August 1, 2025 • 44 mins
Dr. Mark Pimentel, Executive Director of the MAST program at Cedars-Sinai in Los Angeles, shares groundbreaking insights into the small intestinal microbiome that challenge long-held beliefs about gut bacteria. Findings from his team’s REIMAGINE study reveal that the small intestine is far from sterile, as previously thought—instead, it harbors substantial bacterial communities that play a critical role in health and disease, especially in conditions such as IBS and SIBO.
• E. coli and Klebsiella act as aggressive "Ferrari" bacteria that outcompete other microbes and destroy microbial diversity when overgrown inducing a "apocalyptic" disruption of the small bowel microbiome.
• Lactobacillus, commonly found in many probiotics, may act as a disruptor in the small intestine and new research correlates higher small intestinal levels with obesity and unhealthy aging (more research needed)
• The PLACIDE trial found probiotics didn't reduce C. diff or antibiotic-associated diarrhea but did increase bloating
• Food poisoning is the only proven cause-and-effect trigger for IBS, with stress acting as a modifier rather than initiator
• Combining rifaximin with NAC works 10x better for SIBO by targeting bacteria in both intestinal fluid and mucus
• A new compound (CS06) shows promise for reducing methane production and relieving constipation
• Three distinct gas patterns (hydrogen, methane, hydrogen sulfide) correlate with different symptom patterns and respond to targeted treatments
This episode was sponsored by Salix Pharmaceuticals.
Resources:
DDW 2025 Abstracts by the Mast Program and Dr. Pimentel
A Novel Microbiome Therapy, CS-06 (MTD Blocker), Reduces Methane Production in Stool Culture
Real World Study of Three-Gas Breath Testing Nationwide and The Association with Symptoms
Learn more about Kate and Dr. Riehl:
Website: www.katescarlata.com and www.drriehl.com
Instagram: @katescarlata @drriehl and @theguthealthpodcast
Order Kate and Dr. Riehl's book, Mind Your Gut: The Science-Based, Whole-body Guide to Living Well with IBS.
The information included in this podcast is not a substitute for professional medical advice, examination, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider before starting any new treatment or making changes to existing treatment.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Kate Scarlata, MPH, RDN (00:00):
This podcast is sponsored by Salix
Pharmaceuticals.
Maintaining a healthy gut is keyfor overall physical and mental
well-being.
Whether you're ahealth-conscious advocate, an
individual navigating thecomplexities of living with GI
issues, or a healthcare provider, you are in the right place.
(00:23):
Or a healthcare provider, youare in the right place.
The Gut Health Podcast willempower you with a fascinating
scientific connection betweenyour brain, food and the gut.
Come join us.
We welcome you.
Dr. Megan Riehl (00:38):
Hello friends, and welcome to The Gut Health
Podcast, where we talk about allthings related to your gut and
well-being.
We are your hosts.
I'm Dr Megan Riehl, a GIpsychologist.
Kate Scarlata, MPH, RDN (00:50):
Hello, and I'm Kate Scarlata, a GI
dietitian.
Today, on The Gut HealthPodcast, we're joined by a true
pioneer in digestive science, DrMark Pimentel.
Renowned across the globe forhis groundbreaking work in
gastroenterology, Dr Pimentelserves as the Executive Director
of the Medically AssociatedScience and Technology, also
(01:13):
known as MAST program atCedars-Sinai Medical Center in
Los Angeles.
At the helm of the MAST program, Dr Pimentel leads an
innovative team that'sunraveling the complexities of
the human gut.
Their focus conditions likeirritable bowel syndrome, IBS, a
disorder that affects nearly 1in 10 people worldwide, as well
(01:37):
as the lesser-known butincreasingly important small
intestinal bacterial overgrowth,or SIBO, and intestinal
methanogen overgrowth, or IMO.
Today's topic is the gutmicrobiome and dysbiosis.
Welcome back, Dr Mark Pimentel.
Dr. Mark Pimentel (01:57):
It's great to be back with you.
It's exciting.
It's the summertime, but peopleare still interested in the
microbiome.
What a thought time, but peopleare still interested in the
microbiome what a thought.
Dr. Megan Riehl (02:06):
Well, Dr Pimentel, we want to kick things
off today with you with a mythbuster and, you know, with
summer, whatever it may be.
What do you think our listenersneed to know in the myth
busting world of the microbiome?
Dr. Mark Pimentel (02:20):
I think the biggest myth that we deal with
on a daily basis is that themagic is really in the dual
microbiome only.
And if we're going to talkabout microbiome, a lot of what
I'm going to talk about is thesmall intestinal microbiome,
which is harder to get to.
They used to think that thesmall intestinal microbiome was
sterile.
There was no bacteria there, orhardly any, and now we know
(02:42):
it's abundant, and the bacteriathere are giving you things that
you don't want, sometimesgiving you things you do need,
and that's the myth.
The myth is that the bugs thatwe thought were only in the
colon are in the small bowel aswell, and they can create
problems for your health.
Kate Scarlata, MPH, RDN (02:59):
I often think like are we going to
start looking a little closer atthe mouth microbiome, the
esophagus microbiome, thestomach microbiome, all these
places that seem to beinconsequential but maybe are
playing a role, even if thebacteria numbers are vastly
different and less, etc.
But let's kick it off with whatis gut microbial dysbiosis and
(03:24):
why should we care?
Dr. Mark Pimentel (03:26):
You know, dysbiosis used to be a dirty
word or a word that peopledidn't like to use because it
had really no meaning.
It just means there's a problemwith the microbiome, and that's
like saying there's a problemwith your arm.
That's a diagnosis.
No, that's not a diagnosis.
There's a problem with your arm.
We need something more specific.
So I think the term dysbiosishas been thrown around and again
(03:49):
still doesn't have any meaning.
But I think what we're trying todo, or what people are trying
to say, is that it's anoverarching term that says
there's something wrong withyour microbiome and it could be
this, it could be this, it couldbe this, and in each particular
instance, it can have differentramifications on your health
and your condition.
And I think that's really whatthe term dysbiosis ought to be
(04:11):
used for at this point in time,because, like, for example,
there are things that areadvertised oh, help your gut,
dysbiosis.
What does that mean?
I mean you're selling a productto help dysbiosis, but what
dysbiosis are you talking about?
So we don't want to use it inthat context, but as an
overarching term, I think it'sfair to say.
Dr. Megan Riehl (04:30):
Okay.
So it's certainly not specificto just it's too general for the
gut.
Dr. Mark Pimentel (04:37):
Right, exactly.
Dr. Megan Riehl (04:39):
Okay.
So when it comes to a diagnosisof something that you are
studying every day of your lifeSIBO, small intestinal bacterial
overgrowth, do you believe thatthis fits the definition of
small bowel dysbiosis?
Dr. Mark Pimentel (04:53):
So we're doing a study called the
REIMAGINE study and you may haveheard about it, but basically
it's the first and largest nowstudy of the small intestinal
microbiome taking aspiratesusing proper double lumen
catheter techniques so that it'ssterile.
We've been doing this for awhile.
We have well over a thousandpatients on our way to 10,000
patients.
When you look at the smallintestine in a normal person it
(05:17):
barely goes above 10 to the 2,10 to the 3, or 100 to 1,000
microbes per ml.
In the case of overgrowth it'sover 10 to the three.
But that's not the story.
The story is in the reimagineddata.
This is like over 1,000patients.
The most apocalyptic thing wesee is overgrowth, and what I
(05:39):
mean by that is nothing is asdramatic, nothing is as obvious
as when overgrowth is there,because when the E coli and
Klebsiella part of overgrowthblooms or grows, it destroys
everything in its path.
It's like a bulldozer takingout all the rest of the
microbiome.
The higher the E coli is, themore destroyed the rest of the
(05:59):
natural garden is is destroyed,and so it really is apocalyptic.
The only other example ofapocalypse on the small bowel is
antibiotics.
If you take broad spectrum likeciprofloxacin or something like
that recently the microbiome iswiped out.
So those two instances are themost obvious.
Dysbiosis, if you want to goback to that term.
(06:21):
Sibo is very dramatic, veryobvious when it's there.
Kate Scarlata, MPH, RDN (06:26):
Yeah, so you're basically saying I
just want to kind of recap thisfor our listeners that there are
certain microbes that you'refinding are always there with
overgrowth and they're wipingout some of the other
populations.
So they're the primary microbesin that condition, Right?
Dr. Mark Pimentel (06:44):
Exactly, they're the primary microbes in
that condition.
Kate Scarlata, MPH, RDN (06:45):
Exactly , so are they always the bad
guys, like some people haveKlebsiella and E coli and
they're fine, it's just whenthey go rogue in the small
intestine.
Dr. Mark Pimentel (06:55):
Yeah, so it's a little bit tricky.
So one of the other myths if wewant to go back to myths going
backwards in this podcast isthat even I, in review articles
on SIBO, I used to say, as thetextbooks used to say, that it's
coliform microbes moving intothe small intestine that's
overgrowth.
Some people even still talkthat way.
(07:16):
That's absolutely not what itis.
We didn't know that then whenwe were writing these articles.
What we now know it's reallyknow that then when we were
writing these articles.
What we now know it's reallythere is a slowing of the small
intestine and thatpreferentially favors aggressive
bacteria, and E coli andKlebsiella are the two most
aggressive.
There are others Eremonis andother organisms that are minor
(07:38):
parts of SIBO, but the Ferrarisare E coli and Klebsiella and
they are so good at fermentingand capturing the nutrients from
your food that once they'veestablished they're a wrecking
ball, and we call themdisruptors because as they grow
they disrupt the rest of theflora.
Sort of like your garden isovertaken by weeds and the weeds
(08:01):
will win, the garden will lose,and that's what's happening.
So E coli is the biggest one.
Klebsiella is less common butworse to the microbiome, it's
more disruptive, and then theothers are minor.
Overgrowth is not coliforms.
It's the E coli and Klebsiellathat are there that now have the
competitive advantage becauseof the stasis or different
(08:25):
changes in the environment inthe small intestine at that
moment.
Dr. Megan Riehl (08:29):
And this is some of the connection then to
IBS, post-infectious IBS andSIBO.
These microbes are culprits.
Dr. Mark Pimentel (08:39):
Yeah, exactly .
So we've shown this entiresequence.
Like we've given food poisoningto rats and then they develop
the stasis of the gut.
They develop these antibodiesfrom the toxins of the food
poisoning the CdtB andanti-vinculin antibodies,
because they react to the foodpoisoning.
So you get this autoimmunity,and then the small bowel slows
(09:00):
down from that and when it slowsdown the bacteria build up, and
in rats it's not Klebsiella,it's only they don't have
Klebsiella, it's E coli, and Ecoli goes through the roof.
So we've seen this entiresequence in animals.
So we know this happens and weknow that in humans the only
known cause and the only causeand effect cause because this
(09:22):
has been proven with theBradford Hill criteria for IBS
in humans is food poisoning.
