Listen to our 2025 webinar with Dr. Mark Pimentel of MAST at Cedars-Sinai. Dr. Pimentel discusses the newest research on SIBO, IBS and present mock case studies.

Mark Pimentel, MD, is the executive director of the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai and in collaboration with Ruchi Mathur, MD, whose work focuses on links between metabolic disease and gut microbiome, and Ali Rezaie, MD, whose innovative work in GI motility improves the wellbeing of patients, as part of the MAST team they focus on the development of drugs, diagnostic tests and devices related to conditions of the microbiome. - Pimentel Lab

Okay, I'll get started. My name is Jeffrey Roberts and I am the co founder of Tuesday Night IBS and founder of the IBS Patient Support Group and World IBS Day. I'm thrilled to welcome all of you tonight to our webinar series. Tonight we have a special guest, Dr. Mark Pimentel from Cedars Sinai in Los Angeles. Tonight's medical education webinar is supported by an educational grant from our delics and we're very grateful for their ongoing support. So let me go ahead and introduce Dr. Pimentel.

Dr. Mark Pimentel is Professor of Medicine and Gastroenterology at Geffen School of Medicine, UCLA, and Associate professor of Medicine at Cedars Sinai, Los Angeles. He's also the Executive Director of the Medically Associated Science and Technology MASS program at Cedro Sinai. As a pioneering expert and world leader in irritable bowel syndrome and SIBO, Dr. Pimentel has had his work published in the New England Journal of Medicine, Annals of Internal Medicine, American Journal of Physiology, the American Journal of Medicine, American Journal of Gastroenterology and Digestive Diseases and sciences, among others. Dr. Pimentel's role in the reimagined study at Cedars Sinai to analyze the small intestinal microbiome, including its role in sibo, has revolutionized our understanding of the small bowel. A new pediatric extension of the reimagine study, called Pre Imagine, was just announced today by Dr.

Pimentel's mass group. Dr. Pimentel's research led to the first ever blood test for IBS with IBS Smart, the only licensed and patented serologic diagnostic for IBS PIME. Dr. Pimentel has served as a principal investigator for numerous microbiome and human disease studies. He's a diplomat of the American Board of Internal Medicine, a fellow of the Royal College of Physicians and Surgeons of Canada, and a member of the American Gastroenterological association, the American College of Gastroenterology, and the American Neurogastenterology and motility society. Dr. Pimentel's latest book, the Microbiome Guide to IBS, SIBO and Low Fermentation Eating, is an essential read.

It details much of the work that Dr. Pimentel has been engaged in now and how he approaches his patients in his clinic. I've had the honor of knowing Dr. Pimentel for over 25 years, and I'm grateful that he's been a tremendous supporter of my advocacy efforts. So welcome, Dr. Pimentel.

It's a pleasure to be with you, Jeff. I mean, I'VE known you, as I said, as you said, for many things, decades. And I'm excited to be on Tuesday night. But Wednesday night.

But Wednesday night, right. It has to be a special night just for you. So the format for this evening will involve me asking Dr. Pimentel some initial questions. Then I will present some patient case studies, and Dr. Pimentel will work through these while explaining his collection of research and clinical work that he sees in his lab and clinic. So let's get started. So, Dr.

Pimentel, I've got three questions just to get started, and you can answer this any way that you like. What is modern small intestinal bacteria overgrowth, Sibo, and what causes that? Who are the super fermenters? Hydrogen, methane and hydrogen sulfide. And what does our small bowel cleaning wave have to do with sibo?

I'm thrilled you're asking question one. It means people are listening because the there is a tradition or classical Sibo, because Sibo was discovered in the 1960s and back then we didn't have proton pump inhibitors to reduce acid, and people were getting ulcers in the stomach and they had to have their stomach removed. You remove the stomach, you rearrange the bowel a little bit to make the flow of food go correctly, and then you end up with overgrowth in these blind loops and all these deranged anatomies of the humans. And those people would get malabsorption and all sorts of consequences of the rearrangement of the bowel, but also the overgrowth that developed because there was no acid and there's these blind loops. And that's classic overgrowth. What I'm talking about in terms of modern overgrowth, when I refer to it as that way, is that what we learned is that people who've never had surgery on the bowel have overgrowth. And we're finding that, of course, in irritable bowel syndrome, which I'm sure we'll get into. But the other reason I'm using the word modern is not because we're finding overgrowth in the non classical environments, like these rearranged bowels or things that we did to the patient, but because we're sequencing the gut bacteria, it's very different.

We used to think that overgrowth was, oh, it's the colon, all the colon microbes moving into the small intestine because the small intestine isn't flowing correctly. And all we're finding is two bugs, the super fermenters. Which gets me to your second question, which is who are the super fermenters. So in this modern understanding of sibo, it's three bugs, four bugs. Two main ones, hydrogen producers, are E. Coli and klebsiella. Now they're opportunists. So when the small bowel is not moving correctly and you get a buildup of fluid.

So think of it this way. Think of it like, I don't know if you ever watched these survival things up in Alaska where they drop some very fit person up in Alaska and they have to survive. They never drink from the swamp because they're going to get sick. They drink from the flowing stream. And so the same imagery can be imagined in the small bowel. If that small bowel is flowing and cleaning itself correctly, it's not very. There's not much microbes there. But as soon as their stasis, the gut isn't flowing correctly, you get a buildup of bugs because they're.

They sit there longer and they're getting fresh food. But E. Coli and klebsiella will outcompete everybody. And so they just suddenly take over and then they push everybody else down. And when I say super fermenters, when you have sibo, you can ferment carbohydrates 63 times faster, based on a study we published. 63 times faster than the person next to you who doesn't have sibo. And that's amazing because these two, the E. Coli and klebsiella, are like Ferraris at just converting sugars to gas.

