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welcome Australian practitioners to our webinar my name is dr. neurologic OB I'm the chief medical officer here at C Bo tests many of you are probably busy calming your anxious patients and will listen to the recording later so I hope you stay safe in these precarious times and thank you so much for joining us let me get straight to it dr. pimentos presentation is followed by a Q&A and I will conclude the webinar by giving you the information on the logistics of the tests in terms of cost ordering process etc SIBO test is absolutely thrilled to have the opportunity to offer the IBS smart to our Australian practitioners and if you've heard me speak at conferences or have taken some of my educational courses through our other site the C Bo doctor you have probably heard me mention both dr. Pimentel as well as this blood test the IBS smart I've known him now for almost ten years and I'm always impressed with his forward-thinking and truly brilliant medical mind dr. Pimentel is a gastroenterologist professor of medicine at the Geffen School of Medicine and associate professor at cedars-sinai Medical Center in La California he's very busy right now with on preparing his hospital for the pandemic but active in research dr. Pimentel has served as a principal investigator or Co investigator for numerous basic science translational and clinical studies in such areas as IBS and the relationship between gut flora composition and human disease his work has been published in numerous prestigious medical journals a few of dr. Perman tells most significant accomplishments include the discovery of her facts meant as a treatment for irritable bowel syndrome he also developed the very first blood test for IBS on the basis of IBS being derived from acute gastroenteritis and this is what we'll be talking about today he also has described the association between IBS and bacterial overgrowth or siebel and uncovered the methanogens madonna Brava back to Smith the I as an agent for causing constipation in humans so he's been so instrumental in many of the understandings that we have about Zeebo so without further ado welcome dr. Pimentel well it's a pleasure to all of you down there and I know that in this strange times worrying across the globe it seems ironic we're talking about irritable bowel syndrome but despite what's going on people still suffer so I think he carry forward what we're doing and and continue to educate around this disease but putting it into perspective with what else is going on so I thank you for taking time tonight and with all the best and take care of yourselves down there and also please take care of Tom Hanks while he's there as well so irritable bowel syndrome affects about 40 million people in the u.s. nearly 1 billion worldwide so in essence it is the most common GI disorder but also the most expensive GI disorder and one of the reasons it's so expensive is not because we do colonoscopies in patients where we do a lot of testing although that is the reason the main reason it's so expensive is because we have no diagnostic test for IBS we've relied on the Rome criteria which are you know really important to the identification of IBS for clinical trials but the Rome criteria in there in the spirit of the Rome criteria and actually literally in black and white the wrong criteria in its original format was a diagnosis of exclusion so after the doctor does all the work up and they feel like they ruled everything else out then you can apply the Rome criterion and that was the spirit of the Rome credits here in the beginning now data more recently says well maybe you can use the Rome criteria without doing an extensive workup but the point is the patient still feels like it's simply a criteria but I do and I say this quite often but I haven't said this lately it is a little insulting to patients to be called irritable to be called a bowel and to be called a syndrome which means that the disease or the condition is not verified as a disease so it's a syndrome it's a constellation of symptoms and therefore not really legitimate or legitimized by an organic illness or a true cause so we know stress affects motility of the gut we know when people are acutely stressed they can have diarrhea I'm not disputing those terms but the question is does stress cause IBS so in other words if you had a stressful event in your life and it's gone do you now have IBS for the rest of your life and there's never been a true controlled trial to prove that it's always been comparing IBS to healthy people well healthy people don't have anything so you're going to see differences but this study that I'm going to show you here from 2013 looked at the deployment of military to combat zones within the world during the Iraq war and they looked at military personnel deployed and they came back from deployment with IBS not all of them but a good percentage of them and they didn't have it before they were deployed so they looked at whether they were in combat or experiencing life traumatic events that that most people wouldn't know ordinarily experience and yet it didn't precipitate IBS or wasn't associated the only thing that they found in this study that precipitated or was associated with the development of IBS was they got food poisoning that was documented during their deployment so this is truly the best study there is on studying people prospectively in a large scale I believe there was 10 or 20,000 people followed during this trial and so this is proof that stress is not a contributor to IBS but it's also proof that food poisoning is and so let's continue so as we unfold this but hold this thought because we'll get back to it as we try to understand this this pathophysiology but the spoiler is that I and I show this slide now