Validated DNA Stool Testing & Tough Clinical Questions

Doctor’s Data GI360 Stool Test with Dr. David Quig.

Key Takeaways

  • The GI 360 stool test is highly validated and vetted.
  • Not all dysbiosis requires treatment: Consider the presentation of the patient along with test results.
  • Using culture and PCR-DNA analysis together provides better information than one alone.

Stool tests are a valuable clinical tool, but not all lab tests are created equally. I’ve been skeptical about the validity of several brands on the market.

I recently met with Dr. David Quig from Doctor’s Data to hear more about their new GI 360 stool test that blends PCR-DNA and stool culture-based testing.

Validated DNA Stool Testing & Tough Clinical Questions -

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In This Episode

Dr. David Quig’s Background … 00:05:54
Dr. Quig’s Perspective on Stool Testing … 00:06:40
Culture vs. DNA Stool Testing … 00:09:44
False Positives … 00:11:45
Interpreting GI Pathogen Levels … 00:14:28
Interpreting Commensal Bacteria Results … 00:17:33
Doctor’s Data’s Culture Profile … 00:20:59
When PCR & Culture for Yeast Disagree … 00:23:00
What Requires Antimicrobial Treatment … 00:27:29
Does Blastocystis hominis Require Treatment? … 00:31:48
Interpreting Probiotic Species Levels … 00:34:16
GI 360 Test Result Description … 00:38:04
Peer Reviewed PCR Data … 00:45:14

Doctor’s Data GI 360 Stool Test

Stool tests look for bacteria in the stool, as well as other organisms, such as parasites and yeasts.

Dr. Quig said, “There’s no one perfect methodology for stool analysis…”. Doctor’s Data’s new GI 360 stool test aims to provide the best of both PCR-DNA testing and stool culture testing. These two different types of testing have different uses. Dr. Quig suggested that stool culture is “…like trolling a net behind a boat, where we can see what is there….[and] PCR is like only having 7 or 12 fishing lines out with different specific baits where you’re only going to answer the question, “Is it there?”

PCR-DNA testing is extremely sensitive, sometimes able to detect a single organism in a unit of sample.

Stool Culture testing can provide a broader picture of what’s present and at what level.

According to Dr. Quig, both types together give a much better picture of what’s truly going on.

Doctor’s Data’s Validated Culture Profile

The GI 360 uses the GA MAP data from a research group in Norway to analyze the gut microbiome composition, and to evaluate it for dysbiosis. These data “…have been validated and tested in almost 50 different clinical trials to be most predictive and associated with dysbiosis.” Additionally, the two different PCR platforms Doctor’s Data uses in its testing have been evaluated in 20 peer-reviewed clinical trials, on topics from fecal microbiota transplant (FMT) to IBS (irritable bowel syndrome).

GI 360 Test Result Description

The GI 360 reports on two main areas:

  • Dysbiosis of non-pathogenic species. A result three or greater [represents] worsening degrees of dysbiosis.
  • Pathogenic dysbiosis that may need to be addressed, such as Salmonella, H. pylori, or Candida. Not all pathogenic results require treatment. 

Interpreting Stool Tests

How you interpret a stool test is key to using this important tool correctly. I asked Dr. Quig several questions to help flesh out what the various results mean clinically.

False Positives

I asked Dr. Quig if false positives were possible and how he recommends reading the test data to protect against this. Dr. Quig said, “If you’re using highly standardized PCR testing, you really don’t get false positives in the sense that the test is wrong…however, that [result] may be residual DNA left over from a pathogenic bacterial infection or a viral infection that occurred symptomatically three to six weeks ago. So…it’s a false positive in the sense that the clinical symptoms may not be consistent. “False positives” are just a matter of clinicians being educated about how to interpret that.”

Pathogenic Bacteria Results

With the pathogens screened on the GI 360 test, “there is no clinically acceptable level.” If they are present at any level, this is usually an indication that treatment is necessary.

Commensal Bacterial Overgrowth Results

Many bacterial species are considered a normal part of the microbiome, but when overgrown are a sign of dysbiosis. Dr. Quig noted, “We have those opportunists [where] an abundance…is really just a confirmation of a disruption of a healthy microbiome.”

Probiotic Bacteria Results

If by PCR you’re seeing extremely low deviation from normal with Lactobacillus or Bifidobacterium, that patient will likely benefit from a Lacto-Bifido combo type of probiotic.

When PCR & Culture for Yeast Disagree

I asked Dr. Quig what he would recommend to clinicians when a yeast culture doesn’t agree with the microscopy. He outlined two different possibilities:

  • Positive microscopy with a negative culture could indicate SIFO (small intestinal fungal overgrowth)
  • Positive microscopy with a positive culture for beneficial yeasts could also indicate SIFO

He commented, “We use the microscopy to back up the culture…if there’s clinical symptoms of small intestinal fungal overgrowth, and moderate-to-many yeast by microscopy, but not culture, the prevailing thought is that that’s an indication that there are yeast high in the GI tract, but they [won’t] be viable in culture when we get the stool specimen.”