And the hydrogen sulfide is the new kid on the block, which really is toxic. Toxic to your small intestine. The kinds of stuff and changes we see in the lining of the small intestine. When hydrogen sulfide is on the breath of an individual, none of the other sibo or emos compared. Hydrogen sulfide is a disaster for your intestine and causes you to have pain. Much more diarrhea because it's activating these proteins called aquaporins. Aquaporins, sorry to bring water in. And so the diarrhea is more intense.

And that leads me to question three, if you don't mind me taking all three questions in one big breath. But this all stems from your small bowel cleaning waves not working. So, you know, people talk about, and this is why I like the way you've depicted this with the gases and the leaves of the tree. This is the consequence, all these crazy microbes and sibo and modern sibo are the consequence of the cleaning waves not working. And so the root cause is the cleaning waves not working, and that's why the overgrowth occurs. So, yes, cleaning waves are really, really important to this whole process you mentioned.

So to be fair, you know, I read your book, and your. Your book is really fascinating, and it spoke about the cleaning wave. And you also spoke about eating and allowing this cleaning wave to actually occur. And so your suggestion is not for people to munch on things in between meals so that you allow time for this cleaning wave to actually occur. And I have to say, sometimes if I've been in a meeting and all of a sudden my gut makes the loudest sound from the book. I mean, it speaks about this being actually the cleaning wave. I'm kind of a little embarrassed about it because it's very loud, but it actually gave me a little bit of comfort knowing that this is actually normal. This is what everyone should expect.

Yes, it's absolutely normal. And it's, you know, you're embarrassed, but rejoice, because that cleaning wave is what's keeping the overgrowth away. So that is an absolutely beautiful wave to have happen. So I don't discourage it. I love hearing it.

So. So I think I got a lot of these causes of sibo. I don't know if you want to speak to any of them, if they make sense in terms of could these be the causes of problems either in your cleaning wave, or could it be a problem with the fact that it's creating super fermenters? What I've put around this tree? Do they make sense?

Yes. I mean, inflammation of the intestine can cause stasis. Surgeries can cause adhesions. Anatomical problems are also causing stasis. Medications like opiates, autoimmune disease. Scleroderma is an autoimmune disease that slows the gut down. So all of these are actual things that can lead to sibo.

Okay. All right, let's go on to the next slide, which is. It really is about ibs. So what I've read, and I've seen you publish as well, is. And I think it actually may be even higher, SIBO being the cause of. Of, you know, greater than 60% of people diagnosed with IBS. And I just wonder, how does this occur? And we hear a lot about the gut brain access. You do touch on it in your book, but maybe you could just speak to that.

You know, first of all, out of 60% of people who have SIBO are diagnosed with IBS, how does this work out?

So, I mean, it really comes from more than one study, but the first Study that defined this cultured the small bowel of IBS D patients in Europe and compared them to non IBS patients and found that 60% met that threshold of 10 to 3 bacteria on Maconkey agar, which is the agar you grow the bacteria on to define sibo. And so that's how that was defined. If you, if you, you want me to go on to the gut brain axis, I can go ahead and, and take that as well, but.

Yeah, no, go ahead, you know, bring it together. I'm just, I. These are really meant to be little bits of landmarks for you to know what I'm trying to share with everybody.

Well, but I think the second thing is, you know, when you talk about the 60% also, we've developed that blood test which you introduced at the beginning. And food poisoning causes ibs, and we think it's causing the SIBO by damaging the cleaning waves of the gut. And so we find that antibody in about 60% of people. So this lining up to 60% seems to be what's happening. And that's where the CDTB and Vinculin come in. You get exposed to this toxin from food poisoning, and then it leads to antibodies to vinculin, which then damage the cleaning wave of the gut, and then you get this buildup of bacteria. Now, the gut brain axis, of course, the microbes of the gut have all sorts of neurochemicals and chemicals in general that can communicate to the nerves of the gut and alert the brain that there's a problem. And so what we're seeing, especially with hydrogen sulfide, and even more so than hydrogen, is that the hydrogen sulfide activates the nerves of the gut.

We see that serotonin and other signaling pathways in our pathway analysis are really heightened when hydrogen sulfide is there. So we really think hydrogen sulfide is a neuromodulator of gut brain dysregulation, or at least alerting the brain to a lot of pain. Methanogen overgrowth is a different beast. We don't know why people build up methane. We know that food poisoning causes the diarrhea, ibs. We know that it causes it through that, that sequence of events which I've just described. But we don't know exactly why all of a sudden somebody's methane goes up and they're now constipated. We know probably that they probably get the methanogens colonizing their gut from either their family, their environment.

But then why does it go so much higher and then leading to this constipation that we haven't figured out yet.

Okay, so one thing that I've read a little bit from Brendan Spiegel's latest book about gravity in ibs, he talks about the vagus nerve. And the vagus nerve is obviously the one that's involved in likely this. You know, the gut brain axis is really the only way for these messages to go back and forth. Then I've also read latest study that showed that there's a bacteria that's producing serotonin. You mentioned serotonin. Is serotonin involved in your work as well in terms of like an overgrowth of it? I've always been fascinated by the fact that serotonin is involved in regulating the motility of the gut of the large bowel. Too much serotonin and you have diarrhea. Too little of it and you have constipation.

Right. It doesn't quite add up that way. And I think the study you're referring to showed that they saw less serotonin in dibs than in the. So there is a serotonin regulation issue, but it was kind of the opposite when they looked in humans. But there are certainly microbes in the gut that produce serotonin. We have seen that, but we haven't published or released any information about what we found in serotonin and its relationship to IBS yet. It's coming. So we're doing a lot of.

So some of the firsts that we've had, just so you understand, we're doing this systematically. We were the first really to do 16s sequencing of the microbes of the small intestine in any disease. And then we were the first to do shotgun sequencing in the small intestine in any disease, but focusing on ibs, thankfully for those who have ibs. And now we're going to be presenting at ddw. Two things we hope. One is absolute quantitative shotgun sequencing, which is a level up. That means we're not looking at whether you have E. Coli out of proportion to others, but the actual true quantity of E.