all the time see if you've seen it I apologize for showing it again but this is really our map our map to the development of IBS that food poisoning on the left through a toxin called ETB and the development of an auto antibody to vinculum damages the nerves of the gut leading to poor flow of the gut and then bacterial build-up and that makes that IBS and antibiotic responsive disease hmm okay so we talk about bacterial overgrowth here what is bacterial overgrowth so the large intestine half the weight of stool is bacteria the small intestine contains very little bacteria in fact we now have new definitions based on the North American consensus and more recently I published the SIBO guideline document which is a template to suggest that 10 to the 3 really is the cutoff or greater than 1,000 bacteria per milliliter is the cutoff for small bowel fluid based on the evidence now this is this gets confusing for the audience and for doctors even because it's it's a little hard to understand do I have SIBO or do I have IBS or do I have both so I want you to reflect back on h pylori as a cause of ulcers so there was a term in the 1980s called peptic ulcer disease you scope because somebody's bleeding or having pain in their stomach and you find an ulcer in the stomach where we soon learned in the 1980s another Australian discovered that h pylori was the cause of ulcers but it wasn't the cause of all ulcers maybe 60 or 70 percent of ulcers huge discovery and but the term peptic ulcer disease is still what we call peptic ulcer disease we just now know that H pylori is a cause of a percentage of peptic ulcer disease I reflect on that because I think this similar situation it's irritable bowel syndrome and of irritable bowel syndrome patients about 60 or 70 percent are associated with small intestinal bacterial overgrowth and treating that makes them better but remember there are h pylori patients who don't have ulcers and there are SIBO patients who don't have IBS so you could have adhesions that caused IBS Garci Boh you could have pancreas insufficiency that can cause bacterial overgrowth and there's a long list of that can cause overgrowth but are not IBS so it's a similar story as the h pylori story to diagnose overgrowth traditionally we've used breath testing because breath testing is relatively easy and straightforward so you ingest a carbohydrate and most cases it's lactulose but some people also use glucose it gets into the stomach it goes into the small intestine where the bacteria should not be but they are in this case and they ferment produce the gases and then it's expelled in your breath to be found in your breath and and then you're able to do the breath test and say you have bacterial overgrowth but there's been some criticism about breath testing but I think I think this sort of settles it so this is a paper it's it's Australian nights so Nick Talley is part of this paper who's a prominent investigator in Australia and this is pretty much the defining study of the last 10 years in the sense that it summarizes everything that we've been saying for 20 years and proves it so this is a meta-analysis of 25 studies over 6,000 patients and the conclusion is SIBO is more prevalent in IBS than healthy controls period and that is now a true statement based on breath tests second statement is culture of greater than 10 to the 3 shows SIBO by culture is more common in IBS than healthy people so even culture proves that SIBO is in IBS and that methane on breath test is associated with constipation and so this study really is like a capstone to 20 years of research because it finally proves yes SIBO and IBS are together and this is the long form of this description of the meta-analysis and you can see that I only have one paper here so this isn't a Pimentel effect of our study weighing in on this because there's 25 studies here now breath testing is complicated because we originally had a breath test just measuring hydrogen but hydrogen is just the fuel because methane producers use four hydrogen's to produce one methane and we now know methane causes the constipation side of overgrowth and that hydrogen sulfide producers are the diarrhea side although we don't have this breath test yet the three gas breath test which is coming soon but hydrogen sulfide produces diarrhea interestingly you can consider the hydrogen the rabbits and the methane producers the foxes the hydrogen sulfide produces the wolves so we have rabbits either the Wolves win or the foxes win and that will determine what your your symptoms are in general this is the met the same meta analysis for Nick tally showing that methane is associated with constipation but the important thing is the new North American consensus sorry the new SIBO guidelines from the American College of gastroenterology have changed the name it's not methane SIBO anymore it's now called intestinal methanogens overgrowth because methane bugs or organisms are not bacteria so you can't call it C Bo because the B stands for bacteria so we're calling it emo or intestinal managin overgrowth but it leads to the prospect of antibiotic so if you have too much bacteria in the gut could you take an antibiotic and we now know based on FDA approval for a fax women for irritable bowel syndrome the RAF acts woman treats IBS on the basis that IBS is a bacterial disease not only does it treat it but two weeks oven of this antibiotic leads to three months of benefit and this is a very important study again this is not impressed now I should say it's published because it was in the red general just before the holiday so in last part of 2019 this is a very important study because for the first time in a very large-scale study they did a subset of breath tests and they found that sure if you took were facts Minh forty four percent of you would get