Campylobacter particularly isthe worst and so it's been very
well characterized.
In fact, stress has been shownnot to be the precipitant but to
be a cofactor.
So stress, anxiety anddepression is not a cause of IBS
(09:42):
but is a modifier of IBS.
Dr. Megan Riehl (09:46):
That's right.
That's right, and many otherthings too,
Dr. Mark Pimentel (09:49):
and many other things blood pressure,
heart disease, stroke, you nameit.
Stress.
Dr. Megan Riehl (09:54):
Inflammatory bowel disease.
Dr. Mark Pimentel (09:56):
Yes, exactly.
Kate Scarlata, MPH, RDN (09:57):
We got to all chill out.
Dr. Megan Riehl (10:00):
That's right.
Kate Scarlata, MPH, RDN (10:01):
So you also had mentioned lactobacillus
as being a disruptor in aformer conversation and I'd love
you to talk about that, as yourgroup's been really looking at
the small bowel.
Can you talk a little bit aboutlactobacillus as a disruptor in
the small intestine?
Dr. Mark Pimentel (10:15):
Yes, so I mean a lot of our work's been
focused on irritable bowelsyndrome and the relationship
with overgrowth, and that's veryexciting and it's really come
to the forefront now.
But we found some pearls in theREIMAGINE study that are super
interesting.
For example is thelactobacillus so in patients who
have unhealthy aging.
So let me backstep.
(10:37):
Lactobacillus has been studied.
Administering lactobacillus,taking probiotics has been
studied on the basis ofmeasuring stool.
Nobody ever looked at the smallbowel to see the effect of
these probiotics on the smallbowel.
So now fast forward to theREIMAGINE study.
We see that when patients havehigh lactobacillus in their
(10:59):
small bowel, it is associatedwith more obesity and it's very
strong association.
And then the second thing is welooked at aging and unhealthy
aging, and healthy aging andunhealthy aging is associated
with higher lactobacillus in thesmall bowel.
Now is it cause and effect?
Those things need to bedetermined.
(11:20):
So I can't say that, oh boy,because your lactobacillus is
high, you're going to age badly.
If you think about it, we giveyogurt to our kids instead of
fruit cups because we think it'smore healthy.
Is it right?
Is it a good thing?
We don't know the answer to it.
But the third piece of thatlactobacillus puzzle is we did a
study looking at the disruptorsof the small bowel.
(11:41):
The more lactobacillus you havein the small bowel, the more
the garden is destroyed thenormal flora.
So that concerns me a lotbecause I don't know what the
repercussions of that are.
But you can imagine it might besimilar to the E coli and
Klebsiella of IBS.
The lactobacillus is not makingyou have all that IBS symptoms,
(12:02):
but is it doing other things?
Is it leading to obesity?
Is it leading to other thingsthat we need to understand more
consequentially, and so morework needs to be done.
But I think that's worrisome tome.
So I don't really advocate forlactobacillus or probiotics
using lactobacillus in mypractice.
Kate Scarlata, MPH, RDN (12:20):
Would you say that across the board
for everyone, like say you weretalking to someone just
interested in their gut health?
Do you think lactobacillus hasgot a potential problem?
I don't know the answer.
Dr. Mark Pimentel (12:31):
Now that's really got me wondering what is
good about lactobacillus, whatcould be bad about it?
I don't know the answer to it,but it really raises a lot of
questions and a few hairs on myneck because I'm worried that it
could be harmful.
I go back to what our motherstold us too much of anything is
a bad thing, and that has alwaysrung true for all of science is
(12:52):
that too much of one thing isalways a bad thing.
Oh, don't eat fat, don't eatany fat.
So you know, you swing thependulum.
So now we switch it all tocarbs and everybody's getting
obese.
And now they're swinging backand saying carbs are okay or
carbs are not okay, fat is okay.
And so the pendulum swings.
But if you have a balanced diet, if you have a little bit of
(13:14):
yogurt here and there, as ahealthy person I think there's
no problem with it.
But if you want to get 20billion lactobacillus in your
gut every day, is that healthy?
I'm not sure.
Kate Scarlata, MPH, RDN (13:24):
Yeah, it's that whole notion that more
is better.
We just can't get away fromthat.
Everyone thinks, well, geez, if10's good, let's get a million.
And see what happens.
Dr. Mark Pimentel (13:33):
Yeah, if I can live longer, because a
little bit of selenium is good.
More is better, right?
Dr. Megan Riehl (13:39):
So anyway, it's interesting we have to remain
curious and I think that's thething here is and I think
probiotics are a great exampleright that people are just, they
want to feel better.
And to your point, which onehas the highest?
If a little bit is good, thenagain let me find the probiotic
out there with the highestamount of that.
(14:00):
And then they stay on it fortoo long without adequate relief
of their symptoms and itbecomes a very muddy waters or
the garden is very heavilyimpacted by too many weeds and
species.
Kate Scarlata, MPH, RDN (14:14):
exactly .
Dr. Mark Pimentel (14:17):
But even if you're planting a garden, you
don't plant all tomatoes.
I mean, you can't expect oneorganism to correct a thousand,
right?
So it's like I say, if you adda thousand lawyers every day to
Los Angeles, that may not be ahealthy thing for the city.
We need lawyers, but maybe athousand every day is too many,
you know.
So that's the concept of aprobiotic, and not to mention
(14:39):
the other sad thing about theword probiotic is it has the
word or the prefix pro in it,like it's good.
And then this notion anothermyth of good and bad bacteria.
That's a myth.
There is no such thing as goodand bad.
There's.
Bacteria are all good and allbad, depending on where they are
(15:00):
.
Lactobacillus in yourbloodstream, not good.
Lactobacillus a little bit inyour gut, probably good, and so
it just depends where they areand what circumstance.
They all evolved to stay intheir place and their niche, and
when they are too high or inthe wrong place, it's a bad
thing.
Kate Scarlata, MPH, (15:18):
Moderation in all things.
Dr. Megan Riehl (15:21):
That's right.
We've discussed and you cancorrect me if I'm saying this
incorrect.
Is it Placide trial?
Dr. Mark Pimentel (15:29):
Yes.
Dr. Megan Riehl (15:30):
Okay, so let's talk about the Placide trial.
What did this trial look at andhow is this information
clinically relevant for us?
Dr. Mark Pimentel (15:39):
So this was a study looking at patients that
were given antibiotics forwhatever a urinary tract
infection or some sort ofinfection at the moment in
primary care clinics.
And then, as they were giventhe antibiotics, they were
randomized to probiotic or noprobiotic and what they found
was there were no decreasedrates of C difficile or
(16:02):
antibiotic-associated diarrheabecause you're on the probiotic.
That was what they were hopingto see.
Is that that would prevent Cdiff or something like that, and
the only thing they found thatwas statistically different.
The only significant thingreally was that the probiotic
group had more bloating.
So this is what I tell mypatients If you want more
bloating, please take aprobiotic, because it will
(16:24):
provide that for you, becausethe Placide trial is the largest
randomized control trial todate on this.
So it kind of settles the issue.
Now, the probiotic world is aplethora of products, so it's
very easy for the company sayswell, that's not our strain, our
(16:49):
strain doesn't do that, orthat's not bifido, that's
lactobacillus.
So whether I say this or not ina podcast, and whether somebody
hears this or not in a podcast.
The product companies are goingto say, well, that wasn't my
product.
And so the story continues aswe unfold this.
But the problem is that thesecompanies don't have the money
or don't want to do theseincredibly large trials to prove
one way or the other if theirproduct does what they hope it
(17:12):
does.
So it's a tricky area.
I do believe bacteria areimportant.
I do believe there are somethat are better than others.
I just don't think you've gotto over.
You know, jack up the systemwith too much of it.
Kate Scarlata, MPH, (17:23):
Especially if the small bowel is not
working very well.
It just feels like you're justaccumulating.
Dr. Mark Pimentel (17:30):
I can tell you absolutely.
I have patients who have IBS,who've taken probiotics and said
, oh my God, I feel so muchbetter.
It's rare but it happens, andso I say, great, call me when
it's not.
Inevitably they call me andit's not working again.
And then we go back to squareone and we go through the
fundamentals again.
(17:51):
But you know, I can't deny thatthere are occasions where
patients feel better.
But anecdote is not science.
We deal with it in the clinicall the time.
Kate Scarlata, MPH, RDN (18:02):
Yeah, it's true, especially when you
really want to feel better.
You're hoping so hard on thatlittle probiotic capsule.
Dr. Mark Pimentel (18:08):
Exactly.
Kate Scarlata, MPH, RDN (18:09):
So let's talk a little bit about
SIBO and new treatments, and Iknow your group reported at DDW
this year about using rifaximinwith N-acetylcysteine or NAC and
found that this combo workedbetter than rifaximin alone.
I know rifaximin has FDAapproval for IBS-D, so kind of
(18:29):
used off-label for bacterialovergrowth, but is used commonly
.
So what led you to looking atNAC and rifaximin together?
What prompted that idea?
Dr. Mark Pimentel (18:42):
So when we helped develop rifaximin
together, like what promptedthat idea, so when we helped
develop rifaximin in the firstplace, it is a great drug for
IBS.
It's the number one drug forIBS worldwide.
Now If you go to chat GPT youcan ask because it's safe,
because two weeks might get yousix months of benefit, which no
other drug does.
So in that context it's beenvery successful.
(19:03):
But I was never satisfiedbecause what I'm seeing in the
microbiome of IBS more peopleshould get better from rifaximin
.
Something didn't add up to mebecause we're seeing more SIBO
in IBS than rifaximin makesbetter.
So, for example, rifaximintarget three trial, 44% of
(19:27):
people responded to rifaximinbut we're seeing 60 to 70%
having SIBO.
So why are the others notgetting better?
Or why isn't it as good as itshould be?
Where rifaximin'scharacteristic are, it's not
absorbed because it'shydrophobic.
It's like an oil almosttechnically.
It doesn't have an ability todissolve in water.
So there's that part.
(19:48):
And then what we found in theREIMAGINE study in SIBO patients
is that E coli and Klebsiella,those two bad disrupting
characters, those Ferraris, whenwe calculate where they live in
the small bowel, 50% of themlive in the free fluid which
rifaximin has access to, and theother 50% live in the mucus,
(20:09):
not the mucosally associatedwith the mucus, the thick,
stringy stuff.
And rifaximin will never getinto that.
So we did some studiespreliminarily to see if we added
a mucus buster or a mucolyticlike NAC, does rifaximin work
better?
And it works 10 times better inthat situation.
(20:29):
So we are able to get rid ofthe Ferraris more
comprehensively if NAC ispresent and we can use a much
lower dose of rifaximin to getthe same effect.
And we can use a much lowerdose of rifaximin to get the
same effect.
