Breakthroughs in SIBO & IBS Research - Insights from Dr. Mark Pimentel

Live from the Lab! Watch this webinar replay (or read the transcript) and hear Dr. Mark Pimentel, Director of the MAST Program at Cedars-Sinai, share his SIBO & IBS expertise on topics including:

🔬 New Research – Key learnings from the May 2025 DDW Conference about SIBO, IBS, and the gut microbiome.

📊 Smarter Tests – Understanding breath tests, blood tests, and what your results really mean for treatment decisions

💊 Smarter Treatments – Discover what's working, especially for stubborn cases that don't respond to standard approaches.

❓ Live Q&A - Dr. Pimentel answered numerous intriguing questions about SIBO and IBS submitted by viewers.

About Mark Pimentel, MD:

🔬 Dr. Mark Pimentel is a renowned gastroenterologist and researcher, serving as the Executive Director of the Medically Associated Science and Technology (MAST) program at Cedars-Sinai. He is widely recognized for his pioneering work on IBS and SIBO, having published over 150 scientific papers and authored two books on the subjects. Dr. Pimentel's research has led to significant advancements in understanding the relationship between gut microbiome and gastrointestinal disorders, resulting in the development of new diagnostic tests and treatment approaches.

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Read the Full Webinar Transcript

Paige with Gemelli Biotech:

Thank you for joining us this evening. My name is Paige, and I'm with Gemelli Biotech. We are the makers of the at-home GI tests like Trio-Smart and IBS-Smart. We are thrilled to have you here, and hope that this conversation tonight brings you and provides you with some valuable insight on your own gut health journey.

It is an honor to introduce Dr. Pimentel. Thank you for being here tonight. He is an internationally-recognized leader in the field of gastroenterology and microbiome research. Dr. Pimentel is the executive director of the Medically-Associated Science and Technology program, or the MAST program at Cedars-Sinai, and one of the foremost experts in SIBO, IMO, ISO, and IBS.

His groundbreaking research has revolutionized how we diagnose and treat these complex conditions, paving the way for more effective and successful patient outcomes. Tonight, Dr. Pimentel will begin with a short presentation covering the latest updates directly from this month's DDW. And afterward, he will answer some of the pre-submitted questions, and then some live chat questions that come in.

We encourage you to submit your questions throughout the webinar in the chat, and look for some helpful links that are already in the chat as well. We had hundreds of questions submitted, and while we won't get through all of them, we will try to get to as many as possible. So, without further ado, Dr. Pimentel, the floor is yours.

Dr. Mark Pimentel:

Thank you so much. Wow, so exciting to see so many people on this call, as well over 400, and people still coming in. So, make sure they get in the room. Thank you so much for coming out here. I really, really appreciate it, and I'm here to try to answer your questions and help you from a long distance.

We can't see everybody in the United States and around the world here at Cedars, because it's just overwhelmingly busy to be able to accommodate. So, anything I can do to help, I'm delighted to be here to answer your questions as best as I can.

I do have some amazing questions. Actually, some of the best questions I've ever seen for this topic, in what I was given, or were provided in advance. In those questions they are indicated as there's a first name on those questions. So, you might hear your name, and I'll call your name, first name only, so that I don't give away too much information, and then maybe your question.

But I'm going to start with some slides. And some of the slides are going to answer a lot of the questions in here, because we have new data, and that's always very exciting.

So, I know most of you, at least from the questions, seem to be very adept in this topic, or at least have some experience in this topic. So, if you don't have any experience in this topic, don't worry. I will try to explain things at least as much as I can, at a level that you can try to catch up.

But we're talking about irritable bowel syndrome, which is the most common disorder in humans. It affects up to 1 billion people worldwide, 45 million people in the United States. So, I know we're supposed to be talking about SIBO, not IBS. But IBS is SIBO. So, SIBO is accounting for about 60% of IBS. So, if you took 100 IBS patients, 60% of them might have this condition we're going to address today.

Now, SIBO can be caused by other things. Anything that causes the gut to slow down. Narcotics. You have had previous surgery, and there's an adhesion and the gut is slow. All those things can lead to SIBO, as well. So it all applies in that context.

But one thing we've had a problem with, with IBS over the decades, is like many diseases, when you don't understand it, you attribute it to stress. Stress caused this man's heart attack. This is an article from the New York Times in 1972. He was president of the company. His doctor told him he had too much adrenaline, and that's why he had the heart attack.

It wasn't the adrenaline, it was the fact that this president of the company was eating at steakhouses every night, drinking, smoking, and probably had high cholesterol, among other things, due to his lifestyle, not due to stress. And so, we often attribute it to stress. And the worst thing I've seen is attributing it as a women's disease, or that women and anxiety go together, and that's what's causing IBS.

Those kinds of notions are not gone, believe it or not, but are shamefully still there. I'm going to describe a different story, which is that this is a microbiome problem, and stress can modify it, yes, but it's not the cause.

The other problem we have in IBS, which is why it took so long, it's a disease that affects a billion people. There is no lack of people to study, it's a lack of funding. This is inflammatory bowel disease on the left. A study over a 10-year period, IBD research received $250 million for only two or three million people in the United States who have the disease. IBS received about 10 to 15 million in the same period of time.

So, part of the reason is, if you have a disease that's maybe caused by stress, you don't really know what's going on, there's really nothing to fund, because you don't really know what's going on. But another part of it is, we need more funding for IBS. It is the most expensive disease, because of this huge population.

But, let's move on. We want to find root causes of IBS. We don't want to just say you have IBS. We've got to find root causes in SIBO, ISO, and IMO, which we're going to spend a lot of time on, are really probably accounting for 60% of IBS.

So what I want to start with is, this is the root, root cause. What I mean by root, root is, you were fine until... I was fine until in college I went to Club Med in the Caribbean. I got a bad infection from food. And ever since then, my bowels have never been the same. Post-infection IBS is what we're going to talk about.

Well, we know a lot about this. We know for a fact, that if you get food poisoning, if 100 people are food-poisoned, 14.5%, one in every seven people, will develop irritable bowel syndrome as a result of that food poisoning.

This is a really interesting study. So these are people who went to Iraq or Afghanistan during the 2000s for the war in the Middle East. And what they found was, it wasn't that you had stress. Again, stress is not the cause. Look at the kind of stress these people experienced in war. That was not the factor. It was, did they get food poisoning when they were deployed? That's the cause of IBS. That's what starts the whole process.

