Microbiome in Food Allergies with Dr. Tom Fabian: Rational Wellness Podcast 233
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Dr. Tom Fabian speaks about the Role of the Microbiome in Food Allergies with Dr. Ben Weitz.
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Podcast Highlights
1:30 Food allergies vs Food sensitivities vs Food intolerances. Food allergies are mediated by Immunoglobulin E and mast cells tend to play a role. Patients with true food allergies may have very severe reactions such as anaphylaxis and they are immediate after eating that food. Food sensitivities are typically mediated by IgG and they tend to be delayed reactions. They can also be mediated by IgM and IgA, though these are less well defined. Secretory IgA, which is reported on the GI Map stool test from Diagnostic Solutions, is known to play multiple roles in the gut both in terms of reacting to things thought to be threats, but also a protective role in terms of commensal bacteria in which IgA binds to these commensals and by binding to normal food antigens, it helps to reduce or prevent over-reactivity from the immune system.
7:13 A Food Intolerance is a non-immune mediated reaction to a food, such as a carbohydrate intolerance or a histamine intolerance, which can be mediated by a lack of diamine oxidase enzyme, which keeps you from breaking down histamine.
8:46 A healthy microbiome can play a role in our oral tolerance to foods that might otherwise be harmless. Our immune system has a balance of pro-inflammatory and anti-inflammatory. Immune tolerance is a mechanism by which the immune system restrains overreaction, which applies to food allergies, and involves Treg cells. There are a number of products from the microbiome that promote Treg cells that promote immune tolerance and the one that has been best studied is butyrate. Certain commensal microbes seem to be especially important. In the small intestine, the important microbes are Lactobacillus, Bifidobacterium, and Prevotella, esp. a particular species, Prevotella histicola, which has been shown to protect against food sensitivities.
15:46 Leaky Gut. If you have leaky gut or increased intestinal permeability, then you can more easily get food antigens across the epithelial lining of the gut and react with the immune cells in the intestinal mucosa. If you have overgrowth of inflammatory type bacteria, such as E. coli, Klebsiella, or Ciotrobacter, this can cause leaky gut. Certain microbes can modify how antigenic a protein is. Pseudomonas, which is common resident of the small intestine, can break down certain proteins, such as gluten in a way that makes it easier for the gluten to get through the leaky gut. Then the gluten doesn’t break down enough till it is broken into individual amino acids, which is the ideal situation, since amino acids usually do not cause immune reactions. It’s the larger proteins that cause immune reactions. This is one of the reasons why hydrochloric acid is so important to break down proteins and a lot of people do not have enough hydrochloric acid.
Tom Fabian, PhD in Molecular, Cellular, and Developmental Biology. Tom is also a certified Nutrition Therapy Practitioner and he specializes in the microbiome and how it relates to digestive, immune, brain, and metabolic health. Tom offers a Microbiome Mastery course through his website, Microbiomemastery.com. Tom also works with Diagnostic Solutions helping to interpret the GI Map stool test. https://www.diagnosticsolutionslab.com/
Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.
Podcast Transcript
Dr. Weitz: Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me. And let’s jump into the podcast.
Hello, Rational Wellness podcasters. Today, I’m very excited to be speaking with Dr. Tom Fabian on the role of the microbiome in promoting and preventing food allergies, food sensitivities, and food intolerances. Dr. Tom Fabian has a PhD in Molecular Cellular and Developmental Biology, and he’s a certified nutrition therapy practitioner. Tom specializes in the microbiome and how it relates to digestive, immune, brain and metabolic health. And he offers a microbiome mastery course through his website, microbiomemastery.com. Tom also works with Diagnostic Solutions, helping clinicians to interpret the GI-MAP stool test and educate practitioners about stool testing and the microbiome. Tom, thank you so much for joining us today.
Dr. Fabian: All right. Thanks so much, Dr. Ben, it’s great to be here again today.
Dr. Weitz: Excellent. Excellent. So I was thinking, before we get into trying to understand how a healthy microbiome can play an important role in reducing the risk of food allergies, sensitivities, can you explain, what is the difference between a food allergy, a food sensitivity, and a food intolerance? Because I’m not sure most people are really aware of what those differences are.
Dr. Fabian: Sure, yes. And the lines are actually somewhat blurred a little bit with some new information that’s come out from research, plus they often coexist for some patients. So that’s just one of things to keep in mind, it’s not always a case where something fits in a nice, neat and tidy box. But generally, food allergies are caused by or mediated by immunoglobulin E in particular. They often have, of course, involvement of mast cells, so mast cells tend to play a key role in terms of food allergies. So typically, what happens is patients become sensitized to certain antigens through various mechanisms potentially, so that the immune system next time it recognizes that antigen, so the next time a patient consumes that food, they can have a pretty significant allergic reaction to that. So a lot of that’s mediated by mast cell release of histamine, for example, so they’ll often have histamine related symptoms, and of course, it can be pretty severe in the terms of anaphylaxis. So that’s the main concern with food allergies that are severe.
Then there’s the food sensitivity category, which is a little bit less well defined, but certainly we all know that, that tends to be mediated by a different immunoglobulin, which is immunoglobulin G. Again, the mechanisms are similar where patients become sensitized to particular antigens, and then instead of having an IgE anaphylactic type response, they’ll have a more subtle response typically. Again, it ranges across a broad range of significance and often it’s more delayed, so instead of having a more immediate type reaction, it’s something that can happen hours later, sometimes even days later. So it’s a little bit more of a chronic type issue or just longer term issue in terms of the symptoms manifesting.
Dr. Weitz: And I guess it could be IgM or IgA mediated as well, right?
Dr. Fabian: Potentially. Again, those are a little less well defined. So IgA is a mixed picture. It’s thought that Secretory IgA plays multiple roles in the gut, both in terms of responding to things that are thought to be threats, especially pathogens, but it also plays more of a protective role for things like commensals where we don’t want to overreact, and also just normal food antigens, we don’t want to overreact to those either. So it’s thought that Secretory IgA binds to these normal commensals, binds to normal food antigens, and by binding, it’s thought that, that’s part of how that helps to reduce or prevent overreactivity from the immune system.
