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Newest Developments in SIBO Treatments with Dr. Mark Pimentel | Rational Wellness Podcast 476
Dr. Mark Pimentel on SIBO/IBS: 3-Gas Breath Testing, Hydrogen Sulfide, Methane, Diet & Emerging Treatments
Dr. Ben Weitz welcomes Dr. Mark Pimentel to discuss new research on IBS and overgrowth syndromes, including hydrogen SIBO, intestinal methanogen overgrowth (IMO), and intestinal sulfide overproduction (hydrogen sulfide). Pimentel explains that hydrogen on breath tests is a marker for bacteria like E. coli and Klebsiella and that slowed motility enables overgrowth; he also distinguishes bloating vs abdominal distension and critiques Rome criteria for excluding bloating. They review Trio-Smart three-gas breath testing, lactulose vs glucose, timing and cutoffs (methane ≥10 ppm; hydrogen sulfide >2), and evidence that elevated hydrogen sulfide correlates with severe diarrhea and gut cellular dysfunction. They cover GLP-1 effects on motility, FoodMarble pros/cons, low fermentation diet, elemental diet (MBIOTA), probiotics, new therapies (rifaximin + timed-release NAC; methane enzyme inhibitor), and a Cedars-Sinai IBS-D trial recruiting in Los Angeles.
01:00 Meet Dr Mark Pimentel
03:12 Is Hydrogen Always Bad
05:11 Bloating vs Distension
08:40 Where SIBO Bugs Come From
10:30 Why Slow Transit Drives Overgrowth
12:50 Three Gas Breath Testing
16:21 Breath Test Critiques Answered
20:09 Cutoffs for Positive Tests
23:27 Hydrogen Sulfide Gut Damage
24:57 GLP1 Drugs and SIBO
27:37 Methane Weight Gain Explained
29:17 FoodMarble Pros and Cons
30:42 Low Fermentation Diet Debate
32:27 White Bread Misconceptions
33:25 Rifaximin Plus NAC Trial
35:10 New Methane Blocking Drug
36:26 Methane Treatment Challenges
38:00 Methanogens Balance And Phages
40:05 Palatable Elemental Diet
41:22 Next Gen Anaerobic Probiotics
44:23 IBS Versus IBD Relationship
46:31 Hydrogen Sulfide Options
47:40 Mast Cells Mold And Motility
49:18 Vagus Nerve Confusion
51:30 Future Of Overgrowth Syndromes
52:42 Trial Signup And Wrap Up
Dr. Mark Pimentel is one of the world’s leading authorities on the gut microbiome and small intestinal bacterial overgrowth, or SIBO. He serves as Executive Director of the Medically Associated Science and Technology Program at Cedars-Sinai Medical Center in Los Angeles and has dedicated more than two decades to unraveling the complex relationship between the gut microbiome and disorders such as irritable bowel syndrome.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure. Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111.
Dr. Weitz: If you’re looking for clinically useful insights, not wellness hype, then this is the place for you. Welcome to the Rational Wellness Podcast, the podcast for functional and integrative practitioners who wanna practice with greater clarity and precision. I’m Dr. Ben Weitz, and each week, I sit down with the leading clinicians, researchers, and lab innovators to explore the science, lab testing, and clinical reasoning behind modern root cause medicine. This is a show focused on practical, evidence-informed insights that you can actually use in patient care. Please subscribe to the Rational Wellness Podcast on Apple, Spotify, or YouTube. Please tell your friends and colleagues, and if you could give us a ratings and review on Apple or Spotify, we would certainly appreciate it. Finally, to access the show notes and the full transcript, please go to my website, drweitz.com.
Hello, Rational Wellness podcasters. Today, we’ll be speaking with Dr. Mark Pimentel again. Very exciting getting the latest information about SIBO and IBS. And Dr. Mark Pimentel is one of the world’s leading authorities on the gut microbiome and small intestinal bacterial overgrowth. He’s executive director of the Medically Associated Science and Technology program at Cedars-Sinai in LA. He’s dedicated more than two decades to unraveling the complex relationship between the gut microbiome and disorders such as IBS. Dr. Pimentel’s groundbreaking research helped establish that many cases of IBS are linked to microbial overgrowth in the small intestine, fundamentally changing how clinicians understand and treat these conditions.
His team has pioneered breath testing for hydrogen, methane, and now hydrogen sulfide [00:02:00] gases. They’ve identified distinct microbial patterns associated with different forms of SIBO, and they’ve pioneered the development of targeted therapies that are transforming patient care. Today, we’ll discuss his latest research, especially since he and his group have just presented a series of papers at the latest Digestive Disease Week conference in May, about what they’re learning about the evolving science of the small bowel microbiome, diagnostic approaches, emerging treatments, and what we can do to help our patients with IBS and SIBO and other gut symptoms.
So Mark, thank you so much for joining us.
Dr. Pimentel: Oh, it’s a pleasure to be here. I guess this is what it’s called or what’s known to be a regular. I am a regular on your show.
Dr. Weitz: I want to say I think this is the eighth time I’ve had the opportunity to chat with you, and I really appreciate that.
Dr. Pimentel: It’s been [00:03:00] fun, and I look forward to this one.
Dr. Weitz: I want to talk about a few general questions and questions about symptoms, and I want to go into testing, and then I want to discuss treatment.
Dr. Weitz: Let’s see. I have a left-field question. So should we even be trying to lower the amount of hydrogen, since hydrogen seems to promote health? In fact, there’s a big trend now where people are drinking hydrogen-infused water. They’re breathing in hydrogen. They’re applying hydrogen to the skin. Apparently, hydrogen has all these health-promoting benefits, antioxidant. Should we even be trying to reduce hydrogen if there is hydrogen?