So we did an initial studywhich we presented at DDW and it
showed that in a very smallstudy rifaximin and NAC is
better than rifaximin, the oneon the market.
(20:51):
And so the phase 2B study.
I just had a meeting beforethis one.
We're kicking that off inSeptember.
It's the first phase 2B studyat our center that isn't pharma
funded, it's we're doing thewhole thing ourself to see if we
can get this better forpatients.
So it was pretty cool.
No pharmaceutical company.
Kate Scarlata, MPH, RDN (21:12):
No pharmaceutical company, yep,
amazing.
Dr. Megan Riehl (21:16):
Why is that important for a listener?
What does that mean?
Dr. Mark Pimentel (21:19):
You know doctors do a lot of things with
pharmaceutical companies.
You know we try to get thingsacross the finish line.
But I'm not doing this for that.
I'm doing this for patients.
We want patients to get better.
This isn't about pharmaceuticalcompanies.
This is about doing the rightthing and finding the right
answers and getting these thingsfor patients.
(21:39):
So I'm hopeful this will amountto something and then make
patients better more often.
I believe it will.
Our data has shown that we evenhad to use our rat study, the
rats who were post-infectiousand, sure enough, just giving
rifaximin versus rifaximin andNAC.
Rifaximin and NAC wascompletely normalized.
(21:59):
Their cytokines normalized,their microbiome normalized
their bowel movements, whereasthe rifaximin and NAC.
Refaximin and NAC wascompletely normalized.
Their cytokines normalized,their microbiome normalized
their bowel movements, whereasthe refaximin only partially did
that.
So we're going to the nextlevel and we're doing it alone.
Kate Scarlata, MPH, RDN (22:11):
I love that.
So just quickly, how much NACare you using?
The same amount of NAC that youused in the trial that was
reported at DDW?
Can you disclose the amountthat you're using in the trial?
Dr. Mark Pimentel (22:25):
So it's a different formulation than that
trial Now this is the finalformulation, where it's
delivered in the small intestine, specifically in the locations
where the E coli would beexpected to be.
So it's got a special deliverysystem.
It's different than the other.
Okay so we'll see how it goes.
Kate Scarlata, MPH, RDN (22:42):
Awesome , we'll be waiting.
Yes, we will.
Dr. Mark Pimentel (22:45):
And I will have no fingernails left by the
end of it.
Kate Scarlata, MPH, RDN (22:49):
I bet you won't.
We appreciate all the workyou're doing, especially in this
area, because you're reallylike it seems like the one and
only that's just like reallyknee deep in it and pushing the
bar like really knee deep in itand pushing the bar.
Speaker 4 (23:16):
Visit Xifaxan.
com/ IBSD for the PI or talk toyour doctor.
Don't use Xifaxan if you have ahistory of sensitivity to
rifaximin, rifamycin antibioticagents or any components of
zyfaxin.
Tell your doctor right away ifyour diarrhea worsens while
taking zyfaxin, as this may be asign of a serious or even fatal
condition.
Tell your doctor if you arepregnant, plan on becoming
pregnant or nursing.
(23:37):
If you have liver disease,taking warfarin or other
medications, some medicationsmay increase the amount of
Xifaxin in your body, mostcommon side effects are nausea
and an increase in liver enzymes.
Xifaxin.
Kate Scarlata, MPH, RDN (23:57):
So let's switch gears to methane,
and I know there's been a numberof different studies linking
high levels of methane withconstipation.
But I'm wondering, like is thisbi-directional at all?
Like, if you're constipated,does that contribute to methane
being produced or more substratefor those microbes?
Like is there any connectionwith just someone being, say,
someone's just constipateddoesn't have elevated
(24:19):
methanogens.
Do they develop elevatedmethanogens just because they're
constipated, or is it just themethanogens are causing the
constipation through theirmethane?
Does that make sense?
Dr. Mark Pimentel (24:31):
Yes, and that's an argument that's
resurfaced recently, and Iwonder whether some of those
folks hadn't read the earlierpapers that have already been
done, whether some of thosefolks hadn't read the earlier
papers that have already beendone because we've gone through
that argument already.
So yes, if you have methaneyou're more likely to have
constipation.
The higher the methane you haveon the breath test, the more
(24:52):
constipated you are.
It's very proportional, whichis really important for cause
and effect.
But that doesn't mean that themethane is causing the
constipation, because if you'remore constipated maybe you have
more methane, maybe themethanogens love that dry stool
environment and they do betterin that situation.
But we've done the other side ofit, where we've given
(25:13):
methanogens to animals and theyget constipated.
So we gavage them with themethanogens.
We've done the studies of liveanimals where we infuse methane
into the small intestine andthey get 60% slowing of
intestinal transit.
We've done organ baths of thesmooth muscle of guinea pig
ileum, adding methane to thebath and the guinea pig ileum
(25:34):
the peristalsis goes away, itgoes into more of a spastic
contractile activity.
So it's the methane.
And now all of a sudden maybethere's a study that says that I
don't know that maybe they'reconstipated first, then they get
methane.
I'm not sure it hasn't come outyet, but this is coming back to
life.
But maybe they should readthose papers because I think we
(25:57):
pretty much nailed that downthat methane is a constipating
agent period.
Kate Scarlata, MPH, RDN (26:02):
Yeah, I thought so too, but I was on as
I do lurk on Twitter and saw arecent paper and I'm like I'm
going to ask Dr Pimentel aboutthat.
Dr. Mark Pimentel (26:11):
Well, the paper hasn't come out yet, so it
remains to be determined.
Kate Scarlata, MPH, RDN (26:14):
Yeah, I just saw the commentary.
Dr. Mark Pimentel (26:16):
But I certainly hope that they at
least reference those papers,because those are the ones that
show that it's primarily methanethat's causing the constipation
and slowing the gut down, butit's okay.
Kate Scarlata, MPH, RDN (26:27):
You heard it here first.
Dr. Megan Riehl (26:29):
and in more cutting edge research that's
coming out of your lab.
Let's talk a little bit aboutCSO6.
So you presented a preclinicalstudy looking at the molecule in
relation to reducing themethane gas levels, as we've
really identified, methaneassociated with constipation and
(26:50):
also IMO in human studies.
So what is CSO6 and itspotential mode of action?
And, based on the timing of theresearch, if this study proves
itself to work in humans, whendo you think it's going to come
to market?
Dr. Mark Pimentel (27:01):
Well, this is more proof for the last
question.
So we did a double-blind studyof rifaximin with neomycin, with
methane, and only the humans ormost prominently the humans
where the methane went down didtheir constipation resolve for a
period of time as the methanewas gone.
So it wasn't the effect of thedrug, it was the effect of
removing the methane Againproving that methane is the
(27:22):
issue.
So now we have CSO6, whichblocks an enzyme in the
production of methane by themethanobrevibacter smithii bug
or archaea that's causing themethane in humans and we see 70%
reduction in methane with thisdrug.
And the study we presented atDDW was the controlled trial in
(27:44):
animals, where these are animalsthat we can make constipated,
make their methane go up that wespoke about in the last
question.
And then we give the drug andthe methane goes down and the
constipation goes away.
So again, cause and effect ofmethane equals constipation.
So the animals had lessconstipation and less methane.
So we are about a year away.
(28:08):
You got to do all thesetoxicity studies et cetera, et
cetera, to get to humans and sowe're hopeful to be in humans
within a year and that will bevery exciting because then we're
really treating the cause right.
Dr. Megan Riehl (28:20):
Right.
Dr. Mark Pimentel (28:20):
It's not an antibiotic, it's not a
sledgehammer.
It's just a small molecule tomake the bug stop doing what
hurts you, and that's it.
So that's very exciting.
Kate Scarlata, MPH, RDN (28:32):
Very exciting.
So back to methane.
As a dietitian, you know we'realways working with patients
with IMO and want to help them.
You know we're always workingwith patients with IMO and want
to help them, and there's beensome talk that a low-fat diet
would help with methaneproduction.
Is there any diet interventionsthat you're finding useful in
your patients or that you havedata to talk about?
Dr. Mark Pimentel (28:54):
Well, we do know that high-fat diet does
promote methane production.
We see that in animals too doespromote methane production.
We see that in animals too.
If we gavage them withmethanogens and give them high
fat, the methane goes up a lotmore than if we didn't use high
fat.
Don't know why, except we knowthat methanogens use bile acids
as a fuel source as well.
So more fat, more bile, morebile acids.
(29:16):
It's possible that those arethe connections, but we do see
that happening.
We don't necessarily see it.
On high protein.
High protein can cause moreconstipation as well.
We don't necessarily see moremethane in a high protein diet.
But we haven't gotten around tosaying please go on a low fat
diet, this will make yourmethane go away.
(29:36):
We haven't done that.
It's an interesting exercise.
I wonder whether it might help,you know, and when we.
If we get to hydrogen sulfide,there may be things that can be
done there.
I almost see that, because whatwe've identified in IBS if I
can go back a step is threemicrotypes really.
There's the SIBO microtype,with this E coli, klebsiella,
(29:57):
two Ferraris racing to get allyour food.
Then there's the methanogens,which are the constipation side
of things and their needs aredifferent, and maybe there's a
diet for that.
And then, of course, hydrogensulfide.
When it's there, you get moreflora diarrhea and they need
sulfur.
So if you had a low sulfur diet, maybe that would be helpful.
So I think diet's going to playa role in all three over time,
(30:20):
as we understand theirnutritional needs and what's
driving their increasedmetabolism and growth, and so
diet may play a big role in allthree.
Kate Scarlata, MPH, RDN (30:29):
So who's going to do those studies?
Dr. Mark Pimentel (30:32):
Well, I can't do all the studies, Kate.
Kate Scarlata, MPH, RDN (30:33):
I know, I know, maybe Bill Chey.
Dr. Mark Pimentel (30:37):
Maybe Bill Chey.
Let's get Bill.
You know it's like what do theysay Mikey, let Mikey eat it.
Kate Scarlata, MPH, RDN (30:45):
All right, we got to find someone to
do those studies.
Dr. Megan Riehl (30:48):
And it might happen.
You know, we've got Dr PrashantSingh, we've got Dr Chey here
at the University of Michigan.
So, I don't know.
Here's our call outs.
I'll be knocking on some doors.
Dr. Mark Pimentel (30:58):
Bill's an expert in diet studies, so he
anyways, I've talked to him andhe's got a lot on his plate, but
I wasn't trying to commit himto something, but oh, I'll
commit him.
Kate Scarlata, MPH, RDN (31:09):
No, we'll get Prashant.
We go for the younger ones thatare coming up.
Dr. Megan Riehl (31:15):
All right.
So you mentioned the threegases.
Right, we've got the hydrogen,the methane, the hydrogen
sulfide and we now have testingto look at all three of these
gases via breath tests andthey're available nationwide.
And you did a real world study,you know, with a rather large
cohort of people, over 3000,that completed all aspects of
(31:37):
the study with questionnairefeedback.