And we know that Campylobacter, focus on the graph on the right. There's not enough studies on parasites. It looks like it's the most, but there's only two studies out of the 49 on the previous screen. Campylobacter is the big culprit. It is the highest rate of IBS. So we know, and I'm skipping a lot of steps, because we only have 15 or 20 minutes, because the issue always is, "Answer our questions." So I want to spend a lot of time answering questions.

But we know what's going on with food poisoning. It's a toxin in food poisoning called cytolethal distending toxin, or CdtB. And then you form antibodies to the CdtB. But one of the parts of CdtB looks like you, human vinculin. And this protein is really important in the nerve connections of the gut. And so, when you get these antibodies to human vinculin, the nerves disconnect, the gut slows, you get bacterial buildup. And we'll talk about the bacterial buildup later.

But this resulted in the development of the IBS-Smart test, which Gemelli also has. This is the most accurate test for diagnosing IBS ever developed, because the post-test probability of having IBS if both markers are positive, the antibody to the toxin and the antibody to the vinculin, 98% chance you have IBS. Medical certainty is 80%. Nothing else has come close.

So, the way I use the IBS-Smart test is if I have a patient with chronic diarrhea, I do the test. Why do I do the test in all these patients? Because I want to know why. What's the root? The root of everything. Because when these antibodies are positive, they will predict your response to antibiotics. They will predict the ability of us to keep the patient in remission, or the person in remission.

And they will predict that if you travel, you're more likely to get food poisoning and worsen your IBS, and worsen the antibodies, and mean that you'll be harder to treat. I've seen that again and again in our clinic. So knowing if you have these antibodies really dictates how you live your life, really, and how I treat my patients at least. So we do this in all patients with any form of chronic diarrhea, such as the IBS with diarrhea.

But it's more important than that. And so, people have been asking me, and there are questions in here, "Well, what about the treatment for the antibody? Can we get the antibodies away?" Well, this is one of the studies I've been talking about that we haven't been able to talk about. We presented it at the DDW meeting, but it's actually in press, in Digestive Diseases and Sciences, the journal. So it's out there, public now.

If you lower these antibodies, you lower IBS symptoms. They normalize. So, three-quarters of people who were able to take those abnormal antibodies and make them normal, their symptoms either went away, or were dramatically reduced. If you didn't normalize the antibodies, your symptoms did not improve. And what we're working on right now is a drug to push those antibodies down, and we're told in about eight months we should have the first therapy that we could use at least to test in animals.

And so, this is a very exciting time, because this is the root, root. But until then, we have to treat the bacteria that are going abnormal, and that's what we're going to focus on in the second part of my brief talk.

So there are three gases, hydrogen, methane, and hydrogen sulfide, that are important to bacterial overgrowth. Breath testing is important in IBS, because it's more often abnormal. Remember, there are three gases, not two. A lot of breath tests only have hydrogen and methane. Hydrogen sulfide is probably now realized to be the most important gas, and I'll show you why.

Because hydrogen sulfide is associated with diarrhea, methane is associated with constipation, and the hydrogen producing bacteria on the left are producing the hydrogen which is the fuel to make the other two gases.

We know in IBS, if you're constipated, you have methane. That's the red line. If you're diarrhea, you don't. That's the blue line. You don't have methane. It's usually black and white like that. But I do see questions where it's gray, and we'll try to address those.

Hydrogen is high if you’re diarrhea, the blue line versus the red line, where you're methane. Hydrogen sulfide is high if you have diarrhea, as well. But the story is more complicated. Sorry about that. Now, taking the breath test further, this is really important. The Trio-Smart breath test is the most validated breath test ever in history. This is part of the reason why.

The last three slides are important, but when we measure methane on the breath, and on the same day we look at the small intestine, the amount of the methane producers in the gut correlate with the methane on this breath test, this Trio-Smart breath test. So, this breath test is validated against the true microbiome in the most advanced way possible.

It's also validated that if you have hydrogen sulfide elevated on your breath, that hydrogen sulfide, those producers are elevated in your small intestine. So, the gases and the bugs are in the small intestine. And that's really important.

So we boil down to three different subtypes. The intestinal sulfide overproduction, which is the new kid on the block. And we know the bacteria that are important there. For SIBO, it's E. Coli and Klebsiella. Those are the two organisms that are causing regular SIBO, which produces hydrogen. And the number one organism for methane, and it's really mostly only one, it's Methanobrevibacter smithii, which is present both in the small intestine and the colon.

I'm going to barrage you with lots of details, but I'm not going to get too deep into it. We presented at DDW some very complicated understandings, because small intestinal overgrowth, and particular hydrogen sulfide is so dramatic in effect on you, it affects the cells of your gut in such a dramatic way. I'm going to summarize it, but this is some of the complicated stuff we presented, but I'll give you a more concise summary in a minute.

This is humans. If you have hydrogen sulfide in the small intestine and these organisms in your gut, and the hydrogen sulfide on your breath, so many things, genes of interest, have changed in the cells of your gut. If we take these bugs that produce this hydrogen sulfide and put it into animals, we see the same very dramatic changes.

And so, it's like this. It's changing the engines of your gut cells, the mitochondria. It's changing oxidation, or oxidative stress in your gut. It's changing, your fluid shifts in the cells, meaning you get more diarrhea, or less diarrhea, depending upon what your situation is. It's changing nociception, meaning pain. And it's changing motility factors, meaning the movements of the gut. But if you take E. coli BL21, which doesn't produce hydrogen sulfide, that's not happening. It's the hydrogen sulfide.

Some of the questions in these questions and answers are covered in these next three slides. "Does a breath test in an office work as well as the Trio-Smart sent to a home?" And the answer is, Trio-Smart sent to a home works perfectly. Methane is associated with constipation. The higher the methane, the more severe the constipation. Hydrogen sulfide on the at-home test correlates with diarrhea. The higher or more severe the diarrhea, the higher the hydrogen sulfide.

This is an AI model, but what it's showing is that hydrogen sulfide drives the most severe symptoms. If you're methane, and you have hydrogen sulfide, more than likely you'll have diarrhea, because hydrogen sulfide is pushing that towards diarrhea. More pain, more overall severity, if hydrogen sulfide is part of the picture.

