Episode 22: Mastering the Microbiome and Optimizing Gut Health with Dr. Tom Fabian

Evelyne Lambrecht: Yes, I’m so excited. We’ll be discussing the role of the microbiome in food sensitivities and talking about histamine intolerance among other exciting topics related to gut health. Dr. Fabian is a leading expert, educator and speaker on the role of the microbiome in health, immune function, chronic disease, and aging. His primary focus is on the clinical application of microbiome research 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, and more recently has served as 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 scientific advisory board member at Designs for Health. He’s also certified as a nutrition therapy practitioner by the Nutrition Therapy Institute in Denver. Tom, how did you get into this field and particularly interested in the microbiome, and I’m curious, what do your days look like as a translational science consultant?

Tom Fabian: Great set of questions. This has actually been a long and winding road. I actually started off as a researcher. I got my doctorate at University of Colorado in Boulder in molecular biology with a focus on aging back in the day. It was quite a while ago. I did end up in research for a few years, both in academia, then in the biotech sector, but eventually I made my way into the functional medicine realm. Mostly because I really wanted a more practical application, because we all know research, you’re toiling away in the lab and then eventually your research may get published and then there may be some impacts down the line. I was really impatient for using the information that I learned, the training that I had and seeing if there’s a way I could participate in helping in the health field.

At the time, I decided to get my nutrition certification. That opened really a lot of doors, I think, into the functional medicine field. I initially started just seeing my own clients. I was actually working with clients initially, but I really wanted to do more with my background. I was able to get into consulting with a series of clinical testing labs. Along the way I started reading research into the microbiome. This is about 10 years ago. Microbiome research at that time was fairly new, but there was a lot of really exciting paradigm shifting information coming out in terms of this new component that we hadn’t really thought of that was really this intermediary between how does our diet and lifestyle affect our health. Right? A lot of that was through the microbiome as they were learning, but it was early days.

Some of the stuff we thought we knew back then, we found that some of that is not so true anymore, but we’ve learned a lot since then. I think that really had a big impact on me was just how much of an influence the microbiome had on health and that we can actually learn to work with diet and lifestyle in ways that would help to improve health through the microbiome. I ended up working with a series of companies that were primarily focused on microbiome testing. That’s primarily my expertise. But since then, because of my previous expertise in aging and molecular biology, I’ve tried to bring those back into what I do as a translational scientist. A lot of what I do primarily is working for a company called Diagnostic Solutions Lab. They offer the GI-MAP test and other tests.

Part of what I do is consultations with practitioners. I love that one-on-one interaction with practitioners and helping them understand how these results apply to their patients. Also, I spend a lot of time researching the latest information related to the microbiome and how that’s related to health, and then translating that into educational content for practitioners. I do a lot of work directly for DSL webinars. Also, have been guests on podcasts, speak at conferences. Education is really a huge part of what I do from a translational science standpoint, and that’s mostly focused on trying to figure out what’s the most relevant information coming out of research and then how can that apply clinically.

That’s really not being done so much in our field. There’s some translational science happening, for example, in the biotech field, pharmaceutical research, but in the functional medicine field, there’s relatively few of us that have that background where we can take that research, understand it, distill it down into information that practitioners can understand, but then also how do you apply this in terms of clinical testing, interpreting the tests and even treatment implications. I really thoroughly enjoy it because there’s just so many ways in which I think it pertains to what we do every day in practice.

Evelyne Lambrecht: Yeah, thank you for sharing that. Well, now in conventional medicine, I think it’s accepted that the gut does indeed play a large role, that the microbiome is very important. And I think at times we’ve placed more importance on maybe certain things and then realize maybe they’re not as important and there’s so much that we don’t yet know about the microbiome, but there’s a lot we do know. I’m excited to-

Tom Fabian: Exactly.

Evelyne Lambrecht: … delve into that. Let’s talk about the role of the microbiome in food sensitivities specifically. I’d love to talk about what the main types of food reactions are, the differences between them, and then how our understanding of those has changed? What specific regard to how the microbiome is involved in those?

Tom Fabian: Absolutely, yes. I think a lot of us who have gotten into that area, I think, first, nutrition is such a big focus overall in our field, integrated and functional medicine, that I think a lot of us are familiar with that old paradigm that’s been around for a while that you break down the adverse food reactions category. That’s very broad, and then you can break that down into what’s referred to as immune-mediated food reactions. And then on the other side you have the non-immune mediated, or at least what were thought to be non-immune mediated. Those are the intolerances. Primarily carbohydrate intolerance, also histamine intolerance and others as well. Then on the immune-mediated side, traditionally that’s mostly encompassed food allergies, food sensitivities, and, of course, celiac disease. Then there are some other subcategories as well. That’s the traditional way of looking at it.

Some of the new information that has come out recently in relation to the microbiome is that the microbiome actually does mediate a number of those reactions or the symptoms that are involved in the reactions. For example, with food allergies, we’re learning more about specific microbes in the gut that can basically prime the immune system so that patients are more likely to react to certain foods. A similar scenario with the food sensitivities. Probably the most interesting information is coming out about food intolerances. We’re actually learning more and more now that the microbiome mediates those as well. Again, they were thought to be non-immune mediated, but the microbiome, for example, in carbohydrate intolerances, typically what happens in that scenario is when patients are not able to break down their carbohydrates as well, that can be due primarily to a reduction in those disaccharidase enzymes in the small intestine. They’re part of the brush border, or even pancreatic insufficiency is a common cause of that as well.