Dr. Pimentel: I’ve said this a number of times on a number of podcasts over the last year, and it’s what I call your mother’s theory. Your mother told you it’s always good to have a little bit of something, but it’s not good to have a lot of, too much of one thing is a bad thing, or too much of a [00:04:00] good thing is a bad thing. So I guess, we all have hydrogen in our gut. We really do, and that’s okay. It’s okay to have hydrogen in your gut because we’ve evolved with this for, millions of years. But there may be too much that can affect you, and, if you put hydrogen on your skin, your ability to absorb that hydrogen is relatively limited. But in the gut, you can absorb a lot more of it. And I guess the next thing I’d say is that when you talk about hydrogen in the gut or hydrogen, during breath testing to assess the levels of hydrogen being produced in the gut, it’s not the same as what you expose somebody’s skin to the gas hydrogen. Because it’s not the hydrogen that’s affecting you, it’s the lipopolysaccharides and all the junk from the E. coli and Klebsiella that are hurting you. They happen to produce hydrogen, and that’s a way you can measure those things or measure their presence. So it’s not the hydrogen that I [00:05:00] think is causing the trouble, it’s all the bacteria and their junk that makes you unwell. And then of course, too much is a bad thing, which your mother taught you.
Dr. Weitz: That’s a great explanation, and we have to recognize that it’s the bacteria that are creating the problem, and they just happen to give off this hydrogen, and… But the hydrogen does create some of the problems, like hydrogen’s probably is responsible for a lot of the bloating, and I wanted to ask about bloating. And in fact, I heard you talk about how when you apply for funding or to get approval for your research studies, how it’s not really acceptable to use bloating as one of the primary symptoms, and yet that’s one of the symptoms that are most troublesome. And I have to say that some of my most difficult gut health patients are the ones with severe bloating.
Dr. Pimentel: Yeah, and so and then you’re absolutely right. The physical gas, forget about whether it’s [00:06:00] hydrogen or any other gas, the physical gas of it is causing bloating and distension, and then that causes pain. And this is the funny part about the Rome criteria, and we now have Rome V, which you’ve probably heard that was launched at DDW. Rome V still doesn’t have bloating. So you could take 1,000 Rome positive patients, whichever Rome criteria you want, none of them have bloating as a criteria, and ask them what their most bothersome symptom is, and they will tell you it’s bloating. And yet Rome ignores bloating and is stubbornly- who’s,
Dr. Weitz: Who are the members of the Rome criteria?
Dr. Pimentel: Oh, it’s a long list of individuals who are handpicked to be on this not-for-profit group that decides how we diagnose IBS. And some of us are finally standing up and saying, “Look, this is not okay. We can’t keep doing this over and over again.” And Rome V for IBS now goes back to Rome III. So it’s [00:07:00] now pain and discomfort because Rome IV was too restrictive saying you had to have real pain. And so like what are we doing? Why are we going back and forth with different criteria and changing the rules every four or five years? And then changing the patient population. Every time you change the criteria, you change the patient population. So it’s a little bit… It’s enough,
Dr. Weitz: There’s a distinction between bloating and abdominal distension, correct? How should we think about that? Because some of the patients who complain about bloating show me how their gut sticks out even when they haven’t eaten, and some of the time it appears to be abdominal distension and not just bloating.
Dr. Pimentel: Yeah. Abdominal distension and bloating are tricky to dissect because they can be one in the same or they can be different. And I guess the most extreme example is ascites from liver failure. Your belly fills up with fluid, you’re distended, but it’s not gas, right? It’s water in and, [00:08:00] in surrounding the bowel. But, people feel pressure from gas. So let’s say you had gastroparesis, your stomach could be twice the size of a normal person. You’re feeling pressure, but you may not be distended ’cause the stomach isn’t as big as the small bowel, which is 15 feet long, so you don’t get that protrusion. But the patient feels pressure, they feel gas build up, but they don’t actually get distended ’cause it’s a smaller organ inside. So there, there, there are subtleties to the difference between bloating and distension, but mostly in overgrowth, the bloating and distension are synonymous because when they bloat, they distend.
Dr. Weitz: Do we think that the organisms that cause the SIBO, IMO, and ISO, those are the three forms of SIBO-
Dr. Weitz: Do we think that they overgrow from the large intestine into the small intestine, do they come from above down into the small [00:09:00] intestine, or were they in our small intestine the whole time and just overgrew?
Dr. Pimentel: I love that question because that, that’s one thing we’re putting in all our review articles now. We just wrote another review that’s going in. But in essence, this, the old m- the, I don’t want to call them myths, but the old way of thinking, or classical SIBO, was that the colon bacteria are moving into the small intestine like a marching army. So now that we have sequencing, all this next generation sequencing done of stool, the stool doesn’t contain much proteobacteria. What does that mean? Proteobacteria are the E. coli and Klebsiella. They have a low number of those. The stool contains bacteroidetes and firmicutes, two different categories of bacteria.
The small bowel contains proteobacteria and firmicutes we now know from our sequencing of the small bowel, and proteobacteria are now called pseudomonadata. It’s a different term. [00:10:00] I know. Everything changes, and I’m gonna confuse your audience, but the point is, the E. coli and Klebsiella that are overgrowing in small intestinal bacterial overgrowth, for example, came from the small bowel. They just got the opportunity to take over. So they’re not moving up. It’s not an invading army. It’s your own people rising up in inappropriate numbers, like putting a whole million lawyers into Los Angeles. And maybe that’s not a good thing for Los Angeles.
Dr. Weitz: To what extent did they have the opportunity to overgrow because other commensal bacteria were decreased? In other words, did they fill up the parking lot because the parking spaces were empty?
Dr. Pimentel: Yeah, so no. So your healthy microbiome of the small bowel is probably 1,000 different species. And the studies that really taught [00:11:00] me that transit is so important to this it, the small bowel is a fast-flowing river, and if you ever watch those Survivor shows on Discovery Channel to 10 years ago, Survivorman and all this, you end up in an Alaskan forest, and you don’t know where you’re…how to get out. But you never drink from the swamp because that’s slow-moving water, because it has bacteria in it. You drink from the fast-moving stream because chances are it’s clean. And I think the small bowel has a speed and a cadence to it that keeps it clean because it’s fast-moving, as opposed to the colon, which is more stagnant and more dirty that way.