So tell us a little bit aboutwhat you learned because, again,
these things that are availableon the market, people are
interested in and we want toknow what they show us and how
it leads to treatment.
Dr. Mark Pimentel (31:50):
Well, we do it for the sake of science,
trying to understand thesedifferent subcategories of gas
types.
But we also do it for critics,because always there's critics.
Uh, you know, people said, well, oh, breath testing is great,
but now you got to do culture.
Then you do culture to say IBShas SIBO.
You publish that.
They say, yeah, but nextgeneration sequencing is better.
(32:12):
We don't believe it until youdo next generation sequencing.
Then we do sequencing and weshow the same thing and they say
, yeah, but you could do shotgunsequencing.
And so now we've done shotgunsequencing, we published it.
Anyways, the list of thecritics' desires never ends.
But we keep showing the samething with the different tests
and the same thing with breathtesting.
(32:32):
So you know, we show that itworks in clinics.
So methane is associated withconstipation, hydrogen is
associated with diarrhea.
In-person, in-person breathtesting at Cedars-Sinai, for
example, or at Ann Arbor.
But now you're doing mailing,at-home breath testing.
Does that work?
Can patients actually do it athome?
(32:53):
And a 6,000 breath test studysays absolutely.
Methane's associated withconstipation, SIBO and hydrogen
sulfide is associated withdiarrhea.
It all turned out the same wayand the results were equally
impressive.
But what we were able to showis that these gases interact.
Because it's such a large studythere are some patients have
(33:13):
all three and that's prettyremarkable.
But what I used to think isthat methane is the winner.
Like methane will out becauseof its constipating effect, it
will out constipate the diarrhea, but not with hydrogen sulfide.
Hydrogen sulfide is the winner.
Anytime it's present, it isdominating the symptoms and
(33:33):
making all the symptoms moresevere and in particular
visceral hyperalgesia or pain.
So hydrogen sulfide is anactivator of pain pathways.
Then what we also did at DDW,which I don't think we're going
to get into, is we actuallylooked at the biopsies in the
REIMAGINE study of the bowel andthe same thing in the animals
(33:54):
where we gavage these organismsto test whether hydrogen sulfide
is causing diarrhea or not.
And of course it does.
The changes in you, in yourlining of your intestine, when
you have these hydrogen sulfideorganisms are incredible.
It's literally you're killingthe cells almost at certain
levels, but you're causingvisceral hyperalgesia.
(34:14):
Intestinal barrier proteins areaffected, serotonin is affected
, mitochondrial function isaffected.
So your energy of the cells areaffected.
H2S is nasty.
It's nasty, but anyways, in the6,000 patient study we were
able to confirm that hydrogensulfide, the higher it is the
more diarrhea the SIBO and themethane in this very large-scale
(34:36):
study.
Kate Scarlata, MPH, RDN (34:37):
So interesting?
And wasn't hydrogen sulfideconnected with inflammatory
bowel disease?
Didn't they think that yearsago?
I haven't really heard a lotrecently.
Dr. Mark Pimentel (34:47):
Well, what happened with that?
So there was this big movementin the early 90s of the
relationship between hydrogensulfide in the colon and the
development of ulcerativecolitis, for example.
It was ramping up, so to speak,and then infleximab came and
boom.
Everything changed to biologicsand it in essence cut off at
(35:08):
the pass the continued work onhydrogen sulfide.
But maybe now it's going to bereinvigorated in IBD too.
I know there's a few studiesthat are ongoing already looking
at ulcerative colitis and otherIBD patients with H2S.
H2s is toxic, so it's not good.
Kate Scarlata, MPH, (35:25):
Interesting and really there's only one
test, like most hospitalsettings are not testing for
hydrogen sulfide.
It's this meal order.
Dr. Mark Pimentel (35:34):
So it depends on the hospital system.
There are some Stanford does.
I think, Bill Chey is going tostart.
I'm not sure.
Northwestern does all three.
So, it just depends, becauseyou just get the kit, you can do
it at the academic center andsend it, so you can do them in
person.
Still, you just have to havethe kit or you can do it by mail
(35:55):
order.
Kate Scarlata, MPH, RDN (35:55):
That's amazing.
You know, I've been doing thisfor a long time and in the
beginning it was like this bigthing request hydrogen and
methane, like that was a bigdeal because they weren't
looking even at methane.
You know, back in the day andnow it's like okay.
Dr. Mark Pimentel (36:09):
I think the biggest problem we had, even in
the SIBO, has been around.
Breath testing has been aroundsince the 80s and even centers
where they you know they'resomewhat critical of breath
testing they're doing tons ofbreath tests because it makes
money for their institution.
To be honest, that's sad thatyou would be a critic, yet
you're still doing these tests.
Anyways, the tests do work wellin my view.
(36:31):
But people started pullingthese Quintron instruments out
of their basement and turningthem on and starting to run them
.
They need servicing.
I mean, these instruments,these gas chromatographs, need
servicing and we've experiencedsome pretty high level
institutions where the breathtest isn't calibrated properly
and they're getting wonkyresults.
So it's a delicate test to doright and therefore get good
(36:55):
data.
So that's another problem thatwe've encountered over the years
.
Kate Scarlata, MPH, RDN (36:59):
Yeah.
So listeners ask about whatequipment they're using and
maybe inquire about the threegas breath test.
So as we wrap up, I wanted tojust briefly talk about fiber.
I know a lot of the work you dois in IBS and SIBO.
Is fiber a friend or a foe, oris the answer kind of somewhere
(37:20):
in the middle?
Dr. Mark Pimentel (37:21):
Like everything else, your mom told
you keep everything inmoderation.
There was a study that was donein Japan where they fed rats
kidney beans for two weeks.
So that's high fiber.
The rats develop SIBO just fromeating kidney beans.
So beans.
If you were to be on an all beandiet as a human, you're going
(37:41):
to get SIBO, even if you don'thave any underlying reasons for
SIBO.
That is a just an example ofwhat high fiber can do and the
power of high fiber in terms ofSIBO without any other medical
problem.
So too high fiber is not a goodidea.
Too much of anything is not agood idea.
Right?
That's the theme today.
But with people who alreadyhave SIBO, you're basically
(38:05):
putting logs of wood on the fire, in a sense, because now you're
providing more nutrients forthe Ferraris to be able to
produce more gas, bloating anddistension.
So the offset of that is, yes,fiber can make you have more
bowel movements.
So maybe if you have more bowelmovements, you clear some of
these bacteria out.
Maybe that makes you feelbetter because you're having
diarrhea from the fiber orwhatever the manifestation is of
(38:28):
the fiber.
But all in all, we see thatfiber just causes a lot more
bloating for these patients, andso we generally recommend low
fiber.
Not no fiber, just low fiber.
Kate Scarlata, MPH, RDN (38:41):
Yeah, incidentally, the kidney beans
are very, very, very likeprobably the highest fructan
containing bean, so it's a veryhigh FODMAP, small chain
carbohydrate.
You know.
Even compared to like chickpeasor lentils or black beans or
cannellini beans, kidney beansare like the top dog.
They're so, so concentrated, sothey were giving them a lot, a
(39:04):
lot of fiber.
And I do wonder, like inbacterial overgrowth, if the
smaller chain fibers are moreproblematic because they're
easier, they're rapidlyfermentable and, you know, are
they going to be in that smallbowel a limited amount of time?
So those things they can accessa little quicker are more
problematic.
Just, you know, criticallythinking, I don't think, in my
(39:28):
opinion, I'm not sure that allfibers act the same, or maybe as
problematic for SIBO as maybesome that are really quickly
accessible by our microbes inthe small bowel.
But tell me otherwise.
Dr. Mark Pimentel (39:45):
So I like to do everything based on science
right.
Kate Scarlata, MPH, RDN (39:48):
Me too.
Dr. Mark Pimentel (39:48):
And I don't know that there's enough science
to tell me it's got to be thislong, that long, this long, that
long.
All I know is it's fiber or nofiber, and that's really
inappropriate for me to be sodogmatic.
But I don't have any data.
All I know is if the patient ison fiber, if they're on
metamucil or if they're on someproduct that is fiber containing
(40:09):
which is good for some people,it isn't good for SIBO.
It's just the patients dopoorly.
But I would love to see a studywhere you compare different
fibers to see which ones theytolerated.
But again, that's not been done.
Kate Scarlata, MPH, RD (40:21):
Prashant Singh calling.
Dr. Mark Pimentel (40:24):
We're volunteering him for a lot of
studies.
We are yes.
Dr. Megan Riehl (40:27):
We are yes we are and clearly I love the
debates, I love theconversations and clearly I love
the debates, I love theconversations.
It really is important, as Isaid earlier we have to be
curious about this, we can notjust lean into, it's not black
and white is the reality.
Dr. Mark Pimentel (41:03):
I like to tell you things that I have a
ton of data on.
But so my overall gestalt islow fiber for now, until we
figure it out.
Dr. Megan Riehl (41:09):
All right.
Well, you told us last yearthat, in order to navigate the
stress of running this massivelab.
You are a blues guitar player.
Dr. Mark Pimentel (41:19):
Oh my God, did I tell you that?
Dr. Megan Riehl (41:21):
You did tell us that and I've been waiting for,
you know, an MP3 or somethingof hearing you play.
But what are you doing for yourwell-being and self-care these
days.
Dr. Mark Pimentel (41:32):
Well, I have a home up in Banff area in the
Banff area, so I go up there andI write papers up there and
just spend a little bit of timewith nature.
It's very good, it's verycleansing.
I also have guitars up there.
Dr. Megan Riehl (41:45):
Perfect.
Kate Scarlata, MPH, RDN (41:46):
That is a magical, magical place.
We were in Banff a couple ofyears ago.
It is one of the most beautifulplaces I've ever been.
How lucky.
Dr. Mark Pimentel (41:55):
Yeah, now we've gotten to know it quite
well, and if you know it quitewell, you know the real places
because, Lake Louise isbeautiful and all of that.
But there are places wherehikes could be five miles up to
a lake where there is literallynot a human anywhere.
(42:17):
These mountain lakes, andthey're just spectacular.
The water is like glass andthere's nobody.
Kate Scarlata, MPH, RDN (42:24):
Love that.
We went when it was freezing.
So to be honest, there wasreally no one there except for
us in my poorly dressed attirebecause I was so cold.
But it was kind of nice becausewe missed the crowds, but it
was a little chilly yeah, crowdsare too much but that's okay,
same everywhere.
Dr. Megan Riehl (42:42):
Exactly that's the key.
You got to get away in order tokind of clear the brain and
just give yourself the space andso a little slice of heaven.
It sounds like that'sincredible.
Yes, you deserve it.
Kate Scarlata, MPH, RDN (42:55):
So thank you so much for joining us
.
We really appreciate your time,and the first podcast that you
joined us with is still our topproducing podcast.