When patients are not really digesting, absorbing carbohydrates, well, then those basically go through the small intestine unmodified and then they get into the colon where they can basically feed the bacteria that are there and then those bacteria carry out that process of fermentation. Then fermentation results in the production of a range of products, including gases for example, that can lead to symptoms. There’s actually newer information now, for example with FODMAPs, which we know are effective in a range of conditions, especially IBS, low FODMAP diet, that actually some of how those function is actually by indirectly stimulating the activation of mast cells, and then the histamine production from the mast cells. It gets a little complicated. We can dive into some of these little details here. They’re discovering that mast cells are actually thought to be a component of food intolerances in many ways. They’ve already been known to be involved in food allergies. They may be involved in certain types of food sensitivities, and then now we also know that they’re potentially involved in some of the food intolerances.

Evelyne Lambrecht: I have a lot of follow-up questions, because I feel like you just shared so much good information, so we need to go back to some of those. You mentioned that there are specific microbes that are contributing to these reactions. Are these things that you see on GI-MAPs because you’re looking at them all the time, and what are some of those microbes? And is it just that people are eating a poor diet and don’t have enough diversity in general, or is it actually pathogenic bacteria that somehow have come in one way or another?

Tom Fabian: That’s a great question. For the most part with food sensitivities, food allergies and these types of reactions, and even in certain intolerances like histamine intolerance, we now know that there are certain microbes that have been implicated in these processes. Primarily that comes down to what are called opportunists. These are microbes that tend to be present in the gut. They’re not the classic pathogens. They’re often there, and as long as they’re at low levels and in the right place, probably not causing too many issues usually, but they can be overgrown or they can basically overgrow somewhere where they’re not normally present. For example, the oral cavity is a source of some of them. We know Klebsiella, for example, for many patients can come from the oral cavity. If they have problems in their oral health, they have oral dysbiosis, and then you combine that with other imbalances such as lack of stomach acid, which normally helps kill off microbes and pathogens coming through, then they can overgrow in the small intestine.

We know that there’s a number of these microbes, especially in the small intestine that can overgrow. Klebsiella is one of them. Pseudomonas is another one, and also Staphylococcus aureus. Another common one that’s often implicated is Candida. These tend to be more dominant in the small intestine when they overgrow. Sometimes they can also be in the colon as well, usually in the small intestine. Just a little bit of background information there to put this in context is when it comes to food reactions, the immune-mediated food reactions, research actually shows that that mostly happens in the small intestine. For example, celiac disease, we know the pathology for celiac disease primarily involves upper small intestine, same for food allergies and possibly even food sensitivities as well. As far as the research we have right now, they tend to be involved potentially in somewhat different ways, but ultimately they all tend to stimulate the immune system in a way that fosters these allergic reactions, which also involves that mast cell activation.

Some of them are histamine-producing microbes. We can talk about that as well. That’s part of the picture, is these opportunists that can overgrow. You can have situations involving some of them coming from the oral cavity. That’s something to be aware of from a therapeutic standpoint. Digestion is another common contributor to this scenario, particularly low stomach acid, that’s pretty common. Lack of enzymes, pancreatic enzymes, also another big issue. There can be other factors as well. You mentioned poor diet. Certainly we know that simple carbs, that’s actually really well-defined, especially for Klebsiella. Some really interesting research has come out recently showing that even FODMAPs can feed Klebsiella and cause it to stimulate mast cell activation potentially.

Certainly poor diet is part of the picture as well. Stress is always… We know that there’s a connection there with dysbiosis, leaky gut, et cetera. One other thing I’ll mention though, as far as the microbes involved, we’re mostly focused, of course, when we look at these tests on the bad guys. Opportunists are present so that we can potentially target them therapeutically. But it’s also equally important to look at the good guys. These are the commensals, on the GI-MAP test, you’ll see those primarily on page two. Those are keystone species like Faecalibacterium, which is a key butyrate producer. Roseburia, another major butyrate producer. Akkermansia, we know that these are all important species.

We know that from research that they produce these beneficial products such as short-chain fatty acids, which includes probably the best known one, which is butyrate. There’s lots of research now connecting patients who have low butyrate that can affect their oral tolerance. Basically, you need adequate levels of these short-chain fatty acids from the good guys to promote oral tolerance. That’s sort of the flip side of the immune balance that is related to these food reactions. You don’t want to have too much of the ones that are promoting the mast cell activation, but you want to have enough of the ones that are promoting the anti-inflammatory functions to keep that balance in check.

Evelyne Lambrecht: I have some questions for you. Can you define oral tolerance and then can you also define mast cell activation and how that differs from mast cells versus histamine?

Tom Fabian: Absolutely. Yeah, oral tolerance has to do with whether or not the immune system recognizes an antigen is something that it needs to mount a response to. Certainly in terms of allergies, obviously the immune system has learned to recognize that as potentially harmful, even if it may not be harmful. It’s just a little bit of a mistake on the part of the immune system that overreacts to certain antigens, but generally with a healthy immune system have a healthy microbiome, et cetera, then that promotes more of this anti-inflammatory side of the equation, and that keeps this pro-inflammatory reaction in check. That’s considered oral tolerance. Basically, most of the foods we eat, of course, we’re not reacting to, there’s lots of potential antigens in everyday foods. Most of us are not reacting to most of those, and that’s because your body has learned to recognize them as harmless, and so your immune system doesn’t react to that. That’s generally the concept of oral tolerance. Then, I think, the second question was related to mast cells and histamine?

Evelyne Lambrecht: Yeah.

Tom Fabian: Certainly when it comes to histamine, mast cells are one of the key sources. That’s well known in terms of all the years of research on allergies and how they’re involved. When they become activated, technically, essentially mast cells have the IgE, immunoglobulin that’s attached to them, and these are immunoglobulins, the IgEs that have learned to recognize that specific antigen. That’s part of the sensitization process. When patients are sensitized to an antigen, basically these mast cells are just sitting there in the mucosa in the gut when they have food allergies, and when you consume that food, and then when that mast cell encounters the antigen, then that essentially triggers the mast cell to release all these factors basically into the surrounding area in the tissue.

