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

Addressing adverse food reactions goes way beyond simply cutting out the culprits, so I’m thrilled to have Dr. Tom Fabian join us again on New Frontiers to highlight the interventions that will move the needle for our patients. We explore the mechanisms through which specific strains can either exacerbate or alleviate both immune-mediated and non-immune-mediated food reactions, and discuss the fascinating connection between circadian rhythms of mast cells and intestinal permeability, feeding times and increased susceptibility to food reactivity. We look at why some patients may be more sensitive to symptoms and how histamine-producing microbes may lead to visceral hypersensitivity.

But we also talk strategy, with one pearl after another, such as the potential of Lactobacillus reuteri in attenuating immune-mediated food reactions, the role of butyrate and indole in stabilizing mast cells, and using specific polyphenols to calm the immune system and promote a health microbiome. For any practitioner or health-savvy individual grappling with these issues, this is an episode you won’t want to miss. ~DrKF

Special Note to our New Frontiers listeners:

Download the GI-MAP Interpretive Guide and use it to follow along with the episode. This practical guide from Diagnostic Solutions Laboratory can help you better understand and interpret test results for your patients.

More and more people with overwhelming food reactivities are walking through our doors and it’s presenting a significant challenge for both practitioners and patients alike. The traditional approach has largely been focused on identifying the problematic foods, eliminating them, but then just sort of stopping there. But we can do better.

Dr. Tom Fabian comes back to New Frontiers to share his vast knowledge and cutting edge insights that will shift the way you support your patients. He’ll tie both immunological and non-immunological food reactions to the gut microbiome and shine a light on how to create better immunotolerance, starting in the womb and continuing throughout our lives. Dr. Fabian will talk us through the specific bacterial strains implicated in intolerances, IBS, mast cell activation, and the visceral hypersensitivity that is making our patients miserable. But he also calls out the importance of boosting commensal bacteria to increase butyrate and support immunotolerance, and the power of DSL testing technology to create personalized interventions.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald (00:01:23) 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. If you’re watching me on video, you can see I’m sitting next to the brilliant Dr. Tom Fabian. Let me give you his background, and we will jump right into our topic. 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 at Boulder, he conducted aging-related research in the biotechnology industry.

Dr. Kara Fitzgerald (00:02:28) – More recently, he 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 (DSL) and is a science advisory board member with Designs for Health. Tom, as always, welcome, welcome, welcome to New Frontiers.

Dr. Thomas Fabian (00:02:53) – Thank you so much, Kara. It’s great to be here today. Thank you for having me and I’m very much looking forward to this discussion, which I know is kind of fresh on your mind.

Dr. Kara Fitzgerald (00:03:01) – It’s fresh on my mind. Yeah. You guys, we’re going to be talking about really tying food reactions, adverse food reactions, immunological, non-immunological, to the gut microbiome. And Tom, as is mentioned in his bio, translates what he does to clinical application, and it is timely because food reactions have just risen meteorically. The reason you’re saying it’s timely for me, it’s fresh in my frontal cortex here, is because I just delivered the immune module where I talk on this very topic.

Dr. Kara Fitzgerald (00:03:42) – And I’ve been lecturing in the immune module (at IFM) going on 12 years now, and the amount that I cover has just grown exponentially as more and more reactions come forward. Reactions that were rare in our practice become more ubiquitous, or things like alpha-gal allergy (galactose-alpha-1, 3-galactose), from tick-borne illness, cross-reacting with meat becomes a thing. I mean, God, we’re in these really intense times, and really foundational in all of these reactions is what’s happening in the microbiome. And you’re just marrying all of that information, staying extremely current, and then guiding us in how we think about it using the DSL testing technology and just good clinical interventions, something that you excel at. So I want to start by just having you provide us with a big picture overview of adverse food reactions, the major types, and the differences of possible ways we react to food.

Dr. Thomas Fabian (00:04:55) – Absolutely, yes. So I know you just taught on this recently, so feel free to jump in and kind of round out my response as well. But essentially, traditionally adverse food reactions have been separated into categories of immune-mediated, which primarily included food allergies, non-IgE-mediated scenarios like celiac disease. And there are a few others, the list seems to be growing. And there are some conditions that are thought to be kind of IgE and non-IgE mixed. They’re not fully worked out at this point, so we still don’t really know some of those details. But that seems to be a really important category. And I think recently, the applicability of that sort of model of the immune-mediated reactions has been extended pretty significantly into the realm of functional GI disorders, like IBS, functional dyspepsia, etc. So I’m hoping we can dive into it a little bit later on. And then the other side of the equation –  again, we’re looking at the breakdown of these adverse food reactions – then you have what have traditionally been called non-immune mediated.

Dr. Thomas Fabian (00:06:04) – So these are carbohydrate intolerances, lactose intolerance, sucrose intolerance, which I think is becoming more recognized, histamine intolerance, and then you could extend that list almost forever. There are oxalates, there’s salicylates, all these different components of foods that individuals may have negative symptoms from. So you can imagine that it’s sort of a pretty broad category. Again, we traditionally focused more on the common ones like carbohydrate intolerance and probably even more recently, more on histamine intolerance. So that’s kind of the high-level view, and again, there are some categories underneath that. And we’re just learning so much more about what’s behind this, because I think the traditional approach largely has been focused on identifying foods that are problematic and eliminating them, and then just sort of stopping there.

Dr. Kara Fitzgerald (00:06:59) – Right, right. And paying lip service to the idea that the microbiome is involved. I mean, we know if you’re exposed to antibiotics or PPIs as a baby even, the incidence of being on the atopic march and developing food allergies is exponential.

Dr. Kara Fitzgerald (00:07:19) – We know intestinal permeability is essential for sensitization, for the process of classic IgE allergy to happen and we see that as a likely scenario in the others. So we know the microbiome is hugely involved, that we need to address it more broadly, but I appreciate you bringing your brainpower to this and just getting more granular for us. It’s just awesome. What are some of the roadblocks that we’ve been confronting in actually treating it and addressing the plethora of food reactions?

Dr. Thomas Fabian (00:08:01) – There’s quite a few, but I think one of the main ones just has been the traditional focus on food elimination, which often is something that’s just necessary. We know that food reactions do cause inflammation and they can cause other problems that interfere with healing and with patients improving. But ultimately, what we’re looking at, and I know there’s a lot of active research on this, and there are already some therapies out there.

Dr. Thomas Fabian (00:08:28) – I’m a little less familiar with that end of things, the allergy immunotherapy or oral immunotherapy, but there are options. They’re somewhat limited to the foods that tend to be most problematic, like peanut allergy. But then again, not everyone responds to those approaches as well. So I think the tools that we have traditionally and up to this point have been pretty limited. So where a lot of this seems to be going, at least in part, is because of the advances in the microbiome. We are learning so much more about ways in which we can cultivate microbiome balance and the environment that the microbiome is in. Both of those are equally important and hopefully we can do a deep dive into that sort of interrelation today. But there are so many potential points that we can now intervene from a functional medicine standpoint, and I know a lot of these things have already been in practice for quite a long time. It’s just a matter of recognizing which ones are appropriate and when. So I think we’re moving towards more of a framework that we can operate within that incorporates some of these new advances in the microbiome, and particularly how the microbiome interacts with our nervous system and immune system.

