SIBO: New Research Findings with Dr. Mark Pimentel: Rational Wellness Podcast 311

Dr. Mark Pimentel discusses New Research Findings on SIBO and IBS at the Functional Medicine Discussion Group meeting on May 25, 2023 with moderator Dr. Ben Weitz.

[If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.] 


Podcast Highlights

4:24  Dr. Pimentel started a fellowship at Cedars in 1996 on motility and his colleagues questioned why he would want to get involved with treating IBS patients, who are psychologically altered?  Patients with IBS seemed like regular folks who were struggling and it is too easy to attribute medical conditions that are not well understood to psychological causes. He reflected on when heart disease was thought to be primarily due to stress and in the early 70s if you had a heart attack, you were told that you needed to quit your job.  But it turned out that what caused their heart attack was more due to the steakhouse with the cholesterol and the alcohol and the smoking and your genetics and all the other things we learned about cardiovascular disease.  One of his colleagues in 1996 told him that “IBS is a disease of hysterical women.”

5:41  Anti-diarrheals.  Even in the last three years, the AGA guidelines say that anti-diarrheals like Imodium should be first-line therapy for irritable bowel syndrome because they’re cheap.  This is not a good reason to recommend a medication, rather than trying to figure out the cause of IBS and then treating that.  This is because the research that Dr. Pimentel has conducted and published for the last 26 years that demonstrates that SIBO is the main cause of IBS has still not been fully accepted by the GI community. 

6:36  Food poisoning is the cause of about 60% of cases of IBS-D and there is now enough research data to prove this.  The bacteria that cause food poisoning, whether it be E. coli or Campylobacter or Shigella or Salmonella secrete an endotoxin–Cytolethal Distending Toxin (CDT) and specifically the B version of CTD–CDTB–that leads to SIBO/IBS.  The immune system reacts to the CDTB and those anti-CDTB antibodies end up cross reacting with a structural protein in the intestinal wall called Vinculin.  Thus the immune system is attacking the body, an auto-immune reaction.  This leads to damage of the nerves that control the intestinal cleansing waves, which leads to a buildup of the bacteria in the small intestine (SIBO).  These small intestinal cleansing waves are peristaltic waves that are occur when you haven’t eaten for more than 3 or 4 hours, which help to clear out excess bacteria.  These cleansing waves are caused by the deep muscular plexus-interstitial cells of Cajal.  Dr. Pimentel has developed a second generation test that measures antibodies to CDTB and to vinculin via blood testing that is extremely accurate, the IBS Smart test from Gemelli Biotech. 

25:37  Methane SIBO (IMO) does not appear to be caused by food poisoning.  By paralyzing the gut in the case of hydrogen and hydrogen sulfide SIBO, this can lead to diarrhea. In the case of methane, this causes the gut to hypercontract and this overcontraction of the gut muscles leads to constipation.

29:33  In a study published in 2020 Dr. Pimentel’s group showed that a lactulose breath test–not a glucose breath test–and using the 90 minute cutoff of more than 20 parts per million increase in hydrogen it correlated well with the bacteria in the gut seen in culture and the hydrogen-producing enzyme machinery in the small intestine was elevated.  This shows that the hydrogen is being produced in the small intestine and not in the colon. (Leite G, Morales W, Weitsman S, Celly S, Parodi G, Mathur R, Barlow GM, Sedighi R, Millan MJV, Rezaie A, Pimentel M. The duodenal microbiome is altered in small intestinal bacterial overgrowth. PLoS One. 2020 Jul 9;15(7):e0234906.)

30:33  For the first time in 26 years Dr. Pimentel and his group in a study presented at DDW this year have been able to validate a breath test by correlating it with culture done on MacConkey agar but not blood agar and the cutoff should be 10 to the 3 rather than 10 to the 5. And with a network analysis of the data you can see that the microbiome of the small intestine starts to get significantly disturbed by the time you get to an increase in the bacteria of 10 to the 3.  By the time you get to 10 to the 5, the diversity of the bacteria in the small intestine changes drastically with decreased diversity and mostly proteobacter.  With methanogens we know that Methanobrevibacter smithii is the bad actor and with hydrogen sulfide one of the bad actors is Fusobacterium varium, which is very aggressive and is seen in stool as well as in the small bowel.  The cutoff for hydrogen sulfide was originally five and then it became three and now two will be the new cutoff for a positive finding on the Lactulose 3 gas breath test.

36:11  Breath testing validation.  Dr. Pimentel’s group finally published a study that validates breath testing  and in fact a system of breath testing by comparing it to a microbiome analysis. (Villanueva-Millan MJ, Leite G, Wang J, et al. Methanogens and Hydrogen Sulfide Producing Bacteria Guide Distinct Gut Microbe Profiles and Irritable Bowel Syndrome Subtypes. Am J Gastroenterol. 2022 Dec 1;117(12):2055-2066.)  We also see that the patients with methane, the IBS-C patients, tend to have very low hydrogen levels because the methanogens consume hydrogen as fuel.



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 150 scientific papers and he has written two books, A New IBS Solution, and he cowrote The Microbiome Connection: Your Guide to IBS, SIBO, and Low-Fermentation Eating with Dr. Ali Rezaie.  Dr. Pimentel 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 Functional 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 and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast.

                                                I want to thank our sponsor for this evening which is Integrative Therapeutics. And I believe that Steve Snyder is on the line to tell us about a few Integrative Therapeutics products. Steve?

Steve Snyder:                    Actually, since we’re kind of already ready to go, we have a great new curcumin product that’s going like crazy. I’ll just put it in the chat and also an update to the Elemental Diet. I’ll put that in the chat, too. And if you have more questions, you can just catch me after.

Dr. Weitz:                            Maybe just tell us one thing really quick about the Elemental Diets because that’s a very important treatment option for patients with SIBO and IBS.

Steve Snyder:                      So, the big news on the Elemental Diet is that we’ve reformulated it which the big part of it is that there’s a much lower carb content to it. So, we used to be 22 grams of carbs per scoop. It’s now down to 15 grams. And we’ve raised the fat and the amino acid content so it’s still 150 calories per scoop. So, it’s much better tolerated. It’s not nearly as sweet. And we have basically already sold through all the old stuff. So if you’re getting it, you’re getting the new formula and it’s much better. So, there you go.

Dr. Weitz:                            Excellent. Thank you, Steve.

Steve Snyder:                      Yup.

Dr. Weitz:                            Let me introduce our guest. Dr. Mark Pimentel is the head of the Pimentel Lab and executive director of the Medically Associated Science and Technology Program at Cedars-Sinai and a very prolific researcher having published over 200 scientific papers. The Pimentel Lab researches the microbiome and irritable bowel syndrome, one of the most prevalent gastrointestinal conditions.  Thanks to Dr. Pimentel’s research, we now know that most cases of IBS are caused by small intestinal bacterial overgrowth, which now has three categories; hydrogen-dominant, hydrogen sulfide-dominant and intestinal methanogen overgrowth. Each of these subtypes can be diagnosed with the latest SIBO breath testing and this can help guide specific treatments for each subtype.

