Transcript DR Mark Pimentel 3 Gas Breath Test
Transcript DR Mark Pimentel 3 Gas Breath Test
Transcript DR Mark Pimentel 3 Gas Breath Test
with our very special guest, Dr. Mark Pimentel. He’s currently the head of Pimentel Labs and
executive director of the Medically Associated Science & Technology (MAST) Program at
Cedar-Sinai. This program focuses on the development of drugs, diagnostic tests, and
He is in the process of what I think and I like to say “finding the cure for SIBO.” The lab, Pimentel
Lab researches irritable bowel syndrome, one of the most prevalent GI conditions affecting
about 10% of the population worldwide and about 10% to 15% of the population in the US.
In the past, there was no definitive test to diagnose IBS. And for the first time now, there is
called ibs-smart™. There are also three different types of gases that make you “have SIBO”
(small intestine bacterial overgrowth). And he has also created a test for that called
trio-smart™.
And with that, I’m going to hand things over to him and have him explain to us all of these so
So, what I plan to do today is just to take you through some slides. But really, it’s not about the
slides. It’s about how the slides sort of guide the conversation or at least the education about
SIBO. And so I’ll try and walk you through these slides carefully.
Shivan Sarna: Please do, yup! I’m just checking to make sure that all of our streams are
And by the way if someone is listening to this on the podcast versus seeing it in the Facebook
Live or the Zoom session, we’ll give you a link so you can actually see the slides as well.
Dr. Mark Pimentel: Well, here they are. So, I think you can probably understand just from my
conversation part of this… the slides are a very good guide for those who are able to see them
live. But I’m going to talk about irritable bowel syndrome and the microbiome because, really,
things have dramatically shifted in 2020. We now know more about the microbiome and IBS.
And there’s more and more evidence that the microbiome is important in IBS. And I’ll share
One thing I like to start with is… with IBS, you are irritable. So the terminology we use for IBS,
that you’re irritable and you’re a bowel and you’re a syndrome are really sort of derogatory
terms. They’re not really embracing of the patient experience. And the fact that you’re called
a “syndrome” implies that you’re not a real disease – you’re just a syndrome and that there
really is no understanding of IBS. And that’s the part I really don’t like. And I think the
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I recently did a Twitter poll on this concept, whether they’re the public or doctors, whoever
would respond in Twitter. Would they consider this derogatory to consider it a syndrome
rather than a disease? And it was overwhelming that both patients and physicians alike felt
that this terminology really did not represent what was going on for patients.
Now, what that means, a “diagnosis of exclusion” for those of you who may not be familiar
with this term, it means that this disease is the waste basket. After you ruled everything else
out, after you’ve done all your tests, you’re left with this.
You have changes in your bowel function. You have bloating. But we don’t know what causes
And that also drives a problem because you end up getting a lot of investigations. You never
feel comfortable with your diagnosis. You’re never sort of settled and you say, “Okay, I know I
have IBS.” No, you don’t because there’s no test for it or there hadn’t been. And so that’s the
Well, where does that end up for you as the patient? It means you’re going to run around and
see doctors and spend more money. And doctors are going to be doing more tests, all of
which are negative. And then, you’re still going to end up in the same place.
So, we’d like to put an end to that. And that’s part of the story of the microbiome here.
Here’s another ridiculous concept. But this was something that was quite common especially
in the 1990s and before. And I’m quoting here. This is not my quote. This is somebody else’s
So, IBS was, quote, attributed to women. We’re all, it seems, blaming women for this condition
that nobody understood or that it was due to some previous traumatic event or
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psychological event or it’s due to depression or it’s due to anxiety or it’s due to all these
different things for lack of a better understanding of the condition. And this is certainly not an
And so, I want to leave you—well, not leave you with that thought. But I want to start you with
that thought.
Not to mention, there’s no shortage of patients to study. If you wanted to do research on IBS,
you just need to walk down the street, and you pass a bunch of people as you’re walking. So
it’s not a rare disease—40 million people in the US, one billion people worldwide. Research
could’ve easily been done for decades. But you were left with that previous comment I
mentioned.
term—that you do all these tests, they’re all negative, you waste all these money, the patient
pays the co-pay in the US and so on and so forth. I’ve had patients come to me and say that,
out of pocket, they have paid over $20,000 before they finally got to the diagnosis.
But it’s expensive not because of the testing. It’s expensive because of this notion of the Rome
Criteria which are the previous criteria for diagnosing IBS stating that part of their mantra was
that it was a diagnosis of exclusion. “It’s up to you, doc! If you feel comfortable, and you’ve
done everything you need to do, and it’s negative, you can call it IBS.” And that doesn’t serve
Well, we’re now in 2021. So let’s fast-forward to 2021 and this concept here that we now know
food poisoning causes IBS. I’m going to show you that evidence. We now know a toxin in food
poisoning is important to the development of IBS and that that creates autoimmunity to a
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And then, you get a change in the nerve structure or nerve function of the gut—meaning the
gut is slower or it changes its flow patterns. And when it changes its flow patterns, you get
build up bacteria, and that’s bacterial overgrowth. And therefore IBS is SIBO, and SIBO is IBS, in
We’re going to start with the bacterial part of this, the bacterial overgrowth part of IBS, and
Now, I want you to focus on those three letters: small intestine which is the small intestine,
which is the part in the middle here. About 15 to 20 ft. of the bowel is small intestine, about 3 to
5 ft. is colon or large intestine. But the small intestine is where you do all your absorption. You
can take the whole human colon out, and the human will survive just fine. It will be runny, but
you would survive just fine because the small intestine is where you absorb things. That’s your
And that part of the gut is meant to be cleaner—less bacteria eating your food, and you get
most of it. And the number we now refer to as “normal” is less than 1012 bacteria/ml of fluid in
Now, when we’re diagnosing small intestine bacterial overgrowth, it requires a breath test.
