Introduction:
Coming up on this episode of the Doctor’s Pharmacy,
Dr. Mark Pimentel:
We want our I B S patients to feel as normal and as socially non-isolated as possible.
Dr. Mark Hyman:
Welcome to Doctor’s Pharmacy. I’m Dr. Mark Hyman. That’s pharmacy with an f, a place for conversations that matter. And if you have tummy troubles, if you have irritable bowel, if you get bloated, if you feel like you get a food baby after eating well, you’re going to love this podcast. It’s with the man who has basically changed the map of how we understand how to deal with what’s called irritable bowel syndrome. And when I went to medical school, it was this thing that we called Super Tentorial, which is a medical pejorative way of saying it’s all in your head. And it turns out it’s not in your head, it’s in your gut. And we have our guest today, Dr. Mark Pimentel, who is a professor of medicine and gastroenterology at the Geffen School of Medicine. He’s an associate professor of medicine at Cedar-Sinai. He’s also the executive director of the medically associated Science and Technology program or mass program at Cedar-Sinai, which is a group of physicians and researchers that are dedicated to the study of the gut microbiome in order to develop great diagnostic tools and therapies that help patients. He’s had over 150 scientific publications in many high profile journals, and it’s the author of a very important book You should definitely get called The Microbiome Connection, your Guide to I B S sibo, which you’re going to learn about in a minute and low fermentation eating. So welcome Dr. Pimentel.
Dr. Mark Pimentel:
It’s great to be with you today on this podcast.
Dr. Mark Hyman:
Great. Well, I think you’re really a pioneer in this. And we talked, I don’t even remember, maybe close to 20 years ago, I used to call you up and ask you for help with very difficult patients because you had been thinking about how to deal with this differently and recognize that a lot of what we think of as irritable bowel is actually bad bacteria growing in the wrong spots in the gut and causing bloating and distension. And you were the first to identify this important antibiotic treatment called rifaximin, which is a non absorbed antibiotic that’s been approved here at AL Syndrome. It’s also for traveler’s diarrhea. You developed the first blood test that actually helps people link the fact that they might’ve had food poisoning or traveler’s diarrhea or something that then led to irritable bowel after. And that’s a common phenomena. You also helped connect the link between I b s and bacterial overgrowth and also looked at different kinds of bacteria in there that cause different kinds of gases, like methane. We heard of methane from cows, but we also produce methane and that can cause constipation related I B s. And you also developed a really new breath test that can help us figure out what kind of gases there are. There’s three, there’s hydrogen, there’s sulfur based gases and methane based gases, and it tells you what’s going on, what bacteria and guides treatment. So you’ve been such a pioneer in this area. So I really want to first say my gratitude to you because of your work. I’ve helped so many patients.
Dr. Mark Pimentel:
I got to say I remember those early days and our conversations about patients and we shared a number of patients who were challenging at the time. We didn’t have all the tools we have now, but we did our best and I think we got some patients better back then. Even then
Dr. Mark Hyman:
We do, we did. Now what’s amazing is people don’t realize this, but the number one reason that people go see the doctor is gut trouble. There’s over 70 million Americans who have sibo, which is small intestinal bacterial overgrowth, irritable bowel syndrome, or one of a number of other diseases related to gut health and 74%, which is crazy of Americans say that they have some type of digestive discomfort. So can you just start at the beginning and help us understand what is I B Ss, what is SIBO and what are the different subtypes that exist with each, because it’s kind of like a bit of a mishmash, but it’s kind of basically people who are having tummy troubles.
Dr. Mark Pimentel:
Well, yeah, you summed it up pretty nicely, but I think people get confused because of the terminology, irritable bowel syndrome, sibo, and are they the same or different? And so let me try to dissect that, but irritable bowel syndrome on the face of it, this was a term that was touted in the 1980s, but can you imagine telling a patient you’re irritable, it’s your bowel and you’re a syndrome, which means doctors don’t know what it is. It’s not a disease, it’s not legitimate. And so that’s where we started in the 1990s that it’s as you say, super tentorial or it’s in your head because it’s a syndrome and you can only tell me you have symptoms, but I don’t know why. And irritable bowel syndrome is characteristically abdominal pain, changes in bowel function and bloating, and everybody was focused on abdominal pain and changes in bowel function.
Dr. Mark Pimentel:
And we said, but everybody’s bloated in this disease. And how do you get all that gas in there? Well, you either swallow it or it’s made there and it can only be made there by bacteria and enter sibo. SIBO is small intestinal bacterial overgrowth. And back in the day, 20 years ago when you and I were corresponding about patients, we thought, oh, it’s just a bunch of bacteria coming up from the colon and now colonizing the small bowel, we’ll get to that. But we know now that’s not exactly how it works, but in essence, it’s too much bacteria in your small intestines. So when you eat food, the bacteria digest it, they start fermenting, they produce gas, it makes you have diarrhea, and then you have all these symptoms and abdominal pain and so forth. But as the years progressed, we learned that the type of buildup of bacteria or organisms in the gut dictate the symptoms.
Dr. Mark Pimentel:
So if you’re of a particular type hydrogen on the breath test, that’s one way to characterize it. Then you tend to have a little more diarrhea, more bloating, and that type of symptom. If your methane and methanogens, those bugs are not bacteria, they’re different, more ancient type of thing, organism called ArcHa, then the methane makes you constipated. And the new kit on the black is the hydrogen sulfide organisms, which make you have a lot more diarrhea. And so that’s sort of in a nutshell some of the aspects of how these interrelate. But to bring it back together, SIBO is I B s and IBS is sibo. And what I mean by that is out of a hundred i b ss with diarrhea patients, 60% roughly have sibo. So we can explain 60% of irritable bowel syndrome. Not all of it, but similar to h pylori and peptic ulcer disease, not everybody with ulcers has h pylori, maybe 60 to 80%. So it’s the same kind of story evolving
Dr. Mark Hyman:
Here and the whole ecosystem of bugs in there that determines the quality of our digestion, our bowel movements symptoms, and it’s been a black hole, I mean literally, which we never learned about in medical school. And now we’re in the era of the microbiome and there’s just an explosion of research, understanding and discovery. It’s like getting a telescope for the first time and looking into outer space and we’re actually able to see what’s going on and to differentiate things. And before it was just one big lumped in category of people who had tummy trouble call irritable bowel, and it could be irritable bowel with diarrhea, irrit bowel with constipation or mixed, and that doesn’t really tell you anything except what symptoms you have. So it’s really just a, we’ll call a syndrome. And in medicine everything, it’s a syndrome like chronic fatigue syndrome or premenstrual syndrome, fibromyalgia syndrome.