                                            I just read that ChatGPT, the artificial intelligence bot that passed the exam to become an MD and also to become a lawyer, but it failed the exam to become a gastroenterologist. So now, we know that gastroenterology is the most difficult medical field. Dr. Pimentel, very warm thanks for joining us again tonight.

Dr. Pimentel:                      Thank you so much, Ben. Yes, ChatGPT cannot become a gastroenterologist which is good for us. I’m not certain I’d want a colonoscopy from ChatGPT either. I’m sure they’ll figure that out one day.

                                           So, I’m going to talk a little bit about irritable bowel syndrome and the microbiome and SIBO. And just to introduce you a little bit, the MAST program is … I’m in my office which looks like a rubber room but it’s not. There’s a really nice lobby out there and a beautiful lab in the back. But this is what we do. Our job is to try and figure out the microbiome, unlock the secrets of the microbiome and see if we can help some people with what we do here. And so, super excited to have the facility we’re in now.  But I’ve actually redone some of these slides in a way this past month after DDW sort of reflecting on maybe my age or what, maybe I’m having a late life crisis or a midlife crisis, whatever you want to call it.

                                           But 1996 is when I started fellowship at Cedars and I reflect on what … People said, “Are you going into motility? Are you kidding? You’re going to treat all these IBS patients who are all psychologically altered?”   And it turns out that I understood it very differently when I started to see these patients and I didn’t think of them that way. In fact, they seemed like just regular folk, but they were struggling and suffering. But it was all because when in medicine we don’t know what’s going on, we often attribute it to stress, anxiety, depression and other things. And I also reflect back to the early ’70s where if you had a heart attack, you got to quit your job. You got to quit your CEO. You got to lie on a hammock on a beach and relax or you’re going to have another heart attack because your job is killing you.  But what it turned out to be was the steakhouse with the cholesterol and the meat that was killing you and all the alcohol you were drinking and smoking and your genetics and all the other things we learned about cardiovascular disease and we’re all under stress. So, I don’t know. Yeah. So this was sort of the thinking of the time.

                                                This is a true quote from one of my senior colleagues who said, “IBS is a disease of hysterical women,” which in the context of 2023 seems ridiculous. The final thing I’ll point out in this slide is anti-diarrheals. So, Imodium, okay, Imodium works for diarrhea. But even in the last three years, the AGA guideline on IBS says anti-diarrheals should be first-line therapy for irritable bowel syndrome because they’re cheap.  And my hair curls, it’s already kind of curling, but my hair curls because would you ever imagine that an anti-diarrheal would be first line for Crohn’s or ulcerative colitis? It would make the diarrhea better, but there’s no way they would put that in the guideline. Sure, it’s anti-diarrheal, it stops or reduces diarrhea but it’s not treating the disease. We’re still stuck. I mean, if the fact that the AGA still says this is first line is a little bit silly at this point. But anyways, we are where we are and it is what it is.

                                                I’m here to talk to you about this which is sort of the IBS pathophysiological sequence as we’ve studied it for 26 years, which I’ll try to argue explains about 60% of IBS-D. And the methane explains about the same amount of IBS-C or the constipation side of things. So, yeah, we’re not explaining all of IBS but if we get 60% of it figured out, the other 40% will need more time and more effort. But I think that’s a good start.

                                                So, all of these organisms, food poisoning organisms have a single toxin in common which I’ll discuss leading to autoimmunity, some nerve damage and bacterial overgrowth. And there’s a whole lot of stuff that came out at DDW here, the DDW is the Digestive Disease Week, that really is a capstone to the 26 years in a sense and I’ll explain it as I get there.  Well, what I like to do is I like to start with the bookends and say, “Well, does food poisoning cause IBS?” And the answer is yes. This is a review of 45 studies by the Mayo Clinic 2017. So this is a little dated in the sense that it’s five, six-year-old study. But the same thing is true today. If you add more studies to it, you just get greater power.

                                                If you have a hundred people who go to a wedding and the food is tainted with E. coli or Campylobacter, 11% of those people, if a hundred people get sick, 11% will end up with the irritable bowel syndrome as a result of that. So, IBS is caused by food poisoning. The question is what percentage? And what we believe based on mathematical modeling is that it’s about 60% of all of IBS could start from food poisoning.

                                                The second question is, okay, we’ve been sort of saying, and I’m going to get to SIBO later, but we’re sort of saying that bacterial overgrowth and SIBO are interrelated. Well, but can food poisoning lead to bacterial overgrowth? So, this required animal models. And in early as 2008, we actually did this study. We developed the first animal model, not the first animal model of post-infectious IBS, but the first animal model of post-infectious IBS using a bug that actually causes IBS in humans commonly and is the most common cause of gastroenteritis in the United States. And that’s Campylobacter jejuni.  And so, 33 rats on this side, 33 on that side. Three months later after the infection is cleared, so really a total of four months, we then were able to quantitate the bacteria and look at their stool for consistency just before euthanasia. And you can see 27% of the rats who got Campylobacter now have SIBO. So, food poisoning can cause SIBO. Humans, food poisoning can cause IBS. We know IBS and SIBO are related.  And so, this is the first animal model that shows that when you get Campylobacter and you develop SIBO, the rats have altered stool consistency. So they’re getting an IBS phenotype. But it’s more deep than this and I’m going to show you some stuff at DDW that will really, I hope, impress you.

                                                But if you fast forward to 2022, I’m skipping a lot of studies because we only have a certain amount of time tonight. It would take me three hours to go through all the research to get to this particular summary. The Bradford Hill Criteria is sort of like the gold standard for, “Okay, does a bug cause a disease? What is the evidence?” And you have to meet all these criteria to be the strongest evidence. And this notion that Campylobacter causes IBS meets all the criteria.   So, this is pretty impressive. We finally have a cause for IBS and it’s food poisoning and it’s Campylobacter, but we just now need to iron out or understand the nuts and bolts in between, which is what I’ll take you through or part of that journey. So, here’s what that is about, the nuts and bolts in between. You’ve got the CdtB toxin and maybe some autoimmunity that develops that causes nerve damage. So, let’s work through that.

                                                Well, all four of these organisms, Shigella, Salmonella, Campylobacter, E. coli, look, they all look different. But they only share one specific toxin in common and that’s the CdtB toxin. And this is the active part of that toxin. It’s an A, B and a C and the B is the active agent. So, we had done some studies where we deleted the toxin from Campylobacter and administered that Campylobacter to animals and they did better. They didn’t get as much IBS.

                                                And then, if you look at what the animals were reacting to, so in other words, you get food poisoning, you get exposed to the CdtB toxin and you end up forming antibodies to this, vinculin. And vinculin is right at the end of these actin filaments, the green filaments in the cell which are the skeleton of the cell to keep its shape. And you can see it’s like the vinculin is stretching the cell out to reach out to its partner.

                                                And I don’t have time to go into detail of the different kinds of vinculin other than the body, but there’s really only one type where you get this autoimmunity and it’s the 117 kilodalton vinculin. But that 117 kilodalton vinculin happens to be important for the cells that make the cleaning wave of the gut called the deep muscular plexus-interstitial cells of Cajal.

