happening, probably on an annual basis, just as we do many of our other tests. So I’ve got two questions. One is I want to give you an opportunity to articulate additional inflammatory patterns that we should be aware of. But then I want to move into what we do, you know, how do we make sure we have this robust, secondary bile acid rich GI picture that will allow us to mount healthy and normal immune responses, control inflammation, et cetera.

Dr. Tom Fabian, PhD: (32:03) Yeah, there’s certainly a lot to cover there. With the scenario we’ve mostly focused on so far we have this inflammation phenomenon happening in the colon. We talked about low butyrate and an increase in primaries possibly contributing to that. We know that’s mostly linked to the type of inflammation that’s in inflammatory bowel disease, for example, which is largely this Th1 or Type 1 inflammation, and also Th17, which is also known as Type 3 inflammation. There’s also Type 2 inflammation that I do want to touch on a little bit here, because when we’re talking about these different inflammation scenarios, all three of those can apply in the gut.

Dr. Tom Fabian, PhD: Type 2 tends to be something that can happen in the colon as well. It’s that scenario I mentioned where there is an increase in primary bile acids noted in Crohn’s disease, they actually also have it in Ulcerative Colitis to some extent, but mostly in Crohn’s. They have noted that there actually can be an element of the Th2, or Type 2, response. Usually it’s more Type 1 and Type 3, but some patients also develop this Type 2 and we actually have seen that with GI-MAP if you look at the markers in patients with Crohn’s. We have a marker called eosinophil activation protein and that’s basically a marker related to eosinophils when they’re activated, which is part of this Th2 or Type 2 response. We normally think of that as sort an inflammatory scenario related to allergies, but it’s also intimately tied to barrier dysfunction. And so we found, certainly with GI-MAP but also in the research, they actually showed that these primary bile acids can stimulate an increased proliferation of these eosinophils.

Dr. Kara Fitzgerald: Wow.

Dr. Tom Fabian, PhD: So that’s probably one of the dots that we see connecting the most from research in Crohn’s disease. When you see this high eosinophil activation protein you’re also more likely to see this increase in primary bile acids. And that’s part of this Type 2 inflammation scenario and that’s actually also linked to allergies. Not to get into too much detail here, but when you’re thinking of food allergies, food reactions, a lot of that happens in the small intestine. There’s a bit of a different scenario. We know from lots of studies that the small intestine is naturally biased towards these Type 2 allergic responses.

Dr. Tom Fabian, PhD: In a homeostatic situation, eosinophils and mast cells actually contribute to homeostasis, like a lot of immune cells. But in a situation where you may become sensitized to an allergen, which research studies show can happen with a gut infection. Research study actually showed even acute stress can cause you to lose oral tolerance. And then you can have over-activation of these cells, particularly in the small intestine, that then can lead to a low-grade inflammation there. Again, without getting into too much detail, with tests like GI-MAP in terms of the dysbiosis you would typically be looking for organisms like Staphylococcus aureus, Pseudomonas. Those are actually linked strongly in research to promoting these Type 2 inflammation responses. So this is really illustrating how we can start to connect the different types of inflammation and then what players might be involved, what sort of markers do we want to look at to gauge what’s going on and what we want to target? And then that can really inform the treatment from a precision medicine standpoint. As opposed to just avoiding certain foods that you might be reacting to, now we can kind of take that upstream a little bit potentially and start targeting these organisms and see what else is going on in the gut.

Dr. Kara Fitzgerald: (36:07) What about parasites? Parasites could play a role here, potentially.

Dr. Tom Fabian, PhD: (36:11) Yeah, definitely. One of the original functions discovered for this Type 2 inflammation or Th2 is for helminths or intestinal worms, which by and large tend to infect the small intestine. That could be another reason why we have this bias towards that type of inflammation there. So we know that they can engage those Th2 responses that basically help to eliminate helminths. Historically, that’s one of the key things that was studied. There’s newer research that other types of parasites like your single-celled protozoa and on GI-MAP examples would be Giardia, Blastocystis for example. Several of those have actually been shown to be linked to stimulating this Th2 type response, which is probably also geared towards trying to manage them and keep them from overgrowing or eliminating them.