And it’s really the slowness of the gut that allows these bugs to take over. Why? I’m not exactly sure, but the study I was trying to point to is they did a study in rats where they tied the small bowel just to half its normal caliber, like an adhesion, makes it a little bit narrow, and then the small bowel doesn’t [00:12:00] flow. And they get overgrowth. E. coli and Klebsiella take over. So there’s something about the restrictive flow of the small bowel that makes it favorable for E. coli and Klebsiella to just take over in that environment. And don’t know why, but that’s the situation.
Dr. Weitz: I thought the main reason was because of the lack of the cleansing waves.
Dr. Pimentel: That is in essence slowing, right? So the river is no longer flowing fast. It’s not flowing very well at all, and because you don’t have the cleaning waves to drive the flow, and so you get a buildup, and that buildup favors, or preferentially favors, E. coli and Klebsiella. And once they get a hold of things, they’re such dramatic fermenters, they never wanna let go. So they hang on.
Dr. Weitz: Let’s talk about breath testing. Sure. And I know you use a trio smart three gas breath test that you developed, even though I think there’s still probably too many in the [00:13:00] field still using the two breath tests.
Dr. Pimentel: Yeah, as we continued to understand the small bowel microbiome from Reimagine study that we’ve been doing, which is the largest database of small bowel aspirates in the world now we realize there’s really three buckets. There’s the regular SIBO, which is hydrogen, which is produced by E. coli and Klebsiella. There’s what we learned later, IMO, which is intestinal methanogen overgrowth, and the methane is causing constipation. But then there was this third group where we were getting breath tests that are flat lines and no hydrogen at all. We started this podcast by saying hydrogen is produced by everybody. How do you get a, how do you get a flat line, right? And so hydrogen was being eaten by a third group of bacteria that we presumed were hydrogen sulfide, but we didn’t have a test for it. Now that we have a test for it, and now that we’re doing even more directed sequencing for these [00:14:00] hydrogen sulfide producers, we actually think hydrogen sulfide may be the most sinister of all types.
And why do I say that? Because, A, they have the mo- in a 6,000 breath test study, they have the most severe diarrhea when hydrogen sulfide is elevated. They have the most severe illness when hydrogen sulfide is elevated, urgency and pain. And then when we looked at people with hydrogen sulfide elevated on that third gas breath test, those people, when you took biopsies of their small bowel, they had cells that were dying if the hydrogen sulfide was high enough.
They had cells where the mitochondrial function was dramatically dimish- di- diminished because of the redox. Aquaporins were up. That’s why you get diarrhea. Serotonin and all the chemicals that cause pain were up. So hydrogen sulfide, even compared to SIBO and IMO, had more dramatic negative effects on the cells of the gut than the other two gases. I know it’s a long answer, [00:15:00] but what I’m trying to say is we were missing a huge piece and now we don’t. Now we have it,
Dr. Weitz: there doesn’t seem to be that many cases of of hydrogen sulfide.
Dr. Pimentel: So out of 100 breath tests, maybe between eight and 10 are positive for hydrogen sulfide, so about 10%, I would say. And of course, if you, if that’s just the general population of bloaters, but if you look at people with diarrhea, it’s probably 25%, so because it’s a diarrheagenic gas. So I think it’s more than people think you just have to start testing.
Dr. Weitz: There seems to be some patients with hydrogen sulfide that have constipation, though.
Dr. Pimentel: Yeah. So you can have a combination of gases, right? So now that you have three gases, you could have hydrogen plus hydrogen sulfide or methane plus hydrogen sulfide. But in general, if you have methane, it’s possible you can bend the needle [00:16:00] towards constipation. But I would say the majority of hydrogen sulfide patients, and hydrogen sulfide tends to be even more dominant than methane. So if you have methane and hydrogen sulfide, on average, that patient has diarrhea. But the balance can shift, depends how much methane is being produced, so it’s a little more complicated than black and white.
Dr. Weitz: Some have criticized breath testing by saying that it doesn’t account for people who have faster transit and that if the lactulose can actually reach the colon much faster, so we might actually be measuring gas from the large intestine.
Dr. Pimentel: Yeah. I… That’s a great question, and finally we have a great answer for that because there was a Norwegian study, and forgive me, I won’t be long with this one, but I’m a little long-winded today, I think. But the the Norwegian study showed that if you gave lactulose- It distinguished a group in IBS that was [00:17:00] high hydrogen versus low hydrogen, and that when they measured transit, 80 or 90, it’s close enough to 90, they did it in 20-minute increments, was the best discriminator. And only the patients where it was over 20 responded over 20 parts per million for hydrogen, responded to antibiotics, even though they gave you antibiotics whether you were positive or negative. But the part that was the most important was that lactulose never hit the colon when they, when it was 80 minutes, and so they measured transit with the lactulose as well.
And so that’s the final straw of all of this. The second part is in this 6,000 breath test study, lactulose caught people that glucose missed, because some patients, some doctors were ordering glucose, and that was one of the other big revelations of this recent study, which is why we prefer lactulose. But the third part is people are saying things like the breath test is, doesn’t have good sensitivity and specificity.” And my answer to [00:18:00] that is, “To what?” You can’t measure sensitivity and specificity if you don’t have a gold standard, and we now know that culture is not the gold standard because everybody’s doing culture differently, and 20% of culture samples from the Mayo Clinic study, for example, were contaminated. So that can’t be a gold standard. So you can’t even measure sensitivity and specificity. So the way I think of this type of test is you got the symptoms, you got the positive tests, and if they respond to treatment, you had SIBO. You can’t look at it as sensitivity and specificity. You just can’t.
Dr. Weitz: Since IMO, intestinal methanogen overgrowth, and ISO intestinal sulfide overproduction, refer to both the small and large intestine-
Dr. Weitz: Would it be better to use a stool test or do a three-hour breath test to measure gas in the large intestine? And you probably know that some functional medicine [00:19:00] practitioners take the Trio Smart test and do a sample every 22 minutes, so it’s a three-hour test.
Dr. Pimentel: Yeah. I think, when we were doing the North American consensus, and since then there’s been the European, the Asian Pacific with Australia, the Brazilian, the Argentinian, and just last week the Israeli consensus, there is still no validated study that says three hours gives you better information than two, no published validation. That doesn’t mean that’s, three hours isn’t better. What I’m saying is nothing has been published to say, “Okay, three hours is better than two.” And even if you did a three-hour study, you’d have to validate it against symptoms. So in the 6,000 breath test study we did, the 90-minute time point, two-hour time point correlated with symptoms. So methane correlated with constipation, hydrogen sulfide correlated with diarrhea, and so forth. So these gases correlate with your symptoms at [00:20:00] the time points we’re currently using. If you use three hours and you infer something it’s not based on a, like a published paper. That’s my problem.
Dr. Weitz: So what is the latest on what measurement should be considered positive? For example, should we use 3 or 10?
Dr. Pimentel: So the consensus is across the board 10 parts per million for methane, 10 or greater. For hydrogen-
Dr. Weitz: Now wait a minute…
Dr. Pimentel: … at any time during the test
Dr. Weitz: But isn’t there some disagreement among some of the people involved, including yourself?
Dr. Pimentel: So when I went into the North American Consensus, full disclosure, I thought 3 or 5 might have been better. Because we were seeing at even five parts per million, that constipation seemed to be the trend of that gas pattern. Since then we’ve been doing just a tremendous number of studies. If a person is [00:21:00] 5 on their breath test at the zero time point, 95% of those patients eventually breach the 10 part per million during the two hours, so they end up being a positive test anyway. So my argument for 5 didn’t even hold water because eventually during the test at some point, that patient would’ve risen above 10. The other part about methane is it’s a thermometer, so you can be, if you have zero methane, you’re least constipated. If you have 100 parts per million methane, you’re most constipated. So you’re eventually going to be leaning constipation as you get closer and closer to 10. So it’s sort of a gray zone, and so it just depends on your patient, how you want to handle anything between 5 and 10, if you want to treat or not. So I’ve, I have to accept the consensus as well because I’m not always right and, we have to agree with others and play nice. But- … 10 seems to work out, 10 seems to work out. I’m basically [00:22:00] saying I think I was wrong, that 5 isn’t necessarily the best endpoint, that maybe 10 is, and the data keeps pointing in that direction. We accept 10.
Dr. Weitz: I wonder what the Israeli consensus was. Did they think we should carpet bomb Gaza with rifaximin?
Dr. Pimentel: I, this is a scientific program, not a political program.
Dr. Weitz: Just kidding. So Yeah. Hydrogen sulfide- Yeah … should we use 3 or 2 or 1.5?
Dr. Pimentel: So this is a delicate area because we’re seeing some of the transcriptomic changes in the lining of the gut even at 1.5, but 2 is the cutoff we used in the 6,000 breath test study that seemed to discriminate patients with diarrhea versus not diarrhea. But again, everything’s… so the problem with hydrogen sulfide and methane is that they are [00:23:00] linear. That’s not a problem, that’s a good thing. That means that there is a cause and effect relationship. The lower it is, the less diarrhea, the higher it is, the more diarrhea. But at some point, you’re in a gray zone, and then you tip over, and you’re definitively diarrhea. And so there may be a gray zone, again, like methane, between 1.5 and 2, but over 2 seems to be a decent cutoff to be more definitive.
Dr. Weitz: Can you talk about the hydrogen sulfide causing damage to the gut wall?
Dr. Pimentel: Yeah and we touched on this just briefly, but hydrogen sulfide… So w-what we did was a number of experiments, and the third experiment we haven’t published yet, but we put hydrogen sulfide organisms into rats, and then we looked at what happened to the gut wall. And of course, the rats got diarrhea from the hydrogen sulfide that those bugs were producing, basically recreating what we’re seeing in humans. [00:24:00] I’ll get to the gut wall in a second of the rats. Then we looked at hydrogen sulfide-producing humans, and we took biopsies of the wall of the intestine during an endoscopy and looked at what was happening to the gut wall in humans.
Basically, bottom line is rats and humans, same thing was happening. And again, it was the mitochondria were dysfunctional. At higher dose, higher levels, the cells were dying from ferroptosis. There was aquaporin protein changes, which are what causes diarrhea, serotonin, visceral hyperalgesia molecules were being changed, causing you to feel more pain, and all the things that made the most sense as to, basically IBS. If you would l- were to look at the transcriptomics of a hydrogen sulfide-producing patient, and you had no, didn’t know it was hydrogen sulfide, you would say this was irritable bowel syndrome based on the l-literature in IBS.
Dr. Weitz: Interesting. So when it comes to [00:25:00] GI motility, we have millions of patients now taking GLP-1 agonist drugs, which slow GI motility. Do these drugs increase SIBO, and what can we do about it?
Dr. Pimentel: I’ve had a mixed emotional reaction to GLP-1s over time. And obviously they have dramatic benefits for certain disease states, obesity being one. It slows the gut down dramatically, and so my first inclination is this is bad for SIBO because slow means more E. coli and Klebsiella. And so now there are three or four studies that have been presented at meetings that show that GLP-1 treated patients have more SIBO by culture. The problem is you can’t do breath tests very easily in these patients. They often have no rise of anything. The lactulose sits in the stomach, doesn’t ever get out of the small bowel within two hours if they’re on GLP-1s actively.
So we can’t use breath testing to even study these [00:26:00] patients, so it’s a little hard to study. Having said that, I have some SIBO patients who are on GLP-1s, and because it reduces food to the small bowel, it also reduces bloating to some extent because less food, less gas, because the less fermentation. So it’s probably a wash. And maybe it doesn’t affect people too– And also it causes constipation, so if you’re a diarrhea patient with SIBO, you might feel better because it’s a constipating drug. The question is what happens when you get off the drug? Now you got all this E. coli built up. Your food is now moving through fast again. Are you gonna explode with bloating and gas and distension and worse SIBO? And we haven’t really studied that aspect of it yet.
Dr. Weitz: And if you take a patient on a GLP-1 and you put them on a prokinetic, is that gonna undo the effects of the GLP-1 agonist?
Dr. Pimentel: So there’s no study to look at [00:27:00] the stomach emptying of somebody, let’s say, on a GLP-1 and Motegrity, prucalopride. Does it offset the GLP-1 and therefore get rid of the, eliminate the benefits of the GLP-1? In my view, I would imagine that it cannot override GLP-1. GLP-1 is the most potent inhibitor of stomach motility we’ve ever seen, and I can’t imagine, prucalopride can override that. But maybe it makes cleaning waves. Maybe it makes enough cleaning waves that it can prevent some of the SIBO from GLP-1 but again, we’re just, this is all just conversation. There’s no data.
Dr. Weitz: So why does methane, which slows gut motility, tend to lead to weight gain, whereas GLP-1s that slow gut motility lead to weight loss?
Dr. Pimentel: So that’s a very good question, and it has a lot to do with you’re slowing the entire GI tract with methane to the point where it doesn’t affect [00:28:00] gastric motility that much. So you’re able to eat, but that food sits in the small bowel longer, and you’re able to liberate more calories from that food than somebody who doesn’t have methane. But there’s a second, Jeff Gordon, who is one of the, pioneers of the microbiome, contemporary microbiome movement. He studied the presence or absence of methane, and what methane does– So let’s say you have only E. coli in the small bowel. You’re a SIBO hydrogen producer. Eventually, the E. coli is fermenting so efficiently it produces a ton of hydrogen, but when it produces that hydrogen, it pickles itself. It, the hydro- It doesn’t like the hydrogen buildup in the environment, and then it auto-regulates itself. When you have methane eating the hydrogen, the E. coli can fire through faster and more material, creating more calories for you. So they showed in a study that if you have methane, [00:29:00] the hydrogen producers can produce more hydrogen and liberate more calories from, for you than had methane not been there because they would auto-regulate. So methane allows you to even further, harvest nutrients from a meal.
Dr. Weitz: What do you think about the FoodMarble, which allows patients to test themselves?
Dr. Pimentel: So I don’t use FoodMarble often, so I’m not going to say anything too negative about it. I think if people are more aware of hydrogen and methane in their lives, it can be helpful. I think what we want to avoid though is patients checking every 20 minutes just because it’s getting all self-absorbed about methane because it’s so easy to measure when you do it with the FoodMarble. And and then because one of the challenges I’ll just say this from a dietician’s point of view, because I met a dietician who was quite negative on FoodMarble because she was saying [00:30:00] that patients were starting to get really food averse because of it. Because the thing about measuring methane is you, or hydrogen, is you, it might not be today’s meal that’s driving that gas.
It might have been a meal two or three days ago. And then you start eliminating food, and eliminating food. Sometimes less is more in terms of information because you can’t really fight methane so easily, and sometimes you need to talk to a clinician and get the right therapy to get the methane down, rather than using food all by itself. So there’s challenges with knowing too much about the gases that you produce. But for some people who are objective, it can be very helpful. So I have mixed feelings.
Dr. Ben Weitz: Let’s go into treatment. And you just mentioned diet. So when it comes to diet, there have been lots of studies looking at a low FODMAP diet as being beneficial, and I know you feel that this is difficult for a lot of patients to follow, so you recommend the low [00:31:00] fermentation diet.
Dr. Weitz: But the problem I have with the low fermentation diet is it’s too much like the standard American diet. It’s almost as though the patient should just eat McDonald’s or something. Because it focuses on white rice and white bread and foods low in fiber, and that sort of goes against everything we’ve been trained to be recommending for patients.
Dr. Pimentel: Yeah. So I guess the way I sometimes answer this question is, I am not recommending low fermentation diet for the average American who has no bloating, gas, distension, or so forth. And so they should be eating perhaps more fiber or making sure they have enough fiber in their diet as a normal person. But if you start taking excessive fiber as a bloated patient with overgrowth, you will make yourself absolutely miserable. And so you have no [00:32:00] choice but to make some modifications in your diet, but perhaps ones that are more easy to handle, more socially– less socially isolating, and that’s why the low fermentation diet is better because it’s less restrictive and less, less inconveniencing for patients.
But I think, one of the things about low fermentation eating, we’re not– we’re trying not to make people crazy and in terms of their diet choices. But your point is white bread versus whole wheat bread, and so those are maybe un– you’re taking an unhealthy choice like white bread and comparing it to unhe– a healthier choice of whole wheat bread. But, white bread is not unhealthy. White bread gets a bad rap because of the processed breads that we see in the grocery store that are the very soft white breads. I’m not going to name names because I don’t want to get in trouble, but I think you know what I’m talking about. But an Italian loaf, a French [00:33:00] baguette, a sourdough bread are all white breads that are perfectly fine on the list, and they’re very healthy. They don’t necessarily have ultra-processed ingredients. They’re just what you might get in an Italian restaurant in Rome and that’s perfectly fine. It’s not unhealthy to eat white bread. It’s unhealthy to eat unhealthy white bread. Is that sort of the- Okay … finale of the answer?
Dr. Weitz: All right. So when it comes to treatment, I know you’ve developing a number of new therapeutics, including a form of rifaximin with timed release NAC.
Dr. Pimentel: Correct. We’re working on that.
Dr. Weitz: Can you talk about that? When is it going to be coming out? I understand it’s probably going to be a while?
Dr. Pimentel: We’re in phase 2B’s trials, so that’s a good thing. We’re enrolling right now, so for your listeners if anybody has diarrhea, IBS, we’re looking for patients. I’ll give you the number, 310-423-3792. Sorry, I had to get my plug in. 3792.
Dr. Weitz: That’s okay. And these are patients that [00:34:00] live in Los Angeles?
Dr. Pimentel: Yes. We’re looking for people in Los Angeles because, the faster we get the trial done, the faster these things get to patients if they work. And, but basically the gist of it is this E. coli and Klebsiella that you and I have been talking about, and some of the hydrogen sulfide producers, they partly live in the mucus of the gut, and so rifaximin doesn’t penetrate that really well. Adding the NAC gets the rifaximin to the bugs and gets rid of them.
And we hope we’ve seen in a proof of concept study that we have already presented at a nat- international meeting, is that this notion works. It works better than rifaximin alone. The, the question is, does that mean now we can get the bacteria lower? Does that mean less often needing a retreatment? Does that mean maybe we can get some people one and done and never need another treatment? All those questions start to be raised because we’re getting all the bad players where they live so that they can’t repopulate. So that’s one of the [00:35:00] things that we’re working on, and that’s the nearest thing to market, if you wanna put it that way, or nearest thing to be able to give to patients if the FDA trials all get done expeditiously.
The second is the methane, the drug that we’re working on, trying to get the methane production down without necessarily killing the methanogen. And to that extent, we’ve moved on from the drug development. We have our final molecule, and now we’re going into the preclinical phase, which is all the animal safety. So hopefully by 2027 sometime we’ll- Have a green light to start human trials
Dr. Weitz: With methane, this is a drug that blocks the enzyme that leads to the methane production?
Dr. Pimentel: That’s correct.
Dr. Weitz: Did this come out of the research you were doing on lovastatin?
Dr. Pimentel: It’s… lovastatin was the trigger that it could be done but it’s not lovastatin. It’s a brand-new molecule. And lovastatin doesn’t even hold a candle to this product.
Dr. Weitz: Now, blocking the methane-
Dr. Weitz: that’s not the same thing as killing the methanogens.
Dr. Pimentel: So we are basically blocking the enzyme in the methanogen that produces the methane. So to… That’s it. And so whether it reduces the ability for that bug to multiply, we don’t know yet. We’re studying that. But it really reduces methane production.
Dr. Weitz: Now, methane seems to be very difficult to treat, more difficult than hydrogen from people I talk to in the field, especially in the functional medicine side of things. Yeah. And do you know what the recurrence rate is for methane?
Dr. Pimentel: So first of all, the, the eradication rate for methane is lower than hydrogen. Okay. So it was, it’s probably about 50/50 for methane. That doesn’t mean flipping a coin. That means 50% of people, you can get them better with Rifaximin.
Dr. Weitz: And that’s with two weeks of Rifaximin plus Neomycin? [00:37:00]
Dr. Pimentel: That’s correct. And then, but the other 50% are troublesome and problematic, and they keep causing ongoing difficulties for these patients, and so we needed a better solution, something, a better mousetrap to get rid of methane, hence this new product.
Dr. Weitz: Some in the field are using antifungals like Nystatin. Have you tried that? What do you think about that idea?
Dr. Pimentel: Are you meaning for methane or for just,
Dr. Weitz: For methane, yeah.
Dr. Pimentel: Yeah, no, I haven’t. I haven’t used antifungals for methane. We’ve used antifungals for SIFO but not specifically for methane, so I don’t have a good experience with that. In fact, this is the first time I’m hearing this, so that’s interesting. I’ll look at it.
Dr. Weitz: That question actually came from Dr. Rhabar.
Dr. Pimentel: Okay. Yeah, I haven’t, I’ll need to speak to him to see what he’s doing.
Dr. Weitz: Okay. Yeah, he feels that fungus is playing a role in creating an environment in the gut that allows methanogens to flourish.
Dr. Pimentel: Interesting. I’ll talk to him, see what his thoughts are.
Dr. Weitz: [00:38:00] Okay. Methanogens are these interesting microorganisms. They’re not bacteria, they’re primitive archaea. Do you think in general that they’re beneficial to the microbiome? And looking at some of the research, I understand that they’re associated with an increased risk of colon cancer, though they tend to be low in patients with inflammatory bowel disease.
Dr. Pimentel: That’s correct. So I think we’re going back to our mothers again. Having the right amount of methanogens is good, too little is bad, too much is no good. And I think that’s… So look it’s the same thing for probiotics. Too much of one is not necessarily a cure, and not a good thing. And so I don’t know if we’re going to have a question on probiotics. Too many methanogens are not good or too much methane production. E. coli is not bad for the gut, it’s just when there’s too many of them, and they’ve taken over the, and the imbalance is there, that’s when we end up with these situations where we need to correct, have corrective action.
So I think it’s all the same. I, too low for methane for me would be a bad thing, a disaster. I don’t think we wanna eradicate or eliminate methanogens completely, and that’s where phage therapy scares me a little bit, because I don’t want phages to wipe out an entire population of microbes, because you can’t control these phages, they’re just gonna go at it. And I’d rather just kinda correct the numbers. So if we can get below 10 for methane, for example, let’s hold it there.
Dr. Pimentel: Let’s not shoot for zero …
Dr. Weitz: phage therapy a therapy that’s being developed right now?
Dr. Pimentel: There are some. I’ve had questions from- … parts of Europe where they’re interested in phages more, and they’re studying phages more, and there are some phages for archaea that some people have been exploring. Okay. But it frightens me a little bit, because I don’t want to apocalypse the [00:40:00] methanogens. I’d rather just bring the methane down to the normal range, is the way I see it.