There's a question about lactulose versus glucose. Lactulose is better. It detects more patients who could benefit from antibiotics. If you're negative on a glucose breath test, you have more severe diarrhea than somebody who is negative on lactulose. I know it's a double negative. It's hard to understand.

But basically, glucose is missing sick people. Lactulose is missing less people who are sick. And so, that's really important. Glucose misses SIBO. It doesn't miss methane as much, or sulfide, but it does miss hydrogen.

So how do we benefit patients? We know Rifaximin works. This is a meta-analysis, not of Rifaximin for IBS, but of Rifaximin for SIBO. 32 studies. Rifaximin can help plain SIBO, hydrogen SIBO.

But I want to just spend just one minute on this, because we have a lot of drugs for IBS specifically. But this is the number needed to harm. How many people you have to treat before somebody says, "I can't take this drug. It's hurting me." Look at tricyclics. This is a drug. These are antidepressants that have been used for decades to treat IBS as either a stress, or using the side effects of tricyclics.

People stop this drug more often than almost anything else we have, and it's not even FDA-approved. So, the worst drug for harm is the drug that's not even FDA-approved and used off-label. And so, I hardly ever use tricyclics.

But if you have methane, we use neomycin and Rifaximin. And this has been shown in this randomized control trial to be the most effective therapy for methane so far. Hydrogen sulfide, we add bismuth because of this study, and we add that to Rifaximin.

There's a new Elemental diet we presented at DDW, and sure enough, it got published at exactly the same time. So, this is now a published paper showing the Elemental diet, a new Elemental diet that tastes like tropical vanilla, as opposed to battery acid. It tastes good, and you can actually get through the two weeks.

It gets rid of methane. Almost all patients with SIBO will eradicate with one course of this. Of course, the question is, "Can it come back?" And the answer is yes. But we're studying how quickly after an Elemental diet.

I know you've been waiting for this, so I am going to present some of this. This was the oral plenary session that I did on the new combination of Rifaximin with N-acetylcysteine. I'm not going to give you the full description because we don't have time. But the characters, the characters that produce hydrogen and hydrogen sulfide, love to live in mucus.

Rifaximin cannot get into the mucus, which is probably why Rifaximin works for some people, maybe not completely, maybe not in everybody. But if you dissolve the mucus, Rifaximin gets them all, and I will show you data on this.

In this study with humans, we gave Rifaximin the usual dose that's FDA-approved, and then low-dose Rifaximin, with this N-acetylcysteine to break the mucus. And this is regular Rifaximin. Small study. So, a couple things were statistically significant.

And this is Rifaximin with NAC. Look how many different things are statistically improved. It's working better. In a head-to-head, it's working better. This is a small study. You don't need 3,000 patients to see this difference. All we needed was 45 patients. And you already see that the Rifaximin with NAC beats what we have right now.

It starts to beat in abdominal pain, but we need a larger N for this. But it does this by getting rid of hydrogen sulfide. Again, emphasizing the point that hydrogen sulfide is going to be the key to unlocking the improvements that we want to see for patients.

And then it reduced, better than regular Rifaximin, the four horsemen of the apocalypse of IBS and SIBO, E. coli, Klebsiella, Desulfovibrio and Fusobacterium. So that combination in this new capsule with this combination, which we're just about to start the phase two large-scale study, really is going to be the next thing, I think, for IBS.

And then people were excited, "What are you going to do for methane? My methane is not going away." It's a hard one. We have a new drug, finally. This drug, CS-06, it's a codename right now. It reduces methane in most instances by 70%. That's enough to get most people into the normal range.

And in an animal model, and this is the most important part of this study, the animals were constipated. They got less constipated with the drug. The animals had methane. The animals that got less constipated, their methane was reduced. And so, this is really exciting, and we're leading to human trials coming up next year. So, stay tuned. Finally, I can tell you we have the drugs. We just need the time and the resources to move this forward.

So, this is the treatment. Rifaximin with Pepto-Bismol for intestinal sulfide overproduction. The new Elemental diet is very useful for the intestinal sulfide overproduction as well. SIBO, you've got Rifaximin and the Elemental diet. And for methane, it's Rifaximin and Neomycin. Rifaximin plus Metronidazole is all I use, and that Elemental diet as well. But in the future treatments, we've got new things coming, so, stay tuned.

So, this is not your grandfather's SIBO. These are very modern techniques. We now understand the exact bugs, and therefore we're able to get better treatments for patients very soon. So, I'm going to stop my presentation part there, and stop sharing, so you can see me full screen. And now I want to go to some questions. We're going to take some questions, which we got ahead of time first, and I'll call out names.

Hopefully the people who provided the questions are here. And then we'll do that for about 15 minutes. We'll take a one-minute break, and then go to the questions online, because I want to be able to give everybody a chance to get their questions answered.

I got a lot of really, really good questions this time. So, I really appreciate that. One question is, well, thank you. This was very nice. The Microbiome Connection, this is the book that we published a couple of years ago, helped Eileen. So, thank you, Eileen, for that comment. "Is there an updated low fermentation eating guide?"

So, we're doing a new book right now, and hopefully it's going to contain probably half the book will be on diet, because I think that's the most important thing for patients to be able to self-manage and prevent the need for the repeated antibiotic use.

So this is, "In the past, you mentioned you," this is... No name here, sorry. "In the past you've mentioned you've never seen someone change from SIBO to IMO." That's a tough one for this first couple of questions. "Sadly, I was only hydrogen, according to Trio-Smart before, and now I have methane. Any thoughts on what could cause this?"

So methanogens are always there, but it's true. We don't see people go from hydrogen to methane very often. I've seen one or two in 10 years. But when they do go from hydrogen to methane, they become more bloated, and different types of symptoms, usually constipation. And so, then you've got to treat the methane. There is a possibility the methane was there, but at a lower level than 10, and then just went up, depending upon different foods as well.

This is Darlene, "My doctor says, the gut brain connection is my problem regarding IBS. Please explain a little about what this is, from a scientific standpoint." Thanks, Darlene. Yeah. So remember in the older understanding of IBS, there was this, and I'll give you a little history lesson, it was called the brain-gut axis. The brain was the problem for IBS, and then the gut was badly reacting.

