Free Virtual Trainings with SIBO Researcher, Dr. Mark Pimentel

Course Content

1:35:30

Hello, and welcome. I am your cohost today, Siobhan Sarna, founder of CiboSOS and the author of these books. That's the Polish version right there of healing Cibo. I'm very proud. And I also have my fellow cohost, Dr.

Alison Seibaker here. She is 1 of the leading advocates for connecting medical doctors with natural paths with patients on Cboe and chemo. Her site is cboe info dot com. We have co created courses together for the patient population Cboe Recovery roadmap, and she's created a beautiful professional course called the Cboe pro course. And our star today is Dr.

Mark Pimentel, who is going to be bringing us in this annual tradition an update from Digestive Disease Week, also known as DDW. This is 2023, where he has the foundation of his work as well as the newest research. And when I say the foundation of his work, you know, no pressure, doctor Pimentel, but if anyone's gonna find cause placebo, emo, and IBS. We know it's you. And you need beer.

We need a cure. Garn it up. That's what he's working on.

Yeah.

That's right. He's he's coming in hot from Cedar Sinai and the medically associated science and technology program right now. Where he works with a brilliant team, helping to solve the problems and rebalancing ultimately the microbiome, So because of this work that he's devoted his life to, he's the 1 who has developed the first blood test for irritable bowel syndrome for and its connection to food poisoning. He's the 1 who's made in the team a discovery of rifaximin as a treatment for IBS. Sebo, chemo, and describing the relationship between IBS and small intestinal bacterial overgrowth and intestinal mifanogen overgrowth determining the relationship of IBS and Cboe as an autoimmune condition.

And then also, of course, the 1 who's created the 3 gas breath test from Jamelie Labs, the Trio Smart test. So those are just a few of the things he's been up to with his team.

Yeah. You left out, like, 15, at

least. It's not that, like

so it's nice to have monumental discoveries. So thank you, doctor Pimentel. Thank you so much

for being here for

all your good work. I'm gonna hand things over to you,

sir, so we can dive in.

I'm excited. You know, let me go ahead and share my screen and let's get going.

Your background there is exactly at the at the mass program. Right? In California?

If you look way back I don't know if you can see my mouse now. If you look way back here, there's a glass behind there is the laboratory. Back here where there's these carrols there, that's where the clinical team sits told them to behave themselves so they may not move around that much today because they're in the background, but it's usually pretty busy back there as well. So this is our office. It's not full backdrop.

This is a real deal. So Yeah. Hopefully, you can see my screen. Can you?

Yes.

Yes. I can. And I'm gonna highlight camera. And, Mike, and we'll we'll see on the other side.

Alright. Sounds good. Well, thank you for allowing me to present and inviting me to present the updates from DDW and context of the work that we've been doing here. I I sort of reviewed the last presentation I did, and it's and to some extent, it's similar for so though for those of you who've seen this presentation, you're gonna say, whoa, he's talking about the same things again. I am actually not, as you'll see, we have at least 20 new slides in this because so much has happened.

But the base information, the foundations of the work are the foundations of the work. And what I want you to understand is if you listened to last year or previously and then you listened now, you will see how what's been built on the foundation because you now can understand what the foundation looks like and then the new things and how they plug into this puzzle as the puzzle is coming together more and more. So if it if it's boring because you've seen it before, believe me, it won't be boring later. So we'll get we'll get through to it. I as I mentioned in some of our, you know, pre loading the slide discussion here.

The mass program is behind me here. And this is this is what we do. We're we're trying to develop the things that patients need. And to a great extent, what we try to incorporate in everything we do And I don't talk about it in my slides, but I think it's worth noting everything we try to do tries to also reduce health care costs in the spaces we're working in. And we've done cost analysis for the breath testing, for the blood testing, for the drugs that we try to develop to show that if you bind IBS placebo early and treat it sooner rather than going through a shenanigans of testing, you're going to save money and save healthcare costs.

And I've seen too many times patients come to me after 5 or 6 or 10 year journey of 20000 dollars in copays when they might have been able to make an assessment and understand their illness sooner whatever that illness is. And so I think all of this is really important to understand. I want to take you back. This is a new slide. Circa in 19 96.

This is about when I started or I started fellowship here at Cedars. You know, this is what we thought of IBS. Or what the field thought of IBS. There were no FDA approved drugs at that time. So maybe it's early life trauma, maybe it's anxiety, maybe it's depression.

IBS was a disease of women. That was what they people thought. This is a literal quote from a physician. IBS is a disease of hysterical women, literally a quote, shocking. Right?

And IBS was a diagnosis of exclusion, so you applied the Rome criteria, and but you had to have nothing else. So it's a diagnosis of exclusions, so it's a waste basket diagnosis. And then, these are the things that people were trying. There were studies that show some benefit to psychological therapies, antidepressants, anti spasmodics, anti diarrheals, laxatives for constipated patients. And that was it.

So if you're IBS, if you're constipated, you take a laxative, if you're diarrhea, you take an anti diarrheal or maybe a a tricycle at antidepressant, and that was the story. And that that has been a story for some people even to today, those who don't, you know, listen to the new developments because because there are a lot of new developments. But I I pause on this a little bit because in some of the guidelines for IBS. Even today, the guidelines say, well, use an anti diarrheal for IBS. And and why because it's safe and it's inexpensive?

And the answer to that is, yes, it's safe and it's inexpensive. And I just finished saying inexpensive is good. But an anti diarrheal, you're you're taking chronically. Can you imagine a guideline for Crohn's disease, where the first line therapy is an anti diarrheal drug it would be heresy in in the chrome space because, yes, an anti diarrheal would make the chrome's diarrhea better, but it's not treating the illness. And and yet here we are still in 20 23.

Well, we recommend an anti diarrheal first because it's cheap and it stops the diarrhea. Rather than focusing on treating the cause. I like starting with this point because I think you have to understand how physicians still think and the guidance is by the societies still in some ways promote not a treatment for causes of IBS, but rather symptom improvement only, which is shocking. So As you've seen this slide before, maybe you haven't, but this is what we're gonna cover, but we're gonna cover it in a much more greater detail because we have so much more information. So you can see here that it all starts with food poisoning on the diarrhea side of IBS.

So you get sick, you you went on a vacation to some country and then you you ate some bad food, you got diarrhea, and then ever since then, you're valves have never been or never returned to normal. And we've identified the toxin that we think is pausing this cascade. We've identified that that creates autoimmunity to a protein that is you called Vinkulin, as you'll see. And that that changes the nerve function of the gut. So the small bowel nerve function is diminished.

You get a reduction in these special cleaning waves of the gut. And if you don't clean your gut, it's like it's like eating off your plate without every put ever putting in the in the dishwasher over and over, you get a buildup of bacteria on that plate or, in this case, the small bowel and you get bacterial overgrowth. And I'll show you all the evidence for that and particularly excited about the new depth in which we now understand Cboe. And then, of course, you treat it an antibiotic. Faximin is the only FDA approved, well, it is the only antibiotic that's FDA approved, but it is FDA approved for IBS, so that's pretty exciting.

So let's start here on the left, which is E. Coli. Cajunai, Shigela, Samanella, they can all cause IBS. But what's the evidence? Like, the primary evidence that food poisoning leads to IBS.

Really 1 study. It breaks down to this 1 study by the Mayo Clinic. And if you look at the top, the top are bacterial causes and 1 in 9 people who experience food poisoning will develop irritable bowel syndrome. And so in 2023, 2017, this paper, it's very clear. Food poisoning precipitates irritable bowel syndrome will stop.

Okay. So now we have to figure out how that works, why that happens. Now What I want to explain to you before we get into this is that this happens to explain possibly or probably about 60 percent of IBS. Remember at the beginning, I said, I I guess is a diagnosis of exclusion historically. So you do a scope, you don't find anything, do some blood tests.

You don't find anything. Okay. It's IVUS. So if you take leftovers and you put them in in a bin, you know that Some of them could be Xevo, but we're going to talk about some of those patients could be celiac patients or EDS patients or various other diseases. So we don't -- we never believe that Siegel and post infectious IBS is the cause of all of IBS because IBS is just whatever's left.

But to account for 60 percent, that's a that's a big big thing. So here we go. Can AGE acute gastroenteritis cause sibo or IBS? And the answer is yes. So putting this together, we did an animal study and this was all the way back in 2008 and we were already thinking about this I have a lot of fun stories about the CDTV talks in which I don't wanna waste your time, but but really cute and fun interesting stories about how we thought about CDTV talks and then and got to that.

But a couple of actor on the right, given to rats, on the left, placebo to rats, of course, the rats got sick. They completely recovered after about a month, and then we made it 3 more months. So the total study is 4 months. And then we were able to see that the rats who received chamylobacter, now 27 percent of them have small intestinal bacterial overgrowth, whether it's due to eating or guggenome or ileum. That's the first part of a small bowel, second part of a small bowel, third part of a small bowel.

