In this episode of The Dr. Hedberg Show, I interviewed Dr. David Brady about the new GI-MAP stool test by Diagnostic Solutions Laboratory. We discussed many topics including autoimmune disease, stool testing, stealth infections, gut infections, the gut microbiome and much more. This is the stool test I use in my practice to identify bacterial dysbiosis, viruses, parasites, yeast, and overall digestive health.
Nikolas: Well, welcome everyone. This is Dr. Hedberg. And welcome to The Dr. Hedberg Show. I’m excited today to have a long-time friend and colleague on the show, Dr. David Brady. We’re gonna be talking about the GI-MAP stool test and autoimmunity. And for those of you who don’t know Dr. Brady, he has 26 years of experience as an Integrative Medicine Practitioner and over 22 years in Health Sciences academia. He’s a Licensed Naturopath in the State of Connecticut and also Vermont. He’s board-certified in Functional Medicine and Clinical Nutrition. And he completed his initial clinical training as a Doctor of Chiropractic in 1991. He’s currently the Vice President for Health Sciences, Director of the Human Nutrition Institute, and Associate Professor of Clinical Sciences at the University of Bridgeport in Connecticut.
He has a private practice called Whole Body Medicine in Fairfield, Connecticut. Dr. Brady is also an expert consultant to the professional nutraceutical and nutritional supplement and clinical medical laboratory industries. He serves as the Chief Medical Officer for Designs for Health and Diagnostic Solutions Labs. He’s also an internationally sought-after presenter on nutritional, functional, and integrative medicine. He’s appeared on the speaking panel of some of the largest and most prestigious conferences, this includes IFM, ACAM, A4M, IHS, AANP, and many more. And we’re gonna talk about some of his papers today. So welcome to the show, Dr. Brady.
David Brady: Hey, thanks, Dr. Hedberg, great to be on your show. We go back a long way in this journey together in functional medicine and we have amazingly similar paths, although you’re fortunate enough to have gone through it a little later than me which means, you’re younger.
Nikolas: Right, right. Younger but…
David: Younger but we’re pretty similar, so.
Nikolas: Younger but not smarter. So that’s why I have you on the show.
David: Oh, I don’t know about that.
Nikolas: So let’s jump into autoimmunity and you’ve emphasized this topic a lot in some of your papers, and in a lot of your lectures, and you also work with a lot of autoimmune patients in your practice. So what do you think it was that developed your interest in autoimmunity?
David: Oh, I don’t know sheer desperation, probably like yourself, you know? Just seeing so much of this stuff come in on practices over the years, and it’s just grown, and grown. And, you know, even in my couple of decades in practice, I certainly see it as being so much more prevalent as a presenting concern with patients than I did back in the beginning. And what we’ve seen emerging in the literature in parallel to that has really made autoimmunity one of these…well not a disorder but sort of a constellation of disorders that have a similar underlying etiology.
It’s really a group of disorders that is really just innately attached to the functional medicine approach, right? Because of the emphasis in functional medicine on the importance of the health of the gastrointestinal system, gut ecology. And now, we would talk about it in more detail is the microbiota and the microbiome, and certainly an appreciation of the role of toxins and things like that, just make it a natural that patients would turn to providers like us if they had an option.
And they become aware of other types of approaches and certainly with the internet coming, you know, blowing up during that same amount of time, people have access to information now including so much good information, like what you produce that makes patients realize that they have more options than Methotrexate, and Humira, and that kind of stuff. So I think we see so much of it, it’s hard as a functional medicine integrative medicine practitioner, no matter what your core training, to not have to get up to speed on autoimmunity pretty darn quickly because you see it all day long.
Nikolas: Exactly. Like you said, there aren’t a lot of answers from the conventional medical side other than a series of drugs, which, of course, some people need sometimes but we can do a lot as functional medicine practitioners. So this paper you published that was in the Open Journal of Rheumatology and Autoimmunity in 2013 and the title is, “Molecular Mimicry, the Hygiene Hypothesis, Stealth Infections and Other Examples of Disconnect between Medical Research and the Practice of Clinical Medicine in Autoimmune Disease.”
David: Yeah. That’s quite a title, huh?
Nikolas: Right, right. So why did this paper, why was it so well-received by so many in the functional medicine field?
David: Oh, it’s interesting. I’m glad it was. I still get a lot of people coming up to me at speaking events, and conferences, and so forth bringing up that paper. And I’ve had quite a few actually faculty at different institutions be it, you know, naturopathic medical programs, nutrition programs, and so forth, saying that they used the paper in their teaching and which is a great honor to hear that. But I think the reason it probably struck a chord, for the people who have been exposed to it or have seen it is because what my intention was when I wrote it was really to pick out some of these really interesting connections and things that are in the medical research and literature , such as molecular mimicry and actually, you know, looking at novel concepts of etiologies for specific autoimmune diseases based on the phenomena of molecular mimicry.
