Episode 56: SPONSORED Advances in Stool Testing: The GI-MAP™ GI-Microbial Assay Plus with Tony Hoffman

Diagnostic Solutions Laboratory

5895 Shiloh Rd Ste 101
Alpharetta, GA 30005

Phone: (877) 485-5336 | Inquiries | Website

I had loads of fun taking a tour through the wonderment of DSL GI MAP test today with Tony Hoffman, CEO of DSL (and longtime friend of mine!). DSL’s GI MAP stool test is, as CEO Tony Hoffman states, “a clinician diagnostic tool,” not a microbiome test. Yes, of course the GI MAP looks at the microbiome, but it’s not a broad sweep of the myriad bugs taking up residence. Rather, it’s a carefully curated investigation of organisms with demonstrated imbalance potential, be it pathogenic or dysbiotic in nature. The test is designed to be user-friendly, interpreted rapidly, logically, providing clearly actionable data that, when addressed, gets results. I’ve known Tony for years – we were both involved in the development of the first stool test using PCR analysis offered to clinicians. He’s brilliant, fun to listen to, and offers loads of pearls in this conversation….

I am not aware of another individual who has been involved in comprehensive stool testing as much as Tony. From his college days in a hospital microbiology lab to this terrific podcast where he shares the benefits of DSL’s diagnostic tool, you will find a breadth of useful information from one of the top sources in the field. Take a listen, share, comment, and give us a thumbs up wherever you listen to New Frontiers.

Tony Hoffman is a functional medicine veteran who specializes in understanding the intersection of microbiology and technology. He has launched several successful stool analysis labs, including his current company Diagnostic Solutions Laboratory. He is an expert in the ecology of the gastrointestinal microbiome as measured both by traditional culture techniques and next generation DNA analysis. In this episode of New Frontiers, Dr. Fitzgerald talks with Tony Hoffman about new advances in stool testing, how to use test results to improve patient outcomes, and the limitations of stool testing.

Show Notes Links:

GI-MAP Test 

Diagnostic Solutions Laboratory 

GI-MAP Interpretative Guide

Dr. Kara Fitzgerald: Hey everybody, welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine, and today is no exception. If you like what you hear please, please, please consider jumping over to iTunes and leaving a review. I would be most grateful. So today we’re talking about stool analysis, functional stool analysis, with somebody I’ve been working with for most of my career. I know I’ve had the privilege of talking to a lot of my friends, and today we’re going to be talking to Tony Hoffman, who you probably know as the founder of Diagnostic Solutions Laboratory. But really he goes way, way, way back, and he’s a good friend. He’s got just loads and loads of behind-the-scenes laboratory pearls, as well as really clinically friendly tools and pearls for us.

Anyway, let me give you some of his background, and we’ll jump right in. Tony started his career in the integrative laboratory industry over 20 years ago, first as a laboratory tech in microbiology, then moving into technical support sales and finally business development. Tony was at the forefront of the planning, management, and launch of four successful stool analysis labs, and with ownership in two of them before he founded Diagnostic Solutions Laboratory. His experience spans every aspect of laboratory operations from the laboratory bench to the CEO’s desk. Tony has lectured and supported physicians around the world in understanding the utility and interpretation of stool testing. He’s an expert in the ecology of the gastrointestinal microbiome as measured both by traditional culture techniques and next generation DNA analysis. This broad base and depth of knowledge has given Tony a unique perspective into the needs of clinicians, and has guided him in the development of cutting-edge test profiles for Diagnostic Solutions Laboratory. Tony, welcome to New Frontiers.

Tony Hoffman: Thanks, Kara. Thanks for having me.

Dr. Kara Fitzgerald: Absolutely. It’s just really great to talk to you, and I want to say this bio that you’ve constructed is really spot on. I mean your background is extraordinary. One of the things I’ve loved about you forever is that you’ve got a really savvy tech background. We’ve spent the last half an hour just catching up, but you always translate that into something that’s clinically useful. You and I know each other because we both were at Metametrix together, and I was steeped in lab. But now I’m wearing my clinician’s hat, and I find that I appreciate your ability to bridge all that much more as I sit in the clinician chair more often than not. I know I’m yapping too much here, but I want you to just give me a run through of a little bit of your background. You’ve been doing this for a really long time. You started with culture, and now you’re in next, next generation DNA analysis. Just give us a little historical tour before we jump into the rest of the podcast.

Tony Hoffman: I started as a lab tech in a hospital setting, and that didn’t last long. Ended up at…back then Great Smokies, which is now Genova, in Asheville where I grew up. Microbiology when I was in school was my favorite class. I don’t know a lot of people that say that, but I really enjoyed it and I was good at it, so if you excel at something you really…It makes it a lot easier. So, initially of course you start with…You were talking about 25 years ago. Start with culture and microscopy, because that was the technology that was out. We had some EIA tests that are useful and needed, or certainly were back then, to help identify some pathogens a little bit better, et cetera. But that was the technology, and so you do the best you can with the technology you have. Over the years though, the technology has changed quite a bit, and you can’t always just jump on a tech platform, but you certainly look for changes.

But so anyways, I worked in the laboratory, mixed chemistry, microbiology, parasitology, went into tech support as you mentioned, but I’ve always just had this desire to teach. I like teaching people. I think that kind of goes toward what you were saying, that I do a fairly good job of taking some complex things and plating them out in easier-to-use format that has served me well. I know that’s a strength, so I play to it, right? That’s a strength of mine.

Dr. Kara Fitzgerald: Right.

Tony Hoffman: I’ve worked in multiple labs, and because the technology … Because I’m a lab tech also, I understand what goes on in the laboratories. I always stay up on it. I haven’t sat at the bench in years, but I know the technology and I keep up with the technology, and that’s helped also as we move forward in life, in changes in technology, et cetera. Bridging all that together. It’s just a desire or passion of mine too to always see if we can find the best test that we can produce, and usable…

Dr. Kara Fitzgerald: Yeah.

Tony Hoffman: Friendly to a practitioner. That’s really what it comes down to.

Dr. Kara Fitzgerald: Yes. Yeah, that’s exactly right. I agree with you. Let me just say one of the things that Tony and I were talking about off air is a microbiome, a broad microbiome analysis versus a clinician diagnostic tool. That’s how he differentiates what Diagnostic Solutions is doing as compared to say, a company like uBiome that’s really casting a wide net around the microbiome. He would describe that test as a wellness investigation. Maybe something you do at the end of the clinical journey, or somebody if you’re working with patients with a more wellness bent, that he was just stating that he thinks that tool would be really useful.

Whereas for most of us clinicians actively working with people with tough guts, and we see incredibly tough guts these days, DSL is really a clinician diagnostic tool. Tony, just that little soundbite really crystallized two of these stool panels that we’re sort of debating amongst each other of which one to use. I do find DSL to be … It’s just really user-friendly, and I want … You guys are growing by leaps and bounds. I know 2018 was a really amazing growth year for you. I know you’ve adopted some advanced technology, and you’ve recently transitioned into a whole new type of PCR. Can you talk to me about some of the technological updates going on over there?

Tony Hoffman: Sure. So maybe a little background, because understanding a technology and what it’s really capable of doing it, and using the technology for what it’s actually capable of doing is the most important thing. There’s multiple different technologies for looking for bugs and finding them, some better than others, and utility of method is important. Overall, we’re talking about there’s culture and microscopy out there.

Dr. Kara Fitzgerald: Right.