Well, I think as we started to learn things, we then realized, no, the gut's the problem, but the brain's also affected. So then the term changed to gut-brain axis. And then microbiome became popular. So, they said, well, what about the brain-gut-microbiome axis? Or the gut-brain, the gut-microbiome-brain axis, et cetera, et cetera. So, it's become convoluted.

Let me just say it another way. If you break your arm, your brain feels pain. Your brain's not the problem. The arm's broken, not the brain. If the arm doesn't heal, the brain continues to feel the pain, and will try to adapt, but it doesn't mean the brain is the problem.

And so, I think what happens is, we end up treating a lot of patients with a lot of psychiatric drugs, and sometimes they're combining these psychiatric drugs to alleviate IBS. There is no randomized double-blind study of three psychiatric drugs versus placebo for patients. And often we end up taking patients off these medications here in our center.

And so, it's a complicated story. There are people who stubbornly believe that IBS is still mostly a brain disorder. I'm sorry if you feel that your doctor is feeling that way, and you don't feel that way. You need to find somebody who does understand the microbiome a bit better, I think.

Mary, "What is the difference between lactulose and glucose? How do I know if I should use lactulose or glucose with my Trio-Smart test?" If you have a Trio-Smart test, and the primary problem is methane, it doesn't matter. Glucose, lactulose, they work just as well. The problem is, glucose misses many patients who have hydrogen, because it gets absorbed so quickly.

Let me put it another way. If you're diabetic and you get a low blood sugar because you took your insulin, too much of your insulin, the way you can make the blood sugar go up is put a glucose tab under your tongue, because you absorb glucose from your tongue, under your tongue, your cheeks, your esophagus, your stomach. I'm 6'4". I drink glucose? I don't know how much gets to the small bowel. I'm absorbing it from my mouth, my esophagus, and I'm 6'4".

The 5' person is absorbing less through their mouth, because they're shorter and smaller, so they're getting more glucose in the small bowel. So everything is kind of wacky. You don't know how much gets to the small bowel. And then you get this problem where it's a negative test and you say, "Well, but I have symptoms." Lactulose doesn't have that problem. It goes all the way through. It doesn't get absorbed by you. So the bacteria will see it, and so that's why I trust lactulose more.

Cheryl asks, "Why is testing for SIBO/IMO/ISO recommended prior to trying low-FODMAP or Elemental diet options to relieve my symptoms? Are there different treatments for each kind of SIBO?" So Cheryl, I think first of all, and this is a really, really important point. The way I practice in clinic is, I don't just want to know that you have SIBO, IMO, or ISO. I sort of want to know why.

And so, that's why the blood test is so important, because if the blood test is positive, then food poisoning is the why. Because the why can matter. Let me give you an example. You have hydrogen positive SIBO. But what if it's caused by a lump in your small intestine causing a blockage? That's important. What I'm saying is, you need to know what bugs you have before you start treating, and to have a better understanding of why.

Because if you don't respond to the therapy, then you need to take action. You need to maybe do a colonoscopy, you maybe need to do some imaging of the gut. So, how you respond to therapy is as important as what you're taking, and is as important as what gas you have. So, more than ever, I do breath testing in advance of any kind of therapy, because of hydrogen sulfide being so important as well.

So, Zach asks, "Are you close to a cure for IBS/SIBO?" We're as close to a cure as we've ever been, and I think there are facts. If I showed you the animal data, which I didn't have time for, for Rifaximin plus NAC, Rifaximin and NAC completely normalizes the stool form, and completely normalizes the microbiome. Rifaximin by itself, partially normalized.

So, for the first time, we think we can completely normalize the microbiome with this new technique. We just need to continue to do the trials and finish the story, and get it out there for patients. So, we're close. And if we can get the antibody out, then we're done. Then we have to think about some other disease to treat, because that could be the great key to improving IBS.

Frankie asked, "Is it accurate to call SIBO a disease?" Well, so this is complicated, because we're calling the disease IBS. And we're saying SIBO causes 60% of IBS. And that's okay. We're calling the disease ulcer disease, peptic ulcer disease, and we're saying H. pylori causes 60% of peptic ulcer disease. That's okay, because the ulcer is the disease, the IBS is the disease, and the cause of that is really the SIBO.

It's a little complicated in that sense, and it's the way we do things in medicine. But, yes, IBS, though, is a disease, because we found stuff. There are literally things going on. It's not a syndrome. So maybe we should change the name of IBS from Irritable Bowel Syndrome, to Irritable Bowel Disease, or use the word disease in a better way, because it legitimizes the patient's concerns and complaints.

Oh, this is a good one. Jan, thanks for this question. "Could a food poisoning event in 1997 cause SIBO in 2025?" I don't know if I understand that question exactly. If you had food poisoning in 1997, you didn't suddenly develop IBS in 2025. But if you developed IBS from 1997, you could have had SIBO all those 30 years, 20, 28 years. So, that can happen.

One of the questions that I get a lot is, "I think I've had SIBO or IBS for 20 years. Will the antibiotics work?" It doesn't matter how long you've had it, the antibiotics work. So, the duration of the symptoms. But now, the other slant of the question, which it could be what Jan is asking is, "I had food poisoning in 1997, but my SIBO started in 2025."

So what we do see with the antibody measurements, is that we see people where the antibodies go up, but they don't quite cross the line. And then they get another food poisoning, even mild, and it bumps the antibodies over the threshold, and all of a sudden, they get SIBO and IBS. So it can happen, where you have a milder second infection that pushes the antibodies over the edge. Jan, I hope I answered that question for you.

Nicole, same question. "Is SIBO a type of IBS or vice versa?" I think I answered that already, Nicole.

Here's a very important question from Marty. Hopefully you're on, Marty. "Can Ozempic or medications like it cause SIBO, or maybe IMO, because of constipation?" So, last time I answered this question on a podcast or one of these kinds of seminars, I said, "I don't know, I don't have the answer." But now I do.

At DDW, there were two presentations where they were able to take aspirates from the small bowel, and prove that there was SIBO, and SIBO was being caused by Ozempic. We suspected it, because if you slow the gut down, that's a cause of SIBO. Ozempic, GLP-1 drugs slow the gut down. You may not feel the bloating that much, because your food's not even emptying the stomach. So, you're not even delivering much food there.

But then when you stop the Ozempic, might you have SIBO? And the answer appears to be yes. And we're still trying to figure out how many people are getting SIBO from this, and will it go away when you stop the Ozempic, or will you have to be treated? And that still remains to be determined.