That's with duodenum, duodilumine, duodilumine. But 27 percent have overgrowth from that. Not only is that true, but if you focus on the purple column on the far right, you can see that if you got capylobacter, which is c plus, that's the food poisoning. And that capital vector caused the rat to have Cboe, which is the Cboe plus those rats, 84, 85 percent of them had altered bowel pattern. And they also had increased rectal lymphocytes, which is what we see in humans with post infectious irritable bowel syndrome.

So we had an animal model for the first time who are admimicked what we see in humans with a organism or a bacteria, Campolobacter, which is a form of food poisoning. That is the most common form of food poisoning in the United States. So now we have a working model where we can start to dissect and figure out, okay, what's going on here? But what's going on here now? In 2008, 2022, 14 years later, I'm not going to go over all the studies because it's way too much for this presentation.

I will just go over this slide which sums it all up. This is called the Bradford Hill criteria. The Bradford Hill criteria is a a very strict set of guidelines on cause and effect when it comes to diseases caused by bacteria? So, a question posed to the Bradford Hill criteria, is there enough evidence to say, CABLOVEC causes IBS as 1 of the pathogens. And it meets all the criteria, which is not not easy to do.

As this was published in 20 22 in pathogens and disease. And clearly, Candlevactor causes variable bowel syndrome. But how how does that work? And this is where the toxin CVTV comes into play and how it's affecting you and mac making you produce an antibody to yourself. Well, I already mentioned that all 4 of these organisms Jalasammonella, Campylobacter e.

Coli, they're all bad organisms. You travel somewhere or you eat at a bad restaurant and you get food poisoning. These are the kind of bugs that cause disease, acute disease. You get diarrhea, and then a few days later, it goes away, the bacteria, any of these 4, they're gone. After a week, let's say, or even a month, you can't find them in your gut anymore, but they did their damage.

And Part of their damage is with this toxin that they all share, and it's called phytaleethal distending toxin B or CDTV. What CDTV does is it makes you form an antibody to that toxin. But part of that toxin looks like a protein called Vinculin, which is in the nerves of your gut. And you can see the Vinculin. These are cells Let me just choose my mouse here.

The green are the scaffolding of the cell to keep the cells shaped. It's called actin. And at the end of actin is Vinculin, which is like a little motor that moves the cell to you can see the cells kinda reaching out to grab onto the next want to attach. So if the Vinculin doesn't work well, the wires can't connect to each other. And and I think that's the best way to describe what happens if you mess with Vinkillin and you have this antibody, which I'll show you in a minute.

So what's happening is that these cells, I know I showed you sort of cells this way, but now we're looking at them in a little bit of a different way. These are the cells, the brown ones that are called interstitial cells of the hull. You don't need to remember that. You just need to know that these cells are what make the cleaning waves of the gut go, and they need to be connected. So they need to be close to each other, and then their little, you know, side tentacles connect to each other like wires along a chain.

And so these wires along the chain need to be connected. If the rats got campylobacter but did not get Cboe, The chain is there, but it's a little bit less impressive. In the razica ribo, the chain is broken. You can see 1 cell here, but you really can't. Maybe there's 1 there.

It's hard to know, but the cells are diminished. And you can see that the number of cells when you count them blindly, so we didn't know which group was which, and you count them, the number of cells is lower in the group that got capylobacter and that was treated with Cboe. So this is what's happening. This is how it happens. So you have this nerve damage and then you get bacterial overgrowth.

Well, we actually showed this all the way back in 2022. I know the stream of thought is to go from left to right in science, but sometimes you get scattered shot and you have to start to put together the pieces. It's sort of like actually literally doing a puzzle where you're doing the face and the head because that's easier rather than the trees in the background, which is harder when you're when you're putting pieces of a puzzle together. But we already knew back in 22002 that if you have IBS and Cboe, the number of your cleaning waves of the gut, which those little cells I showed you on the last slide, are controlling are down. A lot down, not only that, 50 percent half of IPS patients with Cboe, we didn't detect any cleaning waves at all.

So a bunch of zeros down here that are averaged into this this final average. So the cleaning waves aren't working, and this is a known cause of Cboe all the way back in 19 77. No cleaning waves, poor cleaning waves. You get bacterial overgrowth and and that's sort of how it happens. So let's get down to a little bit more nitty gritty on the CDTV talks and and I know this is gonna get to to some really against science, but you need to know how important CCTV is and is the root.

Because when you know the root of a disease, then you can root it out as and cure it. And so this is a very big focus of our research especially in the come in coming years, future years. So we said, okay. So if CDTV sits not capital backed, It's not Shiguel. It's not Samanella.

It's the CDTV toxin that does all of this. If we just give the rats CDTV, that's it. Nothing else. And we use it like a vaccine like you would get the COVID vaccine. And in fact, it's almost identical.

You take 1 dose 3 weeks later, you take the second booster That's how we gave COVID vaccine. We do the same in rats with the CDTV toxin. Well, sure enough, they didn't have antibodies to CDTV 4. There were clean rats. They didn't C capylobacter.

After the CTV immunization, of course, the antibodies go way up. But look, what happens to Vinkillin antibodies? Vinkillin, we're not giving them Vinkillin. Were just giving them CDTV, o biculin antibodies went up. So they were able to develop autoimmunity as a result of being exposed to CDTV.

And only CDTV, that's all the rats saw. We didn't put it in the gut we put it in their arm under their skin as a vaccine. They got Cboe. So, CDTV antibodies create cbo. And that is a really important finding.

Not only that, they had reduced veinculan expression in their gut. So we were able to see that the CDTb antibodies are damaging the Vinculin going on in the gut. So kind of works like this. You you you get food poisoning. This toxin goes into your body and and you you're reacting to it.

So you form antibodies to this part, to this part, to this part because all of it's foreign, you want to get rid of this toxin. But 1 of the antibodies is similar to the protein sequence in Vinculin, and that's called mimicry. The CDTV is tricking you to form antibodies to yourself. And then you get a lot of these bad changes. Well, this was DDW last year.

Now, this this paper is in process of being published. So it it'll be finally published a few weeks, we hope. And so but it is public information because it was presented at DDW, but it's very important to we repeated that experiment with CDTV. And again, no antibodies before that toxin, a whole bunch of antibodies after the toxin, the wet weight of the stool went up because of the toxin and the antibodies. And the higher the antibody was, the higher the stool wet weight was.

So the antibodies are driving the phenotype or the presentation of diarrhea in these animals. And this second more detailed study. In this second detailed study, we were able to do microbiome sequencing, and we show that nothing's happening in the colon. So the CDTV toxin, the antibodies, they're not changing your microbiome of your colon. They're changing the microbiome of the duodenum, or an ileum, meaning the small intestine.

And and how it does this is a little complicated, so I walk you through this. The rats who got no toxin They're orange. That's normal microbiome of the small bowel. The rat the green rats are rats who got toxin but their microbiomes fine. It's the same.

Didn't change. So remember at the beginning, I said, you get chamylobacter? And about 1 in 9 humans develop IBS. Well, the orange is the 1 in 9 humans. No.

It's a little different with rats, because we're giving a really big load of toxin. It's not like food poisoning. It's a little more industrial strength study. So it may not be 1 in 9 and maybe 1 in 3 for rats. But but the point is that you get the toxin.

Some people, they don't get IBS. They just don't get it. And and that's that's what we're trying to emphasize. But then the blue and the purple do get IBS. And but the rats are going in 2 different directions.

There's a group of rats going into a direction of, oh, my overgrowth is going to be E. Coli. Which is a hydrogen producer and I have diarrhea. My overgrowth is going to go in the direction of the sulfur vibrio which is a hydrogen sulfide producer and I have even more diarrhea because that was their microbiome was set up to go in 2 bad directions. And they either go on 1 or the other and that's what we saw on this.

I want you to remember that because we now call these micro types. So the IBS patient or the Cboe patient can with diarrhea Forget about conservation for a second. The diarrhea can end up with 1 of 2 micro types, hydrogen or hydrogen sulfide And that's what we see in rats when we give this toxin, and that's exactly what we see in humans with vivo, 2 different micro types for the diarrhea side, and I'll show you that later. But it's really important to understand that we're getting exactly the same results in rats as we're getting in humans, which is really important and remarkable that we can duplicate like that. This is a paper that we are a poster we presented at DDW, so it's an extension of this study, same study, but now we take the rat small bowel and we say, What's going on?

What is the what is these micro types? What are these micro types doing to you, the rat? At the tissue level, what are you doing to defend yourself? What are you doing that's causing the illness to be manifest. And what we show is all micro types shared differences in gene expression, but circadian rhythm is affected, barrier function is affected, motility is affected, and visceral hypersensitivity is affected.

A lot of words. But basically, what's happening is your gut becomes leaky that's the gut barrier, impairment that's happening. The motility of the gut is affected, which we already showed you that the motility is affected, and that's why the overgrowth occurs. And visceral sensitivity, meaning the chemicals that make your nerves feel pain more easily are up. So it's sort of like you have a cut in your skin and there's bacteria there.

You feel pain there because of that in affection or that bacteria. Same thing's happening in the gut. So if you get a little bit of gas in there, you're gonna feel pain more than somebody who has the same amount of gas. So all of these things are not surprising, but it's surprising it all comes into this model that we're seeing exactly everything we see in IBS, we're seeing manifested by this CDTV toxin, which is brand new and very, very exciting putting this all together. So can markers of CD2B and Vinculin predict IVF?