Those factors include histamine. They include tryptase. They include things like serotonin. Some of these are neuroactive molecules that can then stimulate the immune system and cause further symptoms. There’s a lot there, and mast cells actually can respond to different things and release different factors under different circumstances. That’s the general idea is that when the antigen binds to the IgE molecule on the mast cell, that triggers this release of factors that ultimately leads to the symptoms.

Evelyne Lambrecht: Okay, and then I want to go back to the species that you mentioned like the Morganella, Klebsiella, et cetera. Are those the ones that are actually producing histamine? And is it that because they are present that this is an issue or is it the lack of beneficial bacteria that allows them to release these? I guess I’m asking if you have more of the good bacteria then whether they release it or not, it might not be an issue. Does that make sense?

Tom Fabian: Yeah, definitely. It certainly makes sense and that is part of the picture. Diet is part of the picture. I mentioned this example about the FODMAPs. Studies show that when certain patients consume FODMAPs, if they have Klebsiella, and particularly this research study that came out last year showed a particular species called Klebsiella aerogenes was the main one involved, essentially when you consume these foods that causes Klebsiella to grow. It’s not entirely clear yet. They still have to do more research on why it starts producing histamine under those circumstances. As you mentioned, there are other factors that can inhibit the bad guys, especially these normal commensals. That is probably one of the key factors that determines why one person who has Klebsiella has this reaction. Someone else who might have the same amount of Klebsiella, but they have enough of the good guys to keep it in check.

An example of how… There’s a lot of research around this, so they actually have a lot of the details now. We now know that those short-chain fatty acids that the good guys produce, you can tell by the name based on the fact that short-chain fatty acids, that last word is acid. They basically contribute to a lower pH in the surrounding area. It’s a little bit acidic in the gut when those short-chain fatty acids are at good levels. That’s enough, they’ve shown in studies, to inhibit these bad guys. That’s probably a key part of the picture is this balance of good guys to bad guys. What sort of diet do you have? Another factor is, of course, that may affect your immune response including genetics and that sort of thing.

Evelyne Lambrecht: I have a follow-up question on that that I just thought of. If you didn’t want to treat with antimicrobials, would giving short-chain fatty acids just supplemental butyrate be enough?

Tom Fabian: That’s a great question. I don’t know if that’s been studied yet. I would say clinically speaking, practitioners typically do more than just that. If there’s an opportunist, digestion is another very important piece. If you’re not digesting foods, then there’s, of course, more foods available for the microbes. That’s one of the advantages of looking at these comprehensive stool tests like GI-MAP is you’re looking at many components of the picture and able to put that together based on is digestion really a factor for patient A? Is it more diet for patient B? Is it lack of these normal commensal bacteria for patient C? And they’re probably all relevant, but whether or not… I personally haven’t seen that just short-chain fatty acid supplements themselves alone will do that, but studies actually have shown, and this is mostly in animal models. You have to take it with a grain of salt, but when they give animals greater amounts of fiber, often that is sufficient to keep these opportunists in check.

That’s assuming everything else is relatively healthy. The short-chain fatty acids, I think, are a good adjunct to these protocols. But, of course, the main constituent in the gut that supports a healthy gut is fiber. There’s lots of other products that are produced by the microbiome from fiber. It could be that the total of all these beneficial products is really what’s needed. Certainly we have seen butyrate for a lot of patients, certainly results in some helpful benefits. But it’s, again, usually in the context of multiple things that they’re doing.

Evelyne Lambrecht: I want to go back to the digestion piece, but before we do, since you’re looking at a lot of GI-MAP reports all the time, how common is it to have overgrowth of these histamine-producing microbes? Do you see it a lot?

Tom Fabian: We do, yeah. I don’t have specific stats to cite, but I would say we see it more commonly in patients that do have food reactions. There’s a pretty strong correlation between what’s known from research and then what we see clinically in patients that have various types of food reactions. Among the ones that we see most commonly on GI-MAP, and this, again, is on the opportunists page, probably Staph aureus is one of the most common. That could be due to the fact that that’s one of the ones that has been linked to poor digestion. Patients that have low stomach acid. Patients that have reduced pancreatic function. Patients that have lower levels of those brush border enzymes, all of those may foster the overgrowth of Staph. That could be one of the reasons why we see that so commonly is that we know that digestion is really not optimal for a lot of patients due to stress, lack of sleep, et cetera.

Probably Pseudomonas would be the second most common of these histamine producers that basically can stimulate mast cells. The best studied in research, and these are people that may be more likely to have actual histamine intolerance symptoms, would be Morganella and then Klebsiella species. You can think of them as turbo producers of histamine. In fact, some of the Klebsiella species have been shown to produce very large amounts of histamine under certain circumstances. I should clarify that some microbes produce histamine, and that’s a way they can stimulate these mast cells. Others produce other factors that also can stimulate mast cells. It’s not always through the histamine, there can be other things that are involved there.

Evelyne Lambrecht: Okay. With the Staph, do you then see an association on the GI-MAP with low pancreatic elastase? Do you see low secretory IgA or do you see other correlations on there?

Tom Fabian: Absolutely, yeah. I would say low elastase, that’s basically indicating lack of sufficient pancreatic enzymes, is one of the most common drivers of dysbiosis in general. Not necessarily just for the Staph and the strep, but also for many of these other opportunists. There’s a lot of research on that actually showing that lack of pancreatic enzymes is one of the biggest factors in terms of causing dysbiosis. Again, a lot of research also on lack of stomach acid, mostly studied in the context of people that are on PPIs. Now, that’s obviously pretty common. I would say the low stomach acid scenario is the one where we tend to see the high Staph and the high strep most often.

Evelyne Lambrecht: Which makes sense, right? Because we need that stomach acid to kill those bacteria. Since we know that enzyme production decreases as we get older, should everybody just be taking digestive enzymes?

