Cytokine Testing with Dr. David Brady & Tom Fabian, PHD: Rational Wellness Podcast 288

Dr. David Brady and Dr. Tom Fabian, PhD discuss Cytokine Testing with Dr. Ben Weitz.

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Podcast Highlights

4:10  Cytokines are small proteins that are produced primarily by immune cells and their role is primarily in cell signalling and cellular communication.  Cytokines promote different aspects of immune cell development, immune cell function, and coordinate between the innate immune system and the adaptive immune system.  For example, if you ingest a pathogen though the digestive tract, there are certain receptors on cells that detect these pathogens and that leads to cytokines being produced that initiate an immune response.  This usually starts with the innate immune response.  Some of the classic cytokines that are involved in the inflammation response are IL-6, TNF alpha, IL-1 beta, and Interferon gamma

7:41  There are a number of difficulties in testing for cytokines, including that cytokines are very short lived and they tend to be unstable, so it is important that the sample arrives at the lab frozen, which is best accomplished by shipping with dry ice.

11:44  Cytokine level testing has been used in critical care medicine, such as analyzing patients with severe COVID-19 whether they are having a cytokine storm, which led to using certain interventions that modulate certain cytokines when used in patients with autoimmune diseases.  For Functional Medicine practitioners, cytokine testing can help to assess the immune system status, the level of inflammation, which can be re-assessed after using certain interventions to see how well we have been able to modulate the inflammatory process.

26:30  Cytokines and gut health.  It is recommended that patients that have cytokine testing also do the GI Map stool test, since the gut plays a big role in immune system function and in autoimmune diseases.  For example, Hashimoto’s hypothyroid has a significant gut component and certain bacteria like Yersinia have been associated with Hashimoto’s and there is a characteristic cytokine pattern for this.  We also know that 70-80% of the immune system is in the gut, so we know that, that’s really going to have a huge effect and it’s also a great place to intervene.   



Dr. David Brady is an internationally known speaker, Doctor of Chiropractic, and Naturopathic Physician. He’s also a Professor at the University of Bridgeport and the Chief Medical Officer for both Designs For Health, Inc. and Diagnostic Solutions Labs, LLC. Dr. Brady is a prolific writer, having published a number of scientific papers, contributed chapters to various textbooks, and he’s written several books, including his latest, The Fibro-Fix, published in 2016. His website is Dr.DavidBrady.com.  Patients seeking the Cytokine Test should contact a Functional Medicine practitioner and practitioners who would like to run the test should contact Diagnostic Solutions Lab at DiagnosticSolutionsLab.com or they can call 877-485-5336 to inquire about the CytoDx panel.

Dr. Tom Fabian, PhD has a PhD in Molecular, Cellular, and Developmental Biology and he is a certified Nutrition Therapy Practitioner.  Dr. Fabian 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. Dr. Fabian serves a consultant and science advisor with Diagnostic Solutions Laboratory, and he is also a Science Advisory Board member with Designs for Health.

Dr. Ben Weitz is available for Functional 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 excited to be talking about cytokine testing with doctors Dr. Fabian Fabian and Dr. David Brady.  I’ve certainly have known about cytokines, but since COVID, and we heard about the cytokine storm that played a role in a lot of people’s demise and made the symptoms more severe, cytokine have been talked about quite a bit. And Diagnostic Solutions offers a cytokine test, and I’m curious to learn more about how this may be a new tool for functional medicine practitioners to be able to help our patients. And my mission is to spread this information to practitioners, and also to the patients, so we can improve the overall health of our country, and the world, actually.

                                So, cytokines, what are cytokines? They’re a group of small proteins, peptides, and glycoproteins, and their main job is cell signaling, communication. Many of these cytokines are secreted by immune cells like macrophages, B and T lymphocytes, and mast cells.  Cytokines made by lymphocytes are known as interleukins. You may have heard the term IL-6, et cetera. These cytokines are very important for the immune system, and they modulate the balance between humeral and cell-based immune responses. They also regulate the maturation growth and responsiveness of particular cell populations. Cytokines are important in many responses in the body, including immune responses to infection, inflammation, trauma, sepsis, cancer, and reproduction.

                                Dr. Fabian is a PhD in molecular, cellular, and developmental biology, and he’s a certified nutrition therapy practitioner. Dr. Fabian specializes in the microbiome and how it relates to digestive, immune, brain, and metabolic health. Dr. Fabian offers a microbiome mastery course through his website, microbiomemastery.com. Dr. Fabian also works with Diagnostic Solutions, helping clinicians to interpret their various tests including the GI-MAP stool test, and the CytoDX test, which is known as the cytokine response profile.

                                Dr. David Brady is an internationally known speaker, doctor of chiropractic and naturopathic physician. He’s also a professor at the University of Bridgeport or, at least, I know he was at one time, and the chief medical officer for both Designs for Health and Diagnostic Solutions Labs, which makes the GI-MAP stool test, which is my favorite stool test. Dr. Brady is a prolific writer having published a number of scientific papers, contributed chapters to various textbooks, and he’s written several books. And his latest book is The Fibro Fix, which was published in 2016. I recently listened to Dr. Brady give a very helpful presentation on how to treat patients with long COVID at the CASI Conference in Orlando, Florida.  So, welcome, gentlemen, for a discussion on cytokines.

Dr. Brady:            Thanks, Ben. It’s good to be back on your podcast.

Dr. Weitz:            Absolutely. Thank you. I love having scientific discussions.  Dr. Fabian, maybe you could start by giving some little more information about what a cytokine is.  Why should we care about cytokines?

Dr. Fabian:          Absolutely. Yeah. I think you gave a great introduction overview. So, these are generally small proteins. We tend to think of them as produced primarily by immune cells, and that is essentially their main function overall, is to promote different aspects of immune cell development, immune cell function, coordinate between the innate immune system, the adaptive immune system, and on and on.  We all know that the immune system is fairly complex, and these play a really central role in essentially regulating those various functions of the immune system. I think another important aspect of cytokines for everyone to be aware of is, they’re not necessarily just produced by immune cells, they’re primarily produced by immune cells. But they can be produced by epithelial cells, for example, adipocytes, IE fat cells. And they can also influence these different cells. So, that’s a big part of this immune crosstalk…

Dr. Weitz:           Right.

Dr. Fabian:         With our whole system, really.   They generally also tend to be fairly short-lived, for the most part. So, they’re really meant to be a way for the immune system, initially, to kind of alert… Actually, for even the epithelium to alert the body to what’s going on. So, if you take a typical example in the gut and say a pathogen, you ingest a pathogen, there are certain receptors on cells that can detect these pathogens, and that sets in motion the production of cytokines that can initiate an immune response.  That often starts, of course, with the innate immune response, and then they play a role kind of in this cascade effect. Then, when those initial cells produce certain cytokines, that initiates a second set of responses, and that kind of gets the whole immune cycle going, and they play a role throughout the entire immune cycle. So, really, from inflammation through resolution of the inflammation, and then the healing process as well.

Dr. Weitz:            What are some of the more important cytokines that we should be aware of?