Dr. Mark Hyman:
It means we don’t really have a clue what’s going on. But now for the first time, and in part largely to to your work, we began to understand what are the underlying mechanisms and what goes wrong and how do we fix it. Maybe we can kind of take a step back and go, what is the root cause of bugs growing where they shouldn’t be in your gut? In other words, most of the bacteria should be in your large intestines, but then it migrates up to the small bowel where it’s not supposed to be, and then you get all these symptoms. Why does that happen? Because it’s not clear. It is not like a human. 74% of people have a defective gene or some bad human design that God designed us poorly. Something’s going on with our modern diet, lifestyle, something that’s causing this epidemic of GI symptoms.
Dr. Mark Pimentel:
That’s a lot to unpack, but we have a lot of answers. We don’t have all the answers, but we have a lot of answers. So we now believe that, and you sort of brought this up as part of the introductions, is that we now believe that food poisoning starts the whole process and eating as part of it back in the day, meaning like 40, 50 years ago when we were in kindergarten, we would sit in a sandbox and eat the sand. Now we eat salad out of a bag until we go to club Med. And for the first time in our life we see salmonella or we go somewhere and we get travelers diarrhea or we get food poisoning or whatever. We start to explore the world of food. But food poisoning triggers this, and we now have identified the toxin in poisoning the cdtb that trips off some antibodies in the human body that then cause your nerves of the gut to fail or to be impaired. And so when the flow of the gut is slowed by this impairment, bacteria build up and there’s two bacteria that just flourish when it’s a little more swampy. So I used to watch survivor shows on TV on Discovery Channel. You probably watch those and they always say
Dr. Mark Hyman:
From, I like the loss. I used to watch loss, which was kind of like survivor.
Dr. Mark Pimentel:
It’s a little bit different. There’s a little more RAness or with survivor, you’re just trying to make it to a road somewhere. But the point was that always this guy on the survivor show would always say, if the water’s not moving, don’t drink it. If the water’s flowing fast, drink it because it’s cleaner. And the same thing with the small bowel. If the small bowel stagnates, it becomes swampy and bacteria grow in it. And the same thing is happening in the human small intestine. And so it’s a sequence. So food poisoning the antibodies, and then you develop the bacterial buildup.
Dr. Mark Hyman:
So you’re almost saying it’s like an autoimmune disease of the nerves of the gut that develops that kind of it is an
Dr. Mark Pimentel:
Autoimmune
Dr. Mark Hyman:
Disease sluggish. So this is a kind of radical idea that irritable bowel is an autoimmune disease, isn’t it? I mean, this is kind of not what most doctors typically think of when they think of I B s. They think of I B D or inflammatory bowel disease, but they don’t think of irritable bowel being autoimmune.
Dr. Mark Pimentel:
Well, the interesting thing about contrasting I B D to I B S, so the antibody that we discovered is an autoantibody that is directly related to the pathology. So the higher that antibody is, the sicker you are, the antibodies in IBD are markers of ibd. They’re not directly implicated in the pathophysiology. The antibody to cullin that we discovered is directly related to the pathophysiology. We can make rats have I B s just by giving them this toxin. And so that’s very cool because it allows us to study new drugs and new therapies
Dr. Mark Hyman:
Coming in the future. Not so cool for the rats though. So this is fascinating. So you were saying there are different kinds of bacteria. Can you explain what are the kinds of bacteria and then what type of food poisoning? Is it any if you get Giardia or if you get salmonella, Ella Campylobacter or tba, or what are the kinds that typically cause the problem?
Dr. Mark Pimentel:
Well, the four horsemen of the apocalypse of I B Ss are campylobacter, salmonella ella, and some e coli food poisoning type of e coli, pathogenic e coli. Giardia can do it too. It turns out it has cullin in its structure. And so maybe that’s how you get the antibodies from Giardia. The viruses are less likely to precipitate I B s. So the four horsemen, kalo, salmonella, ella and e coli, and it starts to occur about three months after you get sick. Patients will remember, some don’t remember, and they’ll say, well, they have a couple of days of diarrhea and they don’t pay much attention to it. But they remember going on a trip to Hawaii and they end up in the hospital with bloody diarrhea. And then ever since then, nothing’s been the same.
Dr. Mark Hyman:
I have heard that story so many times I went to Thailand or India or Jamaica and sort of tripped the whole thing going
Dr. Mark Pimentel:
Or the taco truck in Venice. Yeah,
Dr. Mark Hyman:
Taco truck,
Dr. Mark Pimentel:
A lot of possibilities.
Dr. Mark Hyman:
Wow. So this explains sort of 60% you say, but not all of it, right? That’s right. What are the other things that may be driving irritable bowel syndrome and are they also related to SIBO or is it all something else?
Dr. Mark Pimentel:
Well, so based on culturing the bowel, we’ve been able to isolate. That’s 60% of i B s is the other 40% is a mixed bag. So for example, and you probably talk about this now, LERs down low syndrome, POTS syndrome. We’re starting to recognize those illnesses as characteristically GI centric, at least in their early presentations as well. So some of the leftover 40% have syndrome or pots or some of them are celiac that we’ve missed. Some of them are food sensitivities, some of them are histamine sensitivities. So it’s a mixed bag of a number of other disorders, and some of them are fungal overgrowth. So we see that in about six to 10% of that hundred pie. So there’s still more to unpackage. We’re not ignoring the other 40. We’re trying to figure the rest out, but it’s a little bit harder to unravel.
Dr. Mark Hyman:
So let’s pause there for a minute. You just said something that I think might slip by, which is this whole idea of fungal overgrowth or what often is referred to as sifo, small intestinal fungal overgrowth in my coming of age as a functional medicine doctor, basically people would laugh when we talked about yeast overgrowth or anything like that and candidiasis, and it was just a quacky alternative concept, but it seems to be now understood as potentially playing a role in some of these cases. Can you talk about the current understanding of this and actually some of the treatment? And then I’ll loop back to the how do we start to treat and think about I B s differently?