Dr. Thomas Fabian (00:09:45) – But, at least from my perspective, a lot of the challenges do have to do with people being more sensitive now. We’re just seeing more and more individuals with overwhelming reactivity. So they’re down to just a handful of foods, even those foods they may be reacting to, and they’re just kind of at a loss as to where to go. And practitioners run various tests to identify what’s going on and it can be challenging with so many different things going on to figure out where do you start? What do you focus on? So I think all this research really does give us a lot of additional clues now in where we might want to look to see, for this patient, where is their limiting factor, versus that precision medicine, individualized, personalized medicine approach? Where do we want to intervene based on what’s going on for that particular patient?

Dr. Kara Fitzgerald (00:10:42) – I want to understand that. I think it’s huge. We do see these reactions and I can speak a little bit about some of the cutting edge tools manifesting in the world of classic allergy, like immunotherapy. To your point, we can do desensitization now, and kind of retrain the immune system to have a little bit of tolerance, which is amazing. That’s incredible. There’s also this wholesale shift towards early introduction of foods. You know, in the literature, Tom, as early as two months, introducing exposure to antigenic foods. I think the sweet spot is between four months and six months of age, introducing micro exposures to those common allergens, just to tell the immune system it doesn’t have to react. So I think that is an extraordinary transformation happening in the field. And that will, of course, influence what’s happening in the microbiome. But we’ve scrambled the microbiome, you know, living in this world, being exposed to so many different medications, stress etc., like all these environmental factors.

Dr. Kara Fitzgerald (00:12:08) – And to your point, we see these layered reactivities, immunological sensitivities as well as intolerance, layered on and really a refractory response. We can’t get these people on an expanded diet and they come to us malnourished and eating just a handful of foods. Not everybody, but some people. And it is so difficult. And so, you talk about starting to have a roadmap on this and I want to understand that. So what are some of the promising new developments in the world of science on this? And then, yeah, I want to talk about the gut’s role in this. And then, of course, for both of these, I’m interested as a clinician in the kind of solutions that you’re seeing. So let’s talk about the gut.

Dr. Thomas Fabian (00:13:08) – It’s a big problem overall because there are just so many points that feed into it. And we could talk about the exposome for a whole podcast and just the influence that has. We could talk about the microbiome in infants and what is the normal development of the microbiome, and what are we actually seeing now in so many infants and young children, in terms of how their microbiome is not developing properly based on lots of these environmental factors and just other factors that are happening. So there’s a lot of different things that kind of impinge on this and a lot of that has to do with the exposome. But when it comes to the core pathophysiology that’s emerging, at least for the immune-mediated side, particularly food allergies, that’s the one that’s probably best worked out, we know that the microbiome from the get-go is important in infants. The normal process is, of course, you have immune support from the mother, particularly through breast milk, through exposure to microbes from the family members, from that early environment.

Dr. Thomas Fabian (00:14:13) – But ideally, you do want to see the healthy microbiome developing, ideally right around six months or so and that transition to solid foods that happens. Often by then, though, the children are actually still reacting. They’re just starting to react and so it’s difficult to even introduce some of these foods from the beginning. So there is some research now looking at butyrate for example, and some of these factors that play a role in immunotolerance that actually should be present in breast milk at a certain level. But every scenario is going to be a bit different. Some infants may not be getting the level that they need there. So there are these early points that could lead to intervention based on what we’re learning. But often once these develop later in life, the question is, can we still intervene at that point? Can we work on the microbiome? We know that’s a big piece. So we are going to be diving into some details there, I think, through our conversation today.

Dr. Thomas Fabian (00:15:14) – But in terms of the microbiome, just kind of at a high level, we know that there are certain opportunists, some of these, LPS-type microbes (lipopolysaccharide), microbes that produce other factors, can shift the environment so it’s much less immunotolerant. It’s more of a proinflammatory environment. They can affect the intestinal barrier, so they are a really major component of the intestinal barrier. There’s the influence of these various gut axes. We know that the gut-skin axis is very important, the brain axis, even to some extent the gut-lung axis. So it’s not just about the gut microbiome. We do want to take into account what’s going on in these other areas as well. But just focusing on the gut microbiome, it really does come down to what we know about opportunists and certain key opportunists, but also the beneficial microbes. So we’re talking about both sides of the equation. It’s not all about finding the bad guys and just figuring out what antimicrobial is going to work for them. We want to know how to cultivate that beneficial bacteria.

Dr. Kara Fitzgerald (00:16:27) – Save that thought because it’s really important, but I just wanted to circle back to early infancy and breastfeeding and just underline butyrate. I just think that’s a nice pearl. Of course, vitamin D comes to mind and fish oil and so forth, but that’s awesome. And the piece about butyrate – I want to say this to the listeners that we can address all of this in mom, and we can bring dad into this story as well, for sure, preconception, and then obviously during the pregnancy and during infancy. We’ve got mom front and center, especially if she’s breastfeeding. But what we’re talking about now we can apply to mom to really have her ready to expose baby to the best microbiome possible, and to the most nourishing milk, etc., etc. So I just wanted to bring that forward.

Dr. Thomas Fabian (00:17:36) – That’s a very important point to emphasize because even starting early in infancy, for some infants that process may already be underway. So knowing what you potentially can do even before then, during pregnancy, I think is critical information.

Dr. Kara Fitzgerald (00:17:54) – Yeah, without a doubt. So the pro-inflammatory players we’re thinking about wanting to drop down, and then we’re thinking about nourishing the players involved in establishing tolerance and maintaining balance. I think that that’s where we are right now if you want to talk about some of those specifics and how we might use a DSL (test) to guide us there. And then we can circle over to food intolerances, the non-immunological ones. So let’s talk about the microbiome and some of the characters we want to be thinking about.

Dr. Thomas Fabian (00:18:37) – In terms of the microbes, we actually know quite a bit now. There’s this general idea of the imbalance between the opportunistic microbes, the pro-inflammatory microbes, and then the normal microbes.

Dr. Thomas Fabian (00:18:52) – But when you drill down even further, we’re actually looking at information now from research that you can separate those out in various ways. One would be upper GI versus lower GI. One of the ways that’s been actually fairly well established at this point, where the microbiome can be involved is in affecting the antigens themselves. So of course, antigens are primarily proteins in most cases, not all, and in order to reduce the exposure to those potential antigens, other than of course avoiding them in the diet, would be the digestion process. We know that patients that have low stomach acid, for some that can actually be due to, for example, H. pylori or chronic infection in the stomach that can reduce stomach acids, and that is often one of the microbes that we will see overgrown in patients that appear to have adverse food reactions.