better without knowing anything but if your breath test was negative you're much less likely to respond to relax me then if your breath test was positive where it's 56% and if your breath this was positive and then became negative 76 percent of people met the very challenging at the endpoint again supporting the notion that the breath test predicts who has overgrowth and who will respond to her FAC Samin among IBS patients okay well now let's get to how this all happens what is the origin of all of this mess of bacterial overgrowth and so forth and it leads back to food poisoning and that's what we're here to talk about anyways today food poisoning is a cause of IBS well here's another capstone meta-analysis or capstone study because this is the definitive study 45 outbreaks followed with time and 11 percent of people so few infected a hundred people with Salmonella or Campylobacter food poisoning 11 percent would walk out the back end of that food poisoning with IBS and this study basically says food poisoning causes IBS full stop period that's it we now know that and so in 2020 we can say definitively that we know more about what causes IBS then we do Crohn's are all sort of colitis because we still don't know what triggers Crohn's erosive colitis but food poisoning triggers IBS so one of the risk factors well the risk factors are the sicker you are during food poison more likely you are to develop IBS if you're a woman you're more likely to develop IBS now that may be why more women have IBS but women get more autoimmune disease and we're going to talk about those autoimmune markers here in a minute and so maybe that's what why women are more susceptible but we still understand the genetics of why that is blood in the stool you need antibiotics you got to admit it be admitted to hospital all those things would make you develop IBS more likely well if you want to figure out this story now you have to develop animal models so we developed an animal model this time using food poisoning that's Campylobacter which is the number one cause of bacterial gastroenteritis in the United States and I believe it's similar in Australia and we gave Campylobacter to half of our rats the other half we gave them placebo and then we let them recover and then they hung around for another three months because now they're post-infectious and then we were able to see that some of them had weird stool after the kappa factor and then we did bacterial quantitation and we found that 27% of the rats who got Campylobacter now have bacterial overgrowth so for the first time in history a study shows that just like humans food poisoning causes IBS and we know IBS associated with overgrowth and in rats food poisoning of rats causes over growth but also IBS because they got weird stool forms so if you look at the pink column Kaplow bacter treated now have bacterial overgrowth 80 plus percent of these rats had weird stool form and increased rectal lymphocytes which is a type of white blood cell that is indicating chronic inflammation in the rectum and this is the only thing seen in humans with post infectious IBS up till is the point of this trial so we know that Shigella can cause IBS Salmonella can cause IBS Campylobacter e.coli they're all food poisoning pathogens but what do they have in common and they have really only one toxin in common and that's site illegal distending toxin beat B is the active component of that toxin so we repeated the experiment this time we created a camp love actor missing this toxin doesn't have this toxin we have wild-type regular plain old Campylobacter on the Left we have Campylobacter that's been modified so it doesn't produce the toxins and then we do some a trick where we say okay let's say you're going somewhere where food poisoning is common and you take your facts minore an antibiotic every day to prevent food poisoning so if you don't get food poisoning maybe you don't get IBS and the most important finding here is if you don't CTB you don't develop IBS and this is what it looks like in the raw data but suffice to say if you took four facts Imman every day in a place where there's food poisoning you probably don't get infected and you don't get IBS if you don't have C D TB toxin it's statistically significantly less IBS versus that Campylobacter alone so it's a colorful slide here this is the cleaning wave of your gun so you wake up in the morning you go to work you forgot you couldn't didn't have time to eat breakfast and your stomach is gurgling and you're saying oh boy I'm hungry I should eat because everybody can hear my stomach that's this wave coming through the entire small bowel to clean up it's like a dishwasher so every time you're fasting or through the night every 90 minutes the dishwasher this dishwasher comes through the intestine to clean up all the pieces of lettuce and junk that you haven't been able to digest because humans don't digest those things to keep the dish clean so it's like you put your dish in the dishwasher you wash it in the morning you take it out it's all clean ready for breakfast it's been known since 1978 if this dishwasher doesn't work or this cleaning Lane doesn't work you get bacterial overgrowth well there are special cells that make this wave happen they're called ICC cells and we now know from the Campylobacter experiment that Campylobacter makes these ICC cells that drive this wave go down but the ultimate ultimate experiment is this so if food poisoning causes IBS because of cdtv then you don't need food poisoning all you need is CD TB so what we did here was we took the stalks and purified it and we injected it into the arm of rats and then we saw of course they developed antibodies to cdtv because it's a foreign protein but they also developed antibodies to a protein called vinculum and this took three