So in other words, could you diagnose IBS by measuring these antibodies? And the answer is yes. I'll show you the results. So here's the anti CDTV toxin. Or anti CDTV toxin antibody blood test.

So this is the second generation test. I'll show you the difference in a minute. The second generation test was done because the first generation test was okay, but there's a problem with the way the antibody binds to the protein and we figured out the way to make the protein more exposed in a specific way called epitope optimization so that the antibodies could get to it more easily. And so when we did that, It's better test. It's a much better test.

Eat for anticoagulant and for anti CDTD. And so I'm going to walk you through this so you understand this. If you just had a positive anti CDTV or anti Vanculin, your post test probability of having IBS meaning you have a positive test, what's the chance you now have IBS is 89 and 88 percent. If both markers are positive, 98 percent chance you have IBS. In terms of diagnostic testing, medical certainty is 80 percent or above.

So you want to be above 80 percent because that's considered by diagnostic tests, medical certainty. When you develop diagnostic tests, the most important number is likelihood ratio. We're gonna get really deep in the weeds, but it doesn't matter. I'm gonna I'm gonna explain this to you. The likelihood ratio is what determines your post test probability.

The higher this number is, the better the post test probability. So we did develop the first assay the first 1, and this was the number for CDP 5.2. It's now 5 6.3. It was 2. It's now 5.3 here.

So much, much better. How does that work? Or how does that compare to what's out there. So let's do a post test probability. The gray bar is medical certainty and Anything below 80 percent is suboptimal, but can be used, but is suboptimal if you don't have something better.

So pain perception is just a way of looking at whether patients have an accelerated or an accentuated response to pain. That's useless. Because the pretest probability is 55 percent, so that doesn't do anything. There used to be a 34 biomarker panel, which was an algorithmic sort of AI determined panel didn't really get there. Bile acids in the stool doesn't get there.

There was a 10 biomarker panel that was on the marker temporarily still, it's not there anymore, 79 percent visceral hyperalgesia, you put a balloon in the rectum and you feel paying at a higher at a easier threshold, meaning a lower amount of volume that it gets there, but it's it's not great. Volatile in the stool. Pretty good. Hard to get this test. The first generation test of CDTV Invingulin, which is still on the market as another another test, which I'm not going to mention.

But this is where it sits. Antibinkia in here at 60, CDTV at 80. The second generation test The antivinkulum is 87 percent, 89 percent for CDTV, and if both are positive, it's 98 percent. So you can see this is huge improvement and is the second generation test really is now the gold standard or at least the best test that we know of currently. For the diagnosis of irritable bowel syndrome with diarrhea to diagnose especially post infectious IBS.

So And so here's how it works. I'm gonna summarize this first half. You've got all these beautiful bacteria in your gut. Also, it's colors and shapes and sizes, and they're just wonderful. They're supposed to be there.

Then you get capylobacter. These green things with a flagella on the back, when they invade they produce CDTV toxin which you get exposed to, you start forming antibodies to CDTV first. The antivinkulum comes later. But when the antivinkulum comes, you start to get a breakdown of the nerves, those special little cells I showed you that are reaching out towards each other They're not anymore. You get a diminished cleaning wave, and then you get a whole bunch of these characters.

And I'm gonna talk about these characters when we talk about breath testing next. Than that seaborne. So now let's go to breath testing because we need to look at breath testing And what is the evidence for, what breath test you should she should use, how you should use it, and so forth? So ironically, at DDW, there was somebody who was a very particular expert in meta analysis did not show this meta analysis, which is the gold standard meta analysis, the most recent meta analysis on breath testing in IBS. And it's clear that anything above 1 is significant.

This is the summation of all breath test studies for IBS, and you can see that it's way up there. So breath testing is abnormal and IBS more than it is in healthy controls. People say to me, well, Well, what percentage of IBS should be positive on a breakfast? Well, if you just run the numbers on every trial that's done, it's about 49 percent So if you're getting 80 percent positivity on breath testing, there's something wrong because it shouldn't be that high. It should be I would argue between 50 and 60 percent of IBS is positive if you use lactulose in my experience and you have an experienced clinician.

Remember, 60 percent of IBS is this pattern of things that I've been talking to you about today. But breath testing is more complicated than we knew. If you those of you who are old like me, hydrogen was the original gas on breath testing. There was no methane on the breath test. It was only hydrogen.

Back to me is a useless breath test because you can't just measure hydrogen. If hydrogen is the fuel for the 2 other gases, hydrogen sulfide and methane. So if you don't know the hydrogen sulfide or the methane, You don't know how much hydrogen's being eaten up by other organisms. We now know hydrogen sulfide is associated with diarrhea more. And methane is associated with constipation more.

So you need to know in my view all 3 gases, and I'm gonna provide you evidence for that. Let's go to the culture studies because culture was considered the gold standard. So the argument against breath testing was, okay, breath testing great. But it doesn't tell us what's really going on in the gut. I'm gonna argue that's not true today because of what we some of the new slides I have But at the time in 2007, culture.

Culture's the gold standard. Look at culture. Culture is more abnormal in IBS than healthy. So yes, there's more Cboe. If you use the correct cutoff, which we now prove is correct, I'll show you that data in a moment too.

10 to the 3, meaning 1000 bacteria in the gut or higher. Is considered Cboe in the small bowel. 60 percent of IBS D is Cboe. So that's again the 60 percent rule of of IBS D. 60 percent we think have seeding.

So that brings us to the re imagined study, which we're doing at cedars. Which is a very large scale effort to try to determine whether the small bowel microbiome is important to many, many different diseases and we just had a paper on scleroderma come out. So if you look at other things we're doing, you will see papers on obesity, you will see papers on a lot of different topics and because we're finding things. But let's stay focused on small intestinal bacterial overgrowth. I've shown this before.

Each ring is getting deeper and deeper into the into the depths of what bacteria it actually is. So if you start in the middle, you can see this is bacteria, the the the bacterial kingdom. And then when you go to the next link, it's the thylum. So there's proteobacteria here from acute here, if you know familiar with these terminologies, And then the further out you go, you get down to the species to the genus and the outer ring is the species. You can see we are not naming the species because we don't know with 16 s.

So early sequencing data uses 16S sequencing. 16S sequencing can only get so far to understand the microbiome. But even with this paper, in 20 20 using 16 s. Klebsiella, and this is this gray 1 is Echerishia, which is E. Coli.

These are not pathogens. These are not bacteria that you eat in a bad restaurant and you get food poisoning. These are bugs that are in your gut, but they shouldn't be this man. They shouldn't be this high in your gut. Look at the normal person, if you go to proteobacteria, look how small proteo is, proteo being here, and then you go down to Klebsiello's this little tiny layer here, and Echeresia is this this 1 here.

We'll come huge it is in bacterial overgrowth. And I'll show you more details, a lot more interesting than that. 1 of the interesting things of that paper though is that when we used lactulose breath testing, we were able to get a great correlation. It was the most if you use the 20 part per million at 90 minutes, you have the best sensitivity and specificity against culture. Against the sequencing results and that the hydrogen was coming from activation of hydrogen production pathways in the small bowel.

So when you're giving lactulose and you're getting a positive breath test, it's from the hydrogen producers that are in the small bowel, not the colon. So those who argue that lactulose is checking for colon bacteria, it's not true. This study, this proves that or proves that the hydrogen is elevated in the small bowel. Now I'm gonna talk a little bit about intestinal pathogen overgrowth, and then I'm gonna start to to put this into a really deep concept to get you to understand how much more we know. But we know that methanobrara doctor smithii, that methane producer, is the culprit in producing methane in the gut, And when it produces it at a high amount because there's a lot more of these guys that you get constipated, you get bloated.

We've even shown a lower heart rate and a lot of other properties of methane that are good, but not good in high amounts. A little bit on the sulfate reducing bacteria or hydrogen sulfur sulfide producers. So they take hydrogen from other bugs like e coli, and then they convert it to hydrogen sulfa. But it is the hydrogen sulfide that drives the amount of diarrhea you have, urgency and pain, and then other factors can come in to overproduction. Of these characters.

So we had to develop we had to work on developing a gas breath test that actually measures all 3. And this took years because this is not an easy challenge for 2 reasons. For a lot of reasons, here's here's the list. You're not able to transport hydrogen, sulfide hydrogen and methane across the country with existing technologies a number of years ago, especially hydrogen sulfide because it's so reactive. So it it needs a special bag, a special system for transportation.

You need to develop an instrument that can measure all 3 and in such a way that you're not cross reading other gases inappropriately. So you don't want somebody with high hydrogen to show up on the hydrogen sulfide sensor because it cross reacts with that gas. So you have to orient the sensors in the instrument in a way that that doesn't happen, and then you get that you get an accurate accurate result. And then you have to do science to prove that the test actually works and that hydrogen sulfide is valuable and that the the, you know, what cutoff should we use, and so initially started at 5 parts per million. It moved to 3 parts per million, but I'm gonna argue that it really should be 2 parts per million.