It's got the most downloads, sono surprise, people are really
interested to hear yourbrilliance and expertise and
just you're really making adifference in so many people's
(43:15):
lives.
So thank you and thanks foryour time today.
Dr. Mark Pimentel (43:19):
No, it's my pleasure.
It's good to talk to you both.
Dr. Megan Riehl (43:22):
All right, friends.
Well, don't forget to like,share and subscribe to The Gut
Health Podcast.
Your support means the world,our friends.
Thank you for joining us as wegrow this gut health community.
We hope you enjoyed thisepisode and don't forget to
subscribe, rate and leave us acomment.
You can also follow us onsocial media @The Gut Health
(43:42):
Podcast, where we'd love for youto share your thoughts,
questions and experiences.
Thanks for tuning in, friends.
This podcast is sponsored by Salix
Pharmaceuticals.
Maintaining a healthy gut is keyfor overall physical and mental
well-being.
Whether you're ahealth-conscious advocate, an
individual navigating thecomplexities of living with GI
issues, or a healthcare provider, you are in the right place.
(00:23):
Or a healthcare provider, youare in the right place.
The Gut Health Podcast willempower you with a fascinating
scientific connection betweenyour brain, food and the gut.
Come join us.
We welcome you.
Dr. Megan Riehl (00:38):
Hello friends, and welcome to The Gut Health
Podcast, where we talk about allthings related to your gut and
well-being.
We are your hosts.
I'm Dr Megan Riehl, a GIpsychologist.
Kate Scarlata, MPH, RDN (00:50):
Hello, and I'm Kate Scarlata, a GI
dietitian.
Today, on The Gut HealthPodcast, we're joined by a true
pioneer in digestive science, DrMark Pimentel.
Renowned across the globe forhis groundbreaking work in
gastroenterology, Dr Pimentelserves as the Executive Director
of the Medically AssociatedScience and Technology, also
(01:13):
known as MAST program atCedars-Sinai Medical Center in
Los Angeles.
At the helm of the MAST program, Dr Pimentel leads an
innovative team that'sunraveling the complexities of
the human gut.
Their focus conditions likeirritable bowel syndrome, IBS, a
disorder that affects nearly 1in 10 people worldwide, as well
(01:37):
as the lesser-known butincreasingly important small
intestinal bacterial overgrowth,or SIBO, and intestinal
methanogen overgrowth, or IMO.
Today's topic is the gutmicrobiome and dysbiosis.
Welcome back, Dr Mark Pimentel.
Dr. Mark Pimentel (01:57):
It's great to be back with you.
It's exciting.
It's the summertime, but peopleare still interested in the
microbiome.
What a thought time, but peopleare still interested in the
microbiome what a thought.
Dr. Megan Riehl (02:06):
Well, Dr Pimentel, we want to kick things
off today with you with a mythbuster and, you know, with
summer, whatever it may be.
What do you think our listenersneed to know in the myth
busting world of the microbiome?
Dr. Mark Pimentel (02:20):
I think the biggest myth that we deal with
on a daily basis is that themagic is really in the dual
microbiome only.
And if we're going to talkabout microbiome, a lot of what
I'm going to talk about is thesmall intestinal microbiome,
which is harder to get to.
They used to think that thesmall intestinal microbiome was
sterile.
There was no bacteria there, orhardly any, and now we know
(02:42):
it's abundant, and the bacteriathere are giving you things that
you don't want, sometimesgiving you things you do need,
and that's the myth.
The myth is that the bugs thatwe thought were only in the
colon are in the small bowel aswell, and they can create
problems for your health.
Kate Scarlata, MPH, RDN (02:59):
I often think like are we going to
start looking a little closer atthe mouth microbiome, the
esophagus microbiome, thestomach microbiome, all these
places that seem to beinconsequential but maybe are
playing a role, even if thebacteria numbers are vastly
different and less, etc.
But let's kick it off with whatis gut microbial dysbiosis and
(03:24):
why should we care?
Dr. Mark Pimentel (03:26):
You know, dysbiosis used to be a dirty
word or a word that peopledidn't like to use because it
had really no meaning.
It just means there's a problemwith the microbiome, and that's
like saying there's a problemwith your arm.
That's a diagnosis.
No, that's not a diagnosis.
There's a problem with your arm.
We need something more specific.
So I think the term dysbiosishas been thrown around and again
(03:49):
still doesn't have any meaning.
But I think what we're trying todo, or what people are trying
to say, is that it's anoverarching term that says
there's something wrong withyour microbiome and it could be
this, it could be this, it couldbe this, and in each particular
instance, it can have differentramifications on your health
and your condition.
And I think that's really whatthe term dysbiosis ought to be
(04:11):
used for at this point in time,because, like, for example,
there are things that areadvertised oh, help your gut,
dysbiosis.
What does that mean?
I mean you're selling a productto help dysbiosis, but what
dysbiosis are you talking about?
So we don't want to use it inthat context, but as an
overarching term, I think it'sfair to say.
Dr. Megan Riehl (04:30):
Okay.
So it's certainly not specificto just it's too general for the
gut.
Dr. Mark Pimentel (04:37):
Right, exactly.
Dr. Megan Riehl (04:39):
Okay.
So when it comes to a diagnosisof something that you are
studying every day of your lifeSIBO, small intestinal bacterial
overgrowth, do you believe thatthis fits the definition of
small bowel dysbiosis?
Dr. Mark Pimentel (04:53):
So we're doing a study called the
REIMAGINE study and you may haveheard about it, but basically
it's the first and largest nowstudy of the small intestinal
microbiome taking aspiratesusing proper double lumen
catheter techniques so that it'ssterile.
We've been doing this for awhile.
We have well over a thousandpatients on our way to 10,000
patients.
When you look at the smallintestine in a normal person it
(05:17):
barely goes above 10 to the 2,10 to the 3, or 100 to 1,000
microbes per ml.
In the case of overgrowth it'sover 10 to the three.
But that's not the story.
The story is in the reimagineddata.
This is like over 1,000patients.
The most apocalyptic thing wesee is overgrowth, and what I
(05:39):
mean by that is nothing is asdramatic, nothing is as obvious
as when overgrowth is there,because when the E coli and
Klebsiella part of overgrowthblooms or grows, it destroys
everything in its path.
It's like a bulldozer takingout all the rest of the
microbiome.
The higher the E coli is, themore destroyed the rest of the
(05:59):
natural garden is is destroyed,and so it really is apocalyptic.
The only other example ofapocalypse on the small bowel is
antibiotics.
If you take broad spectrum likeciprofloxacin or something like
that recently the microbiome iswiped out.
So those two instances are themost obvious.
Dysbiosis, if you want to goback to that term.
(06:21):
Sibo is very dramatic, veryobvious when it's there.
Kate Scarlata, MPH, RDN (06:26):
Yeah, so you're basically saying I
just want to kind of recap thisfor our listeners that there are
certain microbes that you'refinding are always there with
overgrowth and they're wipingout some of the other
populations.
So they're the primary microbesin that condition, Right?
Dr. Mark Pimentel (06:44):
Exactly, they're the primary microbes in
that condition.
Kate Scarlata, MPH, RDN (06:45):
Exactly , so are they always the bad
guys, like some people haveKlebsiella and E coli and
they're fine, it's just whenthey go rogue in the small
intestine.
Dr. Mark Pimentel (06:55):
Yeah, so it's a little bit tricky.
So one of the other myths if wewant to go back to myths going
backwards in this podcast isthat even I, in review articles
on SIBO, I used to say, as thetextbooks used to say, that it's
coliform microbes moving intothe small intestine that's
overgrowth.
Some people even still talkthat way.
(07:16):
That's absolutely not what itis.
We didn't know that then whenwe were writing these articles.
What we now know it's reallyknow that then when we were
writing these articles.
What we now know it's reallythere is a slowing of the small
intestine and thatpreferentially favors aggressive
bacteria, and E coli andKlebsiella are the two most
aggressive.
There are others Eremonis andother organisms that are minor
(07:38):
parts of SIBO, but the Ferrarisare E coli and Klebsiella and
they are so good at fermentingand capturing the nutrients from
your food that once they'veestablished they're a wrecking
ball, and we call themdisruptors because as they grow
they disrupt the rest of theflora.
Sort of like your garden isovertaken by weeds and the weeds
(08:01):
will win, the garden will lose,and that's what's happening.
So E coli is the biggest one.
Klebsiella is less common butworse to the microbiome, it's
more disruptive, and then theothers are minor.
Overgrowth is not coliforms.
It's the E coli and Klebsiellathat are there that now have the
competitive advantage becauseof the stasis or different
(08:25):
changes in the environment inthe small intestine at that
moment.
Dr. Megan Riehl (08:29):
And this is some of the connection then to
IBS, post-infectious IBS andSIBO.
These microbes are culprits.
Dr. Mark Pimentel (08:39):
Yeah, exactly .
So we've shown this entiresequence.
Like we've given food poisoningto rats and then they develop
the stasis of the gut.
They develop these antibodiesfrom the toxins of the food
poisoning the CdtB andanti-vinculin antibodies,
because they react to the foodpoisoning.
So you get this autoimmunity,and then the small bowel slows
(09:00):
down from that and when it slowsdown the bacteria build up, and
in rats it's not Klebsiella,it's only they don't have
Klebsiella, it's E coli, and Ecoli goes through the roof.
So we've seen this entiresequence in animals.
So we know this happens and weknow that in humans the only
known cause and the only causeand effect cause because this
(09:22):
has been proven with theBradford Hill criteria for IBS
in humans is food poisoning.
Campylobacter particularly isthe worst and so it's been very
well characterized.
In fact, stress has been shownnot to be the precipitant but to
be a cofactor.
So stress, anxiety anddepression is not a cause of IBS
(09:42):
but is a modifier of IBS.
Dr. Megan Riehl (09:46):
That's right.
That's right, and many otherthings too,
Dr. Mark Pimentel (09:49):
and many other things blood pressure,
heart disease, stroke, you nameit.
Stress.
Dr. Megan Riehl (09:54):
Inflammatory bowel disease.
Dr. Mark Pimentel (09:56):
Yes, exactly.
Kate Scarlata, MPH, RDN (09:57):
We got to all chill out.
Dr. Megan Riehl (10:00):
That's right.
Kate Scarlata, MPH, RDN (10:01):
So you also had mentioned lactobacillus
as being a disruptor in aformer conversation and I'd love
you to talk about that, as yourgroup's been really looking at
the small bowel.
Can you talk a little bit aboutlactobacillus as a disruptor in
the small intestine?
Dr. Mark Pimentel (10:15):
Yes, so I mean a lot of our work's been
focused on irritable bowelsyndrome and the relationship
with overgrowth, and that's veryexciting and it's really come
to the forefront now.
But we found some pearls in theREIMAGINE study that are super
interesting.
For example is thelactobacillus so in patients who
have unhealthy aging.