Dr. Fabian:          That’s a great question. Of course, as always, in research, we’re learning more and more about cytokines and some of them are starting to take center stage that we didn’t know that much about a few years ago.  But the classic ones that we think of is the key signs of what we call, classic inflammation. This is largely involving, at least, initially, the innate immune system, that would be… Cytokines like IL-6, which plays a really wide range of roles in terms of coordinating the immune system, initiating immune responses, something called tumor necrosis factor alpha or TNF alpha. Lot of these are produced, for example, by macrophages. Lot of these are sitting there in the mucosa, just monitoring what’s going on, produced by dendritic cells, also sitting kind of at these barrier sites, skin and mucosa. So, they’re really kind of these initial players in the immune response.  Third one would be, IL-1 beta, which is interleukin-1 beta, it’s another major inflammatory cytokine. Then, interferon gamma. So, those are kind of the big four, so it’s important to really understand what that means when you see those particularly elevated in a patient’s cytokine profile.

Dr. Weitz:            I read a bit about a bunch of issues related to the difficulty of testing for cytokines, so maybe you could talk about how we test for cytokines, and what are some of the issues related to trying to test for these?

Dr. Fabian:          Probably, nearly the top of the list is the fact that not only are they short-lived, for the most part, but also they tend to be unstable. So, it’s really important we have this release, spelled out in our instructions to make sure that they’re kept cold.   We specify that they need to stay frozen through the whole transit, so that they arrive at the lab frozen, because they’re very sensitive to room temperature.  So, if they arrive at the lab thawed, then obviously, that can affect the results of the test. So, that’s part of the picture, is a sort of technical-

Dr. Weitz:            So, after the blood is drawn, it should be put in a freezer for a period of time before it shipped?

Dr. Fabian:          Frozen. And then, ideally, sent, if at all, possible with dry ice.

Dr. Weitz:            Dry ice?

Dr. Fabian:          That will help keep them frozen.

Dr. Weitz:            Wow.

Dr. Fabian:          If they’re going to arrive at the lab really quickly, that may not be necessary. But these days, of course, we know there have been some issues with transports, et cetera. Things can get held up a bit, so dry ice really helps to ensure that they arrive at the lab. So, that’s more of just a technical issue to be aware of.

Dr. Weitz:            How would a practitioner actually get dry ice?  If I drew it on one of my patients here, we’d have to get dry ice to ship it?

Dr. Brady:            Ben, I’ll jump in.  The lab recommends you send it back on dry ice.  It could be sent back frozen with a conventional ice pack, but we do recommend for the best fidelity, dry ice.  And dry ice you can get at your local supermarket.

Dr. Weitz:            Oh, you can?

Dr. Brady:            So, if you’re going to be a practitioner that thinks they might be using these types of tests, it’s probably good just to find some dry ice at a supermarket, locally, and then just keep it in your office in the freezer, so that you have it available to send it back.  There are some cytokine tests out there that it just says, send it back, not frozen, just room temperature. And when you look at the range and the fidelity that they’re stating, they’re trying to achieve, which is a challenge in cytokine testing to… And we’ll talk about that to get down into the ranges where we would play clinically, because we’re not dealing necessarily in acute care medicine in overt cytokine storms, we’re looking for more subtleties.

Dr. Weitz:            Right.

Dr. Brady:            So, it’s half of the function-

Dr. Weitz:            [inaudible 00:10:18] of medicine community.

Dr. Brady:            Right. So, you have to get down to a level of fidelity. That makes sense for us trying to use these tests. And we think the best way, in fact, as far as our laboratory science, people that really control the quality control in the methodology and really, really understand how the sausage is made, basically, on how to make these lab tests very, very reliable. Suggests that, it’s just not virtually impossible when you’re sending it back at room temperature that they’re too fast to decay, they’re too unstable at those types of temperature.  So, while it is a bit of a hassle to do the whole dry ice thing, once you’re used to doing those tests and you find out where to get, it’s not a big deal. But there is a barrier of entry. And the other barrier of entry for functional and integrative providers a lot is simply that, it involves phlebotomy, it involves a blood draw, it’s serum tests, so you can’t do it in your end and you can’t do it in these non-invasive type of samples that people are used to.

Dr. Weitz:            Yeah. We usually bring a phlebotomist in to do functional medicine testing. I just didn’t know anything about dry ice. It sounds scary, maybe.

Dr. Brady:            Yeah, I know. I didn’t know much about it either until we were confronting this issue, and then it turns out it is very readily available because people are sending food stuffs and things like that all the time. So, it is more available than you would think.

Dr. Weitz:            Sounds good.   What does looking at cytokines tell us, specifically, about the immune system? And I guess, we can tie in the gut microbiome as well.

Dr. Fabian:           I was actually glad to stay there.  David, do you want to go first?

Dr. Brady:            Yeah. I’ll let Dr. Fabian dig into this. The real granular side of things in the science side, because he’s more knowledgeable than me about that kind of stuff. I’m just a clinician, but…   From a clinical standpoint, if you remember back… First, it was in chiropractic school, then it was in medical school. You learn immunology, you learn about all these cytokines, right?  And you learn everything that we said in the opening, and then you go into residency, you go practice, and you pretty much don’t use them, you forget it, you forget about them.  They’re not routinely ordered tests, but yet they’re so critical in our understanding of immunology.  Well, that’s not necessarily the case in critical care medicine, right? In critical care medicine, they’re dealing with life and death by the minute situations, and they have to utilize cytokine testing all the time. So, a lot of our understanding from a clinical utility standpoint with cytokine testing does come from critical care medicine with people, actually going into overt cytokine storms, whether it’s in multi-organ failure, whether it’s in sepsis, whatever it may be.

                                When it came down to COVID, COVID is one of these, in certain people, in susceptible people, and have the right set of circumstances. As we know, it can progress very rapidly. And end up in this cytokine storm, that can be, actually, the thing that takes you out, that drowns you in your own lung fluids and so forth.  So, they figured that out right away. And of course, they turned to some of the agents and the different types of interventions that they had used successfully in other reasons for cytokine storms, including non-infectious reasons. Some of them worked, some of them didn’t. And when they worked, they only worked to a degree, and they often only work to a degree.  But what we were able to learn from that experience is that, listen, if they can use them when the fire alarm’s screaming, and it’s really, really a serious situation, maybe we can use those in another way in chronic care medicine or in ambulatory care medicine, even, to try to fundamentally determine where does someone’s immune system, where’s it sitting from the standpoint of how inflammatory is it, how activated is it, how imbalanced is it? And what the cytokine testing can tell you, particularly, if you get away from just looking at one cytokine in isolation, when you look at sort of groupings of them, there’s sort of a bucket of what we would consider pro-inflammatory cytokines, and a bucket of cytokines that we would considered anti-inflammatory calming cytokines.  And we actually grouped them in that way, in our tests, so you can see, “Hey, I got a whole cluster of inflammatory ones that are above the normal situation you see in a normal person, right, person without overt disease or any obvious reason that would be driving cytokines to be elevated.” And then, you can look at what is their status in the ones on the opposite side of the seesaw, and you can start getting a picture in a more objective way of your patients. In addition to what they come in and tell you, “All my joints are inflamed” or “My ulcerative colitis is flared up” or “I have long-haul COVID symptoms.”   Well, that’s very valuable information, but wouldn’t it be nice to be able to actually baseline them and get where they are on this seesaw of inflammatory, anti-inflammatory immune balance, and then be able to, from there, figure out what you’re going to try to do to help them. And you intervene in whatever way, whatever your therapeutics may be. And then, serially assess them downstream, so you can monitor, “Hey, are their symptoms getting better? Are they saying they’re feeling better?” Or other maybe standard laboratory serum markers, functional markers, metabolomics, things like that. Are they changing in a positive direction or not? But you can also come back to cytokine testing and see, are they indeed now less inflammatory and less of an inflammatory stance than they were before I started. That’s the goal of it.