So it’s partly a physical thing whereby binding these antigens or microbes keeps them away from the epithelium. So again, usually closer the organisms or the antigens get to the epithelium, the immune system can detect that and may start to overreact. So they’re still learning some of these features of IgA. It’s pretty fascinating that it plays so many different roles, but a lot of it is protective to help reduce the actions. But of course, if we overreact to certain things, that can be another reason why there might be an elevated Secretory IgA. So for example, on the GI-MAP test we have anti-gliadin one the markers, and that is generally thought to be a marker for gluten sensitivity, gluten reactivity. So it’s not always easy to tell when you have a positive result with IgA, is that a protective response? Is that more of a response [crosstalk 00:05:44]?
Dr. Weitz: So interesting.
Dr. Fabian: Yes.
Dr. Weitz: Because I know like Cyrex testing often includes IgM, and IgA, as well as IgG.
Dr. Fabian: Exactly. Yes, so I think it’s important, if possible, to get the more complete picture of what’s going on, because all these different immunoglobulins serve different roles. So I think that’s an evolving picture, we don’t have all the answers yet, unfortunately.
Dr. Weitz: And is there a sense that food allergies are more longer term or even permanent than food sensitivities which can come and go?
Dr. Fabian: That’s a great question. So I can’t say I have a really good answer for that, I’m not as familiar with the research on the comparative longer term picture with those different immunoglobulins. But definitely, there is evidence that, that can change over time, whether it’s an outright allergy or a sensitivity, depending on lots of factors. If you’re just not exposed to the antigens for a long time, the immune system may not be as responsive after a certain period of time. And again, we do see that with certain immunoglobulins like IgA. And referring back to the anti-gliadin IgA, if patients haven’t been exposed to gluten for, say, the last three to six months, that may go back down to normal ranges, indicating that there may be less responsiveness over a period of time.
Dr. Weitz: And then what is a food intolerance in contrast to a food allergy and a food sensitivity?
Dr. Fabian: So food allergies and sensitivities are immune mediated reactions, whereas food intolerances are defined as non-immune mediated. Again, newer research indicates that those lines are a little bit blurred now, but classically, food intolerances are things like carbohydrate intolerance, so there’s usually no significant immune mediated reaction there, but patients essentially don’t digest and absorb these well. So they end up going lower down to the GI tract, often the colon, where the microbes then ferment these into gases and other products that then can provoke symptoms. Similar scenario to histamine intolerance where normally we have an enzyme in the gut called diamine oxidase that helps to break down histamine. So if you have a lack of diamine oxidase due to a genetic deficiency or possibly due to damage in the small intestine, inflammation in small intestine, that can reduce the DAO enzyme, and so then you’re not able to break down histamine. So if you consume high histamine foods, for example, that can provoke a histamine related reaction. And there are others as well, like oxalates, lots of different components of food potentially are things that certain individuals can react to. So broadly speaking, those would be intolerances.
Dr. Weitz: Cool. So let’s talk about how a healthy microbiome and healthy commensal bacteria play a role in the risk of food allergy, sensitivities and intolerances.
Dr. Fabian: So there’s a lot of research that started coming out in the last, say, 10 years or so on defining the role of the microbiome in oral tolerance. So that’s the concept where typically the harmless foods, day to day foods that we’re eating, of course, we don’t want to react to those from an immune standpoint. And it turns out that the immune system of course has a balance of pro-inflammatory and anti-inflammatory, to keep it simplistic. The anti-inflammatory response is similar and overlaps with the immune tolerance response. So basically, immune tolerance is a mechanism by which the immune system restrains overreaction, and that applies to food allergies, respiratory allergies, et cetera. And mostly that involves what are called Treg cells.
So it turns out a lot of the recent research shows that various products from the microbiome can promote these Treg cells that promote immune tolerance. And probably the best study of these is butyrate, so that’s made primarily by butyrate producing bacteria in the colon from fiber. And lots of studies have shown that in various scenarios, whether it’s autoimmunity, whether it’s allergies, sensitivities, that the butyrate may often be deficient, butyrate producers and the butyrate itself in the gut may be deficient, and then that can lead to a deficiency in Treg type responses. So that’s really thought to be the main mechanism. It depends where you’re talking along the GI tract. So the colon is probably the best study, again, that mostly involves butyrate producers, but also other products produced by the microbiome. And that list is growing as they do more research.
So generally, the commensal normal microbes tend to promote immune tolerance, which makes sense because they’re normal residents of the gut and they don’t want to provoke an immune response, because obviously, then they wouldn’t thrive in the gut. But in the upper GI tract, in the small intestine, they’re starting to define some of the normal microbes there, and among the main ones would be things like Streptococcus, which actually is a normal microbe in the small intestine, Prevotella species are pretty common in the small intestine, of course Lactobacillus, Bifidobacterium to some extent, although Bifido is mostly resident of the colon from what we know, but especially Lactobacillus is important.
And then there’s a particular species of Prevotella that’s been studied recently and they’re actually looking at it as a potential probiotic, similar to Akkermansia where it’s not easy to grow because it’s more of an anaerobic type species, but it’s called Prevotella histicola. And that one has been shown to help protect against things like food sensitivities, et cetera, so it helps to reduce overactive immune responses in the small intestine.
Dr. Weitz: Interesting. Yes, it’d be nice to have some tools besides simply avoiding foods that people are sensitive to.
