IBS 2022 Year in Review with Dr. Mark Pimentel

00:02    it's such an honor to have you here today oh it's a great pleasure to be here thanks for having me yes yes uh I was telling uh mentioning to you off the air and most of my patients know this that you you are definitely changed my career for the better and um back in 2007 things really took off after learning from you and learning and starting to study your work so I just thank you and my patience thank you from the bottom of my heart for all your hard work and dedication you know it's been a great ride and uh

00:40    and uh as we said offline also it's not about us it's about our patients getting better and so hopefully there's more to come yes definitely so I'd love to get into hearing about the last five years of your career because I've been following your work and wow it's really things have really started um taking off um in this field more and more probably for you it probably seems like a a really long process to get here but I'd love to hear about the last five years because I've just noticed some

01:15    a big turning point in your research and in your work and just like to kind of know how things change for you and your career yeah I mean uh I'm gonna do the last five years it's going to reflect for two seconds you know 26 years ago when I started thinking about the microbiome and its relationship to functional GI disorders particularly irritable bowel syndrome and connecting sibo to IBS wow it's controversial uh you know we're talking about a disease that people thought was psychological and now we're

01:45    saying it's microbiological so that was a big uh switch and that switch was more of a very very very large um dial that slowly turns sort of like a dimmer switch for people to get it and and even though we got it and we were seeing it in our patients we ourselves must go through the scientific process uh so even if we believe something you have to prove it you have to prove it you have to prove it you have to prove it but I I think we've convincingly proved that 10 years ago with rifaximin being FDA approved

02:21    and so forth but it's it's not this it wasn't the full story I think we needed to understand why IBS is developing to begin with like what's going on here um and I'm just trying to shut things down so I don't make any beeps all over the place here but um yeah we how does it all come together I mean how does sibo form because if we really want to cure sibo antibiotics aren't the answer they're an answer for the time and and I think that's what the last five years has got us is

02:53    we now know that food poisoning started this whole thing now we know the toxin that does it now we're trying to find a mechanism of how that toxin is doing it and then by putting that together with the sibo uh I think that's that's huge and then the sequencing that we've been doing to try to identify because people say well okay you already proved it see we already proved it's evil but no it's not like that we're now down to three or four strains of organisms that are specifically involved in sibo once we

03:24    get to that level we're done we now know the Bad actors and and when we know the Bad actors it's going to help us with treatments uh immensely and we need to know where they live and we needed to know who they are now same thing with the methanogens we're now understanding that there are different strains of M Smith EI that are producing methane and some are producing it differently than others so it just opens up new avenues for better treatments that are going to work longer terms so sorry for the long

03:53    answer but but it's it's really been uh eye-opening even in the last five years yeah yeah and you know I think one of some of the highlights that I've really learned a lot from from the last five years one of them being the IBS smart test I don't know if that it preceded five years but that was like a big uh Game Changer um to have that tool and then adding um the trio smartcast with the ability to test for hydrogen sulfide and now um some of your latest work on highlighting understanding methanogenesis I mean it's

04:34    it makes us really be able to have good conversations with our patients and educate them and and develop strategies to help prevent recurrence of these conditions those those are really uh beneficial so I I'd love to kind of even go back even further because you mentioned how when you were starting um this was considered I mean I remember the term like a diagnosis of exclusion IBS was sort of a kind of a waste bucket diagnosis when uh clinician had ruled out IBD and other more serious disorders of um and then you're saying that in the

05:17    beginning of your career was considered more of a psychological psychosomatic disorder do you remember your first patient like when you first encountered IBS what what was that like well I'll give you two case examples um one of them was this this 50-ish year old gentleman who um at IBS was told he had IBS had been around the block with probably eight or nine gastroenterologists and we saw him did a breath test as primitive as it was at the time and positive and we treated him what neomycin didn't have a vaccine

05:55    or any of the new stuff and he came back he had had it for 20 years and he was angry um because he says I can't believe in 10 days you fixed something I've been suffering with for 20 years and having seen all these great doctors and he couldn't understand in his head how it's possible that we did something so quote easy and yet nobody else thought of it but but that's how things start right um the second example was actually a 65 year old woman who's again had had IBS for a couple of decades or so

06:36    and had been around the block same story but this time again remarkable 90 improved but on her second visit she came in with a brown paper bag true story and she literally in front of me dumped the bag on the table and she says this is the stuff they've all given me these years I don't need the antidepressants anymore and there was four of those in there I don't need the anti-spasmodic etc etc the bag was just full of pills from doctor previous doctors and so you know anecdote isn't science but it told me