Dr. Mark Pimentel:
Yeah, I mean, Satish Rao, Dr. Satish RA in Georgia has done a lot of the seminal work in this, but more recently we’ve done shotgun sequencing of the small intestine and we’ve been seeing this fungal overgrow.
Dr. Mark Hyman:
That doesn’t mean you shoot somebody in the gut with a shotgun, no
Dr. Mark Pimentel:
Shotgun sequencing means
Dr. Mark Pimentel:
We sequence every single piece of D N A we can find and then characterize it, see what organisms it represents, and it represents fungus about 10% of the time. And that when the fungus is higher, the patients are experiencing more abdominal pain and more diarrhea. So there is a subclass of these patients that it is fungal, but it’s smaller than some would like to believe, but larger than those who are naysayers, as you’ve probably heard. And so it is there, it’s real, but it’s a little more challenging to identify. There’s no breath test for it. You got to go in and chase it. And that’s the challenge.
Dr. Mark Hyman:
Chase it by doing stool cultures or
Dr. Mark Pimentel:
Well chase it could be by stool, but if you want to find small intestinal fungal over both, you’ve got to get into the small intestine. And that’s really
Dr. Mark Hyman:
Sampling.
Dr. Mark Pimentel:
You have to have endoscopy and all of that. That’s how Dr. Rao identifies it.
Dr. Mark Hyman:
And any particular species of fungus or is it sort of a broad array?
Dr. Mark Pimentel:
So what we found in this quote, shotgun sequencing is candida albicans is a big part and a little bit of candida glabrata, and there’s a few other malasia and all these other organisms that are very minor, but they generally aren’t at a high number that we think are as consequential as the first two I mentioned.
Dr. Mark Hyman:
Yeah, no, I definitely have seen that on cultures and in my experience, maybe it’s not universal, but it tends to lead to more constipation. And so people tend to have more constipation. And I also, I can tell because they might have other fungal symptoms, they might eat tons of sugar and starch, they might actually have fungal rashes on their skin or dandruff or other kind of clues that they have a yeasty kind of situation going on. But I think it’s important that it’s been identified. And going back to the treatment of that, how would that normally be treated?
Dr. Mark Pimentel:
Well, generally in allopathic medicine we try an antifungal. There are natural antifungals as well, and you’re probably better versed in those than I am. But we do use fluconazole. We do use Nystatin. Occasionally we use more radical, more advanced antifungals. But those are the typical first two choices.
Dr. Mark Hyman:
Sometimes you can take what we used to call amphoterrible, which is a horrible first-generation antifungal, but it’s not absorbed. So if you take it orally, it’s not absorbed, and that can totally be Exactly, yeah. And then in terms of the bacterial stuff, you talk about these three different bacteria. You’ve got methane producing, hydrogen producing, sulfide producing, and they all are a little bit different and said the methane producers are not really bacteria, they’re archaea, but for simplicity’s sake, let’s call ’em bacteria. And I don’t think most people know what ark is arcane, right? Yeah. So what is your approach to starting to differentiate these, and then how do you determine what the right treatment is for a patient and can guide us through what to do both in terms of lifestyle, diet, any kind of supplements that might be helpful and medication?
Dr. Mark Pimentel:
Yeah, so first of all, we helped develop the first three gas breath tests, so just full. But it’s changed my practice because there are patients who fell through the cracks without knowing hydrogen sulfide. So unpacking each, the hydrogen positive breath test patients are generally, we actually just published this paper. It came out literally yesterday. There are two bugs, that’s it that caused the hydrogen overgrowth. It’s Escher coli, the non-pathogenic one, and Klebsiella pneumonia. Those two characters, when they come into town, everybody leaks because they’re so opportunistic and bullies and we think they produce even toxins to the other bacteria around them to try and get rid of the inhabitants. So it’s like you’ve got a gang that comes into the small town and everybody leaves. So it’s a disruptor of the microbiome. And then they rise very high in number. So that’s the hydrogen one.
Dr. Mark Pimentel:
The second category is the methane or methanogens. And those characters live both in the colon and the small bowel. And we have a paper coming out showing exactly where they’re living. And it’s pretty universal in a lot of these patients. So hence we call it intestinal meth antigen overgrowth and not SIBO methane because it’s not just the small bowel, it’s colon also. And when they produce methane, it gives you a lot of constipation, a lot of gas, and you can’t pass the gas and these people are quite miserable. And then the third is the hydrogen sulfide, which is the new kit on the block, which has changed my practice because some of those patients we didn’t know, breath test is normal, everything looks fine, and then the hydrogen sulfides positive, we get rid of it, and all of a sudden they feel better than they have in their life. And for some reason when you get rid of hydrogen sulfide, it doesn’t come back so quickly, which is beautiful. I have patients who’ve gone a year just one treatment and they’re done. And so I’m really excited about that. So I mean I could talk about the treatments if you like now or Yeah,
Dr. Mark Hyman:
Yeah, yeah. Go through the treatments because I think they’re real different. And this is important to understand for people because just because you have a real bowel, it’s not like a one size fits all approach. You’ve got to differentiate what type it is. And these tests that Dr. Penington developed the tests for anti c d TB and ANIN antibodies are really important. And then the breath test that allows you to look at hydrogen, methane and sulfur. So can you talk about what are the different treatments for each of these?
