The Dr. Hyman Show - How the Gut Microbiome Influences Everything from Cancer Treatment to Inflammation

Episode Date: February 19, 2024

View the Show Notes For This Episode Get Free Weekly Health Tips from Dr. Hyman Sign Up for Dr. Hyman’s Weekly Longevity Journal Get Ad-free Episodes & Dr. Hyman+ Audio Exclusives Your gut microbiome is your inner garden—the more good bugs you have in it, the more likely it is to flourish. Our gut bacteria regulate many bodily functions, from creating vitamins to controlling our immune system, brain function, and, of course, our metabolism and weight. They are critical to our long-term health. But even if you’re eating the right things, you may need outside assistance to maintain plentiful and diverse gut bacteria. In today’s episode, I talk with Dr. Steven Gundry, Dr. Mark Pimentel, Dr. Uma Naidoo, and Dr. Zach Bush about the importance of the microbiome and why it should be considered in any disease treatment plan. This episode is brought to you by Rupa Health, Cozy Earth, AG1, and Essentia. Streamline your lab orders with Rupa Health. Access more than 3,000 specialty lab tests and register for a FREE live demo at RupaHealth.com. Right now, you can save 40% when you upgrade to Cozy Earth sheets. Just head over to CozyEarth.com and use code DRHYMAN. Get your daily serving of vitamins, minerals, adaptogens, and more with AG1. Head to DrinkAG1.com/Hyman and get 10 FREE travel packs and a FREE Welcome Kit with your first order. Receive an extra $100 off your mattress purchase! Go to myessentia.com/drmarkhyman and use code HYMAN at checkout to get this great deal.

Coming up on this week's episode of The Doctor's Pharmacy. Brand new studies in the last year or so have shown that depressed individuals have a depressive microbiome. Hey everyone, it's Dr. Mark. As functional medicine practitioners, we understand the importance of accurate data in uncovering the root causes behind our patients' health concerns. But let's face it, ordering labs to get the data you need can be an administrative nightmare. Luckily, Rupa Health is here with a solution. With their revolutionary platform,

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Sign up for free at rupahealth.com and take control of your lab ordering process today. That's rupahealth.com. Getting quality sleep is incredibly important to me. Sleep is really one of the pillars of good health. So you can imagine my frustration when I used to lie down at night but couldn't fall asleep because I was just too hot. But those sleepless nights are behind me now thanks to Cozy Earth. The bed sheets are made from temperature-regulating fabric

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offer for my listeners. You can get 40% off site-wide when you use the code Dr. Hyman. Just go to CozyEarth.com and use the code Dr. Hyman. That's D-R-H-Y-M-A-N. And now let's get back to this week's episode of The Doctor's Pharmacy. Hi, this is Lauren Feehan, one of the producers of The Doctor's Pharmacy podcast. There has been an explosion of research and understanding about the importance of our gut microbiome. Yet despite regulating so many bodily functions and being critical to our overall and long-term health, conventional medicine has not integrated this knowledge into its teaching or practice. In today's episode, we feature four conversations

from the doctor's pharmacy about the importance of the gut microbiome and why finding a practitioner who understands its significance is vital to your health. Dr. Hyman speaks with Dr. Stephen Gundry about why the microbiome is necessary to consider in treating every illness, with Dr. Mark Pimentel about how IBS can begin with food poisoning, with Dr. Uma Nehru about the connection between gut health and mood, and with Dr. Zach Bush about the important elements of the microbiome and how to care for it. Let's dive in. The average practitioner, or even the exceptional practitioner out there, if they're trained Let's dive in. daughter in medical school is not learning anything about this. And it's unfortunate because it's key to being able to help so many people with everything from heart disease to cancer, to diabetes, to Alzheimer's, to autoimmune disease, to allergies, to digestive problems,

to depression, to anxiety, to ADD, to neurodegenerative. I mean, the list goes on and on, right? So can you talk about how you came to understand this and also how our gut microbiome is directly linked to our health and longevity? What's going on? Holy cow, where do we start? No, but let me continue on what you just said. I have the privilege of seeing third-year family practice residents rotate through my clinic for a month at a time.