Mary asks, "Is there a connection between celiac and SIBO?" And there are two studies, but one in particular that was a very high quality study. So yes, there are patients with celiac who also have SIBO. So, they go on gluten-free, they feel somewhat better, but not perfect. And then, as a result of treating SIBO, they got all the way perfect. So, there are patients with celiac where there's overlapping SIBO. And if you treat both, you're going to get the best result.

This is Samantha. "I'm in perimenopause and think I might have SIBO. Is there a connection between hormone changes and SIBO, or IBS?" So, this is a very cool question, because we have a very special interest in this. Dr. Mathur here in our program is studying the relationship between menopause and changes in the microbiome.

And what's amazing is that in menopause, your microbiome is completely different from pre-menopause. If your menopause on hormone replacement therapy, your microbiome looks like a 30-year-old. So, something about the hormone replacement makes the microbiome come back to normal in the small intestine. So, that's pretty interesting.

And so, I am not saying that postmenopausal women who will have SIBO or IBS should be on hormone replacement. We haven't done that kind of a study. But what we do see is those who are have less problems with their microbiome.

I'm going to answer two or three more questions, then we'll take a one-minute just break for the folks at Gemelli to talk, and then I'll continue with the questions online.

This doesn't have a name. "I'd love to hear Dr. Pimentel talk about the impacts and symptoms of anti-vinculin antibodies on other tissues, or parts of the body beyond the enteric nervous system in the GI tract." We're doing a lot of work in this area. This antibody is important for two diseases, irritable bowel syndrome and SIBO, that nexus, and scleroderma.

Now, scleroderma, for all intents and purposes, is a slowing of the gut, because of a neuropathy of the gut. And in that disease, vinculin antibodies are there. And vinculin, which I don't talk about, that particular vinculin is on the skin of your body and the nerves of the gut. Scleroderma is a disease, autoimmune disease of the skin of the body and the nerves of the gut. So, that's the one condition where vinculin could play a very important role.

This one was answered already. "How was NAC tolerated by the ISO patients?" The ISO patients did the best when we used N-acetylcysteine with the Rifaximin in that new cocktail. And that's from Claudia.

Oh, Cathy asks, "How can I, as a patient, encourage a hospital to adopt a three-breath test, and encourage medical professionals to follow the protocol?" So, Cathy, I appreciate your effort. The responsibility really is mine, and the work of people who are doing research in this area to increase awareness. I gave grand rounds at Cleveland Clinic. I gave grand rounds at various hospitals around the country, educating physicians on this topic.

At the DDW, it's a meeting of 10,000 gastroenterologists. If they come to the lecture when I'm presenting, they will learn and they will understand how to do these things. That's how it goes. And publishing papers. And so now there's a series of papers that are coming. There's at least two more coming out in the next month that take it to the next level and the next level and the next level.

And it's going to become clear that you shouldn't really be doing two-gas breath testing. You really should be doing three, because hydrogen sulfide is absolutely important. The next paper, which we hope will be out in another two or three weeks, really puts a punctuation mark on that.

One last question and then we'll take a one-minute break. This is an interesting one, and often one I struggle with, Katrina. "What causes the fatigue of SIBO, and what can be done to combat it?" So, you say SIBO, but I'm going to cover SIBO and IMO, and ISO. ISO makes you very sick. And what I tried to show you with very complicated diagrams, which I didn't explain because it would take too much time, is that the cells of your gut are almost dying.

If your hydrogen sulfide is even higher, the higher the hydrogen sulfide, the more that cells are basically shutting down. So, imagine that feeling in the gut, and how you are feeling unwell. SIBO is, to a lesser extent, that. That feeling that you're fighting an infection, but it's not an infection, it's a colonization, and you're trying to combat it constantly. So, you're putting a lot of energy into that.

IMO is different. Patients get a lot of brain fog with IMO. Methane is similar to halothane or chloroform, which puts you to sleep, or isoflurane, which they use in the anesthesia lab, or in the operating room for anesthesia. These gases at high concentrations make you have brain fog. So imagine in an IMO patient, that you're going to have some degree of brain fog. So, all of these things contribute to fatigue.

Okay, I've tried to answer as many of these questions. I apologize to those I didn't get to. I'm going to get to the ones on the chat here in a moment, but I'll take a one-minute break. Paige, do you want to take over for a minute?

Paige with Gemelli Biotech:

Yes, yes. When you take a look at those questions, there's some really great ones coming in. Thank you, everyone, for your questions so far. This is really a great conversation. We have a lot of really great content being answered and addressed that we're all looking for. So, thank you for that, Dr. Pimentel.

Before we move into the live Q&A portion, I did just want to let you know that after the live Q&A, I'm going to get into a little bit about what Gemelli Biotech does, and how to access the breath test and the blood test that Dr. Pimentel has mentioned, Trio-Smart and IBS-Smart Online.

We'll also show you a QR code to enter a book giveaway for The Microbiome Connection, with two winners. So, hang tight at the end of the live Q&A, and we'll go through, very quickly, don't worry, some of those things. Great. So, are you ready to dive into some live Q&A, Dr. Pimentel?

Dr. Mark Pimentel:

Let's do it. Yeah, I'm ready. I'm ready. I'm going to try and go through each one, one by one. Some of them are harder to answer, but I'll do my best.

"How close are you to getting rid of the antibodies?" We get rid of them partly now with, I don't want to call it crazy, but advanced immunobiological therapies like IVIg, like plasmapheresis. That's what we did in some of the patients that I showed you in this one study that's now published. That is not a chronic therapy that you want to do for a large pool of IBS patients. The drug that we're developing, we hope it's about eight months away. So that's the answer to your question, Alexa.

Betty, "Does SIBO cause restless legs?" So, there is an association between SIBO and a couple of conditions, where there's a little bit of data. Restless legs is one of them. But there aren't any randomized control trials. So, we can't say with 100% certainty that there's a direct link. And also, rosacea. There's a link between SIBO and rosacea. People say their skin clears up when the SIBO is gone. So, just an extra pearl there.

Meg, that's just thanks for the high five. Somebody called Owner? I suspect they just said Owner. "I've been on antibiotics and on Physicians' Elemental, and I'm still having SIBO. What may be my issues?" So, I guess there is no way to know without more information.