Tony Hoffman: Some advances have been made to the identification of the organisms that they culture by using MALDI-TOF, which looks at proteins in DNA to try to identify an organism. You still have to grow the bug, and there’s limitations with culture on growing a bug, because that organism had been pulled from the microbiome of the host where it’s got a very set nutritional diet based on the host’s diet, and its neighbors that are also feeding those bugs. It has to transport to the lab, and it doesn’t like to grow. We talk about that a lot. People ask us culture versus DNA.

So yeah, you could play something, and you’ve probably seen this on a culture technology. You place them down. You get a no growth for lactobacillus, or a no growth E. coli, and you just know that it’s not remiss of lacto or E. coli. It’s not negative. They just couldn’t get it to grow. Then you can’t quantitate that. So what does a three plus mean, or a four plus? It really doesn’t tell you how much something is there. We really need to know, because ultimately it’s about overgrowth.

If I were to take a pound of stool and measure every single bug in there, we can find almost anything in very trace amounts. Organisms don’t become a problem until they become an overgrowth, until they’re at a high enough threshold. That’s important. Quantitation is key in helping to diagnose something. We’ll come back to that in just a second, but now moving onto other methods, which would be something like a next gen sequencing when you’re talking about doing a microbiome panel. That’s another DNA-type method where they go and look at the sequence. They pull all the genomes apart, and they look at the sequences there, and find the sequence that tells them what organism is present.

They’re really not truly quantitative. They’re probably semi-quantitative methods, so they can give you a good rough … They’re getting better and better. Technology is always changing. But they give you a good estimation of balance of flora across a wide range of them, but they still limit in what they can find. Ultimately, if you’re missing an organism there it doesn’t mean it’s necessarily negative. They just couldn’t get it to show up. There’s some limitations. It’s a great technology. It’s an emerging one. It’s going to get better and better over time to look at more and more organisms all at once.

But in the realm of a patient who comes in and presents with a set of symptoms that you know relate back to the gut, and to a specific set of types of organisms, which is what we do, you need to be able to quantitate that, and really determine whether or not that organism is at a level, or any organisms, certain groups of organisms are at levels that would contribute to symptoms or disease. The GI map profile that we run at DSL is really centered around patients that present with chronic and more towards acute symptoms or ongoing disease processes that you want to make sure you’re not contributing to their symptoms from the GI.

That’s a type of assay that we’ve developed, and in the technology QPCR, quantitative PCR, also known as real-time PCR. You get a very quantitative number. You can measure down to a cell per gram. That low. It’s very sensitive, both on the low and the high end, so you can get real true numbers, and you can understand whether or not the pseudomonas that grew out of four plus … You don’t know if that really is there in a high amount. That’s a technology issue barrier. It may only be in what we would report as E1 or 10 to the first, which might be 20 cells per gram. In which case, now we know that’s pseudomonas. But it might’ve grown to a four plus on a plate in the laboratory. That’s hard to show in an audio recording.

But ultimately that makes a decision, because now you know to move to something else. That’s why we’ve grown and been very successful in technology. But certainly, there’s a time and a place for a culture and microscopy. But ultimately, if you’re looking at any research past 20, 25 years, you can’t find any research that’s been done using that technology. No real outcome studies or research has been done using culture technology for a reason. We’ve had DNA for a long time. It’s just a matter of harnessing DNA technology in such a way that you can get actual results too as a clinician.

Dr. Kara Fitzgerald: All right. Listen, I want to just summarize it, and then you just correct me if I’m wrong or add color commentary. But I just want to summarize what you said, because I think it’s incredibly important. Okay, so you talked about next gen sequencing. They’re using this for the broad investigation into the microbiome overall. There are the microbiome tests. But they’re semi-quantitative, so you’re not going to really be able to determine, at least at this point in the development of these particular assays, you’re not going to be able to determine whether the presence of a particular organism is at levels that we need to be alarmed about as clinicians, or we need to get in there and do interventions around. That’s the microbiome analysis, which you think is useful, and will continue to evolve, and is a good wellness check. I like that.

Then you talked about culture, and the fundamental challenge with culture you outlined two things. One is that it’s an artificial environment, even in transport. The microbes need to be viable through the transport journey, and then at the lab where they’re plated, and they’re grown out in an artificial environment that doesn’t reflect the host gastrointestinal tract, so the host microbiome as well as what the host diet, et cetera. So because of this, there are multiple steps in the journey of the culture assay for error. Then the end result could be that X amount grows out in a plate, and that’s reported, and that doesn’t actually reflect what’s going on in the host.

Tony Hoffman: Yeah. Correct.

Dr. Kara Fitzgerald: Okay, got it. Now you guys have moved into quantitative PCR work. So since this test is a clinician diagnostic tool, the DSL test, you’ve actually selected organisms and associated biomarkers that are clinically relevant to determine what’s going on with the gut. The focus using the quantitative PCR is to actually be able to tell quantitatively what’s going on, and whether this is relevant to what’s happening clinically in the patient.

Tony Hoffman: Yeah.

Dr. Kara Fitzgerald: All right.

Tony Hoffman: That’s absolutely correct. It’s all about the overgrowth. It’s all about how much of an organism there, and an opportunistic type organism, right?

Dr. Kara Fitzgerald: Yeah.

Tony Hoffman: It’s about how much.

Dr. Kara Fitzgerald: Let me ask you this, then. Let me ask you this, because we run DSL here all the time, so we’ve looked at … I’ve looked at many, many, many reports. You actually have reference ranges for some of the pathogens, so I can see evidence of C. diff. I can see toxin A or toxin B, which is … alarm bells ring when you see this, but you might actually pick up toxin A or B below what you consider to be an acceptable finding. Just comment on that. My alarm isn’t ringing. I’m okay with this.

Tony Hoffman: Well, no. I think understanding the reference ranges for different types of organisms is important. Ultimately, the pathogens that we report, the true pathogens, over pathogens that you see on page one of our report, the call range is a high call range. It actually correlates back to another previous DNA method we ran that was an FDA-approved method that only called positive when an organism was a high enough threshold to correlate to disease. They spent a lot of time, energy and money to correlate what level should an organism be at, or most commonly at, when patients present with disease. In most cases, diarrhea, right?

Dr. Kara Fitzgerald: Yeah, right.

Tony Hoffman: The high calls there are for that, but there’s a couple things that go on. Those are only pos/neg. You can’t even report a number. We could see it. We knew it was there. We used to run this method, and we knew it was there, but it was just below. What if it was only three percent below that threshold? We literally were not allowed to call it positive because it was three percent below the cutoff level where they say it’s predictive of disease. Positive negative predicted value. Ultimately, as a clinician, especially in functional medicine, do you want to know if a patient has…

Dr. Kara Fitzgerald: C. diff toxin A.

Tony Hoffman: Well, we’d say 10 to the second of C. difficile in their microbiome as a resident communal population, which is another key thing we teach all the time. When an organism gets to about 10 to the second, E2, it’s most likely at that point a resident communal population. It’s going to stick around. You’re not going to overgrow it in your microbiome, because we get exposures every day. If you’re eating and breathing, you’re exposed to 80% of what’s on our test. Again, we already said they’re all there in trace amounts all the time. It’s about the overgrowth.

Dr. Kara Fitzgerald: Yes.

Tony Hoffman: C. diff is a great example. We talk about C. diff a lot because there’s two things that go on there. Number one, how much is there? If you get over the reference range and it flags high, now you’re at the level that you would likely have diarrheal disease if the organism were actively producing toxin. We measure the SNP on the genome of C. difficile for toxin B or toxin A. The SNP. We’re not measuring the toxin, which is another important thing to note, but still important in my mind, and our clinicians tend to agree once they understand. That gene could turn on at any point in time, and you become symptomatic or diseased. In fact, administration of antibiotics will cause that to happen. That’s why you get antibiotic-associated diarrheal disease from C. diff.