                                                If you look at the top panel, that’s the healthy animals. A lot of these cells, a lot of these cells. If you go to the middle panel, that’s the Campylobacter-treated animals but do not have SIBO. So they still have the cells but they’re a little vague. But if you got SIBO and you had Campylobacter, the number is diminished. And not only is it diminished, you can see that when you count them, and this was a pathologist counting it blindly, you can see there’s a reduction in ICCs. And these are the cells that drive the cleaning wave.

                                                So, is the cleaning wave damaged in irritable bowel syndrome with SIBO? We actually showed that even before that other study that in 2002, we showed that if you take IBS patients with SIBO and compare them to healthy controls and you put a tube through their nose into the small bowel and measure cleaning waves, the IBS with SIBO patients have weigh less. Not only weigh less, 50% of the IBS patients, none, no cleaning waves in four hours of fasting. So, it is quite damaged in the case of the SIBO patients.   Well, we know from as early as 1977 that if you don’t have cleaning waves, you get overgrowth. This is Vantrappen who’s one of the great physiologists of the last generation and he discovered this. OK. So, now that we have an understanding that maybe CdtB is related to SIBO in some way, let’s really sink our teeth into this.

                                                And what I mean by that is maybe you don’t even need Campylobacter. Maybe all you do need to do is CdtB toxin. And that’s what we did here. We purified the CdtB toxin and we administered it to rats like a vaccine. So they get a shot under the skin in the back. They don’t get it in the gut. They don’t get it through the mouth. They get it in the skin. And then three weeks later, they get a booster.

                                                And of course, they didn’t have antibodies to CdtB before but they sure do after the vaccination. And so, the CdtB antibodies go way up. But look what other antibody goes up after, vinculin antibodies. So the rats exposed to CdtB developed autoimmunity to vinculin which is basically molecular mimicry, which I’ll show you in a second.

                                                But they also got SIBO. So, remember, we injected the CdtB under the skin, they formed these antibodies. And now in their gut, they have more bacteria in the duodenum and more in the ileum. And the vinculin expression, meaning the amount of vinculin in the gut tissue is reduced. So, this antibody is going after vinculin in the gut. And by doing so, we believe it’s causing this overgrowth of bacteria.

                                                So, we think it kind of works like this. You get CdtB exposed. You don’t like CdtB, you don’t like any of it, so you’re forming antibody here and antibody here and one here. But CdtB kind of looks a little like vinculin in that one area and therefore you get this autoimmunity. And that term is molecular mimicry. CdtB is mimicking vinculin in order for you to do something to yourself and create autoimmunity.   So, this is from last year’s DDW but this paper is literally on the verge of publication. We have a major revision at a journal and we’re just fixing that up and we hope to get that back and get that published sometime in the next month or so. So, we’re very close for this to be officially published. But it was presented. So it was presented at DDW last year so it’s open to the public so I can talk about it.

                                                But this is the same experiment again, but a deeper, deeper understanding. So, let me show you. And I’m talking about microbiome now. So, we did it again. We gave CdtB this group, nothing to this group. You see they don’t get antibodies to CdtB. They sure do get antibodies. Because they got the antibodies, their wet weight of the stool went up. And the higher the antibodies were, the wetter the stool was. So, this is pretty good evidence.  Second thing is nothing happened to the colon bacteria. Control, CdtB, control, CdtB. All the big changes were in the small intestine which was very interesting. Again remember, the CdtB is injected under the skin of the rat. It’s not injected in the gut.

                                                But what really was interesting was, so the control group, this is where the microbiome sits as a whole. So, the orange balls are the control animals. Three months later, the green balls are the CdtB-treated animals, three months later. And they didn’t change. Because the animals, like the people at the wedding I talked about at the beginning of my presentation, not everybody gets IBS.

                                                And so, what happens is a group stays like controls. A second group gets increased bacteria but of the E. coli type here which is a hydrogen producer. And a third group goes in the Desulfovibrio direction and they’re the hydrogen sulfide group. So the rats in the development of diarrhea IBS in this model develop two micro types, hydrogen-producing E. coli or hydrogen sulfide-producing Desulfovibrio. And you will see that when we get to the micro types that we just published in humans, it’s the same. So, hang on to that thought of the two micro types in D.

                                                I show this slide, it’s a bit complicated. We took these animals. We took their small bowel. And we looked at what was changing in the small bowel as a result of this CdtB. So, the CdtB, again under the skin. And then the proteins and things that are produced by the small bowel, what’s going on there at that level to create the problems that we know are quote IBS? And that’s this. But I’m going to show it in another slide to summarize it so you understand what’s actually happening.

                                                So, I think I got that down here. I don’t want to miss it. But if I don’t, I’ll come back to it. But basically, there are three things that happen. You get impaired barrier function as a result. You get a change in motility, meaning the proteins that control barrier function are negatively impacted by the CdtB. The proteins that control the signaling for motility are changed in a bad way. And then, you get enhanced visceral sensitivity which is what we know as pain in IBS and visceral hypersensitivity in IBS. So the animal model can explain the entire spectrum of what is irritable bowel syndrome.

                                                Okay. So now, we have these two antibodies and the question is, “Can we diagnose IBS using these antibodies?” Well, we did a first-generation antibody test. And the first-generation antibody test was okay. But then we realized that these proteins are really wonky. That’s not a medical term. But they’re wonky, they’re a little unusual. And you need to treat the proteins in a special way to allow the areas where the antibodies bind to be more accessible. And that’s called epitope optimization.  And so, we performed epitope optimization and we developed a second-generation test. And you can see that if you have anti-CdtB elevated, it’s way higher than IBD. Vinculin, even more impressively differentiating IBS-D from other causes of diarrhea like Crohn’s, ulcerative colitis and so forth.

                                                But this is the most important slide. Look at if you’re positive for both markers, even if you’re positive for one or the other, you’re over 80% post-test probability. And that’s medical certainty. Anything over 80% post-test probability is considered medical certainty. People say, “Well, look, the sensitivity is low.” If you do an either/or, this number will be 56. In the normal testing world, 56% sensitivity, yeah, maybe that’s not so great.

                                                But remember that out of a hundred IBS-D patients, we believe only 60 came from food poisoning. And this is a marker for food poisoning as a cause of IBS, not IBS total. So, if we’re at 56% and 60 is the number we want to get to, then we’re darn close to perfect here. The specificity is over 90%. But look at the likelihood ratio. And this is what determines your post-test probability.

                                                Look at the first-generation test. It’s a 2 and a 5.2. It’s now a 5.3 and a 6.3. Let me show you what that means. So, I’m going to show you every test that’s ever been developed for irritable bowel syndrome. So, pain perception does nothing. So by the way, the pre-test probability of IBS if you see a doctor is about 55%. So, you want to get above 55 with your nomogram using the likelihood ratio.    There was a 34 biomarker panel, got you to 74. That’s not on the market anymore. Bile acids in stool doesn’t get you to 80. The 10 biomarker panel from another company, not on the market anymore, doesn’t get you to 80. Visceral hyperalgesia, if you blow a balloon in the rectum and they get pain at an earlier time. Nobody does this, very complicated. Actually a little bit morbid for the patient. But it’s not bad, it’s over 80.