07:15    that these patients were frustrated with what they were being offered were frustrated by the side effects of all those things and could couldn't believe that they got this kind of relief so obviously it doesn't happen like that for everybody but but you get the picture that this was a game changer and we started to see that in our patients yeah I I remember in 2007 I was just out of residency and I was um you know I thought I knew a little bit about helping people with IBS and at a really difficult case uh of a young

07:50    man who couldn't travel more than an hour or two before needing to use the restroom and he was really frustrated and we tried some things I didn't get a whole lot maybe help them maybe a little bit and uh he you know he he said he was going to go talk to a gastroenterologist and get a little more information and uh he came back my link ear to ear on his follow-up visit with me and he's like I'm I'm all better and uh I I said well you know what it what what happened we know what what did they advise you on what was the

08:31    diagnosis what and uh he said I was um Dr Sloan who knows that um Dr Pimentel in in Los Angeles um gave me this test and turned out I have this overgrowth I was given this treatment with rifaximin and I've never felt better and uh it was to me so then that led down um you know my that kind of started my exploration of sibo and understanding it more but um yeah and you know of course um after that there was more work to do to help him stay well um but uh that was that was my first case with you know officially with sibo

09:14    great story I mean there's just you probably have dozens of stories like that uh in in the amount of money patients pay out of pocket co-pays for all sorts of things that have been done over the years only to find out that 10 days or 14 days of an antibiotic made them better again these are points of frustration for these patients when they when they sort of get that wake-up call that this just made them so much better and this was the cause so uh yeah a lot a lot to unpack over the 10 20 years yeah so when we think about

09:50    um that kind of end result of helping people by altering the microbiome and kind of reverse engineering that and kind of going backwards and and seeing like how did they get here in the first place I think these are all the questions that you were saying at the beginning of the conversation that we're trying to understand and I would love to go into a few core elements that you've really highlighted with your work one being just the Keystone microbes that set up which is really fascinating to me and I want

10:32    to maybe set this up by saying you know that there are there's a sort of Norm normal environment in the small intestine where certain microbes should Thrive and others should not and we see in uh sibo and an emo intestinal methane overgrowth that this is different like the the species that are surviving in the small intestine are different can you maybe spam upon that as just sort of like a core foundational understanding of of this uh imbalance yeah I mean 26 years ago when we defined sibo what we said was and this is

11:09    written in my own papers is that the colon bacteria are moving up and overpopulating the small bowel bacteria and 26 years later that's not at all what's happening exactly um it's that there are a few key players E coli and klebsiella particularly those two that they when you have the food poisoning and you have the slower Transit of the gut they find it a delicious opportunity to take over and the higher they are the more we call them disruptors now because the higher their number the more they destroy the

11:48    community um and and they're just they're just terrible for the other organisms and so there's a destruction of the normal microbial Community when E coli the higher E coli  get uh and and that's the issue what's remarkable and you're going to see some more data come out in about four or five months from ddw that we were able to nail it down to very very very specific strains uh so basically we know the exact organisms not just it's Ratio or E coli we know the exact E coli uh and and

12:22    that's going to be huge but the point is it's amazing that if you think about the microbiome it's a thousand different organisms in the small bowel maybe it's five or six hundred and two or three characters are taking up forty percent of everything um it's really dramatic um and so and one of the things I said to my research staff a couple of weeks ago is we're preparing for ddw I said isn't it amazing that two or three characters can can do so much damage and there is nothing in in our reimagined study of the small

12:58    bowel there is no other example of that much destruction of the microbiome in our small bowel samples short of taking high intensity antibiotics just before getting your sample so sibo is highly destructive in the case of methanogens they're recruiting more organisms so there's more diversity of the wrong kind of things so between methanogens recruiting the wrong actors to the field and the sibo typical sibo um destroying the typical actors where they belong um it's an interesting sort of Yin and Yang dichotomy between these two

13:41    examples which is why and then this is something that people maybe people don't know people who have methane always relapse methane we have never I've Dr reside I talked to him he says he's got one patient I maybe have one patient in 26 years who was hydrogen and is now methane so they're either methane or they're not and and so um you get stuck in your bucket and you also introduced this uh topic um or this concept of centropy in some of your recent papers and I think that's really important for people to