Dr. Kara Fitzgerald: Yeah.

Tony Hoffman: It was already there. Different than nosocomial, going into a hospital where you acquire it, but it was already there. Now it’s going to grow faster, and part of turning that gene on and producing that toxin, which causes inflammation for us and diarrhea, allows it to grow. It’s a protective mechanism, and a growth mechanism for the organism. But I want to know if it’s there, because I want to get out of my microbiome, or at least get it to that undetectable level again so that I don’t have disease if I happen to have to go on an antibiotic or some other influence that can trigger that gene to turn on, or that SNP to turn on and cause me symptoms.

Dr. Kara Fitzgerald: All right. Let me…

Tony Hoffman: That’s the chronic patient. Your chronic patient comes in and has it there. That’s different than acute, right?

Dr. Kara Fitzgerald: Yes.

Tony Hoffman: Hospital labs all around the country can run a pathogens panel by DNA on an acute patient. We don’t expect that to come into our laboratory as much. They can get that almost anywhere. There’s probably 200 locations that run a DNA test for microbial pathogens now.

Dr. Kara Fitzgerald: Right. Yeah, I think we can get it through standard reference labs. Okay, so listen. I want to summarize, because you just made an outrageously … A bunch of really important points. The reference ranges, the way that we’re using the reference ranges on the … At least the pathogen section. We can talk about the rest of the test, but is not that it’s normal if it’s below the reference range. Basically, what you’ve said is the reference range is a cutoff where disease is likely to be seen if above, so C. diff colitis if it’s above.

However, I’m actually looking at a patient’s result in front of me now, and she happens to have Vibrio below the reference limit, but she’s got Vibrio hanging out in her gut. It’s not bolded. It’s not in red, but there it is. This particular patient, her gut is actually doing pretty well, but she’s got this critter hanging out. It’s at E to the two, or 10 to the two, which stated is suggestive of likely colonization. This is not just passing through. That’s another really important point you made. Off the cuff you made this really important point that E to the two we should really be flagged about, because in the event that she does have an assault on her gut, which it seems like we all do potentially, this Vibrio could actually rise to becoming a pathogenic player.

So, in my work with this patient, I want to be working on disappearing it. However, because she doesn’t … She’s not in an acute disease state right now, I don’t necessarily need to go in there with big gun interventions. I can do this, as you pointed out earlier in our conversation, diet being this massive leverage point. That could be one of my tools, making sure it’s varied, and making sure she’s got pre and probiotic foods, et cetera. Maybe I would use some botanical combination interventions. I don’t need to go in there with heavy hitters though, I’m assuming. I want your feedback on that. Is this the correct way to interpret the pathogen section?

Tony Hoffman: Well, yeah. Obviously, we would take the entire report into account, because there might be another reason why you might need to go in there with botanical antimicrobials, which would be appropriate for any of the bacteria on page one also, in which case then you’ve already made a determination that that’s the route you’re going. But in absence of any other problems foreseen on a report, and if it’s just isolated to that Vibrio at 10 to the second, yeah, you might want to do pre probiotics, diet, whatever, as an intervention. Generally, some of that’s going to be determined based on looking at some of the normal flora too to see is that in balance or out of balance.

Dr. Kara Fitzgerald: Balance, right.

Tony Hoffman: Each organism is a little bit different. In the case of Vibrio, we don’t see it all that often. Why it’s not that common in the US, and it is in shellfish. That’s the most common way we get inoculated with Vibrio. Think about this too. If somebody has mild diarrhea, similar maybe from food poisoning in the case of Vibrio, but they don’t have full-blown diarrhea, but they have a couple bouts of loose stool, they may not have had much inoculation, and the body’s defenses create diarrhea to flush it out. That may be on the way down. Ten to the second, E2 is where you think this may be a resident communal population. Most likely it is, especially in a chronic patient.

That’s a big differentiation too. When patients walk into your door with chronic symptoms, that microbiome is much more established and in a steady state then after an episode, whether that be after antibiotics, whether after diarrhea or some other event that would cause a big fluctuation in their microbiome. This is a key point I make a lot with practitioners is when they walk in, they’ve been in that steady state and chronic for how long. They got a real stable microbiome, albeit dysbiotic. It’s stable.

When you intervene with a diet change, with pre and probiotics, antimicrobials, antibiotics as needed, or other pharmaceuticals depending on the patient that’s in our care, now you’ve disrupted that microbiome purposefully to get an … To hopefully get the outcome you’re looking for, which is reestablish a steady microbiome that’s not dysbiotic. It’s removed of any opportunistics, and pathogens and whatever, but that period of time post-intervention that it’s in flux, you’ll get a lot of ups and downs in bugs for a few weeks until it becomes stable and steady again.

We don’t even suggest repeating a test for three to six weeks, because you have a microbiome in flux, and eventually … This is just literally due to the fact that you change and shift the amounts of organisms, and your normal flora will get back to where it wants to be, and if you do a good job you’ll get back to where you were … Balance of good microbes to where you were when you were around three or four years old in a balance of percentage when you’re healthy.

Dr. Kara Fitzgerald: Interesting.

Tony Hoffman: You get back to that steady state. Now you have protection, colonization resistance against these overgrowth. It is important to know how the patient’s coming into you, whether they come in acute or chronic. That tells you a little bit more about that microbiome and what you see on a report. There’s many facets that you have to take, so it’s not like you can just look at a report and go, “Hey, there’s C. diff tox B at 4.3 E4 disease.” Well, no. Is there inflammation? The calprotectin looks normal, and they don’t have diarrhea. They have the potential for disease, and much higher potential than somebody without it, so you intervene a little differently than if somebody has acute diarrhea.

Dr. Kara Fitzgerald: So, A: we’re taking clinical history into big primary consideration. B: we’re looking not just at the pathogens, but what are the predominant, what are the good bugs looking like? Do we see evidence of inflammation going on? Do we see pancreatic exocrine function happening? It’s a comprehensive stool analysis. We need to look at the whole picture. I get it. As you pointed out earlier, generally speaking, when we’re using this particular tool we’re looking at folks who’ve got chronic issues happening.

Tony Hoffman: Yep.

Dr. Kara Fitzgerald: Again, as you pointed out, looking at this entire picture is going to help dictate what type of interventions we’re going to use. The other thing that you pointed out is that it’s just not worth it to retest while we’re changing the guards, while we’re really, really actively changing the microflora. I would imagine things could show up crazy during that, you said, three to six weeks, but I think it can be even longer.

Tony Hoffman: Sure. Yeah.

Dr. Kara Fitzgerald: So, if you retested while you’re mid-therapy, I would imagine you could get some pretty crazy results. Listen, so-

Tony Hoffman: Oh, yeah.

Dr. Kara Fitzgerald: … during that time when we’re seeing massive flux in the microbiome, this would be obviously when we might be preparing the patient for die off presentation. Is that really common in your experience when you’re changing the guards like that, or is die off something that can potentially be avoided? I know this is a little sidebar of a question, but I’m curious what your opinion is.

Tony Hoffman: Yeah. I mean I don’t think you can fully avoid die off without having a prolonged treatment approach. You can do things to mitigate the effects of die off. Every patient’s a little different. Some people react to die off much, much stronger than others. Literally, die off is the toxins within the cells that get released as they’re killed, and the cell wall disrupts. A portion of that interacts with mucosa, and that comes through the mucosa, and can cause obvious symptoms. Depending on the treatment approach, you’re going to get more die off with a stronger treatment. You go in with an antibiotic, or an antifungal in the case of a pharmaceutical antifungal in the case of candida, which is notorious for die off effect.