Dr. Mark Pimentel:
Yeah, so I mean if I have an I B S patient with diarrhea or a patient with diarrhea and bloating, my practice, now I do the antibodies because I want to be able to say, was it food poisoning or not? And if the antibodies are really high, it makes it harder to treat, but also you travel, you better take prophylaxis. You could get into further trouble with these antibodies going higher. So I universally do that
Dr. Mark Hyman:
Like prophylaxis. Like what? Like Xifaxan or I
Dr. Mark Pimentel:
Give Xifaxan prophylaxis. That’s what I do in my practice. And a lot of the gis now do that because if the antibody goes higher, the damage to the nerves of the gut is more intense or the effect on the gut is more intense. And at least that’s what we’re seeing in our clinic. So we’re very careful with those patients who have the antibodies positive when it comes to then we do the three gas breath tests in all of our patients. And if it’s hydrogen, and we all know Axman got F D A approved for I B s with diarrhea on the basis that i b s was in part of microbiome disease, and now we understand that microbiome condition is sibo. So I give rifaximin for that. If it’s methane, we have one double blind study that we can lean on and it’s rifaximin plus either neomycin, which is what the double blind study covered or rifaximin and metronidazole. And then the third category is hydrogen sulfide. And we give rifaximin, but we give it with bismuth because bismuth is an anti, it blocks some of the synthetic functions of hydrogen sulfide in the sulfate reducing bacteria. Point is the hydrogen sulfide goes down, the bacteria are reduced and therefore the patient’s normal bacteria take over and things get better more permanently in that group at looks like.
Dr. Mark Hyman:
And that’s basically Pepto Bismol and
Dr. Mark Pimentel:
Yeah. Yeah,
Dr. Mark Hyman:
Yeah. Interesting. So in terms of diet, is there a different approach to each of these in terms of what you would recommend from a food perspective?
Dr. Mark Pimentel:
We haven’t sorted out or had time to sort out the different diet approaches, but I envision smarter people in vegan diet will come up with a way. What we do now is what we call low fermentation eating. So we don’t use low FODMAP in our practice because you can’t do it indefinitely, but low FODMAP will reduce the amount of calories you’re providing to bacteria and therefore they’ll ferment less and that might help. But long-term low FODMAP hurts your microbiome and can cause nutritional deficiencies, so you can’t stay on the full O fodmap. Indefinite
Dr. Mark Hyman:
And FODMAP is like fermentable oligosaccharides that basically,
Dr. Mark Pimentel:
Yeah, fermentable, oligosaccharides, monosaccharides and et cetera. And basically it’s too restrictive, but you’ve probably, most people have probably read about fod, low FODMAP diet. It’s very popular in the last few years, but we use what’s called low fermentation eating not as restrictive. And the philosophy of that was with a low fermentation diet, you can go to any restaurant in the country and you’d find a meal. So you don’t want to be the person at the table just because you have I B S that spends 10 minutes with the trying to explain your dietary restrictions on a low FODMAP diet. So that’s part of the reason we want our i b s patients to feel as normal and as socially non-isolated as possible. And that’s part of
Dr. Mark Hyman:
It. What is a low fermentation diet?
Dr. Mark Pimentel:
So it’s basically when you’re restricting non-digestible carbohydrates, so low fiber, no dairy, and then none of the artificial sweeteners because of course they’re easily fermentable. And then spacing your meals so you don’t eat for five hours between meals because the damage of the nerves, we talked about that earlier. The damage of the nerves causes a reduction in cleaning waves of the gut. So the cleaning waves only occur when you’re not eating. So your gut is sort of like got two computer programs, eating mode, cleaning mode. If all you do all day is spend time in the break room taking a bite of a bagel that’s in the break room, you never go into cleaning mode. So in addition to the construct of what to eat, we tell you when to eat and to try and space your meals out. Anyway,
Dr. Mark Hyman:
Interesting. The typical dietary recommendation when I was in medical school for I B Ss was more fiber like Metamucil. Basically what you’re saying is that you want restrict soluble fibers that are digestible and low fiber diets. It seems like a contrary notion when you want to create a healthy microbiome because good bugs also live on fiber. So how do you navigate that?
Dr. Mark Pimentel:
Well, I may be punished for saying something like this, but everything has fiber in it now. Even Cheerios, they put fiber in it because it prevents colon cancer and its colon health and all this stuff for 20 years. How much have we heard about health and fiber? Fiber, fiber a lot, and what have we got now? We’ve got colon cancer happening in the forties and we’re doing screening colonoscopy at 45. Now, I’m not saying it’s fiber causing that, but all the fiber we’ve been pounding and the cardboard we’ve been eating hasn’t really done as much as we thought it might. So I’m a little unclear about fiber, but from the point of view of bacteria, you put more fiber, you’re going to have more of the bacteria. If you had bad bacteria to begin with, there’s going to be more of them. For a healthy person whose microbiome’s healthy, no problem, but not for these patients with these microbial conditions.
Dr. Mark Hyman:
Now if you’ve gotten these antibiotic treatments, you’ve gotten diagnosed, you’ve gone through the testing, you’ve gotten the personalized treatment, you do the course of antibiotics, what prevents the bacteria from coming back? And in my experience, it often does. So how do we manage this sort of recurrence that occurs? Because you don’t want to keep giving people antibiotics because intuitively people go, wait a minute, antibiotics are bad for the gut. So why are we giving antibiotics to someone who’s got a gut problem? It seems counterintuitive.
Dr. Mark Pimentel:
Well, I can answer in two or three ways, but I’ll try to touch on a little bit of each. We looked at rifaximin before and after treatment, the small bowel, and when you get rid of the bullies in the town, all the inhabitants of the town come back. So it goes opposite of what people think. We’re not being cataclysmic. It’s getting rid of the e coli and the Klebsiella and SIBO that allows the regular bacteria to repopulate and take over again for a period of, but remember, the problem is those is possibly going to come back. It depends how badly damaged, and that’s where that antibody comes in because if the anti cullin, which is that auto-antibody for the autoimmune disease of I B s is very high, the neuropathy is more high or more intense, and you’re going to relapse or reoccur more frequently.
Dr. Mark Pimentel:
So that’s where we were able to have some further strategy. But first of all, take the antibiotics, they actually repopulate the town counter to what you think. We’ve never seen antibiotic resistance to rifaximin so far. Knock on wood. It’s a very unique chemical drug. And then we get them on the low fermentation eating diet. That’s what we do. And for those where the antibodies high or those who relapse, we do put them on a prokinetic. So they space their meals, everything’s going right, but we want to stimulate those cleaning waves at nighttime the longest time you’re not eating and make you clean up as much as possible at night so that the bacteria don’t have a chance to come back. So we don’t do all three things for everybody. It depends on if somebody relapses in two years, we don’t need to put them on a drug every day to prevent, but if they relapse every three months, then we can stretch it out to a year by adding the prokinetic or doing more aggressive diet strategies.