And you're gonna say why does he keep changing the cut off or hydrogen sulfide Well, what you would hate is for me to say, oh, just use 2 because I think that's right. And then later, I say, no. No. No. No.

It was never 2. It was 3. And then a whole bunch of people are getting medications for presumed hydrogen sulfide positive when it really wasn't true. You have to wait for the science to adjust your criteria. You can't make stuff up.

And and I and I try very hard not to make things up as we go sometimes it takes patience from from us and from, you know, viewers to wait for the science to tell us what the right thing is to do. So I know sometimes that frustrates people, but you can't just say stuff. You have to have some backing in science. So this was the original study where we used the 5 Hyper Million cut off. These were diarrhea patients.

What we call functional diarrhea, not D IBS or IBS D, These were functional patients, and you can see that hydrogen sulfide was way up here as compared to the healthy and the constipation patients. And that hydrogen sulfide was proportional to the amount of diarrhea. But I'm not gonna spend a lot of time on this because I have a lot better data now. So this is a study where we -- it's a double blind randomized controlled trial for a drug that we're working on for diarrhea IBS, which you can't talk about. And constipation IBS, a different trial, a double blind randomized controlled trial.

In both studies at the baseline, we did lactulose breath testing with 3 gases. So this is really important because this is this study for the first time is showing that, yay, that the first time we're showing that a breath test using 3 gases and specifically having to use lactulose. We correlate with the gut bacteria at a microscopic level. So the breath test is In fact, telling us very clearly what's going on in terms of the proportion of bacteria in the gut that are causing problems. So this is a really important because it emphasizes lactulose as an important substrate, and it emphasizes that the 3 gas breath test is the only breath test that is validated against the microbiome in this detail.

So let's go and get cut into it. So if you look at methane and you're a diverse IBS D patient, you're the blue line here. You don't have methane. The D patients almost never have methane. It's and we didn't select patients for Cboe.

This was an IBS D IBS C trial. Here you can see that not everybody with c had methane, but the ones that did, this was the methane level. So it was quite high. And it starts high. We always knew that with nothing.

Nothing's either there or not there. It doesn't get necessarily all that much higher with the lactulose. Hydrogen on the other hand is the blue line here again. IBS D. Look at the hydrogen.

On average in a D patient, by 90 minutes, it's over 20. Now, of course, there might be some below there. Remember we said 60 percent, but on average, majority of the patients already reached the threshold that they really truly have Cboe. Look at the methane people. The methane needs hydrogen to make methane.

It has to have hydrogen to make methane and look at the hydrogen values in the methane group. Lower than even the non methane constipated patients. Why am I saying that? Because when you're measuring methane, your hydrogen is lower because the hydrogen's being eaten to make methane. So you can't measure hydrogen without knowing methane.

And I will argue that you can't measure hydrogen without knowing hydrogen sulfide also, same problem. Here's the hydrogen sulfide levels. Are higher in IBS D versus the other 2 groups. Here's where we're we're now getting really exciting. So the new 3 gas breath test using lactulose as the substrate, we can correlate directly with the amount of m smithii in the gut.

And you can see these are the correlations. These are the p values. So the breath test is validated by the fact that, yeah, we're actually measuring methane on the breath. Yeah, we're actually measuring correlating with the amount of pathogens in the gut. And yeah, we are correlating with constipation.

So it validates the breath test more. And these are the correlations. We're able to correlate the methane. Here's the methane. Correlating with methanogens, 2 types of methanogens in the gut, again, proving this correlation.

I'm not gonna get into too much details except I'm gonna say 1 thing about this. These 2 characters, Kristen Cinell ACA and Romano clock ACA, are the gut bugs that produce the hydrogen for the patients with methane. It's not the e coli and klebsiella. This is the constipation side of the story that's really unfolding very quickly now. But I'm not gonna get into all those those details.

In the hydrogen sulfide group, the hydrogen sulfide on the breath test correlates with the hydrogen sulfide producing organisms in the gut. Again validating what we're seeing on the breath test. Let me just emphasize it very clearly. The lactulose is driving hydrogen sulfide production. The hydrogen sulfide we're seeing on the breath test is being measured accurately to the point where we're able to correlate with actual microbes in the gut, so the bags get sent.

5 days, whatever it takes, to get to the lab and still the gases correlate perfectly or very well I should see statistically with the microbiome, never been shown for a breath test. So this is a really important study that was published just before just before New Year's. And that the the breath test is correlating. The hydrogen sulfide level is correlating with fusobacterium, which is a hydrogen sulfide producer. Okay.

I'm gonna skip this because it's now getting too deep and I'm I'm gonna lose you all. But again, Breath test using the 3 girth breath test, methane correlates with all the stuff that makes methane. And on the right, the hydrogen sulfide correlates with all the stuff that makes hydrogen sulfide in the gut all the way to the pathway level. So We now with this 3 gas breath test can see, and I and correlate with the gut bacteria 3 distinct micro types. And so this is all new.

Hydrogen Microtype, the sulfur or hydrogen sulfide microtype, and then the methane or methane Microtype which drives constipation. So constipation here, the diarrhea for these 2 groups. So let's talk about breath testing now as we wrap up, get getting closer to the end. I do have a few more tidbits for you, so I know this is a long presentation, but but bear with me. These are the 3 consensus.

We did the first consensus on breath testing 2018. Here are the follow ons. There's Most of the world who's had consent part of these consensus statements agree with the criteria for Cboe. Most of the world agrees with the substrates and dosing, and most of the world agrees that Cboe and IBS are interrelated now. So we've come a long way from 19 96.

But here's the newest stuff. So now we're trying to get to the point where we're able to say, okay, now we know who exactly is causing all this hydrogen. We know it's as Cherishia. We know it's Club Ciela, but We need to know more. We need to know exactly who they are.

And this is culturing the small bowel. So some centers in the United States culture the small bowel and they take this agar and this agar and they pull it together and they say, hey, if it's over this, you got overgrowth. This Agard does not work. Look how many patients we have in this study. Huge number of patients.

It doesn't work. It does not. There's no difference in diversity of the microbiome using the blood agar. But look what happens when you use maconchi agar and you get to greater than 10 to the 3 already you're seeing a tipping point in the microbiome. So anything over a thousand on this growth media or agar is overgrowth.

This is super interesting. This was just presented a couple day few days ago. This is your network of microbiome. The network is all these lines connecting dots or all the microbes in your gut, all communicating with each other in the sense that hey, if I'm here, you should be here and we're like a family. We got a plumber here.

We got a doctor here. We got a lawyer here. We got You've got a sanitation worker, etcetera, etcetera. The city is in harmony because there's lots of dots and lots of lines. That's a good healthy microbiome.

But the microbiome starts to break apart when you get to over that 1000 mark on that growth media. And when you get to over a hundred thousand of those bad bacteria, it breaks down completely. Nothing's connected. There's only a few dots a few lines and the microbiome really starts to just fall apart. We also presented at DDW the Methanogens, and they are everywhere.

So the point is the biggest group is still the Mthana Brevabacteria ACA, which is Mthana Brevabacteria Smithii, which I've told you about. And they are in the duodenum, and they are in the stool. So they are it's that's why it's called chemo and testinoma, manage, and overgrowth because it's not just in the small bowel. It's in the stool also at almost equal amounts. And then I wanna show you something really sort of interesting and and then 1 more thing interesting after that because I think this it's just getting so be.

This is an app that we use to look at stool. So patients take a picture of their stool before wiping and putting paper in the toilet. And we're able to see exactly what this tool look like in the AI in the in the app calculates this Bristol score, the edge fuzziness, fragmentation, and other factors. And when you have methane, Your bristle stool scores lower, your edge fuzziness is the last meaning the stool is more smooth and tight like a like a like balls and fragments. And and and you have less fragmentation.

Meaning, you don't have, like, little bits and bits and bits of loose stool. Local happens with hydrogen sulfide, and this is really important. So if your hydrogen sulfide is positive, you have more stool volume. Compared to a hydrogen positive patient, when your hydrogen sulfides there, you have more stool long. If you're negative for all 3 gases, the difference is even greater.

If your hydrogen sulfide is greater than 2, that's when the volume starts going up. So 2 may be a better cutoff and that's where we're heading and continuing to learn more science around hydrogen sulfide. Alright. And finally, remember I showed you this circle and I showed you that Cboe is is really important. Now with shotgun sequencing, we configure it out all the way down to the strain level, what bacteria are present.

So similar circle except now we got the outer ring. Which is here. K? So what I'm gonna do is I'm gonna continue this and show you this is cboe. This is what normal people have for this group of bacteria called proteobacteria.

This is normal here on this side. Tiny amount, tiny piece of the pie. More than 50 percent of your entire microbiome is now proteobacteria, but no, it's more than that. Look at this. 18 percent of your entire microbiome is 1 species, klebsiella pneumoniae and another 28 percent is just E.