                                                Volatiles in the stool, not available, but people are studying this and they’re getting some decent results. Look at the first-generation blood test for IBS that we developed. It only gets you to 60 if it’s just vinculin. And it gets you to 80 if you’re a CdtB. Look at what we did to optimize it in the second-generation. Vinculin, CdtB. And if both are positive, the post-test probability is 98%.

                                                So this second-generation test, so there’s only one company with the second-generation test, all the other CdtB and vinculin are using first-generation technology and they just don’t cut it. I mean, they don’t get any … Well, they’re certainly not 80% or 80 with vinculin. And CdtB just barely scratches the surface. So, you have to get the second generation if you want the most accurate test.

                                                And so, it kind of works like this. You’ve got all this beautiful bacteria, all sorts of different shapes and sizes and colors. And then, you get Campylobacter which are the green organisms with the flagella here. They give you the CdtB. You form antibodies to CdtB. And then, you later form antibodies to vinculin. And that takes about two to three months after the food poisoning. Some people never form the autoantibodies. And as these go down, their IBS goes away.  But if you form these anti-vinculin, you’re stuck. You get this change in the nerves. And then you get a buildup of these blue characters which are the bacterial overgrowth. And that leads me to bacterial overgrowth.

                                                So, I’m going to show you some new data, really hot off the press data. So, what we know is that breath testing is abnormal. This is a 2020 meta-analysis. Breath testing is abnormal in IBS, full stop. So, there was a lot of criticism of breath testing because it’s an indirect technique.  So, what does breath testing mean? Is it transit? Is it colon bacteria? Is it small bowel bacteria? And to be honest, if you go back to the 1980s and ’90s, we only had hydrogen back then. And that really looking back was absurd because hydrogen is a fuel for hydrogen sulfide and methane. So if you don’t know methane and you don’t know hydrogen sulfide, you can’t know what the hydrogen level is because the hydrogen’s being used up.  So, if you have … I’ll show you a study that was just published from us. When methane’s there, hydrogen’s down because it’s not that it’s down, it’s being produced a lot, but the methanogens are eating it up. Four hydrogens to make one methane. Five hydrogens to make one H2S.  So, that’s part of the problem with trying to determine if the hydrogen level is high or low. You don’t know because you’ve got these consumers over here on the right. And it turns out methane is what’s causing constipation. And it turns out hydrogen sulfide is what’s leading to or at least associated with diarrhea. So you really got to measure all three gases or you’re kind of in the dark as to what’s going on.

Dr. Weitz:                          And Dr. Pimentel, we don’t think that methane is related to food poisoning?

Dr. Pimentel:                     Yeah. So, the antibodies that I was talking about earlier, they’re only present in about 20% of people with IBS-C. So, whereas 56% of patients with IBS-D have one or either antibody. So, yeah, food poisoning is more the D side.

Dr. Weitz:                          And it’s kind of ironic because by damaging vinculin, you’re damaging motility. And we normally think of constipation as being related to motility problems.

Dr. Pimentel:                     I’m not going to cover that today, but that leads to one other thing about methane. I’ll talk about methane in a minute, but I’m not getting into the details that I think you want to hear. Methane doesn’t paralyze the gut to cause constipation. It causes the gut to hypercontract.  And remember, if your gut is paralyzed, it becomes like a funnel and just drains things through. So the way you cause constipation is you cause the gut to stop moving and hold things. And so, what we see with methane patients is you get these contractions, not like this nice-flowing contractions. It’s like we’re going to hold everything here contractions. We call that segmental contractions versus peristaltic contractions. So methane switches your gears to hold everything as opposed to move everything along.  But in the case of vinculin, vinculin is doing damage to just the cells that cause the cleaning waves. So, you’re just affecting the small bowel microbiome and methanogens are both small and large bowel. And I’ll show you the new data on that which is really interesting.

                                                So even though there were criticisms about breath testing, all this time, people were starting to do culture as quote the gold standard. And I’ll talk a little bit about that later with some new data. But here’s the first culture study 2007 in Sweden. Clearly, IBS has more bacteria in the small bowel.

                                                This is I would argue the most important study because it determines the benchmark number. Again, 60%, similar to the food poisoning thing. This is D, again diarrhea aside. 60% of IBS-D patients in this trial had the cutoff of greater than 10 to the 3 or greater than a thousand bacteria per ML in the small bowel. So, they had overgrowth.

                                                And that leads me to the REIMAGINE study which is what we’re doing at Cedars here for the last few years. And this is a very difficult undertaking because nobody has ever looked at the small bowel microbiome until we started to look at it systematically in the way we have. So, we’re basically taking people who come in for upper endoscopy and no colonoscopy and getting their juice and measuring the bugs in their juice.

                                                And so by doing this, we looked at SIBO. And this is a paper we published now two or three years ago. And you can see that every ring represents a different level of life. So, the kingdom is bacteria, the phylum is here. And you can see right at the phylum level already in SIBO, Proteobacteria is taking up a huge chunk versus non-SIBO.

                                                Okay. And then when you get to, now we’re doing 16s sequencing here. You’re probably familiar with that term 16s sequencing. You’re sequencing the ribosomal RNA of the bacteria. Now, you can get pretty good at identifying bacteria by sequencing ribosomal RNA, but you can’t get past the genus level. So we’ve got Klebsiella and Escherichia, which are taking up the bulk of SIBO. But you’ll see in a minute, we did now in DDW.

                                                But in this study, what we showed is that when you do a lactulose breath test, not glucose, lactulose breath test, and using the cutoff that the experts have all agreed in, 90 minutes, more than 20 parts per million rise in hydrogen. It correlated very nicely with culture. It correlated very nicely with the bacteria of the gut.

                                                And when that was present, when you had SIBO defined by breath test, your hydrogen-producing enzyme machinery in the small intestine was elevated. So, for those who say, “Oh, the hydrogen’s coming from the colon, the lactulose is getting to the colon,” that doesn’t jive with this data. The hydrogen-producing machinery is up in the small bowel. We’re not taking juice from the colon, we’re taking it from the small bowel. It’s up when you have this positive breath test.

                                                But now, let’s go to DDW. Now, we’re really, for the first time, I know this sounds just bizarre. I’ve been talking about SIBO and breath testing for 26 years. But honestly, this DDW, we finally validated a breath test. And let me show you what I mean by that.

                                                So, if you look at culturing the bowel, some groups just culture MacConkey agar, blood agar, anaerobic, aerobic, add up all the colonies on the plates and say, “Okay, is it over 10 to the 5 or not?” Well, 10 to the 5 is not the cutoff, it’s 10 to the 3.