Dr. Fabian: That’s really the whole point of this research is for years that’s been the paradigm in addressing food sensitivities is to run a food sensitivity test or just to approach it with a standard elimination diet or both, and just see what people are reacting to, and then of course eliminating those. Which poses a lot of problems, I mean, that’s difficult to maintain long term, people of course don’t want to give up their favorite foods, plus there’s always the chance that, depending on how restrictive the diet is and what’s being restricted, that can lead to nutrient deficiencies, and of course we all want to avoid that scenario as well. And of course, we’ve known that of these different categories, allergy, sensitivities and tolerances and so some of them can be addressed, such as the lactose intolerance is the classic one, that can be addressed to some extent, of course, by avoiding lactose containing foods, but can be addressed to some extent by taking the enzyme, lactase, et cetera.
The immune response mediated reactions, so allergies and sensitivities, are a bit more challenging to potentially address their protocols that allergist use for desensitization that may be effective in some cases. But the recent research because of these insights about the microbiome … and I think this is really the key concepts on this whole topic is, as we learn more for research, we’re learning the ones that promote the immune mediated type reactions, sensitivities and allergies, and then the ones that basically help protect against. So when you have an imbalance where you start to lose some of those species or they decrease that help protect, and then you have an overgrowth of some of the ones that promote, that’s the classic imbalance that’s thought to be a key factor in driving the immune responses. So a lot of interest in research now in figuring out what these species are and then what they’re doing, and how that may be applied, of course, therapeutically.
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Dr. Weitz: Now, the one concept that we’ve used for years is this whole leaky gut concept, and I think a lot of us have explained food sensitivities partially in terms of leaky gut, especially we get one of these food sensitivity tests back and the patient has a huge number of food sensitivities, and the usual explanation is, well, you have leaky gut, because the leaky gut, these proteins are getting into the bloodstream and creating immune reactions. And so if we just heal up the gut, reduce the leaky gut, then we won’t have as many food sensitivities. But after reading so many articles you sent me and watching your webinar, it’s way more complex than that and there’s all these other mechanisms which I’d like you to start going into.
Dr. Fabian: Sure, absolutely. I mean, the leaky gut thing is still certainly applicable, just one of the factors, and it’s actually related to the whole picture of immune imbalances and microbiome imbalances. So as you can imagine, that concept of when you have leaky gut then these antigens can more easily get across the epithelial lining. And certainly, once something gets across that epithelium where they’re not supposed to be, then that usually is an alarm signal for the immune system where they can detect that and then basically react to that scenario.
Dr. Weitz: For those who don’t understand, the epithelium is the lining of the gut, and if food particles, proteins cross that lining making it directly into the bloodstream.
Dr. Fabian: Exactly. And they can also react to just the immune cells that are already present in the intestinal mucosa that are just underneath the lining.
Dr. Weitz: Right.
Dr. Fabian: And then once the immune system gets going, that can further exacerbate or promote leaky gut, so it’s this vicious cycle scenario. But we know from recent research that, once again, microbes can influence a lot of the different steps in that process. So one is, of course, just general idea of overgrowth of inflammatory type bacteria, such as Escherichia or E. coli, Klebsiella, Citrobacter, these types of more inflammatory bacteria, if they’re overgrown for any reason in the gut, especially mostly in the small intestine because that’s where, of course, these food antigens are first starting to be broken down as part of digestion, that, that can basically then set the stage, when you have inflammation, inflammation then can also cause leaky gut. So it’s a general concept.
But new research actually shows that even the antigens themselves, the state of the antigen or how antigenic a protein is, can be modified by microbes. So there are certain microbes that have been shown to actually break down certain proteins such as gluten. In this case, there’s a lot of research on Pseudomonas, for example, which is a common resident of the small intestine. So when Pseudomonas is overgrown, it can release certain enzymes that break down gluten in a way that makes it easier for the gluten to get through the leaky gut essentially. So then it doesn’t break them down enough to get to a point where they’re no longer stimulating the immune system. If you have good digestion, that’s really efficient, the idea is that you’re going to break down proteins all the way to their component amino acids, and then amino acids are not going to be stimulating the immune system, usually it’s larger structures that stimulate immune response. But because-
Dr. Weitz: And it probably the reasons why hydrochloric acid is so important, because that’s super important for breaking down proteins and a lot of people end up not having enough hydrochloric acid.
Dr. Fabian: Absolutely. Yes. And that’s pretty common and we do see that clinically very often. I’m sure you see that as well that a pretty high proportion of patients seem to have varying degrees of low stomach acid, poor digestion in general.
Dr. Weitz: It’d be nice if there was an easy to do task for stomach acid.
Dr. Fabian: It would. The classic definitive test is invasive.
Dr. Weitz: Right.
Dr. Fabian: There are these ways to approximate that with experimenting with Betaine HCL supplements, the bicarbonate tests, et cetera.
Dr. Weitz: Right.
Dr. Fabian: So that’s really important, but overall digestion is important because, as I mentioned, if the whole digestion process goes efficiently, then you break those proteins down generally pretty efficiently into amino acids so they’re less likely to cause an immune reaction. Some proteins are harder just naturally harder to break down like gluten, so that’s one of the reasons why it’s thought to be more of a problem. But then you have these microbes that can interfere with that process in a way that makes the antigens more available to the immune system to react to. But it’s all about balance. So again, research indicates that various types of probiotic type species, the beneficial species, like Lactobacillus also can break down gluten as well but they tend to break it down more efficiently to smaller components, essentially, that don’t stimulate the immune system.
So it’s thought that it’s not necessarily just the bad guys but the balance of your bad guys to the good guys. And that’s the classic concept of dysbiosis. So oftentimes, just overgrowth alone can be a problem or lack of beneficial bacteria can be a problem, but oftentimes it’s both. And there’s a few other examples of that, but probably the best studied is the Pseudomonas and Lactobacillus scenario, that balance is likely to be pretty important. So that’s really where the interest is in probiotics, for example, and fermented foods, because that helps potentially increase these beneficial Lactobacillus species. And also some of the Bifidobacterium species, like certain strains of Bifidobacterium longum, also produce factors that can actually inhibit some of those enzymes produced by the bad guys that break down gluten in a way that make the gluten more inflammatory.
