SIBO and IBS with Dr. Mark Pimentel: Rational Wellness Podcast 102

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Dr. Mark Pimentel discusses SIBO and IBS with Dr. Ben Weitz.

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Podcast Highlights

4:29  Dr. Pimentel stated we now know that 60-70% of patients with IBS have SIBO, based on culture of the juices from the small intestine, not based on breath testing. There has been some controversy with breath testing, primarily because it had not yet been validated against a gold standard because we did not have good techniques for culture. He said that he’ll be presenting some data at DDW (Digestive Disease Week) with respect to better validating breath testing.

6:17  Re-Imagine Study.  Dr. Pimentel talked about the Re-imagine study who’s goal is to attain juice from the small intestine from 10,000 human samples in order to map out the small bowel microbiome. Some of the results will be presented at the DDW conference in San Diego in May. 

7:47  Autoimmune SIBO.  Dr. Pimentel explained his concept of the autoimmune origin of SIBO.  It starts with a bout of good poisoning from bacteria like Campylobacter, which release an endotoxin called Cytolethal Distending Toxin B (CTDB). The immune system reacts to this CDTB and then cross-reacts and creates antibodies against a structural protein in the intestinal wall called vinculin, which damages the nerves that control the motility of the small intestines. And there is a new blood test that measures these anti-CTDB and anti-vinculin antibodies–IBS-Smart that can help to identify this autoimmune type of IBS.  Dr. Pimentel explained that this blood test is not a substitute for the breath test, which identifies more patients with IBS and also tells the clinician which variant of SIBO is present–hydrogen or methane and these each require a different treatment protocol.  Dr. Pimentel also mentioned that while it hasn’t been published yet, the higher the level of antibodies, the more difficult the condition is to treat. 

13:19  Motility. Of the factors that have been described to potentially play a role in keeping the small intestine clear from bacterial overgrowth: 1. Hydrochloric acid, 2. Digestive enzymes, 3. Bile, 4. Motility, 5. The Ileocecal valve, 6. The GALT, the immune system surrounding the gut, Dr. Pimentel said the motility is the most important factor. Dr. Pimentel said that low acid from taking a proton pump inhibitor doesn’t give all these people IBS, so he doesn’t think low HCL is a big factor.  He also said that having low pancreatic enzymes or low bile are quite rare.  He said he’s seen a weak immune system in patients with HIV, but we don’t see it that often now, given how effective the HIV drugs are now.  As far as ileocecal valve function, Dr. Pimentel mentioned that we see a lot of patients with ileocecal resections in patients with Inflammatory Bowel Disease and they don’t all get overgrowth.  But if you have someone with an ileocecal resection and you have a little motility issue, then you can get overgrowth.

20:20  While it is easy to understand how there is a motility problem when the patient has constipation, but it is difficult to understand how there can be a motility problem when the patient has diarrhea. Dr. Pimentel explained that motility is not a passive process and motility involves the holding and moving backwards and moving forwards.  If you get amyloidosis, which is a type of scarring of the lining of the intestine, you actually get diarrhea because the tube is like a drainpipe, and water just blows right through it. So it’s motility that prevents it from being just a drainpipe.  Methane gas doesn’t paralyze the gut.  It actually causes the gut to tighten, which resists the flow of material, leading to constipation.

25:04  METHANE SIBO. Methane SIBO is particularly difficult to treat. Dr. Pimentel typically uses Rifaximin plus Neomycin. Neomycin is an aminoglycoside. There is another aminoglycoside, a Neomycin derivative drug, Genamycin that is given intravenously that can cause ringing in your ears and some patients are concerned that Neomycin can cause ringing in the ears, even though Dr. Pimentel has not seen it in clinical practice, so he will use Flagyl aka, metronidazole, which is equally effective as Neomycin, though he hasn’t published that yet.  Methane SIBO is caused by archaea, which are primitive organisms but are not, properly speaking, bacteria.  The archaea also tend to live very close to the mucosal surface and antibiotics may not penetrate the mucus layer, so Dr. Pimentel is looking at new drug proposals.  I mentioned to Dr. Pimentel that Dr. Rahbar has spoken about finding patients with methane SIBO often also having co-infections including with Lyme Disease, which could help explain why they are so difficult to treat. Dr. Pimentel said that he hasn’t seen that but he also hasn’t studied that association very much.  Here is a link to a presentation that Dr. Rahbar gave on IBS last year at our Functional Medicine meeting https://youtu.be/fd3fR97ilUA.

29:44  Methane SIBO contributes to weight gain through two mechanisms: 1. Hydrogen producers eat the fiber that we can’t digest and when they derive calories from fiber, we get the calories. If they produce too much hydrogen, they start to pickle themselves and inhibit themselves from continuing. But if there are also methane producers, they eat the hydrogen and allow the hydrogen producers to keep working. 2. Methane slows gastric transit and the more time the food comes into contact with your intestines, the more calories are absorbed from the food.

31:32  Hydrogen Sulfide.  The new SIBO breath test that measures hydrogen sulfide gas, as well as hydrogen and methane will be out soon.  The more hydrogen sulfide the more diarrhea, while the more methane the more constipation.  The hydrogen is the fuel for the methane or the hydrogen sulfide.

33:47  SIBO Recurrence.  In order to reduce recurrence of SIBO, Dr. Pimentel emphasized the importance of using a prokinetic such as low dose erythromycin or prucalopride and Zelnorm (tegaserod) which were both recently approved. In the Functional Medicine world we have a number of nutritional prokinetics, including Motility Activator, MotilPro, and others.  Dr. Pimentel referred to the Reimagine study where they are looking at aspirates from the small intestines and mentioned that they are looking at histamine in the juice. Some of the bugs produce histamine, which can explain some of the food intolerances we see.

37:09  Small Intestinal Fungal Overgrowth. We don’t know how often fungal overgrowth is playing a role in SIBO. Dr. Pimentel did say that there are cases where nothing seems to work and antifungals do work.  We don’t have a validated process for identifying fungal overgrowth of the small intestine, but he hopes that this may come out of the Reimagine study.  Dr. Pimentel said that this study will help to validate the proper way to collect juice sample from the small intestine and the right way to look for bacteria and fungus in this juice using proper extraction techniques.