Now, you could culture the small bowel, but then you have to have a scope. The scope would
have to be placed in there, suck some juice out and send it to the lab… of which is expensive
and invasive. And you have to be put to sleep or at least given some form of sedation. So
You simply ingest a sugar. And then, the sugar gets into your stomach and into the small
intestine. And then, you expel the gases that are produced by the bacteria in the gut through
your lungs, and then out your breath. And that’s how a breath test is done.
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Now, SIBO has been a problem in the sense that there had been no guidelines or consensus
on how to interpret a breath test. And for those who’ve had a breath test, there are doctors
who say, “Well, it’s got to rise by 10 or 12,” or “It’s got to rise by 20 ppm,” or “It’s got to rise by 60
minutes or 90 minutes on the breath test.” And so we set out in two papers. The first paper,
which I don’t have listed here, was the North American Consensus which set the standards for
how you should be doing breath testing and how you should be doing breath testing.
But because of the tremendous interest—and I mean this sincerely, tremendous interest in the
commissioned a guideline (which is presented on this slide). And we confirmed a lot of the
But a very important part of the guideline said—for those of you who know about
a methane form, and a third form of hydrogen sulfide—and I promise, I will get to that. But the
methane part, those bugs aren’t bacteria. So when you look at small intestine bacterial
So, we created a new term called IMO, intestinal methanogen overgrowth. And that’s the new
term.
So, SIBO is now being broken down into maybe three parts. And you’ll see those parts
momentarily.
But we also said you should consider breath testing in the diagnosis of SIBO and IBS because
the evidence is now quite overwhelming. And I’ll show you what that evidence is.
So, using this Venn diagram, we now think SIBO accounts for 60% of the diarrhea and mixed
IBS. So in other words, 60% of people with diarrhea/mixed would have a hydrogen-positive
breath test. That doesn’t mean that all of IBS is caused by SIBO. A part of IBS is caused by SIBO,
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but not all of IBS. And so we now think it’s 60%. And I’ll show you the data that substantiates
that.
But SIBO Is caused by IBS in the bulk of cases. But anything that slows the intestine down—so if
the intestine is slower, whether it’s because you have scar tissue or adhesions, whether it’s
because you’re on narcotics that slow the gut down, you have long-standing diabetes with
nerve problems from the diabetes, many things can cause SIBO and not just IBS. But IBS is
such a huge disease base, 40 to 60 million in the US. That probably encompasses the vast
majority of SIBO.
But there are three types of IBS. So going back to IBS, there’s the diarrhea IBS, there’s the
mixed—which is the middle (mixed means you’re going back and forth between diarrhea and
constipation)—and then there’s the constipation side of IBS. But essentially, what we’re seeing
is two conditions because of the microbiome findings we’re having, that methane on the
breath test or methane or methanogens in the intestine is associated with constipation, and
then the diarrhea & mixed is associated more on the hydrogen and now hydrogen sulfide
side.
There’s two Shah’s in the literature in gastroenterology. And everybody mixes them up. So I
call this “the other Shah” paper. This is the Shah from Australia. This is a very prominent group.
Nick Talley, previously from the Mayo Clinic, he’s now the Chancellor of New Castle University. I
think that’s where he’s at. He’s a very prominent figure in Australia and a very prolific
researcher.
But basically, this was a pivotal moment in 2020 because, essentially, this paper says for the
first time: “IBS, full stop, is associated with SIBO based on breath testing.” And there’s 25
papers summarized in this document. And it’s clear. Done. Full stop.
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Now, that may surprise you that we’re saying “done” now when we knew this two decades
ago. But look, you have to continue to march forward. And then, as people summarize the
Now, the challenge we had with trying to understand SIBO and its relationship with IBS, or just
So, the breath test emerge probably in the 1980s. And the original breath test only measured
hydrogen. And then, later, methane was added. But there was no real understanding of what
methane was related to. But the understanding of the gas dynamics just wasn’t complete
with the breath test, hence the challenges with breath testing.
But let me show you graphically that you’ve got the hydrogen bacteria which are producing
hydrogen (they’re flooding the environment with hydrogen, that’s what they do), but that
hydrogen is like a fuel for other organisms. So the methane organisms, the methanogens, use
So, if you have methane on your breath test—which we can now measure with regular
instruments—you can’t rely on the number for hydrogen because four of the hydrogens are
going to one methane. So the more methane you make, the less hydrogen you’re going to
have on the breath test. So the hydrogen becomes unreliable on that test.
But there were also patients where the breath hydrogen and methane were zero across the
board. And we always suspected that there was a third gas. And that third gas is hydrogen
bacteria. And they use five hydrogens to make one hydrogen sulfide.
So, the point of this slide is simple. If you don’t measure all three gases—and these are the
only three gases that they produce—you don’t get the complete picture. If you don’t measure
H2S, you can’t rely on hydrogen because you don’t know how much is making H2S. if you don’t
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measure methane, you can’t understand that methane is causing constipation, which I’ll get
So, without measuring all three gases, you can’t understand the full patient profile. As a
consequence, breath testing can be confusing without understanding these three gases.
Okay, now we’ve got to take a step backwards and say, “Okay! Well, what about culturing the
bowel? Do we have proof of SIBO based on culture?” In IBS, we do all the way back to 2007.
And you can see this study from Sweden. Clearly, the orange bar is IBS, the gray bar is healthy
controls, and the orange bar is much higher which means that there’s a lot more patients
Taking that one step further, this study took people who are coming in for scope. So these
were sick people, all of them. So the control group in the gray, they’re sick people. They’re not
healthy controls. But the diarrhea IBS patients, the orange, 60% had SIBO. So that’s where we
Now, we know more about SIBO, and we continue to know more. And I’ll show you some really
interesting stuff here in a moment that’s new. But when we took these duodenal aspirates,
this juice from the small bowel, these two characters came out of the mix—klebsiella and E.
coli.
Now, it doesn’t look like klebsiella was a lot of higher than the gray (healthy). But each number
on this y-axis is 10 times higher. So this is a log10 scale. So when you go from four to five, it
means there’s 10 times more bacteria. So E. coli and klebsiella are bad actors.