And they're, you know, about to go into practice. This is their final year. And just probably won't surprise you, but it might surprise our listeners, that not one of these individuals have ever heard of ordering a fasting insulin level. my god i know that's a don't get me started on that that no none of them have ever heard of you know a homa ir which is a way of looking at insulin resistance yeah and they go well what does that have to do with anything? I go, uh, well, um, so you're right. I mean, one would have hoped, uh, you know, you and I, we didn't know about this. You know, we, we thought that the GI tract was a hollow tube and crud went in and some digestive enzymes

happened and whatever was left, we pooped out. And that was the end of the story but the human microbiome project which really just completed in 2017 you know opened our eyes to this incredible tropical rainforest of you know a hundred trillion yeah different bacteria yeah that we just didn't even know were there and so what that's been able to do is okay now we know they're there there's like a hundred thousand petabytes of data in our microbiome like it's doing stuff all the time and you know i argued in one of my previous books that what i think we've done, since they have so many more genes than we do, and that genetic information is constantly being modified by viral genomes being inserted and cross-filtering of genes between bacteria, that I propose that we've actually done most of our computing. We've loaded it into our cloud computer or our brown computer.

And the more we see the influence that these guys have on everything that's going to happen to us, the more you realize what an amazing, elegant design and what a brilliant idea to outsource most of our computing power to this tropical rainforest within us. And this is not that new of idea. You know, Dennis Burkett, which you learned about Burkett's lymphoma in medical school, he was a British scientist and he went to Africa on a missionary trip and he noticed, you know, all the villagers

and the traditional tribal populations had no chronic disease. They were really healthy. And as soon as their cousins essentially moved into the city, they would get all the Western diseases. And for some reason, I don't know how he got this idea, but he decided to study their poop. And he basically found that the urban dwellers had stool weight of four ounces and the hunter gatherers and tribal people had stool weights of two pounds and the hunter-gatherers and tribal people had stool weights of two pounds. And I just came back from Africa, you know, and saw the elephant poop. It's like, it looks like a basketball, you know, like one little piece of it.

And then they have huge amounts of fiber. And I saw, you know, the Hadza population, which is one of the last hunter-gatherer populations on the planet. Now, they have 20%, up to 20% of their diet is honey, which is all you think, oh, that's bad, you know, sugar. But the other thing they do is they're hunter and gatherer. So they gather a lot of tubers, these roots. And these root vegetables, I don't know if you can call them,

more like chewing on wood. But they basically dug one up, they dug up this wild yam, and they eat about 150 grams of fiber a day. And that mitigates any of the harm from the honey that they're getting. And they actually don't have these chronic Western diseases. So I think in our society,

we've just done such a disservice. We saw the same thing in this study years ago about Burkina Faso, like these kids who are eating Western diets versus these traditional diets in Burkina Faso. And they had profoundly different microbiomes, profoundly different health outcomes, no allergies, no autoimmune disease, none of the stuff we see here. So it's so intimately tied to our microbiome. And yet it's shocking to me that in traditional medicine, even though we sort of now acknowledge it, there's no roadmap to do anything about it. And that's why gut check is such a great roadmap, because it provides people an understanding of what's going on, why it's a problem, and actually what to do about it. some of these polyphenols called elagitanins that are in foods called pomegranates,

we can eat, or walnuts, berries. And what, you know, you have this great term called gut buddies, like literally these gut buddies that are good guys living in there. The problem is we don't have that many friends anymore. We don't have any good buddies left or maybe very few good buddies left in our gut microbiome. So when you don't have these, it can have serious health consequences. And you talk about this particular symbiotic relation between some of the foods we eat, our microbiome and compounds they produce, something we call postbiotics. I just had a podcast with Uma and I do, and she was talking about psychobiotics. Not crazy bacteria, but bacteria that act like psychiatric drugs to modulate mood, which I thought was great. But this whole concept of