But what this brings up is the point that if you have SIBO, and it doesn't go away, or you take Rifaximin and nothing happens, or you get better, and a week later it comes back? There's something wrong. There could be an adhesion in the bowel, there could even be a malignancy. There's a whole bunch of different things. There's a long list of things that could contribute to that refractory patient.

That needs to be worked up. You need to do some tests. It could include a colonoscopy, barium studies, CT scans. It depends on the rest of the story. So, my advice to you is that you need to see somebody who will take it to the next level.

Elizabeth, "Where do SIBO and IBD intersect? Do the antibodies correlate with IBD as well?" In fact, when we validated the antibodies, we compared it to IBD. And IBD barely has these antibodies. It may be positive in some IBD patients, because 10% of everybody has IBS, including 10% of IBD patients.

But what's really interesting with SIBO and IMO in IBD, is that IMO patients almost never have IBD. And IBD patients almost never have IMO. So, there's something about IMO that maybe is protective, or we do know that people with IMO have more anti-inflammatory effects of methane. So, methane may be beneficial in... Let me say that in a totally different way.

We like methane. I don't dislike methane. I like methane here. I don't like methane here. If it's here, I think it's good. I think you need to have a little bit of this methanogen. That's why I like the CS-06 drug that we've developed, because you can reduce the methane to where it needs to be, but not get rid of it altogether. You don't have to slam it with antibiotics, you're just reducing it. That's really important. And I think that's where we need to be in a year or two from now.

Let's see. Where am I going here? Okay, this is Joanne. A little long question. "I've been suffering from SIBO for 14 years. I've had positive tests in my doctor's office. I recently had two Trio-Smarts, one glucose, one lactulose, both were negative. Horrible symptoms, bloating, abdominal hardness and pain, a feeling of being full. Is it possible to have SIBO and have a negative test? Every time I take Xifaxan, my symptoms go away and I feel great. Once off for a few weeks, months, it comes back. I'm desperate to get a cure."

So I would love to see those breath tests, to be honest. Because if Rifaximin is working, the only way it would work is if you had SIBO. There is one other possibility, just one other possibility, is that Xifaxan does treat c. diff. And so, you could have recurring c. diff, and Xifaxan is helping. So, make sure you check for c. diff.

I'm not offering medical advice on this call, because I can't know everything about you, but I do see patients occasionally when they're taking Rifaximin, that it does treat c. diff. So, keep that in mind. But I can't give you specific advice, because I don't know the whole story. Hopefully that's at least helpful.

Manish, "My symptoms started after antibiotic therapy for H. pylori. Can an antibiotic course cause SIBO?" So, there was a study that was done in H. pylori, because people said, "Oh, a lot of these patients with H. pylori had bloating, and it went away when we gave them antibiotics." So likely they had SIBO and the antibiotics helped.

Why it would cause SIBO, would be a little bit perplexing. What we do know is that patients with H. pylori tend to have lower acid in their stomach, because the H. pylori reduces the acid production. Acid can fuel, for example, hydrogen sulfide, and it can fuel methane.

So, people might've had SIBO all along, but it was suppressed by the H. pylori. And as soon as you got rid of the H. pylori, all this acid comes back, and maybe brings on the IMO or ISO, maybe not SIBO. So, that could be part of what's going on. But again, more information would be helpful. So, sorry if that's incomplete.

Amber, "Do you recommend for a patient who has seen mild to moderate improvement from Rifaximin alone, but has taken many rounds, do you have a recommendation?" So, again, Rifaximin works almost equally well every time you take it, if it worked. So however well it worked for you the first time, generally speaking, it works that well each time.

We don't see patients needing, like for example, Rifaximin worked. Six months later, you take it again, then you've got to take it in three months, then you've got to take it in two months, then you've got to take it in one month. That doesn't happen. I don't see that. I don't see things worsening that way.

So, if it works, people keep taking it. But if you can get the bacteria down more completely, Elemental diet might do that for you. So, sometimes I see that in my practice that the Elemental diet brings those bacteria levels down way lower than Rifaximin, and you can get a longer duration of benefit.

The other thing that I do for my patients is, I give them a prokinetic in addition to the low fermentation diet, because that will help prevent the need for more Rifaximin, Rifaximin, Rifaximin re-treatments. So, those are things to consider in patients where the Rifaximin works, but they don't want to keep taking antibiotics every three months. You want to try and prolong that.

"What is the type of NAC used?" So the NAC that we're using in the capsule is a special... It's NAC, it's run-of-the-mill NAC, but it's contained so that it will deliver along the small intestine. So, it's a specific type of coating that we're using.

Nina, "I'm taking 262 milligrams of bismuth Pepto-Bismol when I have SIBO bloating and gas. Is that amount of milligrams okay, even though it makes my stool turn black?" Yeah. Bismuth makes your stool turn black. What we want to do, and what I do in my practice with bismuth, is avoid what happened in the H. pylori era.

In the H. pylori era, people started taking bismuth a lot. And bismuth toxicity is real. I've seen it once or twice in my career. People take bismuth for years, because it just makes them feel better and keeps their IBS better. So, it does work. It's just bismuth toxicity causes the nerves of your feet and hands to go numb. So, we don't want that bismuth toxicity.

Two weeks? No problem. Four weeks? No problem. We don't want you taking it for months. That's the problem. So, just intermittently is fine. The kidneys will clear the bismuth once you stop it. But we don't want you to take it for a prolonged period of time.

Dee Mickelson or Michelson. "Recommendations for patients who have failed two courses of rifaximin and neomycin, who are hydrogen IMO-positive. Would you recommend the Elemental diet for two weeks?" So, in general, it's funny about the Elemental diet study, because the Elemental diet study was really, really effective.

It was 30 patients, it's now published, you can read it in the journal. But many of those patients had taken antibiotics and got better, but had to take antibiotics again and again, sort of like some of the things we're talking about. Or patients who failed antibiotics, and it still worked.

So if I have a patient in my practice who fails antibiotics, but I'm convinced they have SIBO, that's where I bring in the Elemental diet. Remember, it's harder than antibiotics, because you've got to take it for two weeks, you can't eat. And the second thing is, it's expensive. You have to pay out of pocket for it. There's no insurance that will cover it, and it's around $700, $750. So, that's a lot.

Now, you won't eat for two weeks, so you save that money with the cost of eggs and groceries these days. Maybe that's cheaper, I'm not sure. But you still have to pay out of pocket, and that is somewhat discouraging for some people.

Donna, "How well do patients with anti-CdtB and anti-vinculin antibodies respond to treatment for SIBO, IMO, and ISO?" So, the higher the anti-vinculin, so I don't want to get too much in the weeds, because this explanation could take a little time. If somebody just has anti-CdtB, I love that. Because that will or tends to go down over time, at least we think it does. We've had some patients where it normalizes by itself.

Anti-vinculin generally doesn't normalize by itself. And the higher the anti-vinculin, the more difficult the patient is to get rid of their SIBO, IMO, and ISO. And so for some of the questions that I've already answered for patients where things aren't working, doing the antibody test is really important, too. I forgot to mention that.

Because the antibodies, when they're really high, that anti-vinculin, we have some people where the anti-vinculin is at the top range above three, and those patients need chronic Rifaximin, because nothing... Rifaximin works, but as soon as you stop it, everything comes back. So, knowing the antibody is helpful.

Dee again. "Any utility in testing for hydrogen sulfide in patients with hydrogen-positive IMO already on two tests prior?" If you didn't use Trio-Smart, there is a benefit to measuring hydrogen sulfide. Because if you have all three gases, and I have a few patients like this now, you've got to use, I use anyways, Rifaximin, Neomycin, and bismuth. It's the only way to get everything in order.

So it starts to get into rocket science when you look at the combinations of gases. But you may miss out on benefits if you don't know the whole story.

Betty, "How can we read the new papers coming out?" I'm happy to provide them to Paige, and she can send them out as an attachment. They are free. We publish our papers, we pay the upcharge to make sure that everybody can read them, because journals sometimes lock them down and make you pay like $40 for them. We pay the advanced fees so that any patient could read any of our papers. It's a courtesy. Patients should be able to read this stuff.

Julie, "If my very symptomatic patient did their Trio-Smart test with glucose, and had within normal limits for all three gases, do we believe the result? If symptoms look like H2S, would that show up accurately with glucose? Note that hydrogen and methane were flat-lined during the entire test."

So if you do glucose, you can have a flat-lined breath test. Glucose may not get to the bacteria, so, that's possible. Flat-lined breath tests can also occur because of gastroparesis, or they're on Ozempic, or a GLP-1. Something we covered earlier. If you're on Ozempic, forget about a breath test.

The lactulose is not getting out of the stomach. The glucose is not getting out of the stomach. You're not going to be able to see anything on the breath test. So, you'll be a flat-line. So, those are other things to consider. Narcotics can also give you a flat-line breath test. Again, some other things to consider. But I would do lactulose, in answer to your question.

NW, "Can one week water-only clear SIBO?" One week of water only is a little dangerous, because you're not dehydrating yourself, but you are really calorie restricting and fasting. When we did the Elemental study, the first Elemental study, back in 2004, we studied seven days of Elemental, which is sort of like fasting, because it gets absorbed so quickly it doesn't get to the bacteria.

We did 10 days and we did 14 days. And all the magic happened between 10 and 14 days. Please do not fast for 10 to 14 days. So, yes, 10 to 14 is... So bacteria will go into hibernation, and they'll just wait and wait and wait and wait, until you eat. But once they hit 10 to 14 days, they run out of steam. At least that's what we feel is happening.

Dee Mickelson, "Any safety concerns when going on a two-week elemental diet? Labs or to monitor?" So, we looked at all the labs of these patients before and after Elemental, and nothing appeared to... We haven't published this yet, but it is in the works, in terms of publication for the next paper from that 30-patient trial. But just to give you a heads up, we didn't see anything. We didn't see any changes in the sodium, or potassium, or any of those things, because the food is balanced. It has all of that stuff.

Tina, "Can IMO convert to ISO?" Good question. Haven't seen many cases of this. I can't even think of one, specifically. But it's early days, and I haven't really paid attention to IMO converting to ISO. IMO can not convert to SIBO, but you have to have SIBO to have IMO. You have to have hydrogen to make methane.

So sometimes you'll have a normal hydrogen curve with methane there, you get rid of the methane, and all of a sudden the hydrogen's up, because you can see the hydrogen now, because the methanogens are not eating the hydrogen. So, we see that.

ISO is a little bit more complicated. So, I'll pay attention some more, and see if I have any cases like that, but I can't off the top of my head think of one. So we've got about... Let me do about two or three more minutes. Oh, my gosh. I know I'm not going to get to all your questions.

"If NAC breaks down the mucus layer, because the mucus layer is what it's supposed to be, why wouldn't it help with IMO? My understanding is that methanogens hide in the mucus layer, which is one of the reasons IMO returns, or is hard to eradicate." So, you are correct, Meg. The methanogens, some of them, hide close to the mucosa, or close to the cells.

And the problem with methanogens, is they colonize the small bowel and the colon. And NAC is a funny thing, that, let's say if you just took NAC, just took it. NAC is consumed by the amount of mucus in the environment. So, if you took it, the stomach is just packed with it. Do you ever vomit, and you get that stringy stuff? That's the mucus. NAC will all get consumed by all the mucus that's in the stomach.

Imagine the mucus along the small intestine, and then trying to get some NAC to the colon. You'd have to design something specifically to get to the colon. So, the answer is, maybe, with the right design of some kind of product. But at the moment, that doesn't exist. But your idea is good.

All right, let's do three more questions. Let's do Becky McCarthy. "I've been diagnosed with gastritis, SIBO, and bile reflux. Which to treat first? Did one cause the others?" So, bile reflux is generally, by textbook definitions, caused by having your gallbladder removed. So, that's one cause. Having a problem with the pylorus, where it's too open, or surgery has been done on the pylorus, so it's open. Or having bariatric surgery where you've changed the anatomy.

So, if you change the anatomy, you can cause SIBO. The other way you can have bile reflux is if you have an adhesion somewhere that's causing the bile not to go forward, but to kind of come back sometimes, and that can cause SIBO. So, if you have bile reflux plus SIBO, in my practice, I make sure that there isn't something else going on that's causing the SIBO, a secondary cause of SIBO. And so, that's how I would go with that in my practice.

"What are your thoughts of IVIg as a treatment for anti-vinculin?" I showed you the study. We did IVIg on some of the really, really sick people, and it does get the antibodies down. And when it does, people get better. So yes, we use it. But remember, IBS affects 45 million people in the U.S. We can't be doing IVIg, it's $10,000 a shot. It's not practical on a broader scale. But for select very, very sick patients, we've had no choice in those instances.

And finally the last question I'll do before I give you your evening back, is Nicole. "Hi, Mark. I'm Nicole. I'm wondering what tests do you suggest I start with? Some history. I've been diagnosed with IBD about six years ago. My lactose sensitivity has increased over the years, despite taking lactase pills." Oh, this is a long one. "Also, a day before traveling around Asia, I got food poisoning, assuming from just expired cow milk.

"Since then, but only on my trip, I experienced more diarrheal instances and abdominal pain, especially with cow-heavy products. Coming back from my trip, I don't have those experiences as much anymore. Just the usual abdominal pain and constipation."

So, in patients that I have with inflammatory bowel disease, where the drugs seem to make the gut heal, meaning you scope and there's not much inflammation anymore, but you still have ongoing symptoms. And our IBD doctors do this all the time. They do a breath test. There are studies that ironically, the original studies looking at breath testing, or gases in the gut in inflammatory bowel disease, were the ones that suggested hydrogen sulfide was contributing to the inflammation of ulcerative colitis, or even Crohn's disease.

So, while we're early days, again, with three-gas breath testing, I'm waiting for the studies to show, again, as they did in the nineties, that hydrogen sulfide is important in IBD.

The other thing I do in my IBD patients where they have an overlap with IBS is, I do the antibody test, because if those antibodies are positive, the person probably has IBD, as they already know they have, and on top of that have IBS. So, that's really important.

All right, Paige, it's all you for the next minute, and I will stay on, if you want me to answer any further questions.

Paige with Gemelli Biotech:

Yes, thank you very much, Dr. Pimentel. Thank you for staying a few extra minutes as well, and getting some questions in there. Very, very nice of you.

I wanted to, just before we get into this, it'll take two minutes of your time. Just wanted to let you know in the chat, there is a discount code that has been offered for all of Gemelli tests on our telehealth platform, so, when you order online. It's for $50 off, and that is until the end of the month. So, DIGEST50 is that code. I'll also put it up on the screen.

And I also wanted to let you know there is a replay that will be sent out to everybody that is registered. So everybody on this call will receive a recording of this. The DDW papers and posters are actually on our YouTube page. So, if you just go to Gemelli Biotech, on our YouTube channel, you'll be able to find six or seven of those important posters that he mentioned earlier tonight.

And then also, if you wanted to join our newsletter moving forward, we do offer some kind of discounts like mBIOTA, the Elemental diet that Dr. Pimentel also mentioned, alongside discounts for Trio-Smart, IBS-Smart, and other things that are in the Gemelli family. So, just wanted to let you know that's what we're going to dive into here, in case you have to pop off.

But these are our at-home mail-in tests. We have a breath test for SIBO, IMO, and ISO. And then we have an at-home blood test that attaches right to your arm, for post-infectious IBS, or IBS that's caused from food poisoning. All right.

The Trio-Smart test is the only at-home test and three-gas test available on the market right now that tests for hydrogen sulfide. So, that is that severe diarrheal predominant symptom that you might have. It could be ISO, which is an overproduction of hydrogen sulfide.

We are trusted by over 1,000 patients for Trio-Smart. We have very sensitive, accurate equipment. We're CLIA-certified, and the greatest part is that there's no doctor's appointment needed. You can order right online through our intake form that we do have a real live doctor go through, and make sure you're okay for the test, and sign off on it for you. And then your kit comes in the mail and you mail it back into the lab, and get your results via email within three to five days from submitting your samples.

We also now have lactulose available. We do have the option of glucose or lactulose through our telehealth platform. Lactulose does require a prescription that we do incorporate into the intake form process, that your doctor will evaluate to make sure lactulose is safe for you. And then you will receive lactulose as a separate substrate in the mail. And you can use it with your lactulose test when that arrives in the mail. But you can order either glucose or lactulose directly from triosmartbreath.com.

IBS-Smart is the at-home blood test for post-infectious IBS. So, again, the IBS that's caused by food poisoning. This is a at-home capillary test, so it just attaches very easily, basically pain-free, and you just fill up a little bit of blood, and you send that in and get your results via email, the same way with Trio-Smart.

Post-Infectious. Again, this is the food poisoning IBS. It's usually a diarrheal symptom, or a mix, which is the mix of constipation and diarrhea, if you go back and forth, but primarily diarrhea for IBS-Smart and post-infectious IBS is recommended.

Here is our DIGEST50 promo code. This will save you $50. We always have free shipping, which is really exciting. We are only available in the United States at the moment, and you can go to ibssmart.com or triosmartbreath.com to access any of these tests, and just make sure you put in DIGEST50. It'll also be in the email that we follow up with later tonight or tomorrow, depending on the replay.

And this is where I'm going to keep this up a little bit. If you want to scan the QR code, or go to this bit.ly address here, you can enter to win a giveaway of one of The Microbiome Connection books, so Dr. Pimentel and Dr. Rezaie's book. Really, really informative stuff. We have patients all the time referencing this book, what's in the book, asking questions, recommendations. Really highly recommend it. Even if you don't win this book, get yourself a copy of it.

But yes, if you could just QR code here, and you can enter your information and we will announce the winner in the email, the follow-up email with the replay link as well.

Again, thank you for joining us. This is the DIGEST50 code once more. If you have any questions for us about the tests, about Trio-Smart, IBS-Smart, please reach out to support@triosmartbreath.com. Or you can go onto our website, and go through the contact form there.

I hope you have a wonderful evening. Thank you for joining us. Thank you, Dr. Pimentel. This was incredibly informative and very helpful. We'll send out the email and you'll get all of this nicely packaged, so you don't have to remember it all. But thank you very much for joining us, and have a great night.

Dr. Mark Pimentel:

Well, Paige, we missed 117 messages. 18.

Paige with Gemelli Biotech:

Oh, wow. Yeah. [inaudible 01:05:45].

Dr. Mark Pimentel:

Looks like there's a lot more questions we never got to. So, thank you. Thank you for everything. And thanks, everybody, for being here this evening.