Now, what we were saying in 2015 is that E. coli and klebsiella were like weeds in the garden,
that they were choking other things out. Now, that was just us hypothesizing as to why these
two characters are so problematic in SIBO and what was happening. But I have proof now
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And we get this proof from what’s called the ReImagined Study. The ReImagined Study at
Cedars is anybody who’s coming in for an upper scope, we offer them the opportunity to be
part of this study. We collect their information. There’d be questionnaires. We get blood. We
get genetics. We get juice from the small bowel and a couple of biopsies from the duodenum,
from the small bowel there. And then, we’re able to archive that and study the microbiome.
And we’ve gotten almost to 500 patients. So we have a very, very good understanding of the
The first provocative finding from our study, the ReImagined Study, was presented and
published this past July in Digestive Disease Sciences. This actually made the cover of the
journal. The reason this is important is this is the first across-the-gut snapshot of what the
I want to point a couple of things out to you. There are many people out there doing stool
testing for the microbiome. Yes, stool testing for the microbiome tells you the microbiome in
stool. But you can see the colors represent families of bacteria. And you can see the colors
here.
But look at the small intestine. You cannot get any understanding of the small intestine from
stool because the small intestine is completely different than the stool. And that’s my point
But here’s another point. As you go further down the gut—and these are patients who were
getting double balloon endoscopies. So we were able to get almost to the end of the small
bowel with these patients—the number of bacteria does not go up. We thought it did. The
profile of the bacteria doesn’t slowly become closer to like colon. No, it just basically drops off
a cliff. Everything in the small bowel looks very similar. And it’s until you cross the ileocecal
valve that everything goes into this format… or this, what looks like stool.
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So, it’s pretty remarkable to describe this for the first time.
Okay! So now we could use sequencing of the bowel which is the most latest greatest
technology for understanding the microbiome. And we can do this in the small intestine. And
what we show here is SIBO. These were patients not with a positive breath test, but these
patients had literally SIBO by culture which is considered the gold standard. The other is no
SIBO. But immediately—I’ll only just describe this. It gets a little tricky to understand.
The first ring is the kingdom of life which is bacteria. That’s why it’s called bact. And same on
this side. The next level is the phylum. Phylum is the next breaking down of what type of
bacteria is present. And you can see immediately even at this super high level look that
As we get further out to the rings—and the second last ring is the genus, the last ring is the
species, klebsiella and E. coli is this other gray ring—is all-encompassing in SIBO. And we see
So, the point is we keep seeing the same thing over and over again—E. coli and klebsiella, E.
The other amazing thing in this study is we were, for the first time, able to validate the breath
test with lactulose. We didn’t validate it with glucose. We don’t do glucose. We validated it
with lactulose.
So, if your breath test at 90 minutes rises to more than 20 on hydrogen, a few things are
noted. It’s the most specific. For SIBO by culture, it’s more specific for all of the factors along
this line, meaning that even though some of the other factors had greater p-values, this lined
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The second point is I want to show you this last two columns. It also lined up that the bacteria
of the small bowel when you had SIBO had increased metabolic function for hydrogen
production seen on their metabolic pathway analysis. What does that mean? That means
that the hydrogen in SIBO is coming from the small bowel, not the colon.
This is the argument that’s been forever. Well, the lactulose gets to the colon and the
hydrogen is coming from the colon because lactulose doesn’t get absorbed. Non-sense! This
study proves that there’s up-regulation of hydrogen in the small intestine in these patients.
So, a lot to dissect on this slide. I’m not going to get too far into the weeds. But very, very
interesting…
So, this was presented at the American College of Gastroenterology. It’s an abstract that was
Okay! So this is called a community analysis or a network analysis. So when you look at the
microbiome, it’s like a community. You have doctors, plumbers, lawyers and others. And in
some communities, the more lawyers you have, the more jails you have. The more plumbers
you have, the more buildings that need plumbing you have. And so, you can see relationships
between things.
And each circle represents a genus of bacteria. The larger the circle, the larger that particular
But I’ve put red circles around two—E. coli at 33 and klebsiella at 45. And there are small, little
circles in this beautiful community. And you can see, it looks like a community. Very nice! Lots
But look what happens when you have SIBO. In SIBO, E. coli is this circle… huge! Forty-five. This
klebsiella, also much larger. And look what it does to the network. The network is broken down.
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There’s less circles. It’s not cohesive anymore. So not only is SIBO an overgrowth of E. coli and
klebsiella. Their overgrowth continues to destroy the networks that are network. And the
bacterial community starts to collapse. And that’s what you see very vividly here on this
picture.
And there’s more details to this that are very complicated to explain. But these two pictures I
Okay! But there’s the hydrogen SIBO. And then there’s the IMO which is methane. And we knew
early on that methane seem to be associated with constipation. Actually, it was the final
figure in a paper from 2001 that I wrote. You never look at the last figure of a paper because
the meat is figures 1, 2 and 3. Figure 4 is sort of like, “Oh, it’s an afterthought,” or it’s a back-up
story.
But it was really important because we continue to show that methane was associated with
Not only that, methane is the cause of the constipation. It’s not the bugs. It’s the methane
itself because if you infuse methane in this animal model, you get 60% to 70% slowing of
intestinal transit.
So, what do we do about SIBO? What’s the best way to treat SIBO? Well, you can treat it with
antibiotics. Rifaximin is one of the ones that we use quite commonly. And that works very well
for IBS. It’s not approved for SIBO. It’s approved for irritable bowel syndrome with diarrhea. But
I think it’s due to the fact that they have SIBO. And it works for up to three months.
And then, the amazing thing about rifaximin is that 36% of people who got rifaximin, they
stayed better after the treatment for an indefinite period of time… which is quite remarkable.
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Interestingly, the meta-analysis of antibiotics and IBS show that there are no unsuccessful
trials. Every antibiotic trial in IBS shows that it works—and again, pointing to this being a
microbiome condition.