Tom Fabian: That’s a good question. Of course, that’s up to every practitioner’s judgment. I would say in the real world, in terms of the GI-MAP results that I’ve reviewed for patients that are, say, generally over the age of 65, some actually don’t have any evidence of reduced digestion. I think it is a general trend, but there’s also this individual component. You hear these truisms where people will say, “Test, don’t guess.” Don’t necessarily treat to the test always, that you want to treat the patient overall. Both of those have validity in different circumstances, but I wouldn’t just assume that because a patient is older that they necessarily have poor digestion just because we have seen plenty of cases in older patients that seem to have pretty good digestion.

Evelyne Lambrecht: How do you think a practitioner can delineate between say, recommending digestive enzymes and/or recommending taking supplemental DAO, which we haven’t even talked about? Diamine oxidase to degrade that histamine?

Tom Fabian: Certainly histamine intolerance is a well-known condition, and there are some specific symptoms there, both GI and also systemic. There may be some clues based on symptoms that it may be more of a specific histamine issue, and practitioners often will try the DAO enzyme in that case, and that does work for a lot of patients. For others, that actually may be just generally this reduced digestion that’s resulting in overgrowth of these histamine-producing microbes. Another thing to keep in mind is that the DAO enzyme is primarily produced in the small intestine. Whether or not that’s going to be helpful for the histamine produced by the microbes depends on where those microbes are. In some cases we do know from research, for example, Pseudomonas is pretty much in the small intestine. Klebsiella is usually in the small intestine, but it can be in the colon sometimes. For some of those cases you may need a different approach where the diamine oxidase DAO supplement may not work. That could be one reason, is that the location of the enzyme and where it works is not the same as where the microbe is overgrowing.

Evelyne Lambrecht: I’ve asked several of our guests this, but do you think there’s ever a point where we can have such great digestion and great intestinal permeability and not impermeability because of the things that we do to where you won’t react to these things or things won’t overgrow? Do you see any perfect GI-MAPs? I assume most people who run the test are having issues, but on follow-ups, do you see that those things go away?

Tom Fabian: We typically see that, I would say, again, we don’t have specific stats based on retesting and treatment, but my impression is that generally these opportunists when they’re targeted, in most cases, do respond pretty well to antimicrobial protocols. Again, it depends on what’s really at the root cause. If it is poor digestion, an antimicrobial might work for a while, but then it’s likely to just grow back. It depends on how much time that they wait to do the retest. We actually do recommend 30 to 60 days, so that antimicrobial protocol, it might initially work, but it is not all that uncommon that it can grow back. You want to know if that’s still an issue. That often is your clue to look at other imbalances that are causing it to regrow, like digestion is probably number one, I would say is the most common. But generally I would say most of the common multi-herb formulations out there do tend to work pretty well against dysbiosis.

Evelyne Lambrecht: And with short-chain fatty acids, I want to go back to those. How can a practitioner identify if there’s low short-chain fatty acid production on a GI-MAP? Would it be looking at the bacteria because you’re not measuring those directly or something else?

Tom Fabian: Yeah, that’s the best way to assess. There’s a debate in research as to what’s the best way to look at short-chain fatty acids. Intuitively, you think measuring them directly in stool would be the best way, but most short-chain fatty acids are absorbed in the colon. I think the general stat is like 95% are absorbed, and lots of studies show that certain short-chain fatty acids like butyrate tend to be produced more in that first part of the colon. You’re going to get a lot of it absorbed in what’s left over in the stool sample may be a pretty small proportion. It’s not always the most accurate. It does give you some good information, but in combination with the microbes, the ones that are producing it, the DNA does tend to stick around. If something is growing in that first part of the colon, that’s a butyrate producer, and then basically once the fiber that it’s consuming is gone, then it levels off and that just hangs out until it gets to the end of the colon.

By looking at the microbes, you’re also getting a little bit of a different picture on the short-chain fatty acids that probably reflects more of the colon overall. That’s a little bit of a technical explanation, but that’s certainly borne out by a lot of the research that’s out there. When you’re looking at something like GI-MAP, we do know that there are two keystone species essentially of the short-chain fatty acid, especially butyrate producers, that’s the Faecalibacterium prausnitzii and Roseburia. Actually studies do show that there’s a strong correlation, especially with Faecalibacterium levels and total butyrate production, and that’s probably because it’s usually one of the most abundant species. It’s widely recognized as a keystone species.

It is one of the most common butyrate producers and it tends to thrive under the same conditions as the other butyrate producers. That’s a really good marker overall for butyrate production. For short-chain fatty acids, overall, we’re looking more at the phylum level. We both have both the Bacteroidetes and the Firmicutes phyla listed. Those are the top two phyla in most people. Those typically make up about 90 to 95% of microbiome. Those are your main short-chain fatty acid groups. I would say probably a little bit more on the Firmicutes side, especially for butyrate. If you see one or both of those deficient on a GI-MAP, then that’s likely indicating that there’s a deficiency not just in the short-chain fatty acids, but also some of these other beneficial products that they produce.

Evelyne Lambrecht: That’s really helpful. Thank you. Especially, I think that’s a great pearl about most of the short-chain fatty acids being absorbed. Therefore, they wouldn’t show up on a stool test. You could inaccurately tell someone they maybe have low butyrate when maybe they don’t. That’s very helpful. I have a question going back to histamine intolerance. If somebody doesn’t have a lot of maybe gut related symptoms, but they do have histamine type symptoms. Are you still looking at the gut? I guess I’m asking about histamine production locally, like microbiome derived or produced versus histamine in the rest of the body systemically.