Dr. Weitz: Now, do we know if those strains of, say, Lactobacillus, if the Lactobacillus that are growing in our microbiome produce those? Do we know if Lactobacillus strains that we consume in probiotic capsules, do they necessarily have the same effects, especially since they’re only temporary visitors?
Dr. Fabian: As far as we know the answer is yes. So some of the strains that have been studied are native to the gut, others are more probiotic strains, and sometimes they’re both, because some researchers, of course, over time have isolated some of these native species and then they’ve been able to cultivate those and now products are available. So one of the best studied Lactobacillus species overall is called Lactobacillus reuteri, R-E-U-T-E-R-I, which is available in a number of probiotic products. There’s quite a bit of research suggesting that Lactobacillus in the small intestine produces factors that help inhibit overreaction of the immune system. So they promote those T regulatory type responses. So again, that’s thought that promoting the native bacteria, of course, can be helpful, we don’t necessarily know all the different ways to do that, we have some clues, but that can be difficult for some people to try to get their native Lactobacillus to come back just through diet, et cetera, and that’s really where probiotics and fermented foods come into play.
There’s actually a recent research article that just came out comparing the benefits of fiber to fermented foods. And this study found that fiber was a little bit more heterogeneous, some people it was anti-inflammatory for the majority, and a subset of people certain fibers may have more of a pro-inflammatory response, probably depending on which microbes those are promoting. Whereas the fermented foods that they studied basically had largely anti-inflammatory effects. So-
Dr. Weitz: Yes, I think there’s a dilemma of, with clinicians, do we recommend more fiber for patients who come in, say, with gut disorders or it seems at least a certain subset of patients do better when they avoid fiber, avoid certain types of fiber, like say fermentable fiber by being on a low FODMAP diet?
Dr. Fabian: Absolutely. Yes. So it’s a complicated picture as always when you get into the details, but I thought this study was very interesting and I think that’s pretty well noted clinically by a lot of functional medicine clinicians that fiber is not always beneficial in terms of symptoms, sometimes it just exacerbates what’s going on, and yet we have this concept that fiber is just always something that you want to try to get more of. So probably it has to do with the combination of the microbiome that, that patient has and how that microbiome reacts to the fiber, but also the type of fiber.
So just a quick aside is that a lot of research has been done on different types of fiber and their effects on the microbiome, and to some extent, in certain conditions like IBS. And so the FODMAP diet, for example, that restricts mostly short chain, so of course, monosaccharides, disaccharides and oligosaccharides, those are all pretty short chain type fermentable carbohydrates. Typically, for patients that don’t do well with those, then they end up getting over-fermented, they rapidly go through the GI tract in some patients, and then they arrive in this high concentration to where the bacteria are that ferment them, and that can create a pretty big spike in things like gas production and other products that might provoke symptoms.
Whereas the longer chain fibers, so psyllium, for example, has been well studied and is actually suggested even in conventional medicine as a possible treatment that can help with IBS symptoms. And so, one study showed that inulin, which is a shorter chain fiber, can cause higher levels of gas and provoke symptoms for some patients, but when you add psyllium to it, it draws that process out so you don’t get this big spike, you get a more gradual increase in gas, et cetera, that can be more tolerable. So the types of fiber and including these longer chain fibers for some patients, may actually be good even though they might react poorly to FODMAPs. So it’s really, I think, opens up some possibilities here because we don’t necessarily want to completely restrict FODMAPs, because patients can end up with a very restricted diet.
Dr. Weitz: Sure.
Dr. Fabian: And then they have beneficial effects, they promote short chain fatty acids, et cetera. So if you have the right mix of types of fibers, then that may work for certain patients.
Dr. Weitz: Yes, I think the concept that a lot of us have been using, is if we have a patient who has overgrowth of certain bacteria that shouldn’t be there in those levels, we’ll restrict the fiber, is restrict the low fermentable fiber and will starve them and then maybe we’ll use, at the same time, other supplements or antibiotics. A lot of us in functional medicine world will use antimicrobial supplements like oregano oil and Berberine and things like this in the idea of killing or reducing some of these bacteria while we hold back their food. And then once we can get that cleared out, then we can restore it and we store those foods back, and then we’ll have a healthier microbiome.
Dr. Fabian: Yes. And I think you hit on this key phenomenon that we see clinically, but also there’s a lot of research coming out that supports this idea that we all know that sometimes antimicrobial protocols, they might work temporarily, but then the symptoms come back at some point, so patients relapse or they just don’t respond that well at all to that approach. And it’s thought that part of that has to do with the diet and also part of it has to do with, again, digestion. So we see this quite a bit with advanced stool testing where you get some markers for the microbiome, for digestion, et cetera, and oftentimes I see results for patients that were treated with antimicrobials, but basically the patients just didn’t respond well to that. In many cases, you’ll see evidence for reduced digestion, so things like lower last days, which is an indicator of pancreatic dysfunction.
And then I think there’s also a couple other things to keep in mind. So there’s some really interesting research coming out about particularly food intolerances, so the carbohydrate related symptoms, so things like FODMAPs, et cetera. A couple things there, I think, that are really important for clinicians to note that’s new information, one has to do with the types of carbohydrates. So we talked about different types of fibers, but it turns out that one of the brush border enzymes called sucrase-isomaltase, that’s an important brush border enzyme that actually appears to be deficient in a pretty high proportion of patients with IBS, for example. So it turns out that some of that can be genetic, there’s some common snips that can reduce that enzyme, but also anything that causes inflammation, even minor damage in the small intestine, infections, et cetera, overgrowth, those can inhibit those brush border enzyme.