Coli, which is this 1 here, this gray 1 here. And now we know all the strains of these organisms that are part of Cboe and all the bad things that they can do. And so When we know the strains in the species, we can direct our treatments even more better. And these species and strains that we identified for Cboe are correlating with bloating, gas, abdominal pain, diarrhea, urgency, etcetera, for both both sides, both Klebsiella and E. Coli.

And they are together in most cases. So we now know the exact strains of bacteria that cause cevote. But can you imagine your beautiful microbiome of 500 different bacteria boiled down to 2 species taking up almost 50 percent almost half of everything there and that's seabrook. Nothing in the re imagined study looks like this. This is very, very remarkable apocalypse of your microbiome.

And and then the last thing I'm gonna show you is this this because this really kind of emphasizes the point So because you have these E. Coli and klebsiella pneumoniae in your small bowel, what happens is these 2 guys, these 2 characters. Are amazing fermenters. So they jack up your ability to digest sugars. To new highs.

So people say, well, I just ate and then hardly getting gassy. The small bowel is so jacked up to ferment because of the high numbers of these very intense fermenters that you get these up regulations like 63 times higher amounts of glucose degradation. Don't be fooled by that. That doesn't mean a glucose breath test is better. I'm saying carbohydrate digestion is all all accentuated.

Hydrogen sulfide production is accentuated. And then there's some of these other pathways which I won't get into today because it really is gonna be too complicated. But super interesting pathways that you will hear more from me about in the coming year or 2. Again, I'm showing you these networks. This is what happens with E.

Coli. When it goes to this level, it's more broken. When it goes to this level, higher level, it's even more broken. Klebsiella is even more destructive. You can see that the network really sort of just starts to fall apart as Klebsiella goes up.

And then finally, these are the pathways in humans. Again, strong association with motility genes with barrier function. So these bugs and the CDTV toxin and everything on top of each other are changing your barrier function, changing your histamine secretion, changing your inflammatory response, changing your motility and causing further worsening of the situation. So, 3 gases is what we measure. Hydrogen, hydrogen sulfide and methane.

This is the physiologic sequence which we've built greater evidence on at all levels since the last time I've spoken to you. We treat IBS based on this study Rifaximin is FDA approved for irritable bowel syndrome. But if your breath test is positive, you're more likely to respond to rifaximin 56 versus 44. And if you make that abnormal breath test normal, those patients respond 76 percent of the time. In methane, we give rifaximin and neomycin based on this double blind study.

That's what we do. It's not FDA approved like that, but if your methane, this study is something to lean on for treating methane positive, we don't have a new thing for hydrogen sulfide out yet, but things are coming. Let's say that. So this is what I do. In my clinic.

But based on everything I've told you, you've got chronic diarrhea mixed. I do the antibody measurements because it helps the patient, it helps me understand what's going on. I do the 3 gas breath test. If it's hydrogen, I give rifaximin, if it's hydrogen sulfide, now greater than 2. For me and my clinic, I give bismuth and rifaximin.

And that's worked really well for some great for some patients. And ironically, some of the patients with hydrogen sulfide a year later, they don't relapse like the ones with hydrogen. Constipation. I I don't need to measure these antibodies because that's not part of the mechanism there, but I do the 3 gas breath test. Because there are patients who have all 3 gases seen this often enough, methane always wins.

So you will be constipated if you have methane. But what you don't want is to get the methane down, not treat hydrogen sulfide and then flip them to diarrhea. So I still want to know all 3 gases. And I use rifaximin and neomycin or sub the Neomycin with metronidazole, which seems in clinical practice to be working just as well. So 3 more slides.

I started with this slide that this is where we were with IBS in 19 96. This is where we are now with the microbiome. I've shown you a lot of this detail. I'm not going to go through this slide, but a lot has happened. And so in conclusion, IBS is commonly a small bowel microbiome disease.

Siegel is very important contributor to that. We now know the characters. Ecola, Clubsylla, pneumoniae, and that they produce a hydrogen and getting rid of that hydrogen, getting rid of those bacteria make you better. It makes the patient better. M smithii or methanogens are responsible for the methane in the in the gut.

And they constipate. Getting rid of methane makes the constipation better. Hydrogen sulfide is really important to further under stand that this third dimension of the microbiome, the breath test, the 3 gas breath test is now validated. The whole system is validated against sequencing of the gut. So what you see on the breath test is what we're seeing in the gut and the microbiome.

So that's super important, and everything we've done uses lactulose. So the lactulose and the system of 3 gases is what's being validated here. And this second generation antibody test is far better than the first generation and is more accurate and important. So we're understanding IBS for the first time in new ways, and I think it's going to change how we treat this disease. So I'm going to stop there and hopefully, wasn't too long.

Keep going as far as we're concerned.

Oh my god. Not too long at all. I'm like, don't skip over that slide. Talk more. It's fabulous.

That's amazing. Congratulations on all the progress seriously.

Lot of progress this year, so I'm really, really excited for patients.

Thank you so much for all your work that you do. Every year on behalf of all of us. This is incredible. Incredible.

It really is. And and and your your advocacy by going and doing podcasts and being with us for our sessions and stuff. Like, we really appreciate it and we're thrilled to get the word out to people because This is exciting. You know, we're not used to having a condition that we get to watch the research emerge and know that there's so much hope coming, like, within our lifetime, within years. So it's it's very motivational for us to stay the course and, of course, we wanna let you know you're very appreciated, so send our best to the team.

We have questions. We have questions. We have questions.

Okay. I'd love to start with something slightly off topic from the research that's new that you presented because so many people are thinking about this now. In the last year, there's been a huge publication or awareness raising an increase of use of some of lutide. And similar drugs. So this is sold as Ozempic, WIGOVI, RABELUS, and We know that 1 of the mechanisms of actions of this drug is to slow stomach emptying, slow and basically slow upper GI motility.

And so I have 2 questions. First off is, should people be concerned that this could be a cause of Cboe by slowing the migrating motor complex?

Well,

all these drugs, including Mondoro, the See, the other 1, are commonly used now, and it actually affects a lot of what we do. For example, if you're on 1 of these medications and you do a breath test, it's a flat line because the lactulose never leaves the stomach. The stomach just doesn't empty. So it's not that it slows the cleaning leaves. It slows everything.

So it it's more problematic than that. Now we don't have a lot of details on, if you're on 1 of these medications, are you getting more Cboe or not, or are you going to precipitate Cboe? We we don't know. I mean, it's really early days on on this, but 1 would imagine anything that slows the gut down. Leads to bacterial build up.

There's no doubt about that in my mind. So what that does in the long run, we don't quite know yet, but But you're right, it's a big problem. Well, I guess obesity is a big problem in solving obesity, and these medications actually working is actually a good thing. But there's always a yin and a yang with everything we do in medicine. So you can solve 1 problem only leading to another.

And another example of that is these, and I'm blanking on the name of the category of drugs, but these new anticancer drugs Amazing. They're amazing, but they cause type 1 diabetes in some patients because they destroy your islet cells. So we're seeing surgeons of diabetes and a lot of patients from these anti cancer drugs which are lifesaving. So, you know, it's you're beating away 1 devil and you're getting another devil and you gotta decide which devil's worse. Cancer is obviously a bad example because it kills you.

And diabetes can be managed, so you take those risks. But, you know, this is what we do in medicine. We have to put in put everything on the balance.

Well, my second thank you. My second question on that is, what about for people who already have Cboe? Who want to take this or start taking it. Have you seen any examples or any concerns there that it's going to make their symptoms worse? Because it's going to slow motility more.

Yeah, I have a few patients, but very, very few, because I think they know that slowing the gut down causes them to be more bloated. But it's always more complicated than you think because what those drugs force you to do is eat less. You eat less and ferment less. If we have less substrate for the bacteria. So maybe on balance, it doesn't do much.

It doesn't make it worse, it doesn't make it better, it keeps it about the same. I don't know, but we need to study it because it's gonna be Almost everybody's gonna be on these medications judging from what I'm seeing in in the news media because even people who are not soul, these wanna lose a few pounds. There are these medications there too.

Thank you. And, Chamond, did you wanna say anything more about that?

I have personal experience with it because I have been on semaglutide because of my blood sugar. And I'm half Indian from India, which know you're familiar with Dr. Pimentel. And, you know, there in my father died of a heart attack and definitely had insulin issues. And I, you know, so, you know, skinny arms and legs on the tummy.

Right? So that's very typical for Southeast Asians. And I've never puked so much in my life because the stomach doesn't empty. And so has it made my sebum worse if I was, you know, feeling positive at the time. It hasn't, but like you're saying there are other implications to it.

So jury's still out. But, you know, it's been a

true When I'm back up, it's not feeding the bacteria. So, you know

There you go. There's a positive.

That's not a positive, but you know what I'm saying? I mean, this is the problem. You're gonna be eating less because of these drugs, and so maybe they get less food, and therefore, it doesn't unbalance, it doesn't change anything. But I'm just speculating, we don't have any data yet.

Yeah. I'll keep you posted if I come up with anything interesting and substantial. Alison, weather questions do you have?

Okay, thanks so much, Dr. Pimentel. That's been on my mind so much since everyone's been exploding with that drug. I mean, you know, Okay, this is interesting. I just wanted to know, I was so so taken with your explanation of the likelihood ratio for your second generation CDTB test.