You’re likely to get much stronger symptoms of die off with that than you would, say, with a botanical. Botanicals don’t work quite the same. They are fairly caustic chemotaxic to the organisms, but they do it at a much slower rate, and shift the metabolism organisms partially too. It’s not all about killing. It’s about slowing down their metabolism, making them not function as well, and lets your body work on things. There’s different approaches needed for different patients, whether you can prescribe or not. Ultimately, if a patient’s symptoms are manageable and you can go botanically, that’s a good route to go.

But then you also have to think about how compliant is a patient going to be, because these treatments can take a lot longer. There’s always meeting the patient where they are, and what their needs are. If you already know they’re sensitive a lot, and they’ve had die off from SIBO, or they’ve had die off from candida or something, then you know you might want to prep them for it and take it slower. There’s not a lot you can do when you’re trying to remove it. You have to kill some organisms. It just depends on what their symptoms are. If they get muscle aches, you can use some amino acid therapies to help minimize some of those. Some detox to help minimize that. It’s really the whole picture. There’s just not a one-size-fits-all to what we do, and that’s why we do what we do, right?

Dr. Kara Fitzgerald: Yes.

Tony Hoffman: It’s personalized.

Dr. Kara Fitzgerald: Yeah, that’s right. Yeah. It makes it really satisfying. I mean just listening to you unpack these ideas, it’s … Folks listening who are clinicians who can witness the complexity of our medicine. These are action decision points that we’re making with all of our patients all the time. It’s really pretty extraordinary. Listen, I want to ask you a question that I’m asked often, and for which I didn’t find a whole lot of data. Maybe some, but that is botanicals having a lasting impact on the predominant microflora like antibiotics do. We know that some research out there on antibiotics can show that they alter the microbiome for years to I think a lifetime has been some of the claims, if I’m not mistaken. You can correct me. You’re in the science around this more than I am.

Tony Hoffman: Yeah. No, most especially if taken … Antibiotics that are taken in the first two to three years of life. There’s three major negative impacts on a person’s longterm microbiome composition. Those happen during the first three years or at birth. Bottle versus breastfed. Antibiotics during the first three years is a real big one. That can have a long-lasting … Cesarean birth versus vaginal delivery. If you have a patient, when you’re taking a history, that has one or more of those negative factors, which would be bottle-fed, C section, and antibiotics early in life, they are much more likely to have GI events at a higher frequency throughout their lifetime. Their microbiome has established a more negative pattern, or just not as diverse.

There are long-term studies that show that they end up with GI issues much more frequently. We also know that they also don’t reestablish a balance as fast. Those patients are the ones who may have more trouble with reestablishing that homeostasis or colonization resistance out past six weeks, because they have a microbiome that’s established. The good thing and the bad thing about the microbiome is once we establish it in the first two to three, maybe four years tops, that balance. That’s our microbiome. So whenever we’re healthy, that’s approximately where we’re going to be.

Now we can influence that on a daily basis by a diet, shift it slightly more one way or the other. Say more plant-based diet. The bacteria it eats are going to be shifted a little bit up. More keto diet, the Firmicutes are going to be shifted a little more up. We can make these kinds of diet changes to impact ourselves long-term if we know we have a bad microbiome, and we’ve seen a pattern of it. There’s things we can do.

Will botanicals have a long-lasting influence? I think that would go back to whether or not they’re utilized in the first two to three years of life. I don’t know. I haven’t seen any real data. My guess is because botanicals, again, are not near as chemotaxic and strong as pharmaceuticals. It would be lessened for sure, but will it have an impact or not? I really don’t know the answer to it, but I would imagine it wouldn’t be near as impactful, by any stretch. That goes back to kids, and whether or not to use an antimicrobial, or to avoid too much oil of oregano during the first couple years of life. Yeah, we shy away from that because we just don’t know, right?

Dr. Kara Fitzgerald: Yeah. Right. Well, and you could use the whole-plant intervention, versus just the isolated constituents, which are going to exert more of a drug effect. I think there’s a pretty massive continuum. If I hear what you’re saying correctly, when we’re thinking about introducing antimicrobials into our adult patients, that we needn’t worry too extensively about negatively and lastingly altering their microbiome. Would you say that’s correct?

Tony Hoffman: Yeah, that’s correct.

Dr. Kara Fitzgerald: Okay.

Tony Hoffman: Going back to kids, I would be … I’m concerned about too many probiotics while they’re developing their microbiome. Because again, you’re influencing what grows there, what establishes itself early on. Surrogate probiotics, it’s byproducts of lactobacillus and Bifido influence … We know they influence the levels of certain organisms. Now they don’t stay. They’re not going to become residents. They’re surrogate. They’re going to live three to 14 days or so and die off, but their byproducts are going to influence the balance of those microbes, and if you do that too long then you’re going to influence certain populations to be more established than others. I think over time you’re going to figure out some designer … Studies are going to give us some designer probiotics and prebiotics to use them on infants. We establish a much more balanced … We’re years away from that, but even probiotics might have a negative influence at too much. Too much of a good thing. We also know that too much…

Dr. Kara Fitzgerald: Yeah, but for…

Tony Hoffman: … lactobacillus is … You get lactic acidosis in some patients. There are studies coming out of gastroenterology research that suggest too much of a good thing. They have to be used. They’re tools. They gotta be used appropriately.

Dr. Kara Fitzgerald: All right, so as usual you just said a whole lot. I feel like I have to unpack it, and underline a couple of things.

Tony Hoffman: Sure.

Dr. Kara Fitzgerald: You’re saying even though I think that there’s been some debate as to whether or not probiotics can colonize or not, you’ve basically just said they can … They might hang around for a little while, but they’re not going to take up permanent residence. As you pointed out already repeatedly in previous statements, we’re going to go back to that original blueprint that we created. So even though they don’t colonize, they’re going to be manipulating the microbiome. There’s going to be various metabolites being produced that can be problem players.

So what you said, which is a huge statement, Tony, is that we want to be mindful about introducing probiotics into youngsters, at least long-term, because we don’t really entirely understand how some of the metabolites from these probiotics, or how they might influence the core microbiome, will play out later on. Which it’s really remarkable, because as you know I’ve got a baby at home who I have on probiotics, and I’m like, “Oh my god.” I’ve got her on infant formula, but I’m like, “Okay, note to self. Let me wrap this up.”

Tony Hoffman: Well, I mean, it’s too much. Ultimately, it comes down to too much of a good thing can be bad. There’s moderation, and there’s thought given. I don’t think probiotics as a general rule in infants are bad, but if you’re trying to manipulate the microbiome, which is how we use probiotics, either post-antimicrobial to try to manipulate the growth. We’re just trying to increase the growth rate of good flora faster first to win and balance out, but you’re developing your microbiome. You’re probably better off letting her play in the dirt, and get exposures, and build an immune system, which is also developing at the same time.

Dr. Kara Fitzgerald: Yes. That’s right.

Tony Hoffman: Now that we understand the interaction of our microbiome with our own immune system, it’s complex, and it’s ongoing long term. Our microbiome even influences our IgA output, and this is really cool, to protect itself. Our good microbiome, the good commensal bugs, help us generate and produce secretory IgA on a constant basis. Not because it helps us. It protects them. It protects them, and allows them to stay adhered and colonized in mucosa by forcing us to produce all this IgA to coat every other bug we are ingesting every day so that it’s coated with IgA, and now it cannot disrupt the commensal that’s there on the mucosa. It’s a protective measure for itself, but it helps influence our immune responses too. It’s pretty complex.

