The GI360 is a smart, evidenced-based stool test that is easily actionable by the clinician. Listen to my conversation today with VP of Scientific Support from Doctor’s Data, Dr. David Quig. One of the most useful tools I am aware of in stool testing is the Dysbiosis Test, which identifies and characterizes more than 45 targeted analytes across six Phyla using PCR and compares the patient results to a characterized normobiotic reference population. DDI is also using the Luminex PCR panel for pathogens, parasites and viruses – an FDA cleared panel for accurate detection of microbes that are almost always a problem. But what if they are not? Hear my discussion with Dr. Q on that. Finally, beta glucuronidase – it’s SO MUCH more complex than we’ve understood. Yes, we’re aware of the estrogen connection, but the BG story has evolved. We also walk through the chemistries – DDI includes a wide range of chems (appreciated by me and my colleagues here in our practice!). Give a listen, and leave us a review wherever you listen to New Frontiers! Thank you! ~DrKF
Doctor’s Data is well-known for offering acclaimed, time-tested, comprehensive stool analysis with second-to-none microbiology. Today, they’ve made major additions to their offerings, including molecular testing (PCR) and a more traditional gastrointestinal pathogens panel. Dr. David Quig has served as the VP of Scientific Support for Doctor’s Data for the past 23 years and, in this episode of New Frontiers, he talks with Dr. Fitzgerald about the company’s new testing capabilities, interpreting test results, and effective interventions for different types of dysbiosis.
- The addition of new, complementary technology in the testing options offered by Doctor’s Data, including PCR and a more traditional gastrointestinal pathogens panel
- How to interpret the dysbiosis index of a Doctor’s Data report
- Assessing types of dysbiosis associated with restricted diets like keto and low-FODMAP
- Identifying and interpreting the presence of specific microbes, including Lachnospiraceae, F. Prausnitzii, Eubacterium rectale, Bifido, Ruminococcus gnavus and Akkermansia muciniphila.
- Importance of soluble fiber for colonization of specific beneficial bacteria
- Different types of false positives/interpreting false positives
- Prevalence of C. Difficile in the normal adult population
- Enhanced sensitivity of Doctor’s Data tests and how to time retesting to account for it
- Comprehensive chemistries that are part of Doctor’s Data analysis
- Testing for glucuronidase as part of the Doctor’s Data analysis
- Elevated beta-glucuronidase and the elevated circulating estrogens in pre-menopausal women
- How enzymes are now being called the name of the gene location from which it came
- Dosing Calcium D-glucaric acid
- SIFO vs. SIBO
- Interventions for SIFO
- Dysbiosis and connections with overweight, obesity, and Type 2 diabetes
David Quig received his BS and MS degrees in human nutrition from Virginia Tech and a PhD in Nutritional Biochemistry from the University of Illinois. After a five year stint as a Research Associate at Cornell University, he was as a Senior Cardiovascular Pharmacologist for seven years with a major pharmaceutical company. David has been a hands-on researcher for 40 years and has numerous peer-reviewed publications. He is adamant about scientific integrity, especially as applied to diagnostic testing. He is committed to helping clinicians make informed decisions regarding the validity of esoteric lab testing in the realm of functional medicine. For the past 23 years David has happily served as the Vice President of Scientific Support for Doctor’s Data.
Marx V. Microbiology: the return of culture. (2017)14(1): 37-40
Beilfuss H, Quig D, Block MA et al. Definitive Identification of Laribacter hongkongensis Acquired in the United States. J Clin Microbiol (2015)53:7385-87
Dr. Kara Fitzgerald Functional Medicine Opportunities
DrKF FxMed Clinic: Patient consults with DrKF physicians
Clinician Professional Development: DrKF FxMed Clinic Immersion
Dr. Kara Fitzgerald: Hi everybody, welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And today is no exception. I’m really excited to be talking to one of my favorite lab guys on the planet (laughs), Dr. David Quig. You know him from his long-time work at Doctor’s Data. Let me give you a little bit of his background:
He received his BS and MS degrees in Human Nutrition from Virginia Tech, and a PhD in Nutritional Biochemistry from the University of Illinois. After a five-year stint as a research associate at Cornell, he was a senior cardiovascular pharmacologist for seven years with a major pharmaceutical company.
David has been a hands-on researcher for over 40 years and has numerous peer-reviewed publications. He’s adamant about scientific integrity, which is one of the reasons I love to pick your brain, David, especially as it’s applied to diagnostic testing. He’s committed to helping clinicians make informed decisions regarding the validity of esoteric lab testing in the realm of functional medicine. Again, a really important tool. And for the past 23 years, David’s happily served as the VP of Scientific Support for Doctor’s Data.
Dr. Kara Fitzgerald: Dr. Quig, welcome to New Frontiers.
Dr. David Quig: Greetings Kara, it’s great to be back for more of your hard-hitting interrogations.
Dr. Kara Fitzgerald: All right. Well let’s just jump right in. I mean, Doctor’s Data, you guys have been doing stool testing forever. You’re really one of the earliest folks to offer comprehensive stool analysis and now, you’ve got a new task that I want to pick your brains on, the GI 360. Just, you know what, give me a little bit of the history. I need to… I just want to know it now that I’ve opened with that question, I’m curious about it, and your movement to adapting PCR.
Dr. David Quig: Yes. You know, we had a very sound, time-tested, comprehensive stool analysis test for many years. And, not to blow my horn but, our microbiology was second-to-none, as commented on by major university microbiologists that visited the lab. But times changed and we changed with the times, albeit slowly, and we’ve had major additions. Those additions have been the addition of complementary technology. That being molecular, PCR, we’ll just call it PCR, and we added two different platforms within the realm of PCR. One platform is applied to a very targeted view of the microbiome, looking at abundance and diversity of what is considered to be the clinically most important bacteria. It’s not a microbiome test, but a very focused view, and it’s actually been CE marked cleared in the European Union as a dysbiosis test for clinical application.
The second platform is the more traditional gastrointestinal pathogens panel, which is an FDA-approved platform, cleared platform, extensively validated and assesses something like 20, 23 different pathogenic bacteria, viruses, and parasites. So that as well, was extensively tested across multi-research facilities, and not just an in-house developed test. Now, I’m not implying that in-house developed tests can’t be good. It’s just we really like to focus on and use things that have been really vetted and validated across different laboratories. And the reason we added the PCR is quite frankly because no single methodology answers all of the clinically relevant questions about the microbes. You know, there’s pros and cons of molecular, there’s pros and cons of culture. So we added the PCR and retained our extensive culture and O&P.
Dr. Kara Fitzgerald: All right. I’m going to stop you there because you’ve gone on for too long with information. And I just want to tease it out a little bit. The dysbiosis index is incredibly interesting. It maps the first aspect of this new test that you’re offering now and it’s neat that it’s established as a diagnostic tool. I mean, can you just kind of talk that through? How they’re using it in the EU and, you know, just maybe a little bit more about what it is and how clinicians might use it. And I know there are quite a few publications on it, so if you can just walk through the dysbiosis index and then I’m going to pick your brain on the pathogen portion of the test.
Dr. David Quig: The dysbiosis test or index was really developed and validated in the clinical setting. This group of Norwegian microbiologists and molecular biologists, they looked at the literature regarding what is different between the microbiomes in people with IBS and IBD against normal biosis. And so based on the literature, they then proceeded and came up with a final combination of 45 different probes and in clinical validation, in applying these probes, found that it was very powerful at discerning between dysbiosis and normal biosis. Dysbiosis being in IBS, as per Rome III criteria, and IBD by scoping and biopsy. So not just saying, “Well, this is a normal population, and this is abnormal”, they did it with a clinical endpoint.
And so originally, it was set up to identify dysbiosis with a dysbiosis index algorithmically derived from those 45 different probes or targets into a single digit. So anything greater than 3 on a scale of 1 to 5, or anything greater than 2, is considered variable degrees of dysbiosis. And then, so looking at the very first page of the report, that dysbiosis index is provided, and it’s really interesting. And then the next three pages, you can look at all those 45 different probes that are genus and species of bacteria. But it’s so simple to look at that, and what’s fascinating is that it’s a separate component. It’s a test within the GI 360. It is specifically for dysbiosis and it does not include in the algorithm, the other findings of other types of dysbiosis, say enteropathogens. Nothing from the PCR for bacteria, yeast, and viruses, nothing from culture or Candida.
It’s much more akin to, and a progression from, our old view of looking at, say, the beneficial bacteria and saying, “Wow, you got a really bad score there.” So that’s insufficiency dysbiosis. This takes it further, looks at a much more expanded view of the clinically significant bacteria, and says, “This situation is dysbiotic.” And what’s fascinating is so many times, clinicians on calls will say… They almost act like we have a crystal ball or a magic eight ball or something because we see these patterns, we see a dysbiosis index of four or five, and they immediately say, “Yeah, but there’s no pathogens.” Well, this is a different type of dysbiosis. We get different types of dysbiosis. And what this is many times, is people on a ketogenic diet, a carnivore diet, some crazy extreme diet. Even published using this model was the ability to distinguish and characterize dysbiosis associated with a severely restricted, low-FODMAP diet. It’s really panning out.
And as you know, so many people, when they look at stool analysis, especially in the past, they’re looking for something to nuke. And so many people had a hard time with the concept of insufficiency dysbiosis, but I know… Now I think that the people are really recognizing that there are, within certain bounds, there is a normal core to the microbiome and when you stray outside of the bounds of that, you can even get GI and systemic symptoms associated with dysbiosis that don’t entail a pathogen yet. Yet.
Dr. Kara Fitzgerald: Right, that’s right. So then, you can layer in the rest of the investigations.
Dr. David Quig: Mm-hmm (affirmative).
Dr. Kara Fitzgerald: You know folks, I just wanted to let you know that we’re going to grab some of those references from David and we’ll put them on the show notes page. For instance, you can look at the dysbiosis test as in IBD, IBS, and in healthy individuals. We can link to that, we’ll find that the FODMAP study that was published, we’ll just pull some of it together because it is incredibly useful and it’s validating.
I’m a naturopathic physician, and of course, we’ve been talking about dysbiosis long before it was chic to talk about … well, you guys have as well … long before anybody even acknowledged it was a real word. And this is validating, the kind of effort they’ve gone into figuring out these 45 microbes, and in what kind of imbalanced situations result in a dysbiotic or a healthy gut and the severity of the dysbiosis, like how significantly it needs to be acted upon.
Just before we move into the rest of the tests… you’ve got a core dysbiosis index score which would be a higher number… I mean, how do we think about our interventions? If this is the piece of information, how do we think about what we’re going to do with this particular individual? Like how do we stratify our approach?
Dr. David Quig: Well just like you would, except with more data, with more information, and just as you would deal with gross insufficiency dysbiosis. The primary things that I look at, I don’t get lost in the weeds with all 45 of the targets. To be honest with you, some of those bacteria I can’t pronounce, and some of those, there’s just not a lot of clinical data. But as I said, they fit in the model such that the model with 98% confidence, could discern between dysbiosis and normal biosis.
But what I look for are the classic things that one would look for. The key butyrate producers and primarily within the Firmicutes phyla, the Lachnospiraceae], the F. Prausnitzii, the 14% of the healthy microbiome. Even in Eubacterium rectale… Bifido, which is not a butyrate producer, but acetate, and that can be converted to butyrate. And even some of the Clostridium species. And also, very importantly is to look at those butyrate-producing bacteria which feed forward for maintaining the integrity of the mucosal barrier, in large part through the induction of the release of those mucins. And that mucous barrier, looking at that balance of, say, F. Prausnitzii versus the mucolytic specialists that actually tear down the mucous barrier such as a Ruminococcus gnavus and even “the” bacteria of the year, Akkermansia muciniphila. Also looking at the pro-inflammatory proteobacteria species versus the anti-inflammatories, again the F. Prausnitzii, Akkermansia, and others.
It does take a little bit of re-learning, but you can spot those key ones very quickly. And to be honest with you, so many of those, especially those dietary situations that I’ve talked about, you find a very similar pattern. And as you know, you don’t supplement with Akkermansia or F. Prausnitzii, but the easiest way to upregulate their colonization is by providing them the food that they need, and we get back to the soluble fibers.
Dr. Kara Fitzgerald: Right, right. Okay. So just a couple of thoughts on that. We can, as clinicians, sort of enter into the laboratory test from a variety of different levels depending on our interest.
Dr. David Quig: Yes.
Dr. Kara Fitzgerald: You could do a drill-down on all of the microbes and we can access your tech staff easy enough and walk through detailed discussions. And you always have a good individualized interpretive guide at the end of the report. You can take a look at the key findings and read a little bit more about them at the end of the report … go ahead.
Dr. David Quig: And we’re also just finalizing the resource, or user’s guide if you will, to really help with… Because like I said, a lot of people will be embarrassed trying to pronounce some of the names and some of the pronunciations I get when I’m talking to clinicians is really funny. I know what they’d mean, but there’s just some…
Dr. Kara Fitzgerald: Yeah, there’s some crazy ones. It’s true, it’s true.
Dr. David Quig: It’s really bizzare.
Dr. Kara Fitzgerald: But we’re going to link to the publications on how they created the index. So you know that even if they’re not obvious major players to us in clinical practice, if they really informed the dysbiosis index. And it’s cool, I just love it! It’s a great tool, I think it’s actionable for us.
The other piece is that if you don’t have the time in practice to do a drill-down or you’re just going to kind of piecemeal the expansion of your understanding, there are key findings on page one. There’s the score there, or the index, and then right below are the key findings. I’m looking at a patient’s test in front of me. She’s in the yellow zone, so there’s a little bit of an imbalance there. I look at key findings, her elastase is low. Boom. Her pH is too alkaline, her IgA is low. And then, I can see that she’s got some insufficient key players including Faecalibacterium prausnitzii, it’s very low. Off the bat, I’ve got easy, actionable stuff on page one. So anyway, it’s a new test for us and we need wrap our heads around it to a certain extent, but you’ll also find it really actionable and I think the layout is nice.
All right. So then now, let’s talk about the Luminex, the next aspect of the 360.
Dr. David Quig: Yeah, the GI pathogens, which was based on. You probably remember the old BioFire test, which was the original FDA-approved test – and that’s used in hospitals. I’d say that hospitals have basically stopped doing culture because these are the 23 most common causes of reasons why people present in the hospital, primarily with diarrheagenic disease. And so, again, these are bacteria, viruses, and parasites. And instead of reporting on a relative scale compared to a reference population, these are just positive or negative. And that’s because with things like Vibrio cholerae, there’s no reference value, okay? There’s no clinically acceptable level of Vibrio cholerae and the Luminex platform for the pathogens detects all levels. It can detect down to one organism per microliter of the stool specimen submitted.
But along with that, and I got this question the other day… Someone was very concerned about, and unlike most people, was saying, “I don’t know about PCR. It just seems like there’s a lot of false positives than…” And I pointed out that there may be false positives. There’s two different kinds of false positives. One, you can have false positives from a bogus PCR platform. Let’s just disregard that. That’s not the case here. But with the GI Pathogens, the FDA-cleared test, you can have a positive because it’s so sensitive that you could be picking up residual DNA from a recent past infection.
Actually, years ago, this occurred, and a classic example was for toxin-producing C. diff. And there was a big collection of key microbiologists and they were trying to decide whether they should use this test or not because it was so sensitive because their biggest concern was docs acting on a positive C. diff toxin-producing C. Difficile, when in fact, the symptoms weren’t present. So long story short, at the end of that meeting, they said, “No, this is clinically important data.”
Number one, up to 15 to 20 percent of adults in the normal population are in fact, carriers. And that’s important to know, “No, you don’t treat it if they don’t present with the common symptoms of C. difficile associated disease”. And then secondly, it’s just an education thing for clinicians. You look at the patient, and you know I’ve said this many times: I’ve been doing this for 23 years and I’ll be the first person to say, “You’re treating a patient, not a lab report.” If your patient isn’t complaining of profuse diarrhea three to six times a day, and yet, they’re positive for C. diff toxin-producing, you don’t treat, okay? You mark it off as a carrier and you investigate whether they in fact, may have had it relatively recently.
And because of that sensitivity, it’s also our position that you don’t retest for cure, even with symptoms, until at least three weeks after treatment, because there will be residual DNA. I mean, that’s the beauty and also the downside of PCR. It’s so darn sensitive that you’re going to pick up stuff, but you just have to use your clinical know-how and treat the patient.
Dr. Kara Fitzgerald: My experience is what you’ve outlined. Identifying C. diff toxins in somebody who’s already been treated… Well actually, and it’s not coming up on culture…
I’m just thinking of one patient in particular who continued to have multiple loose bowel movements and discomfort, but she was being treated actually at a university hospital in the west coast, and she was always negative when they were looking for the toxins via the methods that they were using, but she’s positive on this technology. It was disruptive, the number of loose bowel movements she was experiencing was disruptive, and she was sustaining weight loss… I mean, there was definitely a problem. And she would have been a good candidate for FMT and so we were going back and forth, and they were doing this at this particular hospital, but they refused to let her into that program unfortunately.
We adjusted just using our functional medicine and she responded, but it was a relatively involved protocol, you know, a lot of probiotics, a lot of Sacc boulardii, some periodic antimicrobial botanicals, and dietary changes. It would have been nice to have a little bit more of an aggressive intervention with her, and she’s already been through a whole bunch of vancomycin, so that wasn’t a useful route. So the sensitivity was useful and she was continuing to be symptomatic.
But when you say we absolutely don’t treat, I understand and respect that. If somebody is not symptomatic and you see the presence of a toxin, which we do sometimes, you don’t go after the C. diff aggressively with pharma. However, wouldn’t it, in your mind, and there’s other areas of the test we can look at… But wouldn’t the presence of… A C. diff carrier, would you consider that in the dysbiosis column? I mean, it’s a potential opportunist… It can move into potentially pathogenic. What do you think?
Dr. David Quig: Well, it’s an incredibly potentially aggressive opportunist. It’s like the nasty in-laws. And let me back up just a little bit and emphasize that there are very varying degrees of the symptoms, like you were describing, just inconvenient loose bowels. Some people have very profuse cases, and of course, there’s vancomycin resistant. What’s interesting with carriers is carriers, if they go into a hospital, very commonly, and they’re put on antibiotics, pretty much when you go into the hospital, you knock out Lactobacillus. And there’s lots of research on this, is when that Lactobacillus class goes down, the C. diff rears its ugly head, and so one of the things that might be considered as more aggressive treatment of-
Dr. Kara Fitzgerald: Lactobacillus.
Dr. David Quig: Lactobacillus.
Dr. Kara Fitzgerald: For sure, yeah. Lactobacillus rhamnosus specifically, I think there’s interesting research on it, and it was helpful in her case. And I used more, for anybody interested, she dosed multiple times a day, pretty high amounts, before we were able to control her.
Dr. Kara Fitzgerald: I think when someone’s asymptomatic, as those of us in integrative medicine, it’s another piece of the sort of general imbalance puzzle that we can work on with diet and lifestyle and so forth.
Dr. David Quig: Right.
Dr. Kara Fitzgerald: All right, what else did we want to say about this test? We’ve got viruses, we’ve got parasites… The sensitivity with parasites versus microscopy?
Dr. David Quig: Yes, and it’s the same way whether you’re comparing molecular techniques to O&P, microscopy, or whether you’re comparing to microbiology and culture. It’s not uncommon to see positive by PCR, yet negative by O&P or culture. It’s more sensitive and it’s not a gross discrepancy within the report, it’s just you have to look at the power of each of the two methods. Now, so why do we still use O&P? Why do we still use culture? Guess what? We don’t have that many probes, even for pathogens, compared to the 30 additional parasites that we can readily identify via O&P. So albeit with less sensitivity, we have a much greater scope of coverage. Same thing with culture. We can identify over 1400 different species and genera of bacteria in yeast by culture, which is far, far greater than any number of probes anyone’s ever going to have. And so, that’s why I really emphasize the addition and the complementation of the two methods. They both have their strengths and limitations. You put them together and you have a great team.
Dr. Kara Fitzgerald: I agree. I’m kind of happy that at the end of the day, we’re doing that for the reasons that you stated. I mean, in cultures… We’ve successfully treated people over the many, many years based on culture data. It’s nice to have both, but…
All right. What else do we have on this test? Let’s see. Talk about some of the chemistries. I think one of the reasons I love your test is that you’re pretty comprehensive with the chemistries.
Dr. David Quig: The chemistries are critical. The microbes and they’re telling you one thing but you know… my background in metabolism and stuff, I also want to know what’s going on metabolically in that community. Is there induction of organic or inorganic inflammation? So both the IBD markers, the calprotectin and lactoferrin and the lysozyme for non-IBD inflammation, so we’re covering inflammation as deeply as we can. And having said that, we do see cases where we’ll see calprotectin significantly elevated and lactoferrin not. And we continue to evaluate that, but I did find one paper a couple of years ago where the researchers were discussing differential activation of calprotectin versus lactoferrin, or lighting up in stool I should say, with respect to the location of the inflammation in the bowel, whether it be upper or UC, something like that. There hasn’t been a whole lot in that regard, but you know, for now, we’re going to include both because we don’t want to miss it.
Dr. Kara Fitzgerald: I think it’s very handy to have.
Dr. Kara Fitzgerald: You guys have been writing about beta-glucuronidase and some of the advances regarding specifically gastrointestinal beta-glucuronidase. You guys are looking at that and what’s the new research on it?
Dr. David Quig: We are, and for a long time, people would not use our stool test because we didn’t have glucuronidase. And the reality is now that we’ve added it, we actually don’t see very many elevated glucuronidases. As everybody knows, the body works real-hard [to glucuronidate] as part of phase 2, to try to irreversibly get rid of toxins that have been processed in the liver specifically. And the beta-glucuronidase can work against that by de-conjugating and re-introducing the toxin back into the situation. There was about a 20-year lull, or at least a 15-year lull in research around beta-glucuronidase.
We were all familiar with the elevated beta-glucuronidase and the elevated circulating estrogens in pre-menopausal women, and the fascinating story of the grilled meat and grilled fish-derived carcinogen, abbreviated IQ, the name is just too long to pronounce… It’s a quinoline. But anyhow… So that stuff was around, and people were, you know, “Okay, well if we find that, we’re going to use the calcium D-glucaric acid to try to inhibit that.”
But recently, and as early as last year, there was a hallmark paper, I mean it’s just fascinating… I think I… No, I just sent you the newsletter, but anyhow, there’s a group I believe they’re from Korea, they have identified, characterized, sequenced hundreds of different beta-glucuronidases derived form bacteria across all of the major phyla. Interestingly, they have different structures in certain component of the enzyme, and as a result, very different aglycone substrate specificities, so this paper really pointed out that, “Hey, there’s no such thing as just beta-glucuronidase, in fact, it’s called GUS.” And that’s what’s happened in biochemistry. Enzymes are now being called the name of the gene location from which it came. So, us old biochemists have to just get up with the language. But there’s hundreds of different bacterial-derived GUS’s. There’s that derived from the gastrointestinal epithelium, and even from the liver. Did you know that there’s even circulating GUS activity at least-
Dr. Kara Fitzgerald: That’s pretty interesting.
Dr. David Quig: It’s associated with jaundice in infants. So this stuff, it’s a whole new world of research. And the key points I want to make about it are that I think that in the future, not near future, we’re going to be able to much more specifically evaluate positive versus negative GUS activities. That is with respect to their ability to handle different toxins versus, for example, the essential GUS activity that actually enhances the systemic availability of flavonoids. Flavonoids, they come in our diet that have anti-inflammatory, antioxidant, antiviral, and antitumor effects. And my dream is that someday, we’re going to be able to have a panel of different GUS activities, and it may be just at a molecular level versus at a specific substrate activity level.
I think probably my most important clinical point is that when you do see high beta-glucuronidase, GUS activity… We all need to get used to GUS, my cousin GUS. You know, the old adage of, “Yeah! Calcium D-glucaric acid! 500 mg, couple times a day.” No. You look at the kinetics of and the conversion to the active inhibitory metabolite, number one, the bioavailability is low, the conversion to that active inhibitory metabolite from glucaric acid is low, and its inhibitory half-life is only about five hours. And so you’re really talking about dosing at least 500 mg 3 times a day, preferably with food when you have the bile flow. But even that, I mean, that’s one way to do it.
Another way to do it is to look at the restoration of the microbiome. You get an imbalance in the microbiome, major disruption, you’re going to see a greater preponderance of, say, the not-so-beneficial GUS activities. And then, probably even more important like with all toxicology, remove the source of induction of that GUS activity. For example, that meat-derived carcinogen IQ, it actually induces more beta-glucuronidase activity, which in turn, enhances the exposure half-time in the host. There’s so much more to learn and even at the clinical level, but for right now, I’d say the clinical interpretation of test results really isn’t changed. And clinical intervention, I’d say, in addition to considering using the calcium D-glucaric acid, really think along the lines of toxicologists in trying to remove the source of induction, just like removing the source of exposure with any kind of environmental toxin.
Dr. Kara Fitzgerald: If we don’t have a good drill-down into… If we can’t figure out what’s upregulating, if they haven’t gone on a barbecue over the last month or so, maybe if we do a general five-hour protocol, if we clean diet up in a general way and address the other imbalances that are clear from the test and from the clinical presentation, would you expect that to adequately address it? And then maybe go in with cal D-glucaric later?
Dr. David Quig: Well, I think you could do that concomitantly. And secondly, no doubt, there’s other chemical entities that are going to induce expression of this enzyme. We can’t possibly know all that at this time, so definitely, I’m not saying don’t use the calcium D-glucaric acid, I’m just saying consider the pharmaco-kinetics of that very simple, benign acid and dose it appropriately. And even looking at the literature, for really effective inhibition, they’re talking about up to three and a half grams a day.
Dr. Kara Fitzgerald: Yep, it’s a lot.
Dr. David Quig: It’s a lot. To take every day?
Dr. Kara Fitzgerald: It’s a lot. Yeah, that’s right. You just can’t do it, it’s not sustainable.
Dr. David Quig: No.
Dr. Kara Fitzgerald: Unless you’re really concerned, I would say, about breast cancer, or-
Dr. David Quig: Exactly.
Dr. Kara Fitzgerald: I mean, I think it can be a really important molecule to use, but you’re right. It’s not sustainable.
Dr. David Quig: Right.
Dr. Kara Fitzgerald: Well, great. It’s wonderful. It’s always nice when a laboratory seizes one of these old molecules that we’ve seen forever, and we’ve been thinking about forever and bring new science to it. Indican is another one. It’s gotten a whole new, all new wings, and that was an old school urine marker that we used to… Well, it pre-dated me, like some of my mentors would run it in their clinical practice.
Dr. David Quig: Oh, some of your mentors performed the test right in the office.
Dr. Kara Fitzgerald: That’s exactly right. I know! I know! And now there’s just all sorts of cool science on Indican and neurodegenerative conditions and good reason for us to pay attention to it.
Dr. Kara Fitzgerald: I want to just circle back. I just have a couple more questions I want to ask you on the test. And I guess, using the test, people want to be able to out evaluate small intestinal bacterial overgrowth or small intestinal fungal overgrowth and what are your thoughts on using stool tests for those evaluations?
Dr. David Quig: There’s clearly no diagnostic indicator in stool at this point that can specifically say, “Yes that’s SIBO or even SIFO.” That may happen in the profile… We communicate with the genetic analysis company, the group that produces our platform for PCR, and they’re aware that we’re interested in trying to identify a specific profile within the context of that dysbiosis index model that might… And this again would have to be validated very, very robustly at the clinical level. That may be coming. Short of that, as everyone says, short of a direct aspiration from the small bowel and applying PCR to that, and that’s not even practical, not many patients are going to opt for that, not many clinicians are going to want to do that.
But SIFO, small intestinal fungal overgrowth, is a very interesting… There was a paper in 2015 where they found that it was, I think it was 82%, I’ll say 80% of the true confirmed SIFO patients were on proton pump inhibitors. No surprises there, right? I mean, you raise the pH so much. We can’t do that. I guess you could use a capsule and monitor pH on the way through, that’s also pretty extreme. But for SIFO, one way that we look at that now, is as you know, sometimes, you don’t see yeast culture or identify it, and we can identify over 180 different species of yeast it’s spooky,] with MALDI-TOF. But when they don’t culture, and yet by backup microscopy, you see moderate to many, say in two or three stool specimens, then you have to say to yourself, “Is that consistent with the patient presentation? Is that consistent with SIFO?”
And we’ll just say this is a theory at this point that because the yeast may be so high, overgrowth, so high in the bowel that they don’t survive transit through the entire bowel as to be culturable. And so, they may not be viable to grow in the laboratory, but you can still see them. My suggestion within consultations is, if you see moderate to many yeast microscopically but not by culture, and it’s consistent with the presentation of the patient, then consider treatment. Unfortunately, we don’t have any guidelines for what may or may not work, but a darn good fall back is always a good garlic extract.
Dr. Kara Fitzgerald: Yes, absolutely. As you know, Methanobrevibacter smithii is something that we’re looking at on stool tests more and more often, and Pimentel published on it recently and actually, he’s arguing that it can be in the full gastrointestinal tract. It does colonize below the GI tract. And therefore, he wants to rename methane SIBO intestinal microbial overgrowth so for intestinal methane overgrowth is archaic.
Dr. Kara Fitzgerald: It’s possible that we could actually find some utility in looking at stool Methanobrevibacter smithii, so when would you bring that into the test? Or would you consider that?
Dr. David Quig: We would definitely consider it, but I’d say that I think that we should be a little careful in assuming that that is causal. It’s sort of like… Well, if you’re looking for something and it’s positive and the clinical symptoms are there, therefore it’s the cause, not always the case. It may be informative, but we certainly can’t say at this point that it’s causal because there’s so many bacteria that produce methane, and that may happen to be one of the bacteria of the month that people are reporting, therefore, it’s assumed to be the cause.
Would we consider adding it? Absolutely. Again, I really like to do things based on whether it really is valid or not. So, do I want to wait until the clinical trials are done? Not necessarily. But again, it gets back to number one, Methanobacterium smithii was not found to be a significant contributor in the dysbiosis index model that we use. However, that’s not to say that it’s not important. Again, that was with respect to dysbiosis IBS, IBD, and now we’ve also seen obesity. But as always, we’re not going to just rush into the lab and develop, come up with a probe for it without… We really would rather have a very highly vetted and validated probe. But that’s very doable. It’s v-
Dr. Kara Fitzgerald: Well you know, I will say that I have seen over treatment… You know, much, much over treatment with over-interpretation of results, so I appreciate you wanting to pay attention to its significance, and I know that just using the group in Norway who were developing your probes and making sure there’s some solid science behind is, it’s useful.
Dr. Kara Fitzgerald: All right. Let me just… Let’s see what else I want to ask you. I think we’re into closing minutes here. You threw out the dysbiosis test and obesity. Of course, for a period there, everyone was looking at firmicutes and bacteroides ratio, that was just all the rage. I have to say clinically, I haven’t seen it there out, looking at it over the years, but yeah, so talk to me about how we might use the GI 360.
Dr. David Quig: Yeah, as I call it, the F to B ratio, and you can interpret it any way you want there. I never was a fan of that. I mean, the hardest data came from stinking rodent models.
Dr. Kara Fitzgerald: Mice, yeah.
Dr. David Quig: And then, you had some from some very restrictive human studies, but just in 2019, a mega meta-analysis… That’s a little redundant. But it clearly debunked that… Let’s just say, it’s an extremely equivocal concept. And basically, what the investigators of another study found was that you really need to go deeper taxonomically in that evaluation, and simply looking at two phyla, a ratio of two phyla, at the phyla level, doesn’t cut it at all. In our test, GI 360, we do report on 25 different firmicutes targets and ten different bacteroides, but we don’t have robust clinical backing there, and I don’t think anybody does. But we do report those, and we do, as you’ve seen on the first page of the report, report the patient’s web based on the six primary phyla, of course including firmicutes and bacteroides, and you can look at the relative plotting of those two phyla and form your own opinion.
Personally, I’ve always had a problem with any kind of excuse for overweight and obesity, trying to say, “Ooh, it’s my darn bacteria.” When in fact, we know that the diet is such a driving factor, even in that simple ratio right there. Bottom line is, this is something else that we’re looking to the genetic analysis people to try to develop a very robust ratio of, or not necessarily even a ratio, maybe a unique dysbiosis index that might pertain… And I would predict to say it would pertain to not only obesity, metabolic syndrome, and type two diabetes. And we’re already seeing higher dysbiosis index in obesity and type two diabetic patients using the current model. So I think if anybody’s going to come up with that, it would be that kind of approach where you have a targeted approach with a clinical outcome associated with it.
Dr. Kara Fitzgerald: It’s happening. I think the dysbiosis test and the science behind is so cool, and again folks, we’re going to link to as many studies as I can get from David to just give you more information on it. We’ll put a sample report on there so you can actually see the web that he’s talking about, see the index, the score, and walk through the test as a whole. It really is a beautiful test. I know the level of attention and just the science that you guys put behind your efforts, and I appreciate the work that you’ve done here. So, thanks for joining me today and to walking me through it.
Dr. David Quig: Oh, always a pleasure, Kara. Anytime.