And what I was thinking about was the fact that other than your first generation test, there are I think 2 other versions of that test on the market, you know, copycat labs. And there are a lot of functional medicine practitioners and natural paths who use those other labs because probably because they they order stool tests or something else from those labs who knows. And So then they just are using those labs for their CDTB testing. Do we know anything about the likelihood ratios and a validation of those other laboratories.

Although, I can tell you none of them are using epitope optimization because they didn't even know what that means. It's it's an internal process that occurs with the second generation test. So, basically, they're all first generation technologies. So you can see what what what you get is what you get, and it's not that great. It's great, but it's not that great.

It's not as good as the second generation. So it it it doesn't make sense. I mean, if I was a patient and I'm paying the same price for 2 tests, you get the 1 that works better, I guess, is how I see it. And the more accurate it is, the better it is. The less more more you're likely to do the right thing for the patient and save money, which is, you know, what I said at the beginning.

So the more accurate your test the more money you save in healthcare, period. Everybody knows this. So we tried to improve it to get it more accurate because we knew it wasn't good enough. I think it's good enough now because we can't really improve on it.

Okay, great. Thanks. Just clarifying, it sounds like you're using 2 parts per million now for your criteria for positive for hydrogen sulfide. Will we see a change coming officially in

So I think based on the newest data, they're gonna adjust the report to say, you know, based on new evidence, there there is accumulating evidence that 2 might be the cutoff. So use it in in your in judgment, in your clinical practice. So in my clinical practice, too, will be the new cut off. For me. That's what I'll be treating.

So because I think I haven't. I feel confident enough. But, you know, we we're not done. There's we're still studying this, there's more to be done to define it better, to define new treatments. We're always about 2 years ahead of head of slides I show here.

So we know a lot more things about what's coming. So it's it's it's it there's exciting things coming, so I'm I'm very optimistic.

Howard Bauchner: I

know when -- Siobhan always tries to get it out of you and you never crack

That's why I set it now so they can avoid that.

I know. You beat me to do it.

Okay. Another 1 is so exciting about figuring out the species and strains for the Club Ciella now. You know, also I just wanna say how incredible this is. You know, I love the way you started the presentation with, you know, bringing us back to how it was and how still we're having troubles with the acceptance here in comparison to Crohn's you know, with IBS and and Cboe. And it it's really getting harder and harder for people to maintain that when you're getting down to the species in strain level of exactly which bacteria are causing the problem.

So that's amazing. But I was wondering, you you were talking in 1 of the 1 of the abstracts about how you have a unspecified strain of Anterobacter, I think. Is is that right? Anna has been has been found as 1 of the culprits. That's new, isn't it?

Like,

Are you talking about that table at the bottom?

I was in 1 of your abstracts.

Oh, I see what you're saying. And then specified strip under yeah. 1 of the abstracts.

Yeah, 1 of the abstracts is like, there's, you know, there's E. Coli, there's the 2 strains or species of klebsiella, and then an unidentified Enterobacter. Is Entero I'm not very good with all the genius species strengths and is is in the previous previous work you've had done, you had said there's you would found a little bit of erroneous. And now you're saying Enterobacter, I was wondering, like, is aeromonas underneath the heading of Enterobacter? Or are these just 2 different things you found?

So remember 16 s. I don't know. You're familiar with the 2 technologies, but 16S is measures ribosomal RNA sequences. And so it -- the ribosomal RNA of different bacteria have different sequences. When we do that, there's a lot of overlap between different bacteria a lot.

And so when the computer goes through the algorithm is, okay, then what who does this line up with? Who does this sequence line up with? They make they make estimates. And then there's confidence estimates as well. And so when we say with 16 s that it is erroneous or enterobacter or Eshirishia, it's an estimate.

Shock gun sequencing, we're sequencing the DNA from the central core of the bacteria. And if you sequence long enough and enough of it, you know exactly who that organism is with 99 percent estimation. And so what we could have called Aramonus before with a rough estimate, we now call Eshirishia or something else. We don't we don't know how it'll we'd have to go back and compare the sequences and why it's at Aromonus and now it doesn't. We haven't done that exercise.

But it's not so important anymore because who cares? We now know the truth. The truth is shotgun. And so let's move forward with truth. Forget about aromonus for now.

It's how I see it because we're just wasting time. We need to get to treatments now. We have the the good answers, not not the old answers.

Oh, that's very often.

In the colon, it was always Eshirishia and Clubsylla. We knew that even back then. We just didn't know the details down to the species in strain. So and that continues to hold true.

Okay. Very, very helpful. I also noticed in I can't remember the presentation or 1 of your abstracts. I think it was 1 of the abstracts. It looked like there were the 1 on Methanogens

Mhmm.

-- or at

least 1 of the ones on Methanogens. It looked like there was different syntrophs for methanogens between the duodenum and the stool. Was that so?

There are

What's a symptom growth you guys What's the center of the world?

Is like your buddy. And so you need a buddy to produce hydrogen to give you the hydrogen to make the methane. And -- Got it. -- we're we're we're in early days of understanding that, Allison, so I I don't want to hang my hat on the central thing yet, but it looks like in the colon, the Christmas and Malacia and rheumatococcal ACA holds true. In the small bowel, it may be other syndromes.

Because Kristen Sunella, this is a thing we were confused about. Kristen Sunella and Rumohawk ACA are not common in the small bowel. And then the other thing you may have noticed is that methanol Methanol Masilokakis. Methanol Masilokakis is an official name. That bug is a Methanogen.

And it fights with the Muthana Brevavactor. So the higher the Muthana Brevavactor, the lower the Muthana Muthana Muthana Muthana Muthana Brevavactor, And so they're they're, like, you know, 2 competing gangs trying to win the methane day. But but for the most part, it's m smithii, I would say, 80, 90 percent of the time, but the other ones are trying to muscle in. So so a lot of interesting It's like Game of Thrones. Right?

So we have these different families competing and are yelling at each other to try and win dominance in the depths. So

Okay, great. Okay, and then amazing information about the genes that are affected in in Cboe. You know, you presented on that today. And I just was hoping you could maybe clarify a little bit because, I mean, you were talking about these genes leaky gut histamine, circadian rhythm, all these things, and it seemed to be an effect. These genes get altered from the from the sebum.

But there was also the motility piece. And you called that out a bit. We know that the motility gets slowed for Cboe to occur, but then it sounds like once the Cboe is there, motility is further affected. Could you clarify?

Yeah. So this is a part I can't clarify, not because I don't I I can't talk about it. It's not like that. It's because we haven't done the clarification yet. So We know that CDTV leads to antibodies, that leads to slow motility.

That does affect barrier function in all the things that that CTV poster I showed you. So a lot of the things we're seeing in the end game, the CTV did. It affected barrier function. It affected motility. Affected visceral hypersensitivity.

And then when we're seeing the final result, which is all this elevated E. Coli and klebsiella, we also see the same signals. So we're trying to figure out, okay, so all these signals are screwed up. But is it the E. Coli, e.

Coli, or is it the CDTB that did it, that screwed it up? Which chicken or egg are related to all these findings. And and that part is not exactly clear. You know, because with the CDTV, you're getting these elevations in e coli and klebsiella. So we're trying to dissect out is that the sebum that's causing some of these pathways?

Is it the CDTB antibodies, which are causing some of these pathways? Or is it both? And or what's causing what? So Yeah. It's still a puzzle to be sorted out.

Howard Bauchner:

That's what I figured. I was you know, this is the semester I teach at the college where I teach. And I I shared the new research on genes with them. The moment it came out on, you know, last week, and that was their question. Kinda like, what's Wait.

Chicken egg, what's, you know? So and I figured you were trying to figure it out still.

Howard Bauchner: We are working on it, but it's a complicated question because it's almost hard. It's impossible to separate the 2. So what we would have to do is take the animals who are CDTV positive. Treat their Cboe, get the E. Coli klebsiella down and see if these expression markers recover or if they're still screwed up.

So that's a study we have not done. But that is the study that we need to do to prove that. So heart study to do in humans because it's a lot of aspirates and biopsies and it's just too expensive and cumbersome for patients to go through.

I guess, it might then I'll turn it over to Siobhan. I know you've got questions, but my last question is, was there any were there any other abstracts or presentations at DDW DDW this year that you were particularly excited about, often you'll mention, oh, I want to call your attention to something else, you know?

Yeah. I mean, there well, I can tell you what was super exciting at DDW. This for the first time in history, DDW had an entire session multiple lectures on small bowel microbiome. And we've never had that at DDW. It's always been stool, stool, stool, stool, stool, So there's an entire section now dedicated to small intestinal microbiome, which is really -- and people are working in the area finally.

So, and that's the goal. This isn't about me, this is about patience. And I don't care who finds the final result that helps the patient It's just let's go people. Let's go. Let's get this done.

Let's help some some patients. So I'm super excited to see other people now interested in that. And and they're saying things, and I'm listening to them talking, and they're saying things, and I'm like, well, I can't believe somebody else said that. You know, like, what they're saying, what the in the speaker who introduced the whole session said, well, we know we haven't found too much in the colon and stool. But in the small bowel, it's it's a large surface area.