So recent studies indicate that up to 35% of patients that have IBS-D actually have reduced sucrase-isomaltase that may be contributing to their symptoms. So there’s also additional studies following up on that showing that patients that don’t respond well to low FODMAP diet, it may be because they have low levels of this sucrase-isomaltase enzyme, so they actually do better by restricting starches and sucrose sources. So again, I think this is really where the Precision Medicine personalized diet aspect comes into play where we have these standard approaches that we start with, like low FODMAP diet, but if those don’t work, we need to be aware of this other mechanisms so we can say, okay, well that didn’t work, maybe we’ll try a low starch diet or low sucrose type diet.
Dr. Weitz: How can we know if patients have low deficiency of these brush border enzymes?
Dr. Fabian: That’s a good question. So the snips are being defined and so certain genetic tests may contain that information, so that’s one route to go is potentially doing a genetic test to see if patients have the snips. It’s not really common yet in clinical practice to really assess brush border enzyme activity directly, that’s an invasive process, but potentially indirectly through like a sucrose based breath tests, there’s various types of carbohydrate malabsorption breath tests that can be done, fructose, et cetera, lactose, and sucrose is available. That’s not something I’m really familiar with, but potentially, that’s an option for people. And then, of course, just the elimination diet approach, just restricting those sources for a while and seeing if symptoms improve, which is usually the most straightforward.
Dr. Weitz: And then how do we rebuild these brush border enzymes? I know there are supplements of brush board enzymes we can take.
Dr. Fabian: So it’s a combination thing. So yes, I mean, that’s the replace option from the five bar protocol that when you’re deficient in something, replace that from a supplement standpoint. So there are various options out there that are either supplements that have just the brush border enzymes, plus there are a broad spectrum digestive enzyme products that have the pancreatic enzymes, brush border enzymes, and then sometimes other things like [inaudible 00:32:46] and some supplemental acid, for example.
So those products can be helpful, but they don’t necessarily address the cause, of course. And ultimately, in terms of medicine, root cause is really something you want to try to address if possible. So as I mentioned, genetic snips can be part of the picture, but also just anything that damages or causes inflammation in the small intestine. There was a great review article that I include in some of my webinar slide presentations that’s this table from a review paper showing a lot of the different factors that can affect the small intestine, so that includes infections, including even things like H. Pylori, so it’s not well known that H. Pylori can also infect the upper small intestine, duodenum, and in some patients that can have a negative effect on the brush border, but also things like Giardia, Cryptosporidium, and probably various types of dysbiosis. So as I mentioned-
Dr. Weitz: If we see H. pylori either elevated or maybe just above the detectable level in that zone where it’s not flagged as high but it’s higher than it should be, and maybe there are not any of those … what are the factors called that they react to?
Dr. Fabian: Virulence factors?
Dr. Weitz: Yes, there’s no virulence factors, when do we think that, that could be a problem or should we always be concerned about it? Because there’s a lot of controversy over H. pylori and whether it’s actually a beneficial microbe, et cetera.
Dr. Fabian: Exactly. Yes. So it is something that is very common, worldwide it’s present in I think at least 50% of the population and the vast majority people don’t have obvious symptoms from it. And it is known from just endoscopic studies, et cetera, that patients that have H. pylori can be completely asymptomatic even though they might have low grade or low level inflammation in the stomach, so low grade gastritis. And it’s not clear that, that’s necessarily a problem. Even long term, in most cases, it doesn’t seem to lead to any progression to things like cancer for most patients. And that’s really where the virulence factors come in, because there’re various strains of H. Pylori. So that’s important information to take into account, because if there are virulence factors that suggest the strains that are present may be more aggressive and more likely to contribute to worse gas gastritis, for example, and that can set the stage for ulcers, cancer, et cetera. So the levels, keep in mind that in stool testing.
So PCR is a very sensitive technique and can pick up things at very low levels, which is great especially when you’re detecting something coming all the way from the stomach, so by the time it gets to the colon obviously the levels may be lower than what’s detected directly in the stomach. So the low levels that we see on PCR tests like GI-MAP, for most patients if they’re not high, that’s usually consistent with patients not having significant symptoms related to H. pylori. But because it’s not a completely linear relationship, for some patients, again, that’s really where the assessment comes into play where you have to really focus on symptoms, focus on the rest of the picture. So clinicians sometimes do treat when H. pylori levels are not high and they do often find that, that can be helpful from a system standpoint. So it’s a mixed picture, and again, I think clinical judgment is really key there when it’s not an obvious situation, you have to be careful and make sure you’re assessing the situation properly.
Dr. Weitz: So when I watched your webinar, two things that came out that seemed to be significant that stuck in my mind, and one was the importance of promoting the way in which a healthy microbiome and healthy commensal bacteria can promote T regulatory cells, which seem to blunt these adverse immune reactions like food sensitivities. Can you talk more about that? And then what are some of the strategies we can do to promote that?
Dr. Fabian: Absolutely. Yes. So, certainly there’s a lot of growing evidence that butyrate can be helpful in helping to promote T regulatory cells. So we don’t know all the mechanisms, but it’s thought that one of the key ones is that … so butyrate can basically act on immune cells in various ways. So they have receptors on the outside of the cell that can detect butyrate and then you can have reactions, responses of those immune cells based on the interaction of butyrate with those receptors. But it’s thought that the main way that butyrate affects the function of immune cells, whether they become more pro-inflammatory or antiinflammatory, so of course, butyrate tends to promote the antiinflammatory development path of those immune cells, is through epigenetics, so basically altering long term gene expression.
So butyrate results in turning on and turning off certain genes. So essentially, turning off the more pro-inflammatory type genes and then promoting the primary functions of Treg cells. So in the development process from what’s called a naive T cell that’s not yet become a Th1 or a Treg cell, et cetera, butyrate influences that progression so they more likely to become Treg cells. And then Treg cells secrete various things, especially cytokines that then act on other cells in the immune system to basically quiet them down so they’re less likely to be inflammatory.
Dr. Weitz: So it sounds like one of the real keys is promoting the growth or health of butyrate producing microbes.