Our understanding of the microbiome has grown tremendously in the past 10 years especially, and some of that is technology. Obviously, that’s really led to our understanding of it, but we’re still at the tip of it. I would suggest that 20 years from now we’re going to be having a totally different conversation. Still rooted around our microbiome, and the core organisms and everything else, but we’re going to understand a little bit more of the influence of the microbiome on the host, and the interactions, and probably that’s all going to change.

Dr. Kara Fitzgerald: I think…

Tony Hoffman: You’re right. It’s that moderation. Be mindful.

Dr. Kara Fitzgerald: I think your point is extremely well-taken. In fact, I was just reading about this UK scientist. His name is escaping me right now, but he’s … He is really accusing excessive hygiene in childhood as promoting leukemia. He feels like he’s nailed down the mechanism around this. There’s actually two mutations, one that’s in utero, but one that happens early on. Those two together allow for the occurrence of childhood leukemia. What’s extraordinary is that the antidote to this, as far as he’s concerned, is, as you said, exposure to dirt. Playing. Backing off of this hyper-hygienic world that we’ve lived in. Just very interesting stuff. Your point is well-taken. Even as we sit in this breakthrough, breakneck technological revolution, we still go back to these fundamental precepts of diet, of exposure, of building our immune system by just engaging in life. That’s not going to change what you just said, Tony. I wanted to also back up-

Tony Hoffman: Yeah. No, we have the surveillance, right? It’s just a difference of we had surveillance data. We knew we didn’t build good immune systems without playing in dirt, and establishing a good microbiome. But now we’re learning the mechanisms, and how that actually works.

Dr. Kara Fitzgerald: Yes, that’s right.

Tony Hoffman: The core things are not changing. That’s exactly right. It’s just our understanding and how we modulate those is changing rapidly.

Dr. Kara Fitzgerald: It’s very exciting. I just wanted to underline one point that you made previously. Circle back to it, because I think it’s a really important one. Many, many, many of our patients have had gut assaults. Many of our patients have been C section delivered, or they haven’t been able to breastfeed for whatever reason, or they’ve had early antibiotic exposures. That’s de rigueur in our world today. You’re pointing out the lasting impact on the microbiome. We treat patients who come with this background all of the time. I think we can take heart, and just advise accordingly, probably doing stool analysis.

Putting attention on the microbiome is just going to be a piece of their journey. It needn’t be anxiety-provoking. It’s just one of the pieces that they’re going to have to nurture along. I come into the planet with a familial background of diabetes and heart disease. One of the things I need to do in my life journey here is be mindful of excess carbohydrate. It’s just my background. Likewise, this would be that individual, just a piece of their core journey. Okay.

Tony Hoffman: Yeah, exactly.

Dr. Kara Fitzgerald: I just want to talk about the test a little bit more, because you’ve done some really … It’s just you’ve added some really cool stuff. You’ve got a comprehensive H. pylori section now. You have built that out big time. Talk to me about that, and what makes it so unique.

Tony Hoffman: Yeah. H. pylori, it’s one of the organisms I love talking about. Unfortunately, H. pylori is a notoriously bad guy who can wear many different hats, and present with many different symptoms. We’re learning now why that is. Because we’re using the qPCR technology, PCR technology, we can actually look at SNPs like we were talking about with C. diff. We can look at SNPs on the genome of H. pylori, and measure out what’s called virulence factors. Virulence factors are literally just a SNP on their genome for the ability to produce a particular toxin protein, what have you.

But each of those individual virulence factors may either contribute to certain diseases, or cause certain symptoms. H. pylori is capable of a multitude of different types of symptoms. It’s compounded even further. Think about E. coli here. Let me make a correlation. We talk about E. coli as enterohemorrhagic, enteropathogenic. Literally what that is, is SNPs on a genome of an E. coli before we knew that there were SNPs. They got named based on disease type, rather than what we do with H. pylori. H. pylori we actually named the virulence factor versus changing the name of the H. pylori enteropathogenic or toxigenic. The same thing.

Dr. Kara Fitzgerald: It’s so fascinating.

Tony Hoffman: E. coli has lots of different SNPs. It’s diverse just like H. pylori. But H. pylori is compounded, so we have the ability to measure these virulence factors to predict the potential for particular symptoms or disease from H. pylori. Just like measuring a SNP on a human genome. We’re measuring a SNP on the genome of H. pylori. You can get an understanding if the symptoms a patient is presenting with may or may not be from the H. pylori. H. pylori is a little more complex than that. Part of it starts in the colonization of H. pylori, how it colonizes in the stomach. Exposure to H. pylori is chronic and constant. We’re always exposed.

But when it does get into an overgrowth state in the stomach, initial early colonization is usually the body of the stomach. Regardless of virulence factors, there it infects the cells that produce HCl and causes hypochlorhydria, low HCl production. That’s the initial colonization most generally, most of the time. That can last from three to maybe even as much 24 months that you have hypochlorhydria. Asymptomatic. No ulcers. You don’t have acid reflux because you have low acid. No gastritis. No gastroenteritis, et cetera. Low HCl.

Dr. Kara Fitzgerald: Right. Would this be the like the SIBO epidemic that we’re in? Would this be the…

Tony Hoffman: Well, it’s contributing because H. pylori comes in and colonizes the body of the stomach. It causes hypochlorhydria. But now the stomach acid is low, which is really your only protection in the first half of the small intestine from colonization. The acid from the stomach is what … It’s not competitive like the colon. The colon is competitive. Your normal flora helps you keep things at bay. Your immune system down there helps keep things at bay. The first half of the small intestine, most of the small intestine, the populations are determined by the amount of acid you produce. When you get hypochlorhydria, then you get migration up your small intestine of organisms that normally couldn’t live there, because now the PH is higher, and allows it to migrate further and further north. Of course, you’re always swallowing things too. So yeah, many patients with early colonization of H. pylori develop SIBO, so they end up coming in with SIBO. Then we find H. pylori.

Dr. Kara Fitzgerald: Yeah. This is like the…

Tony Hoffman: Then we look at the elastase, and here’s the good thing. You can actually look at exocrine pancreatic output, look at the elastase we measure, and get an idea of potentially how far along the patient is with their colonization of H. pylori in the stomach by looking at the elastase. So if an average patient runs between 500 and 600, so let’s say 550 for example is a normal, healthy result for elastase, if that’s around 350 or less they likely have hypochlorhydria.

Dr. Kara Fitzgerald: Oh, interesting.

Tony Hoffman: It may not be below the reference range, and that’s a kit reference range, and understand labs are stuck with certain things we have to do, parameters we have to fall within. Around 350 or less, that’s suggestive of hypochlorhydria. You can almost see it. We see the pattern quite a bit too. Those patients, if I’m on a call … I like to do this with new practitioners just learning the test. I’ll look all the way through the test, and I’ll start talking a little bit. I’ll say, “Is your patient experiencing upper GI gas bloating distention postprandial?” A good chunk of them go, “Yeah. How’d you know?” “Well, I just look at the elastase, and know that probably 75% of the patients with chronic low HCl are going to develop SIBO.”

It’s an eventuality more so than anything else. If your HCl is too low, you’re going to develop it over time. It’s going to happen. You’re exposed to everything. That’s the first thing that happens with H. pylori is now you got hypochlorhydria caused by it that has nothing to do with a virulence factor. It has only to do with where it’s colonized in your stomach. The next part of H. pylori has nothing to do with virulence factors. There-

Dr. Kara Fitzgerald: Wait, wait, wait.

Tony Hoffman: Yep.

Dr. Kara Fitzgerald: If H. pylori is present without virulence factors, it’s contributing to hypochlorhydria, and it’s a problem. Is that what you just…

Tony Hoffman: It can be.