Dr. Kara Fitzgerald (00:19:50) – And this could be adult onset? Like, whenever they started colonizing H. pylori would you say?

Dr. Thomas Fabian (00:19:57) – Oh yeah. Immune tolerance can be disrupted, unfortunately, at any point in life by something significant enough, like an infection, gastroenteritis, by antibiotics, or even extreme stress. There’s some evidence now that that may be enough of a trigger, but especially in combination with these other things altogether. So that’s part of what we would be looking at, is the microbes and their location and what they may be doing based on what we know from research. There’s a fair amount of research on these upper GI type microbes. H. pylori would be key because that can often cause low stomach acid. We definitely know that you need to break down proteins completely into their component amino acids for them to no longer have this structure that basically is recognized as a potentially foreign antigen. But it turns out that in addition to H. pylori, that’s indirectly affecting that process, some microbes are now thought to directly metabolize antigens and there are two different types emerging. There are the ones that can actually break them down. Gluten is kind of a classic example. The gluten already is not easy to break down, even if you have decent levels of digestive enzymes and stomach acid.

Dr. Thomas Fabian (00:21:18) – Some of that can still escape digestion to a certain point. So you have certain beneficial microbes like Lactobacillus. Certain Lactobacillus species can basically continue to help break those down further until they’re no longer immunogenic or at least have reduced immunogenicity. On the other hand, you have certain opportunists like Pseudomonas aeruginosa, which is the best studied that produces a particular virulence factor. It’s a type of protease that can act on gluten and other food proteins, break them down just to a certain point where they’re actually more able to cross the intestinal barrier but still have that antigenic potential. So it actually turbocharges them.

Dr. Kara Fitzgerald (00:22:03) – Wow.

Dr. Thomas Fabian (00:22:05) – And that’s been replicated in a number of studies, particularly with Pseudomonas. There’s some implication that it’s one of the microbes that may also be involved in celiac disease, but also just wheat reactivity or gluten reactivity as well. So we’re talking about these upper GI microbes. We know certain things about them, in terms of the conditions that lead to their overgrowth, such as poor digestion in general.

Dr. Thomas Fabian (00:22:33) – So that can be another factor that leads to an increase in, for example, Pseudomonas. Another one that’s really common is Staphylococcus aureus. That one has been widely linked to all kinds of allergic conditions, so it’s pretty much the predominant microbe implicated in atopic dermatitis.

Dr. Kara Fitzgerald (00:22:53) – Right.

Dr. Thomas Fabian (00:22:54) – So there’s this gut-skin connection. Allergic rhinitis or seasonal allergies, that’s thought to be involved, even asthma. So there’s kind of this gut-lung connection, and then Staphylococcus aureus seems to be prominent there, but it can also be in the gut. We know when it’s in the gut, it can also produce a wide range of factors that can accentuate this immune response. So it can essentially prime these immune cells, like mast cells, that are such a key feature of allergic responses. But again, there’s quite a bit of research information that suggests one of the reasons they’re often overgrown is poor digestion. So it sort of becomes this two-way vicious cycle. Once digestion decreases, additional evidence shows that those types of foods, like gluten, for example, can promote the growth of Pseudomonas.

Dr. Thomas Fabian (00:23:52) – So it creates this a little bit of a vicious cycle in the upper GI tract. There’s just accumulating evidence on these guys that they really are troublemakers. So another example that was just published recently, I think in the last year or two, is Staphylococcus aureus can actually interfere directly with the process for production of those disaccharidases. The best-studied one in that case is sucrase isomaltase. So it can directly interfere with our ability to fully break down carbohydrates. So that gets more into the carbohydrate intolerance side. But as far as the food antigens-

Dr. Kara Fitzgerald (00:24:31) – But this would be non-immunological mediated or less likely to be immune… So it’s both, basically. Staph aureus has been implicated in both as well as, you know, when it’s somewhere else, it could be implicated in wherever it’s located, like asthma in the lungs or atopic dermatitis on the skin. That’s really interesting. It’s really interesting. Okay. What else were you saying?

Dr. Thomas Fabian (00:24:57) – Interestingly, both of those have also been implicated in IBS. We’re starting to see this kind of expansion of the traditional spectrum of immune-mediated food reactions and then intolerances. Both of those types of reactions are now known to be common in patients with IBS. So it’s been long recognized that IBS symptoms are triggered by foods primarily, and they fall on that same spectrum. But there are some differences there which we can potentially get into in terms of, for example, the difference between an actual food allergy and then the IgE that’s seen in IBS. So there’s some evidence that IgE can play a role in some patients in IBS. But again, we’re looking at these microbes that play a role more in the upper GI tract, and they tend to be more of the opportunist. The small intestine is kind of an environment that favors these types of microbes, partly because of the availability of these easily accessible nutrients, like amino acids and also sugars. So it kind of makes sense that they would interfere with the digestion of these factors because they benefit from that.

Dr. Kara Fitzgerald (00:26:14) – Yeah, and they’re there, meeting the food. Can I take a second and just summarize what I’m hearing you say, and then you can confirm or correct me? Because you’ve said a lot. There’s a lot of clinical pearls here, there really is, and that’s why I want to take a minute. So we’re thinking about the upper GI. We’re thinking about digestion. You talked about stress being involved in the mechanism of developing food reactions, immunological and non-immunological. And of course, we know stress very efficiently shuts down the whole digestion process, so it makes sense that it would allow for the proliferation of microbes. But I don’t want to just pin this on stress because there are all sorts of other players involved, as you said. So we can analyze digestion really carefully.

Dr. Kara Fitzgerald (00:27:11) – You talked about H. pylori – that’s brilliant – obviously, as compromising digestion, leading to insufficient breakdown of foods, which makes them more antigenic, which just makes them vulnerable to reactivity. But then, further along, we’ve got Pseudomonas aeruginosa, and then we’ve got Staph aureus, and I’m sure there’s a whole host of other critters that you’re aware of. We can look at both of these on DSL, but we can see that they could be in our vulnerable patients driving these reactions. And one of the things you said that was incredible, like really sort of an aha for me, is that they can participate in a variety of mechanisms driving reactivity. They can participate in both immunological-mediated reactions as well as intolerances and a subset of immunological IgG as well as IgE. So that is what we see these days. We see this cross-section of reactions in our patients. Rarely is there a single mediated pathway in our patients’ reactions.

Dr. Kara Fitzgerald (00:28:26) – There’s always multiples. So if somebody comes in with intolerances, you can pick up allergies perhaps, or cross-reactions, or any of those plethora. So I wanted to just point out how useful that is to see that these players could be creating that together. And then I also wanted to ask you if you’ve got any more specific details on the specific Lactobacillus species playing a role in calming this reactivity down? So do I understand that, anything to add to it? And then, you know, let’s continue on.