SInce there is yet to be reliable testing for small intestinal fungal overgrowth, this may help provide guidance for clinicians.

Sponsored Resources

Hi everyone. I want to thank Doctor’s Data who helped to make this podcast possible and who I’m very excited to say has now released a profile called the GI 360 which is finally a validated microbiota mapping measure.

Validated DNA Stool Testing & Tough Clinical Questions - ddi logo centered 2col 300

If you remember back, I’ve discussed numerous times the only lab that is really validating a mapping of the microbiota to have clinical significance is the GA map out of Norway. Well, turns out that Doctor’s Data is not only using the same methodology but also in collaboration with this group in Norway using their parameters to adjust what we call normal, abnormal or dysbiotic and normal. So great news, we finally have a validated measure.

Now this test also offers, in addition to the microbiota dysbiosis index, a PCR assessment for bacteria, virus and pathogens, a comprehensive microscopy for a parasite, a MALDI-TOF bacteria and yeast culture. And as you would imagine, because of the rigorous validation they’ve gone through, they also have approval from the CE, which is equivalent to the European FDA.
So great test, please check them out. Doctor’s Data is offering 50% off a practitioner’s first GI 360 test kit. Go to doctorsdata.com/Ruscio to claim your first kit, limit one per provider. The offer ends October 31st, 2020.


What Stool Test Results Require Antimicrobial Treatment?

One of the most-asked questions about stool test results is whether they show the need for treatment. According to Dr. Quig, the stool test findings don’t always require antimicrobial treatment. “There’s really two schools of thought. Some people like to get rid of something right away…The other approach is…to get things back into balance and work on restoring the health and abundance and diversity within the microbial community. I am a strong believer in restoring balance.”

Dr. Quig agreed with the idea of focusing on a holistic ecosystem approach, like I describe in Healthy Gut, Healthy You.

Does Blastocystis hominis Require Treatment?

There’s a lot of scientific debate about whether or not the unicellular parasite Blastocystis hominis is pathogenic or commensal. Dr. Quig said it comes down to the specific strain, and “You really have to…consider the presentation of the patient because there are many people in the microbiome world that feel that Blastocystis can be very much a commensal bacteria.”

The Bottom Line

The GI 360 is a highly validated stool test, offering an assessment of dysbiosis and pathogenic bacteria in your gut.

Doctor’s Data is offering 50% off of a practitioner’s first GI 360 kit. Go to doctorsdata.com/ruscio to claim your first kit, limit one per provider. This offer ends October 31st, 2020.

Full Transcript (click to expand)

Intro:

Welcome to Dr. Ruscio Radio discussing the cutting edge in health, nutrition, and functional medicine. To make sure you’re up to date on this and other important topics, visit drruscio.com and sign up to receive weekly updates. That’s DrRuscio.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking with your doctor. Now let’s head to the show.

DrMichaelRuscio:

Hi everyone. Today I speak with Dr. David Quig. We completely nerd out and get pretty clinical. This is definitely one of those episodes. I would say, if you’re not a clinician, it may get a little deep and a little sick. We go into nuances of testing, interpretation, and how to use test results to guide treatment. David works with Doctor’s Data and something that I learned today that I did not know prior is that the stool test from Doctor’s Data, their DNA test, actually uses the data set from the GA MAP test in Norway. What does that mean? Well, if you’ve been following the podcast for a little while, you’ve heard me say repeatedly that the only lab that I’ve seen that really correlates DNA stool test results to clinical conditions is the GA MAP out of Norway. They’re using that data set to comprise their methodology and ranges which was really great to learn. So we went into that, how to use their DNA test, and how to best use their stool tests. If we as clinicians are being honest with ourselves, there is not a super clear cut way to interpret stool tests. If someone believes that, no intention to be offensive here, but they’re just not thinking critically enough about the information in front of them, how it’s been validated and how that steers clinical decision making. So we really went deep into this today. It was a very insightful, albeit a clinical and advanced conversation. One of the topics I want to touch on is the fact that for the vast array of findings on a stool test, other than things that are strictly pathogenic and strictly parasitic, we don’t always have to treat those aggressively with anti-microbial or antibiotic therapy.

DrMR:

In fact, he endorses the same approach that I write about in Healthy Gut, Healthy You, which is restoring and working to holistically cultivate the healthiest ecosystem that you can. This ties back to one of the main posits I’ve been trying to champion on this podcast from day one. Test results don’t always require a highly specific and different method of treatment than we would engage in otherwise. Now there are exceptions to this, but oftentimes I think clinicians end up seeing a positive finding and assuming that anti-microbials, antibiotics, or antifungals are warranted. That may not always be the most advisable starting point. That starting point may be to go through the exact steps in Healthy Gut, Healthy You, which outline attention to diet, lifestyle, stress, exercise, and time in nature. All of these things are our inputs to a healthier microbiota, which changes the way things look. So this was a fantastic conversation with Dr. David Quig from Doctor’s Data. If you want to learn more about their lab, obviously go to doctorsdata.com. If you want to learn more about the healthy gut ecosystem cultivation approach, check out Healthy Gut, Healthy You. Now we will jump into the nerdy elaboration.