Dr. Kara Fitzgerald: It can be.

Tony Hoffman: It can literally infect the cells in the stomach that produce HCl. You remove them.

Dr. Kara Fitzgerald: Okay, so no virulence factors, but it could still be a problem because…

Tony Hoffman: Yep, correct.

Dr. Kara Fitzgerald: I generally look at it as not, as potentially being a commensal, because there was some interesting research out to that effect. But you’re actually saying it could usher in hypochlorhydria. Let me…

Tony Hoffman: Yeah, unfortunately. Let me just correct something right there, Kara.

Dr. Kara Fitzgerald: Yeah. Yeah, go ahead.

Tony Hoffman: Unfortunately, when you read literature about it possibly being a commensal they don’t give you quantitation. How much is commensal?

Dr. Kara Fitzgerald: Right.

Tony Hoffman: What’s the normal range of commensal? We don’t know. Actually, on a stool test we can’t tell you how much you have in the stomach. By the time those cells pass from the stomach and the duodenum through 2,250 grams of fecal matter, they’re diluted. We’re seeing what comes out the other end. There’s limitations to a stool test. This is one of them. We don’t know how much is in the stomach really. So certainly if you find H. pylori on a stool test, even in amounts of…

Dr. Kara Fitzgerald: It’s probably a…

Tony Hoffman: … 10 to the first, E1…

Dr. Kara Fitzgerald: It’s probably…

Tony Hoffman: … you’ve got a big overgrowth in the stomach, right?

Dr. Kara Fitzgerald: Yeah.

Tony Hoffman: H. pylori can cause hypochlorhydria just by infecting the cells of the body in the body of the stomach. Then it moves to the antrum, where it then has an effect on gastrin output. It increases gastrin, specifically gastrin-17, which increases acid production. Then it also has a negative impact on somatostatin, which means you don’t counter the gastrin so the acid stays up. You develop hypochlorhydria. Excuse me. Then you develop hyper acidemia, increased acid. Now you start presenting with acid reflux and develop GERD. That has nothing to do with virulence factors also.

Dr. Kara Fitzgerald: This is when you start to see gastritis, and ulceration.

Tony Hoffman: Right. You do the acid, so now you have increased acid. Your elastase now is back to normal levels. Now you have a whole other set of symptoms.

Dr. Kara Fitzgerald: Is that right?

Tony Hoffman: This is compounded further. Chronic colonization in the stomach of H. pylori ends up with three to four different strains. You’re colonized by one strain. It has no virulence factors. Left unchecked you’re going to get two, three more strains eventually, and you know they’re going to come in with virulence factors. Now your symptoms change. Now you develop an ulcer. Why? Because you have virulence factors that allowed for an ulcer, or gastritis occurs. H. pylori is a notoriously bad bug, and I don’t really think that there’s any commensal amount for an H. pylori that we can measure from a stool test, right?

Dr. Kara Fitzgerald: That’s pretty fascinating.

Tony Hoffman: Yeah. Understanding H. pylori … It’s a nasty bug. It is very pathogenic, and it’s going to change over time its presentation based on the different strains you end up colonizing with.

Dr. Kara Fitzgerald: Right. Geez, that’s really interesting, this continuum of H. pylori. Initially hypochlorhydria, but as it evolves and moves-

Tony Hoffman: Yeah, into the antrum.

Dr. Kara Fitzgerald: … then we’re looking at actually a hyperchlorhydric state. Are you going to still see, though, maldigestion, gas and bloating? Those things aren’t going to resolve, and then you present with ulceration?

Tony Hoffman: Those won’t resolve. Right, depending on what’s causing them you get maldigestion from low acid. Some of that will resolve when acid comes back to normal, but now you got over … Too much acid, so yeah. Generally you would presume that you would resume normal exocrine pancreatic output, so right. You go through a period of maldigestion, and then that shifts. But keep in mind, during those periods your microbiome is shifting. This is the other thing that happens with early onset, the early colonization, is that low acid creates dysbiosis all the way through the small intestine, which eventually leads to dysbiosis in the colon. Now we know that the pH of the colon is not really determined by the acid from the stomach, more by the composition that’s there. But if you have shifting populations in your small intestine due to low acid, they’re feeding into the colon. You end up shifting the colon and creating dysbiosis there in the long term on a chronic basis. So yeah, now you have dysbiosis all the way through the colon due to H. pylori in the stomach.

Dr. Kara Fitzgerald: That’s pretty fascinating. Okay. Complex, but really the take home here is that if H. pylori is showing up in a stool test you can bet that there’s a lot in the small intestines, and-

Tony Hoffman: Yeah, if they’re not presenting yet there’s … The progression is going to be through those stages we just discussed.

Dr. Kara Fitzgerald: And as far as you’re…

Tony Hoffman: But the question is then how do you treat? Then you got standards of care. When do you use a triple quadruple therapy? People like to think that you can just look. Oh, there’s virulence factors. Let me use a pharmaceutical. If they’re not presenting it’s really a practitioner’s call, and meeting the patient where they are. If they aren’t presenting with overt symptoms, you can get rid of H. pylori with a mastic gum-based formulation.

Dr. Kara Fitzgerald: You can.

Tony Hoffman: They’re pretty effective. 50, 60% eradication rate first time, first course. Now the course is longer. Compliant patient. But the other side of that is, because even pharmaceuticals are only somewhere around 70% effective first course, so…

Dr. Kara Fitzgerald: Well, and it’s really aggressive if you do…

Tony Hoffman: It is. Oh, it’s bad too.

Dr. Kara Fitzgerald: … quadruple or triple therapy. It’s horrible.

Tony Hoffman: Yeah. But then there’s standard of care. The physicians who have to follow certain standard of care, they don’t have a choice sometimes, unfortunately. They’ve got standards of care they gotta be careful with. But whenever possible, you probably have the least negative impact on the microbiome as a whole in a patient if you can use a botanical, right?

Dr. Kara Fitzgerald: Right. Well, and if…

Tony Hoffman: You’re going to-

Dr. Kara Fitzgerald: If you’re down the continuum where you’ve got some pretty significant gastritis, and if you’ve got…

Tony Hoffman: Right. You’ve gotta meet the patient where they are. That’s right. Exactly. Yeah.

Dr. Kara Fitzgerald: Okay. That’s really fascinating. You revolutionized my thinking around this, since I’ve not been as concerned around seeing H. pylori present without virulence factors. Flip the page. Do I see a nice robust elastase? But really, the take home here is that we always need to treat H. pylori as far as you’re concerned, and it’s just a matter of what we do in our intervention.

Tony Hoffman: It’s a time thing. Yeah, it’s a time thing before you develop symptoms. Those symptoms are going to be determined based on chronology, location of it, how many different strains, and what are they bringing to the party, which virulence factors are these other strains bringing to the party. It’s just a matter of time.

Dr. Kara Fitzgerald: And left…

Tony Hoffman: SIBO is probable in that first initial phase also. SIBO, as you know, is very difficult to treat. It wreaks havoc. That’s where I say a botanical intervention at that point is probably, at minimum, what you’d want to do. For me, I see any raise of H. pylori and I’ve had it. Get it the heck out of me. I don’t see where it benefits me to have H. pylori in measurable amounts, in amounts … That’s the key though. Unfortunately, we can’t finish that story out, is it a commensal or not, because we’d have to go in and do gastric aspirates and biopsies, and basic procedures to really determine that. The same thing with SIBO. It’s hard to really study SIBO in depth, because you’d have to go in and get a gastric aspirate to do so. We’ve run a lot of them actually, because we have a lot of gastros that sent them to us trying to figure it out, but you have to do enough to compile enough data to really figure out the meaning of certain populations in the duodenum.  