Dr. Weitz:            Right. Okay. Interesting. I’ve done a couple of the… Dr. Vojdani developed this lymphocyte MAP test, and that’s a way to map out the various parts of the immune system. And I was trying to figure out what the cytokine testing tells us compared to that. And I was thinking, in my mind, maybe we’re investigating a crime, and then we go to the scene, and we see who’s there, and then we want to hear the conversations between who’s there, intercept those phone calls, and the cytokine testing is telling us what’s going on, the communication, right? Is that a way to think about it?

Dr. Fabian:           Yeah.

Dr. Brady:            It’s actually a good analogy. I think I’ll let Dr. Fabian follow up. But basically, knowing what population of cells and their relative abundance and the things is an important thing to know, it’s a good thing to know. But those cells have the ability to do different things in different scenarios.   So, the fact that certain cell populations in different variations or different iterations in different relative levels can be important, but it’s nice to also know, functionally, what are they doing?    So, the cytokines and the things that they’re releasing in their chatter, like you said, in their conversation, contextualizes, not only who’s there but what they’re doing while they’re there, right?  Dr. Fabian, you can maybe expound upon that, in a better way.

Dr. Fabian:           Yeah. I do think that’s a great analogy, because different cell types, immune cell types, as David noted, can perform a bit differently in different contexts. Kind of the class example, sort of an extreme example would be, like macrophages. We know there’s pro-inflammatory and anti-inflammatory macrophages that have totally different roles, even though it’s the same cell type. So, they’re going to produce different types of cytokines under those circumstances.  You can think, overall, of the cytokine profiling approach. It’s kind of almost like a tiered view of the immune system. Your first question is, do we see a systemic, elevated systemic immune response? That’s important to know because sometimes, you can just have a local issue, local infection that’s not really at the level that’s going to impact things systemically. So, you’re not going to necessarily see a significant signature in serum. But if you have a big enough immune response, say in an autoimmune flare, for example. We see this all the time in various autoimmune diseases, infections, et cetera, inflammatory scenarios. You can certainly often see a pro-inflammatory response.

                                So, that’s kind of the next level is, do you see a generally pro-inflammatory response? And then, what are you seeing with this compensatory anti-inflammatory response? And we know from research, and we see this clinically, that you can have an extensive pro-inflammatory response, but not a sufficient anti-inflammatory response to bring that back down. That’s really the idea. You think of the classic infection, you want that immune response to ramp up, deal with the infection, and then you want the anti-inflammatory part to kick in and help bring things back down to homeostasis. So, that’s a big part of it.

                                And then, the next level down, which I think speaks to some of the information in this other test is, we often characterize immune responses based on these T-cell types. You’ll hear Th1, Th2. We think of Th1 with antiviral chronic inflammatory scenarios, autoimmune conditions. Th2 is more the allergic type scenario, typically, although there’s some nuances there.  You can often see a characteristic pattern with that. We definitely see that with, for example, type 1, type 2 diabetes, inflammatory bowel disease. You’re going to see, oftentimes, those predicted patterns that we know from research.  So, it helps you sort out what the details of that response is, especially important for patients that have multiple things going on. A review cases for patients that had multiple conditions. Sometimes, it’s a little bit hard to understand what’s going on. You look at these cytokines, you can see what’s the overall picture here. What’s elevated is that, they’re innate, immune response elevated, as if they’re adaptive, and then you can start to piece it out from there. From there-

Dr. Brady:            I’ll follow up on just what Dr. Fabian said in that, you have these two sides. And in looking at both sides is often important and not just looking at, “Hey, are the inflammatory cytokines high?” Well, that’s good to know. But also, are the anti-inflammatory cytokines kicking in as a compensatory reaction? So, when you look at some of the data coming out on trying to build an immune profile or an immune signature in something like long-haul COVID, which is a very complicated thing that unfolds over a long period of time.  Various studies have come out. There was just one I presented at CASI, Ben, was from mucosal immunology, and it was looking at, truly, a sticky imprinting of an aberrant immune response or an immune signature, five months, six months, eight months after you had acute COVID. And this is multiple papers showing this. And they didn’t only show upregulation of pro-inflammatory cytokines and eicosanoids, 5-lipoxygenase, and things like that. But they also concomitantly showed a downregulation of the production of pro-resolving factors and anti-inflammatory cytokines.

                                As they build these signatures, they’re using these things. And they’re not just actually looking at a PDF of lab results, I’m talking about studies where they’re looking at hundreds of biomarkers, whether they’re serological markers, whether they’re cytokines, whether they’re other types of compounds. And they’re using non-biased, naive, computers machine learning to try to figure out, what are the patterns you see in this constellation of results in people that meet the clinical criteria or have the clinical presentation of someone having a long-haul syndrome versus people who are normal, versus what it looked like in acute COVID, or what did it look like if they had immune dysregulation that, apparently, was from having COVID itself, versus having an immunization to COVID, let’s say.  So, they can pick this apart and at pretty high levels of detail. And actually, they’re starting to use this kind of machine learning with cytokines and other testing, metabolomics and so forth, to actually finally be able to pick apart, what is the signature of chronic fatigue in me? What is the signature of long-haul COVID from the virus? What’s the signature of long-haul COVID from a vaccine? What’s the signature of, I don’t know, fibromyalgia? Right?  So, they’re trying to build these with very complex digital modeling, but you can do that on a little bit more of a simplistic level. But still, really good way to do it with objective information by looking at a cytokine panel.

Dr. Weitz:            Is it the case… And this might be an oversimplification, that if we look at a cytokine panel, that if we see certain inflammatory cytokines high, or certain anti-inflammatory cytokines low, or maybe just a pattern that we have specific diet lifestyle supplement interventions, that can modulate those?

Dr. Brady:            Well, they’ve looked at some of these advanced models, like I was telling you. If you look at Pat Bruce Patterson’s work and in other groups. In other groups, there’s group at Yale, there’s groups looking at these signatures. And they’re not only looking at these cytokine signatures and other types of biomarkers from the standpoint of who has it? Do they have it or not? From a diagnostic standpoint.  But what drives a lot of their work is trying to figure out, “Okay, let’s answer if they have it.” Number one. But let’s say, they have this pattern that seems to correlate with, I don’t know, let’s pick one long-haul COVID.