Dr. Mark Hyman:
So this is something that’s a chronic condition that has to be continually retreated in some ways, is that what you’re saying?
Dr. Mark Pimentel:
That’s right. It’s sort of that way for now, but that’s the point of the antibody. If the antibody is causative, get rid of the antibody, get rid of the disease. So the focus of our lab right now is get rid of that antibody.
Dr. Mark Hyman:
And how do you do that?
Dr. Mark Pimentel:
Well, I can’t tell you first of all because
Dr. Mark Hyman:
No,
Dr. Mark Pimentel:
We haven’t worked. We haven’t it all out. But there are ways to do these kinds of things and we’re exploring multiple ways or avenues to do this because the ultimate goal is to cure this and not just go what I’m telling you today, hopefully if everything goes according to plan 10 years from now, we won’t be doing what I’m telling you today. Today we’ll be doing something much more permanent.
Dr. Mark Hyman:
Now is it a pharmacological solution or just something else?
Dr. Mark Pimentel:
Yeah, it would have to be be something, and it might even be a biologic agent to try and drag that antibody out of the bloodstream, but then it’s cured and you don’t have to worry about anything. You can go do whatever you want, go wherever you want.
Dr. Mark Hyman:
Interesting. I was just thinking about from my perspective as a functional medicine doctor, I think of things like how do we deal with autoimmune neuropathy, right? One, we look for the cause. Well, if it was some infection, we try to get rid of that, but it could be other things like nutritional deficiencies or toxins or other things, and even certain things might be helpful, like lipoic acid, just kind of theorizing, not there’s any evidence about this, but lipoic acid is great for diabetic neuropathy. Could it help the gut? Plasmapheresis is often used for chronic neuropathies. Peripheral neuropathies or things like Thera. Could that be helpful? So I’m just sort of wondering are there other kind of novel things that we haven’t thought about that
Dr. Mark Pimentel:
Might be helpful? So just anecdotally, and so I don’t like doing anecdotal medicine. We like to do publish our papers and do good randomized controlled trials, as you know. But anecdotally, but
Dr. Mark Hyman:
By the way, all feces of medicine come from anecdotes. So I start with an observation.
Dr. Mark Pimentel:
No, what I’m saying is I’m going to tell you things that we do that have been very, very successful. So that wasn’t meant to be critical of more critical of what I’m going to just now tell you because I don’t want people to go out there and start doing plasmapheresis in I b s patients. But we have in five patients and for one month their IBS is gone until the antibodies repopulate. So we know what you’re saying is actually absolutely the list of things that should be tried. And so you are spot on is what I’m saying.
Dr. Mark Hyman:
But I just made that up. I just was guessing because based on the theory of how he would normally think about these things,
Dr. Mark Pimentel:
As I’ve known you for 20 years, you generally don’t riff. And that riff is based on a lot of scientific knowledge, scientific, scientific, and you riff off at least two things that we’ve tried that have worked very, very successfully. But we need to do something even more advanced than that because you can’t put a catheter in the neck and do dialysis like plasmapheresis on an I B SS patient, 70 million people in the US as you started program. No,
Dr. Mark Hyman:
Clearly not.
Dr. Mark Pimentel:
So it’s not an answer, but it proves the hypothesis as you mentioned.
Dr. Mark Hyman:
Amazing. Now, one question I have is do you worry about giving the antibiotics and then seeing fungal overgrowth because right, it’s all about the weeds. If you kill one plant, then other plants grow. So if is there any kind of necessity to deal with cleaning up after the antibiotics with herbal or natural or nonabsorbent antifungals or even Nystatin or even things like Diflucan? Is that ever needed?
Dr. Mark Pimentel:
Yeah, so I mean, as you probably are aware, I’ve treated thousands of patients with rifaximin, and it’s not zero, but it’s extremely rare that we see people get worse. We did a study where we looked at the number of people who got worse with rifaximin, had to stop the drug from taking it, and you have to treat 8,000 plus patients for one person to feel bad enough to stop rifaximin. That’s how safe it’s, but in the old traditional thinking, yeast should get more if you give antibiotics. But as we’re dissecting the microbiome, they’re almost mutually exclusive. So they don’t always happen together. And so maybe the ones that don’t rifaximin doesn’t work. It’s not making it worse, but you need to go to the antifungal. And that’s what we’re trying to sort out is odds are you have overgrowth of, because it’s 60% start with that and maybe the ones who fail start to think about fungal if the symptoms continue to be typical of an overgrowth of some kind.
Dr. Mark Hyman:
Yeah, interesting. The other thing I think about is probiotics, because typically people think, oh, I have tummy problems. I’m going to take probiotics, but they can make i b s worth and they can make SIBO worse, right? Yeah.
Dr. Mark Pimentel:
A couple of things with probiotics that you love to hear probiotics do make I B ss worse because you already have an overabundance of bacteria. Fun fact, and this goes back to the beginning of the program. You were talking about the microbiome, but the beginning of the microbiome was only looking at stool. Nobody looked in the small bowel, the darkest area of the gut. And that’s when we started looking. So lactobacillus, very nice to have in your stool, who gets a lot of lactobacillus, people who age very badly, they have a ton of lactobacillus in their small bowel. So when we just published our aging paper, lactobacillus in the Small Bowel was a sign of unhealthy older people. And so different regions of the gut, different benefits or harms to different whatever you are taking as a probiotic. So I’m not so big a fan of lactobacillus, we didn’t see that for bifido or some of the other probiotics, but lactobacillus, I’m not sure, maybe it’s not so great to take if you’re older,
Dr. Mark Hyman:
But interesting if you think often I’ll empirically just kind of try to reset the gut after a treatment with rifaximin or antibiotics. And I don’t give probiotics before, but I’ll give them after and I’ll give things to help sort of support gut health like fish oil or vitamin A or G L a, other nutrients that are important for helping the digestion kind of repair. So that’s my of hope that wouldn’t come back. There’s not a lot of great evidence about that, but it’s sort of a framework we have in functional medicine of just putting the whole package together, of restoring the gut ecosystem.