As you continue to use rifaximin, as rifaximin use went up, so did the referral to tertiary care
centers for diarrhea and mixed IBS. And that was very interesting as well.
Shivan Sarna: What does that mean? Can you just re-state what that means?
Dr. Mark Pimentel: So, as you continue over a decade—this was a decade-long period of
time—as the use of rifaximin for IBS continued to increase, our hospitals were seeing less and
Dr. Mark Pimentel: But that means things were happening in the community. Doctors were
Now, in one of the trials, we saw that breath testing was associated with the response to
rifaximin. So in other words, even though rifaximin is approved for IBS, not SIBO specifically, if
First of all, all patients, 44% responded. But if the breath test was positive before they started
rifaximin, 56% responded to rifaximin. And the breath test retained negative. You had a
positive breath test, rifaximin made the breath test negative, you’re the best outcome. You
had 76% chance that you met that crazy, very difficult FDA end point.
For methane, it’s also interesting. You give neomycin + rifaximin, and you get the best
response. This is a double-blind study! Everybody gets antibiotics in this study. This groups
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get neomycin with placebo. But this group gets the combination of neo & rifaximin. You can
see the constipation score after treatment is much lower when you take these two antibiotics.
And this is why, in our practice, we use neomycin & rifaximin for methane, and rifaximin alone
Bloating got better with this cocktail. But forget about the antibiotic! The most important thing
in the patients with methane who have constipation is getting their methane less than 3
Okay! Now, the new kid on the block. This is a new device that measures hydrogen, methane
and hydrogen sulfide. And the challenge for hydrogen sulfide is this. The hydrogen sulfide gas
is highly volatile and toxic. Even hydrogen and methane are not easy to transport over long
distances. So we needed to change all the sensors and array them in a particular fashion in
the instrument. You had to have a transport system to be able to transport the gas without
any of the gases deteriorating—which is not easy, especially with hydrogen sulfide. And then,
But just to show you… these sensors in this instrument are sensitive to 0.2 ppm—not 2ppm,
0.2ppm (2ppm are the older instruments). And it correlates perfectly with older instruments.
That’s not the question. That, we know already, for hydrogen and methane. But hydrogen
sulfide is new.
So, for the first time—and you mentioned trio-smart™, that’s the test—we can measure all
three gases, do it at home, it transports perfectly without any deterioration in any of the
Remember, hydrogen sulfide correlates with diarrhea; methane correlates with constipation.
And by not knowing all three, you really have an incomplete understanding of your SIBO.
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Now, I know I’m talking about the IBS story. And I know it feels like I’m drifting back and forth
between IBS and SIBO. But it’s all the same thing because of this pattern that I showed you
earlier. But I’m now going to talk about how food poisoning causes IBS and SIBO. We had a big
This paper came out in 2017. So, I should say, if in 2017, you don’t realize that food poisoning
causes IBS, then you need to read this paper because this is from the Mayo Clinic. It
summarizes more than 40 papers. But the point is, if you had a case of food poisoning, you
develop IBS 11% of the time. So 1 in 9 people who experience food poisoning gets IBS.
There’s no argument here anymore. Food poisoning causes IBS. It’s not all of IBS though.
Remember, there’s a hundred people with IBS coming in your office who have diarrhea
because their colonoscopies are negative, there are many things that could cause that
But I get this question all the time, “I don’t remember ever having food poisoning.” You’re
having diarrhea now. So you obviously have diarrhea from day one. You don’t know if that
was food poisoning or not. And now, you still have diarrhea which is your IBS.
So you don’t have to remember food poisoning for this to be true. And that’s why the
But the risk factors for food poisoning, the top three are the top three: the severity of the food
poisoning. If you had seven days of diarrhea, if you had fever, if you had to get admitted to
But look at number two… this is not a disease of “hysterical women.” This is women are more
susceptible to developing IBS from food poisoning. And as you’ll see, it’s an auto-antibody
that occurs, and women tend to get more autoimmune diseases in general (i.e. rheumatoid
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So, we’re starting to understand why more women have IBS because of this mechanism of
action.
This is animal work. I don’t want to get too deep in this. But basically, we created the first
animal model where we gave campylobacter food poisoning to a group of rats. And the other
rats just got nothing. They just continued on their way. And then, we were able to see after
three months, after they’ve recovered from the food poisoning, what they had. And the rats
got SIBO.
Twenty-seven of the rats who got campylobacter now have SIBO… but they had food
poisoning! So food poisoning causes IBS, but food poisoning causes SIBO. So could it be the
Not only that, if the rats got campylobacter, and they developed SIBO, more than 80% of them
had weird bowel patterns, weird wet weights of their stool… meaning they developed IBS in
general. We don’t have a criteria for IBS in rats, but that’s what happened. And they got what’s
called increased rectal lymphocytes. So these are white cells, a small increase in number, in
the rectum of these animals. And this is the one thing that’s found in humans with
post-infectious IBS.
So, one toxin in common with all food poisoning is called CdtB. And we don’t think C. diff has
this toxin very often. But I put it here because it occasionally can. C. diff can precipitate IBS.
So, cytolethal-distending toxin, this is the toxin that we think is super important for the
development of IBS and SIBO in general. So, we did another study where we created a
Shivan Sarna: Dr. Pimentel, when you’re moving your mouse around—no pun intended
because there’s a mouse on the screen, I get that—it’s just kind of messing around with the
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Dr. Mark Pimentel: Okay, alright. I’ll try not to move too quickly.
Dr. Mark Pimentel: Alright! So I won’t move my mouse around anymore because I don’t want
to create static.
So, campylobacter in the middle is missing the toxin. Campylobacter on the left has the toxin.
And then, on the right, let’s say you’re going someplace where the chances of getting
campylobacter are very high. If you took rifaximin with every meal, could you prevent IBS?
And the answer is rifaximin works great. Not having the toxin works great as well.