14:18    understand because now there's this uh sort of knee-jerk reaction it's like well let's just kill those bugs and end of story but this conscious concept of centropy paints a little bit of different of a picture of what's going on can you talk about  are organisms that depend on other organisms and so um it's a bit like The Godfather right The Godfather is there it's it's a it's a it's a gang but there's a leader and you need all the henchmen in order to make the leader

14:55    powerful and so in the methanogen situation you need the Christensenellaceae  and the ruminococcus to feed the hydrogen to the methanogen in order for methane to be produced and then the patient to feel unwell and so the methanogen brings in these bugs to help feed it another example is uh What uh what's the name of that big character in Star Wars that just keeps eating things so I can't remember the name but yeah it looks like that looks like a Big Worm but anyways uh um and just eating constantly well that's the methanogen and and he's just

15:32    uh accumulating people around him so um that's that's centrophy and and uh you know these organisms have figured this out long ago how to how to make themselves happy yeah so there's uh basically players that um cross feed and um support the methanogens um in their growth and um also with the hydrogen sulfide it seems as though that's a that's a the case as well yeah hydrogen sulfide is is the new kid so to speak it's not the new new kid but it's something we're starting to unravel

16:13    more clearly you know it stems back from well if you go back 26 years part of the controversy of sibo is that us included but also many of the other scientists could never show a relationship between the amount of hydrogen on a breath test and the severity of symptoms and so there was always this discordance and so it made scientists say well okay fine the breath this is positive but shouldn't it be more symptoms if there's more bugs there more hydrogen uh but the problem is we were missing that organism

16:45    class of hydrogen sulfide because hydrogen has no relationship to symptoms like methane the higher the methane is more constipation the higher the hydrogen is doesn't matter but hydrogen is eating hydrogen sulfide or sulfate reducing bacteria and the higher hydrogen sulfide is the more diarrhea you have so without knowing that gas we were missing a whole piece of the puzzle and now that we've sequenced the small bowel we're identifying those characters as well so you could say that the hydrogen is centrophic to the hydrogen

17:19    sulfide production as well but we'll continue to dig into that yeah so going into that a little deeper I I've seen in some of your recent papers a highlight of um Ruminococcus species being uh present and a key a keystone species in methanogen patients and I think there's maybe one other organism that's been highlighted um it's interesting because I know that I've messaged you so many times about methanogenesis because it's sort of my uh the pain of a lot of our patients existence and difficult challenging

18:01    um it's interesting that ruminococcus is uh is from my understanding one of these like starch feeders um so I I'm kind of fascinated to hear what you're if if learning about Roman caucus change any of your thinking about methanogenesis yeah so the two families are ruminococcus was part and christensenal ACA again they're they're carbohydrate feeders as you point out uh they are intense hydrogen producers so you'll say well but when you have methanogens or when you have methane your hydrogen is

18:36    actually lower because the methanogens are extremely good at picking up hydrogen and running with it and producing methane eating it all up but they are they are really doing um they're they're really channeling the food products to the methanogens one of the things we see uh and maybe this sort of creates a different controversy about your question is that if you have methanogens and this carbohydrate digestion so for example if you eat a piece of lettuce humans don't digest lettuce but these guys might be able to

19:09    break it down and then liberate calories that go to you and so we do see when methane's present that people tend to be heavier in weight or more obese and so by having this ability to digest food products that normally humans don't digest and providing that that methane think think of it this way cows do not eat grass that whole notion cows eat grass cows do not eat grass cows put grass in their stomach and the bacteria of their gut and the methanogens eat the grass then the cow brings that up chews the

19:46    bacteria and gets the calories from the bacteria so cows do not digest grass and I think the same thing is happening in some humans where we're getting calories that we wouldn't have otherwise been capable of of liberating because of these organisms problem is we're sitting at our desks at the bagel room across the hall potato chips on our desk and candy and we have methanogens who under and their centrals who are just very good at getting calories from that stuff we're not living on the you know the

20:17    planes hoping for a kill today you know so it's it's a different environment yeah it's uh it's really interesting to know you know a little bit about what's driving up that much hydrogen um you know it's just and the other thing that was fascinating that I saw in some of your recent work was that uh perhaps the lower the stomach acid the less methanogenesis um that that was uh fascinating because there's all these naturopathic and integrative and functional medicine you know sort of is a big uh promoter of