Dr. Thomas Fabian (00:29:07) – Definitely. Yeah. So there’s a couple. As far as what’s been most studied in research, I would say Lactobacillus reuteri. Also pronounced Lactobacillus reuteri (roo-teh-ree), I’ve heard both. So that’s a particular species and there are strains that have been studied of that species that are now available in certain probiotics. They’ve been studied in research for potentially reducing these immune-mediated food reactions, particularly by acting in the upper gut.

Dr. Thomas Fabian (00:29:41) – Already we’re starting to see Lactobacillus can counteract some of these multiple mechanisms that the bad guys are implementing. One is, for example, through breaking down these proteins more efficiently through their proteases, but also having other ways in which they can modulate the immune system. And that can be, for example, just through the production of lactate. Lactobacillus, of course, is a lactate-producing bacterium and there’s evidence that lactate, in certain circumstances, has a calming effect on the immune system. That may be one way in which it does that. Streptococcus is really the dominant microbe in most individuals in the small intestine. One of the ways in which it can help is it competes. A lot of the ways we view commensals, whether they’re in the small intestine or large intestine, is that they’re competing for nutrients with the bad guys. So in the small intestine, the good guys and the bad guys both like the simple nutrients: sugars and amino acids.

Dr. Thomas Fabian (00:30:49) – Strep is really good and efficient at taking up sugars in particular, probably amino acids as well, rapidly, and it’s not considered under most circumstances to have negative effects in the small intestine. It’s pretty normal. It’s almost always the dominant species by far in the small intestine. So it’s helping to protect against the action of these opportunists by competing with them for the nutrients. A lot of these beneficial microbes also produce antimicrobial factors of their own, and those then can help to counteract some of these opportunists. So it’s sort of like this continual battle going on, both in the large and the small intestine, between the good guys and the bad guys, for nutrients, for space, etc. So balancing the small intestine is important. And then in the large intestine, that’s mostly where sort of the food intolerance symptoms seem to manifest, so we can talk about more of that aspect of the large intestine when we get to that topic. But when it comes to just the effects on the immune system, we know that a lot of the commensals in the small intestine promote the production of particularly butyrate, but also other factors that are known to have effects on promoting a balance in the immune system towards more of these T regulatory cells, with butyrate being the best studied.

Dr. Thomas Fabian (00:32:12) – But even some of the bile acids that they metabolize into these secondary bile acids also can help to affect that balance in the immune system more towards the T regulatory cells. And as far as butyrate, it goes beyond just the T reg cells. We know that overall there’s a lot of effects on the immune system in general from butyrate. Studies, for example, show that butyrate can potentially suppress the activation of mast cells. So it’s just really important across the board to make sure that when you’re looking at GI Map results, for example, we have three common patterns that we recognize that are pretty easy to pick up. On page two in the commensal section, you’ll often see a deficiency, especially in these important keystone microbes that promote these T regulatory responses, immune suppressive responses, particularly Faecalibacterium prausnitzii, a major butyrate producer, Roseburia, Akkermansia, and on and on. It’s very important to look at that side of the equation because for some patients, when they have extensive immune reactions, we don’t necessarily always see a lot of opportunists, but we often can see a lack of these commensals.

Dr. Kara Fitzgerald (00:33:33) – Fascinating. Yeah, we tend to implicate the players involved in inhibiting histamine breakdown or involved in producing histamine. We sort of look for the bad guys and it is difficult to find a pattern that we can comfortably address. But seeing a dearth of butyrate producers is extremely common. And I didn’t realize that butyrate is an antihistamine. Do you know mechanistically how it works?

Dr. Thomas Fabian (00:34:06) – I don’t know if I would directly call it an antihistamine, but it basically helps reduce the activation of a wide range of immune cells, including mast cells. So indirectly, you could potentially view it as an antihistamine, because that’s one of the key factors that they dump.

Dr. Kara Fitzgerald (00:34:23) – Yeah. But it’s more like a mast cell stabilizer, a gastrointestinal mast cell stabilizer.

Dr. Thomas Fabian (00:34:30) – Yeah. And one thing I’d like to add there is that we tend to view these mast cells, we hear about them in mast cell activation, we hear about them in allergies, but they do have normal physiological roles, right? So one of their main physiological roles is to protect the barrier against factors that can damage the barrier and also repair the barrier. And that’s particularly true for eosinophils. One of the normal functions just recently discovered for eosinophils is to maintain the barrier, particularly in the upper GI tract where we’re most exposed to these food antigens. Butyrate appears to be one of the factors that helps promote that more homeostatic form of the eosinophils.

Dr. Kara Fitzgerald (00:35:19) – That’s great. Yeah, it’s always important for us to take a minute and remember that we evolved with this exquisitely sensitive immune system, you know, to not drive the pathogenesis of these modern ailments, right? But to protect us, and to maintain us, and to help with barriers. And yeah, it’s always important that we remember that.

Dr. Thomas Fabian (00:35:45) – Actually, one more example that I like to share, because again, this is just relatively recent research also on this topic of eosinophils promoting a healthy barrier when they’re not activated, when they’re just kind of carrying out their normal functions. Another diet-related factor that actually has been shown to potentially maintain them in that calmer state are actually indoles derived from cruciferous vegetables. So this is where we’re looking at the domino effect that in order to get those active forms from cruciferous vegetables, you need to have adequate stomach acid. And how common is that to not have adequate stomach acid? People are on PPIs. People have H. Pylori overgrowth. So these could be indirect contributors to the overactivation of these cells that are primarily in that small intestine region where the antigens are most concentrated.

Dr. Kara Fitzgerald (00:36:47) – Wow. That’s fascinating. Yeah, because they’re not being adequately supported for their beneficial phenotype because some part of the cascade has been interrupted. And yeah, commonly, we’re not digesting well.

Dr. Thomas Fabian (00:37:04) – Right. It’s so important to recognize that immune tolerance has to be actively maintained. It’s not something that is just set when you’re young, right after birth. It’s something that your body is actively maintaining, which ultimately is a good thing because your body needs to be flexible and adapt when things change. Unfortunately, if that has to do with infections or a period of poor diet, that could be a period where you’re more vulnerable to losing immune tolerance.

Dr. Kara Fitzgerald (00:37:38) – Yeah.100%. Another great point. And it’s a symphony, it’s a complex cascade. It’s not just T reg cells or B cells or any aspect of the acquired immune system recognizing that particular antigen is not a problem. That’s the end of the line. There’s a really involved symphony going on before then that can be interrupted at any point. It could be digestion, it could be poor sleep, the cephalic phase initiating digestion. It could be barrier disruption from some medications or-

Dr. Thomas Fabian (00:38:23) – That’s a big one that’s being studied now in terms of the effects of circadian rhythms on susceptibility to allergies.

Dr. Kara Fitzgerald (00:38:31) – Wow, that’s fascinating. That’s really fascinating. Can you say something about that?