Coli and Klebsiella in sibo. And I think you're going to be shocked, but I'm going to leave it at that. And then we're also doing proteomics of the fluid in sibo and non sibo, meaning we're seeing what proteins are being excreted by the microbes. And then the next level to that will be the metabolics, things like serotonin chemicals that the bugs are producing, but that won't be at ddw. So we're systematically moving through the different levels of things the microbes produce and how that interrelates with the diseases these patients have in this reimagined study.

So, you know, related to emo and methane, you spoke at. I'm not sure it was ACG. I think it was DDW, actually, where you spoke in an investigational medication called CS6, which blocks the MTD protein. How does that work into this? And is it relevant to IBS or is it more relevant to SIBO?

So CSO 6, you know, we helped develop Rifaximan. That's very exciting. And now we've got this new thing, Rifaximax, which you might be asking about next. But. But one of the things I'm trying to move away from, if I can, if I can find. So in the case of methanogens, it's not the bug itself that's the problem. It's the methane that it's producing that's causing the slowing of the gut. So why kill it? If we can just change the metabolism of the organism with a small molecule to block its production of methane, turn the methane down and then the patients are normal.

It's not a laxative. It's just get rid of the methane and people start having normal bowel movements again. That's the thought process. And we can get 80% reduction of methane in vitro and an animal and human stool by using this CSO6. So we're very excited about this. This could be the treatment for emo. We're, you know, we have a lot of data on this already, but we have to go through about a period of a year where we have to do all the pre IND work, which the FDA requires for safety, toxicity. All the stuff that's animal work, that is stuff we can't do has to be go to professional companies that do this on behalf of the FDA before we can start dosing patients.

But we're excited to get to a. Sometime in late 26 or early 27. But this could be a cure for emo potentially, if it works out.

It is very expun. Look, I've been involved in so many medications that have gone from phase one to phase three and then advisory committees at the FDA and so forth. So I'm aware how long this actually takes and how much money it actually takes.

Oh, yeah. For sure.

To bring something to market. Let me ask you one last question about IBS. And is there any diagnosis that is just IBS and not. I mean, 60% of the people who have SIBO you know, have IBS features. But, I mean, what about the other 40%? Is IBS itself a diagnosis?

Well, now you're touching on philosophical considerations. So I guess the question is, is SIBO a diagnosis? Because SIBO is the consequence of the lack of cleaning wave, which is a consequence of the antibodies, which is a consequence. Food poisoning. So is that group, that 60% of IBS that may come from food poisoning, is it an autoimmune? Enteropathy? You could call it that. Maybe that's what we should be calling it. But I think. And Lynchiang wrote a beautiful paper recently, and another author did another paper, and there's another paper coming out that's really saying, look, we need to. To move on from symptom criteria for ibs.

IBS is not a group of symptoms. IBS is a group of disorders, some of which we can identify. And some of those patients are sibo and some of those hundred patients. So maybe 60% are SIBO. Maybe another 10 or 20% are Bile Acid Diarrhea. Maybe another 5 or 10% are gluten sensitivity. Maybe another 5 or 10 percent are EDS or eosinophilic problems or mast cell problems. And instead of thinking, you know, we're.

Instead of this, and I'm not gonna. I'm not bashing Roma, instead of the Rome criteria being the diagnostics, take the whole group and do the tests that's. That are required to break this down into what can be treated at a root level. And I think sibo is part of that root cause. If you treat sibo, they get better. If you don't know they have sibo, then they don't necessarily get better. Do you follow that?

Oh, I do. Yeah. I mean, there's. There's a tremendous number of mimickers that have come out in the last 10 years, and so many patients have been labeled with IBS based on a criteria. And I'm trying to encourage patients to go back to their physicians and have a conversation about the other. The mimickers, because they might be diagnosed with the incorrect condition or illness, and they can be treated quite differently. So I do agree. I mean, it's funny I mentioned to you before we started that I saw that picture that you're at a conference with Dr.

Talley. Nick Talley. Nick and I have spoken for years about, you know, how should we rename ibs? What is the real name that IBS should be? So I love this autoimmune enteropathy notion. And we certainly, I hope, you know, at DDW, we can get our heads together and try and think of where this could be moving and how we can name this. We've been trying to do this for literally 20 years.

Right. You know, I, you know, we, we subcategorize SIBO into emo and eso, but it's a bigger animal to wrestle with to try to change the name of IBS and it can't be one individual like myself just suddenly saying it should be called this. I think it needs to be done by scientific consensus with a group of individuals who are actually studying the different subtypes of IBS and these biomarker based approaches because, yeah, we need new names. I think so. I agree with you.

I do. Okay, let's move on to the case studies. So here's the number one 35 year old woman. Oh, I can't see my screen here.

Hold on, I see it.

Okay, you can see it. Whoops. Let me go back. Oh. A 35 year old woman has been seen multiple times by gastroenterologists, has been told that she has IBS and lactose intolerance. She explained that this seemed to start after she got food poisoning while on vacation. She complains of diarrhea, pain and bloating and gaining weight, along with feeling foggy in the head after eating and a belly that is flat in the morning. But by evening it looks like she's six months pregnant.

She's been told to live with all of this and that IBS is a chronic illness that waxes and wanes and to be less anxious about it. She's had a basic workup numerous times with blood work and stool samples looking for infection and everything is always normal. She denies using any antibiotics in several years for any reason. She does not drink or smoke and her body mass index is 20.5. She appears reasonably well with a soft belly upon examination. So I actually took this from your book, except I added to it a little bit, I made it a little more, I added some creativity to it. And what I thought in red here was what you might do, but maybe can you walk us through, you know, seeing this patient? How would you actually manage this?

So I mean, she obviously has the classic history of post infection IBS and likely has sibo. If we were to test her, you know, the, the thing that Roam ignores is bloating. So if you go back and you look at all the studies that have been done over the last decade where there was a study that was done that enrolled almost 1000 patients with IBS D and they had to meet Rome criteria. So Roam Criteria are abdominal pain and diarrhea. Let's say for the diarrhea side of things, that's it. They have to have abdominal pain, they have to have diarrhea, nothing else. And then they asked them questions. What's your most bothersome symptom? And the most bothersome symptom for them was bloating.

So they weren't selected for bloating. They were selected for pain and diarrhea, but bloating. And so the point, this case illustrates that, yes, she has pain, yes, she has diarrhea, but the prominent thing is she wakes up in the morning, and as soon as she starts eating, the bloating starts to happen. And that is very classic for small intestinal bacterial overgrowth. Now, you always have to be careful. You don't want to miss things. You don't want to miss endometriosis causing a narrowing of the small bowel, which we sometimes see, or other things. But this is a classic patient.

I would put her in a study tomorrow because she's a perfect candidate for a drug trial because she's just absolutely got the classic symptoms.

Okay, so you would basically test her with doing some breath testing.

I would do a breath test on her as a first stop.

Even if she. I'm kind of jumping the gun here. If she was positive, you would be treating her with Xifaxan.

Right. So think and, and think about it this way. If I did that, if I did a breath test and it was positive and I treated her with Xifaxan or whatever combination depends on the breath test result, and in two weeks, she has zero percent improvement. And maybe we were going to get to that, then I can move on and spend more money and maybe think about a colonoscopy or something else. Too often these young people are scoped and scoped and scoped, and it's every time normal. And they've spent $20,000 in CO pays for extraordinary testing. Crohn's will not get better on two weeks on Rifaximin. Celiac will not get better on two weeks on RifaxIMIN.

Microscopic colitis will not get better with two weeks rifaximin. So by delaying for two or three weeks just to get the breath test and to treat with rifaximin, if the patient gets better, that's what they have, you know, and you've saved that patient a lot of time and money.

And it's very refreshing, actually, to hear that you would actually begin treatment based on this, you know, story that she's saying. I mean, you would do the breath testing, which.

Yeah, so I know which combination of antibiotics to use or whatever the treatment combination is. But after that, I would proceed because, you know, if you. Yeah, you could even wait on celiac testing because the chance she has celiac is less than 1%. The chance she has SIBO is greater than is almost 60. So why waste.

That's a huge percentage.

Yeah. Why waste $300 on celiac testing when you start with this, and if they don't work, then test for celiac, then do these. And if you follow that, that process, you're going to save a lot of money for healthcare, plus this patient as well.

So Pepto bismol, you refer to that in your book. When would that be introduced?

Why would you introduce that they are hydrogen sulfide positive? Because pepto bismol inhibits hydrogen sulfide production and can kill the bacteria that are hydrogen sulfide producing. This is from a study in 1998. And then rifaximin with pepto, because you have to get rid of the bugs that produce hydrogen, and that hydrogen is used to make hydrogen sulfide as well. So you kind of have to give both rifaximin plus pex.

So pepto Bismol is always used in conjunction when you have hydrogen sulfide.

That's what I do. That's what I do. There's no randomized control trial. This is based on experience. So far, the new therapy, rifaximin with nac, has a very strong effect, for reasons we don't understand, on hydrogen sulfide, but that's not available yet. So we can't really promote that use yet, but soon.

Oops. Trying to advance my slide here. There we go. Now I'm trying to remember. Right. So basically you kind of said everything we spoke about the mimickers. That could be. We see the overlap of IBSD in this diagnosis with, I guess the microbial overgrowth would be sibo.

But you also can see food intolerances producing similar symptoms. Fructose intolerance or lactose intolerance, but not necessarily with the bloating. The bloating for you was kind of the key indicator of what might be going on. Right.

Well, that definitely suggests to me that she'd probably be positive on breath test. But I actually don't like the word mimickers because it's implying that it's not ibs. It's mimicking ibs. And so you're saying it's ibs, but it's really overgrowth. But maybe it's a subtle point, but I Sort of think of IBS as IBS, and 60% of IBS is SIBO. So rather than calling it a mimicker of IBS, but it doesn't really matter in my view. It doesn't matter, but I just personally think I call it IBS. And 60% of IBS have SIBO, so I'm going to look for it and treat it.

So that's how I sort of frame it for my patients.

Okay, let's move on. 22 year old woman is a student and has complained of constipation for three years. She passes hard stools every four days and also complains of feeling of incomplete evacuation and abdominal bloating. She has no other medical problems and takes only occasional oxidatives and PPIs, but has been told by her physiotherapist that she may have pelvic floor dysfunction. She has tried over the counter regimens intermittently without resolution of her symptoms. She complains of smelly gas that makes her embarrassed to be around other people and that using over the counter Nexium sometimes helps with that. She drinks socially and does not smoke. Her BMI is 30.

She presents with a bloated belly that is firm.

So. Well, she's 22 years old. She's having a bowel movement every four days. So she's definitely constipated. And you know, so there is a possibility she has defecation dysfunction. Yes, there is a possibility. She would need an anal rectal manometry to assess that. The problem with anal rectal manometry though, especially in young people, is if you put a balloon in my rectum, and I'm not saying me personally, but yes, me personally, maybe I'm going to be really shy about what I'm doing.

And so we do get false signals on anal rectal manometry and sometimes that ends up in a Rabb hole for the patient. But I would look for methane because that's extremely common. So three gas breath testing I would do for sure. Anal rectal manometry I would consider, but when I do anal rectal manometry before I do anal rectal manometry, I take a far more detailed history than is here. So typically somebody with constipation, sorry for, who have defecation dysfunction as a cause of constipation, they describe that they feel stool in the rectum but they can't get it out. They feel it in the rectum all the time and they can't get it out and they get a little bit out and then they feel like there's still more there. So if I have that description, I'm definitely going to do an anal rectal manometry. I can't get that from this particular, the words on this particular slide.

So I might, if they don't have that, if they never feel like they want to go to the bathroom and I do a rectal exam at the bedside and there's no stool there, they're going to breath test first because it's not the rectum that's the problem. And so that's a subtlety in this. I wouldn't necessarily do an elemental diet. That's something I would reserve only if, you know, they didn't have meth or if they had methane. And then I gave them rifaximin and neomycin and they didn't get better, the methane was persistent, then I might use an elemental diet. So elemental diets after the failure of antibiotics.

Okay. If you were, if she was positive, let's say she didn't have pelvic floor dysfunction, but you were just treating constipation, that would be rifaximin and pneumycin. That would be your standard.

If she had methane on the breath test and she was constipated? Yes, I would give her rifaximin and neomycin.

Okay, so 26 year old Japanese woman presented to her physician with abdominal distension and recurrent vomiting nine months prior to, to you seeing her. A referral note indicates that she had a four year history of reflux esophagitis that had been managed with continuous PPI treatment prescribed by her physician. However, the patient's nausea and vomiting worsened progressively over time. She completed breath testing, was told she was positive for emo. Her doctor started her on rifaximin, but she did not improve and suspects gastroparesis. Her BMI is 18.5 and she appears thin. Her belly is distended and soft.

Yeah, so the nausea and vomiting is not a sign of methane. So a certain percent of the population could have methane, but the nausea and vomiting is not a typical sign of that. So my concern, in a 26 year old person with nausea and vomiting, obviously gastroparesis is on the list, but adhesions or, I mean, I've had patients where they were a young woman where they had didn't realize they had appendicitis. They had something they went to the ER with five, six years ago and then it resolved on its own and now they have an adhesion on the, on the, in on the ilium and they're vomiting now and they have overgrowth, but it's due to this adhesion. It could be endometriosis. So a lot of different things could be at play here.

I think what's really key is, and I play this game myself because you know, you know that I read a lot of, a lot of data, I read a lot of research and I'm seeing gold standard for a lot of these things. I don't have the clinical experience that you have. And I think a lot of the people that follow you and read your books, they try and make these assumptions based on this, you know, this very basic history. And you're now pointing out all of sorts of things that could be because you're seeing them actually in clinic. And I think that's super important to have your experience and knowledge that it's not necessarily what it looks like on a piece of paper and you don't necessarily treat them easily. Just because I think they might have constipation. It sounds like there's more going on here.

Yeah, definitely more going on. This is not a simple case. And maybe she has emo, maybe she has underlying constipation, but on top of that there's something else going on. You don't have nausea and vomiting from emojis. So even Ehlers Danlos syndrome is possible in this situation where you're having this vomiting and an intolerance to food. And so there's a lot to dissect here. This would take, this is a case that would require a fair bit of investigation, especially since she's so young and nausea and vomiting is one of the worst symptoms you can have and especially for nine months like this. So we would need to get on this case quite quickly.

Even an ulcer in the pylorus. I mean, there's so many possibilities here. I'm imagining a number of things we'd need to do to get her investigated so we can get her under control fast.

Because you've clearly made your point. It's not straightforward. It looks like it might be straightforward, but it's not. Okay, here's the last case. 45 year old man has been seeing his gastenterologist after positive breath testing for hydrogen sulfide plus hydrogen plus methane. His combination of diet and constipation was last treated with rifaximin and neomycin. He's complaining that his symptoms lessen but then return after he eases up on the treatment. And his gastenterologist doesn't have any more answers.

His BMI is 22, and he looks well. So when I looked at this, I thought, well, this guy's kind of a classic back and forth diarrhea, constipation, but, you know, or what do you, how do you treat it? I mean, you don't want to give the person more diarrhea if they're having hydrogen sulfide. How do you read this?

First of all, he's 45. He needs a colonoscopy. Number one, that's the age we do colonoscopies now. I don't know how long he's had these symptoms, but if it's new onset, he needs a colonoscopy full stop. And I'm not saying you have to start with that, but that's got to be on the list. That's got to be scheduled from that first visit. I would schedule him for a colonoscopy, but you know, the fact that he has lessening of symptoms. Neomycin, rifaximin will not treat hydrogen sulfide.

So in this case, we do add Pepto Bismol to the neomycin and rifaximin I have. It's rare to see hydrogen sulfide, hydrogen and methane. I have maybe five cases like this and I use all three and that's when I get the best result. But again, you need to sort out why this is happening in this person. And you know, I might do an IBS smart on them to see if they have anti vinculin, anti cdtb. That'll give me some assistance in this case. I don't necessarily wanna use a prokinetic yet because they're still very symptomatic and all I'm gonna do is drive more diarrhea since we haven't remedied the situation and sorted out the case yet. So more information is needed here to understand.

Yeah, let's talk a little bit about the prokinetic then. Cause, I mean, I read about that in your book. When you do introduce that. But you know, what's the classic case where you would introduce a prokinetic? Is it every time or is it only for the ones that keep cycling back?

I literally see people at the mall. I know it's Los Angeles is a big city, but the west side is not as big as you think. And they say, I saw you two years ago, I'm still great. And they're not in clinic anymore. So there's probably about 20 or 30% of people we treat one time and we don't see them again. They're just doing great. I would say there's 20% of people who just nothing works, including rifaximin. But the middle group tends to relapse, and so about 60% tends to relapse at different intervals.

It could be six months, it could be nine months, it could be three months. And if you're confident that it's SIBO and nothing else, then once the SIBO is eradicated, I put them on a diet and we can talk about that later. And a prokinetic at night. So I don't care if they're diarrhea or constipated once their bowel movements are normal. I'm trying to stimulate the cleaning waves, not the colon moving. So I give it at night. That's the only thing that's happening at night is the cleaning waves. So that's the only thing the prokinetic is going to work on.

And we're able to keep the overgrowth away longer. In a study we did between Tagacerod, which is similar to procaloparide, same kind of 5HT3, 5HT4 agonist, it prevented the recurrence of overgrowth by up to almost 3/4 to almost a year. And so prokinetics really do prevent the relapse. And so I might use it in that situation.

You mentioned also using erythromycin as a prokinetic.

Yes.

How do you decide whether you're going to use erythromycin versus procalopride?

You know, I'm tending to use more procaloparide now. More because it's a more guaranteed success. Erythromycin is pretty safe. It's a very tiny dose of erythromycin. We'd use a quarter tablet of a 250. So it's about 67 milligrams of erythromycin. So. Tiny amount.

And that's. Sorry, I just had a pop up. That's something we do used to do more often. But Prucalopride's so available and so effective that we tend to use more Prucalopride.

Yeah. So everyone seems to be shying away from Ticazerod. It's not really even marketed anymore. I don't know if anybody has access to it.

No, we used to get it from Mexico and Canada and other sources when it was not available here, but that's not the case anymore. So it's not available.

Okay, so we're going to go on to questions now. Let me just stop that. Go back to you. Okay, so let me start with question here. And then I'LL go to the question and answer box and see what's going on there. Okay. For those with post infectious IBS and siboemo, as proven on the ibs, Smart Gymelli test and breath test and two rounds of rifaxima, minimal improvement. Are we able to just manage the ibs and eventually when vinculin antibody decreases, the symptoms, should this fade away? And they went on to say, we eat clean, low fermentation, low fodmap, avoid processed food, gluten and most dairy.

And they managed to go to high school with half an Imodium for two years now. Did you get that?

Yeah, I got it. I mean, look, people come to me and they say, I don't endorse probiotics. I don't think they work. But people come to me and say, I decided to take a probiotic, I feel better. I say, great, continue. Inevitably, two months later, they're coming back. But you've got a situation where for two years they're doing okay on Imodium, they're waiting to see if the antiven goes down, so be it. No problem.

I have no problem with that. If they're fully or relatively asymptomatic, I sort of have. And this is sort of funny because when I say this on stage, my colleagues, you know, Bill, Che and the others kind of look at me like, are you kidding me? But because you never want to, you know, they say you want to set expectations. This is a traditional comment that doctors make. Set expectations because you don't want to set an expectation, and then it's not realized, and then the patient's disappointed. And so I say, one of the first things I say to my patients is, if you're willing to go with me, my goal is 80% better. I want you 80% or greater better. And my colleagues look at me, you're crazy.

Don't tell the patient that you're never going to achieve that. But we do. I mean, we do quite often, and not everybody, but I said, I'm going to damn well try. And I want to get you 80% better. And so if you can get 80% better with Imodium and stick it out, go for it. But what I could tell you about the antivenculate antibody is two years, four years, we're not seeing it go down fast enough. It's taking a lot longer than that. So this is a long haul.

The good news is we're trying to develop a drug to get that antibody out of the bloodstream, which we think will then Remedy ibs that could be three, four, five years away or never come if we don't succeed. So it's a ways off yet, but we're working on it. That would be ideal. We wouldn't need rifaximin anymore. We wouldn't need a lot of these things, but that's pie in the sky. It's a long shot and it's going to be a few years away. Yes. If we can get the antibodies down, we think it's going to work.

Can we get the antibodies down is the problem.

Okay, let me go on to the next one and you can open the box as well and see this one. My teen daughter was recently diagnosed with emo. Her primary symptom is long standing chronic constipation and bloating. Her methane peaked at 13 during a three hour loculose breath test. The peak occurred in the large intestine. She completed two weeks of rifaximin and neomycin, then began a low fodmap diet and 2mg of rucalopride at bedtime. She now reports decreased bloating and increased appetite, but constipation is only minimally improved. She also has a 6 millimeter gallstone and is in Levoxyl and cytomel for Hashimoto's.

Would you advise a follow up breath test or another round of antibiotics? Also curious if the gallstone could be a contributing factor to slow motility in sibo.

So we've not seen an association. I think the question isn't that the slow intestine is causing the gallstone because it's slowing the gallbladder down too. We haven't seen that association but we haven't like gone after it and looked at it very carefully. We do see an association and this has just been published by one of my colleagues, Dr. Mathur, where if you have autoimmune thyroid disease, your chance of developing sibo goes up. And we believe that that's an autoimmune disease and so is anti vinculin. So there may be a relationship between autoimmune diseases. There.

A methane peak of 13 is pretty low, but it is absolutely positive. So we have to say that that's true. You, you might want to consider like I would in this case do another breath test if they're only minimally improved with the constipation just to make sure that the methane's down. I don't use low fodmap. I think it's too restrictive. I think it's relatively unhealthy. This is a teen, so they need all the nutrition they can get and low fodmap can be a little bit restrictive. 2mg of procaloparide is a hefty dose if all else fails.

What I might do in this situation, if this person was in my clinic, I might change that 2 milligrams of procaloparide to the morning, interestingly, because it would cause more effect on constipation just to nudge the bowel movements a bit more. But I would try these things in stages, so I hope that is sort of tells you how I would approach this.

It's funny, not related to that, but I asked you quite some years ago, just an off the cuff question is talking about Linzess actually. And patients want to know whether they should be taking it in the evening or in the morning and could it be harming or working better if they take it at a certain time. And I think at the time you came back saying that taking it in the morning. And so what I heard you say here with procalopride though is prokinetic. It's different than something that's just managing constipation. Why would you take something in the morning or in the evening?

Well, I think, you know, in the case of methane, so as I sort of alluded to earlier and maybe it sort of slipped through the cracks because it's a, it's a subtle thing. When you take a prokinetic, you are acting on the motility events of right this moment. So when you're not eating and it's nighttime, the only motility events occurring right now are cleaning waves. So you're going to augment the frequency of the cleaning waves, which is a good thing for preventing overgrowth. If you take it with breakfast, you're augmenting the postprandial colon contractions. So in addition to the meal digestion processes. So everything that's happening with the meal, including the colon moving, is going to be sort of juiced up. And so if you want to have a bigger bowel movement, you take it in the morning with your breakfast and you're going to get a better influence on bowel movements.

That may be what a person like this needs. But, you know, we have to, you know, we do it in little incremental steps to try this, try that, to see if we can get to that 80%. And you know, but first of all, if the methane's gone great, then play with the prucalopride. Timing is what I would do in my Clinic.

Okay. I'm going to ask you about. There's a device now that's on the market. There's one that's been out for a number of years. Doing your own breath, doing your own breath analysis, and it's tied to fodmap. And somebody's asking, is this a good tool to retest for sibo? Methane and lactose fructose, inulin and sorbitol intolerance. Are you aware of using these devices? I don't want to mention a brand.

Yeah, I don't want to mention a brand either. I don't. I don't. I don't recommend these devices to. To my patients. It's not that I don't like them. I. I don't necessarily.

The problem with doing it free range is that if you eat and then you start measuring your breath, it. It really drives you crazy a little bit in a sense that, like, for example, something you ate today could affect the hydrogen coming on your breath test two days from now. Because let's say you ate beans today. Those beans are fermenting and fermenting and fermenting. And the bacteria levels in your gut are going higher and higher and higher. And then you do a sample of breath maybe tomorrow evening. And all of a sudden your hydrogen is really high. And you said, well, my supper was bad.

I can't eat pasta anymore because you just ate pasta. But it wasn't the pasta. It was the beans from yesterday. And then you start doing all sorts of crazy things with your diet. Because patients always equate the symptoms they have right now to what they last ate. They can't think back two or three days because it doesn't make sense logically, but that's the reality. And so it can really be frustrating when you're measuring things that frequently.

Well, some say that patients can become very consumed by these measurements, and you really have to keep a diary and understand it. You don't want to be handed a diary of one week's worth of food, but you'd like somebody to at least explain how they're eating and what they're eating on a daily basis. Understand it. But I know that some patients will bring a binder into a meeting, and it becomes pretty overwhelming. Somebody asked a question actually from Argentina. Is there any evidence for using Omega 3s to treat SIBO?

I don't know of any evidence for omega 3s to treat SIBO. I do know that there are some herbal preparations that have been described, even one that had similar effectiveness as rifaximin. Predominantly using berberine, among other things. So there are some herbal options, but the challenge is you have to know how to use these things. Berberine can be liver or hepatotoxic. Even our naturopath colleagues in Oregon that I've given many talks to are very cautious of dosing berberine for that reason. So if you don't know what you're doing, be careful. So that's one thing.

But we do see allicin, for example, which is Alimed, is a branded product. I don't want to endorse a branded product, but it's just one that I use in my practice. But allicin is a chemical extract from garlic. It can reduce methane, for example, but usually in about a month it goes away, it stops working. So I don't know if the bugs get used to it or what's happening with that, but I haven't done any research with it. It's only clinical experience, honestly.

You've literally been doing this for 25 years and there's so much. I mean, you've just touched the surface and yet you've uncovered so much. There's just so much more to do. It's absolutely going to outlive us in terms of where this is going. However, it's absolutely fascinating how involved this is and how complicated the processes that are involved. Um, it's just not easy to say somebody has sibo. You need to under truly understand what that means and what's their overload and how are you treating it.

Nothing's ever, nothing in medicine is truly ever simple, right? Even think about H. Pylori. So H. Pylori causes ulcers, but so many people have H. Pylori never have an ulcer, so there's that. And then people said, well, let's get rid of H. Pylori no matter what, because it could be associated with stomach cancer. You get rid of H.

Pylori acid and the stomach goes up. All of a sudden you have acid reflux. Acid reflux causes esophageal cancer. So does getting rid of H. Pylori then lead to an increased risk of esophageal cancer? So again, one question leads to another question leads to another question. So I don't dislike methanogens or methane producing organisms. I don't dislike them at all. I think they're supposed to be there, but I think they're supposed to be there at this level, not at this level.

So we have to understand their purpose. I don't think. And I used to say This a lot. I, I don't like the term good and bad bacteria. I don't like the word probiotic because pro means it's really good. You want the right bacteria in the right place in the right amount. And I think they're not bad or E. Coli's bad in your bloodstream, but there's some in your gut, and that's okay, but it shouldn't be too high, you know what I'm saying? And I think that's the confusion.

And we don't want to just apocalypse everything.

Okay, I'm just gonna. Somebody wants to elaborate on the prokinetic of using procalopride for both emo and SIBO and ISO patients, especially dosing, which is patient dependent. But some general guidelines that they can talk to their doctor about, you know, how much should they be used and what kind of doses should be used. And also different antibiotics that could be used when the standard ones don't work. Does that happen actually when, you know, rifoximin doesn't work? And then what do you, what do you go to?

Well, I, I, I have a long cautionary tale. Not a cautionary tale in that people were, were harmed. But what I, what I'm saying is that neomycin was where we started, and people would take neomycin and get dramatically better, and they would be like, oh, this is fantastic. But then they'd relapse, and I could never use neomycin again. They got resistant to it. The bugs got resistant to it. When it's given alone, funny story. If you give it Ruth, rifaximin, they don't get resistant to neomycin, and there's a mechanism for that, but by itself.