20:55    healthy stomach acid it was I think it was really enlightening to learn that um we need to be careful about that well yeah I mean sodas although that's not endorsed by anybody uh have a lot of acid a lot of acid containing foods like fermented foods are acid containing um you know people are giving betaine HCL or hydrochloric acid to people hoping that it will reduce bacteria but in fact it could be doing the opposite as you say so methanogens can use hydrogen in many forms it can get it from ammonium it can

21:31    get it from Just acid it can get it from acetate it can get it from um you know the hydrogen gas itself so so there are many ways and creative ways that mathematics can get can get hydrogen so in fact if you're giving hydrochloric acid you may be encouraging bad things among your methanogens however getting rid of acid sometimes makes that less so uh it's interesting what we learn as we continue to explore yeah yeah it's uh the um and then just to round out the conversation um a little bit about klebsiella and

22:10    Escherichia coli and its association with hydrogen um hydrogen positive sibo um and then also Desulfibrio species with the hydrogen sulfide um positive Placebo can you talk a little bit about that yeah so um this new breath test as you mentioned the trio smart breath test measures all three gases what we see is that um using the breath test we're actually able to mimic or understand three micro types in the gut this was a paper that just came up so there's the hydrogen microtype which is mostly bloating a little bit of

22:51    change in valve function there's the methane microtype which is the stuff we've been talking about for more constipated and then there's the hydrogen sulfide microtype which is bloating but more diarrhea and more severe diarrhea and we see that the hydrogen sulfide on the breath test predicts the sulfate reducing bacteria like the desulfovibrio and fusobacterium in the bowel uh and and so we're able to see that the breath is in fact matching what we see in the microbiome of the human and the condition of diarrhea or constipation or

23:26    bloating and this is the first time we're able to see that transparently by by just measuring breath testing uh and uh that that's a super important study and uh hopefully very convincing that breath testing is really important in clinical practice great thank you yeah so I've I've seen in some of your recent work that you've been incorporating um your recent research I should say incorporating stool testing to help make some correlations or predictions um like the 16s are RNA testing sequencing testing it uh let us know

24:07    just a little about where we're at with using that as a to complement um our physical exam history taking um breath testing is that a is that a piece that we might see be added to the kind of evaluation of an IBS patient yeah I mean they're they're let me say it delicately uh because there's a lot of stool testing out there and a lot of stool testing based on the microbiome I am not saying that any of that stool testing is wrong what I'm saying is that we still don't understand all the nuts

24:44    and bolts of it um so I can't even today with any of the science tell you for sure in that patient whether that level of M Smith I is the level that causes constipation versus positive methane on the breath test we've had some work done in that area and we think the cutoff is 10 to the four but some people say well nem Smithy eye is bad that's absolutely incorrect We Know M Smith EI is ubiquitous almost everybody has a little bit of it and it's necessary and good and may even be anti-inflammatory we've got one paper

25:20    saying that higher M Smith AI means lower tnf levels in in the circulation meaning it's good for you but you can't have it this high you can have it this high so sometimes messing around with testing not knowing what you're doing can lead to trouble we've had some patients where we dropped the methane methanogens so low they start having diarrhea so and that's not sibo it's just an artifact of treatment and and so we have to know what we're doing what we're chasing and how aggressively

25:55    to chase it so the best way to say this in a very simplistic terms is there are no such things as good and bad bacteria there is such thing as a balance and and knowing that balance is the trickiest part of this whole thing that we haven't gotten there yet so uh methanogens are not bad if they're in the right numbers E coli and klebsiella are not bad if they're in the right place and the right numbers and they may in fact be necessary uh and so let's figure it out and then decide how to handle it and that's what we're

26:32    trying to do makes a lot of sense so another pillar you know kind of moving on to other aspects of this pathophysiology that ends up being IBS or sibo or emo is um the migrating Motor complex um and I think that's a big pillar of treatment and prevention of recurrence can you talk about any new updates that you've learned about um the migrating water complex and how we're thinking about it in 2022 yeah I mean I think it's very clear from a number of studies not lately but these are a little bit older studies that a

27:17    lack of migrating Motor complex equals um people uh not emo not but sibo and so it's important to know that just by changing the bacteria you're going to make people better and you're going to they're going to be better for a while but that lack of cleaning wave which we think starts from food poisoning is related to the anti-cdtv anti-vinculin antibodies and to some extent but that lack of cleaning wave is what's going to bring their overgrowth back so in patients where they relapse it's