It's an absorbing surface. And so bacteria in the small bowel can affect the human more maybe than the colon. I'm like, I said that for a long time. Glad to see somebody else saying that. And and so it's an exciting transition that's part of that.

That is very exciting.

That is very exciting. Good. Good. I'm glad just personally for you that you're you're getting that kind of like Yeah.

Like The only 1 doing stuff otherwise, you know, it part of medicine is part of medicine is you know, you gotta believe stuff, but but validate it. Right? So it can't just be 1 sender publishing an area it's important that other people say, okay, I like the meta analysis on breath testing. You know, almost all those studies weren't us. 1 or 2 of them were, but the rest of them were other centers.

Super important that everybody's getting the same result in the same signal in the same there were more studies on methane and constipation. So I think methane and constipation is a foregone conclusion. There are very few people who disagree with that now because other people have proven this to be true. So, you know, we keep moving forward and other people replicate it and or prove it's right or wrong. If they prove it's wrong, then we have to figure out what went wrong and correct it.

But science, you you take what falls out of science and you publish it, and then other people either verify it or we make adjustments over time.

Fantastic. Alright, Alison. I have questions. Is it okay? I'm gonna take the mic.

Doctor Pimentel, I wanted to just have you say it out loud for anyone who missed it before about what happens once Cboe emo is resolved to the microbiome. That it restores back to harmony. If

you Yeah. We haven't published this, but we've seen it in the in the re imagined dataset that patients who had Cboe who were treated, their microbiome completely comes back. It's again, it's like It's the weeds in the garden analogy. You pull all the weeds out, and then the vegetables grow much better. And and I think that's true at all.

We have we don't see rifaximin resistance genes in the microbiome, which was amazing. We see this microbiome recovery after getting rid of the bullies. So I'm not sure if Faxman is you know, people worry about antibiotics, antibodies, antibodies, vaccines not quite like that. It does something special. At least that's what we're seeing.

Look, I'm you know, we continue to monitor things and watch, but that's what I'm seeing so far.

So that is the really big message of hope for everyone who still has those questions about their microbiome and I hope it's also motivating to everyone who's listening to this to, like, really go for it and get those treatments because the rosacea can improve. Right? The restless leg, all of these other associations. You were talking about with the low heart rate. I find that so interesting.

What Why? Do you know why? There'd be relationship between people with methane and lower heart rate?

Well, you know, so You know what we used to use to put people to sleep to do surgery? Carbon tetrachloride. You know what carbon tetrachloride is? A carbon with 4 chlorine molecules around it. We have a molecule called methane, which is a carbon with 4 hydrogens around it.

So it's just a substituted hydrocarbon carbon dichloride. Now we don't use hydrocarbon dichloride anymore. We use isoflorine which is still a substituted carbon molecule. And these gases, these anesthetic gases are affecting. They affect your blood pressure.

They affect your pulse rate when you're under anesthesia. And methane has, I don't want to say, anesthetic effects but it has groggy effects because it's similar to all these anesthetic gases. It's like the canary in the coal mine when the methane goes up, the canary falls asleep. So and then you know there's too much methane in the coal mine. So that's that's maybe why patients get brain fog and and look methane and we just need to understand the methane effects more.

But yeah, lower heart rate interesting. It's interesting.

So it'd be easy to extrapolate that that could lead to fatigue, right, that kind of feeling of lethargy.

Both it blocks your heart rate or blocks the heart rate from going up appropriately or slows the response because you can't maybe you can't exercise as vigorously because you can't get that response and heart rate. We're guessing here. We're just

I know. Right. Totally guessing.

Including the Louise because we don't have data yet. But There are a lot of potential implications of a lower heart rate and what that means. But if when I say it's lower, We're talking about 3 beats per minute lower. So I'm talking about 20. We're talking about 3 beats per minute.

But but over a lifetime, that's a lot of beats, you know, and and so -- Okay. -- step up.

Okay. I'm gonna go to fungus land now. Through the grapevine, I heard that you guys did start talking a little bit about the fungal overgrowth. Did you just elaborate on that a little bit?

I didn't put that slide in. Wasn't purposefully omitted. I just we had so much stuff. I didn't know how much to put in. But we actually, for the first time, sequenced fungus in the small bowel.

And, you know, or whatever irony it is, if it's over a thousand in the gut, it's associated with symptoms. And now it didn't happen often. So it's not like Cboe where it's common. It's uncommon. But when it is present, we said 2 things in the presentation.

We said that it is If it's over a thousand, you do get symptoms. If it's and it's usually candida. And we're trying to isolate the specific species and strain and all the stuff that we've we've been doing with Cboe and now we have the tools to do it. So it'll happen faster. We'll get that shortly.

But we're we're we're on it. It's there. It's there, but not on.

That's exciting. Okay. And then Let's just I I know there's been a lot of buzz. I've been following you on Twitter. I want everyone to do that.

Is about the sweeteners?

Oh, I didn't put that here either.

Non caloric yeah. It's okay. That's what Twitter's for the non caloric sweeteners and how they affect the microbiome.

Yeah. A lot of new stuff. So we've been saying in our low fermentation diet that aspartame is fine. It's a protein, so it's not a carbohydrate. And all the other ones are carbohydrates and maybe that's bad for Cboe.

And so we finally looked at that question and we imagined study, people who self declare that they take Aspartame, self declare that they take these other sweeteners And the other sweeteners, we saw over 70 different changes in the microbiome with the carbohydrate sweeteners. We didn't see things like that with aspartame. So, yeah, the other sweeteners are doing substantial things to your microbiome. I can't say good or bad, but as you can see, when you have Cboe, your, as I said, jacked up to ferment sugars. And if you put non digestible sugars in there and you have that heightened ability to digest them.

We're gonna get more bloated, and so that's a bad thing. So it reinforces Sort of what we've been saying, but with really good hard science.

I'm literally trying to find the name brand for the Asberg team because I've never I just have never used it.

Yeah. Interesting. The sweet. Nutrisweet.

Nutrisweet. Okay. Interesting. That's so interesting. Okay.

And then when people do clear Cboe back to us a little bit more motivation for, like, taking the treatments on, what else do you see people's symptoms go away? Other than the bloating, they get regular regulation to their bowel movements, I know we talked with a couple of people and Alison and I've talked about this a lot that a lot of times food intolerances disappear fructose can then be, you know, consume more comfortably. What else do you see is, like, other than people, like, getting their lives back, but Any other comments on that?

Well, I do see clearing of brain fog and other things as well. So there's a number of things that seem to get better, how allergy symptoms get better in some patients, not all patients and not all patients have allergy symptoms. So It's just like the rosacea thing where, you know, not everybody with c plus rosacea, but maybe that gets better in some of these individuals. So we see a lot of very interesting odd things that that happen, and they're not just 1 offs. They're they're they're fairly routinely seen.

But remember, these bacteria create an inflammatory condition. They really heighten your immune system. And so if you have immune disease, it's possible that it could flare.

So just 2 more questions before we wrap. When if someone had a positive CTTB from IBS smart, and they have methane on a cboe breath test. Would that indicate or give you clue that it's actually they have enough hydrogen to be feeding the methane. You talked about that a little bit. I just wanted to clarify.

Yeah. So it's a little tricky, right, because I I don't routinely measure the antibodies in in nothing. So Don't quote me on the numbers even though I'm on recording here. So it's gonna be, you know, in in stone set in stone. But if I remember correctly, the antibodies to CDTV and or Vinkillin are about here in the HealthEast.

They're here the prevalence is here for IBS D. And for c, it's here. So I'm not giving numbers. You see how I did that? That was good.

That was good.

Wait. Because I can't remember the exact numbers. I remember the numbers 56 percent for the for the a CTB and biculin for IVST, but I don't remember the other 2. But there is a signal, a statistical signal for methane. But I just feel like if only 1 in 4 or 5 of mapping people are positive, you gotta spend money and in 5 people to get 1 positive.

I I feel like that's not cost effective, so I I tend to not do it. But Right. But then, again, brings up Alison's question is these methanogens and their sentrophs are different. If it's small bowel methane or it's colon colonic methane, And so if you get a bunch of klebsiella and e coli going up in the small bowel, giving fuel to the morphogens in the small bowel, maybe you can become methane positive in this scheme. But, again, these are things we need to work out and figure out.

And it's it's a it's a complicated system to figure out.

Okay. And as far as like the vaginal microbiome, do you feel like that could be impacting the small intestinal microbiome and the large intestinal microbiome due to, like, their proximity or, like, the ability for microbiome bacteria just to, like, move around your body? And that's good.

Generally speaking, the entry for vaginal orifice and the anal canal are close in proximity. So you're more likely to see stool microbes sort of migrate into that area rather than there be sort of this bugs going through the bloodstream more crossing the tissues and jumping into that area. So I I think it's more that than than the latter. So And when we have when you have Cboe, it's possible you there's more e coli around and e coli is a common contaminant, for example, in urine infections. So is that where they're coming from?

Hard to know.