So, we knew the toxin was important. But this is the study that was published just in the last six
months and is very important. What we did is we said, “Okay! Maybe you don’t need
campylobacter. Maybe all you need is the toxin.” And so we injected the toxin into the back
leg of the rat to see if they would develop IBS. And they developed anti-CdtB antibodies
because we gave them CdtB toxin. And they developed autoimmunity to themselves to
vinculin.
And so, vinculin is an important protein on the nerves of the gut that help the nerve stay
Not only that, these animals developed SIBO. And they developed a change in the wet weight
of their stool because they were developing IBS. So, we could make an animal have IBS just by
It works like this. You have the cytolethal-distending toxin. You get exposed to food poisoning.
You see this toxin, your body reacts to it and produces antibodies. But one part of CdtB looks
like vinculin. And then, you form antibodies to yourself. And that was supposed to go on to the
vinculin… and it didn’t. It flew past. But yes, that is what happened.
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So, we took that idea, and we said, “We need to develop a test. Could we diagnose IBS that
you got it from food poisoning, you don’t need a colonoscopy, you don’t need to waste all
that resources? And within 48 hours to a week, you know if you have IBS using anti-CdtB and
anti-vinculin?” And the answer is… absolutely! And we see that here. The red bar is anti-CdtB,
and the red bar here is anti-vinculin. And this is Crohn’s and ulcerative colitis patients. And it’s
So, we could actually diagnose this. And the post-test probability—which is really
important—if you have the test, and the test is positive, it’s about 90% likely you have IBS.
So, I was graced with the opportunity to be part of the Irritable Bowel Syndrome Guidelines for
the American College of Gastroenterology. And one of the mandates that was set by this
guideline is we need to have a positive diagnostic strategy. IBS should not be a diagnosis of
exclusion. That is dismissive to patients. It is suggesting that IBS is not a real disease. And it’s a
step in the right direct to maybe changing that syndrome word to something else because it
And they suffer often at an age when they should be more productive because this can affect
So this is a sequence. I tried to show you as much of the evidence as much as I could.
Obviously, we need a SIBO Symposium a couple of years back. And it was eight hours of
broadcast. So I’m covering a lot of background in a short period of time. But I hope I was able
to at least express to you a lot of the most important parts, and some of the more interesting
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But people ask me, “What do you do in clinic?” What do I do in clinic? And so I actually created
this in terms of how SIBO and the IBS blood testing fits into my clinic—not in the whole
But in the case of chronic diarrhea patients where they’ve had some degree of work-up by
the time they see me, you could just flat out give rifaximin. If they respond to rifaximin, it can’t
be Crohn’s disease. And it probably can’t be Celiac disease because you’d have to be off
gluten for Celiac to improve. And Crohn’s disease doesn’t get better in like 10 days or 14 days
of an antibiotic.
But I prefer to go down the middle path which is I get the anti-CdtB and the anti-vinculin. And
the second generation test, the ibs-smart™ test, is much more specific. There was a study
that piggybacked to our CdtB inoculation studies. This is from Mexico. And of course, Max
Wilson noted that the new second generation test is much more specific for his patients. And
And I also do the 3-gas breath test because if they have diarrhea, I want to know if they have
Now, if the anti-CdtB antibody is positive, then I know they have post-infectious IBS with 90%+
specificity. I’ve got to counsel them about traveling, how to eat, what not to eat, what to be
careful with because, if they get food poisoning again—and we’ve seen this in our clinic—the
And when I put extreme measures, I’m talking about patients who are quite sick. If you’re
traveling, you should consider prophylactic antibiotics. That’s what I do. Of course, it’s not
FDA-approved. This is just the pattern of practice that I practice because I can’t let them get
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Of course, if they’re negative, that’s the patient that should have a colonoscopy. And I have
lots of examples of where the test was negative, and we found something. And so, the test
helps a lot.
The 3-gas breath test, of course, if it’s negative, again, consider further work-up. But if you’re
negative on the blood test, and you’re negative on the 3-gas test, you got to move on.
Something else is going on. And that can be all determined within a week or 10 days. So it’s
very fast to get to this point. And then, consider other things, maybe a colonoscopy and other
things.
If you’re hydrogen positive or you’re hydrogen sulfide-positive, I use rifaximin for hydrogen. I
use rifaximin with bismuth. But there are a lot of emerging cocktails for hydrogen sulfide. So
I’m not sort of married to this cocktail yet because I think we don’t understand everything
about hydrogen sulfide. So don’t take this as gospel. But this is what I do currently.
Shivan Sarna: Can you explain what bismuth you’re using? Is it bismuth subnitrate? Is it
PeptoBismol?
Dr. Mark Pimentel: Yeah, it’s PeptoBismol right now. It’s just the easiest for patients to
understand and get. There are people who get compounded bismuth and bismuth
subnitrated and other forms. I don’t think it matters. I think it’s the bismuth itself more than it is
the formulation.
Dr. Mark Pimentel: Yeah! So, rifaximin three times a day, bismuth three times a day. That’s
what we do.
And then, chronic constipation, we do the 3-gas. You could do the 2-gas because, if it’s
methane, you don’t need three gases for that. But it’s just convenient. And if
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methane-positive, I give rifaximin and neomycin. If it’s methane-negative, I consider further
work-up because something else is going on. I might do anal-rectal testing and other things.
I do consider a prokinetic for all of these situations after treatment because I want to prevent
the need for antibiotics again as much as possible. And that’s why a prokinetic can be
beneficial.
So, the conclusion of my presentation part of this is that IBS is, in part, a microbiome disease.
SIBO is an important contributor to IBS. That’s clear from 2020. The meta-analyses from Shah
and Nick Talley from Australia really capstoned this. They even had a paper which I didn’t
present that is again showing elevated bacteria in the small bowel of IBS. I mean, the data
The most important organisms for SIBO… E. coli, klebsiella, E. coli, klebsiella. I showed you lots
of data on that.
Methane is associated with constipation. Hydrogen sulfide is the key to understanding SIBO
more completely. If you don’t have hydrogen sulfide, it’s an incomplete picture.