Dr. Thomas Fabian (00:38:36) – The two things that kind of jump out to me, I’ve come across  some papers showing that mast cells have a circadian rhythm. And, again, you talked about the symphony, so some of that has to do with the microbiome driving this process. And you can imagine, of course, during the day when you’re consuming foods that promote the growth of certain microbes, your body’s expecting that rhythm. And it’s expecting not to have food at night, but unfortunately, there are a lot of people who are active at night. They might snack or even have a late dinner or something like that, just staying up too late.

Dr. Thomas Fabian (00:39:08) – But generally when circadian rhythms are not really where they’re supposed to be, that can contribute to immune dysregulation, which mostly translates into these immune cells being overactive, because they normally follow a rhythm where they’re supposed to be active during certain times, less active during others. But when that’s disrupted, they tend to stay active, like always on high alert. And then there’s also a circadian rhythm in intestinal permeability. It’s actually normal to have a certain amount of permeability during the phase when you’re consuming food to facilitate digestion. Your immune system during that time is programmed to be more tolerant because food antigens will be coming through, and you don’t want to have too much inflammation, of course, just based on your normal food consumption. And then it’s supposed to be less permeable after that normal eating period. With disrupted circadian rhythms, it’s common to eat at different hours of the day and even into the night. That can completely disrupt that system and you may be consuming antigens that would be less of an issue if you consume them during normal periods. It’s almost mind-boggling, all this different information that’s out there, but it just comes back to reinforcing how important these basic lifestyle factors really are down to this molecular cell level if you really want to address these food allergies, food sensitivities effectively.

Dr. Kara Fitzgerald (00:40:45) – It’s so interesting to me. What else do I want to ask you about this? Well, are there any other types? Do we want to talk about the intolerances now and move away from the immunological reactions? You’ve already touched on it a little bit, but we can go back into that if you want to expand. And then I want to turn back to really talking about how we analyze this using the GI Map, and of course, what you’ve been seeing. I know you consult with physicians around the world. You consult with clinicians all the time, so you’ve got a window of insight into how to apply the tools and what seems to be hitting paydirt. What are patterns that you’re seeing that you’re tweaking that really seem to be important? So dive in there and from any of those points that I just made and we’ll move through.

Dr. Thomas Fabian (00:41:54) – You know, I think it might be helpful to touch on the food intolerance side. It’s a big topic so we don’t have time to cover all that, but just briefly on carbohydrate intolerance, that’s another area that’s also expanded in terms of there’s sort of the traditional viewpoint, mostly coming from, in the past, the observations about lactose intolerance stemming from some individuals not having enzymes that are that are active past a certain point in their life where they just can’t tolerate lactose anymore. That’s been expanded a lot and there have been some recent reviews coming out about how extensive this is, that it’s surprising that many more patients than we were thinking probably have disaccharidase deficiencies.

Dr. Thomas Fabian (00:42:42) – Some of that can be genetic. Probably the majority of that tends to be secondary, meaning that when you have this upper GI dysbiosis and you have these food reactions occurring, you can have immune mediated food reactions occurring at the same time that you have these intolerances, and that’s one reason why it can be difficult to tease them apart. But if you have that reactivity happening in the upper GI, that can negatively affect the brush border enzymes, and then that can lead to reduced digestion and absorption of carbohydrates. And we can get all kinds of details there, which again, there’s probably not time for, but-

Dr. Kara Fitzgerald (00:43:21) – But that’s where the enzymes, just to color it in, the enzymes are produced there in the brush border.

Dr. Thomas Fabian (00:43:27) – Those are the last steps in carbohydrate digestion. So, of course, pancreatic amylases, even salivary amylases, are kind of more on the upstream side, particularly with starch. But the brush border enzymes break down those last few steps and also break down oligosaccharides, disaccharides, etc.

Dr. Thomas Fabian (00:43:49) – And they have to be broken down to be absorbed. So what happens with a lot of these, what they think mostly causes the symptoms is a combination of the osmotic effects of these- So sugars, basically, because of the osmotic effect, draw in fluid from the body into the intestine. Past a certain point, that causes rapid transit down to the colon, so you get this massive delivery of sugars to the colon and a massive burst of fermentation that can lead to gasses, that can produce bloating and distention, for example, and other factors. But one of the differentiators is hypersensitivity, which is really where the microbiome comes into play in a similar way to immune-mediated food reactions. And hypersensitivity, just to kind of cut to the chase, has been mostly so far thought to involve mast cell activation. Again, there can be various things that activate mast cells, including microbes and their products. A key thing to understand with carbohydrate intolerances is the difference between that and carbohydrate malabsorption.

Dr. Thomas Fabian (00:45:04) – Of course, the idea of breath testing is being promoted for detecting carbohydrate malabsorption, but studies show that healthy controls that have no symptoms can have some level of malabsorption with no symptoms, versus the patients that get symptoms are hypersensitive. So whether it’s gas, and they’ve shown in imaging studies that they can produce the same amount of gas as a person without symptoms, but they’re hypersensitive to that.

Dr. Kara Fitzgerald (00:45:34) – What is that mechanism driving the hypersensitivity?

Dr. Thomas Fabian (00:45:37) – They think that part of that, when it comes to the microbes, you mentioned histamine, that’s one of the best-established ones that you can have high histamine-producing bacteria that actually thrive on these types of carbs. Probably the best studied is Klebsiella. So we know it thrives on sugars, it thrives on FODMAPs, it thrives on starches, so when you’re consuming those foods, it tends to be higher. It tends to convert more histidine over to histamine, then the histamine acts to activate mast cells. Mast cells then activate nerves and that process of activating the sensory nerves is basically what causes the symptoms.

Dr. Kara Fitzgerald (00:46:20) – That’s fascinating. So somebody who’s asymptomatic might have evidence, they might have a positive hydrogen breath test, but it’s just completely unremarkable. I mean, they probably wouldn’t be tested, but maybe in some cases they would, because they don’t have this hypersensitivity reaction. Would you still consider that excess production of hydrogen a problem, or not, where this is just within the realm of normal?

Dr. Thomas Fabian (00:46:48) – Yeah. And that’s one of the critiques of breath testing is it’s not very good in terms of specificity, differentiating between people that don’t have any issues with whatever volume of gas is produced. Studies going back to the ’70s have shown if you actually — and they don’t do this so much anymore — but if you actually essentially put a tube into healthy controls and patients with IBS, and you’re basically channeling gas into the intestine, at the same amount of gas level, healthy controls will have no symptoms at all. And then the IBS patients will have discomfort, possibly pain from that.

Dr. Thomas Fabian (00:47:29) – So they’ve known for a long time that there’s got to be something that’s triggering that in patients, which is whatever’s causing that increase in volume, often gas or liquids, or in the case of constipation, it can be stool. But it’s the sensitivity that causes the symptoms. So that’s really the key differentiator and that’s really where these microbes come into play. And actually, now we know it’s more than just Pseudomonas, more than just Staph on the GI-Map. You can see Candida, you see the Enterococcus species, most of the LPS producers, and also the histamine producers like Klebsiella and especially Morganella. We see those elevated in many patients with food-related symptoms.