Dr. Weitz:            Okay.

Dr. Brady:            What are, then, the therapeutic approaches that we’re going to take, that’s informed by this laboratory data?   If you look at groups, like Patterson’s group, many people may be aware of some of the different approaches being used in, let’s say, long-haul syndrome. One of them is this combination of a low-dose statin and maraviroc, which is an antiviral part of an HIV cocktail, but it’s used in an off-label way, and it’s a combination of a low-dose statin and maraviroc.  They didn’t just pick those agents out of thin air, they pick those agents because they have specific modulating effects on the precise cytokines that they found elevated in the signature of those patients. Maraviroc, for instance, is a will downregulate CCL5 or RANTES, and that’s one of the cytokines that has been most correlated. Not the most correlated one when you look across the broad literature, but it’s the one that, for instance, Patterson, really, honed in on early that this RANTES CCL5 was elevated. I believe it is an HIV, and he comes out of HIV research world. So, it makes sense. He applied an agent he knew from the HIV work to downregulate RANTES or CCL5. And it has some value in long-haul COVID.  It’s not a panacea, it doesn’t just fix everything. But they’re not only trying to figure out, what kind of testing can we do to answer the question, do you have disease A, B, or C or not? But then, what do we need to do to try to treat it?

Dr. Weitz:            Okay. Why don’t we go into a little bit about how cytokines can help us to better understand the gut, and how it might correlate with, say, stool testing.

Dr. Fabian:                      Yeah. We actually do strongly recommend, if at all possible, to try to do a stool testing in conjunction, really, for two reasons. Because of course, as we all know, the gut certainly plays a big role in influencing the immune system, and it’s often thought to be involved in a variety of different chronic conditions. Even if those diseases are primarily take place elsewhere. For example, hypothyroidism or Hashimoto’s affecting the thyroid, we know that there’s a significant gut component there, based on the research.   You often see a characteristic cytokine pattern. It is always one of the things to keep in mind when you’re looking at… And learning the cytokine pattern and combining that with gut testing is really understanding those general patterns. Is it a Th1 dominant scenario? Which is what you’d expect in an autoimmune condition? Do you see a lack of the compensatory anti-inflammatory response, which is, again, pretty common?

                                It’s actually often driven in part or influenced strongly by, what’s going on in the gut? For example, we know your commensal bacteria, your normal beneficial bacteria produce a whole range of factors. Probably, the best known would be short-chain fatty acids. Butyrate is obviously the most famous of those. Butyrate is known to have an anti-inflammatory effect. Pretty significant studies show that it can actually kind of downregulate the activity of many different types of immune cells, and shift that profile, like we talked about, more towards an anti-inflammatory type pattern.

                                So, we often see a deficiency for patients in their normal bacteria. That can mean that they don’t have this stimulus to produce enough of these anti-inflammatory factors. And that’s actually widely characterized in a very long list of diseases and conditions. Everything from autoimmune disease, chronic inflammatory disease, allergic disease, et cetera. So, you can kind of [inaudible 00:28:41] this balance, so you need to have a sufficient amount of these normal bacteria cranking out these homeostatic molecules that keep the immune system from overreacting.  But also, at the same time, you’ll often see overgrowth of some of these opportunistic bacteria. Commonly, the more ones. So, things like Klebsiella, Citrobacter, that many of you may be familiar with, Proteus, Fusobacterium. A lot of these are implicated in chronic diseases, autoimmune disease, et cetera.

                                We see those same types of imbalances noted now in long COVID studies. For example, low butyrate producers, especially low faecalibacterium is probably the most commonly noted factor in these various studies. So, that basically says that, that could be a contributor to these chronic inflammatory scenarios that you see associated with long COVID, because you don’t have that ability to bring those cytokines and those immune cells back down. So, very, very important connections there.   There’s a lot of details we could get into, in terms of specific microbes. Microbes that produce LPS, et cetera. But that’s kind of the general idea is, this balance in the gut. We know that 70-80% of the immune system is in the gut, so we know that, that’s really going to have a huge effect. So, it’s a great place to intervene as well.

Dr. Weitz:            Now, one of the things I always find fascinating on the GI-MAP test is the potential autoimmune triggers, and managing a lot of patients with autoimmune diseases. We’d also like to try to prevent them. It’s fascinating to consider that some of these gut bugs can play a role in becoming triggers for autoimmunity.  And I wonder if there’s a correlation like, if you see an elevation of a potential autoimmune trigger bacteria, and we see a certain cytokine pattern cannot reinforce the potential or the relationship with some autoimmune disease that’s either existing or might exist in the future.

Dr. Brady:            There’s different levels of linkage in some of these organisms. If you look on a GI-MAP, you’ll see there’s a section, I think, on the latest revision of the test. Well, I have one here. What do we call it? It’s like, autoimmune inflammatory triggers. And it’s in the opportunistic organism section. I thought I had one here somewhere, but… Anyway. But as Dr. Fabian mentioned, you see things like Citrobacter, and we’ll look at the species level or the genus level, and sometimes down to the species. Klebsiella, in general. But Klebsiella pneumoniae, for instance, is not only linked from an association standpoint. An association relationship, as you know, means if you take… Let’s say, people with rheumatoid arthritis, and then you test subjects without rheumatoid arthritis, and you do microbiome analysis, you have a higher prevalence of finding Klebsiella in those with rheumatoid arthritis.  And you can spin it around the other way. People with elevated Klebsiella have a higher propensity of having rheumatoid arthritis. It doesn’t mean if you find Klebsiella pneumoniae or if you find Citrobacter freundii, that the person will get rheumatoid arthritis. Other things have to line up, genetics and other factors and so forth. But there is this association.

                                Now, in some organisms, there’s actually beyond association data. With prevalence, there’s actually causal understandings of how this can actually cause an autoimmune response. Some of these organisms, like Dr. Fabian mentioned, Hashimoto’s, right? Above Yersinia enterocolitica, it has been shown to have proteins expressed on its surface that look structurally very similar to TSH receptors on the thyroid. As your immune system says, “Hey, this Yersinia shouldn’t be there, I’m going to attack it.” It can get confused and latch onto to TSH receptors, and you get a inflammatory immune erosive thing going on against your thyroid, and inflames your temporarily hyperthyroid, you eventually go hypothyroid. And that’s when you usually get diagnosed, right?  But that’s an actual cause of relationship. In that case, it’s molecular mimicry. In other cases, some of these organisms produce enzymes which modify host proteins, turn them into a hapten, and then you’re off to the races because now it’s an abnormal protein. So, the immune system goes at it.  There’s multiple ways by which this can happen, but the dominoes, really, often, do start to fall in immune dysfunction systemically in the gut, in mucosal immunology. And some of it is mediated through these responses of these organisms, whether it’s structurally or whether it’s through messaging molecules.

                                There was a paper that came out post-COVID on the microbiota regulation of viral infections through interferon signaling, so we know that different microbes can actually alter interferon responses, and how you produce interferons, and how you’re able to fight viruses or not. And you saw during COVID, that the status of the microbiota in the gut was one of the predictive factors on whether you did well or did not do well or you actually perished from it.  The paper I was talking about, in particular, also looks at important commensals, Bacteroides fragilis, certain clostridia, bacillus species, lactic acid producing bacteria, including lactobacillus and strep, promoting the production of antiviral interferon, including interferon beta, specifically, and bolstering that antiviral defenses of the host. And if you were devoid of those things or you had lower levels, you didn’t have that protection.  So, we’re still just trying to unravel all this, and you were probably just scratching the surface on it, right? In 50 years, we’re probably… If someone watches this podcast, I’ll probably bust out laughing, right? Because they’ll know a whole lot more. But it is interesting stuff. But the connections are just wild. They’re just wild.

Dr. Weitz:            Are there certain cytokine patterns that, if we see that and we see that they have these potential autoimmune triggers, would that change our clinical strategies?

Dr. Brady:            I think if you actually have cytokine expression leaning toward the inflammatory side, that is a functional marker telling you, there is an upregulated immune response, and there is inflammation. There’s got to be a reason for it. It doesn’t tell you it’s from rheumatoid arthritis or it’s from this or that, but there’s something going on.  It’s like, getting an ANA, right? Unfortunately, you have doctors now telling females, mainly females, “Oh, ANA. But everything else is negative. That’s normal.” It’s not normal, it’s common. It’s not normal. It’s not normal to make antibodies against nuclear, right?  Same thing here with the microbiota. You can have someone that comes back and they have higher DNA catch for Klebsiella or Citrobacter, or Prevotella, or Proteus or what have you. But clinically, they have no signs or symptoms of an autoimmune disorder. It may, though, mean that, if that is left there to fester, eventually, with other things combined in the whole ball of wax, they would be more likely to progress to eventually end up with an autoimmune disease.

                                But if the cytokines are already raging, something’s already going on. So, it’s almost like our conversation about the cell test versus the cytokine test. It’s almost like, what is potentially going to happen, and then what’s actually being expressed? Another analogy is, when you do genomics and you look at snips, it’s predilections toward things. It’s not anything is necessarily happening or not, but when you do things like metabolomics organic acid, proteomics, you’re actually measuring something that’s functionally occurring, you’re me measuring the downstream effects of actual biochemistry and metabolism. So, they make great one two punches, for sure.

Dr. Weitz:            So, you mentioned thyroid issues, Yersinia, et cetera. Let’s say, we’re managing a patient with Hashimoto’s thyroiditis, which is an autoimmune condition that leads to a decreased function of the thyroid.  From a conventional perspective, even though, sometimes, thyroid antibodies are measured, conventional endocrinologists and physicians don’t really pay any attention to that because there’s really no strategies to do anything about it, so they basically just forget about it. But from a functional medicine perspective, we’re measuring thyroid peroxidase antibodies and thyroid globulin antibodies. And we’re trying to see, what are some of the underlying triggers that might be leading to this hypothyroid, Hashimoto’s, and those could be gut dysbiosis, and they could be food sensitivities, and they could be chemical toxins.   Let’s try to get a little more clinical here. We have a patient who has Hashimoto’s, they have elevated TPO antibodies of 500, and we also see a cytokine test that indicates a more pro-inflammatory profile. How can that help us? How can that, potentially, change our clinical judgment?

Dr. Brady:            Well, it’s a multifactorial thing. In autoimmune thyroiditis, you bring up a particularly interesting one because we see it all the time. Number one. It’s extremely prevalent.  And you’re right. I mean, the medical management is, well, let’s just watch it until it gets out of… They may look at antibody levels, but they do them to figure out, when do we need to oblate the thyroid and get it out of the picture and use HRT? We’re looking at them often more serially to figure out, how autoimmune active in this patient? Are they trending better or worse, or what have you? And you got to take some of that with a grain of salt on minor changes, because these antibodies are variable, but you can see big changes in trends over time.  But in something like autoimmune thyroiditis, we know about these hooks to changes in the gut ecology, so we’re going to look for things like Yersinia, we’re going to look for things like Citrobacter, Klebsiella, all the inflammatory things. But just general dysbiotic state, leaky gut, barrier function problems, digestive problems. I mean, because you mentioned foods, we know certain foods are correlated with autoimmunity, including autoimmunity to thyroid.

                                Great people with Graves and Hashimoto’s have about 20 times the rate of… Or I should say, the other way around. For instance, celiac disease patients who clearly have a problem with gluten, a major food peptide, have 20 times the rate of autoimmune thyroiditis than non-celiac patients. So, we know that people don’t have celiac disease, but they have non-celiac gluten sensitivity, also have a higher propensity of having autoimmunity.  Some of that might be permeability of the gut, not digesting it, so we look at markers like elastase-1 and make sure… We need to get them digesting their proteins. We need to get their barrier function better. We need to treat dysbiosis, if it’s there, particularly if there’s these autoimmune inflammatory ones.   Then, your job’s not done because you mentioned other great stuff. Environmental stuff, a lot of these pesticides and flame retardants and all of that, they glob on thyroid receptors.

Dr. Weitz:            Bisphenol A, et cetera, et cetera, and Teflon.

Dr. Brady:            And then, viruses, I mean, probably, the most common triggers, Epstein-Barr, reactivation with long-haul COVID, tons and tons of thyroid autoimmunity that crops up because one of the biggest things it does… And multiple speakers talked about this at CASI, CASI reactivates EBV, right? So, if your EBV is reactivated or CMV or any of those ubiquitous stealth viruses, it can drive an autoimmune response.   They’d love to hang out in the thyroid, and it’s called the bystander effect. They go to the thyroid to hide out, and then the immune system attacks them there, and the thyroid gets obliterated because it’s the battlefield, essentially.  So, it’s interesting, but the more ways you have to triangulate on this and look at objective markers, it can push you toward the right types of therapeutics.

Dr. Weitz:            Let me bring up another case on the same thyroid topic. Let’s say, we have a patient who has, what some people call, subclinical hypothyroid. Meaning, the person has an elevated TSH, maybe they’re T3 and T4, within range, and they have elevated antibodies.  And the question is, is this somebody who should have an intervention? Does this person need to take thyroid hormone? And let’s say, we see a pro-inflammatory cytokine pattern. Does that change the way we might handle this patient?

Dr. Brady:            Dr. Fabian, do you want to go first, or me? I can give you my clinician’s perspective on that. But if you have [inaudible 00:42:58] first.

Dr. Fabian:           Just because we do see that gut immune connections so often… If they’re not quite at the point where they necessarily need the typical clinical treatment, they don’t have the outright meet the criteria for the outright disease, obviously you can often still see some of the underlying causes starting to trend out of balance.  That really is where focusing on the gut is very helpful, because you can typically see in many of these scenarios. And a lot of people run GI-MAP, just from more of a preventative standpoint. So, you can start to see some imbalances already in people that may be preclinical, subclinical, et cetera.  So, I think it can give you really valuable information and specific targets that you can act on, particularly based on the gut testing.

Dr. Brady:            Yeah. I think you got to clean up all the stuff we already talked about in that scenario. If they don’t have overt, medically, defined primary hypothyroidism, so-

Dr. Weitz:            Yeah. Let’s say, they don’t have fatigue, they don’t have weight gains-

Dr. Brady:            [inaudible 00:44:01] aren’t overtly low, their TSH isn’t above the normal. But we know those are wide ranges, right? You got to be pretty screaming hypothyroid of your TSH go above the range now.  But we see them up in the threes and in the fours. T4s hanging in the normal range are usually midpoint or lower, but then the T3 levels are way lower. So, the total T3 and the free T3s are often right at the rock botDr. Fabian of the normal range or even reported overtly low. And-

Dr. Weitz:            I have patients who are men where the TSH, maybe they’re in their sixties or seventies, and the TSH is even seven or eight. And they’re still there. T3 and T4 is in a normal range.

Dr. Brady:            Yeah. Well, in those cases, if their TSH is really high, but all their hormone fractions are within the normal range, find out where they are in the range. Or usually, in the lower end of the range. And I would look at their autoantibodies. This is a phenomena you see much more in females, biological females, than males.  And there’s various hypotheses why that is, that involve estrogen receptors, that involve a lot of other things. The differences in the immune response of females versus males, because they have potential to carry the fetus, and they have to have a more dynamic immune system. But in the end, you clean up all those things. And we all know the things from clinical nutrition on trying to promote the 5 crime deiodinase enzyme is what converts T4 to active T3, and its sister enzyme, the 5-deiodinase will convert it to reverse T3. You can look at those balances and so forth.

                                And we know that certain things suppress the deiodinase enzymes and imbalance them, cortisol, stress, steroids, things like that. But lots of environmental toxins. So, you clean up everything you can, you do the best you can, you serially assess them. But if you have someone who clinically is hypothyroid, they’re tired all the time, they’re slow bowels or constipated, hair falling out, all that kind of stuff, body composition changing, you do everything you can to rebalance it itself.   But usually, if they’re past a certain point, particularly if there’s autoimmunity and they’ve had destruction of enough of the thyroid gland itself, therefore it’s functionality. Usually, we’re talking, usually a female, usually in that forties and up, particularly if they’re postpartum, they’ve had a couple of kids, all of a sudden, boom, this thyroid immunity hits like crazy, autoimmunity.

                                Oftentimes, they do need to optimize their metabolism, and get them to feel like they didn’t get hit by a truck. I think, top them off on the T3 side with something with T3 or a combo T4, T3 kind of compound it, HRT, just to optimize them in the normal range, never to make them too hyperthyroid. But you don’t want them hanging right down on the bottom of the ranges, if they really feel bad.  Caveat to that is, do all everything you can to self-correct them. But oftentimes, you’re dealing with someone that’s tipped over that line, where you’re never going to get their metabolism optimized if you don’t backfill the thyroid a little bit directly.

Dr. Weitz:            Just to hit on the cytokine thing, again, let’s say we get a pro-inflammatory cytokine pattern. We take some interventions from a functional medicine perspective, we take out gluten and dairy and soy, et cetera, we clean up the gut, we create some of the dysbiosis that we saw there on a GI-MAP, maybe we give them some antimicrobials, some other nutrients, et cetera. And then, we see the pro-inflammatory pattern on a cytokine test, become less inflammatory. Does that tell us, for example, that we are potentially on the right pattern at helping the-

Dr. Brady:            Yeah, it’s-

Dr. Weitz:            … underlying-

Dr. Brady:            Yeah, it’s really good assessment. If you change your diet, now you’re using curcumin or… Whatever you’re doing, whatever your interventions, we all know a million natural anti-inflammatories and how to have a less inflammatory, less autoimmune stimulating diet and so forth. Yeah. You should serially assess and see those things coming down, just like you would look at a A1C or a blood glucose in other circumstances where you’re trying to improve their glucose tolerance. Yeah, exactly. That’s the exact intention.

Dr. Weitz:            How about with autoimmune gut conditions like Crohn’s and ulcerative colitis? Can cytokine testing give us an idea of what’s going on, as to the state of their autoimmune condition?

Dr. Fabian:          Yeah, absolutely. I’ve seen a number of cases of both Crohn’s and ulcerative colitis. We know, in research, that they’re a little bit different, in terms of their cytokine profile. Crohn’s tends to be generally more sort of Th1 dominant, some Th17. Ulcerative colitis, actually, has a bit of a Th2 component to it, which we normally associate with allergies and things like that.  So, there’s a bit of a different immune response that you may see there. And same with what’s going on in the gut. I mean, you can connect those dots, if you have that data, and you can see how they correlate on this.  One thing I would note is, it’s can get a little complicated in terms of correlating what we know by the immune system with the gut. And I would just certainly advise everyone who is trying this, initially, Diagnostic Solutions Lab does have these 30-minute consultations which, when you’re first getting going, can be really invaluable to help understand and help you connect those dots, because it can be a little daunting. I think that’s one of the barriers, for some clinicians, in adopting this type of testing is, they see this panel of 18 cytokines. They’re not used to working with those cytokines. So, it can be a little challenging at first, and that’s really where our resources and our consultations can be so helpful.

Dr. Weitz:            Does that different cytokine pattern, in ulcerative colitis versus Crohn’s, does that give us any ideas about clinical treatment strategies?

Dr. Fabian:           It can, yeah. I mean, the classic picture is, with Crohn’s, you tend to have more in the guts of a inflammatory microbiome dysbiosis pattern. Actually, we often do see. Ulcerative colitis can have a combination of an overgrowth of normal commensals. Long-

Dr. Weitz:            So, how might we treat those differently? What does this tell us that clinicians can use, practically?

Dr. Fabian:           I think, to David’s point, certainly, when it comes to the gut, I mean, having that comprehensive picture, we know that there are all these upstream factors that can contribute to downstream displaces [inaudible 00:51:12] that sort of downstream. In optimizing digestion, for example, can be very important, especially for addressing that overgrowth type of pattern.

Dr. Weitz:            What do you mean by optimizing digestion? What does that mean?

Dr. Fabian:           Of course, when we think of digestion, the common pieces would be sDr. Fabianach acid, hypochlorhydria is pretty common. We know that H. pylori, for example, is one of the contributors to low stomach acid. So, C high H. pylori patient also has some symptoms of hypochlorhydria, not only can improve their hypochlorhydria, also improve some of that downstream dysbiosis.  Optimizing pancreatic function-

Dr. Weitz:            Let me just stop you, real quick. So, you’re saying, if you see H. pylori, maybe use herbs that we know can reduce H. pylori. If you don’t, maybe supplement with HCL.

Dr. Fabian:           Certainly, the herbal approach is the most common, especially mastic gum. Based formulas, those are really popular, and those seem to work quite well.  Typically, they’ll do that in conjunction with some other things like [inaudible 00:52:18], for example. And then, the use of HCL with H. pylori is kind of controversial. Certainly, with significant gastritis, you wouldn’t necessarily want to go that route. When it’s kind of a low level infection, some clinicians… It’s really a clinician judgment. Some clinicians do use HCL supplementation, others may just strictly avoid it until they have already eliminated a reduced HCL.