And then, in parallel to that research on the hygiene hypothesis, right, the whole idea that we’re too clean now and our immune systems don’t really get to adequately sample a diverse environment of potentially antigenic material while our immune system is maturing, and learning to deal with its world. And then just some other disparate types of really interesting research as it pertains to autoimmunity and how all of that information seems to be lost on the conventional practitioners who are dealing with autoimmune disease such as rheumatologists, for the most part. They really don’t seem to in their very orthodox standard of practice paradigm and standards of care pay much attention to all this great research that’s going on out there.
You know? How many times does a rheumatologist do a stool analysis to assess the microbiota and see if there’s overgrowth of any of these organisms that the research has clearly said are often tied to a much higher incidence of the disorder. And now, beyond just association, we have actual causal data on some of these things, but they never even look there. There’s been no real effort to educate people in from public health types of folks on getting young people more adequately sampling their environments so that they have a healthy immune system when they grow up.
And we have more and more atopic disease. We have kids, you can’t walk through an elementary school without young kids, without every classroom has some sort of sign on it, “Food allergy this,” or some sort of significant immune dysfunction that’s even posted on the darn doorways. So there’s clearly something major going on. It doesn’t seem to be being addressed by the clinicians but yet the researchers are all over it. And I found that that was an interesting disconnect like a chasm between the researchers in Western medicine, which I think are really doing a great job when it comes to immune dysfunction and then the practice of clinical medicine, which I think is doing not a great job.
Like you said there’s regimens of drugs from various anti-inflammatories to Methotrexate to response modifiers and strong immunosuppressants and certainly, those drugs have their role in the properly selected patient but it’s usually when the patient is far down the line and they’re actually having arrays of joint destruction or they have some other serious tissue damage going on and degenerative neurological conditions or what have you. And then, it’s just basically putting the band-aid over it, and helping them out certainly symptomatically.
But what was going on in the research, I found, had the opportunity to open up a whole new approach, right, to these kind of disorders and actually climb very upstream and try to find patients, even before they have these disorders, and risk assess them for potentially getting the disorder downstream and making some significant changes in their lifestyle, and their dietary intake, and their GI health that might actually truly prevent them from getting the disorder.
So it’s almost a golden opportunity for preventive medicine in its actual true form rather than the lip service that many providers both conventional and complementary painted to the whole idea of preventive medicine. And then, when you look at what they’re doing, they’re doing very little in the way of actual prevention.
Nikolas: Exactly. Yeah, it’s interesting, you know, you bring up stealth infections in your paper, that’s probably one of the most common questions I get from practitioners. And it’s just interesting because, like you said, there is so much literature out there on stealth infections and autoimmunity but there aren’t really any conventional interventions being developed for those, at least not that I’m aware of. But it’s interesting because a lot of those drugs are immunosuppressive and…
David: Right, and counterintuitive, right?
Nikolas: Yeah. And if they have, you know, like an Epstein-Barr or a tick-borne infection or anything like that then they’re just kind of going up and down through the process and then they usually end up going down a downward spiral after that. But so this is, at least in your estimation, a modern epidemic and I would say that’s definitely true, the research that I’ve looked at, we’re just gonna continue to see autoimmune disease skyrocket in its prevalence. So can you add on that?
David: Yeah. I actually did address that… Yeah, I even addressed that in that paper you referenced. And I have another paper in the “Townsend Letter,” that kind of covers a lot of the same ground. But I really opened it up with some of the epidemiological data on incidence of autoimmune disorders and how it’s changed over the last 100 years. And to give you an example, if you look at something like a classic autoimmune disorder or like inflammatory bowel disease, like ulcerative colitis, let’s say, the best we can tell is the incidence for that in the Western countries like the United States at that time, around 1900, for inflammatory bowel disease was somewhere at about one in 10,000 patients or 10,000 subjects. Now, it’s about one in 250. 250, right? I mean that’s a massive difference.
And you see that similar kind of incredible change statistically when you look across a broad swath of autoimmune diseases, whether they were classically considered Th1 or Th2-dominant types of disorders, it’s really amazing. And when you look at that level of increase clearly, there’s something going on that’s environmental, right? Because we know that genes certainly play a role in autoimmunity, and we certainly know a lot about the different ways to test for genetic susceptibility to autoimmunity.
But this meteoric rise in incidence of autoimmune disease can’t be explained by genes alone because the genes don’t change that quick, in a population. So clearly, there’s something dancing with our genes and particularly with the genes of those who are very susceptible to these specific disorders that is making them exceedingly more prevalent. So what is changing in our environment or what has changed?
And you can go down a lot of roads when you start bringing that up from the amount of exposure to all kinds of toxins, man-made toxins and that weren’t around until this century. The hygiene hypothesis people, of course, argue that we’ve really changed the landscape in particularly for our children as they’re growing up and sampling their environment with modern hygiene, and water treatments, and the use of antibiotics, and just how, and the way we live our lives right now compared to our ancestors.