27:51    important to keep trying to make that cleaning wave more to try and encourage that cleaning wave and so that we can get a longer time between uh between relapses in a study we did oh my gosh probably 2009 we compared nothing to erythromycin which at a low dose is a promoter of cleaning waves at that time to gaser Rod which is similar to what we have now with prucalopride it's the same category serotonin Agonist and nothing it was just a few weeks to relapse with erythromycin it got you some gain but with the more aggressive

28:30    prokinetic you've got maybe three quarters of a year without relapse and so that's what we do we try to give the right treatment for the right patient I have look I have patients where they took antibiotics I don't see them for two or three years they don't relapse so you don't want to give it to that patient but that's really 20 of the patients the rest of them need something yeah and along those lines are another pillar that we talked about is vile assets and um you know I I think one of the first

29:04    times I got introduced to the importance of bile assets with sibo was a paper that incorporated rightfaximin in combination with quorgum it was like a combo treatment and I think the proposed mechanism was that it somehow pulled bile assets into the bile acid metabolism into the treatment to help address the sibo I know you've been looking at bile assets recently can you share anything about that for yeah I mean by losses are extremely complex let me start with that uh somebody did a mass spec of stool from

29:43    humans for biolas has been found over a thousand different file assets so uh I it's almost a 10 years of study over the next 10 years to try and figure out what's going on exactly but in general bile acids are soap for the gut so they're soaked to help absorb fats and they uh break these sort of uh little cells of of material to bring fat into the body and other other products but bile acids also when they encounter bacteria certain bacteria methanogens do this have bile salt hydrolases that can change the bile salts into nasty bile

30:23    salts and some of the nasty bile salts are irritating and can cause diarrhea that's called bile salt diarrhea um but in the terms of guar gum it could have two effects it could be bringing bile in like a soap encouraging bile production and by doing so it's like a soap cleans the bowel a little bit and and that's helpful uh but the bacteria if it converts the bile acids to bad bile acids that's a bad thing so sometimes it's uh it's so you can get one or the other um and the other thing that guar gum

30:57    does is guar gum is sort of like a fiber so it can feed the bacteria and fed bacteria are easier to kill so if you're feeding the bacteria then instead of being on these restricted diets you have a higher chance of getting rid of sibo because of bacteria who are starved are in hibernation sometimes they form spores sometimes they form specialized membranes to prevent themselves from dying while they wait for food let me see yeah and so there's another big division of um IBS which we all is called post-infectures IBS and I think 2014

31:37    um was the first time I one of your updates talked about really um drilling down the potential mechanism with chemical bacteria to Genie and um how that leads to antibodies against finkelin and the development of the IBS smart test and it when diagnosing a patient with post-infectious IBS um how how has that conversation changed because I I know the conversation I was having with people in 2014 and I imagine it's much different now um now that you've had you know seven or eight years of of beta yeah I mean the first few patients moved

32:20    there was a patient who came to my office literally she was in tears because her doctors told her she was crazy that this is not a real disease that there's nothing that we know that causes IBS and then here she gets a blood test that says it was food poisoning and she's like well that's what I've been telling my doctors I had food poisoning ever since then I haven't been well and now you have a tested affirmed my what I've been telling the doctor so I mean again there's always stories behind this but what's

32:50    remarkable and will continue to be remarkable as you'll see in the coming months we are now able to create these animal models where we just give them the toxins cdtb and the Animals develop sibo they develop the three microtypes just like humans and and all the changes in the lining of the intestine that are typical of IBS and so it's this has truly been a really important part of the story the question is how do we get those antibodies out of your blood to cure you because if we do that we think we can cure you and as a

33:24    patient and that's our real Focus for the next five years because that could be the game changer like just during the patient and maybe indefinitely yeah yeah it's uh I think that one thing that I always point out to people with who had you know have IBS and you know sort of were entertaining this question of post-infectious IBS is that it's not like you go to Mexico get food poisoning and come back and then IBS starts up it's usually like a a start a stop and then a delay and then the IBS kicks in right is that still the

34:06    current thinking so that's that's exactly what we see is we see this um you get the cdtb going up right away and the patient starts to get symptomatic but food poisoning it's really severe diarrhea and then after about a week it seems to settle and then gradually you start to get these symptoms of course the food poisoning symptoms are here the IBS symptoms are here but normals down below the screen so um it's never as bad as the food poisoning but the point is that you get this like this and then down and then