Dr. Kara Fitzgerald: That’s pretty fascinating. But in your opinion, obviously it’s not … I know you’ve looked at thousands. You’ve looked at more stool tests than probably anybody else in the world…

Tony Hoffman: Yeah.

Dr. Kara Fitzgerald: You’ve looked at more of the comprehensive stool tests like these.

Tony Hoffman: I don’t know what that says about me, but yes.

Dr. Kara Fitzgerald: All right, so that’s pretty compelling. We’ve got so much to cover. I just want to say as an aside, folks, DSL has a really fabulous white paper. Just very useful. Really comprehensive, and we’ll link to this on the show notes. Tony is giving us really important links for you to be able to access whatever you need over there. For further discussion on the other aspects of the test if we don’t get to them right now just grab that white paper, and that will start your journey. I want to talk to you about sensitivity testing, which you were involved in. That’s major in using culture-based technology, but you’ve moved beyond that. Just talk about that.

Tony Hoffman: Sure. We talk about doing sensitivity testing for pharmaceuticals. Those cutoff levels are well-established. Millions and millions of dollars spent to determine how much drug is needed to cause a certain amount of inhibition, to then say that equivocates to a normal dosage would be effective against a particular organism. We understand that. That’s point one.

The second part is we don’t really understand how much of a botanical is needed, because when you’re looking at zone of inhibitions there’s a couple methods you could use to test microbes against botanicals. One would be a drop disc method where you impregnate a cotton little disc, and you streak a plate with an isolated organism, and you put this filter paper disc on the plate, and you measure a zone of inhibition where it doesn’t allow it to grow, the colonization around the disc with a botanical on it, an herb.

We don’t really understand, and there’s very little change in growth around this. It’s almost microscopic that people are using to suggest this might work. That’s one part about botanicals. It’s just we don’t understand. We don’t have a way to really measure the effectiveness in vitro. The other part about it is a lot of these herbs that we can get our hands on come in a tincture. That’s antiseptic by nature to get it in solution. That might be what’s causing the zone of inhibition, which is already too small compared to a pharmaceutical’s zone of inhibition. Those are key in saying, “Okay, I don’t feel we could put out a good result.”

But the other part of it is even working with multiple labs and running these tests myself, if you called in about a botanical with a result, with a sensitivity test and said, “Well, this shows berberine would be a good choice for this Klebsiella and ammonia,” I would turn that around and say, “Yes, but it’s not a sterile site. You’re not treating Klebsiella and ammonia in absentee of the rest of your microbiome.”

The best approach to treating anything in the microbiome where you want to be the least disruptive into the overall balance is to use a multi-formulated botanical product so that you are more broad spectrum in your approach to lowering the threshold of some organisms. Sure, you’re going to kill some. Not a lot, but you’re going to kill some. But you’re also going to change the metabolism in the microbiome, which is byproducts that it’s producing, and cell division, et cetera.

You’re going to have the opportunity to allow the normal flora to overgrow the organism, which is another key thing about thinking about the microbiome, the GI tract when you’re treating something there. You get a urinary tract infection. Whatever bug’s found there, that’s probably the only bug there, because it’s a sterile site, normally. So, when you get a metabolite of a drug that can be delivered there, it’s going to kill it all. When you treat an organism in your GI tract, especially in a colon, do you honestly think that 10 days on a pharmaceutical wipes out that population of that target organism? It doesn’t. It lowers the threshold enough that symptoms may be reduced, and that you kill off enough of that population that your normal flora overgrows it to finally get it out of your microbiome as a resident.

Dr. Kara Fitzgerald: Potentially. Potentially it does.

Tony Hoffman: Right, potentially.

Dr. Kara Fitzgerald: I mean if it’s successful…

Tony Hoffman: But that’s really it. It’s just that mechanism. That’s with pharmaceuticals too. You’ve got pounds of microbes there. To think you can target one organism in absentee of the rest … Just to put it into perspective. We decided not to put botanical sensitivities on our test for that reason. Number one, we don’t feel we can get a fully accurate … It may be okay, but fully accurate picture of one bug versus one botanical.

But the second part of that is I would never recommend one botanical because it might also be selective, where some organisms are going to grow just like you get with pharmaceuticals. If you’re using oil of oregano, some organisms might be growing at a faster rate because you’re suppressing other ones. You’re creating your own shift and dysbiosis. But multi-formulate botanical will do what’s more similar to diarrhea, which is our own natural defense, which is lower the threshold and allow your larger populations, which is generally your commensals, to grow, go through cell division at a faster rate because there’s more cell division. More organisms mean they’re going to divide at a multiple higher than other things, and they overgrow it. But again, like you pointed out, there’s times you need a pharmaceutical. Go to the first choice. The Merck Manuals are there. If you have this particular bug, this is one, two, and three. That’s the way we’d suggest to go.

Dr. Kara Fitzgerald: Well, listen. As usual, you…

Tony Hoffman: The other thing. One more thing, though.

Dr. Kara Fitzgerald: Yeah. Yeah, say it.

Tony Hoffman: Talking about pharmaceuticals. We do, instead of sensitivity testing, we look at the antibiotic resistance genes. So if you wanted to know if amoxicillin worked or not, the reason that organism might be resistant to amoxicillin, or it wouldn’t work in the sensitivity test, is literally a genetic thing. We can measure the gene, the SNP on the genome of the organism, just like the SNP for virulence factors or for toxin B for C. diff. It’s genetic. The resistance is genetic. We can measure those. You check the box for antibiotic resistance genes. We will measure, like for H. pylori. You can get a phenotypic. These genes are specific to H. pylori that convey resistance to a particular pharmaceutical. You can get it as a microbiome for a number of drugs to see if there’s resistance within the microbiome. We would suggest avoiding that drug if possible, regardless of whether it’s for your organism, target organism, or not, because you’re going to certainly cause shifts in microbes if there’s already some resistance genes in the microbiome.

Dr. Kara Fitzgerald: Right, so you may not be successful in your treatment.

Tony Hoffman: Or you cause something else, yep.

Dr. Kara Fitzgerald: Yeah. You can cause some serious harm either by not successful eradicating the organism that you’re trying to eradicate, or just wreaking serious havoc, and whatever organism is allowed to proliferate because it possesses it.

Tony Hoffman: Yeah.

Dr. Kara Fitzgerald: Yeah. That’s useful. I just want to point out, Tony, you keep making these big statements just off the cuff over and over again in this podcast. I know people are going to really value it. We’ve got somebody who listens to it, and goes to the transcription, and she’s going to sweep through all of these pearls and summarize them for folks. So if you go to the show notes, you’ll see some of these really useful statements Tony’s made corralled together so that you can think about them, and think about enacting some of them in clinical practice. But one of the big things you just threw off the cuff was the fact that you always recommend using botanical combinations, and not single botanical interventions. We don’t have to circle back to it. I think you argued your rationale for that nicely, but it’s just-

Tony Hoffman: Good.

Dr. Kara Fitzgerald: … it caused me to pause again because I don’t always do that, although I do tend to rotate people, and I’m using diet. But at any rate, it’s a big thing. We’re rolling towards the end of our time here. I have two more questions. One is I think there’s some cool surprises that you’re launching, but before I do that I want … Actually, I have three questions. One is we didn’t have a chance in this conversation to cover the entire test, and so I just want to ask you about that. Then I want to ask you about how practitioners can further educate themselves, and then I want you to share with us some of the surprises coming our way. Those three questions.

Tony Hoffman: Sure. So being mindful of time, I’ll try to move through here. People are busy. Get as much in as we can, but we could do this for hours, for sure.