42:12  Probiotics.  I brought up the topic of probiotics with Dr. Pimentel and I said that I had heard him say previously that he does not believe in probiotics.  I also mentioned that many Functional Medicine doctors use probiotics when treating SIBO, including some who will use Saccharomyces boulardii, which is not known to grow in the small intestine, or they’ll use a spore-based probiotic, which is believed to get all the way into the colon before it opens up.  Dr. Pimentel made it clear that he’s not anti-probiotic, but he does not feel that the data is strong enough to support their use at this time.  Most of the studies on probiotics are not that strong and they all use many different strains, so it is hard to even compare them in a meta-analysis. He said that once they can map out the organisms in the small intestine, which he will do in the ReImagine study, he does believe that there will be a probiotic way of manipulating the flora for the better, such as by putting some organisms that can crowd out the hydrogen producers. He just wants to make sure that we use the right probiotic, or probiotics, for the right thing.

46:06  Diet for IBS and SIBO.  Dr. Pimentel said that a low FODMAP diet has a lot of good data that it will reduce gas and bloating in patients with SIBO.  But long term it will lead to measurable nutritional deficiences and it will reduce microbial diversity in the microbiome. Thus, it is important to broaden out the diet for patients after 2-3 months.  Dr. Pimentel recommends a low fermentation diet that he developed at Cedars Sinai in 2001 that’s a little more lenient than the low FODMAP diet.  Here is the paper that Dr. Pimentel published in The American Journal of Gastroenterology in 2019 on Influence of Dietary Restriction on Irritable Bowel Syndrome.

 

 

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Dr. Mark Pimentel is a Gastroenterologist who is head of the Pimentel Laboratory and Executive Director of the Medically Associated Science and Technology (MAST) program at Cedars-Sinai, which is focused on the development of drugs, diagnostic tests, and devices related to condition of the microbiome, with a focus on IBS. Dr. Pimentel has published over 100 scientific papers and speaks around the world at conferences, esp. about SIBO and IBS. Here is a list of some of Dr. Pimentel’s key publications: https://www.cedars-sinai.edu/Research/Research-Labs/Pimentel-Lab/Publications.aspx

Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or by going to www.drweitz.com.

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Podcast Transcripts

Dr. Weitz:                            This is Dr. Ben Weitz with the Rational Wellness Podcast bringing you the cutting edge information on health and nutrition from the latest scientific research and by interviewing the top experts in the field. Resubscribe to Rational Wellness Podcast on iTunes and YouTube and sign up for my free ebook on my website by going to drweitz.com. Let’s get started on your road to better health.  Hello Rational Wellness Podcasters. Thank you so much for joining me again today. For those of you who enjoy listening to the Rational Wellness Podcast, please go to iTunes and give us ratings and review. That way more people can find out about the Rational Wellness Podcast.

Our topic for today is Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome and our special guest is Dr. Mark Pimentel. Irritable Bowel Syndrome is the most common gastrointestinal condition with an estimated prevalence of between 10 and 15% in the United States. IBS is a condition marked by abdominal pain, gas, bloating, diarrhea or constipation or both, sometimes urgency, sometimes nausea, et cetera. When patients with IBS undergo a colonoscopy, there’s no visual pathology, unlike patients with inflammatory valve disease, like Crohn’s. For many years, IBS was seen as a condition arising primarily from psychological stress until Dr. Pimentel discovered that an overgrowth of bacteria from the colon into the small intestine was the causative agent in a majority of cases of IBS.  However, this has not been easily accepted by the medical profession and, from my perspective, for the most part it still looks like it’s not fully accepted. For example, the website for the American Society for Colon and Rectal Surgeons states, “No clear answer exists as to what causes IBS. It’s believed that the symptoms occur due to abnormal functioning or communication between the nervous system and bowel muscles.” Even Cedars-Sinai’s website, where Dr. Pimentel works, states that “Health experts have not been able to find an exact physical cause for IBS. It’s often thought that stress is one cause.” Quote, unquote. Most gastroenterologists continue to treat IBS with an array of drugs that control the symptoms that the diarrhea or constipation pain or one way or another modulate the symptoms without even trying to address what the underlying causes might be.

Dr. Pimentel is the head of the Pimentel Lab and executive director of the Medically Associated Science and Technology Program at Cedars-Sinai, which is focused on the development of drugs, diagnostic testing, and devices related to conditions of the microbiome with focus on IBS. Dr. Pimentel has published over 100 scientific papers and among his many accomplishments are the following. He’s pioneered the use of the Lactose Breath Tests for SIBO and has published studies correlating with IBS and he’s been development a new version of the breath test that will include a third gas besides hydrogen and methane, which is hydrogen sulfite. He’s discovered the use of rifaximin as a treatment for IBS. He’s developed an autoimmune model of IBS. He’s developed a blood test looking at antibodies to be able to diagnosis this autoimmune cause of IBS. He’s discovered that the methane-producing organism, methanobrevibacter smithii causes the constipation. And Dr. Pimentel has really spurred the development of a SIBO community, complete with SIBO testing, SIBO drugs, SIBO supplements, the SIBO doctor podcast, SIBO conferences like the one in Seattle that I’ll be attending later this week. But most importantly, he’s given hope to millions of patients with IBS that they might be able to feel better and stay better. Dr. Pimentel, thank you so much for joining me today.

Dr. Pimentel:                     Thanks Ben. That’s quite an introduction. I appreciate it.

Dr. Weitz:                          So what is your best estimate of the percentage of patients with IBS that’s caused by SIBO?

Dr. Pimentel:                     So the data are quite clear on this. It’s about 60 to 70% of IBS is SIBO and this is not based, not just on breath testing, but actually on culture.

Dr. Weitz:                          Okay. Because there still seems to be some controversy. People continue from time to time to cite different studies that show these big ranges for what’s positive and question whether breath testing is really effective or not.