prebiotics and probiotics, people understand. Fibers, prebiotics, and probiotics are like taking lactobacillus. But then there's these postbiotics, which are things that are made by your bacteria from eating certain foods that are molecules that then you absorb and regulate your biology in ways that have profound impacts on your health. So one of those metabolites is called urolithin A. And I've talked a little bit about on the podcast, but this is such a great story because it illustrates it well. And there's so much research around it. So it's one of the most researched factors around this whole postbiotic phenomena. So can you explain, you know, the data around this phenomena of erythinae on super centenarians and their microbiome versus people who don't have this microbiome that

actually can metabolize these phytochemicals. And so basically you can eat pomegranate all day long, but you're not going to make urolithin A, right? Right. Like 20% of the general population is able to do this. That means 80% of us aren't. But in the super centenarians, a lot more have this microbiome that actually makes urethane. So can you explain this whole interaction between our alleged tannin content in our diet and the bacteria that are regulating it and this metabolite that it creates, urethane, and what that does and how it relates to our health in general, our mitochondria, and mitochondrial uncoupling that you talked about? Yeah, maybe it's a bad... I mean, that was a lot, but it's really important. And I think it's such a beautiful story because it illustrates this phenomenon so clearly for

people and why it's important to take care of your gut buddies and invite more good gut buddies in there. Yeah. I hate to use the expression, but it takes a village and what we're learning and what I want people to understand from gut check is we, we used to think, okay, you need prebiotic fiber and your gut buddies will take prebiotic fiber and they'll make postbiotics. And by the way, gasotransmitters are postbiotic. And that's a good thing. But what we now know is you may have to have four or five guys each doing one job, almost like an assembly line.

And if the first guy doesn't make the next product, the second guy can't make what he needs. And it may need four or five different bacteria to get the end product. So let's take, for example, urolithin A. We know that the precursor is in pomegranates, in walnuts, in raspberries. But that you're right, only about 14 to 20% of individuals, you could give them all of these precursors, they will never make urolithin A. And so you then look at super old people, and at least 50% of them make urolithin A. It could be as high as 70%. So we now understand that there are multiple guys that are involved in making this compound. And if you don't have those multiple guys, you could eat all the pomegranates in the world,

but you'll never come up with this compound. So what's so cool about this compound is, and this is work out of Switzerland. I've had the folks from- Amazentus. Yeah, Amazentus on my podcast several times because I'm so impressed with what they've done. So this stuff is actually makes mitophagy, makes mitogenesis. And I, off camera with them, I'm pretty convinced it's because of mitochondrial uncoupling. And they have a recent paper that shows it has some really cool anti-cancer properties as well.

And I'll argue it's because of mitochondrial uncoupling. But it's fascinating that these super old people have this set of gut bacteria that are able to accomplish this job. the husband and wife team, the Sonnenbergs, about the importance of understanding that it's more than just, say, prebiotics as a part of this. They gave individuals prebiotic fiber, and they looked at their gut microbiome diversity, and they looked at their markers of inflammation, which was HSCRP, C-reactive protein. They took a second group and gave them the same prebiotic fiber, but they also gave them fermented foods. It was primarily yogurts and vinegars. And lo and behold, the group that only got the prebiotic fiber had no change in gut diversity and no change in inflammatory markers. It was the group that got the fermented foods plus the fiber that had a change in the gut

microbiome diversity and lowered their inflammation. And again, it's this conversation, it's this communication that makes the difference was it because of the fermented foods that had bacteria in them and the probiotics in them was that the reason or was it because of the polyphenols in in those it's even better than that i've got a whole chapter in gut check that dead dead men tell no tales, but dead bacteria do. And it turns out that there's folks don't eat your yogurt to have active yogurt cultures. Most of those probiotics will be killed by your stomach acid. the dead bacteria cell wall and it's the postbiotics that are made during fermentation that is what you're actually looking for. And we now know that these compounds carry messages that are read by other bacteria. And that one of the things that was interesting in acromantia research is that dead