                                                And you can see this is the diversity chart so diversity on the y-axis. And you can see that SIBO has a lower diversity based on culture. But blood agar doesn’t distinguish SIBO at all. The diversity is no different whether it’s 10 to the 5, 10 to the 3 or lower than 10 to the 3. On MacConkey agar is where you see the microbiome deteriorating.

                                                So, let’s take that one step further. This is a network analysis. So a network analysis is like, okay, you got a city and every one of these little round circles is a occupation. In here, it’s a microbiome, it’s a microbe. But let’s call it an occupation. So you’ve got doctors. You’ve got lawyers. You’ve got bakers. You’ve got plumbers. You’ve got gas station workers. You’ve got sanitation workers. You need everybody in harmony in the right proportion interconnected so the city is healthy. So the more interconnected this looks, the better the city, the better the function. And so, this is a healthy human non-SIBO.  And the tipping point for the microbiome to go awry is 10 to the 3. It’s falling apart already. And this is on MacConkey agar. And then when it goes to greater than 10 to the 5, look at this, there’s nothing left. Everything is just destroyed. So, it’s as if you’ve put too many of one character in the city and everybody’s leaving the city, we’re done. Or it’s like the city’s full of criminals and now everybody’s leaving the city because it’s dangerous. And that’s sort of what happens in SIBO.  But I’m going to give you even more details, which is even more exciting in a minute.

                                               Quickly on methanogens, we know the methanogen now. We’ve been working on this for years. M. smithii is the bad actor. It produces high methane and that causes the constipation and the bloating.  This DDW, for the first time, we’re able to see exactly where the methanogens live in humans using sequencing. And it’s in the duodenum and it’s in stool. And it’s usually that Methanobrevibacter smithii that’s causing the trouble. And so, that’s why we changed … We believed that to be true and that’s why we changed the name to intestinal methanogen overgrowth and not SIBO methane. It’s intestinal methanogen overgrowth because it’s not just small bowel, it’s everywhere. And when it goes up, it goes up everywhere.

                                                And then finally, the hydrogen sulfide-producers, we have a lot of data on this character which is Fusobacterium varium, a very aggressive-

Dr. Weitz:                          Dr. Pimentel, let me just ask a quick question. So, the fact that methane is IMO, does that mean ideally, to see significant improvement in symptoms, we need to treat the colon as well as the small bowel?

Dr. Pimentel:                     You need to get the methane down. And if the methane’s coming from the colon and the small bowel which I believe that’s true in the case of methanogens, you have to get the methane down by reducing those organisms in both locations. That is correct.

Dr. Weitz:                          And that could be one reason why rifaximin may not be as effective for methane.

Dr. Pimentel:                     By itself, correct.

Dr. Weitz:                          Right.

Dr. Pimentel:                     Yeah. And we combine it. Yeah, you’re right. And then I’m going to show at least that one study a little bit later. Now, hydrogen sulfide, as I said here, hydrogen sulfide is associated with diarrhea. It’s a different animal because hydrogen sulfide is very reactive. So, the transport of hydrogen sulfide in breath in a bag or in a tube, it’s not stable. So you have to get a very special material to construct the bag.  You have to be able to prove that that transports and that it measures things correctly. You’ve got to develop an instrument that measures all three gases without cross-reacting with each other with the sensors and the orientation of those sensors in the instrument.  And then, you got to do a study to create a cutoff. So, the original cutoff was five and I’ll show you that. And then it became three. And now it’s moving to two and I’ll show you why. It’s always better when you start a new technology that you don’t say, “Oh, anything over one is positive,” because then everybody’s positive. And then, people are disappointed when the science says, “No, no, no, no, it’s two.”   We don’t want to overtreat our patients until we know the science. The first science said if you take a diarrhea patient, this is not D IBS, this was functional diarrhea. They were over five. So, diarrhea patients are over five, generally speaking. And the more severe the diarrhea, the higher hydrogen sulfide. But we learned a lot about hydrogen sulfide in this study. And I’m going to show you another study later that says two is a better cutoff.  But let me just set this study up because this is the first and this is published now as of December 2022.

                                              This is the first study in all the years of breath testing that compares a system of breath testing. And what I mean by that is the bags, the patient, the mailing to the company, the instrument, the result and the patient having either constipation or diarrhea, and that the gases on this whole system correlates with the microbiome. Never been done with a breath test in this way.  And you’ll see the results and you’ll see for yourself that for the first time, there’s a breath test that actually does correlate with the components or micro types of the microbiome. So, it’s a double-blind study for IBS-D, not of SIBO study. It’s a double-blind study for IBS-C. So D is here, C is these two. And they all had breath tests and they all provided samples so we could do the microbiome.  You can see that … Let’s look at D which is blue and look at their breath test just focusing on methane on the breath test. D patients, nada. We didn’t hand-select these for SIBO or non-SIBO, these were just D patients. In the C group, not all of the C had methane. You can see some of the Cs are this orange line down here, but the ones who did have methane, they’re up here. They have a lot of methane and they start with methane. They don’t go up with the sugar, with the lactulose.

                                                Now, I want to focus on hydrogen only. So you’ve got the same three groups. Look at hydrogen. By 90 minutes, in just unselected D patients, you’re already over 20 on average. Yes, there are some who are negative. Yes, there are some who are even higher. But on average, they have SIBO.  Look at the C patients with methane. They have the lowest hydrogen. But I already told you the secret answer to that. Methane patients eat hydrogen. So, they have to have hydrogen. You can’t make methane without hydrogen. So, they’re eating the hydrogen.  So, if you only measured hydrogen on your breath test, that patient would have been a low hydrogen. You wouldn’t know. You have to measure methane. The same thing is happening for hydrogen sulfide. Look at hydrogen sulfide on this test. It’s higher in D and not in C. So, you’ve got to measure all three gases.

                                                But this is the part I was trying to get to and this exciting part that if you have methane on your breath test, M. smithii is elevated. Not just that, it correlates. So the higher the methane levels, the higher the M. smithii was in stool. And the higher the methane levels were and the M. smithii was in stool, the lower your hydrogen got at the end of the breath test with lactulose because all the hydrogen’s being shunted to methane. It’s a negative correlation.

                                                So then, everything’s fitting for the first time looking at breath test, really complicated diagram. Everything with stars in it is statistically significant but let me focus on a couple of things. When the methane, when it’s blue, it’s a positive correlation. When it’s orange or red, it’s a negative correlation. You could tell by the graph here. So hydrogen is down if the methanogen is up. Methane is up if the methanogen is up. And so, that’s how it goes.

                                                But let’s move through. The hydrogen producers that are producing the hydrogen for methane are not E. coli and Klebsiella. They are Christensenella and Ruminococcaceae. And if you want ask more questions about that, we can do that at the end. But we now know sort of the micro type of methanogenesis and it’s not what we used to think.

                                                Okay. So let’s go now to hydrogen. And breath hydrogen is negatively correlated with methane. I’ve already said that. Fusobacterium, positively correlated with hydrogen sulfides. So this is your hydrogen sulfide-producer. And I’m going to go to this. This is basically the same as this just in a more easy to read format.