Dr. Weitz: Let’s see. We talked a little bit about diet. You have a new version of the elemental diet with the MBIOTA, and can you talk about that? And that seems to have a high rate of effectiveness for both hydrogen and methane.
Dr. Pimentel: Yes. Correct. So the new diet, MBIOTA, is meant to be palatable. At least this is the moniker, is that it’s a palatable elemental diet because all previous elemental diets were a little bit hard to drink because they had unfavorable tastes. But 30 patients in the trial, all 30 finished the diet, which is remarkable for an elemental diet trial, and they, the methane went to normal and the hydrogen went to normal among those who were positive for those gases, and the symptoms also. But we know elemental diets worked from a study I did in 2003. It’s just now we have a diet that’s more [00:41:00] tolerable, so easier to take, but has about the same effectiveness as 2003.
Dr. Weitz: Though this one seems to work better for methane than that one did.
Dr. Pimentel: Yeah. Maybe. Maybe better for methane, but also maybe better for compliance, and that’s why methane’s better. It’s hard to know. Because it tastes better, so people actually do it, right? It’s hard to know the difference, but yes it’s it’s quite effective.
Dr. Weitz: You mentioned probiotics. In the functional medicine world we’re always seeing new research on probiotics and somebody’s always developing a new probiotic. And one of the new types of probiotics that are being developed are anaerobic bacteria.
Dr. Weitz: We, yeah, we have a number of them out there. What do you think about, we have Akkermansia, we have Faecalibacterium prausnitzii, we even have Roseburia, and these are also known as keystone species, and the claim is made that these anaerobic bacteria have more [00:42:00] potential for colonizing the gut, becoming permanent residents.
Dr. Pimentel: Yeah, I guess just on the superficial s- notion of it, the anaerobic bacteria are going to colonize the colon more because the small bowel doesn’t colonize with anaerobes as much. And the worry I always had with Lactobacillus, and we see this and now in our data, is Lactobacillus is actually harmful for the small bowel microbiome. The more Lactobacillus you have, we saw, we see more obesity. Unhealthy aging is associated with high Lactobacillus, and Lactobacillus in the small bowel is a disruptor like E. coli and Klebsiella. It destroys the natural, nice, normal microbiome to an extent. Maybe it’s not the case for the colon, but the problem is it has to transit through the small bowel.
But maybe anaerobes, because of the way they operate, they’re not gonna colonize the small bowel. They’re gonna get to the colon and operate there, and maybe that’s a better thing. And yes, these keystone [00:43:00] species may be more sensible, may be a more sensible approach. Another one that you didn’t mention is Prevotella, which seems to be what we call a convener. It tends to convene bacteria and bring the sort of balance back. So perhaps these are the better ones. Perhaps these, in time, will prove to be more harmonious in bringing in bacteria with them or harmonizing the microbiome a bit more. Time will tell.
Dr. Weitz: Since IMO and ISO are both conditions that involve the colon, isn’t addressing the colon to some extent makes sense for a complete resolution?
Dr. Pimentel: So the answer is yes to some extent, but we see that the breath test hydrogen sulfide levels correlate directly with small bowel hydrogen sulfide producers, as well as colon, and the same with methane. So the problem with those is you gotta get both. You gotta [00:44:00] get the colon in line, and you gotta get the small bowel in line, and we don’t know if these new probiotics make the methane go down, make the hydrogen sulfide go down yet. So it remains to be seen, but hey, I’m open to the opportunity to see probiotics that work, and maybe because this is, these probiotics are better informed, we’re gonna have better results. Let’s wait and-
Dr. Weitz: What’s the relationship between irritable bowel syndrome and inflammatory bowel disease? Is there a relationship?
Dr. Pimentel: So I’m struggling with this because I had a, some very interesting conversations at DDW. But in the 30 years I’ve been practicing gastroenterology, in the beginning, I said maybe IBS is a precursor to IBD.” I’ve never seen it. I have not seen an IBS patient in my practice… Let’s say I’ve had an IBS patient for 10 years, all of a sudden they develop Crohn’s disease. I’ve never seen it. I can’t even count on one [00:45:00] hand to see, having seen thousands and thousands of people, that happening. I’ve seen microscopic colitis in IBS. When, a woman becomes 60, 65 years old, the risk of microscopic colitis goes up. I’ve seen some IBS patients develop microscopic colitis, but never Crohn’s or ulcerative colitis. So having said that, a certain percentage of IBD patients have IBS, and there is this thing that happens after Crohn’s and ulcerative colitis heals that they have these IBS-like features. But that may be different. That may be just the nonspecific nature of the Rome criteria, and maybe the nerves of the gut are affected by the inflammation and take time to heal, and it’s just a sort of a shadow of the original IBD. I don’t know what that is, but it’s not like regular IBS.
Dr. Weitz: I suggest not that IBS causes IBD, but that patients with IBD can get IBS on top of their IBD that can account for flares. And when you treat the [00:46:00] IBS, their flare calms down. That’s what I’ve seen.
Dr. Pimentel: Yeah, and I have seen that, too. But I haven’t seen the reverse. I haven’t seen IBS become IBD, but I’ve seen IBD become IBS. And, as Crohn’s disease can cause strictures and stasis in the small bowel. So sometimes treating a SIBO, the patient’s already done well on the biologic agents for their IBD, but they have these remaining symptoms. They get rifaximin and all of a sudden that last bit of symptom goes away. I’ve seen that a lot.
Dr. Weitz: Are there any new treatments for hydrogen sulfide?
Dr. Pimentel: So the combination of rifaximin with NAC, the thing we were talking about, the one signal we saw that we presented at the DDW last year on the proof of concept study was hydrogen sulfide went down, and that was what was dictating the response. So wait, we’re doing three gas breath testing on this phase IIb study. We’ll be able to present that hopefully in six months or eight months. [00:47:00]
Dr. Weitz: Is there a good form of bismuth that you recommend other than Pepto-Bismol? Because, I hate to recommend a product like that- … that has all this artificial stuff in it.