But then we have this whole modern understanding of how shifts in the microbiome can really have devastating events or devastating outcomes on our health if they don’t go the right way and they actually cause autoimmune phenomena through molecular mimicry. So it seems like a perfect storm honestly, like there’s a whole bunch of things that are all adding up to an environment where we’re much more susceptible to having an autoimmune disorder or more than one.
Nikolas: Let’s plant a flag there and lay some bedrock for the listeners. So talking about stool testing and the microbiota, can you give us kind of a foundational overview of why we want to assess the microbiology in the gastrointestinal tract for those with autoimmunity?
David: Sure. Well, it’s pretty obvious the body as we all learned in medical school or wherever we trained, 75% or more of the body’s immune resources are dedicated to the enteric immune system, right, to mucosal immunity, and to the GI tract so, why? I mean the body is not stupid it’s dedicating resources where they’re needed. And it’s clear that we need an incredible amount of immune surveillance regarding our gastrointestinal environment because we have this hollow tube running right through the core of our body, we have this tube running through the middle of us that’s technically outside of us and it’s full of bacteria, fungi, viruses, protozoa, it’s full of foods that we ate that have a lot of toxic material in them, have a lot of potentially antigenic proteins in them. So we have to really pay attention to what’s going on there and make determinations. You know, what are we gonna react to? What are we gonna tolerate? What do we need to mount an immune defense against? And it’s a really complicated business.
And then, the only thing that separates us from all of that potentially lethal material, that if it was all of a sudden to be in our systemic blood supply or in our lymphatic supply or directly interfacing with our systemic immune response, is a one-cell-lining-thick membrane called the GI mucosa. So there’s been a lot of, of course, attention paid to the health and the function of the GI mucosa and the whole concept of hyperpermeability and leaky gut, and we’ll talk about that a little bit. But it’s also of great importance what the composition is of that luminal material, and particularly from the standpoint of microbes.
So and this is a fairly obvious thing when you think about it now but Metchnikoff, for instance, at the turn of the last century, was a real pioneer in the whole concept that the health of the GI environment, and he even knew it to the level of the microbes that live there is very important to the health of the overall organism. And this isn’t an overall concept that was new before Metchnikoff long before that, these are tenants that run through Traditional Chinese Medicine, Ayurvedic Medicine, European Eclectic Medicine, I mean you name it. These older forms of medicine, they didn’t understand the specifics like we do now but they got the concept that if someone has really bad gastrointestinal health, they’re not gonna be a particularly healthy individual.
But now, fast forward, with the Human Microbiome Project, and looking at metadata that’s been collected, and the ability to actually analyze the composition of the GI microbiota with molecular-type of technologies, they’ve created all kinds of different associations, of course, as we know, between overgrowth of certain microbes in the gut and the incidence of certain autoimmune conditions, examples of which are, we know, for instance, subjects that have autoimmune arthritides, like rheumatoid arthritis and ankylosing spondylitis are much more likely if you test their GI microbial composition to have elevated DNA for Klebsiella, for Citrobacter, for Proteus, for Prevotella, for E.coli. We know, for instance, Fusobacterium overgrowth in systemic sclerosis, or scleroderma, micobacteria, and psoriasis, and Crohn’s disease, Yersinia, and Grave’s, and Hashimoto’s, and on, and on, and on. So these are all associations that have been made by looking at these things.
But now, we’ve actually moved beyond that to understanding how overgrowth of a certain microbe in the gut ecology, let’s say, can interface with the subject’s immune system and actually cause it to attack its own tissue. And the most obvious way that that can occur is through this phenomena of molecular mimicry, which it’s a complex thing but it’s really simplistic when you break it down. And that is, this bacterium, generally, in the case of the GI microbiota, that may be opportunists. Often, in fact, usually, they’re not overt pathogens, they are usually opportunistic organisms. So they can overgrow if they are provided the right opportunity or the right environment. And when they do, they can become problematic.
They can cause a lot of vague GI symptoms like, you know, it might render someone a diagnosis of IBS, let’s say, particularly, if they’re a female. But sometimes they don’t even cause any GI symptoms at all, but if they’re overgrowing and these microbes have on their surface a peptide or they secrete a metabolite that has a protein S or peptide structure made up of amino acid sequences or motifs that have a certain sequence or structure to them and that’s the structure that the immune system keys on when it’s trying to combat that infection.
So when that microbe overgrows, let’s say Klebsiella or Citrobacter and the gut is overgrowing, well, the immune system figures out real quick, “Hey, that’s not me. It’s not one of my normal resident commensal microbes in the gut that I wanna get along with. It’s something different.” So, “Is it a threat?” And if particularly if you have a unique characteristic to your immune system like a certain HLA-pattern let’s say, in the case of the disorders we’re talking about like RA and ankylosing spondylitis, it’s often an HLA-B27 where the peptides expressed by these on the surface or through the metabolites of these microbes, if you have that HLA-pattern, you grab those things and you then present them on the HLA molecule to your naive T-cells and you make a big fuss about it basically your immune system is sort of waving these things around saying, “Hey, immune system, look at this shape. When you see this shape or structure, you need to mount a response against it,” which often means building antibodies against that structural antigen.