Dr. Mark Pimentel:
Yeah, I mean, some of the things that I’ve seen done, and I’ve done it in a few patients is first of all, if you’re going to use a probiotic, you could try bifido because bifido actually has been shown to stimulate cleaning wipes and also isn’t associated with sort of a bad microbiome, but some of the other things you’re talking about to restore. So it’s sort of like you’ve gotten the bullies out of the town, now let’s get limousines and drive all the people back into town, which is what you are doing, instead of letting them gradually come back, sort of push them back into town quickly so that everything normalizes. And I think some of the things you’ve proposed, even fiber, which I was sort of negative against, giving it in the right timing to nurture the normal flora back could be beneficial. So all of these things need further contemplation and study.
Dr. Mark Hyman:
It’s right, it’s all about timing. If you give prebiotics to someone with sibo, it’s disaster. If you do it with someone after you’ve treated them and give some probiotics often it’s fine. I wanted to talk about methane SIBO because it’s a bit different. It isn’t typically caused by the food poisoning. What causes it, and you mentioned a little bit about the different treatment using different antibiotics, but what seems to cause the intestinal methane overgrowth?
Dr. Mark Pimentel:
Yeah, so we know a lot about how the hydrogen overgrowth, which we just talked about, the blood test is really important there. The blood test isn’t very helpful here. As you said, the food poisoning isn’t usually the cause of this. We think you get colonized with these methane producers from your mom, your parents sharing the bathroom and so forth at a young age, and then they supposed to be there a little bit. Why they, as we call it in the microbiome community, bloom or expand their population so broadly. And then cause illness is not clear. We don’t see a trigger. We don’t know of a trigger. We seem to see that it is more gradual over time rather than some kind of event like a food poisoning. And then it reaches a threshold where it’s just crosses over and then you’re really unwell. But the people with intestinal meth antigen overgrowth or this methane, they’re more sick than the patients with diarrhea. So just to put it in perspective, if you never go to the bathroom reliably and you are bloated and you can’t get the gas out, you can’t, at least the diarrhea patients, they go to the bathroom and they feel a little relief after, and some of the gas comes out and they feel something benefit even if it’s only for a few hours. The methane people never feel relief. They always feel bloated, they always feel distended and they just can’t get a break. And so they’re pretty miserable folks.
Dr. Mark Hyman:
One of the things I found also helpful if there’s much data about this, but is after I’ll treat with antibiotics, I’ll often give an herbal course of treatment as a way of keeping the bacteria down. So there’s things that are typically helpful like oregano or thyme or there’s a product that’s for methane, zebo, cotran, and there’s other products out there on the market that seem to be effective in helping keeping things under control hopefully until you come up with a permanent cure over there in your lab. But I think I find these very helpful. Have you found those helpful as well?
Dr. Mark Pimentel:
Yeah, I mean one I gravitate towards a lot is Allison
Dr. Mark Hyman:
Garlic. Yeah, that’s garlic
Dr. Mark Pimentel:
Because it does have an anti meth antigen property. I probably shouldn’t say this on your podcast, but there is a seaweed from Hawaii that they’re using in cows and it reduces methane dramatically, but they don’t know the safety in humans and they don’t know what dose Exactly. I’ve been doing a little work on that recently.
Dr. Mark Hyman:
Yeah, yeah, I was going to say that actually they’re talking about cow cause contribution to climate change because of their methane burps and farts and everything. And actually they’re giving them different diets changes the methane production, like the seaweed diet.
Dr. Mark Pimentel:
Yeah, yeah. The seaweeds do reduce methane by about 60%. At least that’s what I read in the last couple of days on the newest literature. So that’s fascinating. If we knew what chemical agent in the seaweed was doing that, that would be helpful. Maybe it’s a new product, a natural product that could be beneficial. But yeah, I mean berberine, oregano oil, things that you mentioned do have effects that, and we try all of the above when we have these really tough desperate patients.
Dr. Mark Hyman:
Yeah, it’s been such a learning curve for all of us as we’ve sort of gone from, oh, it’s all in your head to actually there’s something going on. And I remember this paper you probably remember too, it was in jama, I can’t remember the author. I think it was an Indian author, and it was 20 plus years ago. And essentially it said how in medical school we all learned that people who were anxious and had anxiety disorders, basically mental health issues were the ones who would get irritable bowel and that was the cause of their irritable bowel. In other words, their emotional irritability would cause an irritability in their gut. And the author was like, Hey, wait a minute. No, it’s actually the opposite. It’s like when there’s a change in the gut flora, when there’s an increase in inflammation, when there’s dysbiotic bacteria, when there’s a leaky gut because there’s this deep connection between the brain brain and the gut brain. You’ve got this whole enteric nervous system that feeds back to the brain irritable signals that makes you have an irritable brain. So the irritable bowel causes the irritable brain, not necessarily the other way around. What are your thoughts on that?
Dr. Mark Pimentel:
Well, they’re now terming this disorders of gut brain interaction is what they’re now the new term for I B S. But if I take a knife and I make a one inch cut on your arm and you feel pain, is that a problem with your brain or your arm? Your brain? Because the pain is the brain’s experiencing the pain, but the arm’s having the problem. So I’m trying to wrestle with this terminology and the whole thing of stress. The other fascinating thing about bacteria in the gut, some of the bacteria produce serotonin. Some of them produce insulin-like peptides. Some of them produce glucagon-like peptides. Some of them produce. I mean, we’re just right here trying to unpackage all the chemical possibilities of what the bacteria are doing. But going back to the original part of your comment in 1972, if you had a heart attack, you were in the hospital for a month because you can’t walk, you’re going to have another heart attack, you’re going to die. We didn’t put stents in back then. We just didn’t want any aggravation and put you in bed
Dr. Mark Hyman:
For
Dr. Mark Pimentel:
If you were a c e O of a company, you are too stressed. Your job is killing you. That was what they were saying in 1972. Your job is killing you. Not the stakes, the smoking, the alcohol, the hypertension, the cholesterol. We didn’t know any of that then. So medicine evolves whenever there’s a disease we don’t understand. Doctors use stress as an excuse to explain it until we know more. And maybe I’m being too aggressive with my comments, but that’s the point, is the truth will eventually unfold. And I do believe these patients have anxiety, and I do believe these patients have stress, and I do believe the disease makes many of those things worsen them. But I don’t believe that stress is the cause of ibs.