Dr. Kara Fitzgerald (00:48:21) – That’s fascinating. Okay. So again, a positive breath test, not a huge issue, but looking at the microbes involved. And we talk about IgG as a hypersensitivity response to foods and this is not that. This is gut microbiome-mediated.

Dr. Thomas Fabian (00:48:57) – This is the term visceral hypersensitivity, mostly referring to the nerve endings being activated or having a lower threshold for activation. The immune system can be involved in that, but it’s not the same as hypersensitivity in terms of the immune system.

Dr. Kara Fitzgerald (00:49:15) – It’s secondary- So the immune system isn’t the initiating feature, but it’s sort of brought into the picture with the change to the microbiome. Is that correct?

Dr. Thomas Fabian (00:49:25) – It’s kind of an intermediate in many cases. Sometimes it can be foods directly activating the mast cells, in terms of the antigen binding the IgE, which is bound to the mast cells. But even then, the microbes influence the likelihood of that mast cell reacting. It’s the gut environment overall, including microbes that can influence how much that antigen binding triggers symptoms.

Dr. Thomas Fabian (00:49:53) – But in terms of carbohydrate intolerances, it’s thought to be more of an intermediate factor for some patients, where these microbes are creating  immune-activating molecules like histamine. There’s also proteases, there are also LPS. Mast cells have receptors for LPS as well. All of those potentially can trigger mast cells to be activated and then activate the nerves and that process is essentially visceral hypersensitivity.

Dr. Kara Fitzgerald (00:50:22) – Fascinating. Thanks. That’s really useful. Okay. Do you want to move on and talk about some patterns that you might see in these cases and how you’ve addressed them?

Dr. Thomas Fabian (00:50:41) – Absolutely. Yeah. We do see some common patterns. And of course, they’re more of the idiosyncratic ones, but I would say, patients presenting with your standard GI symptoms, bloating, abdominal discomfort after they have certain foods, in many cases, they’ve pinned it down. They know they react to gluten and dairy, some of the common ones, so of course elimination is an option there, as always. But it can really expand beyond that if that process isn’t really addressed more comprehensively.

Dr. Thomas Fabian (00:51:16) – So when you look at a GI-Map for a patient like that who has a number of food sensitivities, one of the things you’ll commonly see is a lack of commensals, particularly the butyrate producers. Faecalibacterium prausnitzii is one of the major butyrate producers. There’s also Roseburia. Akkermansia is another one which we will actually often see reduced. That may have to do with the fact that it can also support immune tolerance in different ways. Also, it’s kind of an indicator about mucus, and if the mucus is deficient, that’s another factor that’s known to predispose to food reactions. So already just looking at the normal commensals you can get some clues. And then if you look at the next page, of course, that’s where we see all these opportunists that we’ve been talking about, like Pseudomonas, Staphylococcus. But if you’re already starting to see this overgrowth pattern, that’s often a clue that maybe digestion is an issue, particularly if you also saw high H. pylori. So these are all really common in patients.

Dr. Kara Fitzgerald (00:52:23) – With or without virulence factors. Does it matter?

Dr. Thomas Fabian (00:52:28) – Commonly without. They’re not as common as you might think. We see them in a subset of cases, but H. Pylori, even if it’s not particularly pathogenic, can still potentially suppress stomach acid.

Dr. Kara Fitzgerald (00:52:46) – Okay.

Dr. Thomas Fabian (00:52:47) – And then moving on, sometimes we’ll see an increase in Candida. That’s pretty common. That’s kind of a two way street. That’s one of the microbes that we often see elevated in patients that are not digesting well. But it is another one that can be involved in food reactions in various ways. It’s also another microbe that’s known from numerous studies to promote mast cell activation and also visceral hypersensitivity. Parasites are on page four and we’ll often see those as well. They’re less well studied as far as their potential role in food reactions, but we often do see them there in patients that have food reactions, so there may be a connection. Then in the intestinal health section, there’s quite a bit there in terms of evidence for poor digestion.

Dr. Thomas Fabian (00:53:35) – If you see the steatocrit elevated, that’s high fat malabsorption. Poor elastase, that would be a big one. That can also cause dysbiosis as well. Secretory IgA can go both directions. So you often see low secretory IgA, which usually reflects lack of commensals, but you’ll also often see high secretory IgA when they’re currently actively reacting to something. And that could be either a gut infection or food reactions. So there are food reactions that can stimulate an IgA-type response. In that context you might see the anti-gliadin IgA pretty high and that would suggest that this patient may have a broad range of food reactions. Eosinophil activation protein is another great marker that’s often elevated in patients that have food reactions. We know from what we’ve talked about earlier, eosinophils can be part of that picture, especially in the upper GI. It’s kind of a two way street, normal eosinophils protect the barrier, and elevated activated eosinophils can damage the barrier when it produces those factors. Inflammation, like calprotectin, of course, when that’s elevated, inflammation can damage the barrier.

Dr. Thomas Fabian (00:54:56) – And then lastly, we have zonulin. Zonulin is definitely something that will indicate intestinal permeability. As far as the most common microbes, I would say are the top three. Candida would be kind of up there. As far as these intestinal imbalances, low elastase is common, low secretory IgA, higher anti-gliadin is pretty common. Eosinophilic protein we’ll just see sometimes, calprotectin, not that often, and then certainly zonulin, so leaky gut is known to be a major factor. So those are common things that you’ll see in patients that have this type of reactivity.

Dr. Kara Fitzgerald (00:55:38) – And you might see those butyrate producers low as well.

Dr. Thomas Fabian (00:54:56) – Exactly

Dr. Kara Fitzgerald (00:55:44) – And then maybe some of the histamine producers or supporters could be high. And you mentioned I think the chief was more Morgonnella followed by Klebsiella?

Dr. Thomas Fabian (00:55:56) – Klebsiella, yeah. Those are widely known as the top two and those we would see more commonly in patients that are thought to have histamine-type reactions. Practitioners will report that they have hives after eating certain foods, for example.

Dr. Kara Fitzgerald (00:56:16) – That’s very interesting. I have a patient with eosinophilic esophagitis (EOE) who had tons of steroids over the course of her illness. She was managed on steroid tapers quite frequently, and she had a lot of Candida from this, which is demonstrated in the literature, EOE associated steroid use prompting IgE sensitization to Candida. And what was interesting for her is after we walked her through and turned the volume down on her immune response, and she was symptom-free, she was able to expand her diet, sugar seemed to be what kicked in her EOE symptomatology. She had dysphasia and a pretty obvious set of symptoms, and sugar triggered it more than anything. More than gluten, more than her other identified reactivities, and my hypothesis was that she was stoking the Candida. So there was some residual reservoir there and she had an IgE sensitization to it, so sugar might stoke the Candida and she would become reactive.