Dr. Kara Fitzgerald: (37:03) Interesting.

Dr. Tom Fabian, PhD: (37:09) But they actually found that some of those can have protective effects because the Th2 responses can actually counteract Th1 and Th17 responses to some extent. Mostly Th1.There’s a little bit of a debate and research about blastocystis and whether that actually is a beneficial microbe. In that context, it may be. It might actually help protect against, for example, inflammatory bowel disease.

Dr. Kara Fitzgerald: (37:09) Interesting. And it makes sense to me understanding that they all balance each other, or particularly I guess Th2, to your point, can have a sort of mitigating attenuating effect on 1 and 3. That’s really fascinating. OK, where do we want to go with this? Do we want to move into talking about treatment? Are there other imbalance patterns that you want to point out?

Dr. Tom Fabian, PhD: (38:12) So dovetailing on the Th2 scenario, for patients that do have parasites, and especially, of course, if they do have food reactions, you certainly do want to look for certain organisms that might be stimulating that. The ones I’ve mentioned would be Pseudomonas, that’s pretty well characterized. Staphylococcus aureus is widely linked to a range of Th2 responses, and then of course, various parasites. Candida is sometimes part of that food reaction scenario, but actually one of the main targets for the Type 3 response is Candida.

Dr. Kara Fitzgerald: (38:46) Interesting.

Dr. Tom Fabian, PhD: (38:53) So, you really do want to look at those organisms and then what are the key ways to target those. Those protocols for parasites tend to be somewhat different from say targeting Staphylococcus aureus or Pseudomonas. So that’s part of the targeting scenario is which protocols would you want to employ for which microbes. But you’re also looking at the immune picture and the digestion picture. Without getting into too much detail, we know that digestion is one of the factors that, when not optimal, can promote overgrowth of many of these microbes. So you certainly want to be looking at digestion. Digestion can also predisposed to food reactions because you’re not breaking down proteins as well. So they are more likely to be targets for these allergic responses.

Dr. Tom Fabian, PhD: If you have something like eosinophil activation protein as part of that picture, which we do see in patients that have food sensitivities or food allergies, we know that butyrate and Tregs are an important process in terms of keeping those from being overactive. There’s actually quite a bit of research that we think of butyrate as having an anti-inflammatory effect. Historically, that’s been mostly focused on these T regulatory cells but we know that butyrate also tends to downregulate the activation of mast cells and eosinophils. So that’s kind of where you’re connecting the dots. We see eosinophil activation protein elevated. And then if you’re looking at StoolOMX and GI-MAP and see that butyrate and butyrate producers are low, that could be one of your key targets. You want to support with butyrate supplementation, with fiber, and also polyphenols of course.

Dr. Kara Fitzgerald: (40:44) Yeah, any word on fiber around when we might back off a little bit around using? Speak to that.

Dr. Tom Fabian, PhD: (40:54) Yeah, there’s really interesting research has come out in the last few years. I would say I’ve probably come across six or seven different studies now showing that under certain circumstances, certain fibers can actually promote different types of inflammation. That’s almost 180 degrees opposite of what we’ve been told all these years, is that, fiber is good, fiber promotes short-chain fatty acid production, and then helps promote the anti-inflammatory responses. So that is largely true. It mostly has to do with the effect on short-chain fatty acids from what we know. But now that we’re looking at bile acids more in depth from research, and we can also see this clinically, that does make it a little bit more complicated. When you have a scenario where patients may have a low level of commensals that can metabolize fiber, then that can predispose to these inflammatory scenarios.