or four years to figure out it's a very long and drawn-out process and I can't show you all the slides because we'd be here for hours but the point is the vinculum antibodies developed as well so again just to reiterate we inject there with CD TB and they develop antibodies to you a protein on you called vinculin which is important for nerves to stick together in the gut not only that the higher the antibody to CD TB was the more bacteria you had in the duodenum the more bacteria you had in ileum meaning you developed overgrowth and the less vinculin was in the gut wall because it was sopping up the vinculum and the weird weirder your stool was the more the aunty cdtv was elevated so the point is just the CD to be alone created altered bowel pattern overgrowth and all the things we saw with Kapla vectors so what is vinculum so if you look here you've got these green filaments in a Cell which is the skeleton of the cell holding the cells shape at the end our Tufts of vinculum is red part and vinculum is like a motor at the end of actin going along that line or chain of actin making the cells reach out like there you can see them reaching out here and then they grab onto the cell next to them and then they stick to them and that's how nerves connect and in the in the gut the cells that we were talking about earlier have the type of vinculum for which the antibody forms here so it's like this you get an infection you get exposed to this toxin on the Left cdtv you form antibodies to it because it's not you so you form an antibody to different parts but one part looks like vinculum and so you develop what's called autoimmunity so now that we know this could we measure these two antibodies and diagnose IBS so we did a very large study of 2,300 patients I'm not going to show you that I'm going to show you the second generation test which is much more accurate and we're going to we measured these antibodies anti C D to be an anti vinculum and compared this to people with Crohn's disease or ulcerative colitis so the orange column is IBS for aunt ACD to be anti vinculum and these columns are inflammatory bowel disease in general all sort of colitis and Crohn's disease so what we showed is that these antibodies are elevated in IBS but they're not elevated in these other inflammatory conditions but it also gave us a very very good post-test probability and I'll show you that on the next slide the in graphic form and a very high specificity now some people say well the sensitivity is low it has to be low because first of all we want the specificity too high to be high so you set the cutoff of the test to be very specific for IBS so people stopped doing colonoscopies unnecessarily secondly only 60% of IBS is post infectious or Seba so you can't even get a sensitivity more than 60 because only 60% of the hundred people with IBS you test are potentially positive so this is really nothing to be worried about what I'm saying but I want you to focus on this this is the likelihood ratio so this is the most important factor here the likelihood ratio of six point three and five points we are very good for a test and how do you use that so Alex Ford published a paper said that a good gastroenterologist after seeing a patient has a pretty good idea that it's IBS let's say their post test run after seeing the gastrin ologist their accuracy is about 56% if you then pass this line through the 6.3 I told you about on the last slide that gives you a post-test probability of IBS of about 90 but if both tests are positive you get to 98% post test program if both tests are negative it drops to 22% post-test probability so in other words a negative test is also valuable because you're less likely to have IBS and you should look for other things a positive test is gives you a very strong confidence that you have IBS now the gray is medical certainty so there was a study that looked at all tests that were available for IBS and so we go back to this nomogram we go back to medical certainty and we look at everything that's ever been looked at for IBS so some people used to think that you know if you do a colonoscopy you feel pain that's a good indicator of IBS well remember 56 percent is what Ford says and it actually makes it worse it doesn't really diagnose IBS know better than what we already knew there was a 34 biomarker panel that will get you to a 74% post-test probability bile acids and still will get you to 78 there was a 10 biomarker panel that will get you to 79 visceral hyperalgesia is you put a balloon in the rectum you inflate it and patients with IBS have more pain at lower volume so that was in the medical certainty range but kind of invasive so volatiles in the stool gets you to 86 this is volatiles that look at you know bacterial products again suggesting this is a bacterial disease anyway but Antibes England's 87 and CB 3 is 89 and both together are 98 so we're getting to medical certainty with the two best tests that are out there which isn't a CD to be an echo vinculum this is a really important study that was published not really studies a case report because so this patient went to Mexico City got diarrhea came back still suffering now it's eight weeks later still severe bloating and this is what happens with the antibodies so anti CD TV is up right away within eight weeks but anti vinculin down here is still normal and doesn't reach abnormal until 12 weeks so you start with CD TV you later develop anti think you'll ever time and that's what we see clinically so this is sort of a template of how we now think the test is working so if you're low for both well you either don't have IBS you should be looking for something else meaning the post-test probability which I showed you goes down to 22% so you need to look for something else just in case still could be IBS of