Dr. Thomas Fabian (00:57:33) – I think it makes a lot of sense, since we know that Candida can activate mast cells, and mast cells can then activate eosinophils, so there may be a connection that way as well.

Dr. Kara Fitzgerald (00:57:43) – Yeah. It made sense to me and I just witnessed it clinically so I was piecing this together from what I understood pathophysiologically. All right. What else do you want to cover today? Do you want to talk a little bit about interventions? How clinicians might approach this clinically?

Dr. Thomas Fabian (00:58:09) – In many ways, it’s pretty straightforward. It’s going to be based on, of course, your patient history and what you know about their exposures. But in terms of the GI-MAP, if you see evidence of poor digestion, that could be either the direct evidence from low elastase or steatocrit, or the indirect evidence from H. Pylori overgrowth, which suggests low stomach acid, or general overgrowth of the opportunists, where we know that there’s lots of research showing, especially the ones that are at the top of page three, like Staph, Strep, Pseudomonas, and Enterococcus. Those are commonly shown to be elevated in patients with low stomach acid. There are some clues here that suggest you may want to explore supporting digestion. Food elimination, especially if patients are very reactive, it’s hard to know how much you want to eliminate foods. Because the food reactions themselves cause inflammation, particularly in the upper GI tract, you do have to calm that inflammation down. So at least for a period of time, pretty strict food elimination, at least for the most reactive foods, is likely to be very helpful. Seeing evidence with a high anti-gliadin IgA, for example, or generally high secretory IgA, could be part of that picture. Or you may want to do some other exploration of food reactions with other tests.

Dr. Thomas Fabian (00:59:40) – But oftentimes, if they’re super reactive, you’re going to want to rebalance the gut first so that you’re not having to recommend eliminating so many foods and you have a chance at reducing that reactivity overall. Antimicrobial herbs, which of course are standard, that’s definitely been part of the 5R program for a long time. With the remove step, that can be very important. But just understanding that you can do an antimicrobial protocol and often they’ll bounce back unless you address these other factors. A multifactorial approach ultimately is very helpful. Probiotics, as we talked about, Lactobacillus reuteri, Saccharomyces boulardii, for many patients can be helpful. Immunoglobulins I think, across the board, for many patients can be very helpful, whether it’s colostrum or the non-dairy immunoglobulins. And then these various factors-

Dr. Kara Fitzgerald (01:00:35) – You mean the serum bovine immunoglobulin you’re referring to.

Dr. Thomas Fabian (01:00:39) – Sorry about that. Yeah. And then a lot of these plant extracts, polyphenols that we know can calm the immune system in general. Butyrate supplementation. Of course, you want to promote those beneficial microbes with plenty of adequate fiber, different types of fiber. Again, that’s where polyphenols can come into play as well in promoting the microbiome. So lots of different ways to intervene, but again, it would depend on the specifics. What seems to stand out for a given patient as their most important factor. For some, it’s simply elastase. You’ll see that in the tank for some patients, and if it’s below 100, supporting their digestion can make a really big difference.

Dr. Kara Fitzgerald (01:01:27) – Huge. Immediate. Yeah. What about HCl? Are you recommending HCl these days to clinicians?

Dr. Thomas Fabian (01:01:36) – It can be very helpful. It depends on if they have a significant H. pylori overgrowth, where the HCl might irritate the lining of the stomach if it’s already irritated from the H. pylori, probably not a good idea there. But generally, it’s at least worth trying some way to support stomach acid, whether it’s more gentle, like bitters, or HCl to see if that helps. In most cases, it does seem to help.

Dr. Kara Fitzgerald (01:02:02) – I think it can be a really important tool. I know we’re not using it quite as much in clinic as we used to. It was a workhorse intervention for me. I used it a lot early in my career. But I think we’re in this era of more sensitive guts. I think most of us have had an experience where HCl exacerbated the situation, and so we’re a little bit more conservative with using it. But to your point, it’s an incredibly powerful tool. Yeah.

Dr. Kara Fitzgerald (01:02:34) – What about the other piece? In our practice we’re always trying to minimize elimination because it’s just such a problem for many, many reasons, to cut somebody’s diet way down. And we want to expand. So when we’ve got these people coming in on five different foods for a protracted period of time, we’re definitely working on expanding their diet as quickly as possible. But, in some of these early cases where we’re seeing these multiple patterns of reactivities, which you really elegantly walked through, the layering of non-immunological intolerances with immunological reactivity and sort of the nexus where both of those meet, we’ll use a short-term elemental. And by short-term, I might use an elemental diet in a patient like this for a long weekend. Sometimes we use it longer, and I think it’s indicated to use longer sometimes.

Dr. Kara Fitzgerald (01:03:37) – But just sort of cleaning the reactivity slate so that we can then start to reintroduce the foods that we think are going to be best tolerated and work on that expansion. I’m curious about your thoughts on doing that, while concurrently doing the work based on what we identify on the test?

Dr. Thomas Fabian (01:03:59) – I definitely think it can be helpful, particularly from a standpoint of just cutting down on potential antigens, irritants. So I think that’s one of the ways in which it can be very helpful. Interestingly, and this gets a little bit in the weeds, so I’m going to try to make it really short, but there’s growing research now on fibers and potential detrimental effects in certain scenarios. So for example, just in the last couple of years, there’s been a lot of research on inulin, which we know is generally beneficial, promotes the growth of the good commensal bacteria so they can crank out some butyrate and that may be something potentially helpful.

Dr. Thomas Fabian (01:03:59) – But in patients that don’t have enough of these beneficial bacteria, some of those FODMAPs in inulin can actually be metabolized by the bad guys. And the study showed a different mechanism recently where inulin actually can bind to a certain receptor that triggers inflammation if the inulin isn’t broken down already by the healthy microbes. So it kind of suggests that the context is really important. So that if you’re using an elemental diet, you’re removing those fibers temporarily, so you’re kind of depriving the bad guys in the gut of one of their sources of fuel. But also, if those fibers were irritating the lining of the colon, for example, in the absence of enough of the beneficial guys, then you can first work-

Dr. Thomas Fabian (01:05:31) – Once you calm that inflammation down, you can then work on slowly building up the good guys so that you have enough of them to metabolize these carbohydrates. And that comes down to this competition sort of scenario again. Another study just came out showing almost the same thing for polyols, particularly sorbitol. Without enough of the good bacteria in the colon, which overlaps with the butyrate producers, basically patients cannot adequately break down the polyols. So overall, the microbiome acts as a competitor and a way to safely handle many of these carbohydrates and convert them into beneficial products. But if you’re thinking that the microbiome is deficient, just giving a lot of fiber right off the bat and trying to get that microbiome to recover, that might actually be counterproductive for a lot of patients. So maybe a period of elemental diet followed by slow reintroduction, and then also introducing these other means of benefiting the microbiome with polyphenols, maybe butyrate supplementation. And that study did actually show that butyrate alone helped the Clostridia recover enough so that they could then handle these sugar alcohols, the sorbitol.