Well, what we’ve come to find out is some of these proteins that are conserved across these classes of microbes have a similarity in their structure, they’re not exactly the same but the amino acid motifs are similar enough where if the person already sort of is inflamed has a kind of a hyperactive immune response, they have a genetic susceptibility to sort of over respond to that specific environmental antigen or something structurally similar, they can lose the ability to discriminate between that peptide that’s keying on the bacterium and a peptide that’s resident on a host tissue.
So it could be a receptor on a host tissue like a TSH receptor in the case of Yersinia or proteins expressed on the synovium in the case of rheumatoid arthritis and ankylosing spondylitis or type II collagen in the case of rheumatoid arthritis and in Proteus, for instance. So it’s a really interesting concept. And what it means is we really need to understand what is the composition of the microbiota in patients that we’re dealing with who have autoimmune conditions, where we know their specific overgrowth patterns or triggers. But not only the patients who already have the autoimmune disease but patients who we have a higher suspicion might end up with the autoimmune disease.
And how do we know that? Well, we know that from family history. So if you take a family history, in a patient in front of you, let’s say they’re in their 20s or 30s, and it turns out that their father has rheumatoid arthritis or they have a lot of RA or AS or something in the family, or sometimes it’s a lot of autoimmune thyroiditis, it’s a woman and her mother or older sister or aunts on Synthroid, you do some thyroid testing, thyroid’s not looking good, and there’s auto antibodies or thyroid antibodies present, you wanna look at that GI microbiota to make sure some of the triggering organisms that we know can play a role in molecular mimicry if they are in play or not even in that patient long before they actually have the clinical expression of that autoimmune disease.
Because if they do, at least theoretically, we don’t have long-term studies to back this up objectively, but it just intuitively makes sense that if we have someone with a lot of family members that have gone on to develop this autoimmune disease and we find known triggers of it in the GI microbiota, that we might be doing a good thing for them if we can improve the landscape and the composition of the GI microbiota to basically get rid of the triggering organism to make sure their GI mucosal health is better so they don’t have the leaky gut phenomena allowing even more interface with systemic immune response, and that we may chase down other things as well, such as known food triggers, in the case of, I know you know more about this than me, but in the case of immunogenic thyroiditis, whether it’s Hashimoto’s or Grave’s, we know we have potentially triggering organisms in the gut like Yersinia, but, of course, EBV, CMV, and a lot of ubiquitous viruses play a role in triggering that, and manifesting that autoimmune response but so do foods.
We know, you know, gluten, gliadin antigen-antibody complexes have an affinity to stick in the thyroid gland, and then cause an attack against the thyroid. And we know from celiac research, for instance, that celiac subjects have anywhere from 10 to 20 times the rate of Hashimoto’s and Grave’s as non-filial, for instance. And what does that mean for all those people who are not fully-tolerant to gluten, and gliadin, and field grass grains but are short of celiac disease, do they have higher incidence of autoimmune thyroiditis as well? Well, there’s not a great amount of data on that but from my clinical experience is yes, they do.
Nikolas: Definitely, right. And so speaking of clinical experience, let’s dig into how we can help our practitioners listening and/or the patients just have a better understanding of really what we’re looking for as to why all this happens to a patient’s microbiota. So I’d like you to elaborate on the things that I’d look for and add anything you think is also important. So and, kind of, a start from the beginning, so if the patient was a C-section versus a vaginal birth, that can be a red flag, if they were formula-fed and were never breastfed and then we look at their antibiotic load, not just as a kid but throughout life. And then, the other thing that I’ve been reading about a lot lately is early adverse life events and how these actually change the microbiome.
So abusive parents, it could be verbal or physical abuse, bullies, if a family member is an alcoholic or an overbearing mother where nothing was ever good enough. I mean there’s just this huge list of things that can happen to us when we’re young and when we’re kids when that microbiome is still developing. Plus, I don’t know about you but my diet as a kid was just absolutely horrific when I look back at what I ate just the sheer amount of sugar, gluten, dairy, and just junk, you know, growing up like a lot of us did. Those are the real things that stand out for me. Anything that you want to add there or elaborate on?
David: Yeah. I think you hit a lot of the big ones for sure. And most practitioners would probably think of most of those kind of things as pretty obvious at this point, but you hit on one that’s not, which is the adverse early life events. Peter Mohl, M-O-H-L, if you wanna look up his work, has done a lot on, greater incidence of all kinds of chronic diseases, and early mortality, and things like that based on life distressing events, particularly early in life. And we know certainly, the females seem to be much more affected by being in these very bad abusive, unsafe, overly-critical, filled with strife sort of upbringings, they tend to go on to develop most commonly, irritable bowel syndrome. You know, funny enough, right?