another reason but it's not post infectious if anti-sea need to be as high you could have had a recent infection that was driving this and and that's what's happening and or you do not develop autoimmunity and I'll show you a case which illustrates that if aunt ICD TB is low in turbulence high and the infection was long ago no more CD TV those anybody's have slowly when gone down but you're now autoimmune to yourself if both are high it's a recent infection it's sort of like this case here where both are high at 12 weeks after infection that's possible and then we see anti ving feeling super high and these are the sickest patients we have so we actually feel like anti vinculum now having run these tests for a while is proportional so these patients really have a motility disorder because of it yes they have over a growth because the motility disorder is so significant and you yes you treat the overgrowth but they're more likely to meet Pro kinetics or other things so let me tell you three cases and then we'll go to the summary of all this case one is a 35 year old male swam in their neighbor's pool and developed gastrin Rytas now this neighborhoods pool wasn't filtered he didn't know that and and then has had IBS since then so we measured the antibody and his anti CTD was super high three oh three point oh six but think Yulin was normal so he didn't have an F he didn't develop autoimmunity at least not at that point and he was treated with four facts when he was having recurrences we treat him with peppermint oil and a number of other things and he was doing okay sort of getting by and then we measured his antibody again and then on December I saw him and I said how you doing he says I'm doing great I said what do you mean he said well I'm taking nothing I'm not on any any medication whatsoever and I said for how long he says for six months so weary measured the antibody and the antibody was basically gone so his CD TB disappeared so we've seen this a few times that if you don't develop the autoimmunity and you don't get food poisoning again eventually the only bodies disappear and I think that's a very interesting result and I actually liked when patients Orsini to be positive because I think if they don't get food poisoning again they could remit and if you go back to the outbreaks in that big Mayo Clinic study some of the patients never remitted never I mean so people got food poisoning they developed IBS and about half of them it disappeared over four or five eight years depending upon which study and how long they followed them so this may be that patient or the patients who had this antibody profile the second case is a 20 year old man the patient was a usual state of health until a year ago no gastrin rightists so remember if a patient comes to my clinic with diarrhea that's the patient I do be anybody's on because they may not know ferm they may not remember the food poisoning obviously if somebody comes to our offices say look I had food poisoning six months ago and now I've have all this problem that's it becomes more obvious to do the test but I do with my patients with chronic diarrhea and if it's positive that I know but look at this this page another colonoscopy ultrasound stool studies all negative CBC chem panel celiac testing and fecal calprotectin all negative and then we did this test and his anti Bencoolen was positive at 1.63 anti cdtv was negative so clearly has IBS post infectious IBS because the antibodies are positive now in the family history I happen to see his mother and his mother is quite sick with this with these super-high vinculin antibodies and she needs a lot of treatment and a lot of care because she's much more affected so I'm thinking to myself okay if the mother is this and he is on TV during 1.63 I can't let him get like her because if he gets another food poisoning he's gonna have it even higher and higher and it actually become more difficult to treat and interestingly we gave him her fax Minh he's he responded brilliantly ninety percent improved and it's now six months later and he's still feeling great because this antibody isn't all that high contrast that with his mother who these were fax him and half a pill every day to keep the Overdorf away and she's one of the one of the few patients have my clinic where I need to use chronic therapy I know it's not the typical therapy that's approved by the FDA for IBS but that's the only way she stays well so same same young man could have saved at least in American dollars and an American system between two thousand four thousand dollars if none of this testing had been done and we'd have gone straight to the I auntie vinculin and auntie CD TB test or the obvious smart test well so cost savings would have been a big thing for this young person I told you what I did for treatment told you about the family history but now he wants to go to Southeast Asia to some rural areas in December that's this year in 2020 and he asked me what should I do and so what I am doing and again it's not FDA approved to use this way but I'm giving were facts I'm and based on that animal study prophylactically so he'll take a little bit of her facts Minh half a pill with each meal and we can prevent food poisoning and that there is a study in humans that it does work that way based on a study from Texas so we don't want those anybody's to go higher and he needs to practice good careful eating habits when he travels the third case is a young woman who presents with diarrhea seen by at least one outside GI doctor no blood no red flag symptoms started over a year ago it still has diarrhea calprotectin is normal CT abdomen i'm not sure why somebody did that but that was normal and so I was gonna do I treat her does she have IBS do I need to do further tests her mother wanted to do a colonoscopy she has no history of travel or food poisoning she meets the Rome criteria for IBS and then again we did some stool studies just to be sure she doesn't have anything going on and that's all normal but her antibodies now we got them back and they're negative she has nothing she was live aunty vinculum and she doesn't have an tcdt B so I said well I guess we need to do a colonoscopy so he did a colonoscopy and we looked for celiac disease and she doesn't have celiac disease so the biopsies were normal and of the duodenum but on colonoscopy she had microscopic colitis so the diagnosis here is microscopic colitis as she needed to get treatment so we come back to the final story here which is after all of what I've told you this is the path that you develop you have to food poisoning you have these antibodies to cdtv anybody sevinc Yulin and the profiles of those can give you some good information about what's going on with the patient you get a reduction in these nerve cells you get bacterial overgrowth because of the lack of flow of the gut and then IBS is an antibiotic responsive disease so in summary these are the tests that are available or were available Rome criteria are easy but they don't tell you what what caused IBS they don't they don't have any specificity but 70% of Crohn's patients meet Rome criteria so that's not helpful genetics there was genetic testing but really we're not very specific and so they've been removed from the market in the US there's a fecal calprotectin sure if it's positive maybe you have Crohn's maybe you have ulcerative colitis but if you're negative you're still scratching your head and shirt it certainly doesn't tell the patient why they have IBS it doesn't even tell them they have IBS because it's not a test for I guess it's a test for inflammation breath testing can be helpful because it can tell you that how to treat the patient maybe if your methane you take a certain treatment if your if your hydrogen you take another treatment and then finally IBS smart is sort of checks all the boxes because it's easy it's just blood high specificity and it told you it's over 90% it's a diagnosis of inclusion so for the first time we can tell IBS patients okay you have IBS it's real it's not in your head here's the test that proves it it's from food poisoning we know that so that's the pathophysiology of it and it can guide therapy I've just told you that if if certain tests are positive or abnormal I'm changing the way I'm speaking to the patient tons to avoid food poisoning maybe even prophylaxis on one travel with travel it reduces costs and there's a cost analysis that's going to be published later this year that shows how much it reduces and it reduces costs in multiple countries in the modeling and it's available so in sort of finally auntie van keulen an anti CD to be are important to test because one they save cost number two they validate the patient and the patient feels confident that they finally have a diagnosis they know that food poisoning was the cause and we may be provided opportunities from preventing patients from being worse off if they get further food poisoning because they now know what they have so that was all I was gonna say today and I look forward to any of your questions at this rate thank you so much dr. Pimentel I hope you can hear me yeah great thank you that was really very informative and you know I I was going to sort of talk about the IBS Martin how to order it right now but I think due to your busy day I think we'll just get to the questions right now and just participate participants if you could put your questions into the Q&A if you click on the little Q&A box down there you can put your questions and I will read them out to dr. Pimentel but I can start it off because there were a few things that you said that we're really interesting and new we like for example the whole email that I'm very happy to hear that emo is a thing now or intestinal mat methanogens overgrowth so that's that's finally happened for those of you who have heard me talk about this methanogens overgrowth can also happen in the large intestine and so often it's a very confusing picture with with constipation but back to the IBS smart so one of the slides you you talked about how when CD TB is elevated but vinculin is negative that that may not actually be a car or a time to put to prescribe pro kinetics did I get that correct so it's more that I mean if I were me who had IBS I would be more happy if I had CDT be positive and not they killing because I think knowing what I know now that patients avoiding food poisoning their symptoms will gradually be high that's what I but but you know a prokinetic could still be useful it depends on how the patients respond but my experience is the patients with just CDT seem to respond just antibiotics and may not need pro kinetics but we need more more experience with the tests to know that for sure great first question is is there any point email people getting this test so we don't see a lot of positives so we think it's not necessarily patient factors so if you if you took other people with IBS with diarrhea or mixed between 40 and 70 percent would be positive on this test if you took email patients or people with meth meth antigen overgrowth only about 25% would be positives but it's less helpful and in fact in the studies that I was summarizing constipation is a less common outcome of food poisoning so I sort of think of methane overgrowth or methanogens overgrowth as different than the food poisoning derived sort of causes of IBS on the on the other side okay I think you've answered a few of the people's question about confirming IBS smart to be used for IBS C or just IBS B and I think I BSD is definitely a priority they're not a question is what is the incidence of comorbidities with