Dr. Fabian: Indeed, yes. So main ways to do that tend to be, of course, generally fiber, but it does depend to some extent on the type of fiber. And again, that’s likely to be somewhat specific to the types of microbes that an individual has, so certain microbes respond to certain fibers. So in general, probably the best studied fibers for promoting butyrate production would be inulin, so the combination of FOS, fructooligosaccharides, and inulin, those are often together in various products. Resistant starch, I mean, that’s certainly a very well studied group of fermentable carbohydrates that can promote butyrate-
Dr. Weitz: So for those who don’t know what resistant starch is, can you explain what resistance starch is?
Dr. Fabian: Sure. So basically, starch contains different subtypes of starch. So there’s the type of starch that’s more easily broken down just in the small intestine into sugars and then absorbed, then there’s a type of starch that’s much harder to break down by our digestive enzymes, so then that basically travels down into the colon just similar to fiber, basically, it’s like a type of fiber, then the microbes have additional enzymes that we don’t have that can further break that down. And then once they break it down, then they can take up those component sugars, and then they can basically metabolize those into producing butyrate and other short chain fatty acids.
Dr. Weitz: And what are the best sources of resistant starch? I’ve certainly heard about eating cold potatoes and things like that.
Dr. Fabian: I can’t say that we necessarily know overall what are the best sources, there are certainly some that are more convenient than others. So there’s a growing amount of products out there that contain things like potato starch, green banana or plantain starch, those are probably among the most common.
Dr. Weitz: And there’s something about the potato starch that after you cook it and then cool it down or put it in the fridge, and then you eat it, that it becomes more resistant, right?
Dr. Fabian: Right. Yes, somehow that changes the structure a bit into the more just resistant type starch so that our enzymes can’t break it down as easily, and again, more of that ends up in the colon to fuel the growth of these butyrate producers.
Dr. Weitz: But this is probably not a good excuse for eating day old french fries or any french fries.
Dr. Fabian: No, because it’s all in the balance, and of course, those types of foods have a lot of bad things in them that can disrupt the microbiome and promote inflammation, so it defeats the purpose.
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Dr. Weitz: So what are some of the other sources of resistant starch besides potatoes?
Dr. Fabian: That’s a good question. So pretty wide range of foods have some levels of resistant starches, and I can’t say that I’m familiar with all of them.
Dr. Weitz: Okay.
Dr. Fabian: There are some that are more natural. So as you mentioned, you can cook rice and let it cool and then a fair amount of that if you eat it cold instead of reheating it, then it will retain that amount of resistant starch. So that is how some people get their resistant starch, whether it’s potatoes or white rice, and so those are pretty common. Then when it comes to supplements, again, green banana powder, plantain powder, and then typically potato starch are all pretty common as well.
Dr. Weitz: Okay.
Dr. Fabian: Those are the ones that I’m most familiar with.
Dr. Weitz: Okay. And what are some of the other strategies for promoting butyrate producing bacteria in our gut?
Dr. Fabian: So it’s mostly looking at the big picture. In terms of foods and supplements, we know that polyphenols in general help to promote beneficial bacteria and at the same time typically help inhibit bad bacteria, so they’re good balancers. Research indicates that they’re often synergistic with fiber. So along with getting more fiber in the diet, which of course is typically from things like fruits and vegetables that happen to also contain polyphenols, that’s probably, of course, one of the key reasons why those foods tend to be very health promoting.
And then in terms of supplements, there’s a pretty wide range of different types of supplements that have these polyphenols. And it’s a broad category, so examples would be things like curcumin, quercetin, resveratrol, green tea extract, those sorts of plant extracts that we typically think of as more antiinflammatory and antioxidant.
Dr. Weitz: Okay.
Dr. Fabian: Generally, most of those that have been studied, so curcumin, quercetin, resveratrol, grape seed extract, pomegranate extract, those are among the best studied sources of polyphenols that have been shown to help balance. But even things like chocolate tea, cocoa extract, there’s a growing list of things that have been studied. So polyphenols in general, especially in combination with fiber. And then there’s also supplementing with butyrate directly, and there are a variety of different types of supplements out there. There is quite a bit of research on butyrate supplementation and a wide range of health benefits. In addition to promoting those Treg cells, butyrate can promote a lot of other beneficial functions. So it helps-
Dr. Weitz: So are butyrate supplements absorbed? I’ve heard some controversy about this.
Dr. Fabian: So it’s a bit of a mixed picture, and to my knowledge, it’s not as well studied as it should be at this point, but there are some products that are known to be more likely to reach the colon. From what I understand, that would include products that include butyrate in the form of tributyrin, but also some of the products basically, I don’t know technically how they do it, but basically the butyrate is bound or attached somehow to the probiotics. So essentially, the butyrate isn’t released until the bacteria in the colon start to break down the fibers and then release the butyrate. So there are various ways to deliver it and I think that’s an ongoing effort in the industry to look at the best ways to deliver butyrate.
But one thing I would mention is, some release of butyrate in the small intestine may not be a bad thing, because there is evidence that some butyrate is produced also in the small intestine. So one of the species that’s pretty common in the small intestine is called Fusobacterium, which is another one of these, it’s a good guy and a bad guy, depending on the circumstances. It can produce hydrogen sulfide, for example, which can-
Dr. Weitz: Yes, Dr. Pimentel mentioned that. Yes.
Dr. Fabian: And in the small intestine it’s normal. On our tests we do have Fusobacterium on GI-MAP, and virtually everyone has detectable Fusobacterium. And we know from research that it’s normally present from the oral microbiome down to the small intestine, sometimes in the colon where it’s not really supposed to be as much, but it produces butyrate.
Dr. Weitz: So do you think taking supplements of butyrate would be more likely to be effective or I know there’s at least one or more products on the market that contain the other short chain fatty acids, acetate and propionate as well?