Rifaximin is the first treatment for causative agent in IBS because we think that the bacteria
And so this is really sort of the capstone of what’s going on. It’s 20 years of work to get to this
very brief lecture. But you can see that we understand this more completely. I would say that
we understand the starting point of IBS more than we do Crohn’s and ulcerative colitis now
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I will say one last thing, and then I will open it up to questions or comments. But that quote I
put at the beginning of the lecture where it says, “IBS is a disease of hysterical women,” we
talked about in the 1980s and ‘90s where stress and psychology were the mainstay of IBS
pathophysiological understanding… but that quote was from 2018. And that’s the sad part
because, in 2018, we knew post-infectious IBS, we knew SIBO. We knew all these things, and yet
there are still practitioners out there who haven’t evolved into these new concepts and still
reside in the ‘90s and ‘80s. And that’s unfortunate for patients who might see these
practitioners.
Shivan Sarna: Well, thank you so much, Dr. Pimentel. That was very illuminating and really
comprehensive. If anyone has any questions about the trio-smart™ breath test, email Paige
A lot of the questions we’ve been receiving could be answered through those emails. And
because we have a limited amount of time, I wanted to give you another resource. So it’s
Also, because if you’re part of the SIBO SOS® Community, we have a special on the
ibs-smart™ test… which is 25% off. You don’t need a doctor’s script. You can use their in-house
physician, filling out the questionnaire at no extra charge. And make sure to look for your
email that we will send to you because we’ll put a link there. You can also find that at
Dr. Pimentel, here’s the big question. So, just to clarify, does hydrogen SIBO exists? You’ve
been talking about it, but there’s this question about how the hydrogen feeds the methane.
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Dr. Mark Pimentel: Every two years, I think I understand what’s going on. And then, I think
So, I showed you that figure. That hydrogen predicts that you’re going to respond to rifaximin.
So that throws a little wrench in the fact that hydrogen is important because you can’t make
So, I think the starting point for SIBO or IMO is you have to have elevated hydrogen because
you need the gas to make the other two cars go. But the analogy I use is you need a lot of
rabbits so that the wolf population or the coyote population is satisfied. And the wolves are
methanogens and the coyotes are sulfate-reducing bacteria that produce hydrogen sulfide.
Interestingly, they don’t like to exist together. So if the wolves are there, they’re eating all the
hydrogen, and they don’t want the other guys there. If the sulfate-reducing bacteria are there,
they tend to not want the wolves there. So usually, the two don’t go together.
But as with anything in medicine, there are examples of where that doesn’t work. And some
This is from Ramona, one of our long-time participants. If you do get antibodies being positive
from the ibs-smart test™ showing that the food poisoning episode has impacted your
migrating motor complex, you have these antibodies, and therefore you have post-infectious
IBS/SIBO. What do you do for treatment to impact the antibodies? Is there anything you do to
Shivan Sarna: So, we had extreme examples of things we’ve done. But I don’t recommend
these for the general practitioner or even the regular gastroenterologist. IV Ig is something
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that we have use. And IV Ig seems to bring the antibodies down, and some people get better.
We’ve done plasmapheresis in some of the most extreme cases of distension and
bloating—five cases, and their IBS completely disappears for a month. The point of that is
don’t do plasmapheresis please, none of you. What I’m saying is that we know that if you get
rid of these antibodies, it looks like IBS goes away. That’s a super important finding. We’re not
going to publish that because we don’t want people doing that because that’s like dialysis.
You can’t put IBS patients or SIBO patients on dialysis to get their antibodies up. Plus, they
don’t form antibodies if you do that. But it just goes to show you that we’re really, really, really
close to what could be the end story of how to make this better. And that’s what we’re
Shivan Sarna: And in June of 2021, we already have our time booked for a 2-hour
Shivan Sarna: I’m sure you are. I’m sure you are. Well, we’re all very excited.
Okay! If someone needs help with their doctor interpreting the results of the trio-smart™
breath test, how can we help them? Get to support? I gave the email address a few minutes
ago? I mean, I guess some people are getting their doctors to give them the test, and then
the doctors aren’t totally being clear about the interpretation…? That’s coming soon.
Dr. Mark Pimentel: Yeah, I think the support of the company will give guidance to the doctor
or the patient as necessary. But there’s a lot of things that can guide that clinician. There are
review articles and other things that I think the company can provide as guidance. So that’s
not a problem.
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Shivan Sarna: Okay! I’m just going to ask this in a different way. I do the trio-smart™ breath
test, it shows high hydrogen. I have hydrogen SIBO… true? It shows high hydrogen sulfide, I
have hydrogen sulfide. It shows high methane, I have methane. So once again, I’m still getting
a barrage of these questions. So do I have hydrogen SIBO and should I treat it that way versus
I know I keep asking you the same question. Just keep coming at me with an answer.
Dr. Mark Pimentel: So hydrogen sulfide predicts diarrhea, methane predicts constipation.
However, if you think about it, there’s going to be a different treatment. Rifaximin, we know
works well for hydrogen. Neomycin and rifaximin (you can substitute metronidazole if you
For the hydrogen sulfide, we’re still working that out. And we’re doing a randomized control
trial right now to see if this new thing works great for hydrogen sulfide or various forms of
SIBO. So we’re coming to some conclusions on what will work best for hydrogen sulfide.
But just to think it another way because I’m sure this question comes up… think about diet. We
think there might be actually three diets for SIBO—one for hydrogen, one for methane, and
one for hydrogen sulfide (because if you go on a low sulfur diet, maybe that helps hydrogen
sulfide).
So, there are a lot of things coming down the pipeline that we think will help you understand
better, help you treat your patients better. But it starts with knowing you have it, and then
Shivan Sarna: From one of your colleagues, Dr. Steven Sandberg-Lewis: “If a patient has
IBS/IBD, say Crohn’s and SIBO, how does ibs-smart™ distinguish that? They have both.”