A+ IBS smart test ie can you rule out IBD if the IBS smart test is positive or can more serious conditions such as bowel cancer IBS coexist with a positive IBS smart test well I mean I think we need to practice as we practice guidelines so in other words if you're at least in the u.s. now over 45 in other countries it's over 50 required or at least recommended so I don't think this changes that question is so let's say you're patient with diarrhea clinic and you have a positive then you more than likely have IBS by by a strong margin because very few IBD patients have this but remember a certain percentage of all patients have ids/ips or might have IBS overlap but I would say it's based on our data I think it's less than 5% of chromes patients will have a positive test so probably those have IBS as well like 70 percent of IBS patients are positive so it's a stark difference great what is the treatment when someone has high vinculum low CD TB and they're having severe dire diarrhea again suddenly what is the preferred treatment start with four facts I mean all these other over-the-counter or even natural therapies that are that are available and I this conversation to get into all of that but but I think if the anti Bencoolen is very high if you can get them down the diarrhea then I would start a prokinetic that's what I do in my clinic so either low dose erythromycin some people who used low dose naltrexone both frank inflammatory and prokinetic but we're also using a lot more putalik right now I'm and low dose again half a milligram at bedtime all these prokinetic and are there any specific diet changes to make between positive result and say SIBO or IBS not positive I'm not sure I understand this Lisa maybe I move on maybe clarify a bit more Lisa on that question okay next question is have you used probiotics EG sacra my C's or travel n which is a colostrum that prevents travelers diarrhea in the prevention of TD or traveler's diarrhea for those who may be susceptible to autoimmunity it's an interesting point I'd be curious this is B if patients or people have that experience over the next year if people start doing the tests and and exploring those but I don't have experience using those okay I usually use things like berberine and I do use sacra my C's also because it tends to increase the Katori IgA and stuff but you know that's sort of case-by-case basis my big question is about how do you do so two questions one is my initial sort of assumption when the IBS smart first came out was that you only ever need to test one but in one time to see if they're positive or negative but in your as time has gone on it looks like you have tested people repeatedly to see what these antibodies are doing so how do you prove ring test I guess is my question know what how do you when would you retest a patient so we're collecting data on all of these patients and over time we'll continue to publish iterations of what to do but here's what I can tell you for perfect if you test the antibodies and let's say you give her a fax Minh and then you test them again two weeks later nothing they don't shift because depending upon whether you respond to a fax them and their antibodies they're going to be stable in your blood over months or years the cdtv anybody is in anybody - let's say you were to get tetanus no thanks you have to get it every ten years because the antibodies wear out if you don't get tetanus you don't get the antibodies to continue so they eventually diminish I think that's the same thing here if you got CDT be anybody's you don't get food poisoning again eventually anybody's diminished and your symptoms get better but the vinculum is autoimmune you can't get rid of your wrinkle and in your body you keep producing it so it's probably fueling ongoing nature of it so I guess to answer the question more definitively I wouldn't order it more than at least you know more frequently than every six months or every year because I don't think it will change that much but if you're interested in seeing the evolution of it in a patient then that's that's what I do I'm probably once a year now just as they're going up or down because the problem with Devaney one is a danger oh let's say at food poisoning two months ago well the if you measure it now it's gonna be one way but two months from now it may be different because of what I said about vinculum it comes out three months so if you know when the food poisoning occurred you may need to enter it more closely together but if they're established patient than once a year is plenty I know I went all over the place with that but I think okay great okay my camera just came on excellent okay another question I had about breath testing you know a lot of people are going to ask this is does this take the place of breath testing so I look at it as complimentary because the thing is you can have overgrowth but why do you have overgrowth I always want to know the why is it help if the patient has negative antibodies and overgrowth and maybe it's not different kind of workup for that patient if they have over growth and positive anybody then its food poisoning related so look I mean my job is to find out what the patient has and why and the patient has overgrowth and why they have overdoses food poisoning and these antibodies and then I can protect them from getting further food poisoning and take different precautions depending upon the two partner tests what I've been telling people is and correct me if I'm wrong but I I think got the IBS smart really it is just a test for the underlying cause but not this necessarily the severity of the overgrowth because that can't really be measured with that so it's it's really finding the underlying cause to their SIBO which is so important to prevent relapse with the proper medication I