So let me backstep.
(10:37):
Lactobacillus has been studied.
Administering lactobacillus,taking probiotics has been
studied on the basis ofmeasuring stool.
Nobody ever looked at the smallbowel to see the effect of
these probiotics on the smallbowel.
So now fast forward to theREIMAGINE study.
We see that when patients havehigh lactobacillus in their
(10:59):
small bowel, it is associatedwith more obesity and it's very
strong association.
And then the second thing is welooked at aging and unhealthy
aging, and healthy aging andunhealthy aging is associated
with higher lactobacillus in thesmall bowel.
Now is it cause and effect?
Those things need to bedetermined.
(11:20):
So I can't say that, oh boy,because your lactobacillus is
high, you're going to age badly.
If you think about it, we giveyogurt to our kids instead of
fruit cups because we think it'smore healthy.
Is it right?
Is it a good thing?
We don't know the answer to it.
But the third piece of thatlactobacillus puzzle is we did a
study looking at the disruptorsof the small bowel.
(11:41):
The more lactobacillus you havein the small bowel, the more
the garden is destroyed thenormal flora.
So that concerns me a lotbecause I don't know what the
repercussions of that are.
But you can imagine it might besimilar to the E coli and
Klebsiella of IBS.
The lactobacillus is not makingyou have all that IBS symptoms,
(12:02):
but is it doing other things?
Is it leading to obesity?
Is it leading to other thingsthat we need to understand more
consequentially, and so morework needs to be done.
But I think that's worrisome tome.
So I don't really advocate forlactobacillus or probiotics
using lactobacillus in mypractice.
Kate Scarlata, MPH, RDN (12:20):
Would you say that across the board
for everyone, like say you weretalking to someone just
interested in their gut health?
Do you think lactobacillus hasgot a potential problem?
I don't know the answer.
Dr. Mark Pimentel (12:31):
Now that's really got me wondering what is
good about lactobacillus, whatcould be bad about it?
I don't know the answer to it,but it really raises a lot of
questions and a few hairs on myneck because I'm worried that it
could be harmful.
I go back to what our motherstold us too much of anything is
a bad thing, and that has alwaysrung true for all of science is
(12:52):
that too much of one thing isalways a bad thing.
Oh, don't eat fat, don't eatany fat.
So you know, you swing thependulum.
So now we switch it all tocarbs and everybody's getting
obese.
And now they're swinging backand saying carbs are okay or
carbs are not okay, fat is okay.
And so the pendulum swings.
But if you have a balanced diet, if you have a little bit of
(13:14):
yogurt here and there, as ahealthy person I think there's
no problem with it.
But if you want to get 20billion lactobacillus in your
gut every day, is that healthy?
I'm not sure.
Kate Scarlata, MPH, RDN (13:24):
Yeah, it's that whole notion that more
is better.
We just can't get away fromthat.
Everyone thinks, well, geez, if10's good, let's get a million.
And see what happens.
Dr. Mark Pimentel (13:33):
Yeah, if I can live longer, because a
little bit of selenium is good.
More is better, right?
Dr. Megan Riehl (13:39):
So anyway, it's interesting we have to remain
curious and I think that's thething here is and I think
probiotics are a great exampleright that people are just, they
want to feel better.
And to your point, which onehas the highest?
If a little bit is good, thenagain let me find the probiotic
out there with the highestamount of that.
(14:00):
And then they stay on it fortoo long without adequate relief
of their symptoms and itbecomes a very muddy waters or
the garden is very heavilyimpacted by too many weeds and
species.
Kate Scarlata, MPH, RDN (14:14):
exactly .
Dr. Mark Pimentel (14:17):
But even if you're planting a garden, you
don't plant all tomatoes.
I mean, you can't expect oneorganism to correct a thousand,
right?
So it's like I say, if you adda thousand lawyers every day to
Los Angeles, that may not be ahealthy thing for the city.
We need lawyers, but maybe athousand every day is too many,
you know.
So that's the concept of aprobiotic, and not to mention
(14:39):
the other sad thing about theword probiotic is it has the
word or the prefix pro in it,like it's good.
And then this notion anothermyth of good and bad bacteria.
That's a myth.
There is no such thing as goodand bad.
There's.
Bacteria are all good and allbad, depending on where they are
(15:00):
.
Lactobacillus in yourbloodstream, not good.
Lactobacillus a little bit inyour gut, probably good, and so
it just depends where they areand what circumstance.
They all evolved to stay intheir place and their niche, and
when they are too high or inthe wrong place, it's a bad
thing.
Kate Scarlata, MPH, (15:18):
Moderation in all things.
Dr. Megan Riehl (15:21):
That's right.
We've discussed and you cancorrect me if I'm saying this
incorrect.
Is it Placide trial?
Dr. Mark Pimentel (15:29):
Yes.
Dr. Megan Riehl (15:30):
Okay, so let's talk about the Placide trial.
What did this trial look at andhow is this information
clinically relevant for us?
Dr. Mark Pimentel (15:39):
So this was a study looking at patients that
were given antibiotics forwhatever a urinary tract
infection or some sort ofinfection at the moment in
primary care clinics.
And then, as they were giventhe antibiotics, they were
randomized to probiotic or noprobiotic and what they found
was there were no decreasedrates of C difficile or
(16:02):
antibiotic-associated diarrheabecause you're on the probiotic.
That was what they were hopingto see.
Is that that would prevent Cdiff or something like that, and
the only thing they found thatwas statistically different.
The only significant thingreally was that the probiotic
group had more bloating.
So this is what I tell mypatients If you want more
bloating, please take aprobiotic, because it will
(16:24):
provide that for you, becausethe Placide trial is the largest
randomized control trial todate on this.
So it kind of settles the issue.
Now, the probiotic world is aplethora of products, so it's
very easy for the company sayswell, that's not our strain, our
(16:49):
strain doesn't do that, orthat's not bifido, that's
lactobacillus.
So whether I say this or not ina podcast, and whether somebody
hears this or not in a podcast.
The product companies are goingto say, well, that wasn't my
product.
And so the story continues aswe unfold this.
But the problem is that thesecompanies don't have the money
or don't want to do theseincredibly large trials to prove
one way or the other if theirproduct does what they hope it
(17:12):
does.
So it's a tricky area.
I do believe bacteria areimportant.
I do believe there are somethat are better than others.
I just don't think you've gotto over.
You know, jack up the systemwith too much of it.
Kate Scarlata, MPH, (17:23):
Especially if the small bowel is not
working very well.
It just feels like you're justaccumulating.
Dr. Mark Pimentel (17:30):
I can tell you absolutely.
I have patients who have IBS,who've taken probiotics and said
, oh my God, I feel so muchbetter.
It's rare but it happens, andso I say, great, call me when
it's not.
Inevitably they call me andit's not working again.
And then we go back to squareone and we go through the
fundamentals again.
(17:51):
But you know, I can't deny thatthere are occasions where
patients feel better.
But anecdote is not science.
We deal with it in the clinicall the time.
Kate Scarlata, MPH, RDN (18:02):
Yeah, it's true, especially when you
really want to feel better.
You're hoping so hard on thatlittle probiotic capsule.
Dr. Mark Pimentel (18:08):
Exactly.
Kate Scarlata, MPH, RDN (18:09):
So let's talk a little bit about
SIBO and new treatments, and Iknow your group reported at DDW
this year about using rifaximinwith N-acetylcysteine or NAC and
found that this combo workedbetter than rifaximin alone.
I know rifaximin has FDAapproval for IBS-D, so kind of
(18:29):
used off-label for bacterialovergrowth, but is used commonly
.
So what led you to looking atNAC and rifaximin together?
What prompted that idea?
Dr. Mark Pimentel (18:42):
So when we helped develop rifaximin
together, like what promptedthat idea, so when we helped
develop rifaximin in the firstplace, it is a great drug for
IBS.
It's the number one drug forIBS worldwide.
Now If you go to chat GPT youcan ask because it's safe,
because two weeks might get yousix months of benefit, which no
other drug does.
So in that context it's beenvery successful.
(19:03):
But I was never satisfiedbecause what I'm seeing in the
microbiome of IBS more peopleshould get better from rifaximin
.
Something didn't add up to mebecause we're seeing more SIBO
in IBS than rifaximin makesbetter.
So, for example, rifaximintarget three trial, 44% of
(19:27):
people responded to rifaximinbut we're seeing 60 to 70%
having SIBO.
So why are the others notgetting better?
Or why isn't it as good as itshould be?
Where rifaximin'scharacteristic are, it's not
absorbed because it'shydrophobic.
It's like an oil almosttechnically.
It doesn't have an ability todissolve in water.
So there's that part.
(19:48):
And then what we found in theREIMAGINE study in SIBO patients
is that E coli and Klebsiella,those two bad disrupting
characters, those Ferraris, whenwe calculate where they live in
the small bowel, 50% of themlive in the free fluid which
rifaximin has access to, and theother 50% live in the mucus,
(20:09):
not the mucosally associatedwith the mucus, the thick,
stringy stuff.
And rifaximin will never getinto that.
So we did some studiespreliminarily to see if we added
a mucus buster or a mucolyticlike NAC, does rifaximin work
better?
And it works 10 times better inthat situation.
(20:29):
So we are able to get rid ofthe Ferraris more
comprehensively if NAC ispresent and we can use a much
lower dose of rifaximin to getthe same effect.
And we can use a much lowerdose of rifaximin to get the
same effect.
So we did an initial studywhich we presented at DDW and it
showed that in a very smallstudy rifaximin and NAC is
better than rifaximin, the oneon the market.
(20:51):
And so the phase 2B study.
I just had a meeting beforethis one.
We're kicking that off inSeptember.
It's the first phase 2B studyat our center that isn't pharma
funded, it's we're doing thewhole thing ourself to see if we
can get this better forpatients.
So it was pretty cool.
No pharmaceutical company.
Kate Scarlata, MPH, RDN (21:12):
No pharmaceutical company, yep,
amazing.
Dr. Megan Riehl (21:16):
Why is that important for a listener?
What does that mean?
Dr. Mark Pimentel (21:19):
You know doctors do a lot of things with
pharmaceutical companies.
You know we try to get thingsacross the finish line.
But I'm not doing this for that.
I'm doing this for patients.
We want patients to get better.
This isn't about pharmaceuticalcompanies.
This is about doing the rightthing and finding the right
answers and getting these thingsfor patients.
(21:39):
So I'm hopeful this will amountto something and then make
patients better more often.
I believe it will.
Our data has shown that we evenhad to use our rat study, the
rats who were post-infectiousand, sure enough, just giving
rifaximin versus rifaximin andNAC.
Rifaximin and NAC wascompletely normalized.
(21:59):
Their cytokines normalized,their microbiome normalized
their bowel movements, whereasthe rifaximin and NAC.
Refaximin and NAC wascompletely normalized.