34:40    this up again as a second cycle where the IBS just less and definitely yeah and the antibodies match that so it's pretty interesting yeah I think that in the IBS smart test also has in my in my patient population um helped people make a decision of whether you know they have IBS or if they should pursue further testing with you know colonoscopy or other more pathology that's related to like IBD so it's it's been a it's been really good from a primary care standpoint too you know just to um no I think that's I think that's

35:18    where that the IBS March should sit is in primary care because the thing about and we've known this for more than 10 years is that a primary care physician if they have somebody with constipation in their office they're pretty Adept at and they're not going to be Adept at Emo or intestinal mechanism overgrowth but they're going to be Adept at treating constipation and they're not stressed out of unconstitutional but if you put a diarrhea patient in front of a primary care physician who isn't experienced

35:45    with sibo and all these things they're having a little anxiety about this patient because what if it's serious what if it's Chrome systems what if it's all supplied what if it's microscopic colitis what if it's parasites on and on and on but if you did the test and it's positive you're done it's IBS treat and and I think that's where the patient will get benefited faster and less money to the Health Care system if you can do it at that stage and your doctors the doctor's comfortable it says

36:13    okay it's IBS it's not likely to be anything else let's move on let's try some IBS therapies rather than being stressed yeah yeah reminds me I when I was just getting further into you know wanting to make gastrointestinal gastrointestinal disorders or my specialty I went to a Board review course um just to fit in for like three or four days of dots getting ready for their board reviews I I signed up for the conference and the FI the um the Debo portion was like five minutes I was I was so disappointed and uh the

36:51    constipation versus diarrhea component was a very long segment and even the the teacher said you know think about constipation and diarrhea a little bit like sitting on the middle of a boat like you know if you're gonna rock the boat if it's rocking one way you move the other way and uh there was kind of like diarrhea versus constipation treatments and then you know sibo was uh but that that was a long time ago I'm sure it's changed that was maybe 10 years ago but that's really sad because

37:22    that's you know whenever I talk about the FDA and treatments for IBS about the fds well if Thea doesn't come up with the treatments the companies you know uh it was a race to the bottom uh for drugs because if you have a patient with diarrhea you want to have the best drug that made them constipated and if you had a patient with constipation you wanted the drug that would make them have liquid stools because that one's going to win and that one's going to meet the FDA endpoint instead of well don't we want to make

37:54    people normal don't we want to keep them in the middle and there was no drug that brought them to the middle until the vaccine came up because it was treating you know the cause but this whole boat notion is the reason we're sort of half in this half been in this mess and patients have been on this patients have been seasick on this boat let's put it that way yeah yeah yeah it's uh I'm glad we're you know able to have conversations I mean I think people who are really into functional digestive

38:26    disorders are you know really thinking deeply and you know sitting in front of patients who are suffering with this it's often a um it's often like a silent suffering that a patients have because nobody really understands them um and understands the extent of what it's like to have a digestive tract that's really out of balance um that being said you know I I'm curious about your thoughts with you know what makes a good gastro doc like when you're you know what are some of the qualities because I

39:04    I think you know we have this notion that people just pick a specialty you know for but people who get really good and exceptional at a specialty I'm sure there's some things that really shine um the only thing you can share with us about that well I I I I can share what I do and what I think is important as a physician I mean look there's textbooks textbooks are always the extreme examples they're always the extreme examples when they talk about low thyroid being a cause of constipation I've never seen it all I do

39:41    is treat constipation I have seen some of the most bizarrely low thyroids and no constipation so I think what we got into is this sort of it's a bit of Mythology of medicine is that back in the day when these textbooks were written and this Dogma was created there was some dude on a farm whose thyroid was so low that he was constipated and then he comes in it gets recorded as that and then it's forever indoctrinated in the medical literature we don't see that anymore we don't see the tumor this big on a on a

40:14    person's leg because they couldn't leave their job Workforce for a year everything we see is this big now and it's really hard because you can miss things because you're looking for things very very early now it's not like it used to be in the in the old days as they say uh but what I what I like in a position is somebody who's willing to work hard for the patient because you don't nobody can know everything but you sure can try to know as much as you can to help that patient so that's one