Dr. Tom Fabian, PhD: One of the studies actually showed that inulin in particular can promote an increase in the Bacteroidetes phylum. This is the group that I mentioned that can produce bile salt hydrolase. So when you’re getting a little bit of bile acid malabsorption into the colon and then you’re getting this conversion through the bile salt hydrolases to deconjugated bile acids in a low diversity scenario. You’re not getting that conversion to secondaries and fiber can actually make that process worse.

Dr. Kara Fitzgerald: Interesting.

Dr. Tom Fabian, PhD: I think this is a really good scenario where you’re looking at the StoolOMX, you’re looking at GI-MAP, putting these pieces together and in that scenario you might decide maybe fiber is not right for this patient at this point in time.

Dr. Kara Fitzgerald: (42:25) That’s really fascinating. For any clinician out there who’s using GI-MAP and you want to use StoolOMX and you’re excited about it, but– Tom has just outlined a ton of patterns. You can consult with the team. They’re available and they’re really brilliant. And off air, just before we started recording the podcast, I invited Tom to join us on our rounds and walk through some cases so we can see it in action. We’ll add the StoolOMX, it’s an add on. We’ll add it onto our GI-MAPs for a handful of patients and then have Tom come in and talk through those cases with us, which is going to be really useful. So we can see these patterns in action and really talk about some key interventions. A lot of what you’re saying makes sense. It’s intuitive, but you’re saying a lot. And so I just need to metabolize it.

Dr. Kara Fitzgerald: And also I have a caution around overtreating and you mentioned sometimes you may not want to go in there aggressively and kill these. It’s more about a delicate balancing act. And it’s like the symphony of digestion and food to the antimicrobials that we might use or tweaks in fiber or maybe just a low introduction of fiber. And I think all of that’s really incredibly important. The other thing I just want to say that’s popping into my mind is to be able to distinguish different types of IBD patterns. I mean, extraordinarily useful. Probably all of us in clinical practice have come across patients we’ve been able to treat really quickly, in a very straightforward manner, turn around their IBD and maybe put them into remission for years and it’s an extraordinary achievement. You know, they’re happy, they get on with our lives. And then we’ve got other patients that we’re not seeing the same outcome with. And I’m actually thinking of one individual who could really benefit from these. As you were speaking I was wondering what type he might be and how I might refine his plan to address that.

Dr. Tom Fabian, PhD: (44:59) Yeah. I think it’s all about just having this key information to further connect the dots. That’s really what we’re doing. Some of the science may initially seem kind of complicated because you’re thinking of the different microbes and then what’s the role of these primary versus secondaries and what’s the short-chain fatty acid picture. Once you get some of these basics down though, just through training materials, interpretive guide, et cetera, especially just going through a few cases, as you know, I think you can really start to connect those dots quickly and get some breakthroughs potentially for your patients.

Dr. Kara Fitzgerald: (45:28) It’s exciting. Yeah, it’s really exciting. You know, maybe I’ll do old school and print it out and take notes. This to here, this to here, which I do all the time. Anything else that you want to add? And actually, I also want to just hit home the cool utility of the StoolOMX in optimizing an already pretty healthy gut. And moving towards that centenarian, and that super diverse, robust amount of those cool secondary bile acids. Just using that for our patients who are already healthy. Keeping them that way or moving them even more so.

Dr. Tom Fabian, PhD: (46:19) Yeah, I think it’s a great monitoring tool because there are a lot of studies. You know, I think the general movement in looking at chronic disease is trying to identify things that are going off track early and catch them early and then get them back on track. Because we know further down the line when things are too far off track, it can be really difficult sometimes to get those to really recover. So I think as an early screening, this is a great tool as well.

Dr. Kara Fitzgerald: (46:32) Yes. Yeah, of course, just as an annual screening or semi-annual screening, think it makes sense. All right, what else do we have here? Do we want to talk a little bit about some of the treatment approaches that you’ve seen work in your consultation?