Dr. Kara Fitzgerald: I know we could.

Tony Hoffman: Yeah. The GI map test was, as we alluded to earlier, the type of test it is, being qPCR, we have to target what we’re looking for or we can’t see it, whereas when you do a next gen sequencing you’re blasting through anything you see. You may or may not be able to see actually, but anything that shows up you can do. Another advantage is being able to look at things like SNPs on the genome of the microbes, which is a differentiation between the methods. They can’t do that yet in the next gen-type test, so there’s some differences there. But ultimately, we have selected organisms that are well-known to either cause GI symptoms directly, or influence other diseases and other symptoms, extra intestinal symptoms, whether or not they produce LPS and contribute to permeability, or other issues with LPS.

We’ve made it a very specific selection of organisms. In fact, when we started we were on multiplex PCR, and we had a pretty good profile. When we moved to this new technology platform, we upgraded the test. We added 22 more markers to it, which included some more protozoa, and some worms, and some other autoimmune triggering organisms like MAP has been added. It’s an evolving test. The organisms we’re looking for, and the markers, and the other GI health markers we’re measuring are specific and thoughtful. We put the thought and design into it so that we could…

Dr. Kara Fitzgerald: It’s always geared toward clinical utility. That’s always your bottom question, right?

Tony Hoffman: It is. It’s meant for the patient. Yeah. Yeah, exactly. It is clinical utility, and research-driven too. There’s a lot of things we could measure. But if we don’t know if they have a direct, like you said, clinical utility impact on the patient or the host, then we’re not looking for it. This test is meant to be used in a certain way. There’s other tests you could do for other things. We never try to say, “Yeah, everybody should just get a GI map.” Obviously, a lot of patients would benefit from running it, but you use it on the right patient. Patients have limited funds, too. We never say, “Always run one.” What do you need to do? If they’re coming in with women’s health problems, you’re not starting with a GI map always. It might be part of something you add based on some of those symptoms. It’s clinical utility. The test is built for clinical utility, and we hope our practitioners use it in a proper way so that they have results that they can impact their patient with.

Dr. Kara Fitzgerald: Right. Well, to that end, Tony, what about further education?

Tony Hoffman: We have a much different test than all of our competitors, so we spent a lot of time on the phones. In fact, we have more clinical educators on staff than we do customer service reps. There’s a lot of education process that goes along with the test, which we of course offer 30 minute consults if somebody needs to. That’s always a good idea with early use adoption of the test. But certainly if you’re on our website, which is diagnosticsolutionslab.com, and you go to the top rib and you see clinicians, click that and go down to learning.

That’ll take you to our learning center, and there there are articles. There are webinars, previously recorded webinars that you can utilize. There’s the white paper you mentioned earlier, which is a very well-documented publication by 130, or 120 something literature sites. But also we put out an interpretive guide now that you’ll see on the right hand pane there that summarizes a lot of stuff, and puts it in perspective. I would point out there’s a really good webinar talking about microbiome, and the differences and stuff. There’s some patterns to note even on our test that are key.

We did a webinar a couple months ago, and it’s really understanding different … The pattern analysis, right? There are patients who come up with insufficiency dysbiosis. That’s well-established in the literature, but it’s also a pattern we see on our test, and we’ll help you walk through that versus inflammatory dysbiosis where there’s much more inflammation induced based on certain organisms and populations there. Then digestive dysfunction dysbiosis. There’s a webinar on that, and if you click on that webinar, Dr Tom Fabian did it. Just scroll down. You’ll see a hotlink there. There’s a compendium piece that you can print out that has four … It’s a four page piece that tells you which organisms belong to which groups that influence which of those three main patterns. The learning center will be your place to go to get a basis, and then certainly we’re always producing new webinars and new pieces. This podcast will be one thing. But the clinical consultations, we love to speak to our practitioners and get feedback and help them understand our test.

Dr. Kara Fitzgerald: That’s fabulous. All right, well listen. Any of those links that we can put on the show notes to guide people over to the education center and all of that content you’ve just mentioned is great. I’ll just make sure that we circle back with your team and get that.

Tony Hoffman: Yeah.

Dr. Kara Fitzgerald: Then finally, 30 seconds, what’s next for DSL?

Tony Hoffman: Well, the cat’s out of the bag already. We’re working on a SNPs panel, a human SNPs, like a 23andMe on steroids, but it’s really meant for the clinician, too.

Dr. Kara Fitzgerald: Very excited.

Tony Hoffman: We have a SNPs panel. More of a broad SNPs panel. Rather than measuring just 10 or 20 SNPs in a key area, we’re going to be measuring over 9,000, almost a million SNPs. But we’re developing, and licensed and developing software that will help us with the interpretation. Ultimately, you can measure a million SNPs, but about 5,200 of them have really actionable consequence for a patient. But still, it’s 5,200 SNPs that you would look at and go, “What do I do with this?”

The panel name will be The Genomic Insights. We don’t have an exact launch date set, but we’re close to finishing up the interface that will power this test, and make it a lot easier to bridge the gap of understanding SNPs, and being able to use all 900,000 million of them if need be. But really being able to plate that information in such a way that’s usable, but it’s also inclusive. If you just run a cardiogenomics panel with somebody, a cardio panel, most of the time you’re looking at 10 to maybe tops 20 SNPs. But you’re missing a whole lot more of the SNPs that still belong in that category based on their methodology.

We’re not limited by methodology yet again. That’s our thing. Technology is key, but also being able to deliver this information in such a way that a newer practitioner to SNPs can utilize it. We’re layering in the use of this interface in such a way that it meets the clinician where they are, but they can keep going back and learning more on a particular patient all the time. If your practice is women’s health most often, and you click on estrogen genomics, and you want to look at methylation and detox you can look at all those, and just deal with that on this visit, this encounter. But then they have something else happen to them down the road and they come back to see you a year later, you’ll still be able to go back in and look at their SNPs and say, “Oh, well now I really need to look at cardiovascular. Oh, their doctor’s putting them on something else. Let me look at their PGx, pharmacogenomics.” You can dig right back into the same patient, but…

Dr. Kara Fitzgerald: That is cool. Yeah, go ahead. Finish that thought.

Tony Hoffman: Yeah. No, but it’s put together in such a way that there’s a lot of learning there. There’s a lot of tools for learning, and if you really want to dig in deep on a particular SNP it’ll take you right out to the databases, or you can just read our synopsis, and the patient-centric synopsis of the particular SNP and the impact. But it also directs the, which nutraceuticals, which herbs, which supplements, which diets might impact your patient on a long-term basis. There’s some lifestyle modifications that are needed when you find out what your SNPs are. It includes all that. It’s going to be great. We’re hoping to bridge the gap between the 23andMe-type test, or having to take a big data file and load it up into Promethease, and try to figure out what’s going on, and curate a report that takes you an hour to do. That’s the problem. That’s solving the problem. If I said one thing I like and what I usually excel at is figuring that out, because if I can figure that out then we can take care of more patients, because now everybody can adopt the technology faster.

Dr. Kara Fitzgerald: That’s right. Again, making, creating tools that are clinician-friendly. I love it.

Tony Hoffman: Yeah, and tests that are clinically relevant, and tools that are clinician-friendly. That’s my thing. That’s what I like, and if we do that then we have a great business too. It’s a win-win-win.

Dr. Kara Fitzgerald: All right, Tony Hoffman, listen. It was great to be able to catch up with you today. It’s been a long time. Just thanks so much for sharing your brilliance with us on New Frontiers.

Tony Hoffman: I mean, thanks for having me. I really appreciate it, Kara. It’s been great.

Dr. Kara Fitzgerald: Absolutely.