Their cytokines normalized,their microbiome normalized
their bowel movements, whereasthe refaximin only partially did
that.
So we're going to the nextlevel and we're doing it alone.
Kate Scarlata, MPH, RDN (22:11):
I love that.
So just quickly, how much NACare you using?
The same amount of NAC that youused in the trial that was
reported at DDW?
Can you disclose the amountthat you're using in the trial?
Dr. Mark Pimentel (22:25):
So it's a different formulation than that
trial Now this is the finalformulation, where it's
delivered in the small intestine, specifically in the locations
where the E coli would beexpected to be.
So it's got a special deliverysystem.
It's different than the other.
Okay so we'll see how it goes.
Kate Scarlata, MPH, RDN (22:42):
Awesome , we'll be waiting.
Yes, we will.
Dr. Mark Pimentel (22:45):
And I will have no fingernails left by the
end of it.
Kate Scarlata, MPH, RDN (22:49):
I bet you won't.
We appreciate all the workyou're doing, especially in this
area, because you're reallylike it seems like the one and
only that's just like reallyknee deep in it and pushing the
bar like really knee deep in itand pushing the bar.
Speaker 4 (23:16):
Visit Xifaxan.
com/ IBSD for the PI or talk toyour doctor.
Don't use Xifaxan if you have ahistory of sensitivity to
rifaximin, rifamycin antibioticagents or any components of
zyfaxin.
Tell your doctor right away ifyour diarrhea worsens while
taking zyfaxin, as this may be asign of a serious or even fatal
condition.
Tell your doctor if you arepregnant, plan on becoming
pregnant or nursing.
(23:37):
If you have liver disease,taking warfarin or other
medications, some medicationsmay increase the amount of
Xifaxin in your body, mostcommon side effects are nausea
and an increase in liver enzymes.
Xifaxin.
Kate Scarlata, MPH, RDN (23:57):
So let's switch gears to methane,
and I know there's been a numberof different studies linking
high levels of methane withconstipation.
But I'm wondering, like is thisbi-directional at all?
Like, if you're constipated,does that contribute to methane
being produced or more substratefor those microbes?
Like is there any connectionwith just someone being, say,
someone's just constipateddoesn't have elevated
(24:19):
methanogens.
Do they develop elevatedmethanogens just because they're
constipated, or is it just themethanogens are causing the
constipation through theirmethane?
Does that make sense?
Dr. Mark Pimentel (24:31):
Yes, and that's an argument that's
resurfaced recently, and Iwonder whether some of those
folks hadn't read the earlierpapers that have already been
done, whether some of thosefolks hadn't read the earlier
papers that have already beendone because we've gone through
that argument already.
So yes, if you have methaneyou're more likely to have
constipation.
The higher the methane you haveon the breath test, the more
(24:52):
constipated you are.
It's very proportional, whichis really important for cause
and effect.
But that doesn't mean that themethane is causing the
constipation, because if you'remore constipated maybe you have
more methane, maybe themethanogens love that dry stool
environment and they do betterin that situation.
But we've done the other side ofit, where we've given
(25:13):
methanogens to animals and theyget constipated.
So we gavage them with themethanogens.
We've done the studies of liveanimals where we infuse methane
into the small intestine andthey get 60% slowing of
intestinal transit.
We've done organ baths of thesmooth muscle of guinea pig
ileum, adding methane to thebath and the guinea pig ileum
(25:34):
the peristalsis goes away, itgoes into more of a spastic
contractile activity.
So it's the methane.
And now all of a sudden maybethere's a study that says that I
don't know that maybe they'reconstipated first, then they get
methane.
I'm not sure it hasn't come outyet, but this is coming back to
life.
But maybe they should readthose papers because I think we
(25:57):
pretty much nailed that downthat methane is a constipating
agent period.
Kate Scarlata, MPH, RDN (26:02):
Yeah, I thought so too, but I was on as
I do lurk on Twitter and saw arecent paper and I'm like I'm
going to ask Dr Pimentel aboutthat.
Dr. Mark Pimentel (26:11):
Well, the paper hasn't come out yet, so it
remains to be determined.
Kate Scarlata, MPH, RDN (26:14):
Yeah, I just saw the commentary.
Dr. Mark Pimentel (26:16):
But I certainly hope that they at
least reference those papers,because those are the ones that
show that it's primarily methanethat's causing the constipation
and slowing the gut down, butit's okay.
Kate Scarlata, MPH, RDN (26:27):
You heard it here first.
Dr. Megan Riehl (26:29):
and in more cutting edge research that's
coming out of your lab.
Let's talk a little bit aboutCSO6.
So you presented a preclinicalstudy looking at the molecule in
relation to reducing themethane gas levels, as we've
really identified, methaneassociated with constipation and
(26:50):
also IMO in human studies.
So what is CSO6 and itspotential mode of action?
And, based on the timing of theresearch, if this study proves
itself to work in humans, whendo you think it's going to come
to market?
Dr. Mark Pimentel (27:01):
Well, this is more proof for the last
question.
So we did a double-blind studyof rifaximin with neomycin, with
methane, and only the humans ormost prominently the humans
where the methane went down didtheir constipation resolve for a
period of time as the methanewas gone.
So it wasn't the effect of thedrug, it was the effect of
removing the methane Againproving that methane is the
(27:22):
issue.
So now we have CSO6, whichblocks an enzyme in the
production of methane by themethanobrevibacter smithii bug
or archaea that's causing themethane in humans and we see 70%
reduction in methane with thisdrug.
And the study we presented atDDW was the controlled trial in
(27:44):
animals, where these are animalsthat we can make constipated,
make their methane go up that wespoke about in the last
question.
And then we give the drug andthe methane goes down and the
constipation goes away.
So again, cause and effect ofmethane equals constipation.
So the animals had lessconstipation and less methane.
So we are about a year away.
(28:08):
You got to do all thesetoxicity studies et cetera, et
cetera, to get to humans and sowe're hopeful to be in humans
within a year and that will bevery exciting because then we're
really treating the cause right.
Dr. Megan Riehl (28:20):
Right.
Dr. Mark Pimentel (28:20):
It's not an antibiotic, it's not a
sledgehammer.
It's just a small molecule tomake the bug stop doing what
hurts you, and that's it.
So that's very exciting.
Kate Scarlata, MPH, RDN (28:32):
Very exciting.
So back to methane.
As a dietitian, you know we'realways working with patients
with IMO and want to help them.
You know we're always workingwith patients with IMO and want
to help them, and there's beensome talk that a low-fat diet
would help with methaneproduction.
Is there any diet interventionsthat you're finding useful in
your patients or that you havedata to talk about?
Dr. Mark Pimentel (28:54):
Well, we do know that high-fat diet does
promote methane production.
We see that in animals too doespromote methane production.
We see that in animals too.
If we gavage them withmethanogens and give them high
fat, the methane goes up a lotmore than if we didn't use high
fat.
Don't know why, except we knowthat methanogens use bile acids
as a fuel source as well.
So more fat, more bile, morebile acids.
(29:16):
It's possible that those arethe connections, but we do see
that happening.
We don't necessarily see it.
On high protein.
High protein can cause moreconstipation as well.
We don't necessarily see moremethane in a high protein diet.
But we haven't gotten around tosaying please go on a low fat
diet, this will make yourmethane go away.
(29:36):
We haven't done that.
It's an interesting exercise.
I wonder whether it might help,you know, and when we.
If we get to hydrogen sulfide,there may be things that can be
done there.
I almost see that, because whatwe've identified in IBS if I
can go back a step is threemicrotypes really.
There's the SIBO microtype,with this E coli, klebsiella,
(29:57):
two Ferraris racing to get allyour food.
Then there's the methanogens,which are the constipation side
of things and their needs aredifferent, and maybe there's a
diet for that.
And then, of course, hydrogensulfide.
When it's there, you get moreflora diarrhea and they need
sulfur.
So if you had a low sulfur diet, maybe that would be helpful.
So I think diet's going to playa role in all three over time,
(30:20):
as we understand theirnutritional needs and what's
driving their increasedmetabolism and growth, and so
diet may play a big role in allthree.
Kate Scarlata, MPH, RDN (30:29):
So who's going to do those studies?
Dr. Mark Pimentel (30:32):
Well, I can't do all the studies, Kate.
Kate Scarlata, MPH, RDN (30:33):
I know, I know, maybe Bill Chey.
Dr. Mark Pimentel (30:37):
Maybe Bill Chey.
Let's get Bill.
You know it's like what do theysay Mikey, let Mikey eat it.
Kate Scarlata, MPH, RDN (30:45):
All right, we got to find someone to
do those studies.
Dr. Megan Riehl (30:48):
And it might happen.
You know, we've got Dr PrashantSingh, we've got Dr Chey here
at the University of Michigan.
So, I don't know.
Here's our call outs.
I'll be knocking on some doors.
Dr. Mark Pimentel (30:58):
Bill's an expert in diet studies, so he
anyways, I've talked to him andhe's got a lot on his plate, but
I wasn't trying to commit himto something, but oh, I'll
commit him.
Kate Scarlata, MPH, RDN (31:09):
No, we'll get Prashant.
We go for the younger ones thatare coming up.
Dr. Megan Riehl (31:15):
All right.
So you mentioned the threegases.
Right, we've got the hydrogen,the methane, the hydrogen
sulfide and we now have testingto look at all three of these
gases via breath tests andthey're available nationwide.
And you did a real world study,you know, with a rather large
cohort of people, over 3000,that completed all aspects of
(31:37):
the study with questionnairefeedback.
So tell us a little bit aboutwhat you learned because, again,
these things that are availableon the market, people are
interested in and we want toknow what they show us and how
it leads to treatment.
Dr. Mark Pimentel (31:50):
Well, we do it for the sake of science,
trying to understand thesedifferent subcategories of gas
types.
But we also do it for critics,because always there's critics.
Uh, you know, people said, well, oh, breath testing is great,
but now you got to do culture.
Then you do culture to say IBShas SIBO.
You publish that.
They say, yeah, but nextgeneration sequencing is better.
(32:12):
We don't believe it until youdo next generation sequencing.
Then we do sequencing and weshow the same thing and they say
, yeah, but you could do shotgunsequencing.
And so now we've done shotgunsequencing, we published it.
Anyways, the list of thecritics' desires never ends.
But we keep showing the samething with the different tests
and the same thing with breathtesting.
(32:32):
So you know, we show that itworks in clinics.
So methane is associated withconstipation, hydrogen is
associated with diarrhea.
In-person, in-person breathtesting at Cedars-Sinai, for
example, or at Ann Arbor.
But now you're doing mailing,at-home breath testing.
Does that work?
Can patients actually do it athome?
(32:53):
And a 6,000 breath test studysays absolutely.
Methane's associated withconstipation, SIBO and hydrogen
sulfide is associated withdiarrhea.
It all turned out the same wayand the results were equally
impressive.