Tom Fabian: Obviously it’s going to depend on what’s going on with the patient and do they have activated mast cells in serum? Also, basophils can release histamine. If they have more of a respiratory type allergic scenario that may be driving some of that, there could be other sources. They’re usually mucosal one way or another. Even the skin can be a source, skin reactions. Anything that’s sort of a barrier tissue, could be a source potentially. As far as the gut, studies actually do show that histamine produced by bacteria in the gut does get into systemic circulation and it can actually influence immune reactions elsewhere. There’s a growing recognition of these various axes, the gut-brain axis, the gut-skin axis, and the gut-lung axis. Just one study I remember off the top of my head, they showed that bacteria in the gut that produce histamine, histamine actually did influence reactions in the lungs. The short answer is yes, potentially, but the gut microbiome is necessarily the only source, of course, of the histamine.

Evelyne Lambrecht: Generally, when we think of systemic histamine, we think of using things like quercetin to stabilize mast cells. Then when we’re looking at gut like food-derived histamine, we think of treating with DAO. But do you think that those could almost be used interchangeably or both to address the other?

Tom Fabian: Probably, yeah. I’m not aware of specific studies on quercetin inhibiting bacterial histamine production in the gut. The studies that are available tend to focus on some other things. One of them is the pH in the gut. This whole reaction where bacteria take the amino acid histidine and then convert it into histamine, those bacteria in that reaction tend to thrive at a higher pH. This could be another reason why when you have that slightly acidic environment from the short-chain fatty acids from the normal microbes, that can inhibit the histamine production. I think a lot of it does come back to that balance. I think there are some other polyphenols in general that have been shown to inhibit that enzyme, but unfortunately off the top of my head I’m not able to recall which ones. I do recall that in general, we know polyphenols are good for so many things, and it doesn’t surprise me that they may be good for inhibiting that process too.

Evelyne Lambrecht: Right. We can get those through food and also through supplementation, though ideally we’d get them in our diet, right?

Tom Fabian: Yep.

Evelyne Lambrecht: Something else that I’ve seen you speak about is focusing on the gut barrier, but not just the leaky gut part. Can you talk more about that and about repairing and regenerating the gut barrier?

Tom Fabian: Absolutely. Yeah, that’s a hot topic in research. We certainly have known about leaky gut for a long time, and there are some good markers out there, including zonulin, that can help us understand whether leaky gut itself is part of the picture. But research has really revealed over the years that the intestinal barrier is actually multiple components. Beyond just the tight junctions you’re zooming out and thinking of… Probably a lot of us have seen those little schematics or you see the microbes and then the mucus layer and then the epithelial layer and below that the lamina propria. All of those basically constitute the intestinal barrier. It’s this really highly interactive dynamic system. All of those components influence one another, especially the microbiomes. We know that they do release these factors like short-chain fatty acids that have really well-documented effects on all the other components of the barrier.

Just to give a couple examples here, when you’re looking at the short-chain, fatty acid producers, butyrate producers, that can be a sign indirectly that the barrier is not so healthy because we know lots of studies show that you need good butyrate levels to keep those tight junctions closed, prevent leaky gut, to stimulate normal turnover of those epithelial cells. Butyrate also stimulates normal secretory IgA and also normal butyrate production. Butyrate itself is known to help reinforce many of those other components. When you’re looking at the barrier from the big picture, you’re really looking at more than just zonulin or some of those other leaky gut-type markers. You’re really looking at the balance of microbes. We know bad guys in general, lots of studies show pathogens, other opportunists can damage the barrier. You want to take that into account as well.

If you see pathogens, probably the barrier is disrupted. Then secretory IgA again is another major component of the barrier. Indicators of mucus, the mucus layer would be primarily Akkermansia since that lives in the mucus layer, depends on the mucus layer, and it actually stimulates mucus production. If you don’t have enough Akkermansia, you probably have deficient mucus. There are a few others as well, like Escherichia lives in the mucus layer. Depends on mucus and then some of the bacteroidities. That’s a common pattern that we see on GI-MAP in patients that have a deficient barrier.

Evelyne Lambrecht: With all of that said, because you’re advising practitioners all the time, right? And I know that everybody’s individual and it’s going to depend on their symptoms and on what a stool test shows, but generally, what are some of the ways that you recommend sequencing a gut protocol in terms of duration and where to start and what the most important components are?

Tom Fabian: That’s a great question. It’s a little bit of a loaded question because there’s so many ways to do that.

Evelyne Lambrecht: Right.

Tom Fabian: Traditionally, a lot of practitioners will follow that 4R, 5R type program and we’ll start with the remove step, for example, which oftentimes does make sense if you see really significant pathogens, opportunists, it’s hard to get the gut to heal while they’re still there and causing trouble. But a newer way of looking at it that a lot of practitioners tend to use nowadays is this top-down idea, which makes a lot of sense because we know if there are imbalances upstream, say, excuse me, you’re not digesting well, we know that causes dysbiosis downstream. You don’t want to just treat the dysbiosis with antimicrobials. You want to treat that upstream root cause. That’s how the whole functional medicine philosophy of treating the root cause is really transforming things that you’re really trying to identify what’s the driver of these.

Sometimes it’s a little complicated. There can be multiple things driving it, diet, stress, all those things, but that’s pretty common. On GI-MAPs, say for example, when practitioners see a high H. pylori and maybe a low elastase, we know H. pylori can suppress stomach acid. That’s one of its most commonly known documented effects. If patients have those symptoms of hypochlorhydria, they have symptoms of generally not digesting well. We see maybe some other signs like some overgrowth. Then that can be a sign that maybe you want to treat those initial upstream factors, like maybe treat H. pylori first. Maybe also support digestion.

And if you see other factors that may be more downstream, like those commensals that we talked about on page two, normal bacteria, if those are not in balance, it’s possible that those upstream factors are contributing to that imbalance. That may correct itself, but you also may want to do some directed treatments in supporting those beneficial bacteria a little bit further down the line because a lot of times you don’t want to overwhelm patients with too many supplements at once, and they’re trying to remember what to take when. I would say the top-down approach probably these days is the more common approach.