I do have 1 more comment also. Thank for that. The first slide, which was talking about back in the 90s, where people were thinking that, you know, it was a disease of historical women and all of that. And I saw on the left hand side of the slide, you know, stress, trauma, things like that. There's there's a still a contingency of people who and I understand why they're thinking that, who're like, well, I got really stressed and I got Cboe.

You've talked about the military example in the past. Could you share that 1 more time for people who are just hearing it or as a reminder for the first time?

Yeah. So my good good colleague and friend Mark Riddle, doctor Mark Riddle from used to be at the research institute for the US military and Bethesda and and Silver Spring actually. And so he he act is no longer there. But what they found was that if you were in deployment, they looked at the factors in employment. Because people these people were coming back from deployment in Iraq and Afghanistan.

They were coming back with IBS. So what in deployment was the highest risk factor? Well, it turned out wasn't stressed. It wasn't whether you shot a gun, witnessed human death, or suffering, or yourself was injured, remained, or or had some kind of traumatic event. It was flu poisoning.

If you got flu poisoning in combat. So it was the first example of looking at a person going through time what they experienced and why IBS developed. And it was fukewarm and it wasn't all these stressful events. And I can tell you, in the US, in general, we're not gonna be experienced type of stress. That somebody in combat military operations might experience.

That's extreme. And so if that doesn't do it, how was it that you know, my boss got mad at me today and I'm stressed going to do it. I mean, you know, it's it's I'm not saying, you know, we need to do more studies on stress and its effect on the gut. We know stress affects the gut. We know it changes the migrating motor complex.

Does it make it worse? Yes. Is it the cause of IBS? I would argue that we have evidence that it's probably not the cause of IBS. It is a modifying factor.

Right. Okay. Just thank you so much for saying that because that gives a lot of clarity. People get in fights in the Facebook group are like, yes, it does. Right?

It's a contributing factor. And so

let me think about it just let's say your antibodies are just I mean, putting it into the perspective of what I've shown you. Maybe your antibodies are borderline. And then you got stress as an additional factor, which is reducing your cleaning waves just that much more. And then you say, oh, it's distress. But no, it's, you know, you're at your tipping point, and then you tip it over with a little bit of stress, which makes the motility worse.

So I can I can understand why people will actually feel and say that physiologically, this is what's happening? And, yes, it tips you over, but I I don't think that's the mechanism of IBS, so I think it's a cofactor.

Howard Bauchner:

And also, I think no 1 would argue with the idea that if you have IBS or Cboe and you do stress control measures, you decrease your stress, you will feel better, and, you know, all around, and your digestive symptoms may improve some. Like, you know, stress, as you say, it's a modifier. But, you know, will it cure it, that that's gonna be rare that I think that would happen, where, you know, you handle Absolutely.

This is what you know, if you're doing your favorite thing, you say you have pain in your leg and you're doing your favorite thing, You forget about the pain for a while. Let's say you're playing the piano and you just get into the zone of the piano and you forget about the pain in your leg that you have, I mean, that's distraction techniques and or mindfulness or whatever you wanna call it. Great. But it doesn't it's not changing the physiology of what's going on in your body. It's just it's trying to get you to cope, trying to get you So it's things to allow you to live your life with illness.

What we're talking about today is how to cure the illness so you don't have to do all of those things to try and live with it. So yes, there are important things to help you live with it. What? Why should you live with it?

Great question. Great question. I think we should wrap up on that. There's so much hope. We hope that you all have taken this information and will watch this recording over and over again so you can really absorb it talk to your doctors, talk to your clinicians, your practitioners, absorb the information so that you can turn this learning into your thinking.

And that you can support your medical practitioners. So if they have it, feel free to share the recording with them. They need it. And and and we have

lost auditioners who watch this, of course, too. Thank you.

You all for your commitment to ongoing learning. Yes, cheers to you. Dr. Pimentel, thank you so much for joining us. We can't wait to do it again, and we wish you gotten speed.

Thank you, Dr. C. Becker, as always fantastic questions, a great co host.

Thank you so much, Dr. Pimentel.

Great talking to you both. Always good questions.

Thank you.

Hosted by Shivan Sarna and Dr. Allison Siebecker.

Highlights from this one-hour presentation followed by 35 minutes Q&A:

Twenty new slides covering all the new research
More research validation for the #1 underlying cause of SIBO
An in-depth explanation of antibodies (CdtB and Vinculin as a root cause)
The two types of microbiomes (microtypes) and the impact of SIBO on your genes
Improved gold standard for breath testing
New methane/IMO and hydrogen sulfide insights and indicators
A must-watch for newbies and advanced SIBO patients and practitioners

Be sure to watch the Q&A where we discuss a variety of topics, including the impact of Ozempic (semaglutide) as well as the vaginal microbiome on SIBO.

Dr. Allison Siebecker and I are so honored to co-host these updates for you from Dr. Pimentel and we so appreciate his generosity with his time.

Dr. Pimentel is the top SIBO researcher in the world, making new discoveries every year. He is the person we have to thank for...

Identifying food poisoning as a primary cause of SIBO/IBS
Creating the test to diagnose SIBO/IBS from food poisoning (IBS Smart)
Identifying the bugs that are overgrown in each type of SIBO/IMO
Reclassifying methane-SIBO as IMO (intestinal methanogen overgrowth)
Pioneering treatments for SIBO, including Rifaximin, Rifaximin + Neomycin, the Elemental Diet, and Prokinetics
Creating the Cedars-Sinai low-fermentation diet
Creating the hydrogen sulfide breath test Trio Smart (which tests all 3 gases: hydrogen, methane and hydrogen sulfide)
Sequencing the small intestine microbiome
and more

🧾 SHOWNOTES

Shivan Sarna's Healing SIBO: Fix the Real Cause of IBS, Bloating, and Weight Issues in 21 Days
👉 https://sibosos.com/book

Join the SIBO Recovery Roadmap Course® here (for Patients):
👉 http://sibosos.com/sibo-recovery-roadmap

Dr. Allison Siebecker's SIBO Pro Course (for Practitioners only):
👉 http://sibosos.com/procourse

Watch our FREE videos on YouTube!
👉 https://www.youtube.com/c/SIBOSOS

Join us in the SIBO SOS®️ Facebook Group:
👉 https://www.facebook.com/groups/SIBOSOSVirtualSummit/

Support Dr. Mark Pimentel's Gut Microbiome Research
👉 https://support.cedars-sinai.edu/fundraiser/2127909

Dr. Allison Siebecker's FULLSCRIPT Dispensary
15% off 20,000+ professional-grade supplements
🛒 https://sibosos.com/fullscript

Dr. Allison Siebecker's Rupa Labs Functional Testing Library
🧪 https://sibosos.com/rupa

Trio-smart™ is the only breath test to measure all three gases: hydrogen, hydrogen sulfide, and methane. Available from Gemelli labs which you can order for yourself by filling out the questionnaire.
https://www.triosmartbreathtest.com/

The IBS Smart Test. A simple antibody blood test that is making IBS easier to accurately diagnose... and revealing the root cause behind the disorder! (You may have heard of it if you follow Dr. Mark Pimentel's groundbreaking research.
https://sibosos.com/ibs-smart-test

// ABOUT

Dr. Mark Pimentel is the top research doctor in the fields of IBS (Irritable Bowel Syndrome), SIBO (Small Intestine Bacterial Overgrowth), and other functional gut disorders. As head of the MAST-Pimentel Laboratory at Cedars-Sinai Medical Center in Los Angeles, Dr. Pimentel and his team work tirelessly to find a cure for gut motility diseases. He is the world's leading expert and researcher in the fields of IBS (Irritable Bowel Syndrome), SIBO (Small Intestine Bacterial Overgrowth), IMO (Intestinal Methanogen Overgrowth), and other functional gut disorders.

Shivan Sarna is the author of Healing SIBO, TV host, and the creator of the SIBO SOS® Summits and Community, the Digestion SOS® documentary series, the Gut & Microbiome Rescue Summit, the Lymphatic Rescue Summit, the Dental-Health Connection Summit, and Chronic Condition Research, a 501(c) 3 non-profit to further research under-funded medical conditions. After a lifetime of struggling with health issues, Shivan made it her mission to demystify her own health struggles - and to share that information with others who were struggling. Her special skill is finding and connecting with the leading expert doctors and connecting those experts with the people who need their help. Her personal mantra is SOS: Save Our Selves, and that's what she has helped thousands of people do!

Dr. Allison Siebecker is an Instructor of Advanced Gastroenterology at NUNM, an award-winning author, and the 2021 Lifetime Achievement Award recipient from the Gastroenterology Association of Naturopathic Physicians. She was the former medical director and co-founder of the SIBO Center for Digestive Health at NUNM. Dr. Siebecker has specialized exclusively in SIBO since 2011, serving as a second and third-opinion referral doctor for patients who have failed previous treatments and is the creator of many staple SIBO treatments. Dr. Siebecker is passionate about education, she has been teaching physicians, medical students, and patients internationally since 2010, with many going on to become SIBO specialists and teachers, sharing alongside her at conferences and in their own courses, websites, and books.