Dr. Pimentel:                     Yeah, I think the problem we had was with breath testing. So breath testing is a really good technology. However, it had never been validated against a gold standard because culture, at the time that breath testing emerged in the 19 late ’70s, early ’80s, we didn’t have good techniques for culture, so it really wasn’t ever properly assembled in the way that would make people confident. And yet, despite all of that, all these doctors across the US were using breath testing. So they didn’t like it, but they still used it and they were able to diagnose SIBO and make that affirmative. It’s only when we said that IBS could be SIBO that people started to sort of say, “Well, breath testing isn’t accurate” and all of this. But all that’s sort of disappearing because we’re now showing with culture, and there’ll be some data at DDW [Digestive Disease Week] that I can’t talk about yet. I think we’ll be able to say that breath testing is accurate to a certain level and that what we were saying all along just with breath testing alone was relevant. And we can talk more about that, during your Q and A.

Dr. Weitz:                          Right. Well, what do you think about when we start using PCR testing instead of culture? We’ll probably have even more accurate results.

Dr. Pimentel:                     Yeah, that’s what we’re doing here. We have a study, which, I’m sort of jumping the gun, but is called the Reimagine study. And we’re … Our goal is to attain 10,000 human samples, juice from the small bowel to try and figure out who’s who, what’s what, and what bacteria belong there, what don’t, and what is SIBO. And the first slice of the pie of that data is going to be at the D.E.W. meeting in about six weeks. And the one on … One particular is getting a plenary session and I think your viewers may be very interested in the results from that because it’s very compelling.

Dr. Weitz:                          Right. And yet, we’re still only able to get the juice from the proximal part of the small intestine, right?

Dr. Pimentel:                     Right, but what we’re doing with this study is that anybody who gets what’s called a double balloon enteroscopy, meaning they’re going the full length of the small bowel.

Dr. Weitz:                          Oh, okay.

Dr. Pimentel:                     Also getting juice. So we have 20 or 30 patients already in the trial who’ve gone all through the bowel. So for the first time, some … Another way of saying what the Reimagine study is, it’s really the first study in the world looking and mapping the small bowel microbiome. Because everybody’s focused on stool and we’re really redirecting to the small intestine.

Dr. Weitz:                          Cool. Can you explain your concept of the autoimmune origin of SIBO?

Dr. Pimentel:                     To me, this is probably the most exciting thing because it’s one thing to say you have SIBO. It’s another thing to treat it with antibiotics or even natural products. The problem is it just keeps coming back, so we’ve really been determined to find out why the heck is this happening? And can we get in there and stop it before it starts? Or intervene once it’s there to really … maybe we don’t need antibodies, but that’s a long way away. The point is, we started to show … And this predates us, that food poisoning could be a trigger for IBS. We then took it to the next level and said, “Well, we need to develop an animal model where a food poisoning we know causes IBS in humans,” and the biggest culprit is campylobacter. Could we create a model in rats where we infect them with campylobacter and they develop IBS? And we did. And it’s that model that we’ve been able to dissect every step of the process of how this happens. And so we now know most of the steps.

So there’s a particular toxin of food poisoning called CDTB, Cytolethal Distending Toxin B. And most of the bugs that cause IBS have that toxin. So we actually proved that if you just inject that toxin in the skin of a rat like a vaccine, they get IBS. But that toxin is a marker for the food poisoning, so that’s important, but it triggers an auto antibody call to a protein that’s you called vinculin. And then you get these anti-vinculin antibodies, which are really important for the nerves of the gut. And so we think it’s the anti-vinculin that damages and keeps the nerves damaged because the nerves that are damaged recover very quickly if the antibody’s gone, but it’s there and it’s keeping the situation tenuous. So the nerves are effected. The flow of the gut is effected and then the bacteria are allowed to accumulate. And so that’s the new philosophy and there’s a new blood test that sort of measures those antibodies and we can actually diagnose IBS. But people think, “Oh, you’re diagnosing IBS.” We’re not. We’re work … Yes, we’re identifying you as IBS, but we’re also identifying you as IBS having come from food poisoning. So the test is actually much more specific than it even suggests.

Dr. Weitz:                          So it can’t be a substitute for a breath test.

Dr. Pimentel:                     No, in fact, it works synergistically. So think of it like you have a heart problem and you go to the doctor and the doctor does an EKG and they do an echocardiogram to see the function of the heart. It’s the same sort of thing. If you do the blood test, which I think for my patients now is really important because I can tell them how it all started, number one. Number two, I can tell them “This is a real disease. Not in your head. You don’t have antibodies like this because it’s in your head or it’s psychological. This is an organic disease.” So that, I can tell you a lot of stories from patients who are in tears. They say that finally somebody found something in my blood that tells me I have something because all the doctors have been saying I’m crazy and everything is normal.  So that’s important because it’s not just about the doctor. It’s about the patient. The patient wants some comfort and knowing that they have something real, but the second part of that is, if you have a positive antibodies, then you know you need to be careful with food poisoning. You can’t just be eating off food trucks or being a little more risky with your eating behavior because if you get another food poisoning, those antibodies go higher. And I know from clinical experience, this hasn’t been published yet, higher the antibodies, the tougher you are to treat with antibiotics or any other remedy for this SIBO that develop.

Dr. Weitz:                          Interesting.

Dr. Pimentel:                     The SIBO tells you what type of treatment to use, what antibiotic and so methane versus non-methane and so forth.

 

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Dr. Weitz:                          I’ve really been enjoying this discussion, but I’d like to pause for a minute to tell you about our sponsor for this podcast. I’m proud that this episode of the Rational Wellness Podcast is sponsored by Integrative Therapeutics, which is one of the few lines of professional products that I use in my office. Integrative Therapeutics is a top-tier manufacturer of clinician-designed, cutting edge nutritional products with therapeutic dosages of scientifically proven ingredients to help our patients prevent chronic diseases and feel better naturally. Integrative Therapeutics is also the founding sponsor of Tap Integrative. This is a great resource for education for practitioners. I’m a subscriber to Tap Integrative. There’s videos. There’s lots of great information constantly being updated and improved upon by Doctor Lise Alschuler who runs it. One of the things I really enjoy about Tap Integrative is that it includes a service that provides you with full copies of journal articles and it’s included in the yearly annual fee. And if you use a discount code, Weitz, W-E-I-T-Z, you’ll be able to subscribe for only $99 for the year. And now, back to our discussion. Here is the link to TAP Integrative.