David: So clearly, that usually has some level of dysbiosis and problems in the GI environment, including the microbial composition but, of course, they go on frequently to develop depression, anxiety, insomnia but quite frequently, chronic global pain disorders like fibromyalgia as well, where the males tend to not develop those things as much but then to develop more easy frustration, anger, violence, repeat abusing. They tend to be these like they were abused, females don’t do that.
So just some inherent differences in the female versus the brain…female’s brain and the male’s brain and how they sort of respond on average. Kind of interesting and fascinating work that is just evolving but it’s just amazing how much the microbiome researchers are establishing these clear signatures of an aberrant microbiome to very specific chronic diseases that go way beyond just autoimmunity, but autoimmunity probably provides the most clear direct line between changes shifting in the microbiota and developing the autoimmune disease.
And, for a long time, it was a chicken or the egg argument, you know, like, “Does having the autoimmune disease shift the microbiota or does the microbiota shifting contribute to the genesis of the autoimmune disease?” And more and more the research is suggesting the latter that actually an interesting phenomena in autoimmune diseases is they, as we know as clinicians, they tend to wax and wane, right? They flare, and then they get better, and then they flare, and then they get better, regardless of treatment like an ulcerative colitis patient, they’ll flare, and then they’re pretty good, and then they can’t leave the house again because they’re having bloody diarrheas all day.
Same thing with MS patients or RA patients. And when you track and serially assess the composition of their microbiota, it’s amazing that when they’re clinically flared up, they have the aberrant pattern of the microbiota associated with that disorder. So like in RA, they have lots of Klebsiella, Citrobacter, Proteus, and things like that, but when they go into a relatively quiet period, when they feel good, their microbial composition looks more like normal people, if you will, they don’t have overexpression of those bugs. So what is shifting what? When they look at it, it seems that the microbiota shifts for some reason, and then drives the disease to be much more and are clinically expressive, which is fascinating. And we don’t really quite understand exactly why all those shifts take place necessarily in a patient but I’m sure they’ll figure that out eventually.
Nikolas: Yeah. I mean I’ve been staying up on the gut-brain axis, you know, research, and it just kind of leaves your head spinning. There’s something new every month with more and more intimate details there.
David: That’s , yeah.
Nikolas: So that shift into testing…so we have Diagnostic Solutions Laboratory offering a stool testing, which I’m extremely impressed with, I just want to throw a couple of patterns at you and maybe give us some general insights. One of the things that I’m seeing in some patients is an elevated Firmicutes and Bacteroidetes pattern.
Nikolas: Now, sometimes, they will have a positive SIBO breath test and then sometimes they won’t, do you see any correlations there? And what does that finding generally mean to you?
David: Well, it’s interesting when you look at the Firmicutes Bacteroidetes ratio. Again a lot of people call it the adiposity index or ratio because some of the first research came out on that appreciating the fact that people who are overweight and even more so, people who are obese tend to have a tilting of that ratio toward the Firmicutes. And just as a matter of I guess more global explanation, Firmicutes and Bacteroidetes are two phyla of organism which mean a large family, so this is beyond the species, beyond the genus, this is up to the phyla level.
And the predominant amount of your GI microbiota composition falls into one of those two phyla, either Firmicutes or Bacteroidetes. And those people who are really overweight tend to have a higher Firmicutes the Bacteroidetes ratio. Now, they saw that and they tried to figure out, “Well, why might that be?” And it turns out that the Firmicutes organisms, which are made up of a multitude of genera of bugs, by and large, are more efficient at extracting calories or caloric value at a dietary substrates and particularly starches, and fibers, and things like that, than the Bacteroidetes.
So if you have more of the Firmicutes and less of the Bacteroidetes than someone else and you eat the same exact diet, you will get more calories from that diet than they will. So that might be part of why those people tend to be more obese. But certainly, it’s not the end-all-be-all panacea, right? And I mean obesity is a complex metabolic disorder. It goes beyond just, you know, the Firmicutes-Bacteroidetes ratio. But then they started looking at that ratio in the context of various autoimmune disorders, for instance, and we know that shifts in that ratio can make you more or less likely to have a certain autoimmune disease or not.
So that research is ongoing and they tend to report that in a lot of different autoimmune diseases. And it’s not predictable like one pattern is bad there’s some autoimmune disorders where a higher Firmicutes the Bacteroidetes ratio imparts more risk and there’s other disorders where a lower ratio imparts more risk. So there’s still a lot to be learned about how to apply that ratio. But it is an interesting phenomena and the jury’s still out. I wish I can tell you everything about it, but it’s a bit confusing actually when you follow the research on that ratio. Because it’s much easier if you could say, “Oh, this pattern is good and this pattern is bad.” Well, it’s more complex than that, unfortunately.