Evelyne Lambrecht: When it comes to using antimicrobials, what’s the duration that you usually recommend? And do you recommend cycling them? And if so, how long do you use each one?

Tom Fabian: It’s somewhat variable, but I would say the most common timeframe overall is probably 30 days up to 60 days for treatment. For really tough cases, if they’re not responding so well, a lot of practitioners might go up to 90 days. Beyond that, I think, really it’s time to reassess the approach. Is something else going on? Do you need just a different protocol? I would say that’s the most common timeframe scenario.

Evelyne Lambrecht: And since you brought up H. pylori, this is a common question that I get from the practitioners I work with is when to treat it. I think that sometimes I’ve heard, “Okay, treat it depending on the number.” Or, “Treat it depending on whether there are virulence factors or not.” Or, “Treat it depending on whether there are symptoms.” What are your thoughts around that?

Tom Fabian: All of the above.

Evelyne Lambrecht: Okay.

Tom Fabian: You want to take all of that into account. You don’t want to necessarily treat just on one of those factors. We do report pretty low levels of H. pylori. I think that can throw off some practitioners that are not used to seeing it on other tests so commonly. On our test, the cut-off for being considered high is the E3 level, but we do report down into the E2 range. Sometimes you’ll see it’ll be like two E2 range. We do get a lot of questions from practitioners, is that bad? Do we need to treat that? Even though we can’t really give direct medical advice in these consults, we give them the information that they need to try to make that decision themselves. One key piece of information is about 75 to 80% of patients that run the GI-MAP have detected H. pylori.

And we know from both research and just what we know about how the Practitioners describe their patients, a lot of them don’t have the relevant symptoms at these low levels. Really do you want to be treating something when they’re not symptomatic, and there may be other bigger fish to fry in this report. You might see something else that’s more obvious that then needs to be treated. But each practitioner is different. We do know some practitioners that are more likely to treat even at low levels, and that may be because in their experience, they find that their patient population does benefit from that. We just would not want to advocate over treatment. I think there’s a bit of a misunderstanding that just because it’s there and a lot of people consider it a bad guy that you need to treat it. We’re learning a lot more from research that bad guys alone, especially at low levels, may not be a problem for people.

Evelyne Lambrecht: I was going to ask about that. We all have H. pylori, right? Well, tell me what the latest research says, but is it still that we all have it, it just becomes a problem if it’s overgrown? And do we know based on what research shows what that cutoff may be?

Tom Fabian: The research is a bit mixed, and it depends on the methodology that they use. A lot of times they’ll use sequencing, for example. They may use other different types of tests, whether it’s the urea breath test, the stool antigen test. Each one has its own level of sensitivity. Their cut-off level may be higher than what we consider a cut-off level. They may consider below that, it’s negative, but if you use PCR, it might actually still be detected. In terms of the research out there, it’s still a little bit unclear as to how many people actually have detected H. pylori. We know from our data it’s about at least 80%, maybe more.

Evelyne Lambrecht: That’s high.

Tom Fabian: Yeah, that have these very low levels, but using other methods that aren’t insensitive, they may find that it’s actually only 30% of the population. It’s a little unclear, again, from the research, but certainly in developing countries, it’s much higher. It’s thought to be something that may have actually been a normal commensal in the past, thousands of years ago, and that modern antibiotics may be causing that prevalence to decrease. That’s a possibility. These are all open research questions. I wish we had more answers on some of these specifics, but they’re really still looking at it. But it does generally, when they use more sensitive methods, does seem to be a lot more common than they used to think.

Evelyne Lambrecht: I feel like we also can’t talk about H. pylori without talking about parasites. Well, just because you’re looking at those on the GI-MAP, and right now it seems like there’s this idea out there, thanks to social media, that everybody has a parasite and people are training it without measuring it. I’m wondering what your thoughts are on that, and since you’re looking at a lot of tests, what do you actually see?

Tom Fabian: Yeah, I would say our prevalence rates with GI-MAP, and again, qPCR is a very sensitive method. It’s been in research for a long time. It’s a tried and true method when you really want to precisely identify and quantitate something. We’re pretty confident about when it is detected that it’s there. When it’s not detected, it’s either at a really low level or it’s likely not there. The thing to remember with a test like GI-MAP is it’s a targeted test, so we only see what we’re looking for.

Evelyne Lambrecht: Right.

Tom Fabian: If patients have a less common parasite, obviously we’re not going to detect that if we don’t have that as one of the ones we look for. But generally the overall prevalence of the ones that we have, which are among the most popular, the most common parasites, Blastocystis, for example. Giardia, we see those pop up here and there pretty commonly. My guess is they’re in the range of 10%, maybe 20%, but certainly not in the realm of we would say everybody has them, or even the majority have them. Some do. A little bit of a clinical pearl, at least based on my experience is that a lot of times when we do these consults, practitioner will say, “I suspected this patient may have parasites.” Or even the patient themselves may just insist that they think they have parasites, so they want to run a gut test to see what’s there. They run a GI-MAP and often we’ll see just regular dysbiosis. It could be one of these bacterial opportunists. But pretty commonly in those scenarios where patients are convinced that they have parasites, it turns out to be something like Candida.

Evelyne Lambrecht: Interesting.

Tom Fabian: I’m not sure, and we see that about the same prevalence overall, maybe about 20, 30%. Certainly not all the time, but a lot of times when they’re convinced they have parasites. I’m assuming that these symptoms of Candida overgrowth mast mimic a lot of the symptoms from parasites as well.

Evelyne Lambrecht: Very interesting. I have a question going back to… I know we’re jumping all over the place, but there’s so much great information that you’ve shared about FODMAPs. Were you saying or implying maybe that if somebody were to go on a low FODMAP diet or that could be used therapeutically if they have histamine issues or mast cell activation issues?