DrMR:

Hi, everyone. Welcome to another episode of Dr. Ruscio radio. Today, I’m here with Dr. David Quig and we are going to be going into stool testing and the lineup of tests offered by Doctor’s Data. I should start off by mentioning that one of the few stool tests I continue to use today is Doctor’s Data. If any of you are subscribed to our clinicians newsletter, you will see that in the case studies is one of the tests that I’m using. So definitely a lab that I like and use. We’ve also vetted the science behind some of this testing several months ago in the April, 2019 issue of the Future of Functional Medicine Review. We reviewed this test and the science behind it in detail. Today we have David here to go into some of the common questions that I hear from practitioners and how to best use this technology. So David, glad to have you here and thanks for taking the time.

DrDavidQuaig:

Thank you, Michael.

DrMR:

Can you tell us just in brief about your background?

DrDQ:

Yes Sir. I did my bachelor’s and master’s in human nutrition and did my PhD in nutritional biochemistry. Then I did five year research associate position at Cornell, mostly in cardiovascular research. Then I thought I’d make a lot of money in the pharmaceutical industry and worked as a senior cardiovascular pharmacologist for seven years. It wasn’t as much fun as I thought it would be and so I jumped the fence and have now been vice president of scientific support for Doctor’s Data for the last 23 years.

DrMR:

Oh, wow. So a good run over there.

DrDQ:

Yes, sir.

DrMR:

So, you know, obviously the people listening to this understand from a high level the utility of a stool test, we’re trying to figure out if there is essentially stuff there that shouldn’t be there. Things like H. pylori, potentially parasites. There is a little bit more of a gray area when we get into dysbiosis, determining exactly how do we define that? We know what might be normal for one person is abnormal for the other person. So how do you look at this from a really high vantage point? Well, what is the way you’re looking at stool testing and engaging in the process of stool testing, where do you start? Then obviously we’re going to get into correlations of detail here, but I want to try to start really big and then zoom in.

DrDQ:

Right. I think that we’ve really progressed. You know, we used to just be looking for things to nuke, and then we moved into beneficial bacteria and really developed the full appreciation for why we need that army of bacteria and all those different groups of soldiers. We’ve advanced now to the point where, beyond a culture, we can get a much, much more definitive view of what we call normal biosis. So while you correctly stated that everybody has a slightly different microbiome, there is a basic core of these commensal bacteria that have vital functions. That’s really where we start now because it’s usually when things go awry in the abundance and diversity within that community, then we set ourselves up for serious impacts from pathogenic bacteria, even H. pylori. We can have H. pylori that are pretty benign, but when other factors go wrong it can become more serious. So that’s really the approach that we’ve taken and just progressed from looking at just the standard beneficial bacteria like lactobacillus bifido, to really being able to much better define what is normal biosis.

DrMR:

As we start drilling down into some of these details and trying to get a better read on whether there are some abnormalities present. Symptoms help give one indication. Let me rephrase that. On the one hand symptoms can be very helpful because you can track those over time and use those to assess empirically the effect of a given therapeutic, let’s say a probiotic. For example, a patient is bloated and has joint pain, did the probiotic lead to resolution of those symptoms? If yes, then we can presume that what’s going on from a biota perspective is a healthy shift. But, these things aren’t always quite as neat and as linear and able to be distinguished. This is, I think, one of the arts of the clinical practice, which is trying to reduce variables and get the best signal to noise ratio. One of the things that we can do to help clarify this obviously is testing. You made a remark, and here’s another kind of point to help people better understand from a high level drilling down in the details. We have two main types of testing I’d offer. There’s exceptions to this, but generally speaking, we can go to a stool test that will use culture or a stool test that will use DNA. One thing I should mention, and I think we’re on the same page here. Sometimes culture testing is portrayed as antiquated, but there’s still very good data for culture testing. It definitely has an impressive list of pros although there are some cons. So how are you starting to look in your mind at the DNA testing versus the culture testing?

DrDQ:

Absolutely. There’s no one perfect methodology for stool analysis, bacterial microbiome and microbes in general, that answers all of those important clinical questions. As you said, culture has limitations. Primarily, the vast amount of particularly obligate anaerobic bacteria are not routinely cultured. On the other hand PCR isn’t the be all to end all. It also has limitations. A major limitation of PCR is you only find what you are looking for. We’ve always looked at culture as a more like a trolling net out from behind the boat where we can see what is there. Whereas PCR is like only having seven or 12 different fishing lines out with different specific baits where you’re only going to answer the question “is IT there?” So culture is more of a what is there test, while PCR is a very accurate determiniation of is it there.