Nikolas: Right. Right. So the GI-MAP is now a quantitative PCR test. I believe that’s as of December last year. And can you tell us what that means, and when I mean, obviously, some of these are going to be flagged as being elevated but then we will also see some level of them, some of the bacteria or the yeast or viruses, there is some level there reported but not elevated. So how do you approach those types of results?
David: Yeah. Well, I mean, I guess, starting at the beginning here, what really changed our ability to look at the microbiota and its composition to a level that really allows us to make some, you know, viable clinical decisions was the molecular revolution, right? The advent of PCR and amplifying sample DNA to levels that we can actually test it and work with it and so forth, but that took a long while for that to mature properly. But now, it clearly has and we are in the era where molecular is definitely the way to go because it overcomes some of the obvious inherent long-term challenges that we always had with culture technologies, including the fact that basically with culture you’re really limited to looking at aerobes and some facultative organisms, which, you know, you’re talking about definitely less than 10%, probably less than 5%, of the microbial composition of the GI microbiota.
So with molecular, you don’t have to keep these organisms alive and viable, so you can actually drop them in a formalin solution which then basically freezes everything right there and then, right after the patient collected the sample versus putting it in a nutritive media and having it in a FedEx truck and all of that, and everything’s changing by the time they can plate it out, grow it, and try to identify the organisms. And even then if they’re entirely accurate, which is usually not the case with culture, they’re looking at like I said, 5% of the microbiota. So molecular, just on its face is a much more viable way to look at this.
But the problem is a lot of clinicians don’t understand the basic molecular technologies that are available. And right now, there are two major types of molecular or DNA-based stool testing. One is using what’s called Next-gen sequencing, and the other uses real-time PCR or quantitative PCR. And they’re both very good methodologies, they’re just meant for inherently different purposes. The Next-gen sequencing types of tests are what most people are used to seeing when they do a uBiome or a Gut Zoomer or one of those kind of tests.
And if you’ve ever tried to take the results of one of those tests as a clinician and make heads or tails a bit and make clinical decisions, it’s hard to do because those tests were never meant for clinical decision-making like a point of clinical care with a patient. They’re not meant to say, “Does Mary Jones in front of me have an overgrowth of C. diff?” or, you know, “How much of a certain commensal organism is there?” They are research tests, they’re metadata tests. And what they’re meant to do is they have very wide lenses, right? They’re gonna test a lot of different organisms, the vast majority of which, have no known clinical significance, okay? But they’re looking at it all because they’re trying to develop compositional macro signatures of the GI microbiota over a large population group so that they can develop these associations. Like, “People with X disease have higher levels of X organism in the gut,” or, “What does the composition of the GI environment look like for a vegetarian living on the West Coast of the United States on average?” Right?
So they’re meant to answer those questions. They’re metadata collection tests for researchers. They don’t quantitate, in other words, they don’t tell you how much DNA is there and they don’t get very specific on the organism, they usually check to the genus level. In some instances, they can go to the species level, but they have a hard time doing that with a lot of organisms and they certainly can’t go to levels that you can with qPCR, which is down to looking at not only the genus and species but genetic characteristics of the organism, like characteristics that make it likely to be pathogenic or cause tissue damage or not.
Like in the case of Helicobacter pylori, we look at genetic characteristics of specific virulence factors or with quantitative PCR, we’re not just saying, “Is there Clostridia there?” we’re saying, “is there Clostridia difficile there?” and, “If Clostridia difficile was there, does it have the genes capable of producing C. diff toxin A or toxin B or different types of issues?” So quantitative PCR is not meant to look at thousands of different microorganisms at the genus level and report them only on the percentage of the total DNA recovered, which is what those other tests do, the Next-gen sequencing.
Quantitative PCR looks for specific targets and measures, “Are they there?” not only, “Are they there, but how much DNA is there? And is it above a threshold that’s considered problematic?” So with pathogens, that’s what you wanna know, you wanna know, “Is there C. diff or is there Enterohaemorrhagic E. coli or is there Yersinia or is there whatever the organism is?” Not only, “Is it there, but how much is there? And is that amount considered clinically-significant enough to warrant you taking a treatment intervention step?”
And while they’re using this worldwide now at, you know, all the Centers of Excellence in their pathology labs to identify and determine if you’re gonna treat a pathogen, what we’ve done is use this technology across a much broader type of stool analysis or a GI microbial assessment, which we call the GI-MAP. So we’re looking not only at pathogens but also commensals or beneficial organisms, and also a whole host of opportunistic organisms, including specific sections on autoimmune triggering organisms.
So organisms that we know can be associated with molecular mimicry. And this goes across bacterial, viral, protozoal, Hellman, fungal, you know, across all those organism types in those categories, pathogens, commensals, opportunists. And then, added onto that, of course, which you don’t get in these Next-gen sequencing research tests are the stool chemistries, things that answer, “Is there inflammation in the gut? Is there leaky gut? Is there blood in the stool? Is there beta-glucuronidase? Are you making digestive enzymes from your pancreas? Are you absorbing your fats?” All of those questions are clinical queries that are not answered on a uBiome metadata test. So the qPCR GI-MAP was designed for clinicians at the point of clinical care to make decisions.