Dr. Pimentel: Yeah, no, I use it because it’s convenient but there are bismuth tablets. As long as it’s around 500 milligrams of bismuth each time, I think that’s the most important rule. It’s not that Pepto is the best or, I’m not picking on any one product as being ideal. Look, there’s no randomized control trial with Pepto-Bismol or any other bismuth product. There’s only case control studies that show that bismuth in general reduces hydrogen sulfide.
Dr. Weitz: How often do you see SIBO patients who also have mast cell activation syndrome?
Dr. Pimentel: So this is an interesting thing because one of the organisms that goes up in SIBO is Klebsiella, and we know, and everybody knows Klebsiella can be a histamine producer, which can be a primer for mast cells [00:48:00] and other food allergies or food intolerances as well. So there is a relationship between the microorganisms in the gut and mast cell activation, and mast cell contribution to all of this. There’s a lot to be done to unravel this whole mystery, but we do see it, and we do see biogenic amines in patients with different types of SIBO when we suck the juice out of the small bowel. And of course, those are also primers for mast cells.
Dr. Weitz: What about mold as being associated with SIBO?
Dr. Pimentel: So mold meaning yeast or candida, or mold meaning mold? No,
Dr. Weitz: Yeah mold in their home that, yeah, ends up with mycotoxins in their body that affects their gut symptoms.
Dr. Pimentel: Yeah. Those are difficult studies to do, but obviously in my p- practice, I have patients who have these problems with mold in their homes, and they have suffer from chronic symptoms. And to an extent, some [00:49:00] of them get overgrowth and do better with antibiotics. But when the mold is there, they have trouble getting rid of the overgrowth. So we do see that. But how these mycotoxins work, we’ve done zero work on it, unfortunately. But I know there’s some, some clinical practices that specialize in this.
Dr. Weitz: To promote gut motility a number of people have come up with ways of stimulating the vagal nerve.
Dr. Pimentel: Yeah. So the vagus nerve is a complicated thing. It’s it’s, I asked this question at a meeting recently to some of the people who were presenting on the new therapies for IBS. So they were touting that tricyclics are good for IBS, which, sure they’re anticholinergic, right?
So they cause more constipation in a diarrhea patient, and that patient feels better. But tricyclics are anticholinergic, and they’ve been pushed for IBS for decades. Now we’re saying vagal nerve stimulation [00:50:00] is good for IBS-D, which is the opposite of tricyclics, and that’s also good for IBS. And they’re using both as an argument that this is a gut-brain disease because if you affect the vagus, you affect, and I’m like, can, and I said to the, I asked this question and, to the experts, and I said, “So you’re telling me that if you turn off the vagus, it works. You’re telling me that if you turn on the vagus, it works.” And I’m saying, “How can you say both?”
Dr. Weitz: It’s more starting a conversation between the brain and the gut.
Dr. Pimentel: That’s the way I think of it. One’s turning the conversation off, one’s yelling. And so I… It confuses me that both could work. I don’t deny the communication between the gut and the brain in terms of the vagus nerve and the importance of the vagus nerve. That’s not what I’m saying. I just find it… I don’t want the vagus to be an argument that the gut-brain axis is the reason for IBS simply because there’s communication. [00:51:00] It’s like saying, “I have pain in my hand. It’s the brain that’s the problem, not the broken bone in my hand.” But there are nerves that are, like vagus nerves, that are carrying that information to my brain saying, “Please take care of your hand. It hurts. Don’t go typewriting right now.” So we have to… The, the vagus is important. It carries traffic information for diagnostic purposes to the brain. The question is: Is the vagus broken or not broken? And I don’t think we have an answer to that question.
Dr. Weitz: Okay, one final question. If we sat down five years from now, what do you think we’ll realize that we were getting wrong about SIBO in 2026?
Dr. Pimentel: Yeah I, first of all, I would hope we have a couple of new therapies for IBS, for SIBO. I think what we’re going to realize is that the overgrowth syndromes that we are just scratching the surface of [00:52:00] are one of many, that it isn’t as simple as just ISO, IMO, and SIBO as we understand now. Now we have ISO, and we’re like we didn’t even know that existed five years ago.” I think there’s going to be other extensions of this that are going to further improve our ability to understand this. And it probably is not as simple as high E. coli and Klebsiella. There’s probably a cascade of organisms that change, and we need to understand that better. Maybe perhaps we’re still oversimplifying the story, and usually that’s the case. So that’s how I would leave it at the moment.
Dr. Weitz: That’s great. Thank you for another excellent interview.
Dr. Pimentel: No, it’s good to talk to you again.
Dr. Weitz: One, one more time, you want to tell people the phone number to get involved in the study?
Dr. Pimentel: Yeah. If you ha- please, you have to have diarrhea, and you have to have met the Rome criteria for IBS, so there’s gotta be some degree of discomfort or pain. And you have to have a colonoscopy in the last three years that’s negative so that, we’re sure you don’t have [00:53:00] Crohn’s disease or ulcerative colitis. The number is 310-423-3792, and you can ask for Ava. She’s our, one of our senior coordinators. So thank you for allowing me to do that. Just trying to help some patients and get the trial done sooner rather than later.
Dr. Weitz: Absolutely. Thank you so much for all you do and for all the research you’re doing for the patients suffering with gut symptoms.
Dr. Pimentel: It’s my pleasure, Ben. Good to talk to you again.
Dr. Weitz: Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would very much appreciate it if you could go to Apple Podcasts or Spotify and give us a five-star ratings and review. As you may know, I continue to accept a limited number of new patients per month for functional medicine. If you would like help overcoming a gut or other chronic health condition, and want to prevent chronic problems, and want to promote longevity, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at 310-395-3111, and we can set you up for a consultation for functional medicine. And I will talk to everybody next week.