Dr. Fabian: Exactly. Butyrate definitely is the best studied as far as on promoting immune tolerance, et cetera. The other ones are a little bit more of a mixed picture, but propionate would probably be a close second, a lot of research does show that, that can have similar effects to butyrate. There’s a little bit of concern about overdoing propionate just due to some early research on possible links with things like autism. I don’t know where that research has headed in the last few years. That was earlier research from five to 10 years ago. But there are quite a few studies showing that propionate does have beneficial effects under certain circumstances, especially on metabolism and things like glucose regulation.
Dr. Weitz: And then what about probiotics, prebiotics?
Dr. Fabian: Absolutely. Yes, so there are quite a few that have been studied that have been shown to have key beneficial effects. So we know that things that can predispose are involved in food reactions. Of course, we mentioned leaky gut, we mentioned overactivity of the immune system, we mentioned dysbiosis and there’s other factors as well. So a lot of different probiotic species, Lactobacillus and also some of the Bifidobacterium species are known to promote a healthy intestinal lining, part of that might be through cross-feeding. So Bifidobacterium tends to promote acetate and the butyrate bacteria can then take the acetate and make butyrate. Also Lactobacillus, of course, produced lactate, and then some of the butyrate producing bacteria can take the lactate and produce butyrate. So that might be one of the ways in which they can help promote a healthy gut environment, healthy intestinal lining. But they also have a positive effect on the immune system as well.
Dr. Weitz: How important is it that we take specific probiotic strains versus just blends of probiotics? Because right now there seems to be quite a bit of confusion in the probiotic market and there are some prominent practitioners out there who simply group probiotics in a few different categories and we basically just talk about Lactobacillus-Bifido blends as though we can’t really distinguish. On the other hand, there’s a lot of promotion of specific strains, some strains that we know are more specific for being butyrate producers. How important do you think it is that we take specific strains of probiotics?
Dr. Fabian: That’s a really great question, I think that leads to a lot of confusion in the field. So on the surface that’s the ideal scenario to be able to use a particular strain that has a lot of research backing up that it has these particular demonstrated positive effects. So generally, that would be the recommendation is it has to be as much as possible evidence based, but the challenge there is, once again, the individual scenario where based on the patient’s microbiome, based on how they would react to that particular strain. And of course, any bacteria produces multiple products, so just because they produce certain beneficial things for some patients, they may produce things that don’t work well for them. The classic example for Lactobacillus species is some produce a form of lactate called D-lactate. So even though they might be anti-inflammatory, for example, some of them might also produce D-lactate that some patients may have some issues with.
So I think that’s part of the picture. So a lot of clinicians that have tried to do the targeted approach by using well researched strains, they found that in some cases those don’t work, of course, for all patients, so they end up having to still go back to the drawing board and try other probiotics. So you’ll hear that a lot in our field that some clinicians feel it’s more of a trial and error type of approach where you try to go with the well researched products first, because they have good evidence basis, but if they don’t work for a patient, ideally, you have some backup products that you can try, and hopefully they respond well to one of those products. So it’s still a bit of not a full science yet, you still often involves a lot of trial and error to see what works.
Dr. Weitz: Has Diagnostic Solutions considered adding butyrate and short chain fatty acid levels to the test results?
Dr. Fabian: That’s a great question. So I’m not aware of an immediate upgrade to the test that will include those. We do have some of the key butyrate producers currently on the test. We do get great results in terms of scenarios where you expect those to be low inflammatory conditions, they’re low, et cetera. So what we see with our existing markers does reflect well what we see in the research. And there are some concerns about measuring butyrate in stool. So generally, it can be useful information, but just keep in mind that short chain fatty acids, the vast majority of them, estimates are more than 95% are already absorbed by the colon before they reach the stool. So what you’re seeing is just a small remnant, so you have to know how to interpret that properly and then even the techniques that are used to measure those can be important. So it’s a little bit less straightforward than I think we assume, it’s not always directly measuring production, because there’s that absorption aspect that can affect the results.
Dr. Weitz: So what would be the recommendation for which probiotics we should recommend to patients if we want to try to reduce food sensitivities?
Dr. Fabian: Great question. So among the best studied species, as I mentioned, is Lactobacillus reuteri.
Dr. Weitz: Okay.
Dr. Fabian: Now, I think that at least some strains of that species may produce D-lactate, so it may not be something that works for everyone.
Dr. Weitz: Okay.
Dr. Fabian: But there is good evidence indicating that, that can help reduce. And there are specific strains that have been studied that I’m aware of in certain products, so there are products that reflect the specific strains that have been studied.
Dr. Weitz: So there’s a specific strain of Lactobacillus reuteri that we know is more likely to be beneficial?
Dr. Fabian: Probably more than one strain, yes, because different studies have used different strains. And I’m not aware of all the ones that are commercially available, but that would be one that I would say is well study, plus a number of the Bifido bacteria strains also, so at least a few within the Bifidobacterium longum species, those have also been studied for helping to improve aspects of food sensitivities. And again, you’d have to really drill down into the specific evidence, some of those are, for example, just studied in the context of gluten, doesn’t necessarily mean they’ll help with other food sensitivities. So it really depends on what you’re targeting there.
Dr. Weitz: And now, I think I mentioned here earlier, I just interviewed Colleen Cutcliffe from Pendulum Therapeutics, and they’ve just been able to develop the first commercially available anaerobic probiotic supplement that contains Akkermansia muciniphila, and we know this is a type of bacteria that produces a lot of butyrate.
Dr. Fabian: It actually primarily produces propionate, but it can help with the butyrate scenario.
Dr. Weitz: Okay.
Dr. Fabian: So the research indicates there’s potential cooperation between Akkermansia and some of the butyrate producers. And especially one of the more proposed … I mean, again, this isn’t necessarily something that’s completely proven yet in research, but supporting evidence is out there suggesting that Akkermansia is also a keystone species, which means it’s plays an outsized really important role for the ecosystem. So one of the proposed ways in which it does that, so it consumes mucus as its main food source, and mucus basically is a protein that has sugars attached to it, sugar chains, so there’s-
Dr. Weitz: So it consumes mucus, interesting.