Dr. Mark Hyman:
Yeah, I agree. And I hear this over and over from my patients. Gosh, when you treated my gut, my psychological symptoms went away. Or when my gut’s really bad, I get more cranky and moody and I have all this anxiety. So it’s actually something I hear quite a bit from my patients. I’m like, well, that’s interesting because it sort of makes me think that it’s actually the microbiome that’s going on. And now we know that the change in the microbiome can lead to depression, anxiety, all the neurodegenerative diseases. So it’s like the microbiome is quite an important container for an ecosystem of bacteria that are intimately connected with the rest of your health. And pretty much every known disease now that we can think about, it’s a chronic disease unless you get hit over the head by the hammer. But basically it’s integral to our health and we’ve ignored it for so long, and that’s why I was so excited to see your book, the Microbiome Connection, and it’s really how we need to learn to take care of our inner garden a little bit better. And I’m wondering if you could share as a GI doc who specialize in this, how do you help people restore their intestinal ecosystem? What are the sort of tricks of the tree that you found most effective?
Dr. Mark Pimentel:
Well, I think what we now understand in the microbiome and this shotgun sequencing again, and all the exploration we’ve done in the small intestine particularly, remember the small intestine is not just your garden, it’s your grocery basket. Because the small intestine is where you absorb everything, your food. So the bugs in there are dictating what they get, what you get, how they help you. They produce vitamins, et cetera. And so they’re really special in the small intestine. So keeping those normal is important. But what we’ve seen in the small intestine is there are bullies that take over. I’ve mentioned the SIBO bullies. Lactobacillus is a disruptor too. The higher it is, the more destroyed the small bowel microbiome is as well. We sort of touched on that, but I didn’t get into a lot of details. So we’re looking for the bullies. Interesting, fun fact is that we just found a bug in the small intestine that is associated with polycystic ovary syndrome, the number one cause of infertility in women because it produces testosterone. We just presented that at a meeting. Dr. Mathur in our program is an endocrinologist who just knows this stuff, and she discovered this in the mass group. And so we’re starting to see amazing things that are happening in the small bowel that could be associated with a number of diseases we were not expecting.
Dr. Mark Hyman:
Fascinating, fascinating. Wow. P C O S, I never would’ve thought of that, but it makes sense. The hormones are regulated in part by the microbiome. There’s certain piece of bacteria clostridia that make an enzyme called beta glucuronidase that actually uncouples estrogen from its package that’s excreted from your liver and then lets you reabsorb it. And those women tend to get more cancer and antibiotic use has been associated with more breast cancer. So it’s all these things seem to be really connected. One of the things I’d love you to comment on is some of the sort of really important bacteria that I see very low in patients, which is akkermansia. And I think this is a keystone species that is important for keeping the mucus layer and the lining of the gut and preventing you from having this leaky gut issue. So I want to explore that a little bit.
Dr. Mark Hyman:
And also this idea that maybe when we see irritable bowel syndrome, it’s sort of on this spectrum of bowel diseases that goes from irritable bowel all the way to full-blown colitis and Crohn’s, and that even systemic autoimmunity that if your gut’s not healthy and you have a damaged gut microbiome, it can cause damage to the gut lining and then create this phenomenon we call leaky gut or increased permeability that creates a flood of antigens and bacteria and toxins and food toxins or food antigens into your bloodstream that then you react against and creates generalized systemic inflammation. And I think a lot of these IBS patients have this kind of stuff, and that’s why when you fix it, they feel so much better.
Dr. Mark Pimentel:
Yeah, no, I mean you’re touching on these keystone species. I think that they are there, and that’s true. Akkermansia may one of them, previ is another one. Anytime we see super healthy people, we see a lot of prevotella. The older you are, meaning you survive to your nineties, the more previtt you have. So Prevotella seems to be sort of a super bug for a good health and good aging and less diseases. And so yeah, that’s
Dr. Mark Hyman:
More in hunter gatherers. We see those more in the hunter gatherer species.
Dr. Mark Pimentel:
It’s true. Yeah, it’s true. And so the question is, whenever you have, maybe I always do these stupid analogies, so bear with me. But if you have a bad king, the country suffers. If you have a good king, people love the country, the country flourishes. And I think in SIBO there are bad kings that are just, people want to leave the country. And then you have the good king who’s giving all good food and maybe some chemicals that cause the right things to flourish. And so the country’s stable, the country’s flourishing and the population’s doing really well. So I think that’s how we have to look at least in the small bowel, is that we want to have the good kings or the good kingdoms of things that keep the balance and diversity and balance are critical.
Dr. Mark Hyman:
And with akkermansia, one of the things that I learned, and I think this is something that I definitely missed along the way is, is that a lot of these bacteria in the gut that are good guys actually love polyphenols. So it’s not just prebiotics and probiotics, but they actually love these plant chemicals, these dark colorful compounds and plants that are the medicines and plants. And we’re just beginning to understand these relationships. Can you talk about what you know about how to include things in your diet that actually help the good guys flourish?
Dr. Mark Pimentel:
So it, it’s so complicated, but polyphenols can be beneficial to some of these species keystone species. I don’t specifically give specific chemicals in that way, but there are things that patients take. We see that in the reimagined study where people are taking certain herbal preparations or certain products and they have more of the keystone species. And what that tells me is we need to do more research in that area. We need to study that more definitively because it’s not just about killing the bad ones as our approach Now, I think what you’re suggesting is that bringing up the good ones may kill the bad ones or prevent the bad ones, and that’s a side of medicine that you all are familiar with, your clinic is very familiar with, but we don’t approach it that way as much. And I think we need to both come together that way and understand from each other.
Dr. Mark Hyman:
Yeah, so you were talking about some of the compounds produced by the microbiome. Akkermansia produces gaba, which is basically a natural Valium, so that might help deal with the anxiety or free example, or it produces GLP one agonist, which is like ozempic. So we know that you can swap out the microbiome from a thin mouse into a fat mouse, and the fat mouse gets thin, even the same amount of calories. So it’s just kind of mind blowing when you think about how these relationships are, how complicated they are, and how important they are to our overall health. It’s not just your real bowel, it’s all of us need to be thinking about how to take care of our gut a little bit better.