                                                So, if you’re methane and you’re constipated, these are the enzymes that are upregulated in your gut. Methane production, this is objective measurement. I’m not making this up. This was actually the output from the science. And F420 which is the methanogenesis enzyme. If you’re IBS-D, it’s hydrogen sulfide pathways that are elevated.

                                                So in this study, we defined finally the two micro types for D which are hydrogen E. coli micro type and Desulfovibrio and Fusobacterium hydrogen sulfide micro type, the same as the rats. The rats didn’t get C but this is the C micro type which is Methanobrevibacter. And then these two characters which are the synthroph. Synthroph means your buddy who’s giving you hydrogen or the partner that allows this organism to flourish. So, these three guys go together and these characters go together and break down into two micro types, three total if you look at the whole IBS group.

                                                So now, we started in 2018. We did a consensus on breath testing. Well, the Europeans came along and they said, “We were doing our own consensus.” The Asia-Pacific Australian Group got together and they’re saying, “Now, we’re doing our consensus.” But the bottom line is they’re all about the same. They agree on the criteria of SIBO. They agree on the dosing of the substrates. And they mostly agree that SIBO and IBS are interrelated.

                                                Okay. And now, we have an app that we use. Patients take the app and they take a picture of their stool. The problem with research in IBS is that the patient at the end of the day if they’ve had six stools, which one are they reporting in terms of diarrhea or constipation? Is it the last one they had? Is it the first one they had? Is it because they had six today that they decide what they’re going to put? None of that matters. They take pictures of every stool. We get all of it.

                                                So, we’re able to see exactly what the stool looks like. And basically if you’re methane positive, you’re more constipated. If your hydrogen sulfide positive, you are more diarrhea, more stool volume. But look at when it starts to go up, two. That’s when it’s already statistically elevating. And so, we think two is the proper cutoff because that’s when the diarrhea and the volume of stool is increasing.

                                                Okay. And then I promise one final sort of bit of stuff here. At DDW for the first time again, the small bowel has been sequenced using shotgun sequencing. Different shotgun, it is not 16s, it’s sequencing all the genes, all the DNA of the bacteria. And so, it’s whole genome sequencing. And you’re able to get to the actual species and even strain.

                                                So, let’s look at SIBO versus non-SIBO. Non-SIBO on the left, SIBO on the right. Still, Proteobacteria but look at what’s going on here. This is non-SIBO. More than 50% of everything in the small bowel of a SIBO patient is Proteobacteria. But look at who’s there. One species of Kleb and one species of Escherichia, I’m going to tell you the names of in a second, are taking up nearly half the microbiome. So, it’s literally like an infection.

                                                So, let’s break it down because it’s two species when we get to this low. It’s Kleb. pneumoniae which is taking up 18% of everything, a little bit of aerogenous and then E. coli. E. coli is taking up the other 20%. Now, you see a bunch of E. colis here. These are the strains that are part of it.

                                                But 28% plus 18%, we’re talking about almost … It’s 46% if you add those two together, 46% of the micro biomark, two species. We thought SIBO is just colon back in the beginning like 26 years ago, “Oh, the colon bacteria are blooming in the small bowel.” That’s not it. We thought, “Okay, coliforms are blooming in the small bowel.” That’s not it. It’s two species only, E. coli and Klebsiella, that’s it, Klebsiella pneumoniae specifically.

                                                And when you look at the strains, it even gets even narrower. These two strains, especially K12, correlates with bloating, correlates with gas, correlates with abdominal pain, correlates with diarrhea and correlates with urgency. So, one strain is actually causing a lot of the symptoms. And in the case of Klebsiella aerogenes is worse than the pneumoniae.  So, then when we looked at the metabolic function of these bacteria based on their genome, so this is true metabolic capacity now. We’re not doing 16s. This is deep sequencing. This is shotgun sequencing. Look at the ability to digest carbohydrates.

                                                Now, when I say glucose degradation, it really means all of these things are representing carbohydrate digestion potential. So, the gut of a patient with SIBO is 63 times more powerful at breaking down carbohydrates in a period of time, you could say it like that, than a normal person. So it’s no surprise that if you’re eating non-digestible products or non-digestible carbohydrates, you’re fired up. Your engines are on full alert to break down these sugars and hydrogen-producing pathways are all upregulated.

                                                This is why low FODMAP can work. This is why low fermentation can work because these pathways are so jacked up. Hydrogen sulfides jacked up. And then, some of these histamine pathways are jacked up which could be why people get food sensitivities. We need to do more work on this. It’s just the beginning of trying to understand what’s going on with this microbiome.  But then looking at this network, this city, this harmonious city on the left, that’s normal. As soon as E. coli goes up a little bit and then goes up more, everything breaks apart. So now, we’re not talking about just culture, we’re talking about just one organism going up. And Klebsiella, it’s a disaster. So as soon as Klebsiella starts to go up, the whole network starts to fall apart. The city falls apart.

                                                So, you got to measure all three gases. For the first time in history, these three gases using this test, you’re able to know what the microbiome is doing because these gases correlate with the exact microbiome we see on sequencing and the symptoms. So, for the first time, we’ve really validated breath test. If you use this system, this system is proven.   So, this is what I tried to show you today in a brief presentation because I could spend hours going through all the data for all the different points because there’s so much to talk about now. But food poisoning starts to process. And then this toxin we believe is causing autoimmunity, changing the gut nerves. And then that leads to stasis or reduction in migrating motor complexes, leads to overgrowth now proven by breath test, by culture, by PCR, by deep sequencing both 16s and now shotgun sequencing, which is why IBS is antibiotic responsive.

                                                Well, let’s talk a little bit about treatment because that’s really what it boils down to for people. Rifaximin was FDA approved on the basis that IBS was a microbiome in part condition. And I think we now know more about how rifaximin is working than even when it was approved based on what I just told you.  But we do know even from 2019 that if your breath test is positive, you’re much more likely to respond to rifaximin. And if you make that breath test negative, that’s the patient who responds best to rifaximin. So even then, the signal was there.

                                                When it comes to methane, this is the only double-blind study we had. Neomycin alone doesn’t do it. Neo plus rifaximin does it. And it makes the constipation better and the methane go down. Now, as Ben was saying, maybe rifaximin gets part of it down, neomycin gets the other part down or maybe they’re synergistic in some way. We don’t understand why the two of them are required.  Now, I’ll explain a little bit about neomycin and the problems with neomycin right now that have probably been resolved, but we’ll get to that in a minute. For hydrogen sulfide, the only thing we can lean on is this bismuth study from the 1990s. So, we actually use this with rifaximin as I’ll show you. That’s what I do in my practice, but not a lot of data using rifaximin and bismuth yet although we’re collecting patients.

                                                So, this is my way of doing things in my clinic. You can use the data as you wish and decide on your own how you want to do things. But if I have a patient with chronic diarrhea or mixed, I want to know if they have these antibodies because if they do, it changes how I have to treat the patient. It changes how I tell them to travel. Be more careful because this anti-vinculin antibody, in my experience, the higher it is, the harder the patient is to treat.