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Dr. Mark Pimentel: So, let me explain the sensitivity and specificity for the blood test. People
say, “Well, it’s a low sensitivity, 43% to 56% sensitive.” Well yeah, it can’t be more than 56%
sensitive because, I’ve already told you, out of a hundred people who show up at your office,
So if you knew who had food poisoning, it would be 100% sensitive. So I’m not worried about
that.
The specificity is more important. If you’re positive, it started from food poisoning with more
Now on the other side of the equation, which is the point of the question, in the IBD group, the
reason our specificity is 90% and not 100% is because 10% of people with IBD have a positive
Dr. Mark Pimentel: Because 10% of the entire planet has IBS, including 10% of IBD. So you’re
always going to have a few patients who have IBS and IBD together. And that’s why we can
So, if you understand the statistics of things, you understand that the test is quite impressive
But I think Dr. Sandberg-Lewis’ point is, if you have both, how do you treat both? Well, you have
to treat both in order to get the patient better. There are many patients, for example, with
Crohn’s or ulcerative colitis, the primary treatment that’s been used in the past is steroids. So,
the patient goes to the doctor, they have IBD, they have Crohn’s or ulcerative colitis, they get
whacked with steroids… a lot of side effects. Part of it gets better. But they still have bloating
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and a little bit of diarrhea. So the doctor says, “Well, let’s go more steroids… and more
steroids.” And then, they do a scope, and they see nothing… the Crohn’s is gone.
So, they were jacking up the steroids treating IBS on top of IBD instead of the Crohn’s that was
gone.
So, my point is knowing that they have both is really important so you don’t jack up all these
drugs that are harmful while you can just so easily treat both there.
Shivan Sarna: If someone has a breath test, and only has hydrogen show up on that breath
Dr. Mark Pimentel: I still call it SIBO because it’s E. coli and klebsiella. And maybe the rabbits
Shivan Sarna: Okay. When it comes to the future… okay, that’s going to be revealed, you guys,
Go to the SIBO SOS® Facebook Community because a lot of the questions that you guys are
asking are answered there. Dr. Allison Siebecker and I created a course called The SIBO
Recovery Roadmap. Also tons of information there. And then, we’ve done two masterclass
summits which Dr. Pimentel has participated in. You can find it all in SIBOSOS.com.
Your questions are amazing. We have covered a lot of them. This is sort of Dr. Pimentel’s
How often do you see people have negative SIBO breath tests and it’s actually parasites or it’s
Dr. Mark Pimentel: So what I understand from Satish Rao who does a lot of getting juice from
patients where antibiotics have failed… generally, if you’re taking an antibiotic and it’s not
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working, or you have a negative breath test and it’s not SIBO, but everything else is negative,
Obviously, with parasites, you should look for it. And people do parasite testing. I do it at
Cedars as well. But it’s not my first thought because, if you look at the data, and if you had a
hundred consecutive patients coming in with IBS, most of them would not have a parasite
quite infrequently). So, my point is parasites are not as common as SIBO itself. So to treat it
Again, it depends. If the breath test is negative, then you can go at it and look for other things
like that.
Shivan Sarna: Because we do get people with negative SIBO breath tests, and they’re
confused about “well, what else could it be?” So you do suggest the scoping, a parasite test…
and then, you can’t really easily test for SIFO, for fungal overgrowth. But Dr. Satish Rao for all of
that information.
Dr. Mark Pimentel: Probably about 10% of his population—I’d have to ask him what his latest
numbers are—could have SIFO. And the 10% of the patients he sees is different than the 10% of
the general population because he’s seeing patients that have been around the block a few
times.
Shivan Sarna: When it comes to adhesions—that is such a big proportion of people with
adhesions who have SIBO. In case someone’s new… welcome! But could you explain what
Dr. Mark Pimentel: So adhesions are you’ve had surgery. Sometimes, you didn’t have surgery.
Maybe you had an appendix that got inflamed and healed on its own. You didn’t even know.
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But you have scar tissue in the cavity, but on the outer side of the bowel. And it basically
creates a kink in the hose, like your garden hose, where the water doesn’t flow through it that
There are therapeutic ways where massage and other abdominal massage can break
adhesions down. It’s hard to quantify that because you can’t quantify adhesions to begin
with. It’s very hard to know. We’ve seen CT scans, everything looks like normal, you go on
inside and there’s adhesions everywhere. So you can’t, with regular radiology, quantify
adhesions. But that works! Or surgery unfortunately is sometimes the option we have to go
down.
Shivan Sarna: In case someone’s also fairly new, like they’ve been playing around with this
whole hydrogen and methane dominance, and they’re like, “Hydrogen sulfide? Wait a minute!
I didn’t know about that!”, what are some of the symptoms to suspect hydrogen sulfide?
Dr. Mark Pimentel: Yeah, the two main symptoms that the hydrogen sulfide patients have
that the others don’t have as much of is diarrhea and abdominal pain, those two. Hydrogen
sulfide is pretty toxic. So it causes pain fibers to be amplified, and then also, the diarrhea,
Shivan Sarna: And what about SIBO causing GERD, breaking news there!
Dr. Mark Pimentel: Long ago, when we did what’s called a factor analysis—so we broke SIBO
down to two buckets (we didn’t have the third, we didn’t have hydrogen sulfide. It was only
two buckets at the time), methane, it turns out, was associated with constipation. We know it
slows the gut down. But we showed that, because it’s slowing the gut down, it was associated
But anything that causes the abdomen to distend and create pressure means the pressure
to back up into your esophagus is higher. Esophageal reflux is pressure below the diaphragm
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relative to pressure above the diaphragm to make the acid come up. And if you increase that
Shivan Sarna: One minute to go… you know I like to keep you on your schedule because I so
appreciate you giving us so much time. There’s a big virus running around right now. And a
lot of people are very interested in getting vaccinated. And I’m just wondering if you’ve seen
in your practice any correlation with people with SIBO and IBS having an adverse reaction?
Any advice you have for us on our gut patient population and the vaccine.