agree I agree I think that's the right video okay a couple more questions how are we defining diarrhea can we tell if it is overflow as opposed to diarrhea and do we think of loose stools as diarrhea or just watery diarrhea well this is that's a full diarrhea question because there's many reasons for diarrhea overflow can be a cause of diarrhea if you're very constipated usually those are nursing home patients but there are patients who are walking around like that but but you know in general when we talk about diarrhea in in terms of IBS someday they're constantly areas I mean it's diarrhea tends to be all over the map very very different day by day if somebody comes in with ten watery bowel movements a day I can tell you for a fact they probably don't have IBS anyway because IBS never presents with that kind of vigorous watery bowel movement so though but I can get into more details about diarrhea you've got blinds to save out there above trying to speed this up for you so that you can get back to preparing your hospital for a pandemic so but I think for how I would how I would think about that is when somebody comes in with these different symptoms that I would think of as SIBO IBS I would do a breath test and if they're positive you know I usually start there and if they're positive then I consider doing this anti vinculin antibody test because you know do you think that's the the proper sort of sequence or would you do it the other way around I don't think it matters which way around you do it I tend to do both so I can get the most information possible I mean I really want to know he is food poisoning the cause and that gives the patient and because you know look even if you did though right and you got a stable positive test the patients are saying well how the heck did I get this why do I have this and this will give at least some information about why this is happening to them ok great ok I think there's more clarification about that question with the diet I think it has to do with autoimmunity and and and diet so positive for IBS smart test patients or patients with SIBO or IBS but not positive to IBS smart any different diet recommendation I can I'm assuming it relates to the autoimmune component if you would change any part of the diet so we've only had this test for a little while so it's hard to know how died influences the test or vice versa it's a great question whoever is asking that question if you can do some tests and you figure something out let me know but I I haven't been able to pin something down like that not yet anyway couple more is there any are there any types of SIBO that could be missed with this test great question so well the test is not going to tell you what type of SIBO you have at least we don't think so yet no we don't have the hydrogen sulphide available yet we're just coming so maybe it'll help with that so I let me just the jury's still out on that but generally your methane positive on your breakfast you're constipated I don't see the need to do this test I really I'm not sure it's gonna be valuable especially if they're constipated because the likelihood of it being positive is lower but definitely for your diarrhea patients I mean I do it for all my diarrhea patients down great I did have a patient with anyways we move on but it was a microcytic or microscopic colliders patient after all and not a osebo patient but it lasts shouldn't on my part is that they you know there are other tests out there that are touting this the this this particular panel or this test can you briefly talk about that the look-alikes that are out there well I mean you know they're calling themselves by different names but the point is this is the original test this is the test that's validated in publication and the second part of it is the second generation which is obviously art there's a problem with the antigens so CD TB and vinculum so what we did in this to make it better than the original test is epitope optimization so the proteins are unstable and we figured out a way to stabilize the proteins so that the test would even be better and that's how we got such specificities and so it works much the original so whatever you call them knock up to whatever they are they're they're not the test that was in these publications and they're certainly not optimization for ideal characteristics so I don't know what they are to be honest okay okay all right but this one the idea is smart I think is FDA approved right yeah what's called lab directed tests run by CLIA certified laboratories and so this is an allowed test under the lock laws of the United States has a lab directed test great I think that was it the the rest is the other questions really relate to the logistics of ordering the test I think there was one last one squeezing in I noticed that you're only seeming to use four facts men do you also use neomycin for treatment to remembering that this is diarrhea dominant or usually hydrogen dominant SIBO so i'm that's usually disturbing facts amend based treatment unless you want to comment on that dr. Pimentel is less used in the diarrhea side more we combine it with earth and methane or constipated side the question is a good question but we use it neomycin backs them and more on the methane constipated patient great well I think that answers all of your all of the questions that have come through participants please stay on the webinar so that we can walk you through the cost of the tests how to order the tests etc so but really thank you so much for your time and these really crazy times that we are living in and I wish you all the best and stay healthy please stay healthy and yeah and really thanks again and I'm sure we will talk again at some point well thank you very much nicest talk to you all and same same thing to you be healthy