                                                I do the three gas breath test on everybody now because now, we’ve validated this three gas breath test against the microbiome and now it’s very clear. And so, if they’re hydrogen, I try to give them rifaximin alone. If they’re hydrogen sulfide in my practice, I use rifaximin with bismuth. I sometimes travel prophylax them if they’re vinculin antibody is really high.

                                                And I do follow these antibodies because if they only have CdtB, it will go down with time and then they might come off everything. I’ve got patients who are done. Their IBS disappeared as we watch the anti-CdtB disappear. And then I start to withdraw therapy.

                                                In the constipation side, I don’t know. I don’t really do the antibody test because it’s only about 20 to 25% that are positive. I’m not sure it’s as cost-effective as it is in the diarrhea side. I do the three gas breath test again for one other reason which I didn’t mention. We do see this quite often. If you have hydrogen sulfide and you have methane, let’s say you have both positive, methane wins. And what I mean by that is you’re constipated, methane overpowers the diarrhea effect of hydrogen sulfide.

                                                But if you treat the methane and the hydrogen sulfide is there, you could have diarrhea because the hydrogen sulfide will be unleashed, so to speak. So we do see these changes in dynamics in the three gases depending upon what we use to treat. But if it’s methane, I use rifaximin and neomycin because the double-blind study supports that.

                                                You could substitute neomycin for metronidazole. We do that in our practice. When patients are either allergic or other reasons like kidney function, we use metronidazole. But recently, neomycin was not available. So the generic company that makes neomycin had some trouble with supply chain and had to I guess shift gears to make other products in their product line. But now, neomycin is available again. So, I’m thankful for that because I thought they were getting rid of it all together.

                                                So, here we go. Circa 1996, I’m going back to the beginning of my presentation again. This is what we thought of IBS. This is how we treated IBS. This is how we treated the women with IBS by saying these sorts of things or feeling these sorts of things. And this is now what we know using the microbiome studies that we’ve done over the years. There’s stuff in here I hadn’t talked about because we just don’t have time, but lot is going on now.

                                                So in conclusion, IBS is commonly a small bowel microbiome disease. SIBO is an important contributor to this IBS. E. coli, Klebsiella, two species, who knew? I mean, that’s what’s causing SIBO and it’s accounting for the hydrogen. And if you get rid of hydrogen, as I showed you on that breath test study, the IBS gets better.

                                                This is the character. M. smithii for methane causing constipation. Get rid of that, get rid of the methane, the constipation gets better. Hydrogen sulfide, now we need to know this one to understand more completely the diarrhea. And we see in our practice, we need to do more studies. We have one randomized control trial which I can’t talk about that shows that hydrogen sulfide goes down, diarrhea gets better. But I can’t talk about the drug yet. We’re still working on it.

                                                This new three gas breath test is the first breath test ever validated against the human microbiome. So, the whole system works in that breath test and you can rely on it. Second-generation testing, it’s the only one that actually gets you above the threshold of 80, which means it’s medically accurate.

                                                And now that we all know all this stuff, new treatments are coming, we’re developing new treatments. Right now, we’re doing an experiment in the lab trying to block methane with some chemicals and drugs that we have. I was doing that earlier today with our lab people. So, lots going on. Very exciting time.

Dr. Weitz:                            Excellent, excellent. I’d like to ask a question that’s coming from Dr. Rahbar who I guess didn’t make it. But is it true … It’s a several part question and it relates to potential relationship between archaea and fungal overgrowth.

Dr. Pimentel:                     Yeah.

Dr. Weitz:                          So the first question is, is archaea generally need an anaerobic environment?

Dr. Pimentel:                     So, archaea are generally strict anaerobes so they generally need strict lack of oxygen. But remember, we say that and yet in the small bowel where we believe there’s more oxygen because it’s a more vascular area, they’re growing. And so, the problem is if you have a lot of bacteria in the small bowel eating up oxygen, then maybe it makes it relatively oxygen-deficient. And so, we don’t understand that dynamic completely, but certainly stool is more anaerobic and more likely.   But methanogens, we did our first SIFO, fungal overgrowth data at DDW also. And SIFO, anything over 10 to the 3, it correlates with symptoms. So, we’re starting to see SIFO less common but it’s there. And it doesn’t correlate with methanogens, but it does correlate with SIBO. So, what I mean is you can have SIBO and you will have no SIFO. But if you have SIFO, you often have SIBO at the same time. Does that make sense?

Dr. Weitz:                            Yes. Now, it is the case that there’s a number of doctors, especially in the functional medicine type space, who feel that treating fungal overgrowth helps patients with methane, SIBO. And so, the thought is that perhaps fungal overgrowth is making the small bowel more anaerobic. And apparently, there is some data that when you’re trying to grow methanogens in the lab, they add fungi to the dish to facilitate that.

Dr. Pimentel:                     Yeah. So, I don’t know that data. I’d love if somebody has it to send it to me because I’d love to read it. But I had have not seen that study. What we do see in the microbiome of the duodenum is that we don’t see methanogens go up when we see the fungal go up, but we do see SIBO go up. But it may be different in the colon. So, maybe exactly what you say on the colon. I don’t have an answer to that from our data yet, but we certainly have all the sequences so we can check that.

Dr. Weitz:                            Okay. Let’s see.

Dr. Pimentel:                     You want me to go through the questions or are you going to go ahead?

Dr. Weitz:                            Yeah. Carrie, you’re asking about relationship between probiotics. What is this over under-absorption of fat in the small intestine, Carrie?

Carrie:                                   I was up in the middle of the night.

Dr. Pimentel:                     Oh, lost.

Dr. Weitz:                            Yes. Are you there, Carrie?

Dr. Pimentel:                     You’re on mute, Carrie.

Carrie:                                   Sorry. Hi. So, I was up in the middle of the night reading about SIBO like nighttime read. And I was curious about the effect of fat absorption on SIBO because I see a lot of people with SIBO that don’t absorb fat well. And I came across a study that was finding a correlation between certain probiotics that could improve the fat absorption and also hinder the fat absorption in people that were hyper-absorbing.   And they didn’t mention what they were. And I was curious if you have read anything about that, heard anything about that, could talk to that at all?

Dr. Pimentel:                     Not in those specific terms but what we do know is that when SIBO is present, there is a change in bile acid degradation. And you can often get bile acid being converted prematurely like in the small bowel instead of the colon into these more toxic bile acids. But also inhibiting because you’ve degenerated the bile acids, maybe it will inhibit the absorption of fat because bile acids are critical for fat absorption. So, it’s possible to get fat malabsorption with SIBO. And that’s been seen in the past.

                                                In terms of probiotics, what’s interesting and I’m not going to dive too deep into probiotics unless you want me to. But one of the things we see over and over and this is going to maybe surprise to maybe some of you or maybe you already know this, lactobacillus does no good for this small bowel. It’s a disruptor like E. coli and Klebsiella. So, it’s like the gang moved into town and it disturbs the microbiome.  And then, the second thing that we see is there are three bugs that are associated with bad unhealthy aging when they’re present in the small bowel. Again, it’s E. coli, it’s Klebsiella and higher lactobacillus growing in the small intestine. So, that’s kind of shocking to me and we’re very surprised by that. But we just published that age paper about a year ago and the disruptor paper about two years ago that lactobacillus is not good for the small bowel.  So, bifido might be okay but not lactobacillus. So, hopefully that’s a little bit helpful to your question.