Dr. Mark Pimentel: So, what we’re seeing with the virus itself is a lot of patients are getting
digestive symptoms. It ranges from 10% to 30%. The biggest question I get is: “Is CoVID causing
There are people who they call “long haulers.” They don’t get better over time, or they take a
long period of time to get better. That’s usually not the digestive part. It’s more body aches,
Shivan Sarna: Can you say that again because it just bleeped. That was like a cliffhanger. The
Dr. Mark Pimentel: The virus is in the gut. It can be in the gut. And it can bind to ace receptors
in the gut. So yes, the virus can be transmitted through stool, it’s believed. All of that is true
But in terms of the vaccine, we haven’t seen any GI consequences of the vaccine that we
know of… just fatigue, fever, all of those sorts of things in the early days. So, so far, so good with
the vaccine.
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Shivan Sarna: That’s great. Thank you so much, Dr. Pimentel. We’ll look forward to speaking to
you again after Digestive Disease Week. Keep up the fantastic work. Let’s talk to you in June.
And in the meantime, let me do my best to get this information out to as many millions of
Shivan Sarna: I’m going to have Dr. Pimentel sign off. And I want to say thank you to everyone
who has been here for this presentation from SIBO SOS®. And if you have not gotten into our
Facebook Group, for those of you in the zoom call and not on the Facebook Live feed right
A lot of the questions that you all have been asking are fantastic of course. And SSL, I think
you’re going to have to ask him some of those questions directly. Water, making you bloat…
Dr. Pimentel has explained that before where it’s like a balloon from a kids’ birthday party with
a clown just tying them up into different knots. It just has to do with the plumbing and the
tube. So yes, even drinking water can cause bloating if you have issues.
What I want to also let you know is that we have a whole library of Dr. Pimentel’s previous
presentations where a lot of these questions are ultimately answered. We call it The Pimentel
Chronicles. And it is on SIBOSOS.com. You can go to the Resources area, you can see our
on-demand learning library… and there are tons of fantastic resources there.
That is something I have not done a fabulous job of getting out to the world. It’s a little bit
hidden. And I’m working on getting that more out there. A lot of times, they’re part of our
summits, the SIBO SOS® Masterclass Summit and then the Next Steps for Treating Tough SIBO
Masterclass Summit which we’ve just wrapped. You can find it all in SIBOSOS.com.
Also, there are tons of free resources at SIBOinfo.com, Dr. Allison Siebecker’s website.
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The book, #HealingSIBO, is going to be the best $20 you’ve spent on figuring out what to do
next. It’s based on everything Dr. Pimentel was talking about. On page 111 is the algorithm that
so many people have followed that he started and that Dr. Allison Siebecker and Dr. Steven
Sandberg-Lewis added to. It’s right here. That’s also a free download on SIBOSOS.com.
Okay, I’m going to wrap it up! We are very appreciative of you. Thank you so much for being
here everybody. I really, really treasure you. And I want to wish you the best. Do not give up.
There are tons and tons of hope. Dr. Pimentel and his team are working basically 24/7 to
figure this out. I do think, in June, there are going to be some revelations that we’re going to
feel really good about it. But that hydrogen sulfide treatment he just talked about with
PeptoBismol is terrific.
Also, Dr. Siebecker, another world-renowned SIBO specialist like Dr. Lisa Shaver who’s joined us
today, and Dr. Steven Sandberg-Lewis and so many more—thank you guys for being here—if
you go to the SIBO SOS® Facebook Group, and you look under “Files,” tons of information
Remember that if you sign up—I don’t get a kickback or anything on this. If you want to do the
ibs-smart™ test, use the coupon, sibosos2021, when you order it, and you get 25% off which is
And if you have any questions about the ibs-smart test™, which is the anti-vinculin, the test
and all of that for the food poisoning leading to SIBO, email [email protected] and
And the coupon is case sensitive. Ooh, that’s complicated. Okay, it’s SiboSOS2021. That’s
complicated, sorry! Well, look for it on SIBOSOS.com because I think we have it typed up there
really nicely.
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And then, I just wanted to find the email address again for anybody who wants to get their
questions answered about the trio-smart™ breath test, like directly from the lab itself.
And international, they’re working on it. I know that it’s not as prevalently available as they
want it to be. So they’re constantly working on it. Paige, are you with me? Can you type that in
Love you guys! Thank you so much for being here. If anybody is interested in the lymphatic
system—my mom passed away in the ‘90s from lymphoma. And so, with all of my gut work, at
the back of my mind, I had another summit brewing, and it’s called the Lymphatic Rescue
Summit. And if you’re interested in that, please email us at [email protected]. Make sure
you’re on our email list. I’ll send you out the opportunity to sign up for that for free. That’s
happening in April.
And so, it’s a tribute to her. I didn’t know what was going on with SIBO. What’s the lymphatic
system?! In the ‘90s, no one knew! And I wanted to make sure no one went through what we
Also, in September, I’m doing a summit on Biological Dentistry, the connection from the
mouth to the rest of your body, and your amalgams… we’re the only country that separates
the mouth from the rest of the body! So it has been incredibly illuminating. I can’t wait to
And the next year, I’m doing the Liver & Gallbladder Summit.
So, be sure to stay on the email list. And we will keep you posted. Okay, I’m going to wrap up.
Clarissa, who’s in the background… would you do me a favor and gather all the questions?
Throw it into a spreadsheet and let’s see what we could do with those.
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Yes, you will have a replay sent to you on Friday. That’s our goal. And yes, if you go into the
Facebook group, you will find this recording. And yes, I’m going to have this transcribed, so
If you’re listening to the podcast, you obviously won’t be able to right now see the slides. But
we’ll give you a link so you can go watch the video too! Peace everyone. Thank you.
Yes, we’ll send all the URL’s and website info. Sure! Absolutely! I’m going to send you
everything and make your life easier… all kinds of stuff. So I’ll send you all the links that I was
just trying to read… and the coupon. But you can find that at SIBOSOS.com if you’re really
Okay! Bye!
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