The other tests are interesting. They answer larger global questions of diversity, abundance, and they develop meta-signatures of the microbiota. And those are very necessary and useful because it’s from information extracted from those Next-gen sequencing tests that are reported in the literature that then drive decisions like, “Which bugs do we actually go after with quantitative PCR and add to the GI-MAP?” So they’re just by intention very, very different animals.
But the test is meant to give you things that you need to know as a clinician, and things that are actionable, that you can actually change, that will drive decision-making not a whole bunch of data that might be interesting to throw into a supercomputer for a researcher but it’s a clinical test. So I hope that kind of clarifies it a little bit.
Nikolas: Oh, yes, definitely. I was very pleased to see the recent addition of Epstein-Barr virus and Cytomegalovirus because I know our practitioners out there will benefit a lot from that, who are working with patients with autoimmunity and, of course, things like chronic fatigue syndrome and other issues, so.
David: Yup. You know, it’s interesting that clinicians are even in integrative world are certainly aware of that fact that if you have a lot of ubiquitous viruses like EBV and CMV going on in a sort of a stealth fashion, the subclinical, which you can detect with antibody tests in the blood, those organisms are also much higher represented in the GI microbiota. So we take advantage of that fact and actually report them out on the GI-MAP test as well.
Nikolas: Right, right.
David: And, you know, what allows us to get a lot more detailed on a lot of these organisms down to the genetic characteristics on whether they can produce a toxin or not, whether they have the virulence factor production or not is that unlike the Next-gen sequencing test, which really utilizes what’s called 16S rRNA analysis, they’re looking at a specific structure or part of the ribosomal RNA of these organisms to identify them down to the genus level basically. But the 16S characteristics are conserved across lots of different organisms and are similar or the same across multiple species in the same genera.
So we go beyond 16S rRNA. We’re using 16S rRNA in many cases but we’re using 23S rRNA, we’re using RNA in the case of viruses, we’re using SNPs, we’re using specific gene patterns for virulence factors. So depending on what the organism we’re dealing with, what question we’re trying to answer, we’re using the best methodology and zeroing in on the right segment of the genome of the organism to answer that question. Where Next-gen, you know, automatic, you know, sequencing is just an automated process just using 16S rRNA.
Nikolas: And one last clinical question just for our practitioners, when are you generally recommending retesting after putting together a comprehensive treatment plan for a patient?
David: Well, that’s a good question. It sometimes comes down to what organism you’re dealing with. Is it an overt pathogen? Is it just an opportunist? Is the patient, you know, symptomatic or not, right? If they have ongoing diarrhea, let’s say, that’s sort of different than just finding an overgrowth pattern of an opportunist that puts them maybe at greater risk for developing an autoimmune disease down the line but they have no GI symptoms. So it’s somewhat of a clinical decision case-by-case but generally speaking, if I have a dysbiotic pattern, I’ve a bunch of opportunists overgrowing, and maybe I have moderate elevation, even a DNA of a specific pathogen, I’m usually intervening. And when we intervene to try to actually get rid of organisms, we don’t tend to use prescriptive agents even in SIBO I rarely use a Xifaxan or Rifaximin or something like that because we know that that sort of obliterates the entire landscape, and then trying to reestablish a good composition later is very hard, and they tend to slide back to where they were before you used the agent.
So in things like SIBO, when you look at the clinical outcome studies on Rifaximin and Xifaxan and when you talk to patients that have used them, even the patients who respond well to the medications, and that it reduces their symptoms, and they feel better, it tends to all come back in a couple of months versus when you use the classic antimicrobial botanicals, volatile oils, and things like that that we use more in functional medicine, you tend to actually get a better effect, particularly when it comes to treatment persistence. So they stay better much longer because you’re really knocking things around more functionally than just obliterating everything.
And we know that those botanicals and the volatile oils that we tend to use in our kind of medicine are very interesting. And they have long traditional uses, of course, but and the people who first started using them didn’t know what I’m about to say as far as what bugs, how they act with different classes of microbes and stuff like that. They just know that when they use those botanicals that people that had a gut problem seem to fare really well when they used other stuff, they probably didn’t.
But if you’re using berberine-containing botanicals, for instance, Barberry or Berberis vulgaris or any Berberis aristata or if you’re using Caprylic acid or a grapefruit or citrus seed extract or Juglans nigra, Artemisinin, and Tribulus. I mean whatever you’re using as a classic GI anti-microbial, most of those things are dose-dependent on how they behave with different microbial communities. And it usually takes a heck of a lot more of those agents to kill commensal organisms, like Lactobacillus, and Bifidobacterium, and all the good guys. It takes a lot less of it to kill pathogens and opportunists actually. So that’s why they’re kind of the perfect agents, they are selective. Could they kill some of the good guys? Sure, they kill some along the way but usually, you have to go a lot harder and heavier with them to kill the commensals than you do the bad, the ones you’re trying to get rid of. So in that case, they’re very, very good agents to use.