Dr. Weitz:                            Steve, what’s your question? Patients have a history of SIBO, probiotic Strep if history, rheumatic fever.

Dr. Steve Wasserman:                    Yeah. Some probiotics contain Strep, Streptomyces, whatever. And if they have a history of that, I never give that because a cross-reaction especially if they had a history of rheumatic fever or bacterial endocarditis. Is there a cross-reaction with giving that strep and a probiotic?

Dr. Pimentel:                     Yeah, I don’t the answer to that question. It could be okay but I don’t know. But I see your point and I agree with you. I mean, I wouldn’t give Streptomyces. So, you’re talking about Streptomyces specifically streptococcus.

Steve:                                Correct.

Dr. Pimentel:                     Streptomyces. Yeah, exactly. Also, Streptomyces produces streptomycin which is an antibiotic and you could be allergic to streptomycin. And so if you’re taking Streptomyces and you’re allergic to streptomycin, that’s not a good thing either. So, there’s a couple of reasons why that might not be a good idea.

Carrie:                                   Thank you. And what probiotics do you like with your patients that have gotten well?

Dr. Pimentel:                     So, I think my house is turned upside down in the last three years. The reason I say that is when you do the lactobacillus studies, when you see the lactobacillus studies from the early days, it might be good for the colon. It’s not good for the small bowel. So now I’m thinking, “Okay, I have to rethink what probiotics are good or bad because they might have differential effects on the small bowel versus the colon.” And until I know, I don’t even know what I’m doing anymore.

                                                And so, I feel a little confused. I don’t feel like I want to give up on probiotics, but I need to know more because as we know more, it’s just like anything else. You don’t know what you don’t know until you know it. Sorry, that was a very twisted sentence. But we’re learning so much about all these different regions of the bowel that it’s fascinating and unraveling. It’s like we found SIFO. We weren’t sure we were going to find SIFO.  Everybody talks about Candida in the small bowel and how important it is and how it can be pathologic. But until you actually sequence, here we are, we found it. It’s true. And that’s a really important finding. We need to continue to study that.

Dr. Weitz:                          And how often did you find the Candida?

Dr. Pimentel:                     Remember, the patients who are getting endoscopy in our unit are getting it for a reason. We’re in the middle right now of doing what’s called a Healthy Control Study. Complicated because you got to take super healthy humans and scope them which is a bit of a risk. So, the IRB just finally approved that protocol for us.  So, the current REIMAGINE study has all people coming for endoscopy for a reason. So they all have some, whether they have GERD, mostly it’s GERD and other things. So, they’re symptomatic for a lot of reasons. So, about 25% of them have SIBO as it turns out. And about 3 or 4% of them, I have to get the exact number and I may get back to you but it’s roughly that, might have SIBO. So, it’s a low number but it’s not zero and it needs to be looked for. And in particular, patients who don’t respond to SIBO treatment might respond to SIFO treatment.

Dr. Weitz:                            And is there an overlap? Do most of the patients with SIFO also have SIBO or it’s a separate?

Dr. Pimentel:                     It’s often an overlap, too. So maybe the mechanisms that cause SIBO lead to SIFO in some instances or in some individuals where they’re susceptible to that fungus. So, yeah, very interesting. And some of the weird things we find in SIFO is that it’s not hyphated organisms. They’re more the yeast-type organisms. So, it’s just different. It’s fun. It’s going to be fun to continue to explore that.

Dr. Weitz:                            It’s interesting. Maybe some of the practitioners who are seeing the worst of the worst patients are seeing a higher percentage of patients who have this SIFO with SIBO. And maybe that’s why given the antifungals is helping those patients.

Dr. Pimentel:                     Absolutely. Because we’re taking a hundred patients in the REIMAGINE Study, these are from all sorts of gastroenterologists. They’re not SIFOs or SIBO specialists. So, this is all comers. In my practice where I see a lot of SIBO, the percentage could be higher, absolutely. So, you’re right. I mean, because you’re sub-selecting your population.

Dr. Weitz:                          Now, some of your research is showing a correlation with blood sugar and even artificial sweeteners with SIBO.

Dr. Pimentel:                     Right. We just presented that at DDW, big DDW for us this year. But it turns out that we found, I think the number was somewhere with 50 to 70 different organisms are changed in the small bowel because of sweeteners that are not aspartame. Aspartame is a protein but all the carbohydrate-based sweeteners, they’re the ones that change the microbiome and not always in a good way.  Aspartame hardly does anything. It’s a protein. And so, it sort of substantiates this notion that maybe you can take aspartame, but you can’t take these sorbitol, Stevia, Splenda, Splenda meaning sucralose. If you have SIBO and you take those, and I showed you, the fermentation potential, the small bowel is jacked up. And if you take sucralose, you’re going to ferment that like crazy because the E. coli and Klebsiella pneumoniae there are jacked up to ferment it as quickly as possible before anybody else does. And that’s really what’s going on I think.

Dr. Weitz:                            JoEllen asked what was the third species associated with abnormal aging? You mentioned E. coli, Klebsiella and what’s the third one?

Dr. Pimentel:                     And lactobacillus. And I’m blanking on the exact species of lactobacillus we put in that publication. But I’ll try and get that to you, Ben, the publication.

Dr. Weitz:                            Great, thanks. Are you still working on using the statins for blocking the methane?

Dr. Pimentel:                     Well, we did the first statin work and it does reduce methane. But the problem with lovastatin is it’s got this weird thing where it converts to hydroxy acid then gets absorbed. And so, we tried to formulate a version of lovastatin that would get released in specific areas of the gut.   And I guess the design was overcomplicated or what, but it reduced your cholesterol but it didn’t reduce the methane too much. So, it kind of faltered. So I think the way the formulation was made, made it even better for cholesterol but didn’t really do much for methane. So, we have to figure out a way to drop methane. And we’re working on that in the back here and we’ll have something shortly I think.

Dr. Weitz:                            Okay, excellent. I think that’s the rest of the questions. Thank you so much for your time, Dr. Pimentel. This was excellent.

Dr. Pimentel:                     I appreciate it and I appreciate all your attention and great questions. So, thank you so much.

Dr. Weitz:                            Great, thank you. And bye, everybody. We’ll see you next month.



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 certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a five-star ratings and review. That way, more people will discover the Rational Wellness Podcast.   And I wanted to let everybody know that I do have some openings for new patients so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions or for an executive health screen, and to help you promote longevity and take a deeper dive into some of those factors that can lead to chronic diseases along the way.  And that usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing. And we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective.  So, if you’re interested, please call my Santa Monica White Sports Chiropractic and Nutrition Office at 310-395-3111 and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.



0 replies

Leave a Reply

Want to join the discussion?
Feel free to contribute!

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.