Dr. Mark Pimentel:
Amazing.
Dr. Mark Hyman:
Yeah. So I want to talk about some of the workup on this because you’re kind of at the apex, right? You’re the OG guy in SIBO that I learned from decades ago and read your stuff and read your papers and applied it and helped thousands of patients. But there’s one of you now most doctors that I know of, don’t check for the three gases that you mentioned on a triple breath test, this hydrogen methane in the sine, and they don’t check for the anti or the anti CD TP antibodies, which is available. Actually, you can get it online through this website called IBS Smart where you can order without a doctor and it’ll get interpreted and sent to you. So how do people start to access this kinds of testing and get to the right treatment? Is this widely available? Are GI doctors now understanding this, the average? Are they internist or family doc who treats i b s probably not too aware of it. Where do we go from here?
Dr. Mark Pimentel:
Well, these two tests are available anywhere in the United States, so you can just go to the websites and order them as you’ve described. So it’s freely accessible. Even the patient can arrange it themselves.
Dr. Mark Hyman:
Even the hydrogen, can you get those triple breath tests from my Quest or LabCorp? They do.
Dr. Mark Pimentel:
No, it’s only from the TRIOS smart website because that’s the only company that has it at the moment. But again, I am part of that and so full disclosure, but people are doing it. It’s more and more and more people are recognizing the importance of sibo, the importance of doing three gases because three gases gives you more information. And that third guess has been a super important addition. So it’s available. What the problem is, is there’s a gap in education. I mean, look at how much information’s coming out every day. And so as an internist, how do you keep up with everything? I mean, I have a tough time keeping up with gastroenterology and I b s let alone everything as an internist. So I kind of feel bad for some of the doctors out there who are treating these patients. The patients are frustrated, says, doc, why don’t you know about this? And the internist is saying, well, I got a lot to learn. There’s so much out there. It’s really tough for them. And so this helps. Podcasts is amazing. I’m so grateful to be on your podcast. And if it helps a few patients, that’s amazing. But disseminating the knowledge and then having the doctor take an interest in trying to understand how to apply the knowledge because you have to take the test and know what to do with it, and that requires a little more work or effort by the physician.
Dr. Mark Hyman:
Now is all this in your book? Is all this described in the microbiome connection?
Dr. Mark Pimentel:
It’s in the book.
Dr. Mark Hyman:
So often I find that medicine goes from the bottom up that patients will bring stuff to their doctor and that have to be their own advocate. And I think it’s important for people to learn about this. For those, we’re going to put a link in the show notes, but the website for the antibody test that Dr. Pimentel talked about is called ibs smart.com. And the one for the gases is trio smart breath.com. Treat T R I o smart breath.com, and you can learn about them there and learn how to get them and advocate for yourself with your doctor to get these tests. If you have tummy troubles, if you are bloated, if you have a food baby after eating, that ain’t normal. It’s not something you have to live with. It’s something you have suffer with. And I can tell you, it’s for me, one of the most satisfying areas of medicine because I’m able to help so many people.
Dr. Mark Hyman:
Now, there are those cases that are tough and that recur and come back, but it’s really remarkable how many people you can help just following this approach that has really reshaped our thinking about irritable bowel and digestive health. And I think, again, we’re just sort of at the beginning and we’re developing new tests all the time and new ways of analyzing what’s going on. Like you said, the physician who discovered there was doing small intestinal sampling with an endoscope is able to see fungal overgrowth and treat that and sort of differentiate things. And I always say, if you know the name of your disease, it doesn’t mean what’s wrong with you, right? Saying irritable bowel doesn’t really mean anything. You have to figure out what is it and what type, and then personalize the treatment. And this is just sort of taking us on this advent of this era of personalized medicine, which is coming fast and furious, and I’m just so excited about the work you’re doing. I constantly learn from you and I coach everybody if they want to learn more to check on his work. He’s at Cedar-Sinai. You can go on PubMed and search for his name. You’ll find all the research papers or linked to a number of them in the show notes. And I wonder if you have any last thoughts for our audience about what they should do if they’re feeling miserable and their gut’s a mess, and besides getting your book, which you shall do, the Microbiome Connection, your guide to I B S, SIBO and Low Fermentation Eating.
Dr. Mark Pimentel:
I think the way I approach medicine and the way I approached the last 20 years is it’s all about the patient. It’s not about me. It’s really, it’s not supposed to be about me. And so we fight really hard to enable patients to empower them. I would like I b s to be considered a disease. And I think having worked with you for 20 years, you’re doing the same thing on a lot of fronts as well, because Yeah, and I’ve watched a lot of the things that you do. And so I appreciate having known you this period of 20 years, and it’s great to do this podcast because I learned from you, you as well. You
Dr. Mark Hyman:
Got gray hair now.
Dr. Mark Pimentel:
Yeah, we both do. I know, right? But it’s just the patients need to be empowered. Whatever they have, they need to be empowered and they need to be able to take sometimes the stuff into their own hands because their physicians can’t always keep up with the latest. So I appreciate the opportunity to be on the show and get a chance to talk about this very interesting area.
Dr. Mark Hyman:
Well, thank you. Yeah, I think that just underscores the point that we have to be the CEO of our own health and own our own data and figure out what’s going on. And doctors can help us be allies in that, but we need to advocate for ourselves. And so thanks for your work. That’s what you’ve been doing for the last decades and decades to make so many, literally millions of people have an answer to things that they suffered from for years without any benefit. And particularly, I’ve benefited too, because I actually traveled all over the world. I had horrible traveler’s diarrhea. I was sick many times. I was in Jamaica and Thailand and in and out of hospitals really bad. And I developed oral bowel. But I’ve been able to fix it by using this approach. And so it’s just fantastic. So thank you so much for your work and look forward to seeing again soon. And for those of you who love this podcast, please share with your friends and family. I’m sure since about 75% of Americans have bad tummies that they’re going to benefit from this. Leave a comment, have you worked with your own I and what’s worked? What’s not worked? We’d love to learn and subscribe wherever you get your podcasts, and we’ll see you next week on the Doctor’s Pharmacy.
Closing:
Hi everyone. I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you’re looking for help in your journey, seek out a qualified medical practitioner. If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.