 

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Dr. Weitz:                          So of the factors that result in increased risk of bacterial overgrowth, we have hydrochloric acid production that helps to keep the small bowel clear, digestive enzymes, bile has been shown to do that. We have the motility, the migrating motor complex. We have the integrity of the ileocecal valve. We have the GALT, the immune system around the intestines. What do you think is the most important factor that help to keep the small bowel from being overgrown with bacteria?

Dr. Pimentel:                     So if I were to rank it based on my experience, 50,000 patients in the last 10 years running through our clinic doing breath tests and so forth, hands down motility is the highest rank. So I’m ranking them based on the likelihood they’re causing overgrowth and the commonness combined because the most common cause, I think, is motility and the most provocative cause is a poor motility. Of course if you have an adhesion of the small bowel, like scar tissue from surgery, almost universally you have overgrowth. Fortunately, that’s not as common. But again, the functional part, low acid … We make people low acid all the time and they don’t suddenly develop IBS. So the link between having low acid, using a proton pump inhibitor, something like Nexium or … it’s not so well defined. Yes, you do get some bacterial buildup, but I think the other mechanisms can compensate to some degree. That’s why not everybody who goes on a PPI suddenly blows up and gets distended and then gets diarrhea. Some do, but it’s not so clear cut. Pancreatic enzymes, fortunately most people produce pancreatic enzymes and the juices that digest bile and so forth, so yes, if those are deficient, you can get overgrowth, but that’s quite uncommon to have pancreatic atrophy or something to that nature.

And then the GALT, the immune system of the gut, we do see … We used to see people more commonly with HIV who progressed in their illness would get some form of overgrowth, but fortunately, we don’t see that these days. The therapies are quite good.

Dr. Weitz:                          And what do you think about the ileocecal valve? Do you think that plays a role?

Dr. Pimentel:                     So we see a lot of people with ileocecal resections here at Cedars because it’s a large IBD program as well.

Dr. Weitz:                          So these are patients with Crohn’s who have part of their colon removed, right?

Dr. Pimentel:                     Yeah, exactly. And so they don’t have a valve anymore, and yet they don’t all get overgrowth either. I guess if they motility is really, really good, you’re able to clear it out. Nobody’s really studied the ilium motility very well because it’s really hard to access that area for motility studies, but I think about it like the esophagus. So when you have reflux or food or liquid from the stomach going into the esophagus, the esophagus immediately starts contracting. It doesn’t like the acid. It detects the acid and squeezes it back up out into the stomach. That’s normal and that’s why most people don’t get heartburn because they just … A little bit of acid comes in every day and we know how to squeeze it out automatically. I think the ilium probably has some similar things that go on. Yes, the ileocecal valve, if it’s not there, you’re at risk, but as long as the motility is good.

So and there are … I know this gets complicated, but there are people, for example, that have overgrowth and you treat them once. Then you don’t see them for two years. So they probably don’t have that bad a motility. The motility’s just a little off, but not deeply damaged. Maybe the antibodies aren’t high enough. So I think if you combine an ileocecal resection, you’ve lost the ileocecal valve, and you have a little motility issue, it doesn’t have to be strong, then you can suddenly have overgrowth and it becomes an issue. So it may be a combination of factors. 

Dr. Weitz:                          What about people who don’t have a colon at all? Do you want there to be overgrowth then in the small intestine?

Dr. Pimentel:                     Yeah, I know-

Dr. Weitz:                          I know that’s a little bit off the topic, but …

Dr. Pimentel:                     So people live forever … Not forever, but they live a pretty similar length of life without a colon. So your lifespan is not reduced simply you have part or all of your colon removed because the small bowel’s where all the action is, in terms of absorption. I sort of make a joke with the … It’s not really a joke, but I joke with the fellows and the residents. When I train them, I said, “The greatest gift for us is a colon and an anus” and it’s really the anus, but we can get into that because birds don’t have that. They can let go of their excrement all day because they’re flying and nobody’s going to trace them back to their nest. If you’re dragging this stuff along all the way to your cave, the lions, they’re going to find you and they’re going to eat you. So our survival depended on creating packages and delivering the packages at a time that is most safe or convenient, when the lions aren’t around or whatever, so that you’re not tracked back. And so another way of looking at the colon is really your trash bin and you’re basically preparing the trash for pickup. And it doesn’t have as much of a role in your health as we used to think.

Dr. Weitz:                          On the serum test for antibodies, one quick question is, isn’t it the case that the primary immune factor in the gut is IgA versus IgG? And why not test for IgA reactions?

Dr. Pimentel:                     Yeah, so we tested it early on and the problem with IgA is that it’s mainly in the gut. So how do we get our IGA? We could test it in the blood, but maybe it’s not there. Maybe it’s just in the gut. You’d have to get the right kind of sample. There’s that problem first of all. But second of all, for autoimmune disease, we don’t know a lot about IgA-driven autoimmune disease. I don’t even know of an example of one. Since IgA is mostly secretory, it goes into the gut, I don’t know how that would get to the nerves of the gut. So we followed the breadcrumbs and found that the breadcrumbs led to more of a really systemic autoimmune response and then kept going in that direction. Haven’t gone back to the IgA, but it’s a good question. 

Dr. Weitz:                          When it comes to motility, and I know addressing motility is a factor I’m sure we’ll get into in a few. When trying to keep SIBO from recurring, one of the questions a lot of people have is, when they have constipation, it makes sense that they have a motility problem. But when they have diarrhea, they don’t understand how they could have a motility problem.

Dr. Pimentel:                     Yeah. So for the viewers, this is sort of a thing even a lot of doctors don’t quite get and I try to explain it to them. So motility is not a passive process. So if you paralyze the small bowel, completely paralyze it, like it’s rigid. Let’s say it’s thickened with tumor or amyloidosis, which is a type of scarring in the lining of the intestine, you actually get diarrhea because the tube is like a drainpipe, and if water just blows right through it. So it’s motility that prevents it from being just a drainpipe. So your gut is not moving things through in one direction. It’s actually holding and moving backwards and moving forwards. There’s a complicated process that goes so that you aren’t just a drainpipe. Otherwise, you’d put food in and about 10 minutes later food would come out if it was just a drainpipe. So that’s what confuses people. For example, when you talk about methane and constipation, methane isn’t paralyzing the colon or the gut. It’s actually causing the gut to tighten, and by tightening, it resists the movement or flow of the material and so then you get constipated because it isn’t allowing things. Things can’t go because it’s holding it up. And so it’s a little difficult sometimes to explain to patients how that all works, but that’s some of the nuts and bolts.

Dr. Weitz:                          Yeah, the whole constipation thing is way more complicated than we realize. A lot of times I’ll be a conversation with a patient about constipation and there’s a bunch of things that are all called constipation. There are patients who don’t go to the bathroom for days on end. There are patients who go to the bathroom multiple times a day, but nothing comes out. There are patients who can go to the bathroom, but they have to strain like crazy and it’s hard. So there seems to be multiple variations of what’s called constipation.

Dr. Pimentel:                     Yeah, you should be teaching my residents and fellows because you almost said it exactly the same as I do. So constipation is what the patient feels, not the textbook. The old textbook definition of constipation is less than three bowel movements a week is constipation, but as you very accurately point out, I have patients coming to my office say, “I’m constipated,” and then I say, “Do you go every day?” “I do, but it’s like two hours on the toilet every day before I can get anything out.” So of course they’re constipated. It’s obvious, but they don’t meet the definition that 30 years ago, doctors set in textbooks as the definition. So constipation’s complicated and you need to take a proper history, as you described.

Dr. Weitz:                          And is one of those forms of constipation more related to methane?

Dr. Pimentel:                     Yeah, so what we’ve seen … So there’s … I sort of bucket in three ways. There are the patients where it’s more of an anal-rectal problem. They feel the stool there and they just can’t get it out or they have trouble getting it out. And those patients, we need to do some physiological testing. Sometimes, more commonly in women, because they don’t have a prostate gland, the anterior front of the rectum can bulge and the stool gets trapped there and that’s called a rectal seal. And there are other little structural things that can happen that can make that particular type of constipation. That history’s pretty clear. I usually can pin it down with history and then do a couple of tests and we’re on our way to figure it out.  The middle group are the patients where they’re constipated. Every week’s a little different, but they have some bloating with it. And those tend to be more the methane patients, where they’re probably going two or three times a week completely, and then they have a smattering of other things.  And then there’s the third group where they’re not going for two or three weeks at a time. Like literally not a drop. And those are called colonic inertia and that’s a different animal all together. That is not methane, at least we haven’t seen it that way.

Dr. Weitz:                          Okay. So why is methane SIBO so difficult to treat?  Not that either form is easy to treat, but the methane seems to be particularly problematic.

Dr. Pimentel:                     Yes, this is why we’re working on this Centene project because we know even from our double-blind study using rifaximin and neomycin versus neomycin, yes, rifaximin and neomycin was superior, but a month later, things start coming back. So we know on the diarrhea side, people can go a month, six months, two years and not have recurrence. On the methane side, that’s not the case. They’re more troublesome. So-

Dr. Weitz:                          By the way, just to stop you for a second. I read something online, it was an interview with you or somebody talking about the fact that you prefer now flagyl, rather than neomycin. Have you changed your protocol on methane SIBO?

Dr. Pimentel:                     Happy to talk about the neomycin versus flagyl topic. So neomycin is a drug that’s been around for a long time. It’s a categorical drug called aminoglycoside. Now, back in the ’70s and ’80s and even further back, aminoglycosides were used intravenously because, in general, they’re not absorbed. They don’t get into your body. When you use gentamycin, which is a neomycin derivative intravenously, if you use it for an infection of a heart valve you got to be on it for three months back then. And so you’re on it for three months and then you started to get ringing in your ears and so they realized that that category, when it gets in your blood, can eventually cause ringing in the ears and those kinds of neurological changes.  So the FDA basically brush stroked neomycin with the same potential side effects, but neomycin’s taken by mouth, not absorbed. 95% stays in the gut, so it’s not like gentamycin where you would give it intravenously. And so people have said, “Well, what about this ringing in the ear business?” And I have never seen ringing in the ears after neomycin and we’ve treated thousands of people. Not even one case. There was one case in a trial. The neomycin and rifaximin trial. The first patient in the trial complained of ringing in the ears and they were getting the neomycin. And we had done, because of the FDA, ear testing before and then we did ear testing after. Turns out the day after he described the ringing in the ears, he developed a sinus infection and cold and all this stuff. So it as an impending flu that he was developing that was causing. And then we did ear testing two weeks later and his testing after neomycin was better than before neomycin. So I’m not saying neomycin makes your hearing better, but there was no damage even in that one instance that I’m describing to you. So for people who are uncomfortable about neomycin because of what I just described, we have used metronidazole in the clinic and it seems to have the same sort of efficacy as neomycin with rifaximin and so we’ve suggested that as an alternative, but haven’t published it.

Dr. Weitz:                          Okay, so let’s get back to just in general, why methane is so hard to treat.

Dr. Pimentel:                     Yep. Again, we don’t know. I’ve spoken to a lot of archaea experts and methanogens or methane-producing organisms are in the category archaea. And they seem to think, in the veterinary world, because they study methane production more, that these organisms are very close to the mucosal surface and maybe the antibiotics penetrating the mucus layer, maybe that’s a challenge. We don’t know the answer to that, but we’re working towards trying to find better and better treatments. And that leads us to the Centene proposed drug because we’re using a different mechanism.

Dr. Weitz:                          I spoke to Dr. Rhabar, an integrative gastroenterologist in LA, and he said that often when he has patients with methane, he often finds other infections, like Lyme, et cetera. And then so you have a complicated factor and that’s what he deals is one of the reasons why it’s so difficult to treat methane.

Dr. Pimentel:                     There can be complicating factors with methane. We haven’t seen that association with Lyme so much, but I should admit that I haven’t studied it as much as he has, perhaps, and so I’m not … I don’t know. I don’t know.

Dr. Weitz:                          How is methane SIBO related to increased risk of obesity?

Dr. Pimentel:                     Yeah, that’s a very interesting story. There’s sort of two perspectives on that and probably two mechanisms. The first mechanism is, you need hydrogen to make methane. So you need hydrogen bugs sitting beside methane bugs to give the fuel. Hydrogen is the fuel for methane production. So it’s like you have a car, but you have no gasoline. Nothing happens. So, but the fumes from the gasoline, all that hydrogen intoxicates the hydrogen producers. Now, the hydrogen producers, let’s talk about them for a second. They’re eating all the junk that you can’t eat, the lettuce, the fiber. They’re chewing on everything to get calories. And when they do that, they give the calories to you, but if they produce too much hydrogen, they start to pickle themselves and inhibit themselves from continuing. So they can’t fire through as much material when their hydrogen is intoxicating them, but when there’s methane bugs around, the methane’s sinking the hydrogen away and allowing the hydrogen producer to keep firing through and they get actually creating more calories for you by burning through all that lettuce and material that humans generally can’t digest. So that’s one mechanism.

The second mechanism is methane slows your transit. Slower transit, more time to absorb food. So I tell patients this if they’re methane. If you look at the calories on the back of a box that you’re buying at the grocery story, that’s not the calories that you’re going to get from this material. It’s going to be something different, something higher, because of the mechanisms I just described.

Dr. Weitz:                          Can you talk about the new breath test? And when is that going to be available?

Dr. Pimentel:                     Yeah, so it’s coming out shortly. It’s weeks or months. It should be weeks, but it’s basically measuring three gases, hydrogen, methane, and hydrogen sulfite. And just to explain, methane is causing constipation. We know the higher the methane, the more constipated. We put methane into animals, they get constipated or slowed transit. So we know methane’s the culprit and hydrogen is the fuel for methane. The higher the methane, the more constipated you are. We were never able to correlate hydrogen with diarrhea. So you could have a hydrogen of 200 or a hydrogen of 50. Your diarrhea could be the same, the bloating could be the same. It was not statistically different, even thousands of breath tests analyzed, we couldn’t see that signal.  So we knew there was another gas. We knew hydrogen sulfide was there because that’s been known for decades, but nobody’s measured it on the breath. So we did and we presented that last year and the more hydrogen sulfide you produce, the more diarrhea you have. So basically what we now understand is hydrogen is a marker for SIBO, but it’s a fuel marker. So it’s providing the fuel for either methane or for hydrogen sulfide and depending on who’s winning the battle for hydrogen in that game of thrones, so to speak, you either have diarrhea or constipation.

Dr. Weitz:                            Interesting. So would that mean in the future you’re going to focus on just treating the methane or the hydrogen sulfite and not treat the hydrogen?

Dr. Pimentel:                     Well, the funny thing is, it just goes back to what I said earlier. If you get rid of the methane, the hydrogen goes up and pickles the hydrogen bucks. So you could, in fact, by getting rid of methane, impact the amount of hydrogen produced by hydrogen organisms. So as in medicine, the story is always more complicated than when you first start and we’re getting more complicated, which is why we’re doing podcasts so people can be educated and as up to date as possible.

Dr. Weitz:                            So what do we do about SIBO recurrences? In the functional medicine world where we usually don’t use antibiotics, we’ll use antimicrobial herbal combinations. And when we treat once and then it recurs, we of course think about using motility agents. And a lot of times we’ll use a motility agent like things … 5HTP and ginger and things like that. And there’s a number of products on the market. And then if they don’t resolve in two or three months or they recur, then we think about changing the antimicrobials. We sometimes think about getting a biofilm busing agent or we wonder, could this be a case of fungal overgrowth or could there be another infection? Could it be histamine intolerance? That’s another common concept now in the functional medicine world that some of these patients with these functional gut disorders who have SIBO but they don’t get better, one of the reasons could be histamine intolerance.

Dr. Pimentel:                     Yeah. Well, so you asked a very compound question with a lot of facets.

Dr. Weitz:                          I threw a bunch of stuff out there.

Dr. Pimentel:                     Yeah, you did, but it’s all important and so one of the mainstays of preventing SIBO is we use a prokinetic of some kind. You mentioned some of the natural prokinetics, so we use a low dose of erythromycin, which is a prokinetic and not an antibiotic at that dose. Prucalopride just got FDA approved and so that’s available now. Zelnorm (tegaserod), which is another product which hadn’t initially got approved in December now got approved. So we’ve got, at least on the allopathic side, we’ve got a plethora of prescribable preventative or maintenance therapies that we think are very effective. We’ve been using resolor or prucalopride, it’s called motegrity here in the US, extremely successfully with some patients lasting a year or two years with no recurrence. But the histamine story is very interesting and again, I go back to what we first said at the beginning of this interview is the Reimagine study that we’re doing. We’re not just taking aspirates and looking at bugs. We’re looking at the juice, what the bugs produce. We’re looking at histamine in the juice, histamine in the blood, serotonin in the juice, in the blood, genetics. We’re looking at immune markers in the blood, in the biopsies.  The collection of data that we’re getting around … because bugs produce histamine. There are many organisms in the gastrointestinal tract that are histamine-producing and can explain maybe some of these food allergies or food intolerances, especially if you’re feeding that one organism that happens to be producing histamine, that’s not a good thing. And so there’s … We don’t have all the data yet, but I am greater than 90% certain we’re going to see some really interesting signals because bacterial can also produce serotonin, as you probably know. And if we happen to be feeding the wrong types of bacteria in there, we’re going to overproduce those chemicals that can make people unwell.

Dr. Weitz:                          And when is fungal overgrowth or what we could call SIFO, how often is that seen?

Dr. Pimentel:                     So we’ve treated a lot of people with antibiotics and we would imagine that they would get worse if it was fungal, or at least that’s the old teaching, but we do see some patients where nothing works and antifungals do work. We don’t … Dr. Cynthia [Shroun 00:37:33] in Georgia has a process by which she identifies SIFO. We haven’t validated a process like that here at Cedars, so I think we should. I think as we’re doing this Reimagine study we’re actually looking for fungus as well, and as we identify who would be the target, I think we’ll have some better … So again, not continuously going back to this Reimagine study, but part of the Reimagine study was people were doing cultures from the small bowel wrong. People were getting juice from the small bowel wrong. People were handling the juice wrong.  We’ve been validating every step of what … because at the end of this next year, we’re going to educate on how to get those samples, how to process those samples in papers that we’re publishing. How to look for fungus the right way. How to look for bacteria the right way, because we get 10 times more bacteria after we pretreat our samples. And so if we’re getting 10 times more bacteria, we’re getting a better perspective on what all is there because some bacteria are locked in certain compartments of the juice and if you don’t unlock them, you don’t even know they exist. Same with fungus. So the problem with just taking the juice and looking for fungus is none of this has been bedded through proper validation and extraction techniques. So we’re going to educate around all of this over the coming years. Maybe we’ll do more podcasts.

Dr. Weitz:                          Have you considered urinary organic acids as a way to screen for fungal?

Dr. Pimentel:                     Absolutely, I think there’s something to be said about that. So we are not collecting urine as part of this. We’re looking at blood as a hopeful area. So let me paint a picture for you so that you can see where we’re going. So let’s say we find a bug. Maybe it’s candida, maybe it’s klebsiella or something in the gut that’s the culprit for that patient. Is there are a marker in the blood that tells us it’s there? Because we’re collecting blood and so we’re able to find some chemical that that organism produces that happens to be spilling over into the blood. We can measure it and then a doctor can diagnose that patient with that bug in their gut as a cause of that disease and then be able to get it. We haven’t turned towards urine, only because urine is important right now, but urine tends to be a filtrate of blood. So it only detects some of the things in blood. Blood has everything in it, so we think we’re going to have a better capture rate by doing blood rather than urine as we refine our searching. But you’re right, maybe we have to do some urine in this as well eventually.

Dr. Weitz:                          Now, when it comes to treatment, we have all these complicated protocols, but can we just drink celery juice? I read on the internet that it cures SIBO. I’m kidding.

Dr. Pimentel:                     There’s a lot of things on the internet report to cure many things. I never bash anything because the way I look at … There are doctors who will say, “Oh, that’s just rubbish.” And this. We don’t know what we don’t know and until we study it, we don’t know. There were many people in the 1980s and ’90s who said that H pylori is a joke. It doesn’t cause ulcers. There are people who said that the herbs are not antidepressants and then we learned about studies from St. John’s Wort and other products and they are antidepressants. So I don’t say no til I see a study that says no, a good study. And so I’m sort of giving you a vague answer. I’m sorry.

Dr. Weitz:                          That’s okay. So-It wasn’t a serious question anyway.

Dr. Pimentel:                     I know, but I really don’t … I don’t really like criticizing until I know that … What I don’t … Here’s what I don’t like. I don’t like when there are companies making a lot of money on the backs of patients suffering and not putting the money where their mouth is and do a couple of trials and give us some good information about it. That’s what I like. And I’m happy to talk all day, all night about good trials and good products.  Whatever it is, I don’t care.  If there’s good trials and good information around it, let’s help some patients.  Let’s get them the black, white, or gray answers, but let’s get the answers.

Dr. Weitz:                          I’d like to talk about probiotics. I know I’ve heard you say in the past that you didn’t think there was any benefit, but in the Functional Medicine world, we tend to use probiotics for patients with SIBO. And I did see a meta analysis in 2017 from Zhong, and others in the Journal of Clinical Gastroenterology, who did find that even though probiotics didn’t prevent SIBO, they were effective at decontaminating SIBO and reducing hydrogen gas levels. And I know one prominent Functional Medicine doctor is very big on using probiotics and I know other Functional Medicine who want to use a probiotic to see. They want to make sure we maintain the integrity or improve the microbiota and so they’ll use Saccharomyces boulardii, which is not known to grow in the small intestine or they’ll use a spore-based probiotic, which is believed to get all the way into the colon before it opens up. What’s your thought about probiotics and SIBO?

Dr. Pimentel:                     So I’m not, again, anti probiotic. I think people get that perception that I’m anti probiotic. I’m not. Again, I’m pro data. And so yes, this meta analysis came out and kind of affects us in a way because you’ve got a whole bunch of tiny trials that … and mostly small trials that if you pool them all together, you get some power. So I’ve heard the probiotic companies say, I’ll quote a trial that says, “Look, this probiotic didn’t work.” And they say, “Yeah, but that’s not our strain. Our strain is different,” right? And I said, “Okay, so we need a study with your strain.” But then the probiotics will come and they’ll quote this meta analysis, which is 10 different probiotics that are totally unrelated and say, “Look, probiotics work for SIBO.” So that seems dichotomous to me. On the one hand, when a study’s negative you’re quoting that’s not our strain. On the other hand, when there’s a meta analysis of 10 different strains, you’re saying, “Look, probiotics work.”

It’s a little mysterious to answer in that way. My answer is, once we understand the organisms better, I do believe there’s a probiotic way of manipulating the flora. I do believe if you put more of one organism in, you’ll overcrowd some of the hydrogen producers and maybe that will reduce hydrogen and so forth, but I also know that no matter what bug you put in there, it’s producing gas because that’s what they do. So the question is, are you just shifting it from one phenotype of overgrowth to another type, because the motility’s still bad. So you’re shifting it to another type of overgrowth that may have a different phenotype, so maybe you’ll say, “Oh yeah, my bloating’s better, but now my diarrhea’s worse” or my … What are we really, really doing? And again, this speaks to the Reimagine trial because the Reimagine trial is going to say, “Okay, this is what the normal small bowel bacteria look like.” Never had that answer. So until we have that answer, we don’t know how to make it look normal because we don’t know what bugs to put in there.  So we’re going to educate around probiotics eventually, but I know it’s a long answer to a tough question. I’m not against probiotics. I just want to make sure that what we end up doing in the end is the right probiotic for the right thing. And it may be five different probiotics with five different scenarios, or maybe even more. It may be much more complicated.

Dr. Weitz:                          On diet, I read your paper on diet and IBS and you talked about the low FODMAP diet. Which type of diet do you use with your patients?

Dr. Pimentel:                     So everybody is pretty convinced with the research that’s been published on the low FODMAP diet. So it’s sort of like I put the things on a spectrum.

Dr. Weitz:                          It certainly is the most common diet used in the Functional Medicine world for SIBO.

Dr. Pimentel:                     Well, absolutely. And for good reason. There’s good data. But I look at diet on a spectrum. If you don’t eat anything, you won’t be bloated. So that’s the ultimate extreme. If you go on a low FODMAP diet, which is fairly extreme, you will reduce gas and bloating. I’m convinced of that, because you’re not eating anything that produces much gas. We tend to lean more towards the low fermentation diet because it’s more tolerable. The problems we’ve encountered and seen in the science on low FODMAP is, after three months, there are measurable nutritional deficiencies on the low FODMAP diet.

Secondly, and functional medicine people know this almost better than anybody else. Low diversity of bacteria is a bad thing. That’s why you’re administering probiotics and other things, trying to expand the diversity. Low FODMAP equals low diversity over time, so it’s … You could say in the 2019 way of thinking of the microbiome, it’s damaging the microbiome and we don’t know … And a lot of times when we damage the microbiome, it doesn’t bounce back after stopping. We see that sometimes with antibiotics as well. So in essence, it’s acting like an antibiotic because it’s destroying a part of the microbiome in some way. So we try to be a little more liberal with the diet and that’s why we favor the low fermentation diet, something that we started in 2001. Never really published a lot about it because we’ve been focused on the other stuff that you and I’ve been discussing today, but we like it because it’s more lenient and a little bit more tolerable for patients.

Dr. Weitz:                          Yeah, we usually just use the low FODMAP diet for no more than two to three months and then we try to expand the diet as much as possible.

Dr. Pimentel:                     And that’s the right way to use it. So it is effective, but you have to start reintroducing for the sake of the things we talked about.

Dr. Weitz:                          In that review article, you mentioned Curcumin, which I thought was really interesting because it’s one of my favorite herbs and I use it regularly with patients with inflammatory bowel disorder. And you mentioned that it reverses gut hypersensitivity, which can be beneficial for IBS. So I thought that was really interesting.

Dr. Pimentel:                     Yeah, Curcumin is a fascinating chemical. You think about all the stuff that has been done over the millennia, pickling, anything to preserve food. You didn’t have a refrigerator back then. You couldn’t even get ice. So how do you keep food from spoiling? So herbs were one of the mechanisms and my wife said, so it’s an interesting story. We were watching a movie and there’s a scene that … There was a battle and the new person in charge said, “We’re going to move the capital of India to Delhi.” And they said, “No, you can’t do that because the river is contaminated.” And the king says, “We’ll figure it out.” And the way they figured it out, and actually, I think it’s a docuseries to be honest. The way they figured it out was they added spices, which were able to ward off some of the poisonings and things and kill the bacteria that was in there, and tumeric was one of the roots. Think about it, roots growing in a dirt of bacteria and it manages to survive. So roots are interesting and so I guess they figured out that tumeric doesn’t have a lot of flavor, just preserves. So it’s an interesting compound and interesting root.

Dr. Weitz:                          Yeah, I followed up with your references, the paper from Dilbecco, and he was particularly talking about the Curcumin phytosome form, which seemed to be particularly beneficial. So I think that might be something for us to consider in the functional medicine world for adding to our SIBO protocol.

Dr. Pimentel:                     Yeah.

Dr. Weitz:                          So your clinic at Cedars, are you guys still looking to see more patients or are you not accepting new patients there?

Dr. Pimentel:                     So I’m, as you can imagine, full to the gills.

Dr. Weitz:                          With research, yeah.

Dr. Pimentel:                     Not just research. I’m trying to do the research. So there’s two problems for me. If I don’t have time to do the research, we don’t get the new things that are really good for patients because I’m too busy with clinic. But I still see patients in clinic. It’s just … The number of calls we get a week to see me is more than my capacity, so I’ve sort of shut things down because what happens, and I’ll be very transparent here, is that they wait six months to see me and then when I see them, I find something catastrophic that should have been diagnosed six months ago. It’s not fair for people to wait six months. Better not to accept a patient than to have them linger on the hope of finding something for six months with an illness that’s more tragic than they expected. So there’s a lot of things that I’ve encountered over the years that have made me stop seeing news until I have room again and then I open up and then I close down again. But we have other motility doctors who work with me who have the same sort of skill and experience I do and they’re still accepting patients and we’ve just hired a new doctor who’s starting in September and I trained her way back and she’s coming back and she’s incredible. So we’re trying to find the space for all the patients.

Dr. Weitz:                          Great. Do you want to leave a way for patients who are listening to this to contact your clinic?

Dr. Pimentel:                     Our clinic … No. If you look on the website at Cedars-Sinai, you can definitely find the telephone number, but I don’t want to have a … Our call center is already overwhelmed. And if I leave that …

Dr. Weitz:                          Right.

Dr. Pimentel:                     But I do want to say one last thing if I can. I think the biggest thing I experience with some of our discoveries, like the blood test for example, is that patients are frustrated. It’s, “Well, my doctor doesn’t know about it and I really want it and I can’t get it and my doctor is … ” We had the same problem with rifaximin back in the day. The doctors weren’t believing. Now everybody believes. Everybody’s onboard with the SIBO IBS concept. It’s not a mystery anymore and so that’s really good, but all this stuff takes time and I … If your viewers are patients, I’m sorry for the frustration that your doctor doesn’t know about this stuff yet. This stuff takes months or years to filter to them. And we’re doing our best, like this, to try and get as far out there as possible and educate. And I appreciate you taking the time to do this podcast with me now.

Dr. Weitz:                            Excellent. Thank you so much, Dr. Pimentel.