DrMR:

Now with the topic of PCR, DNA testing, false positives seem to be something thatis always one of the thorns in the side of that type of testing. That does, at least in my clinical experience, lend itself to being offset by good clinical decision making and not making all of your treatment decisions based upon a lab test. How are you looking at false positives? What should clinicians know regarding when they’re looking at an exotic infection that causes really severe symptoms in an otherwise asymptomatic individual, which is one scenario that may pop up, how are you advising people to look at this information?

DrDQ:

That’s a really good point. In reality, if you’re using highly standardized PCR testing, molecular testing that has been well vetted and validated across multiple centers, research centers, and clinical centers, you really don’t get false positive in the sense that the test is wrong. Which raises the whole other issue. PCR and molecular testing is so awesomely sensitive that you can detect up down to a one organism per milliliter of the sample. It becomes very clinically useful information. So you if you have a positive, that may be residual DNA left over from a bacterial infection or a viral infection that occurred primarily symptomatically three to six weeks ago. In the case of our really strong PCR platform, it’s false positive in the sense that the clinical symptoms may not be consisten but then one has to question, was that the case three to six weeks ago. A classic example is the C difficile toxin producing positive by PCR. An estimated 20% of healthy individuals walking around are carriers for that. So the clinician needs to be aware of that. Look at the patients and say to them, you’re not having multiple rounds of profuse diarrhea every day, so you may in fact be a carrier, so I certainly don’t need to go in there and treat that. False positives when you’re using a solid platform is just a matter of clinicians being educated, how to interpret that. Whereas if it’s a bogus PCR platform you got a real issue on your hands.

DrMR:

I’m really glad you brought up the piece about being validated. One of the questions that springs up from that is that part of the validation establishing reference ranges. The reason why that could be relevant of course, is that, theoretically, you could be seeing a clinically irrelevant amount of a given bacteria. This is something that some of the contemporary literature is echoing although there is a kind of counter-argument nuance that the virulence strains may be more important for H. pylori than the absolute levels. One of the arguments that’s put forth is that it may not be an issue of strict eradication of H. pylori, but rather dampening down the level of colonization so as not to allow it to exert a potentially negative function. So that begs the question, might one of the important parts of the validation be establishing the right reference range so that we know if we see a positive on the lab report that is fairly well guaranteed to me that that positive is likely to be correlating with a clinical detriment.

DrDQ:

Well, for the GI pathogens part of the GI 360 tests from Doctor’s Data, there is no clinically acceptable level for those pathogens. So measuring down to just positive and negative. There is no such thing as a normal reference range for something like Vibreo cholera. When you’re talking about those strict pathogens, which is a bit different than H. pylori, you’re talking about basically no acceptable level. Again, you apply the thought process of yes, we detected something, is it from a past die off? And is it, is it associated with symptoms?

DrMR:

To clarify one point, with the pathogens, let’s say the flag positive range is at 0.05. If someone is at 0.01, so there’s something detectible, but it’s not high enough to be flagged positive by the lab, clinicians should be interpreting that as likely some sort of self resolving infection that’s no longer an issue.

Speaker 4:

Yes, but on the GI pathogens part of the test, we don’t report a number. It’s just base. This is an FDA approved platform and it’s not associated with a symptomatic condition. Like I said, there’s things like Vibrio cholera where you don’t want any level. You want to know if there’s one organism per milliliter of that prepared stool specimen or microliter even. I mean, it’s so sensitive. So you really don’t have the ability to look at well, is it just under the threshold. There’s no threshold reference value for such very virulent pathogenic bacteria.

DrMR:

Okay. All right. So simplifying the reporting for people, which is great. Then we get into dicier territory which is difficult to categorize? Are they commensals? Are they opportunistic? It’s likely in my opinion, not going to be quite that simple because there’s a lot of other stuff going on in the microbiota. Is there a degree of inflammation? How healthy are the other players making it, interpreting some of this a little bit more challenging? How are you guys at Doctor’s Data, helping clinicians sort through this, this kind of tough fog that we’re all presented with?

DrDQ:

Yes. As you’ve used our microbiology before that, and that’s part of the reason why we have retained the very powerful microbiology that we have. We can identify, we can grow and identify up to 1,400 different species of bacteria and yeast. Within those, as you implied, we have those opportunists that we say, you know what, an abundance of these opportunists is really just a confirmation of a disruption of a healthy microbiome. Then we get into those potential pathogens that when they get to a certain level, say 3+ or 4+ in culture, then they get shifted into the dysbiotic bacteria. So those are slightly different from the pathogenic bacteria. So with culture, you can have some bacteria that are pretty neutral players, but if they grow to a certain level, they can become dysbiotic or potentially pathogenic. So that is very clear from the culture as opposed to the yes or no for the virulent pathogens by PCR.