So we’ll usually use those types of things or I use combinations of those, you know, I use a sort of a formulary, put together a product that has a lot of those things along maybe with an oil of oregano kind of separate pearl, away from meals, maybe TID like three times a day. And then, I’ll keep giving them, good potent probiotics with meals during that same time and for a couple of weeks after. But oftentimes, I’ll do that antimicrobial protocol for anywhere from three weeks to even four weeks, depending on the kind of organism. And then, I’ll usually give the person probably a good month of a washout period before we test again. And if the only thing I found on a GI-MAP, a comprehensive GI-MAP list, let’s say, a pathogen then when I’m retesting, sometimes I’ll just do the pathogens profile which is smaller, less expensive, and so forth.
If the things that were aberrant, I need to do a full GI-MAP on repeat testing I do. If I had a very minor dysbiotic pattern with not particularly virulent organisms, and the patient was a little bit symptomatic, like IBS and we treated them with that kind of regimen I just talked about and they feel entirely better, I mean remarkably different, and better, there are times I don’t even do a retest. So it really depends.
Nikolas: Right, right. Well, that’s a really great overview of everything. I’m definitely excited about the tests and I do recommend it for any of our practitioners listening. And if you’re a patient, definitely talk to your practitioner about running this test.
David: You know, what’s nice, Nick, also is, you know, while you have all of that high-tech molecular qPCR look at the microbiota, you also get a really good chemistry some chemistry section with things like not only total secretory IgA from mucosal immunity, but anti-gliadin secretory IgA to see if at the mucosal level, if they’re intolerant or not immuno-friendly, let’s say, with gluten and gliadin-containing grains. You know, you’re getting things like calprotectin for inflammation and potential infection, digestive markers with Elastase-1 for pancreatic exocrine output and steatocrit for fat in the stool. Beta-glucuronidase to make sure particularly in the female patients, you don’t have a resident population that’s producing glucuronidase and deconjugating estrogen, for instance, and contributing to estrogen dominance and breast cancer risk, you’re getting a referendum on blood. But also, the one add-on to the GI-MAP is fecal zonulin, so it’s the most direct laboratory measure we have of an objective marker for leaky gut or hyperpermeability, which is much better than looking at serum zonulin, which has some issues. But fecal zonulin is the best we have right now.
Nikolas: Very comprehensive. So I think the labs definitely covered it all with this test. So where would you like people to learn more about you, and your books, and your practice, and then anything you’d like to add regarding the Diagnostic Solutions Lab?
David: Yeah. Thanks. Well, if they wanna know more about me personally, you just visit my website at drdavidbrady.com, so D-R davidbrady.com. And if you go to the Media tab, there’s all kinds of articles, and interviews, and all that but those two papers that I mentioned in, “Townsend Letter,” and the one you mentioned in the Open Journal of Rheumatology and Autoimmune Disease, they are there in full-text PDF if you’d like to have those.
If you wanna learn more about the GI-MAP molecular qPCR stool analysis from Diagnostic Solutions Lab, you can just go to diagnosticsolutionslab, no S, diagnosticsolutionslab.com. And when you are there, there’s all kinds of resources for the clinician, including a full scientific whitepaper, there’s webinars with me, there’s webinars on going through the tests analyte by analyte with one of our PhDs, and there’s other kind of scientific information, and papers, and all kinds of things.
And there’s an area there where you can order kits, you can sign-up to be a provider for the tests, and they offer full technical support, so the first couple tests you can do, you do please call in, and have one of our technical clinicians go through the results with you, and then on an ongoing basis, as you need after that. And it’s the cheapest, you know, it’s the cost point is very, very attractive, the turnaround time is very rapid, there’s third-party insurance billing. So it has a lot of advantages over the other technologies that were around before it.
Nikolas: Excellent. Well, I appreciate you coming on, taking the time to share all this with us.
David: Hey, my pleasure. I really admire and appreciate all the work you do. And I’ve followed you your whole career. And we both go back to TCC in the beginning and you do proud.
Nikolas: Yeah, yeah. We definitely go way back. Well, thanks again. And for everyone listening, I’m going to post all the show notes on drhedberg.com. And I’ll also be posting a transcript with all the links and everything we talked about today. So thanks for tuning in, everyone. And take care. And I will see you, at the next podcast.
Here is Dr. David Brady’s paper on autoimmunity:
===> Molecular Mimicry, the Hygiene Hypothesis, Stealth
Infections and Other Examples of Disconnect between
Medical Research and the Practice of Clinical Medicine in
Here is a link to Diagnostic Solutions Laboratory:
Dr. David Brady’s website:
Dr. Brady’s book on Fibromyalgia: