Unmasking the Truth: The Science Behind qPCR Stool Testing with Dr Tom Fabian

In this episode, we delve into the world of qPCR stool testing, with Dr Tom Fabian unravelling the common myths surrounding its validity and reliability. 

Throughout the episode, we explore the scientific evidence that underpins qPCR stool testing, addressing misconceptions and highlighting its role in clinical decision-making.

Listeners will gain insights into the types of conditions that qPCR stool testing can effectively uncover and get an insight into the interpretation of test results, offering practical tips on integrating qPCR stool testing into routine clinical assessments. 

The episode also covers technological advancements that enhance test accuracy and reliability, demonstrating its effectiveness in clinical practice.

Whether you're a seasoned healthcare professional or new to the field, this episode offers a deep dive into how qPCR stool testing can enhance patient care and decision-making, leaving you well-informed and equipped with the knowledge to make confident diagnostic choices.

Meet Dr Tom Fabian, PhD

Dr. Fabian is a leading expert on the role of the microbiome in health, immune function, chronic disease, and aging. 

As a translational scientist, his primary focus is on the clinical application of microbiome research in the integrative and functional medicine space. He received his PhD in molecular biology from the University of Colorado, Boulder, and has worked as a biomedical researcher in the biotechnology industry, and more recently, as a consultant in the microbiome testing field.

 Currently, Dr. Fabian serves a consultant and science advisor with Diagnostic Solutions Laboratory, and he is also a Science Advisory Board member with Designs for Health. In addition, he is certified as a Nutrition Therapy Practitioner by the Nutrition Therapy Institute in Denver.

Get in touch!

Shownotes and references are available on the Designs for Health website


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DISCLAIMER: The Information provided in the Wellness by Designs podcast is for educational purposes only; the information presented is not intended to be used as medical advice; please seek the advice of a qualified healthcare professional if what you have heard here today raises questions or concerns relating to your health

Episode Transcript

Speaker 1 (00:11):
This is Wellness by Designs.
I'm your host, amy Skilton, andjoining us today is Dr Tom
Fabian, an educator and medicalconsultant, who I'm so excited
to speak to.
Dr Fabian is a leading experton the role of the microbiome in
health, immune function,chronic disease and aging.
As a translational scientist,his primary focus is on the

(00:34):
clinical application ofmicrobiome research in the
integrative and functionalmedicine space.
He received his PhD inmolecular biology from the
University of Colorado, boulderand has worked as a biomedical
researcher in the biotechnologyindustry and, more recently, as
a consultant in the microbiometesting field.
Currently, dr Fabian serves asa consultant and science advisor

(00:59):
with Diagnostic SolutionsLaboratory, and he is also a
science Advisory Board memberwith Designs for Health.
In addition, he is certified asa Nutrition Therapy
Practitioner by the NutritionTherapy Institute, and today
we're going to be talking allabout microbiome testing.
I can't wait to pick yourbrains, tom, and welcome to the

(01:21):
Designs for Health podcast.

Speaker 2 (01:23):
All right, well, thank you so much, amy.
It's great to be here today,looking forward to the
conversation.

Speaker 1 (01:29):
Me too.
There is so much I want to askand I know as a clinician who
works in this space and all ofthose that are listening, I feel
like microbiome testing isstill a landscape and territory
that people are exploring withexcitement, but also it feels a

(01:51):
bit like uncharted territory attimes, and it's really gaining
knowledge and confidence in.
This area is an ever emergingspace because there is so much
to know and, of course, there'sfar too much to know that we
could ever cover in a singlepodcast.
But what I want to talk withyou today about is some of those

(02:11):
areas that I thinkpractitioners get a bit tripped
up on, and perhaps because thisisn't something that was in the
naturopathic curriculum at thetime when we trained, it's
really one of those postgraduateareas that we're all, I guess,
catching up in, and I supposewhere I'd like to start is
looking at the variousmethodologies that can be

(02:35):
applied when it comes toassessing what's going on in the
microbiome and what the keydifferences are.
Can you start there, for?

Speaker 2 (02:46):
us Absolutely.
Yeah, we do get a lot ofquestions about that as well.
So it turns out whenpractitioners are considering
what sort of methods, what sortof tests may be best for
assessing the microbiome and guthealth.
We know that there are severaloptions out there, of course,

(03:11):
but I think one of the startingpoints for practitioners to be
aware of is it's really aboutcomparing apples and oranges.
We're not always comparingapples to apples, so it's not
sort of there's a lot ofquestions about you'll see these
in social media which gut test,which microbiome test do you
like the best?
Which do you think is the bestfor clinical practice?
And so it is important tounderstand that they're really

(03:32):
apples to oranges comparisons.
And so we want to look at whatare those differences among the
tests, and there's quite a few.
So a lot of it boils down tomethodology, and there's quite a
few.
So a lot of it boils down tomethodology.
So, when it comes to themethodology, really, the two
sort of main current methodsthat are out there these are
both DNA based methods.

(03:54):
One of them is referred to asmetagenomic sequencing, one of
them is referred to as PCR, inparticular, something called
quantitative PCR.
So I'll start with metagenomicsequencing.
So that's a method that'scommonly used currently in
research.
So a lot of the researchscientists who are studying the

(04:15):
microbiome like to usemetagenomic sequencing because
they can get this big pictureview of the microbiome they're
studying the community.
There's a lot of researchquestions that you can answer
with that.
Also, there's a lot of data.
So it's certainly a big deal totry to figure out how to
analyze all that data.
Oftentimes it's sort of in thecontext, for example, of

(04:39):
understanding what patterns ofmicrobes may be related to a
given disease or givenenvironmental change or even
dietary factors.
But when you really look at thatpipeline, so research I think
we all know when it comes to thepoint of research often is for
clinical applications.
So there's the idea of basicresearch and sort of that

(05:03):
preclinical research.
Then there's clinical researchfor the development of
diagnostic type tests.
So that's really one of the bigdifferences is metagenomic
sequencing was really developedfor research purposes Because
there's a lot of data to dealwith.
A lot of the microbes that comeup on metagenomic sequencing.

(05:24):
You'll see these lists ofhundreds of microbes in the
microbiome.
We don't really know what mostof them do.
They haven't really been wellstudied.
And that's really important whenit comes to clinical
interpretation.
When you're looking at microbesthat can inform clinical
decisions, you want to knowsomething about those microbes,
you want to know what they'relinked to.

(05:44):
You want to know somethingabout those microbes, you want
to know what they're linked to.
You want to know somethingabout what you can do about them
, what sorts of things they'redoing in the gut.
So oftentimes, with thatmetagenomic sequencing and
research, the ultimate goal isto identify a small subset that
can be used in a clinical typetest, and those clinical tests
will often use PCR.

(06:05):
So it's really more of adiagnostic type test when you're
talking about PCR.
Of course, that was somethingthat I think became better known
during the COVID epidemic, apandemic where suddenly a lot of
clinicians became much moreinformed about testing and the
types of testing.
For COVID, the gold standardfor detecting these types of

(06:26):
pathogens is quantitative PCR.
So that's really one of the maindifferences there, and so,
again, you're casting a wide net.
With metagenomic sequencing,you can look at things like
diversity and sort of all thedifferent microbes that are
there up to a point.
One of the other advantages,though, of quantitative PCR
other than it allows you tofocus in on the microbes that

(06:48):
are most clinically relevant,based on the research often
using metagenomic sequencing isthere's really kind of a long
list of advantages.
One of them is rapid turnaroundtime.
So metagenomic sequencingthere's several weeks before you
can get the results, butoftentimes you want those
results quicker to be able tomake decisions for patients.

(07:10):
The other things come down to.
Really a lot of it has to dowith specificity and sensitivity
.
So when it comes to specificity, metagenomic sequencing it's
really good at identifyingspecificity.
Metagenomic sequencing it'sreally good at identifying kind
of the big picture, but when itcomes down to specifics specific
pathogens, for example,specific opportunists it's not

(07:40):
always as good at doing that,for several reasons.
One is a lot of these importantmicrobes that we think of as
pathogens and opportunists arelow abundance, so they can be
present in amounts in themicrobiome that are far lower
than the typical commensalmicrobes, and yet they can still
cause a lot of problems, eventhough they may be present at a
million times lower inconcentration, because they can
do kind of a lot of damage inthe gut.

(08:01):
That's where qPCR shines.
It was specifically developedto be able to zero in on these
particular pathogens andopportunists and other important
microbes so you can kind ofidentify those needles in the
haystack.
So that's how you can reallythink of this quantitative PCR.
You're not really looking atthe whole haystack, you're

(08:21):
trying to identify reallyprecisely and quantitatively
these needles in the haystack.
So I'll kind of turn it back toyou because there's a lot of
subtopics we can talk to or talkabout here in terms of the
differences, but a lot of it hasto do with clinical and
diagnostic versus more sort ofresearch focused, and then also

(08:43):
the specifics of reallycarefully quantitating and
identifying the microbes thatyou're looking for.

Speaker 1 (08:50):
We can certainly get into some of the details about
methodology and sort of whythere are these differences, but
that's kind of a little bit thehigh level in terms of the
differences yeah, thank you forclarifying that, because I think
you know there there are somany different ways to approach
any problem or assess data andthere's always limitations and

(09:11):
pros and cons.
And I suppose, if I was tosummarize what you just shared
then is that you know,metagenomic sequencing provides
just a huge volume of data, butat this, based on what we know
as far as clinical applicationof that data goes, it's quite a
small fraction of that andthereby quantitative PCR testing

(09:35):
is allowing us to cut straightto the chase for the things that
we need in a much quickertimeframe, but also focusing on
those things that are clinicallyrelevant based on the
scientific literature that wehave today.
And I suppose that really andyou can correct me if there's
more to this but answers thequestion around which method is

(09:58):
most accurate, and I'm sure it'sa little bit more nuanced than
what I just said, but it's notthat either method is inaccurate
, but there is a difference inapplication and the way that we
pull that information togetherand why.
And if we're considering what'smore relevant to clinicians, at
this stage I can see how PCRtesting is going to give us the

(10:22):
quickest access to the datathat's most clinically relevant.
But in terms of microbiomefunctions, whether it's LPS
production or something else, isthere anything further?
We need to understand eitheraround the accuracy of the
testing or which methods aremore important to understand the

(10:43):
functional aspects of what'sgoing on.

Speaker 2 (10:46):
Absolutely yeah.
So there's different ways youcan look at that, and that's
actually one of the sort ofpoints that often the
metagenomic sequencing typecompanies tend to promote is
that they can look at a range ofdifferent functions.
Technically, you can do thesame thing with PCR, as long as
you target those functions.

(11:08):
You can do it at the specieslevel and look at specific
butyrate-producing bacteria orLPS-producing bacteria.
I think the key there is thereare different ways of looking at
functions.
You can group microbes by theirfunctionality.
Again, you can look atbutyrate-producing bacteria,
lps-producing bacteria.
Ultimately, though, you canlook at butyrate producing
bacteria, lps producing bacteria.
Ultimately, though, you want toknow a lot more about that

(11:29):
context.
So context is important.
So if you're just, say, doing ametagenomic sequencing test and
they're giving you sort of ascore for LPS production, that
doesn't really tell you some ofthe information you'd want to
know.
That can still be useful, butyou want to know who's producing
that, because, for example, lpscan be produced by microbes

(11:50):
that are commensals.
E coli is one of the sort ofbest known commensals that
produces LPS.
Commensal E coli is actuallygenerally harmless.
It can be overgrown in certainscenarios, but it's not the same
thing as detecting, say,salmonella.
Salmonella is closely related.
It also produces thisinflammatory type LPS.

(12:12):
It's very similar to E coli,but you want to know is it
salmonella or is it E coli?
And again, with qPCR, you canbe much more confident because
salmonella is present, usuallyat low levels.
Qpcr is able to detect down to10 to 100 cells per gram of
stool, and that's, on average,about 100 billion microbes per

(12:37):
gram of stool.
So, again, it's really theneedle in the haystack.
Sequencing is not able.
Generally, the type ofsequencing that's done
commercially, sort of thesedirect-to-consumer type tests do
what's called shallowsequencing, so you're basically
only able to look at the moreabundant microbes, so important

(12:59):
pathogens like salmonella wouldnot generally be detected as
reliably, or not detected at all.
So, again, when it comes tofunctions, you can look at
functions either way.
You can look at it based ongroupings, based on genes.
Ultimately, though, you want toknow who is involved in that
function and what is the context.

Speaker 1 (13:20):
I think that's such an important point and I suppose
that really establishes whyquantitative PCR is so important
in terms of specificity as wellas the actual quantity.
Because lipopolysaccharides,yes, they can generate
inflammatory responses in thegut wall and, of course,

(13:41):
systemically from there, butknowing that they're present
doesn't give you much directionaround what needs to be done
about it, because thedistinction between commensals
that might be producing themversus pathogens is a big one,
and also the volume of that.
You know, are they present?

(14:02):
Sure, but in what quantity?
And is this a quantity we needto do something about?
So I think, from a clinicalperspective, that really can
guide a practitioner reallydirectly in terms of what needs
to be done, if anything needs tobe done.
But I guess one of the otherchallenges then that can come up

(14:22):
with quantitative PCR isbecause it is so sensitive.
We also can get a report thathighlights low-level pathogens
that might otherwise be missed,and I would love to hear from
you about the clinicalsignificance of these kinds of

(14:43):
results that come through.

Speaker 2 (14:45):
We get that question quite a bit as well, as you can
imagine, because of thesensitivity, we do pick up low
levels of opportunists andpathogens.
That often raises questions andof course a lot of that has to
do with just knowing how tointerpret the test properly.
So education is a big piecepart of that solution.
When you're looking at thepresence of, say, a pathogen, so

(15:10):
there are differences in termsof levels, of course,
quantitative levels, and that'sreally again where PCR shines.
We do want to know is this justsort of a very small amount?
You might have just had a minorexposure and then the patient
isn't necessarily symptomatic.
So symptoms are obviously veryimportant to assess in terms of
their relevance.

(15:30):
So once again, it does comedown to context.
So when it comes to pathogens,we know that their presence
sometimes can be indicative ofsome of those protective factors
being less robust than theyshould be, even though they may
not be developing the clinicalsigns and symptoms of a

(15:53):
full-blown infection and sotherefore may not necessarily
need to be treated for thatpathogen.
We still know that if it'spresent, for example, stomach
acid might be insufficient orthe protective commensal
microbiome might be insufficient.
So it's still kind of a cluefor us to look for these other
imbalances and ask the questionwell, why is this pathogen there

(16:16):
in the first place?
So that's, one of the reasonswhy they're still reported, even
though they may not always beat a level that's causing
symptoms, and I think that's aconcept that really kind of gets
misinterpreted.
There's a lot of misconceptionsaround there.
You hear practitioners refer tothis term false positives.
I think some of that sort ofmisunderstanding comes around

(16:40):
this idea that oh, I seesalmonella or I see C difficile
on the test.
My patient doesn't have thosesymptoms at all.
So what does that mean?
Is that a false positive?
In most cases, of course, thevast majority of cases, that's
not the case.
Pcr, again, is considered veryspecific, very sensitive.
It can pick these up, but itdoes mean in most cases that

(17:04):
it's there.
Sensitive, it can pick these up, but it does mean in most cases
that it's there but it's likelyto be an asymptomatic infection
, and that's an area that'sbecoming better studied now that
we have these more sensitivetechniques like PCR,
quantitative PCR.
So we know that many of thesepathogens we can get exposed to
and some individuals may go onto develop an infection if their

(17:25):
immune system is compromised,if they don't have a good amount
of commensals, et cetera.
So once again, there's theseindividual differences and it's
good to be aware of thosedifferences and that that
influences how you interpret theresults there.
We even see a few cases wherepatients might have higher

(17:46):
levels of pathogens and yetthey're still asymptomatic.
So that would suggest andoftentimes in those cases we'll
see that their commensalmicrobes are actually at a
really good level and sopresumably, based on the
research, their microbiome isable to basically kind of keep
those pathogens in check, whichis one of their important roles

(18:08):
in the gut.

Speaker 1 (18:10):
Thank you for sharing that because I think, you know,
as we develop more sensitivetesting across the board in
medicine and we also learn moreand more about the interface
between the innate and theadaptive immune system, we're
really seeing the meeting of ourinnate immune system's ability
to protect against infection.

(18:31):
And when it comes to pathogens,for example, it's not a binary
situation where you either havean infection or you don't,
meaning there's an absence ofthose microbes.
It's that we have a wholeecosystem that works together.
You know, using an example,with skin you can pick up staph
on.
You know, let's say, a sampleof 100, but only maybe 20% have

(18:55):
an actual staph infectionbecause their hydrolipid film,
their antimicrobial peptidesthat are produced at the skin
and their commensal skin florastaying on top of the other
things that could otherwisebecome pathogenic.
In the event, the immune systemgoes down and I think, when
we're looking at the gut, thesheer volume of what comes

(19:16):
through there in terms ofantigenic material, we've got
secretory IgA, which is part ofthe mucosal glycocalyx, plus the
commensals, you know, and thoseother things like stomach acid
production, bile acid production.
So what we're really seeingwith these really sensitive
tests is where, all of a suddenlifted the lid on.
You know what else is in thereon a more, you know, smaller

(19:40):
scale, but that doesn'tnecessarily mean there is an
infection, or even that there'snecessarily been a past
infection or maybe you know itcould be.
But what we're reallyidentifying is, or really
witnessing is, you know, theinnate immune system at work and
managing the presence of thosethings.

(20:01):
And you know, is thatclinically relevant or is it not
?
That's going to depend on thecase history.
You know so many other factorsbut in terms of you know that
coming up, probably the questionthat I've seen come up the most
is around Helicobacter pylori,and I think that's because you
know it's one of those pathogensthat can cause pretty serious

(20:23):
symptoms when there is aninfection present.
If an infection is present,usually treatment is pretty
rough and has some collateraldamage around.
You know the gastrointestinalsystem and I think a question on
some practitioners' minds arelike when it pops up on a PCR.
You know, in this case, withthe GI map, where do you make

(20:44):
the distinction around whatneeds to be done?
Is it, you know, is it acollation of symptoms?
History, are there any othervariables we have to take into
consideration in addition tothose?

Speaker 2 (20:58):
So you definitely hit the nail on the head.
That context is always isreally important.
So it does come down toclinical judgment.
But also we provide theadditional information for a
reason.
So of course the quantitativeamount of H pylori does make a
difference.
But keep in mind that these arenot sort of, as you kind of

(21:19):
alluded to, the cutoff set.
It's either positive ornegative in some of the older
tests.
It's not like you meet somemagical threshold level and
suddenly it's either positive ornegative in some of the older
tests.
It's not like you meet somemagical threshold level and
suddenly it's a problem, right?
So for some individuals justbelow that threshold it could
still be a problem.
For other individuals who havea healthier gut, they can
probably tolerate higher levelsand it's really not as much of a

(21:41):
problem for them.
But it's still a good guideoverall.
I mean you want to know overall, especially if you're treating
or you're doing something withthe gut and you're comparing it
before and after.
If you see that it's down, saytenfold, then that means it
might still be present.
Because a lot of people stillhave low-level H pylori, that
may not be a problem.

(22:02):
But, that tells you that yourprotocol is certainly going in
the right direction.
There is, of course, acorrelation with symptoms, so
you alluded to these moreserious symptoms.
That gets into sort of more ofthe conventional medical sort of
view of H pylori as a cause ofulcers and can even cause

(22:22):
stomach cancer.
So certainly very seriousoutcomes for some individuals.
The virulence factors certainlyplay a key role there.
They're considered risk factors.
So, like any risk factor, ifsomething's present that could
be potentially serious, it doesnot necessarily mean you're
going to get that condition, butit's a piece of information for

(22:44):
the clinician that says youmight want to weigh this a
little bit more.
If you're kind of on the fenceabout, should I use antibiotics,
should I just treat with anherbal protocol or even not
treat?
There's not a lot of symptoms.
Presence of virulence factorscan basically weigh in on that
decision.
And there's also in our fieldfunctional integrative medicine.

(23:07):
Of course we look at things ina different way, beyond just
kind of the conventionalmedicine scenario where, okay,
so the patient doesn't haveulcers, doesn't necessarily have
a family history risk forcancer.
Is there a problem here withthis H pylori if it's still high
?
Is there a problem here withthis H pylori if it's still high
.
We do know that H pylori, forexample, can affect stomach acid

(23:29):
and that may not be somethingthat in the conventional
medicine field they're tooconcerned about, but certainly
in our field we know thatoptimizing digestion certainly
can be one of the goals whenyou're working with patients.
So some practitioners maydecide to treat usually
typically more with herbaltreatments in those scenarios
where you might be moreconcerned about some of these

(23:50):
less serious scenarios, butscenarios that might still be
affecting patient health, likehypochloridria.

Speaker 1 (23:57):
Yeah, thank you for pointing that out, because I
think this is where appliedfunctional medicine is where it
really steps into the fore andwhen we sort of zoom out and
look at germ theory versusterrain theory and how those two
meet when it comes to assessingpatients.

(24:19):
For someone who has low levelstress, who's asymptomatic, who
appears to be producing, youknow, doesn't have any digestive
issues whatsoever, that doesn'tmean it's necessarily something
we need to treat.
But if another patient had theexact same test result, but we
can see their ALP is low, whichmeans their zinc's down, which
means their stomach acid isn'toptimal, you know, their protein

(24:41):
and creatinine scores are down,we're seeing signs of
malabsorption or elevated muscleturnover and any of those
secondary signs that areindicative either, you know,
catabolism issues, stress issues, adrenal, you know, poor sleep,
maybe co-infections of othersorts that are obvious, then to

(25:03):
me that would say the weight oflike the pathogenic information
is this person's overall system,innate immune system isn't
particularly strong.
They've already become weakenedin other areas and therefore
this potential pathogen is moreof a threat than it is for
someone whose terrain is verystrong.

Speaker 2 (25:23):
Exactly, yeah, and I actually wanted to expand upon
that just a little bit in termsof the terrain.
I think that's a great term.
Overall In the research thereis just sort of this growing
focus, not just on themicrobiome.
In the early years that was thefocus, using metagenomic
sequencing and other ways tokind of characterize the
microbes that are there, andthen they would see there are

(25:46):
these differences in differentdiseases and conditions.
And then of course, eventuallythe question is, why is that the
case?
So looking at the gutenvironment is really important.
It's not just a one-way effectwhere the microbiome affects gut
physiology Certainly it doesbut the physiology in turn turn
affects the microbiome, and sothat's another key piece of the

(26:09):
puzzle that you really want tohave in a clinical test when
you're looking at gut health andthe microbiome.
To the point where I think itwas just three or four years ago
in the research community theyactually redefined the term
microbiome to not just includethe microbes themselves, which
is referred to as the microbiota, but to also include gut

(26:31):
physiology, the environment.
That that's equally importantbecause the two are sort of
integral.
So you mentioned the immunesystem.
We certainly know thatinflammatory microbes, pathogens
, lps-producing microbes, caninfluence inflammation, but in
turn one of the reasons they do,that is, inflammation actually

(26:52):
creates a favorable environmentfor those pathogens and
opportunists and it's alsodetrimental to the commensals.
So it's sort of like they'rekind of tipping the balance in
their favor by promotinginflammation.
Sometimes you can haveinflammation, of course,
starting for other reasons.
We even know that actuallyantibiotics, under certain

(27:13):
circumstances, can start thatprocess of low-grade
inflammation gut infections,poor diet, stress to some extent
.
So if you're looking for theseroot causes, what might be
influencing microbes and why youhave these imbalances, it's
really essential to have accessto that information on digestion

(27:36):
, immune function, intestinalbarrier, health, et cetera.
That's incredibly important forinterpretation.

Speaker 1 (27:46):
Yes, as you say, context is everything and you
can't just look at themicrobiota out of context with
all of the other elements of thephysiology that make up a good
gut and again, zooming out theelements of physiology in a
human that sets up gut healthfor better or for worse, and I
think that's one of thechallenges of applied functional

(28:08):
medicine is you have to takeinto consideration all of those
moving parts and how they fittogether.
And ultimately, I think thisbrings us back to that
naturopathic principle of reallytreating the human in front of
you and not just the data thatyou're looking at.
You have to find a match interms of appropriate treatment

(28:29):
response.
But because we are now in a dayand age of more data and I
think it's very sexy and veryexciting and very interesting.
I think another thing that ischallenging that I'd love to
explore a little more with youis the impact of live organisms
versus dead organisms and alsowhat's being picked up as far as

(28:53):
genetic material inquantitative PCR or metagenomic
sequencing.
And you know, I think when Ithink about this from a clinical
point of view, I understandthat even dead microbes, their
DNA and their pathogenassociated molecular patterns or
PAMPs or DAMPs can stilltrigger toll-like receptor

(29:17):
activity.
But again, in the context ofthe physiology, you know where
is the weight sitting in termsof disease versus.
You know something that theweight sitting in terms of
disease versus you knowsomething that we don't have to
worry about so much.
But I think now that we haveaccess to these more sensitive
tests in a clinical setting,they've left the research, you
know, academic labs and arrivedin our clinics.

(29:40):
When we look at these DNAmethods, where is the line in
terms of what it's picking up oforganisms alive versus dead,
and what does that meanclinically in terms of infection
indications?

Speaker 2 (29:54):
It's really an interesting topic.
We got this question prettyfrequently when I first started
with diagnostic solutions awhile back, because there's this
idea that, just as youmentioned, dna can be released
by dead microbial cells.
And do these methods detectthat and is that still
clinically relevant to detectdead microbes?

(30:14):
So one of the overallconsiderations is once again,
you have to look at the context.
So the short answer is yes, dnamethods, whether it's
sequencing, or PCR can pick upDNA as long as it's still intact
, right.
So you need a sufficientlyintact amount of DNA.
If it's all kind of degradedand the pieces are too small,

(30:37):
then neither of those methodsare going to work to reflect
that.
So you'd have to have fairlyintact DNA present to reflect
that.
So you'd have to have fairlyintact DNA present.
That's really one of the keysis is there intact DNA present?
Some estimates suggest that, inwhen you're sampling stool with
DNA methods, again, eithersequencing or PCR somewhere in

(30:58):
the range of 20 to 30% is frommicrobes that are basically no
longer intact.
The question is, though is thatfrom past infections or is that
just because microbes died anhour before?
Because microbes have this veryrapid lifestyle, and that's
likely still relevant if theydied just a few minutes or a few

(31:19):
hours before.
But mostly what you want tothink of because we hear this
all the time I think people havethis concept that we're
thinking more kind of confusingthe concept with antibodies,
antibodies that are detected inyour blood or your serum, two
pathogens.
Those can reflect pastinfections, and that's kind of
the definition of you know, kindof a principle for how vaccines

(31:43):
work, et cetera.
But ultimately, when you'rethinking of the gut.
The material in the gut ofcourse is passing through the
vast majority of, even microbes.
We lose a pretty largepercentage of microbes every day
just through your normal bowelhabits and of course that's kind
of continually moving throughthe GI tract and an average

(32:05):
transit time.
I know it varies quite a bitbetween people who have fast or
slow transit, but the roughaverage is somewhere around 28
hours.
So at the very least, for themost part, you're not going to
be picking up any microbes thatare weeks or months old because
they've already been flushed outof the system, that are weeks
or months old because they'vealready been flushed out of the

(32:26):
system.
There's this idea that well,maybe they're hanging out in
biofilms.
If they're actually in biofilms, almost by definition they're
still active right, because theyhave to be able to form the
biofilm.
They have to be able to stillkind of be in the biofilm and
stay alive because they're kindof just protecting themselves
temporarily.
So I don't want to get kind oftoo in the weeds here, but it's

(32:49):
important to think of microbesin the gut as live, dormant and
dead.
So dormant is kind of acategory we don't hear too much
about, but a lot of the microbesactually are thought to be
present in dormant orsemi-dormant states, because
they're only going to grow whentheir particular food is
available and, of course,generally we're not eating 24-7,

(33:12):
right?
So we're going to have a periodof fasting, where the microbes
don't have access to theirfavorite food sources, for
example the ones that thrive onmucus, they're probably going to
be a little bit more steady.
But the question is, you know,once again it comes down to
clinical relevance.

(33:32):
So, for example, when youcompare DNA methods to you may
have heard the termmetatranscriptome these are
expression-based type tests.
Those are only going to detectmicrobes that are essentially
active at the time that themicrobes are sampled, because
you have to be active in a livecell to be able to express your

(33:53):
genes, whereas DNA, again, couldbe around for a while, at least
a few hours or so.
But the idea there, though, isthat you can detect, with DNA
methods, microbes that may bedormant in stool but were
clinically relevant when theywere in the small intestine or
in the stomach.
So that's essentially theprinciple, for example, behind

(34:15):
detection of H pylori.
So, without getting into toomuch detail, we know that,
generally, h pylori present instool is dormant.
Detail we know that, generally,h pylori present in stool is
dormant.
It's present in a differentsort of form of cell that's
still alive but not active likeit would be in the stomach,
because, once it's out of thestomach.
That's just not its favoriteenvironment anymore, but it can

(34:38):
stay alive.
So long story short is a lot ofthese clinically relevant
microbes like H pylori, giardia.
We know Giardia causes problemsin the small intestine and yet
we pick it up in stool.
So if you were just to go withone of these metatranscriptomic
tests, chances are you wouldn'tsee those at all because they're
no longer really very activeWith DNA.

(35:00):
You can pick them up comingfrom these higher places higher
up in the GI tract.
So I think it's important tokind of distinguish that
temporarily where somethingcoming from the stomach like H
pylori, that again takes severalhours to get down into the
stool.
But it's not from a pastinfection.

(35:20):
That's once you know in thepast infection, that's once you
know in the past.
So that was kind of a lot ofinformation there.

Speaker 1 (35:30):
But it's not as simple of a topic as as you
might initially think so it'simportant I think to have some
of that context around it Ithink so, and I think that is
something we really need to beaware of as clinicians is the
limitations and the context forpathology testing.
And that is, you know, in thecase of metatranscriptomic
testing, you know if you are.

(35:50):
If you're actually taking asample directly from the stomach
or a sample directly from thesmall intestine and you're
looking for microbes that areactually active in those areas,
then it becomes more clinicallyrelevant.
But if what you're doing issampling the stool that has been
through an entire life cycle ofroughly 28 hours or whatever it

(36:12):
is, and has gone through pHchanges and undergone various
different mechanisms ofdigestion, you have to view the
data that you're getting in thecontext of that.
And again, it's not this binaryconversation that you either
have an infection or you don't,or the microbes are active or
they're dead.

(36:32):
You have this dormant statewhen they are not in the
environment in which theyactually come alive.
There's also, in terms of thevolume, there's a threshold
after which quorum sensingswitches on and pathogens can
actually become pathogenic, asopposed to just the little guys
that are kind of hanging out notreally bothering anybody.

(36:54):
And I think it, yeah, wheneverwe're looking at this data,
we've got to look at it in thecontext of all of those those
aspects.
So thank you for sharing thatbecause I do think there is.
You know, some people might viewum dead dna first of all not to
have any effect on the immunesystem, which of course it can.

(37:17):
But it also doesn't mean thatit's an old infection or is
irrelevant to the situation,because you know the the bulk of
the stool is microbes and it'sbeing sheared off the gut wall,
you know, within the last 28hours or so give or take, which
means it's still, you know,contextually relevant to today

(37:38):
or the last few weeks, notsomething that happened years
ago.
That's still kind of kickingaround.
I think the only exception tothat might be where someone has
done a stool test post.
You know a massive bowel, youknow, and gastrointestinal
protocol that's included.
Shearing off, you know, plaquesand old material that maybe has,

(37:59):
you know, collected there.
But typically when cliniciansare running a GI map, it's after
an initial presentation andtypically before a protocol,
it's being used to guide aprotocol.
So in the way in which it'sadministered, typically that
information can be consideredcurrent rather than a reflection

(38:21):
of something old that's beensitting around in the gut.
But I think what that leads meto, then, is the next question
around how it can be used todiagnose things, and you've
given us a really goodexplanation around how to filter
the information that we'regiven regarding Helicobacter
pylori, but I know that SIBO isanother big thing that comes up,

(38:44):
and, from a clinical point ofview, where do you see the GI
map informing what we know aboutSIBO?

Speaker 2 (38:53):
actually um, just before we dive into that though,
because to me that's a veryinteresting question, we get
that one, probably it's in ourtop three, four questions.
We get um.
One of the things I wanted toadd a little bit though, about
the DNA thing, because it isfairly nuanced is this idea of
biofilms or plaques in the gut.
Certainly, plaques, biofilmsthey might sort of be kind of

(39:16):
the same concept, but it'sactually known that biofilm is
dynamic, right?
So biofilm itself is constantlyremodeled by the organism.
So even you might think, kindof biofilm is this thing that's
just sitting there, um, andthere might be certain organisms
that are maintaining thatbiofilm.
So if you were to basicallydetect that in stool or sample

(39:38):
it directly, over time you stillsee those same microbes, but
they're they're sort of dividingand changing over time.
The biofilm's changing andthey're attached, typically to
the mucus or the underlyingepithelium.
That's constantly turning over.
So what we think of and seemsto be kind of this constant
thing, oh you have biofilm.

(39:58):
It's been there for quite awhile.
It actually is very dynamic.
So I just wanted to kind ofmake that point that, once again
, what we're looking at in stoolis still not really reflecting
the past very far back, becauseeven biofilms are constantly
changing so that's a good pointyeah, that's something I think

(40:20):
that's just come out of researchin the last few years and takes
things a while to kind offilter down, but we could
probably have a whole podcastjust on that whole
topic.
As far as this question, we geta lot.
Can you use stool testing in aparticular GM app, to quote,

(40:40):
diagnose SIBO or even to getsome clues?
Does the patient maybe haveSIBO?
So, in terms of certainlydiagnostic, there are
definitions out there for how todiagnose SIBO, based on either
taking a sample directly fromthe small intestine and then
using culture and thenessentially counting the
colonies on the culture to get acolony forming unit or CFU

(41:05):
count.
So there are definitions there.
The most common, of course, isbreath testing.
So breath testing is certainlydifferent from stool testing,
and that's considered theaccepted way, or at least the
most common way, to assess SIBO.
But keep in mind though, thedefinition there is based on
gases when it comes to thebreath testing, so it's based on

(41:28):
microbes that produce gas.
When you look at GNMAP we justtalked about that we can get
detect DNA from microbes thatare coming from higher up in the
GI tract, so it's giving usclinical insights into some of
these key microbes that we knowfrom research live or cause
problems in different parts ofthe GI tract, and that's

(41:51):
certainly true for the smallintestine.
So we talked about Giardia.
Giardia is well known toprimarily infect the small
intestine, Cryptosapridium aswell, and a number of the
opportunistic microbes tend toovergrow in the small intestine.
Now they're not necessarilysynonymous with quote SIBO,
Again, because SIBO is based ongas-producing microbes.

(42:13):
We know that most of thoseopportunists on GMAP either
don't produce those types ofgases they're not hydrogen
producers, they're not hydrogensulfide producers, methane
producers they're not hydrogenproducers, they're not hydrogen
sulfide producers, methaneproducers or they don't produce
sufficient amounts becausethey're present at really low
levels and yet we know they'reclinically significant.
So the short answer to thisquestion is no, it's not

(42:38):
technically SIBO.
But you're looking at a smallintestine potentially in a
different way.
We would call that potentialsmall intestinal dysbiosis and
it depends on the microbes andsort of what's known about them
for research and where they live.
Pseudomonas is another classicexample.
Research shows in multiplestudies that that's largely a

(43:00):
resident of the stomach andsmall intestine, not really a
resident of the lower GI tract.
We know from research thatthat's linked to everything from
IBS to food sensitivities.
So we're getting a lot ofinsights.
And then, on top of thosemicrobes, we're also getting
insights into digestion, whichof course takes place in the

(43:21):
small intestine.
Of course takes place in thesmall intestine.
We're getting some insightsinto food reactions based on the
anti-choliodin marker and alsoeosinophil protein X, which is
the eosinophil activationprotein.
Those tend to be those immuneresponses to foods tend to
happen primarily in the smallintestine.

(43:41):
So again we're getting someadditional insights.
That is very different fromwhat you would get from a breath
test.
When you're looking at testing,there are cases where patient
might have some issues in thesmall intestine but it's not
SIBO and yet we can see thingslike GMAP frequently that could

(44:02):
still indicate problems in thesmall intestine GMAP frequently
that could still indicateproblems in the small intestine,
but it's just not technicallySIBO.

Speaker 1 (44:09):
So in terms of when we're looking at that
information that comes through,we're getting a much broader
range of information that tellsus what's happening in the small
intestine or potentially, andcertainly we can see patterns
that could indicate SIBO by itsyou know classic definition and
also other indications ofdysbiosis in the small intestine

(44:33):
that aren't SIBO in air quotesand I suppose clinically
speaking, it would allow us toperhaps say, okay, there's a lot
of other activity going on inthe small intestine that could
actually be contributing tothese symptoms, SIBO type
symptoms or actually there'ssome red flags here that this

(44:54):
might actually be SIBO in itspurest definition and therefore
the next step would be to lookat breath testing to confirm
that that's the case.
Is that how you would approachit?

Speaker 2 (45:05):
Yeah, and there's also just different scenarios.
So we often will get caseswhere patients had kind of gone
down the SIBO path.
They had symptoms that thepractitioner kind of assumed
were SIBO.
They went and did breathtesting and confirmed from that
cutoff that they had SIBOtreated and either the SIBO

(45:27):
symptoms came back or they neverreally responded that well in
the first place.
So then often they'll follow upwith a test like GMAP to see
well, what else might be goingon.
There's a lot of things that cango on.
I would say one of the mostcommon things we see is high H
pylori.
So of course SIBO doesn'treally take into account
potential H pylori.

(45:48):
We see candida is pretty commonin those scenarios.
So you're getting a lot ofthese other pieces of
information that can lead tosymptoms that seem like they
might be SIBO.
And if you think about some ofthose symptoms like bloating,
bloating is such a commonsymptom.
Most infections parasiteinfections, candida et cetera

(46:09):
can also cause bloating.
So you really want to.
A lot of people will start withsomething like GiaMap to get
kind of that broader picture andget a differential diagnosis
sort of take on things.
One of the other things thatshould be mentioned is.
You may be aware there's somecritiques about breath testing.
Certainly there has been somereviews by prominent IBS

(46:31):
researchers about breath testingand some of the drawbacks.
One of them is the potentialfor false positives due to rapid
transit of the sugars that areused in testing to the colon.
So you get this early peak butit's actually not taking place
in the small intestine for somepeople.
If they have rapid transittaking place in the small

(46:52):
intestine.
For some people, if they haverapid transit, then that can be
basically the early peak ishappening in the colon.
There's a lot of research on thegas producers in the colon and
those are on GMF.
So if you want to know aboutthe hydrogen producers that are
in the colon.
So again, that could be one ofthe reasons why some patients
that were thought to have SIBOyou go down that path of

(47:12):
treating SIBO, maybe didn't getthe response that you were
looking for.
In some cases it might just bethat that actually was happening
in the colon.
We can get great insights intomethane producers in the colon,
gas hydrogen producers in thecolon and hydrogen sulfide
producers as well.

Speaker 1 (47:30):
I think that's so helpful to know.
I can see how it would be souseful to do a GI map first and
then perhaps add in thoseadditional tests.
But I think, conversely, forclinicians who've gone, this is
absolutely SIBO and then theyrun a breath test and then it
doesn't come up.
Then where to from there?

(47:51):
And I think that's where the GImap can fill in all the rest of
those gaps, because it's such abroad range of information that
you get, and not just on themicrobial side but also the
immune function and some of theterrain in terms of secretory
IgA as well.
So I guess the short answer isit can't be used to diagnose
SIBO per se, but it canabsolutely give us some

(48:13):
wonderful insights into thesmall intestine, including
microbial patterns that couldpoint to SIBO and would justify
ordering a SIBO test and alsocan save us from ordering a SIBO
test unnecessarily when we cansee other microbes that are
actually contributing to thatbloating and those SIBO type
presenting symptoms, which Ithink is just so helpful,

(48:37):
especially when we again zoomout and consider how are we
treating the whole patient?
You know we always have to thinkof whether or not they have
SIBO or dysbiosis of some othertype?
How did they get there?
Is it, you know, an innateimmune system issue?
Does that stem back to chronicstress which reduces blood flow
to the gut, which then set thisup in the first place?

(48:58):
Was it, you know, a course, ormultiple courses, of antibiotics
, you know, whatever the casemay be, you know, is the
secretory IgA still down?
Well, you can treatantimicrobially all you want,
but if you don't bring that backup, you'll just see relapsing
infections.
So it does, I think, give us amuch broader ability to approach

(49:20):
things when we can see all ofthe pieces on the table.

Speaker 2 (49:24):
Exactly, and.
I would add to that listprobably at the top would be
digestion.
So whether it's list probablyat the top would be digestion.
So whether it's of course gmfdoesn't have there really aren't
any gut tests to have directindicators of stomach acid.
You have to kind of triage thatand sort of get a picture
together to see, of course basedon symptoms as well.

(49:44):
But yeah, map, we know wetalked about h pylori is a
potential cause of low stomachacid.
There are low stomach acidrelated patterns very well known
and defined in the research,including high levels of
streptococcus.
Also high levels ofstaphylococcus enterococcus,
those types of overgrowthmicrobes that are in that

(50:08):
section on opportunists.
Those are fairly closelyrelated to reduced digestion.
So that can be a sign thatmaybe you want to look at
digestion.
But then of course we haveelastase which is a direct
marker for pancreatic enzymeproduction.
I would say that's one of themost commonly deficient markers

(50:28):
in patients that have gone downthis SIBO path.
So when we get this for apopulation of patients in our
consults that have been downthat SIBO path and you're
looking at GMAP again, the topones tend to be H pylori,
pseudomonas, staphylococcusevidence, food reactions and

(50:49):
then poor digestion so just toyour point.
Why not start there and look atthose, because these are all
different factors for manypatients.

Speaker 1 (50:59):
That kind of covers the basis and that can explain
why they have those symptoms andthey may not need to go down
the placebo route yes, you canstart with improving digestion
and allow the innate immunesystem just to get back on top
of what's going on microbiallyand I think you know, sometimes
going back to those basics weoverlook in the name of fancy

(51:23):
testing and fancy protocols.
And certainly one of the thingsthat I find myself saying a lot
in practice is there are noteeth in the stomach.
If we're going to take it tothe bare basics, you know,
people often don't chew theirfood properly.
They're often eating standingup or running out the door while
they're driving.
You know, a hundred miles anhour on the freeway, and there

(51:46):
are just so many things thatwe're doing that put extra
pressure on our digestive systemthat need to be addressed, you
know, before we dive into afancy protocol.
But certainly picking up thosethings like elastase as to how
well our organs are currentlydoing their job is so powerful.
Because then it also I find youknow, and it's understandable,

(52:09):
that people are very data drivenand I think telling a patient
you need to do X, y and Z, theycan be a bit noncommittal
sometimes or perhaps notconsider some of those basic
pieces of advice to be ofparticular importance, but when
you can actually point to amarker sort of say this is what

(52:33):
that means.
It gives them a reason to bedoing what you're sharing with
them also, and you've mentionedsome really interesting markers
already.
And I want to just to circleback to the eosinophil
activation protein, because Ithink this is one of particular
interest to me, because I'm inthe environmental medicine space

(52:54):
and looking at some of thoseexternal drivers of eosinophil
activation.
But I'd love to hear from youwhen a clinician's looking at it
on a GI map, what is thatinforming them about and what
should they do about that?

Speaker 2 (53:09):
That's a great question.
So we do get a lot of questionsabout that.
It's not one of the markersthat comes up frequently.
It's fortunately not thatcommon.
I would say maybe 10% ofpatients tend to have elevated,
but it's something that's muchmore commonly elevated when
patients have food reactions.
So there's a lot of research onthe role of eosinophils in food

(53:35):
reactions, particularly foodallergies, and also the
interactions between eosinophilsand mast cells.
So these are kind of both yourkey cells that are picking up on
what's going on in the mucosa.
Are we being exposed to toxins?
Are we being exposed to certainmicrobes, allergens etc.

(53:55):
So they're kind of thesesentinel cells in the gut.
So when it's activated, ofcourse that's telling you by
definition that eosinophils areactivated.
Studies actually show that mosteosinophils in the gut tend to
be in the upper GI tract,particularly in the small
intestine, to some extent in thestomach.

(54:15):
We certainly know they're notcommonly in the esophagus but
they can be in eosinophilicesophagitis.
But they're actually even justby default present in the small
intestine.
So the key there is are theyactivated or not?
Because they have normalfunctions in the gut where

(54:36):
they're actually helping tomaintain the intestinal barrier
and immune balance.
But once basically somethingtriggers them, they detect
something that they need tofight off.
Then they become activated andso that's really kind of your
key marker to let us know thateosinophils are activated.
It's a different type ofinflammation than the type of

(54:59):
inflammation that's reflected incalprotectin.
So that's really one of theadvantages of having more than
one immune activation marker.
Calprotectin is kind of moreyour classic inflammation that's
involved in inflammatory boweldisease, infections in the gut
et cetera.
So that's really a little bitabout eosinophil activation

(55:19):
protein.
And one of the things I thinkthat's not as well recognized is
how the gut sort of interactsas a whole.
I know we kind of touched onthis a little bit interacts as a
whole.
I know we kind of touched onthis a little bit sort of
systems level approach.
So just to kind of give you onereally important example, of

(55:42):
course with GI map you canassess the commensals, some of
those key commensals likeacromantia fecalibacterium.
So fecalibacterium is one ofthose important butyrate
producers.
In fact it's significantlyimportant enough that overall
butyrate levels track withfecalibacterium is one of those
important butyrate producers.
In fact, it's significantlyimportant enough that overall
butyrate levels track withFecalibacterium.
Well, it turns out thatbutyrate is one of the factors
that can help keep eosinophils,mast cells and other immune

(56:04):
cells from being overlyactivated.
So if you see that eosinophilactivation, protein high,
patients having a lot of foodreactions or other types of
reactions sometimes it's thingslike mold, environmental
exposures One of the things youpotentially can do to reduce
that is work on the commensalsif you see that those are

(56:26):
deficient.

Speaker 1 (56:27):
Yeah, that's a great point.

Speaker 2 (56:29):
Put all those pieces together.
But once you start to learn howto connect these dots, it gives
you a lot more that you can acton and you start to see how
these things are connected.
It gives you new avenues forbasically helping to support
patients.

Speaker 1 (56:43):
I think that's such a good distinction and I think
also when we're looking at thateosinophil activation where
you're having food reactions,you can then also filter through
is the secretory IgAappropriate and therefore
mucosal biofilm okay?
Or is it low and therefore thegut wall is vulnerable and more
reactive and would perhapssettle down if we could raise

(57:04):
that?
Or is it highly elevated,meaning there's probably some
sort of infection that thebody's trying to respond to?
That then is having a dominoeffect into the rest of the body
and certainly for me, I wouldalso pop in there an exposure to
mycotoxins as well.
When we see an increase ineosinophils as a potential,
potential issue and the otherthing I wanted to ask you about

(57:27):
was occult blood.
In terms of that, either it'spresent or it's not, or looking
at it through the lens of a moreof a spectrum, of a reference
range, and what cliniciansshould be interpreting that data
as.

Speaker 2 (57:42):
That's a great question.
So, of course, with anyreference range, the cutoff
level is meant to indicate alevel below which it's less
likely to be an issue and alevel above which, when its flag
is high, that it's more likelyto be an issue.
Of course, on GMF that cutoffis right around 10.
So it certainly doesn'tnecessarily mean that if you

(58:04):
have a 9, there's no problem atall and if you have 11, it's
really bad.
You have to take into accountthe context of the patient.
A lot of practitioners do getconcerned if they see any level
of occult blood detected becausethey feel that in a healthy gut
you know that shouldn't reallybe the case.
It's more just to give you anindicator of overall, based on

(58:26):
the reference range and a lot ofthe scientific information that
kind of goes into determiningthat.
On the reference range and alot of the scientific
information that kind of goesinto determining that, are the
levels detected more likely tobe benign sources such as
hemorrhoids, et cetera, or justminor inflammation, or is it
more likely to be something thatyou really want to pay closer
attention to?
So that's the whole point of areference range.

(58:47):
It's we just reported it aspositive and negative and you
didn't know that there was anynumber there at all below 10,
which is considered the cutofffor high.
You wouldn't know to kind ofpay attention to that right.
So a lot of practitioners see,say five, something is okay.
I don't need to necessarily acton this right away unless the
patient has symptoms that wouldcause her concern.

(59:09):
But I want to keep an eye onthat.
So I might want to recheck thatin a few weeks, a month or so,
and just make sure that's notincreasing.
It's similar to this idea ofthe low-level pathogens Do you
want to know that they're thereor not?
It sort of makes it simpler ifyou don't report the low levels
because it's like, okay, alittle bit of the ignorance is

(59:32):
bliss, we don't know it's there,we're not going to worry about
it.
But having the information doestell you something.
It's telling you there might besomething.
You are less likely to be a bigconcern, but do monitor it,
just to make sure it doesn'tbecome a big concern Do?

Speaker 1 (59:49):
monitor it just to make sure that it doesn't become
a big concern.
Yes, I think you know againthat this is the challenging
aspect to more and moresensitive pathology testing,
which we're so grateful to haveas practitioners.
But it is, you know, bydetecting, you know, more
sensitive levels of things, itdoes then become a little murky.
It's no longer you know, seethis do that kind of situation.

(01:00:10):
There is a bit of a gray areathat people are operating in and
I think, just sort of goingback to the Helicobacter pylori
conversation again, I know we'vetouched on it a couple of times
already and gone into it fairlyin depth, but just thinking out
loud about what we were talkingabout to do with SIBO and

(01:00:30):
whether or not the informationthat comes through suggests,
okay, it would be worthwhileinvesting in a SIBO test based
on what we're seeing here, wheredo you stand as far as the
reference ranges forhalicobacter go in terms of?
I know we've discussed there'svirulence factors to consider
and there's also what is theoverall volume and of course

(01:00:51):
that's always going to be lookedat through the lens of is this
patient exhibiting any symptomsthat we know to be either
directly or indirectly relatedto helicobacter infection?
But in terms of you know, whenwe see that come through on the
GI map, just like with SIBO, theGI map is not a replacement for
breath.
The GI map is not a replacementfor breath testing.
Gi map is not a replacement forantigen testing or breath

(01:01:15):
testing or even biopsy withhelicobacter.
How do you see those piecesfitting together clinically for
someone in practice?

Speaker 2 (01:01:24):
I think it really depends on sort of, to some
extent, what the purpose is forusing the different tests.
So when it comes to a tool likeGMMAP, that covers a lot of
bases right, it depends onreally what the symptoms are and
sort of what you're looking for.
But it's a great screening tool.
So if you see that H pylori ispresent but it's not high, you

(01:01:49):
know, it's maybe in that E2range, so it's there, but the
patient may not have anysymptoms consistent with H
pylori.
Some practitioners will justleave it at that and they'll
focus on other imbalances.
Others may decide well, basedon this patient's presentation,
we're seeing evidence of lowstomach acid or something that

(01:02:10):
might cause them to decide totreat.
The test itself, of course,doesn't dictate whether her
practitioner treats or not.
That's clinical judgment.
If it's above that cutoff level.
Again, the cutoff levels aremeant as a little bit of a red
flag to say, hey, this may bemore significant, pay a little
more attention to it, because itcould be a cause of the

(01:02:30):
patient's symptoms.
It's not the test itselftelling you yes, the patient's
symptoms are definitely causedby H pylori because it's above
that number.
So they're really meant to beguidelines.
They're not meant to really bestrict.
As soon as it's above thislevel, you must do X, y or Z.
As soon as it's above thislevel, you must do X, Y or Z.

(01:02:51):
That clinical judgment isreally very important.
And clinical judgment of coursedepends on a lot of factors,
including how well educated youare in interpreting the test.
So that's really a big focusarea for Diagnostic Solutions

(01:03:12):
Lab is really to help educatepractitioners so you have the
science-based background, theevidence-based background, to
help you decide what you feel isbest for your patients yeah,
and I think that perhapsaddresses some of the concern
around over amplification andover treatment.

Speaker 1 (01:03:25):
And I think with the amplification, that has more to
do with, you know, the PCRmethodology, but also whether
having these things appear onthe GI map is going to result in
overtreatment, and I think youknow, for better or for worse.
It really comes back to theclinician being responsible for
their own understanding andexperience and being able to use

(01:03:47):
their clinical judgment whenlooking at data in the context
of the patient in front of them,their symptomatology, what
their other pathology is alsotelling them in terms of what
direction they're going to go innext.
Is that something that youagree with or is there anything
further to add there?

Speaker 2 (01:04:06):
No, I think you definitely hit the nail on the
head and one of the otheranalogies I like.
It's not a perfect analogybecause it comes to blood sugar,
for example.
Imagine that you got apatient's blood sugar result
that just said in range or outof range.
Right, you didn't get a numberrange, we're good to go, or it's

(01:04:32):
out of range.
We need to do something aboutthis.
Having the actual number forblood sugar, it could be sort of
high, normal, and you know that.
All right, we need to try tooptimize this further.
It could be normal, low, normal, etc.
Or just a little bit out ofrange versus.
If it's, you know, a fastingblood sugar of 180, then you
know that's a pretty significantissue.
So I think that's in some waysa good analogy, because having

(01:04:54):
those numbers and having areference range gives you an
idea of sort of how you want toapproach it, how aggressively
you want to approach it.
What's the context again,versus just sort of this
positive, negative, it there,it's not there yes, yeah, I
think that's so important.

Speaker 1 (01:05:12):
Um, again it comes.
It's not that binary you haveit or you don't.
Or it's a problem or it's not.
Where do you sit on thespectrum and when you look at it
in the context ofsymptomatology and what else is
going on that we can seeclinically and you know
pathology wise, putting thosepieces together, everything
tells a story, doesn't it?
And can you interpret thatstory properly and translate

(01:05:35):
that into what does this patientactually need to feel better
and get better?
Yeah, well, look, I I know I'vepicked your brains an awful lot
in this conversation and I'm notgoing to keep you for too much
longer, but I am really curiousI know this is such an area like
a passionate area of expertisefor you and, given you are in

(01:05:59):
this, working in this area ofthe microbiome and its
connection to chronic diseaseand aging, are there any
insights that you can give us,not necessarily in the context
of what we can see on the GI mapalready, but what's sort of to
come in the research andacademic space around what the
gut can inform us around agingand how well we're going or what

(01:06:23):
we might need to do to agebetter?

Speaker 2 (01:06:26):
that would be a whole additional episode yeah, yeah.
Yeah, I mean that's a reallyfascinating area of research.
It's kind of just at the earlystages.
So I'm not sure if you've heardof this concept of hallmarks of
aging.
People are in the longevityfield, that's something that's
sort of a big focus area, kindof almost a framework.

(01:06:47):
So the latest iteration is thatthere are 12 hallmarks of aging
that have been identified.
That was updated from a version, say, 10 years ago.
Dysbiosis is one of the newhallmarks that was added, so
they're now kind of recognizingthis set of research from the
last 10, 15 years.
Certainly there arecharacteristic imbalances that

(01:07:09):
happen with aging and they arelikely related to the other
hallmarks of aging.
So one of the other newly addedhallmarks of aging is chronic
inflammation, right?
So we know that's a feature ofmost chronic inflammatory
diseases, age-related diseases.
It's also a feature of aging,to the point where there's this

(01:07:31):
term inflammation.
So it turns out that there'sevidence that this sort of
dysbiosis that happens withaging, which is often
characterized not so muchdifferently from what we
typically think of, so a lack ofthe good guys and then an
increase in quote the bad guys,the opportunists, is pretty
common.
Those sorts of things can startto drive chronic inflammation.

(01:07:54):
So there's evidence that thatmay be one of the factors that's
sort of contributing to thisage-related increase in
inflammation.
But it kind of cuts across theboard.
I mean, we can get into allkinds of details which I'm sure
we don't have time for now, butone of the ones that to me was
fascinating.
There's kind of a subset of thelongevity medicine field and

(01:08:15):
the sort of healthy longevityfield that has to do with this
regenerative medicine concept,right.
So that's involved stem cells.
We think of them in terms ofstem cell injections and those
sorts of approaches.
It turns out that the microbiomenow is known to play a role,
certainly in the gut, inregeneration.

(01:08:35):
So the microbiome balance has abig influence on that
epithelial turnover, right.
So when we're talking about guthealing.
Everybody thinks about leakygut, intestinal permeability.
They're not so much thinkingabout this turnover of all the
cells and lining the gutcompletely turning over every
five days.
That to me is really theessence of gut healing.

(01:08:58):
You want that process to gowell and so the microbiome
influences that process.
If you have dyspliosis, thatprocess is not going well.
That's.
There's a lot of researcharound that.
But even in terms of you know,there's more focus now on muscle
health.
With aging, for example, in itsrelation to this muscle loss
called sarcopenia, it turns outthat we talked about butyrate.

(01:09:21):
Butyrate can help kind of tampdown on these inflammatory cells
and kind of influence thatbalance.
That process is known.
What happens in the gutinfluences this muscle
regeneration process.
So in distant tissues now we'refinding that the gut microbiome
has these influences.
So I think it's just it'sfascinating to see these

(01:09:44):
different concepts coming out ofresearch for how just this
simple concept of balance ofyour microbiome and gut health
balance can influence oursystemic health in so many
different ways, including inaging.

Speaker 1 (01:09:59):
I just think that's so fascinating and just brings
us back to Hippocrates' age-oldquote all diseases begin in the
gut and I think, know the, theinformation we get from the GI
map really can quite literallybe the key to not just gut
health but for the rest of ourbody, the rest of our well-being
and for the rest of our life.

(01:10:19):
It's just fascinating.
Well, I would I'd certainlylove to have you back for
another conversation on on thatanother time, tom, but thank you
so much for being so generouswith your knowledge with us
today and just so appreciate youtaking us through all things
microbiome.

Speaker 2 (01:10:37):
It's been my great pleasure, so thank you so much
for inviting me.

Speaker 1 (01:10:40):
Thank you so much, Tom, and thank you everyone for
joining us today and rememberyou can find all the show notes
and other podcasts on theDesigns for Health Australian
website I'm Amy Skilton, andother podcasts on the Designs
for Health Australian website.
I'm Amy Skilton and this isWellness by Designs.