SponsoredResources:

Hi everyone. I want to thank Doctor’s Data who helped to make this podcast possible and who I’m very excited to say has now released a profile called the GI 360 which is finally a validated microbiota mapping measure. If you remember back, I’ve discussed numerous times the only lab that is really validating a mapping of the microbiota to have clinical significance is the GA map out of Norway. Well, turns out that Doctor’s Data is not only using the same methodology but also in collaboration with this group in Norway using their parameters to adjust what we call normal, abnormal or dysbiotic and normal. So great news, we finally have a validated measure. Now this test also offers, in addition to the microbiota dysbiosis index, a PCR assessment for bacteria, virus and pathogens, a comprehensive microscopy for a parasite, a MALDI-TOF bacteria and yeast culture. And as you would imagine, because of the rigorous validation they’ve gone through, they also have approval from the CE, which is equivalent to the European FDA. So great test, please check them out. Doctor’s Data is offering 50% off a practitioner’s first GI 360 test kit. Go to doctorsdata.com/Ruscio to claim your first kit, limit one per provider. The offer ends October 31st, 2020.

DrMR:

Tell people a little bit about the culture profile, cause you do have, in my opinion, quite an impressive culture profile with the MALDI-TOF. There’s definitely some pretty solid evidence there, and I think that’s worth underscoring for people.

DrDQ:

Absolutely. Our microbiologists are really second to none. We report the imbalance, the dysbiotic, and the pathogenic bacteria. Now by PCR, there’s a standard list of, as we discussed, the virulent bacteria. Using culture and the MALDI TOF, the proteomic method of analysis, we can identify rather unique and emerging pathogens, such as Arcobacter butzleri, Leribacter hongkonggensis, and other Helicobacteria and bacteria species like canadensis, canis and puloram. So these are other Helicobacter species that don’t reside in the stomach, but rather in the bowel. We can pick those up by culture. In addition, we can identify over 180 different species of yeast. Most of them there’s no PCR probe for, so there we can get into much greater detail even of environmental yeast and fungi that we used to think were only a problem in the home. We have worked with many environmental medicine docs and sure enough, we have found environmental yeast such as Exophiala dermatitis colonizing in the colon of the patient. So, not just getting it out from being a respiratory issue, systemic issue, but even causing problems in the gut. So culture is here to stay and it’s really a complimentary component to the molecular approach.

DrMR:

I think it is important to echo for people that new doesn’t always mean better. Just because there is a technology that has an additional capability, that we should just throw out, in this case, culture. I think that’s really important for physicians to be aware of that. On the topic of yeast, this is something that I’m sure other clinicians are confronted with. When you will see a positive on the microscopy for yeast, but the culture comes back negative, or the culture comes back with something positive. I know that there are kind of two different questions there. Earlier in my career, I think this is something that whenever we go into the integrative space, whether you’re coming from conventional medicine going to integrative, or whether you’re just integrative the whole way through, there can be this tendency to act too quickly on a lab finding. I think it’s important to bridle ourselves. If we see, at least as I’m interpreting it, a microscopy positive, but the yeast is a beneficial yeast, I’m not really inclined to jump and say you have a yeast problem. That’s at least the way I’m looking at it. It’s an easy interpretation when the microscopy is positive and the pathogenic yeast or dysbiotic yeast is where the culture is coming positive. But if you’re seeing a microscopy positive with no culture or a beneficial culture, how are you helping people with the decision making from that?

DrDQ:

That’s a really good point. We use the microscopy to backup the culture. You’ve all heard of SIBO, small intestinal bacterial overgrowth, but there is a phenomena that has been recently published about known as SIFO, small intestinal fungal overgrowth. So the case there, and small intestinal fungal overgrowth is most commonly associated with the abuse of antacids and proton pump inhibitors, increasing the pH way up high in the bowel. So in a situation like that, if there’s clinical symptoms of small intestinal fungal overgrowth and moderate to many yeast by microscopy, but none cultured, the prevailing thought is that that’s an indication that those yeast very high in the GI tract don’t survive as to be viable in culture when we get the stool specimen. But again, coupling that with the presentation of the patient, you might say, Whoa, okay, this is consistent with small intestinal fungal overgrowth, nothing cultured because they didn’t survive transit through the whole gut. Again, being in this industry for almost 24 years now, I would be the first to tell you that you’re treating the patient and not the lab report. So I love that question. So the approach is, couple those observations and differentials in some cases with the presentation of the patient.

DrMR:

Are you applying that same logic, if the microscopy is positive in either case, but the microscopy is positive in this second case, but the culture is showing beneficial, are you still thinking that this is an overgrowth and just an overgrowth of good players.

DrDQ:

The beneficial yeast would be more the Saccharomyces cerevisiae. The problem with Saccharomyces cerevisiae and boulardii is that you cannot differentiate them without getting into genetic sequencing. So vast majority of the cases that I’ve seen, where S. boulardii / cerevisiae are cultured and identified, it’s often patients that are actually taking S. boulardii. That’s something that you or the patient initiated, so obviously you’re not going to treat that.

DrMR:

I think that’s a really important point for clinicians is sometimes they’ll see an elevation of an organism that is what they’re taking as a probiotic. It’s important not to assume that that’s an issue. It’s iatrogenic, I guess we could say. Now another question that I think clinicians are always pondering is, does an abnormality always require treatment with either an antibiotic, and antifungal prescription or some type of herbal antimicrobial. Two thoughts really quick here. One, I know there there’s a bit of a line between the diagnostic and then the clinical recommendation. So I don’t want to hold you on the hook too firmly for our clinical recommendation, but I am curious to get your thoughts. Let me just lead with my take on this. I think we’ve fallen into this pattern in integrative and natural and functional medicine of being overly quick to use either antimicrobial drugs or antimicrobial herbs when we see an abnormality on a stool test. We may be bringing a grenade launcher into what could otherwise be a knife fight. Things like probiotics or dietary changes might be able to get us to a level of normalcy. But I’m curious to hear your thoughts there.

DrDQ:

Absolutely. I agree. And that’s why I use the term nuke because you know, some of these botanical agents, they’re not so benign, we don’t know exactly what they have the capacity to do to the beneficial and other commensal flora. So there’s really two schools of thought. Some people like to get rid of something right away, because they think the patient is going to be more impressed with that. Yes, we took it out. Well, did you really get better or not? The other approach is, you know what, that really wouldn’t have surfaced unless the microbiome was disrupted and the community was disturbed as to permit colonization and overgrowth of that dysbiotic bacteria. So some people will take the approach of “we need to get things back into balance” and work on restoring the health and abundance and diversity within that microbial community. In some cases, that can be a real challenge because as you know, one of the ways you do that is not only with seeding with the probiotics, but also feeding with the prebiotics. Some things like Klebsiella pneumoniae, for example, and Blastocystis, a parasite, they like those soluble fibers. So in some cases, if you go in and try to take the more gentle, more natural approach of reestablishing and restoring the microbiome, you may be inadvertently feeding something. So it’s really a case by case basis. I am a strong believer in let’s restore balance.

DrMR:

Exactly the way I approach this and for our audience, if you’ve read Healthy Gut, Healthy You, I talk about this approach of cultivating an array of healthy inputs, encouraging the healthiest microbiota possible first in kind of an escalatory fashion. Leaving stronger antimicrobial therapy till later down the line. Sleep, stress, time in nature, exposure to sun, dialing in your diet, probiotics, these are all predecessors to really allowing the healthiest ecosystem to form. Then we work our way up to the antimicrobials at a later date. Again, there can be exceptions to that rule, but it seems to be a higher probability of success if you use antimicrobials in that healthier garden kind of context.

DrDQ:

I can’t emphasize enough with your statement about stress. There is just fantastic research on adrenal stress, chronic stress knocking down specifically lactobacillus and suppressing secretory IGA. So there’s two primary players in a normal fighting off of dysbiotic bacteria that chronic stress can just really rock the boat on.

DrMR:

Yeah. We’ve got to lay our foundation first. You mentioned blasto. are you looking at blasto as something that needs to be eradicated all of the time? I guess I should be more precise in how I ask this question because one can make the argument that probiotics may be sufficient to eradicate blasto. So let me ask you this way. Is blasto something that you’re thinking always requires direct treatment or are there cases where blasto is a commensal?

DrDQ:

Absolutely. There are up to 17 different strains of Blastocystis hominis and one can detect the more virulent strains. I believe it is one in three. But when you’re doing O and P you see many blastocystis, particularly on multiple stool specimens collected on different days. Even there you really have to consider the presentation of the patient because there are many people in the micro world that feel that blastocystis can be very much a commensal bacteria. It really gets down to the strain level. So once again, treating the patient and not the lab test.

DrMR:

Would you echo that same kind of thinking for something like Endonana? There seems to be kind of this host of of organisms that sometimes practitioners, I think with good intentions, are very quick to jump to some type of antimicrobial therapy. I’ve gotten in the habit of really double checking these in various medical databases. Oftentimes you see a narrative, just like you were describing with blasto, where there is a whole lot of credible evidence suggesting that this isn’t always a problem. So it’s really tempered how quickly I go after a number of these. Are there a few choice, examples that you think also fall into that same category?

DrDQ:

Yes. The Endonana. Then you get into situations where you see, and not so infrequently, say blasto and another questionable dysbiotic parasite. Many times when you see multiple of those gray area parasites, it may be an indication that it’s not such a healthy situation. Again, using the forward approach, as opposed to going in and trying to nuke it might be a better course to take.

DrMR:

Gotcha. Another question that I think is a pretty salient one is how should clinicians be looking at probiotic species on either a PCR or a culture? If there’s a delineation, I’d love to hear how you look at those differently. Also how does this predict how someone may respond to a given probiotic or is there a lack of prediction.