But what we were able to showis that these gases interact.
Because it's such a large studythere are some patients have
(33:13):
all three and that's prettyremarkable.
But what I used to think isthat methane is the winner.
Like methane will out becauseof its constipating effect, it
will out constipate the diarrhea, but not with hydrogen sulfide.
Hydrogen sulfide is the winner.
Anytime it's present, it isdominating the symptoms and
(33:33):
making all the symptoms moresevere and in particular
visceral hyperalgesia or pain.
So hydrogen sulfide is anactivator of pain pathways.
Then what we also did at DDW,which I don't think we're going
to get into, is we actuallylooked at the biopsies in the
REIMAGINE study of the bowel andthe same thing in the animals
(33:54):
where we gavage these organismsto test whether hydrogen sulfide
is causing diarrhea or not.
And of course it does.
The changes in you, in yourlining of your intestine, when
you have these hydrogen sulfideorganisms are incredible.
It's literally you're killingthe cells almost at certain
levels, but you're causingvisceral hyperalgesia.
(34:14):
Intestinal barrier proteins areaffected, serotonin is affected
, mitochondrial function isaffected.
So your energy of the cells areaffected.
H2S is nasty.
It's nasty, but anyways, in the6,000 patient study we were
able to confirm that hydrogensulfide, the higher it is the
more diarrhea the SIBO and themethane in this very large-scale
(34:36):
study.
Kate Scarlata, MPH, RDN (34:37):
So interesting?
And wasn't hydrogen sulfideconnected with inflammatory
bowel disease?
Didn't they think that yearsago?
I haven't really heard a lotrecently.
Dr. Mark Pimentel (34:47):
Well, what happened with that?
So there was this big movementin the early 90s of the
relationship between hydrogensulfide in the colon and the
development of ulcerativecolitis, for example.
It was ramping up, so to speak,and then infleximab came and
boom.
Everything changed to biologicsand it in essence cut off at
(35:08):
the pass the continued work onhydrogen sulfide.
But maybe now it's going to bereinvigorated in IBD too.
I know there's a few studiesthat are ongoing already looking
at ulcerative colitis and otherIBD patients with H2S.
H2s is toxic, so it's not good.
Kate Scarlata, MPH, (35:25):
Interesting and really there's only one
test, like most hospitalsettings are not testing for
hydrogen sulfide.
It's this meal order.
Dr. Mark Pimentel (35:34):
So it depends on the hospital system.
There are some Stanford does.
I think, Bill Chey is going tostart.
I'm not sure.
Northwestern does all three.
So, it just depends, becauseyou just get the kit, you can do
it at the academic center andsend it, so you can do them in
person.
Still, you just have to havethe kit or you can do it by mail
(35:55):
order.
Kate Scarlata, MPH, RDN (35:55):
That's amazing.
You know, I've been doing thisfor a long time and in the
beginning it was like this bigthing request hydrogen and
methane, like that was a bigdeal because they weren't
looking even at methane.
You know, back in the day andnow it's like okay.
Dr. Mark Pimentel (36:09):
I think the biggest problem we had, even in
the SIBO, has been around.
Breath testing has been aroundsince the 80s and even centers
where they you know they'resomewhat critical of breath
testing they're doing tons ofbreath tests because it makes
money for their institution.
To be honest, that's sad thatyou would be a critic, yet
you're still doing these tests.
Anyways, the tests do work wellin my view.
(36:31):
But people started pullingthese Quintron instruments out
of their basement and turningthem on and starting to run them
.
They need servicing.
I mean, these instruments,these gas chromatographs, need
servicing and we've experiencedsome pretty high level
institutions where the breathtest isn't calibrated properly
and they're getting wonkyresults.
So it's a delicate test to doright and therefore get good
(36:55):
data.
So that's another problem thatwe've encountered over the years
.
Kate Scarlata, MPH, RDN (36:59):
Yeah.
So listeners ask about whatequipment they're using and
maybe inquire about the threegas breath test.
So as we wrap up, I wanted tojust briefly talk about fiber.
I know a lot of the work you dois in IBS and SIBO.
Is fiber a friend or a foe, oris the answer kind of somewhere
(37:20):
in the middle?
Dr. Mark Pimentel (37:21):
Like everything else, your mom told
you keep everything inmoderation.
There was a study that was donein Japan where they fed rats
kidney beans for two weeks.
So that's high fiber.
The rats develop SIBO just fromeating kidney beans.
So beans.
If you were to be on an all beandiet as a human, you're going
(37:41):
to get SIBO, even if you don'thave any underlying reasons for
SIBO.
That is a just an example ofwhat high fiber can do and the
power of high fiber in terms ofSIBO without any other medical
problem.
So too high fiber is not a goodidea.
Too much of anything is not agood idea.
Right?
That's the theme today.
But with people who alreadyhave SIBO, you're basically
(38:05):
putting logs of wood on the fire, in a sense, because now you're
providing more nutrients forthe Ferraris to be able to
produce more gas, bloating anddistension.
So the offset of that is, yes,fiber can make you have more
bowel movements.
So maybe if you have more bowelmovements, you clear some of
these bacteria out.
Maybe that makes you feelbetter because you're having
diarrhea from the fiber orwhatever the manifestation is of
(38:28):
the fiber.
But all in all, we see thatfiber just causes a lot more
bloating for these patients, andso we generally recommend low
fiber.
Not no fiber, just low fiber.
Kate Scarlata, MPH, RDN (38:41):
Yeah, incidentally, the kidney beans
are very, very, very likeprobably the highest fructan
containing bean, so it's a veryhigh FODMAP, small chain
carbohydrate.
You know.
Even compared to like chickpeasor lentils or black beans or
cannellini beans, kidney beansare like the top dog.
They're so, so concentrated, sothey were giving them a lot, a
(39:04):
lot of fiber.
And I do wonder, like inbacterial overgrowth, if the
smaller chain fibers are moreproblematic because they're
easier, they're rapidlyfermentable and, you know, are
they going to be in that smallbowel a limited amount of time?
So those things they can accessa little quicker are more
problematic.
Just, you know, criticallythinking, I don't think, in my
(39:28):
opinion, I'm not sure that allfibers act the same, or maybe as
problematic for SIBO as maybesome that are really quickly
accessible by our microbes inthe small bowel.
But tell me otherwise.
Dr. Mark Pimentel (39:45):
So I like to do everything based on science
right.
Kate Scarlata, MPH, RDN (39:48):
Me too.
Dr. Mark Pimentel (39:48):
And I don't know that there's enough science
to tell me it's got to be thislong, that long, this long, that
long.
All I know is it's fiber or nofiber, and that's really
inappropriate for me to be sodogmatic.
But I don't have any data.
All I know is if the patient ison fiber, if they're on
metamucil or if they're on someproduct that is fiber containing
(40:09):
which is good for some people,it isn't good for SIBO.
It's just the patients dopoorly.
But I would love to see a studywhere you compare different
fibers to see which ones theytolerated.
But again, that's not been done.
Kate Scarlata, MPH, RD (40:21):
Prashant Singh calling.
Dr. Mark Pimentel (40:24):
We're volunteering him for a lot of
studies.
We are yes.
Dr. Megan Riehl (40:27):
We are yes we are and clearly I love the
debates, I love theconversations and clearly I love
the debates, I love theconversations.
It really is important, as Isaid earlier we have to be
curious about this, we can notjust lean into, it's not black
and white is the reality.
Dr. Mark Pimentel (41:03):
I like to tell you things that I have a
ton of data on.
But so my overall gestalt islow fiber for now, until we
figure it out.
Dr. Megan Riehl (41:09):
All right.
Well, you told us last yearthat, in order to navigate the
stress of running this massivelab.
You are a blues guitar player.
Dr. Mark Pimentel (41:19):
Oh my God, did I tell you that?
Dr. Megan Riehl (41:21):
You did tell us that and I've been waiting for,
you know, an MP3 or somethingof hearing you play.
But what are you doing for yourwell-being and self-care these
days.
Dr. Mark Pimentel (41:32):
Well, I have a home up in Banff area in the
Banff area, so I go up there andI write papers up there and
just spend a little bit of timewith nature.
It's very good, it's verycleansing.
I also have guitars up there.
Dr. Megan Riehl (41:45):
Perfect.
Kate Scarlata, MPH, RDN (41:46):
That is a magical, magical place.
We were in Banff a couple ofyears ago.
It is one of the most beautifulplaces I've ever been.
How lucky.
Dr. Mark Pimentel (41:55):
Yeah, now we've gotten to know it quite
well, and if you know it quitewell, you know the real places
because, Lake Louise isbeautiful and all of that.
But there are places wherehikes could be five miles up to
a lake where there is literallynot a human anywhere.
(42:17):
These mountain lakes, andthey're just spectacular.
The water is like glass andthere's nobody.
Kate Scarlata, MPH, RDN (42:24):
Love that.
We went when it was freezing.
So to be honest, there wasreally no one there except for
us in my poorly dressed attirebecause I was so cold.
But it was kind of nice becausewe missed the crowds, but it
was a little chilly yeah, crowdsare too much but that's okay,
same everywhere.
Dr. Megan Riehl (42:42):
Exactly that's the key.
You got to get away in order tokind of clear the brain and
just give yourself the space andso a little slice of heaven.
It sounds like that'sincredible.
Yes, you deserve it.
Kate Scarlata, MPH, RDN (42:55):
So thank you so much for joining us
.
We really appreciate your time,and the first podcast that you
joined us with is still our topproducing podcast.
It's got the most downloads, sono surprise, people are really
interested to hear yourbrilliance and expertise and
just you're really making adifference in so many people's
(43:15):
lives.
So thank you and thanks foryour time today.
Dr. Mark Pimentel (43:19):
No, it's my pleasure.
It's good to talk to you both.
Dr. Megan Riehl (43:22):
All right, friends.
Well, don't forget to like,share and subscribe to The Gut
Health Podcast.
Your support means the world,our friends.
Thank you for joining us as wegrow this gut health community.
We hope you enjoyed thisepisode and don't forget to
subscribe, rate and leave us acomment.
You can also follow us onsocial media @The Gut Health
(43:42):
Podcast, where we'd love for youto share your thoughts,
questions and experiences.
Thanks for tuning in, friends.
Popular Podcasts
Fudd Around And Find Out
UConn basketball star Azzi Fudd brings her championship swag to iHeart Women’s Sports with Fudd Around and Find Out, a weekly podcast that takes fans along for the ride as Azzi spends her final year of college trying to reclaim the National Championship and prepare to be a first round WNBA draft pick. Ever wonder what it’s like to be a world-class athlete in the public spotlight while still managing schoolwork, friendships and family time? It’s time to Fudd Around and Find Out!
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.
The Breakfast Club
The World's Most Dangerous Morning Show, The Breakfast Club, With DJ Envy, Jess Hilarious, And Charlamagne Tha God!