Tom Fabian: Absolutely. Yeah, there’s actually good research now showing that low FODMAP diets, one of the ways that they may be effective is because they’ve been shown mostly, again, in animal studies, but I believe that there are at least small scale human studies that have been published that going on a low FODMAP diet can reduce histamine production. I think in those cases, in the human studies, they were looking at urinary histamine. They found that in patients that were on a high FODMAP diet, that they had a higher histamine output in the urine. Patients put on the low FODMAP diet, had a lower histamine content in their urine.

Evelyne Lambrecht: Interesting. Okay. Is that different from our previous understanding of how, say, low FODMAP diets work in SIBO?

Tom Fabian: Absolutely. Yeah, the research on SIBO is really interesting when you dive into the details. It’s always been assumed that symptoms typically when you have bloating, distension, for example, that that’s caused by gas. There’s quite a few labs now that have done these really careful MRI or CAT scan type studies where they’re quantifying the amount of gas produce, and they’re finding that the difference between IBS patients and healthy controls is negligible. On average, they’re actually not finding more gas production, but what they do know partly through this mast cell and histamine scenario that patients are more sensitive. Their nervous system is more sensitive to whatever level of gas is there.

An average person might consume a certain amount of FODMAPs that produces a certain amount of gas and they get no symptoms at all. An IBS patient that consumes that same amount of FODMAPs gets the same amount of gas, but then they’re going to have symptoms because of this hypersensitivity, and they think that the hypersensitivity is caused primarily by mast cell activation that releases those factors that we talked about, like histamine, serotonin, a lot of those are neuroactive components that then activate the sensory nerves so that patients have more symptoms. It’s really an interesting story that’s emerging over this research the last few years, and I think we’re just going to see more and more of this research around the mast cell and histamine and other factors that the microbiome and mast cells produce as well.

Evelyne Lambrecht: This is really interesting. You’re saying if someone who has been maybe diagnosed with SIBO or thinks that they have it, takes a test, like a breath test or eats a certain food and then measures methane, hydrogen, hydrogen sulfide, somebody who does not have SIBO will also have elevated levels of hydrogen, methane, hydrogen sulfide?

Tom Fabian: Exactly. Yeah, there’s a lot of studies that show that a high proportion of healthy controls who don’t have symptoms still can come up positive on SIBO tests.

Evelyne Lambrecht: Is that just a normal food reaction? Is that a bad thing? Because I do see when practitioners treat SIBO and then they retest or they use a device like, say, the FoodMarble AIRE 2 device where you could measure it yourself, they do see reductions in… Well, that one’s not measuring hydrogen sulfide, it’s measuring hydrogen and methane, but they do see reductions in those with treatment? How do you explain that?

Tom Fabian: It depends on how they’re treating. If they’re going on a low FODMAP diet, certainly FODMAPs are fermented. There’s this open question of where are they fermented and there’s an ongoing debate in research that’s still calls that into question that there’s a lot of evidence that actually FODMAPs are really primarily fermented in the colon. This early rise or early peak idea for a lot of patients, and there are careful studies, published research showing that a lot of those patients have rapid transit of the FODMAPs to the colon, and the peak that they’re seeing in many cases is often in the colon. This gas production is part of the picture for a lot of patients because as we talked about earlier, that healthy controls also have gas production from FODMAPs. They just don’t get the symptoms typically, and that a lot of this really does come down to the hypersensitivity.

Evelyne Lambrecht: Very interesting.

Tom Fabian: Yeah, I think we’ll see more and more about this because it’s one side in the research that promotes the idea of high gas production in the small intestine and the other side that says, “Well, so far the data doesn’t really consistently support that and that these other mechanisms involved.” It could be that the reality is somewhere in the middle, but I guess over time we’ll see how the research pans out.

Evelyne Lambrecht: Very interesting. Also, ultimately we want patients to feel better, right?

Tom Fabian: Exactly.

Evelyne Lambrecht: Depending on how we go about that, I guess that’s the main goal that we’re looking for.

Tom Fabian: Yeah, I think, also it’s important to recognize that when patients are treated with antimicrobials for SIBO, of course, herbal antimicrobials are nonspecific. If you think you’re targeting these hydrogen producing microbes, in reality, you’re also treating other opportunists that may be there. That’s a common scenario that we see with GI-MAP is patients that have gone down the SIBO route, treated multiple times, but so far have not really gotten the response that was desired. They run a GI-MAP, oftentimes we’ll see organisms like H. pylori or Pseudomonas or Staph aureus, and those are not hydrogen producers. Certainly you could have a negative SIBO test. Patient still has all those symptoms. You treat with similar antimicrobials, you can address that dysbiosis and they may feel better because those microbes are causing other problems in the gut.

Evelyne Lambrecht: Is there research though on, because you said they’re non-specific, but aren’t there specific antimicrobials that are specific to certain organisms? Because I do remember learning about that.

Tom Fabian: Yeah, it tends to be more the type of organisms. A lot of them are actually, if you look up the research on them, they have activity against bacteria, against parasites, against fungi, and even against viruses in some cases. Certainly there’ll be differences from individual antimicrobial to the next and the dose, et cetera. Probably also related to their mechanism of action. But most practitioners that we work with tend to use these combination formulas that are pretty broadly targeted, so you’re getting just about anything that’s going to be quote, “Dysbiotic.” Or, “Out of balance.” With those formulas. It’s a little hard to say, and I don’t think there’s any detailed studies for the most part on these broad spectrum formulas in terms of specifically which ones that they target versus others, although there may be more data after some than others, of course.

Evelyne Lambrecht: Great. I’ll keep monitoring the research for that. That’s very interesting. Before we wrap up, I’d love to ask you some questions that we ask every guest on the podcast. The first one is, what is something that you’ve changed your mind about through all of your years in this field?