Dr. Fabian: Yes.
Dr. Weitz: So it helps break up mucus layer?
Dr. Fabian: Right, but it produces factors that can in turn stimulate mucus production, which makes sense because that helps it grow in the gut.
Dr. Weitz: Okay, interesting, because when I was talking to Dr. Pimentel a few weeks ago, I was asking him if he thought that taking Akkermansia might be beneficial for SIBO. And he said that since some of the organisms involved in SIBO live in the mucus, anything that increased the mucus might be make it more difficult to get rid of them?
Dr. Fabian: Well, I think it depends on the detail. So Akkermansia is mostly known to be a resident of the colon.
Dr. Weitz: Okay.
Dr. Fabian: The colon has two layers of mucus, the outer mucus layer is a thinner mucus layer that actually is where most of the mucus consuming bacteria in the colon live.
Dr. Weitz: Okay.
Dr. Fabian: So some of them break down the mucus sugars and release the sugars, and so it’s thought that, that’s actually how Akkermansia helps support the ecosystem. So in between meals, for example, when you don’t have fiber available to the fiber degraders, they have to exist on something, so it’s known and really well established and research that mucus actually serves as that interim food source directly for the mucus degraders like Akkermansia, but indirectly because they’re releasing the sugars and essentially sharing them with the ecosystem. And so it’s thought that, that’s one of the ways in which they help support the butyrate producers.
Dr. Weitz: Interesting. Boy, it’s such a complicated picture.
Dr. Fabian: It is, but that is my main area of study.
Dr. Weitz: [crosstalk 00:58:32] And then what about specific prebiotics that facilitate the growth of the butyrate producers?
Dr. Fabian: So those again would be the things like inulin-FOS.
Dr. Weitz: Okay, the fibers. Yes.
Dr. Fabian: But then you have to think of it in the bigger picture of cross-feeding, that’s a big aspect of how the ecosystem works. So even though you may not be necessarily supplying directly what the butyrate producers need, you can supply that potentially indirectly, and as I mentioned, that’s where the probiotics can come into play because they produce factors that then can be used by the butyrate producers to produce butyrate.
Dr. Weitz: Is there a role for some of the other typical nutritional products that are included in gut healing supplements like L-glutamine, and mucilaginous, herbs and things like that? Do they play a role in this or could they?
Dr. Fabian: Yes. I mean, so I’m less familiar with the research around the mucilaginous herbs and their effects, but glutamine certainly is thought to be pretty beneficial for the small intestine, the cells align the small intestine because that’s one of their key energy sources. And I’d like to promote the idea which is emerging from research but also it’s really how we operate in functional medicines, is to take the bigger picture, the integrated picture into account when you think of the gut as this domino effect. So if you’re promoting health of the upper GI, so the small intestine, for example, by gut supporting supplements and include L-glutamine, for example, then you can help support these brush border enzymes in the overall digestion absorption process, so then you’re going to have less undigested food getting into the colon and throwing things off. So everything is interlinked as you can imagine. There’s even a lot of research now on oral dysbiosis that then contributes to dysbiosis downstream.
Dr. Weitz: Right.
Dr. Fabian: But again, it complicates the picture a bit but I think the good news out of all that is there’s ways that we can intervene that we hadn’t thought of before, that actually making sure oral health is where it should be might actually help have a positive impact on gut health.
Dr. Weitz: Cool. Well, that was a very thought provoking, Tom, you gave us a lot of useful information about the microbiome and the more we learn about this, the more we’ll be able to develop effective strategies to help our patients.
Dr. Fabian: Absolutely.
Dr. Weitz: So any final thoughts for our listeners or viewers?
Dr. Fabian: I think some of the key take homes in this topic of food sensitivities, allergies and intolerances are definitely think, as I just talked about, more the big picture integrative. And we do know a lot now about dysbiosis in the small intestine, for example, or in the stomach with H. pylori overgrowth that can affect digestion and absorption, which then can cause dysbiosis downstream and can affect the balance of butyrate producers, for example. So really thinking big picture. And I would say, probably one of the key take homes just based on both the research and what we’ve seen clinically with stool testing is that reduced digestion does seem to play a really big role in dysbiosis and then symptoms across a pretty broad range of conditions, not just the food allergies, sensitivities and tolerances, but other conditions as well. So really focusing on that as being a key component.
I think that’s often overlooked when clinicians see dysbiosis and their first thought is, antimicrobials, which certainly can be helpful, but that may not be the full picture. I think, we all deal with situations where there’s a lot of complexities, complex patients that aren’t really responding the way we expect, and when we have those scenarios where we’re clinicians have gone down those paths and then they do a stool test to see, what does digestion look like? What does the dysbiosis look like? What does the immune system look like? Then you can start to piece that picture together a bit more and see that maybe we haven’t really addressed the digestion picture fully yet, or we haven’t looked at H. pylori, we were looking at something else. So I think that’s where the whole precision medicine idea comes from as well, that you’re trying to look at all the different factors and see, which ones are likely playing a role for that patient? And then you can target it more specifically to what’s likely causing the problem or in a root cause type picture. So that would be my overall take home on how to take this complicated information and put it back together.
Dr. Weitz: Great. Thanks, Tom.
Dr. Fabian: All right. Thank you so much, Dr. Ben. It was a pleasure.
Dr. Weitz: Same here. Talk to you soon.
Thank you for making it all the way through this episode of the Rational Wellness podcast. And if you enjoyed this podcast, please go to Apple podcasts and give us a five star ratings and review, that way more people will be able to find this Rational Wellness podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition clinic. So if you’re interested please call my office, 310-395-3111, and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you, and see you next week.