Dr. Brady:            Well, I mean, we use a full digestive enzyme complex, a full pancreatic enzyme that mirrors what the exocrine output of the pancreas. And oftentimes, those products, some have, some don’t. And you can make that differentiation in your recommendation, whether they have any hydrochloric acid or not.    Some of them have enough to activate the enzymes, but not like a super heavy payload, like if you were taking a separate betaine HCL.

Dr. Fabian:           Right.

Dr. Brady:            And I think some of the decision comes down to, if they have frank ulcers, if they have frank gastritis, duodenitis, you’re probably not going to use hydrochloric acid. But if you find H. pylori, that’s sort of a resident population’s been around a long time… I know, way, way back, when this H. pylori thing first emerged, I was in school, right? And the thought was, the H. pylori dig in, they make you overproduce all this stomach acid, and it rips your stomach apart, and can cause… Oh.   And what Dr. Fabian said is right. Actually, the story is unfolded very different than that. A longer term chronic H. pylori infection can actually down-regulate the production of your endogenous hydrochloric acid, so you end up in a hypochlorhydric place. And if you give a little stomach acid, as long as there’s not exposed tissue, it can improve everything about the digestion, it can kind of treat that upper dysbiosis, if you want to call it SIBO or whatever you want to call it. A lot of that is a function of pH not being right. And a lot of that is a function of not enough hydrochloric acid.

Dr. Weitz:            Okay. Let’s get back to, where were we. We were talking about how… I forgot what we were talking about. Ulcerative colitis or Crohn’s, right now.

Dr. Brady:            Exactly. Yeah. We were talking about H. pylori.

Dr. Weitz:            Right.

Dr. Brady:            And then, you were asking, does testing the cytokines change what you’re doing clinically?

Dr. Weitz:            Right. Right

Dr. Brady:            Sometimes, it does. Sometimes, it doesn’t. To me, it’s just more objective evidence that I have someone that’s in an inflammatory posture, immunologically, and I need to take action steps to reverse that.  And some of those action steps will be determined by, what I figure out, is the driver of their inflammatory status in the gut, right? I’m going to treat them different, if they’re long-haul COVID, versus if they’re ulcerative colitis, or if they’re… It’s not just an easy O. When that cytokine is high, give this, it’s not that linear. Right?

Dr. Weitz:            Right.

Dr. Brady:            But it’s just another tool to serially assess, am I really getting this person better or not, objectively? Versus just them saying, “Oh, yeah. Well, I’m having less flares or… I’m a little less fatigued.” I mean, that’s fuzzy around the edges, right? It’s hard for us.

Dr. Weitz:            For sure. Yeah. Maybe you can talk a little more about long COVID and how cytokine testing can help us to assess, what’s going on and what we can do about it? And I guess, the new term that I’ve seen in some of these studies is post-acute sequelae of COVID 19-

Dr. Brady:            That PASC-

Dr. Weitz:            … PASC. Yeah.

Dr. Brady:            Post-acute sequela of COVID-19 infection or of SARS-CoV-2 infection. Yeah, that’s the fancy medical term for long-haul COVID. They couldn’t name it the same thing as the patient’s name. They have to have some fancy acronym that no one understands. That’s just medical ego at play, but it is what it’s… Right. So, PASC is long-haul COVID.  And I mentioned some of this research that has been done by multiple investigative groups at CASI. We had Bruce Patterson, his group is one of the ones who’ve done that, that have tried to typify these changes that occur in long-haul COVID patients. And actually, even different variants of long-haul COVID patients. And they found typical suspects, inflammatory cytokines like IL-10 and IL-6, TNF alpha, TNF gamma. VEGF is another big one that they find the RANTES or CCL5 that I talked about.  And then, that paper in mucosal immunology, I reference… I have it here, actually. They show elevated expression of interferon beta, interferon gamma, IL-6, and various other cytokines. But the biggest thing that popped out most for them in this study was pretty big group was, IFN beta or interferon beta. So, they’re still working on it and figuring it out, but there’s definitely patterns that are associated with long-haul.

                                Actually, Patterson’s group have… I think they have IP on an algorithm, that they use a computer model to look at cytokine testing, and come up what’s called, a long-haul or index. And that’s a mathematical calculation using things like CCL5 or RANTES and VEGF, and some of these other cytokines.  I can say, clinically, I’ve had patients with long-haul syndrome, no doubt. I mean, it’s just in your face, the definite long-haul COVID syndrome. No other thing it can be. And it’s hit or miss, whether they hit on that long-haul index or not. So, I don’t use it as a binary, “Yes, they have it. No, they don’t,” kind of thing. It’s not there.   But certainly, they generally have a more than one, a multitude of these inflammatory cytokines high when you cytokine test them.

Dr. Weitz:            And is that a questionnaire?

Dr. Brady:            What? The long-hauler index?

Dr. Weitz:            Yeah.

Dr. Brady:            No, it’s-

Dr. Weitz:            Oh, it’s a computer.

Dr. Brady:            … it’s a computer algorithmic output based on the laboratory assessment behind the scenes. You know what I mean?

Dr. Weitz:            I see. Okay. Okay, good. Yeah. All right. Any other things we want to talk about, how cytokine testing can help clinicians?

Dr. Brady:            Well, I mean, a big part of the understanding of cytokine testing and what ended up turning into these commercial cytokine analysis and testing… A lot of it came out of, like I said, critical care medicine, but also out of cancer research. Because with precision personalized medicine in cancer therapeutics, where they’re trying to phenotype the cancer, and then give very specific agents that modulate the immune system in very specific ways based on the person’s genetics and the cell line’s genetics, all those drugs were pretty much proved out with very advanced cytokine analysis, all the way through the process. It was part of the drug approval process. In fact, one of our main science brainiacs at DSL, actually ran the largest CRO lab that did a lot of the cytokine testing for the approval of a lot of these different biologicals, if you will, right? Response modifiers.  So, when they’re considering using PD-1 checkpoint inhibitors and things like that, they’re using cytokine analysis to make those calls in a lot of different situations. So, there’s a lot of use for this throughout many different phases of medicine, especially at the highest levels of precision medicine and cancer therapeutics.  But I think there’s definitely a role for it in functional integrative medicine, because when it’s all said and done, as you know, we’re dealing with all these complicated downstream issues that are fundamentally creating very common, a common set of physiological responses. And usually, it evolves around inflammatory and immune responses.

Dr. Weitz:            Okay. Great. Any final thoughts, Dr. Fabian?

Dr. Fabian:           Yeah. I would say, the clinical utility, to me, has been pretty phenomenal in many ways, for a lot of patient cases. So, you can really zero in on what’s going on in the immune system for certain patients. And again, especially if you combine that with gut testing… I’ll just give you a couple of quick examples. One would be, patient that had a chronic Bartonella infection. It was really just not doing well, pretty sympathatic. I’m certainly not a Bartonella expert, so I can’t comment…

Dr. Weitz:            By the way, for those who don’t know, Bartonella is a common co-infection often related to Lyme disease.