Tom Fabian: A lot. Since I’m into the research, of course, things we used to think and then a new study comes out, and that totally changes what we think about something. There’s many of those examples. I definitely think more from a health standpoint, both in terms of my previous work and working with clients, just my own health journey over time, is that things that you think, whether it’s you think, “Oh, it runs in the family, it’s genetic, and that’s just the way it is and I can’t really do much about it.” Or that, “I’ve had this for so many years, I’ve tried everything, not working.” I think there’s always a lot of hope that if you keep at it, keep consistent, oftentimes eventually you do get those breakthroughs. For me, that’s how it’s been with my own health. I’ll just give one example, when it comes to hypertension, which runs in the family, I had my genetics done about 10 years ago. I think it was just 23andMe, and one of the hypertension genes came up that was off the charts like, “This one really is a big player in hypertension.”

The more I got into it, the more snips I found that all add up to you’re likely to get hypertension. But at the time I didn’t have it. My blood pressure was pretty good, but as soon as I turned 50 or so, all of a sudden it started going up and I was doing all the usual things that they recommend and sort of general health practices, exercise, good diet, et cetera. But it was still going up. I was a little bit to the point where I’m like, “Well, I’m going to have to go on one of those pharmaceuticals. I really don’t want to.”

I really dug into the genetics more and started connecting the dots with what sorts of natural factors could affect these specifically this general idea of precision medicine. I’m taking these details into account and then adjusted my supplement regimen in my diet to some extent. Then my blood pressure went back into the normal range. But that was after many, many years where I gave up many times thinking, “Well, it’s just genetic and I can’t change it.” But I think if you can stick with it, oftentimes you do get these breakthroughs.

Evelyne Lambrecht: Yeah, that’s awesome. Thank you for sharing. Going along with that, maybe what are your three favorite supplements that you take and also what are your top health practices that keep you healthy and balanced?

Tom Fabian: Supplements is a tough one because I tend to rotate. I’m not one of these super consistent people. I like trying new things and I feel like I’m always trying to get it better over time. It’s a bit of an evolving thing even now. But I would say currently my top ones, other than the basics would be taurine. And that’s for many reasons. Part of it is the genetics that is something that’s involved in and can help with hypertension. My genetics show that I have snips in that pathway that leads to taurine, plus there was this recent study that just came out and one of the major journals linking higher taurine to better healthy aging across-

Evelyne Lambrecht: I saw that.

Tom Fabian: … a number of species. Yeah.

Evelyne Lambrecht: I was going to say it’s like the new anti-aging nutrient or healthy aging.

Tom Fabian: Absolutely. Yeah, it’s really got some great research so far this very promising from that standpoint as well. I think for anyone who is wanting to make sure that they age healthfully, that’s something to consider. It’s also one that tends to be calming. I think there’s just lots of different potential benefits from it. Also, certain supplements I might react to. That one I don’t have any issues with. It’s that sweet spot. Has some benefits that are well-documented. Personally, I feel like I do well on that one. Second one, I would say extra DHA on top of just my normal omega-3s. I started reading more about this a number of years ago that DHA, of course, is especially good for brain health, and I did seem to notice after taking it that my overall cognitive function, brain function seemed to be better, especially memory.

I definitely like that one because we all depend on our brains to get our work done.

Evelyne Lambrecht: Yes.

Tom Fabian: I really like that one. Then the third one, I would lump more as a category, because this is one I definitely rotate and that’s the polyphenols. There’s, of course, so many documented benefits to many of these polyphenols. Things like quercetin, I certainly take that during allergy season. It’s one of the things that will help with my allergies. Curcumin, whenever there’s concerns about inflammation. Magnolia extract is one of the ones I generally like. I am rotating these out depending on what’s the current thing that I want to focus on.

Evelyne Lambrecht: Great. And your top health practices?

Tom Fabian: Top health practices, number one, probably for me would be exercise, particularly outside. I’m fortunate that I live in Colorado near the mountains and love hiking in the mountains. We try to get out almost every weekend if we can for a hike in the mountains. Anything outside. That way, I think, you get the benefits of just being outdoors. We all know the benefits of that, fresh air, but also variety of different types of exercise as well. The second one I would have to say is certainly diet. That’s just been an evolving thing for me. Currently, I would characterize what I’m on as paleo-Mediterranean type diet. That seems to work pretty well for me. That’s just been a long evolution and every time I’ve had a diet breakthrough, I’ve been able to address a particular health issue. That’s been really, really helpful overall. Then the third one, which is a bit of a surprise at the time, I started doing this about 10 years ago and I was starting to read about intermittent fasting.

Just a tiny little background on that is back when I was younger, I used to do a lot of triathlon training. This is at least a couple of decades ago when it was pretty common to do this idea of carb loading. You always had to have your power bar with you or some sort of energy bar. You had to keep refueling yourself all the time. But when I read about intermittent fasting and this whole idea that your fat stores are there for a reason to help provide this long, slow, steady energy that you didn’t have to rely so much on the glucose part of the equation.

I gave it a try. We decided to go for a long hike and not bring anything with us to eat. I was pretty amazed at how good I felt. I was really worried that I was going to just hit the wall or be brain-dead to a certain point, but your body does adjust if you’re reasonably metabolically healthy. That to me was just a surprise, that for me, personally, that seems to work quite well. Then basically as a side positive effect, I ended up losing some weight, which was even better.

Evelyne Lambrecht: Awesome. Thank you for sharing those. Those are great. Well, Tom, thank you so very much for sharing your expertise with us today. Lots of clinical pearls, lots of great research pearls to dive into. Thank you.

Tom Fabian: My pleasure. Thanks so much, Evelyne.

Evelyne Lambrecht: Thank you for tuning in to Conversations for Health. Check out the show notes for the resources shared on today’s podcast episode. Please share this podcast with your colleagues, follow, rate, leave a review wherever you listen, and thank you for designing Well World with us.

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