DrDQ:

I’d probably have to say a lack of prediction. If, for example, by PCR, you’re seeing extremely low deviation from normal biosis with say lactobacillus or bifido, that patient will likely benefit from lacto bifido combo type of probiotic. Of course, keeping in mind that the probiotics that the person swallows is not truly going to colonize, but while it’s there for approximately two weeks after every time you take it, it’s going to be doing some of the wonderful things that those species do. So in any case where they’re really, really deficient in specific commensal beneficial bacteria, then it’s probably very predictive that you’re going to see a beneficial effect. Then there are others like the F. prausnitzii and Akkermansia where you cannot get probiotics for them because they’re obligate anaerobes, that just wouldn’t survive. They don’t produce spores. You just can’t provide those. F. prausnitzii for example, is up to 14% of the total bacteria in a healthy gut. You can feed forward and induce better colonization of F. prausnitzii, a major butyrate producer major anti-inflammatory species by feeding the proper things in the diet, not only the soluble fibers, but also the polyphenols.

DrMR:

Then when we come down to a challenge, and this is something else that I discuss in Healthy Gut, Healthy You. Let’s say someone does have low levels of F. prausnitzii, and they also have IBS. They may be somewhat intolerant, at least acutely to fiber. So what, on a lab finding, looks like a good decision, clinically may actually really flare the patient. There’s just an importance to make sure, as we’re both agreeing on here throughout the body of the conversation, to look at the lab results in context of the patient, and really use the labs to guide in treating the individual, rather than treating the lab marker at the expense of the individual.

DrDQ:

Right. And those butyrate producers are notoriously low with the many different, six or eight different categories of IBS. So there’s a situation where a lot of the symptoms that are being expressed or exhibited in the IBS patient are in part due to those low level of butyrate producers. It’s a matter of just slowly introducing the soluble fiber to get those species colonized back, to get their anti-inflammatory effects back, to get their butyrate production back to bolster the mucosal barrier. As you say, you don’t just go into somebody like that with 10 grams of inulin, and then wait for the phone call. You’ve created a flatulence machine here and that doesn’t go over real well. You’ve got to wade before you swim.

DrMR:

Well said. Coming back to the mapping of the microbiota, if you will. Or the 360 snapshot that you guys get with your GI 360. I know there’s a lot that can go into the answering of this question, but can you tell the audience how the reporting looks and how the results can help with navigating the clinical algorithm.

DrDQ:

Yes. What’s unique to the way that we use the PCR or the molecular technique to go in and profile the microbiome is very different. There are two extremes. One extreme is to sequence everything and say, here’s everything, good luck clinicians trying to figure out what it means and what do with it. Then there’s the other extreme where they say, well, we think this, this bacteria X, Y, and Z are really important, so that’s what we’re going to report. What we’ve done here is we’ve taken a model and a platform from a research group in Norway, where they used a very scientific process to profile the very complex microbiome.

DrMR:

Sorry, really quick. Is this the GA MAP you’re referring to?

DrDQ:

Yes, sir. From Norway. So it looks at the bacteria that have been validated and tested now in almost 50 different clinical trials to be most, predictive and associated with dysbiosis. It is really a model of dysbiosis where it identifies and then defines dysbiosis. You asked about how does the clinician navigate through that? Well, yes, there are 45 different targets. It looks like a very small town phone book, but what we’ve done right in the beginning of the report is shown a nice little web on a hexagonal diagram. It shows how the patient’s overall profile looks compared to normal biosis. Then even more simplistically using an algorithm based on all of those results, there is a single digit dysbiosis index. So from one to five, with anything three or greater being variable worsening degrees of dysbiosis. I just want to stress that this dysbiosis model was approved in the European union as a test for dysbiosis. Now that is really a separate component. It’s a test within the test of the GI 360, because that doesn’t incorporate dysbiosis. So you can have a dysbiosis index of five, which is as bad as it gets, but that doesn’t factor in the Salmonella or the Yersinia or the Candida albicans that we found in other parts of the test. So it’s very important that that part of the test is really for overall dysbiosis of that particular patient’s microbial community. Then the rest of the report further defines the more pathogenic dysbiosis that can also happen. So it’s really a test within the test.

DrMR:

Is it your view that the DNA adequately answers both the, of the question of the biosis status, whether it’s eubiosis or dysbiosis and the question of pathogen screening, or do you feel it’s best to pair the biosis assessment via DNA with a MALDI TOF culture for the pathogens?

DrDQ:

Even further than that, number one, yes. The dysbiosis profile. So the targeted profiling, how much do you deviate from normal biosis as defined by over 500, very well defined healthy patients. Then we also use PCR for the pathogens and we also use culture and your traditional O and P for the parasitology. So all of those components are important, but the point I’m making is instead of just saying, “wow, here’s everything in your microbiome”, in the molecular analysis of the microbiome that we use, it’s very targeted. When you see, for example, a dysbiosis index of four or five, there may not be a pathogen present at the time, but if you stay that course and don’t restore that microbiome, you’re really setting yourself up for those subsequent pathogens that are reported in the following parts of the test.