So I really shy away from general antibiotics for Sibo. I use rifaximin, and if that doesn't work, I will use an elemental diet because I'm not gonna just shuffle through ciprofloxacin, metronidazole, and some of the augmentin or ampicillin, clavulinate, and keep funneling through different antibiotics. I haven't done that in years. Because we have the option of elemental, which is sort of the best thing we have.

One thing, actually we didn't talk about was your diet protocol. I mean, this might be a good segue to talk about that. You do mention it in your book. You don't like the fodmap diet because it is very restrictive. You have a modified diet. You mention some foods. You do mention the elemental diet as well. Can you, you know, 32nd.

What's your diet protocol and when is it introduced? Is it introduced for both hydrogen sulfide overgrowth as well as the emo people?

Yeah. So the diet was, again, I'm. I'm all patient centered in my approach, and that is I want my patients to be able to go to a restaurant, pick something on the menu, and not have to ask any questions because that's the embarrassing person who's embarrassed at the table, has to ask 10 questions while everybody else just orders the burger. And they have to ask, well, is there a butter? Are you cooked with butter? And all this kind of stuff? So we came up with this diet long before fodmap. And it's basically, you can't have too much fiber, no non absorbed sugar, so there's really red lights. And no cruciferous vegetables or beans, any root or fruit. Vegetables are fine. No apples, pears, bananas, because that's constipating and also has a lot more fructose in it.

And all the other fruits are fine. So it's more complex than. Slightly more complex than that. But the opportunities for eating are wider open, and the opportunities for not getting malnutrition are wider open, and patients tolerate it really well. Most of my patients find it so much easier than lofodmap. And so I use it in all three types.

Oh, okay. All three types. Interesting. Okay, let me go on to the next question. This is technical only. You could probably answer this. Are biofilm disruptors important or helpful prior to antibiotic treatment for sibo?

So the next generation of rifaximin, we're. We're working on right now. The study starts in January. January 1st, I think. Well, January 2nd would be our first patient, probably. It's combining rifaximin with NAC in a specific way so that the NAC can break the mucus. Maybe you call it the biofilm. You can call it that.

And then the rifaximin can actually get the Ferraris who are hiding in the biofilm. We're pretty confident, based on the animal randomized trial we did, that we're gonna get a better effect than rifaximin alone. But if we get all the E. Coli and Klebsiella, will we have a longer durability? That's what I'm excited about because we're getting it down to the bare bones level. And then the microbiome can recover nicely. And maybe instead of lasting three months, it'll last six months. Maybe it'll last a year. Maybe it's more permanent.

We're super excited about Seeing what that study shows.

Okay, this person, and we haven't actually spoken about this overflow diarrhea with. They're calling it ibs C. I can call it constipation. So they have overflow diarrhea. How would you treat this? They've had it for 25 years and it's got worse as they aged and nothing seems to work. So maybe you can talk a little bit about overflow diarrhea for people who don't know what that is.

Yeah. So overflow diarrhea is when there's so much stool in that rectum and it's so hard that nothing can get past it except for liquid. I don't make that diagnosis often. I reserve it mostly for people in nursing homes where they're lying on the bed and they can't move and get to a toilet and they just get so clogged that it's too hard for them. So I don't like to use the word overflow too often in normal aged people.

Oh, okay. So what do you call it?

Well, when they overflow, but I don't know that it's overflowing. I think it's just alternating.

Oh, you call it alternating more so.

I call it alternating.

Oh, interesting. Okay, so the way that I've read it is that it's a liquid stool that's passing around this large clump of. Not an impaction necessarily, but you've got a large mass that's not moving or it's moving extremely slowly. And you call that alternating. Oh, that's very interesting.

Yeah.

Okay, let's go to one last question here. High fiber diets are now often recommended for best general health. High fiber typically results in having severe diarrhea. Are there any books that you could recommend how to deal with this condition? And you just answered that saying that you don't really recommend fiber.

I don't recommend. I don't say low fiber. I don't say. I don't say no fiber. I just say not high fiber. High fiber is just going to cause more bloating. It's like fish food for the microbes.

I'm sorry. You know, I will ask you one last one because this one is near and dear to me. It's C. Diff. I've had C. Diff twice. My daughter had it four times before she had FMT. And this person asked.

They contracted C. Diff in 2015. Their doctors could not eradicate it even with fecal transplants. They just left her on oral vancomycin for over a Decade and they're really, really quite ill. Is this something that Cedars, you know, seize because they're just relapsing on C. Diff? Do you see this in clinic?

I don't treat C. Diff in clinic. Not, not that I don't know how. It's just we have some experts here at Cedars that do treat C. Diff. Fecal transplant and other mechanisms of treating C. Diff. We don't see C.

Diff coming from rifaximin because rifaximin can kill C. Diff also. So we don't see a lot of our IBS patients getting C. Diff in the last year. I can't even count on one hand the cases of C. Diff I've seen. It's just not been happening.

So. Wow, that's, that's incredible because I remember when we first, when rifaximin first came, was being marketed. The, the, all of the studies showed it was incredible profile the drug. Really. You didn't never saw C Diff really in any of your clinical studies.

And now there was one case in the clinical trials, but it was a patient who took another antibiotic for some cold or flu or something else.

So now you have a track record of 15 years or so, plus the fact that rifaximin is being now used for some cases of C. Diff.

Yep. Yeah, exactly.

That's very interesting. Okay, I'm going to leave it there. I want to thank you for the discussion tonight because it was great. It was not your typical and you were on your A game and I'm sure you heard a lot of the same stuff, but hopefully there was some new things for some of the people that like to follow you. So thank you for that. I want to remind everybody that next week we'll be sending an email with a link to tonight's recording. We want to thank everybody for actually joining us tonight and we hope to see you on December 2nd for our next Tuesday night IBS webinar. So goodnight everyone and thank you and a very happy Thanksgiving to you all.

Thanks, Jeff. Take care.