Dr. Tom Fabian, PhD: (47:05) I think one of things I definitely would want to highlight when it comes to this bile acid malabsorption scenario is, again, we’re always trying to see how we can move the needle forward in our field. Some of the traditional approaches, as we get more information, we start to learn there might be some downsides. A perfect example of this would be emerging research around these bile acid binders, like cholestyramine, which are a go-to for many patient scenarios where there’s bile acid malabsorption, especially if there’s diarrhea along with that.

Dr. Tom Fabian, PhD: Again, more research would really need to be done to firm this up, but so far the research suggests that unfortunately some of these bile acid binders, by sort of increasing the bile acid content in the colon, we think of them as sort of bound so they shouldn’t really cause problems. But the studies are showing that they still can cause problems and might actually further contribute to this inflammatory scenario for some patients. Which would explain why there are some patients that just don’t do well on those binders.

Dr. Kara Fitzgerald: (48:15) That’s right. Yeah.

Dr. Tom Fabian, PhD: (48:33) So this might be a way to help just differentiate if you see somebody who’s really got a bad scenario. And we see a pretty wide spectrum. Some people just have a little bit of a problem. There people that are barely producing any secondary bile acids, and it’s almost all primary. So there’s lots of different ways to look at this. There’s the total amount, et cetera. So it really does give you this sort of nuanced view into what’s going on so you can decide which way you want to go with a patient.

Dr. Tom Fabian, PhD: And then one last thing I’ll mention about that scenario is that research that I mentioned about identifying these biofilms in the ilium, it also can kind of carry over into the cecum, the first part of the colon. There’s a growing emphasis in our field and in research on ways to reduce these pathogenic biofilms. So recent research indicates that NAC, which we kind of have known, has been a bit of a biofilm buster. Recent research shows that that really can help quite a bit in certain scenarios, especially in the small intestine. It can reinforce the intestinal barrier and also can help basically break up the biofilms. So NAC might be a good option in those scenarios that we might not have connected to the bile acid malabsorption scenario. So it might be worth considering.

Dr. Tom Fabian, PhD: (49:50) Another study showed that the combination of vitamin D and vitamin K also may inhibit biofilms. So again, there’s some different ways to look at this that we might want to look at some of these common supplements that we already know are safe. In these scenarios, are they worth looking at for certain patients? And then the third one I’ll mention, which is something that we’ve talked a lot about when we talk about Pseudomonas, because Pseudomonas is the key biofilm former as well, is cinnamon extract or even just cinnamon as a spice, but generally most studies are on the extracts. That’s a well-characterized biofilm inhibitor. So there’s quite a few studies, a little surprising, on cinnamon as being a key factor. So again, this kind of expands our tool set for consideration. Now that we understand that biofilms upstream might be part of this process, and if you’re not able to work with, say, a bile acid binder, if the patient’s not reacting well, you may have some of these other options to explore.

Dr. Kara Fitzgerald: (50:29) Yeah, that’s really interesting. Right. And I think that in our practice these days, we’re not using bile acid binders much because of just poor tolerance. And it’s concerning that they could be driving inflammation further. I know they’re pretty popular in the functional medicine arena, and it’s a real pearl to know that they can be problematic. I mean, they’re not well tolerated. I think that’s obvious for a lot of clinicians, but that they could actually be furthering damage is an important piece to consider because they are being really widely used.

Dr. Tom Fabian, PhD: (51:26) And I think I’d want to just kind of bring it together a little bit by, again, when you think about inflammation, start thinking that inflammation isn’t really one thing anymore. We’re not just looking for “inflammation”. You really want to be thinking, well, what type of inflammation? You know, there’s three pretty well-defined types. If you see Candida overgrowth, that suggests the patient has other evidence of inflammation. You may have more of this Type 3 scenario. If you have this Staphylococcus, Pseudomonas, parasite overgrowth scenario, it might be more of a Th2 and that could be contributing, for example, to a patient’s food sensitivities or food allergies. So again, it really helps you target and recognize, what do I need to address in understanding the patient’s scenario a little bit better.