DrMR:

Just to make sure I fully understand all of the methodologies, in the DNA test, you’re not doing any kind of a reflexive auto testing of culture criteria? That assessment is strictly DNA? Then if you want to do the MALDI TOF, that would be a separate test kit. Right?

DrDQ:

Correct. There are actually different tubes for the different types of profiling.

DrMR:

Okay. You do feel that the PCR is more of a early screening and is it not ideally suited for, let’s say you’re worried about certain pathogens and H. pylori, is that where you feel it’s best to bring in the culture test?

DrDQ:

Uh, yes and no. Depends on the pathogen. Some of those pathogens, as I said earlier, you don’t want any. So PCR is more sensitive than culture for that, but for those other more dysbiotic bacteria, for example, potential pathogens, that’s the real strengths for the culture.

DrMR:

Gotcha. Okay.

SponsoredResources:

Hey everyone. This is Dr. Ruscio. I quickly wanted to fill you in on the three main resources that are available to you in case you need help or would like to learn more. Of course, I see patients both via telemedicine via Skype and also at my physical practice in Walnut Creek, California. There is of course my book, Healthy Gut Healthy You, which gives you what I think is one of the best self-help for optimizing your gut health and, of course ,understanding why your gut is so important and so massively impactful on your overall health. Then finally, if you’re a clinician trying to learn more about my functional medicine approach, there is the Future of Functional Medicine Review, which is a monthly newsletter, which is a training tool to help sharpen clinical skills. All of the information for all three of these is available at drruscio.com/resources in case you’re on the go, that link is available in the description on all of your podcast players. Okay. Back to the show.

DrMR:

Is there anything else here that you think is important for clinicians to be aware of or any other news or updates you want to touch on?

DrDQ:

Yes. I would say that at this point, using the two different PCR platforms that we use, unlike any other laboratory there have now been 20 peer reviewed publications using this platform. So I mentioned validated and vetted, this has really got a life of its own. Some of the clinical trials are just fascinating. There was a trial where they studied the dysbiotic effects of artificial sweeteners on overweight, obese patients who were dieting. They’ve studied the effects of a severely restricted FODMAP diet on causing significant dysbiosis. Most exciting to me is documenting the staying power of fecal transplants. Looking at how long does it last. One of my pet peeves with that is, if you get into a really dysbiotic gut and nothing seems to work, a fecal transplant can do wonders. However, if a patient doesn’t follow and here we get back to my seed and feed, you put in those nice, healthy microbiome from the fecal transplant and you don’t feed it what it needs, you keep sitting on the couch, eating the Doritos and your bad diet, then it’s not going to have any staying power. So I can’t emphasize enough the seeding and feeding of a healthy microbiome.

DrMR:

I want to commend you guys for using that data set out of Norway. I’ve said on the podcast many a time, I felt that that was the lab and/or the body of research that has really gotten the farthest along the path of validating DNA testing. Being able to say this actually correlates as in one study, I believe we wrote up in our clinicians newsletter, dysbiosis and IBS compared to dysbiosis and IBD and they’re actually tying to clinical conditions, this dysbiosis finding and really giving us meaning. Otherwise a lot of the information seems to be so academic as to be very difficult to extract clinical meaning from it. So just, great work in using that data set.

DrDQ:

Absolutely. As we keep moving forward, we are appreciating more and more all the time that there are many different types of dysbiosis and this type of targeted approach is how we’re going to really be able to pinpoint and define those different dysbioses.

DrMR:

I think we’re going to learn. We’re just in the infancy right now of our learning. It is going to be exciting to see in 10 years, in 20 years, what granular level of details and predictiveness we’re able to establish with these tests. So anything you want to leave people with? Tell people, again, the names of the tests in case they’re trying to order one andanything else you want to kind of close on?

DrDQ:

Well, I mean we still offer the comprehensive stool analysis with parasitology, which is culture based. Then the GI 360 profile. We maintain all of the comprehensive stool analysis, the CSAP, and have simply added the two PCR platforms. So some people elect to stay with the CSAP and other people want progress and add those PCR components and get a more detailed view.

DrMR:

Great. Well, David, thank you for taking the time. I know I gave you a kind of a litany of questions there, but it was really great to be able to pick your brain, get into some of these details, provide clinicians with answers. They’re ordering these tests and they’re always looking at this one area and saying, huh, I’m not really sure how to interpret this. So hopefully we’ve shed some light on some of those confusing areas for people.Again, just love the fact that you’re validating the testing that you’re using. So, so important in this wild west of microbiota research that we stay grounded in science and just really, really appreciate it.

DrDQ:

Oh, you’re very welcome. It’s a pleasure to be with you.

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