Dr. Brady:            Also, very commonly flared up in long-haul patients.

Dr. Fabian:           Yeah. And so, one of the things that you can potentially see is this classic ideas. You might have an overactivity of the pro-inflammatory side and insufficient anti-inflammatory. But in some cases, you have the opposite. So, you have a chronic viral infection, and ideally your immune system wants to try to deal with that.  But on some of these patients, I’ve seen patterns where they don’t have a detectable pro-inflammatory pattern, and they have elevated IL-10, interleukin 10, which is a really well-known anti-inflammatory cytokine. And I looked in the research on that when I reviewed that patient’s case, and there’s a fair amount of research on these various chronic bacterial viral infections that many of them can actually cause an upregulation of your anti-inflammatory response, that then kind of blocks this antiviral function.   So, that gives you some key information, because normally, what comes from the gut standpoint, you might want to work on an inflammatory scenario, increasing those beneficial bacteria, trying to increase that IL-10. But there may be cases where that may not be the best strategy. So, this really speaks to precision medicine. And knowing these details can really help influence your overall strategy. One other quick case would be-

Dr. Weitz:            Hang on. Just one quick second. Let me just give a little extra information to those listening, who aren’t familiar with what we’re talking about is, you’re pointing out something which is really important which is there’s a tendency to think of inflammation as all bad, and the more anti-inflammation you can get is better.  But inflammation is also a marker of immune system function, and we need a certain level of inflammation to fight off microbes and help us heal from injuries, et cetera. So, it’s not as simple as inflammation is bad.

Dr. Brady:            It’s how much how long what’s causing it, and is the response in appropriate for what’s going on. And is it becoming too persistent in locked loop.  And even what Dr. Fabian just pointed out was interesting. One of the things you do see a lot on, let’s say, a long-hauler population is IL-10 being elevated. And you might go, “Well, hey, that’s anti-inflammatory.” Right? Well, sometimes, it’s… When you look at a cytokine test, it’s not only important to see that someone has upregulated inflammatory cytokines. Sometimes, upregulation of anti-inflammatory cytokines is telling you, they’re trying to react to it, they’re trying to fight something. So, you need to look at it from both directions.  And so, again, it’s not as draw this line linear, as you think. You got to kind of think your way through it a bit.

Dr. Fabian:                      Yeah. And I’d say, just to kind of add to that picture a bit more, and again, really, the precision medicine approach and parsing out what’s going on, I’ve seen a number of cases where patients with autoimmune conditions that are on biologics, they are highly targeted to suppressing certain inflammatory cytokines.  So, anti-IL-6 is a pretty common class. Anti-TNF alpha is another common class. Remember one particular case where this patient is on the biologic. We looked at the cytokine profile results, and that particular cytokine was not detected. So, that’s telling us the biologic. It did appear to be working. Patient was still very sympomatic. We saw all kinds of other pro-inflammatory cytokines lighting up. So, that’s telling us that, that was effective in a narrow way, but not really effective in generally suppressing that overactive immune response.  So, that gave the practitioner digital information that there’s more work to do, to try to find out, what’s causing this inflammation, and what can they do to compliment this biological therapy.

Dr. Brady:            Or they might need an entirely different response modifying medication, because it’s just not hitting the optimal target.

Dr. Weitz:            This brings up a really interesting example. Imagine that you’re managing a patient with autoimmune disease, who’s on one of these biologics and you do a cytokine test. It may be that, immune modulating drug is actually not working. Maybe that cytokine that’s supposed to be suppressing is elevated, and you might actually be able to interact with their rheumatologist and say, “Hey, look, this interleukin-6 suppressing drug, actually their interleukin is elevated. They probably need a higher dosage of that. Or maybe the opposite. Maybe they’re taking-

Dr. Brady:            Or they’re using IL-6 targeted drug, and they’d be better off with a TNF alpha. And you can show that on the cytokine analysis.   And while they may use this kind of testing in a very precise way, in many cancer therapeutic situations, generally, I don’t find that’s the case in standard rheumatology. I think they’re just clinically working up a patient, maybe doing rheumatoid panel or what have you, but not advanced cytokine testing. And then, saying, “Well, we’re just going to use the drugs we use, so we’re going to try a TNF alpha or we’re going to try in IL-6.” Well, they’re not testing it to that level, they’re just not doing it.

Dr. Weitz:            Yeah, that’s really insane. Imagine that you were going to put a patient on a drug for diabetes, and you don’t test his blood sugar to see if it’s working or not.  So, I think we just pointed out something that’s really, really crucial for managing autoimmune patients.

Dr. Brady:            Yeah.

Dr. Weitz:            Okay, great. Thank you so much, guys.  Dr. Fabian, why don’t you tell us how clinicians can… These tests are available for clinicians, right?

Dr. Fabian:          Correct. Yes.

Dr. Weitz:            Right. So, you can either contact a functional medicine practitioner, like myself, you can go to find a practitioner from the Institute of Functional Medicine. Or if you’re a clinician, you’re a practitioner, to tell us how we can order the cytokine test and the GI-MAP stool test.

Dr. Fabian:          So, you can either call our customer service. Just go to our website to get the contact information. You can either fill out the form, call customer service. If you want, just more information about these tests, we have a lot of great information on our website about the test and specific information there on how to order.   And if you’re just kind of wanting to know a little bit more before you do place an order, we do have a lot of educational information that can help you better understand utility of these tests, clinically.

Dr. Brady:            All of that is on the website at diagnosticsolutionslab.com. So, Diagnostic Solutions Lab. Or again, just Google Diagnostic Solutions Laboratory and you’ll find it.  And the tests are orderable, also, through a lot of the big lab distributors, whether it’s Rupa or Evexia, or any of those as well. So, it depends how the clinicians order their diagnostic testing, but if they have the authority for ordering diagnostic laboratory testing, they can come right to DSL as well.

Dr. Weitz:            Great. Thank you, guys.



Dr. Weitz:     And thank you for making it all the way through this episode of the Rational Wellness Podcast.  And for those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcast or Spotify, and give us a five-star ratings and review. That way, more people will be able to discover the Rational Wellness Podcast.

                                And I wanted to say, thank you to all the patients that we’ve been working with us at our Weitz Sports Chiropractic and Nutrition clinic who, most of whom, we’ve been able to help with a range of various health conditions from various types of gut disorders to thyroid and hormonal issues, autoimmune diseases, and various other cardiometabolic conditions.  And so, I very much appreciate you, and I’m excited about going forwards helping you to improve your health on your journey towards optimal health. And I wanted to let everybody know that I do have a few openings now for new clients, and you can take advantage of that by calling my Weitz Sports Chiropractic and Nutrition, Santa Monica office at 310-395-3111, and we can set you up for a new consultation for functional medicine nutrition, and we can get that going as early as the new year. So, give us a call and I’ll talk to you next week.


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