40:49    quality I look for in a physician uh the second is I've learned more about what to do in science from my patients than I did my own head because you know you're you're seeing things you just have to observe and put the pieces together but the patients are telling you everything I I I give you an example I gave a lecture um and uh I can't remember was about 10 years ago it was the first time the first refaxman lectures I did and I was in some rural town and this 70 year old doctor gets up and he's he's old and and he looks old

41:31    and seasoned and he says you know what in the 1970s I used to get Flagyl for this IBS thing and it used to work I'm not surprised I'm not surprised I'm like why didn't you say something you know so you know they people saw this people thought it was Giardia but the tests were negative you know stuff like that um so it's it's funny you just got to be a keen Observer and then put the pieces together I think that's what I'm trying to say makes sense yeah that's that's really helpful

42:07    um to hear that and I think you know one of the things that um you know I want to highlight or just kind of that resonates with me is you know the being able to um learn from your patients because you know that that shows a quality of like listening right and being open and really trying to understand the person who's sitting in front of you and I think uh with with IBS that's so important because it's there's so many different versions of it right it's yeah and the remarkable thing about IBS which

42:41    is also keep makes my me scratch my head there's rare diseases that we know a ton about genetic diseases that may be happening one in a million people look at uh gastronomers right we don't see that very often IBS is everywhere it's 10 of the population and nobody was sort of assembling the pieces very well and and uh there's no shortage of suffering you know it's not life-threatening but it's suffering and immense suffering for these patients so but that's fine you know now it's a new

43:18    day it's a new age and hopefully it will continue to improve for these patients yeah so I'd love to finish our conversation just hearing um a little bit more about the masked program and um just how people could support that I think it's just really fascinating how you're integrating with other Specialties um in really highlighting how the microbiomes interfacing with other especially can you talk about that and and also about your new book oh sure um well let me start with the book and then I'll go to the mass program so every

43:54    time I write a book it's because somebody poked me to write a book it's not that I don't like to write books I just again my whole practice as you've heard they hear it's not about me nothing is about me I I we even donated the the launch proceeds to the World Health World kitchen with uh Jose Andres because he was feeding all the people in Ukraine who were suffering and so forth because it's not a this is not about me this is about patience but it helps the patient educate themselves and it helps

44:26    some Physicians who read it understand the next level of nuance um but the mass program is uh really something that took about 10 years to convince Cedars to do that we wanted to do a program where we develop things because drug companies weren't and I think that's what got me it's this both phonology you said where you're giving diarrhea drugs to make constipated people better and constipated drugs to make diarrhea patients better and it's just frustrating so I said we have to do something because nobody else is really

44:58    doing it so let's see how far we can get and Cedar's got into it so uh I'm very happy we're able to do this but if you think about it who else is doing IBS pathophysiology research in the United States very few people and uh you've got 10 of the human population suffering from a condition and very few people doing the work NIH doesn't sponsor anything they know you know I've applied 13 times to the NIH Grant I applied about emo everything in that Grant we eventually did improve emo was

45:33    true I applied about sibo everything that we put in that Grant we eventually did Through Blood Sweat and Tears scraping barrels to get cash to be able to do those and it worked I applied about cdtb and vinculin all the animal models that we eventually did the grants never got funded so we had to you know scrap scrape together dollars and cents here and there I'll tell you one story because it's really I think you'll your audience will find it interesting a randomized controlled trial to do let's say 80 patients in a trial

46:13    probably costs two million dollars the first study we did we had no money the first study we did with neomycin and Placebo we bought neomycin and we bought placebo and we just did the work two thousand dollars wow and the neomycin study worked it was a double-blind study and that study started the whole story so it's just to show you that we we really were determined to help patients at all at any cost we could I mean just get it done um and it was an interesting time yeah that's wonderful wow yeah what a great a

46:57    story to wrap up with um so um the uh if there's any closing parting words you'd like to give us that'd be great um otherwise I just want to thank you for your time and again you know so much appreciation um for what you do and um I've helped so many patients because of the work that you do and it's very rewarding to help people and and see people you know move forward and not not need this type of care anymore you're just going to go out and live their life that's that's why I'm in this is I want

47:31    them not need me so um that's uh I just want to thank you and if there's anything else you'd like to leave us with but this has been wonderful and been just a great experience for me thank you no it's been a pleasure talking to you and it's been a while I've known you for a long while and certainly over emails so uh it's been a great experience talking to you today and great questions as always as you always give me you challenge me and uh let's do it again sounds good thank you so much and

48:04    um I hope you have a happy holiday season YouTube