Dr. Kara Fitzgerald (01:06:49) – Wow. And I just want to remind people, the butyrate producers are some of the Clostridia players, Akkermansia, and then Faecalibacterium prausnitzii, right.

Dr. Thomas Fabian (01:07:01) – Particularly the Faecalibacterium. That one is such a major player that overall butyrate levels tend to trend just with the Faecalibacterium.

Dr. Kara Fitzgerald (01:07:10) – So another pearl into our FODMAP patients, particularly polyols,  if you’ve been able to identify, which we do in practice. With our FODMAP-sensitive patients, we will have them move through a challenge. It’s quick because it’s just in the course of metabolizing the foods, you don’t have to wait for an immunological reaction. You can identify what collection they’re reacting to pretty rapidly. So if you have a polyol-reactive patient, you can immediately be thinking about these butyrate producers as needing to address them to help with polyols digestion.

Dr. Thomas Fabian (01:07:52) – And I think that’s so-

Dr. Kara Fitzgerald (01:07:53) – You’re so full of pearls all the time. This is awesome.

Dr. Thomas Fabian (01:07:57) – I do love to research, and I just kind of like to hone in on the ones I think will have some beneficial applications in our field and that one really stood out to me. If you can do something as simple, and it won’t be that simple for every patient, but, butyrate, particularly in the form of Tributyrin, was the one that was studied, almost single handedly- This first part was done in an animal model, so you have to take it with that grain of salt. They followed up with some additional human-related studies that indicated that likely that would happen in humans as well, a similar mechanism. But I think it really does show that we have to be a little more sophisticated sometimes, and that timing and how do you approach these things. We shouldn’t always look at it simplistically in the sense that if they’re lacking good bacteria, just immediately give them a ton of fiber? It’s likely that their microbiome just can’t handle it and you may actually be feeding the bad guys first if you haven’t first made sure that they’re not a problem.

Dr. Kara Fitzgerald (01:09:03) – My team is going to work on corralling together as many of the pearls that Tom has shared with us today and we’ll just feed them out on our social media. Be sure, folks, to circle back to the show notes page where the full transcript will be there. We will be grabbing some of these references from Tom, as we always do. I’ve conversed with Dr. Fabian multiple times over the years, so we’ll also link to those podcasts as well. They’re all similar. If this is your first podcast with Tom and I speaking, our prior podcasts are equally enriching to the clinician and the curious, regular person. Tom, I think that’s it. Is there anything else you want to add?

Dr. Thomas Fabian (01:09:51) – I think maybe just a couple of take-home points would be-

Dr, Kara Fitzgerald (01:09:54) – Yeah, do that.

Dr. Thomas Fabian (01:09:55) – I think beyond the food elimination standpoint, I think in functional medicine, everybody’s pretty well-versed in ways to increase gut health. But now that we have some of these specifics that we talked about, I think that’s the next level. So if this is a patient population that you’re frequently dealing with, and I think most practitioners are.

Dr. Kara Fitzgerald (01:10:15) – We all are. Yeah.

Dr. Thomas Fabian (01:10:17) – Having these additional details can really make a difference in certain cases. And that’s really where comprehensive stool testing with GI-MAP can be so helpful because a lot of what we talked about, insights into opportunists, into the normal microbiome, into digestion, immune status, the status of the intestinal barrier, all of those are critical. And you really want to know, where is the patient’s weak point? You don’t know that unless you look and see where you really want to intervene and focus your intervention? So I think that a big part of it is moving beyond just food elimination, which is still necessary, often up to a point. But that can be just a runaway train for so many people that their whole life is focused on being anxious over foods that are going to trigger symptoms and that’s really negative for our quality of life.

Dr. Thomas Fabian (01:11:10) – So if there’s a way that you can reduce their reactivity by improving gut health in a very targeted way, I think that can be very rewarding in the sense that you’re likely to get better patient outcomes in many cases.

Dr. Kara Fitzgerald (01:11:27) – Yeah. For sure. What polyphenols do you recommend? You’ve mentioned polyphenols as a broad group a few times. And of course, there’s a lot there. So what are the ones that you’re recommending?

Dr. Thomas Fabian (01:11:39) – It depends on the goal, but generally if you want to boost the beneficial bacteria, particularly Akkermansia and Faecalibacterium, you’re looking at cranberry extract, quercetin, and grape, pretty much anything from grapes like resveratrol, grape seed extract, pomegranate extracts, those are some of the best studied. Curcumin, kind of across the board as an anti-inflammatory. In terms of specifically those that are documented to inhibit mast cells, luckily there’s overlap. So once again, quercetin, resveratrol, and curcumin are among the ones that are studied. There’s a broader list. There’s actually a good review that I’ll share with you that covers a lot of these. Vitamin D, really important, and butyrate supplementation. But as far as plant extracts, those are some of the best-studied ones.

Dr. Kara Fitzgerald (01:12:36) – Perfect, perfect. Well, Dr. Fabian, it was great to hang out with you again. Thank you for all your wisdom. And folks, do go over to the show notes to grab our summary, grab citations, and have access to the full transcript.

Dr. Thomas Fabian (01:12:49) – Thank you so much for having me today. It’s been my pleasure.

Dr. Kara Fitzgerald (01:12:52) – Yeah. Always.

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. More recently, he 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 Science Advisory Board member with Designs for Health.

tom.fabian@diagnosticsolutionslab.com

Dr. Thomas Fabian, Ph.D., CNTP

Diagnostic Solutions Laboratory

Study: Understanding food allergy through neuroimmune interactions in the gastrointestinal tract

Review article: The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes

DSL Webinar: Neuroinflammation and the Gut-Brain Connection

Article: Mechanisms Underlying Food-Triggered Symptoms in Disorders of Gut-Brain Interactions

Study: Lactobacillus reuteri induces intestinal immune tolerance against food allergy in mice

Study: Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation

Study: Epigenetic histone modification by butyrate downregulates KIT and attenuates mast cell function

Study: Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI-mediated signaling

Study: Time matters: The circadian rhythm in intestinal homeostasis and food allergy

Study: Unfermented b-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients

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

Study: High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota

Study: Effects of Dietary Components on Mast Cells: Possible Use as Nutraceuticals for Allergies?

Study: Nutraceutical Aid for Allergies – Strategies for Down-Regulating Mast Cell Degranulation

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

FxMed Podcast: Hydrogen Sulfide in Health, Disease & Longevity with Dr. Tom Fabian

FxMed Podcast: Latest Insights into the Role of the Gut Microbiome in Healthy Aging with Dr. Tom Fabian

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

Bio Age Lab Test

Bio Age Self Assessment Quiz

Younger You Group Program

Younger You book

Better Broths and Healing Tonics book