Dr. Kara Fitzgerald: (52:19) Yeah, that’s right. And then Th1, what would we be thinking about? Or type 1, what would we be thinking about?

Dr. Tom Fabian, PhD: (52:25) So that’s, again, probably most relevant in inflammatory bowel disease. Classically, you’ll see the typical inflammatory microbes overgrown. Those usually can be targeted with just standard broad spectrum herbal products in those cases. But now that we know this sort of metabolic scenario, this immunometabolic scenario in the gut, certainly you want to be considering what’s going on with butyrate and whether butyrate supplementation or other ways to support butyrate might make sense. And then certainly the bile acid scenario. Now that we know that that can be a contributor, you really do want to look at that and see, is that a problem for the patient? And if so, what are the ways to potentially address that?

Dr. Kara Fitzgerald: (53:14)

Again, folks, you will find in our show notes, PDFs on the GI-MAP and on StoolOMX. You will find the references for all of the many papers that Tom has mentioned. You’ll find links to our previous conversation, including the nice drill down into the wonderment of bile acids. It’s interesting. It’s actually really interesting. And again, think about bringing this brilliant team or consulting with this team as you make your way through learning how to use these tools, applying these tools in clinical practice to best efficacy. We will, and we have for years. So even though we’ve been using GI-MAP for many, many years, and I’ve been in this space for a long time, to stay current on the education requires these conversations. I always like to hold it with our whole team. so we all get the benefit of the experience and that’s just one of us consulting with you.

Dr. Tom Fabian, PhD: (54:17) I very much look forward to that.

Dr. Kara Fitzgerald: (54:19) Cool. Thanks, Tom. Well, thank you again for joining me New Frontiers.

Dr. Tom Fabian, PhD: (54:21) All right, thanks, Kara. Always a pleasure.

Dr. Fabian is a leading expert on the role of the microbiome in health, immune function, chronic disease, and aging. His primary focus is on the clinical application of research in the microbiome and mucosal immunology fields in integrative and functional medicine. After receiving his PhD in molecular biology from the University of Colorado, Boulder, he conducted aging-related research in the biotechnology industry. Dr. Fabian is a consultant in the microbiome testing field. Currently, Dr. Fabian serves as a translational science consultant and science advisor with Diagnostic Solutions Laboratory, and is a Science Advisory Board member with Designs for Health.

Dr. Tom Fabian

Bile acid–induced metabolic changes in the colon promote Enterobacteriaceae expansion and associate with dysbiosis in Crohn’s disease

Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn’s disease

Plasma bile acids in association with Crohn’s disease

The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

Bile Acid Signaling in Inflammatory Bowel Diseases

Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis

Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation

Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation

Epithelial hypoxia maintains colonization resistance against Candida albicans

Review Article: The Spectrum of Inflammatory Responses

Ruslan Medzhitov, PhD

Article: Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians

Research: N-Acetyl-l-cysteine-Loaded Nanosystems as a Promising Therapeutic Approach Toward the Eradication of Pseudomonas aeruginosa Biofilms

Research: Vitamin D and vitamin K1 as novel inhibitors of biofilm in Gram-negative bacteria

Podcast: Cutting-Edge Metabolomic Testing for IBS, Longevity, and Metabolic Health

Podcast: Challenging Food Reactions? Addressing the Gut Microbiome and More with Dr. Thomas Fabian

Podcast: Gut Healing in Aging & Disease: Emerging Roles of the Microbiome and Diet in Intestinal Barrier Regeneration with Tom Fabian, PhD, CNTP

DrKF Clinic: Patient consults with DrKF physicians including Younger You Concierge

Bio Age Self Assessment Quiz

Younger You book

Better Broths and Healing Tonics book