acromantia have much the same effect as live yeah really it's live yeah and it's like what well um i have three male dogs and they're i'm not gonna ask why but they're rescues, but that's okay. They, they're out sniffing at everything and they're putting urine on anything they can. And you go, well, my dog gone, what are they smelling? I don't smell anything. Well, they're getting messages. They're the other dogs have left for them. And we now know that bacteria leave messages that other

bacteria read. And it's those messages that are necessary to tell the other bacteria what to do with that prebiotic fiber. Hey everyone, it's Dr. Mark here. When you're overtired, it's super easy to start defaulting to caffeine to get you through the day, but that just masks the symptoms of why you're tired and it can make things worse in the long run. So if you regularly lean on caffeine, I got a better solution for you. AG1. AG1 is a science driven formulation of ingredients that supports your body's foundational needs, which means you'll be able to reduce your caffeine intake while feeling less tired throughout the day. I drink AG1 every day and ever since I started consistently, I have felt better and have had more energy. I just add a scoop to my water in the morning and I feel the effects all day long. Try AG1 now and you'll get a free

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organic foam is ultra-adaptive and contours to your body for comfort, pressure relief, and support. The sleep surface also actively cools to help you sleep better and longer, which just might be my favorite part since I sleep so hot. Right now, enjoy an extra $100 off your organic mattress purchase with the code HYMAN at checkout on Essentia's site. Visit myessentia.com forward slash Dr. Mark Hyman. That's M-Y-E-S-S-E-N-T-I-A.com forward slash D-R-M-A-R-K-H-Y-M-A-N. And now, let's get back to this week's episode of The Doctor's Pharmacy. I want to dig into more of this realethane story because I think, you know, when I looked

at the research on this, this is really well done research published in peer-reviewed journals. It's not like, oh, I heard about some supplement and I'm just taking this. When they did the work, this is in JAMA, Open Network and Cell Reports and Neurotherapeutics, the data is really impressive. And basically what it does is kind of shocking to me. When you think about, you take this basic food, you have bacteria in your gut, it makes this molecule called urolthin A, it gets absorbed in your bloodstream and then goes to work in your body. And they found that it increases, without exercise, this is crazy,

without exercise, increases muscle endurance, muscle strength, increases your fitness level, measured by VO2 max, which is like what you'd have to do, wind sprints to fix. It increases ATP production. It reduces C-reactive protein, improves your upper metabolic profile, meaning your insulin resistance. It reduces ATP production. It reduces C-reactive protein, improves your metabolic profile, meaning your insulin resistance. It reduces muscle loss.

It stimulates mitophagy or cleaning up the old mitochondria. It improves mitochondrial gene expression. It inhibits something called mTOR, which we've talked a lot about on the podcast, which is important for longevity. It basically causes autophagy or cleaning of your cells. It upregulates SIRT1, which we'll talk about in a minute, which is a really important set of transcription factors that is involved in longevity and insulin resistance and DNA repair. So it basically helps all the things with aging. It even improves your immunity by improving stem cell regeneration for T cells.

And it has anti-tumor activity. So I'm like, whoa, wait a minute. You were talking about eating a pomegranate, having some bug in your gut, and having all these downstream effects. And just to be clear, everybody, we're talking about one food and one compound. We're talking about not all of the other things that are going on in your gut with, with, you know, trillions and trillions, like probably 40 trillion bacteria in your gut and two to 3 million bacterial genes doing all kinds of stuff. But that's, that's a hundred times as much genetic material as we have. And what, what genes do is produce proteins. So that means they're producing all these molecules. And I was sort of on a panel

with Stan Hazen at Cleveland Clinic. And he was like, yeah, I said, Stan, how much of the metabolome comes from our microbiome? Meaning how much of the things that we can measure in our blood, not when we get on a regular lab test, but when you do these scientific studies, comes from the microbiome? He said, probably a third to a half. And I'm like, what? A third to a half? So we literally are kind of in this constant dance with our gut. And this is why your book is so critical, this gut check book, because it helps us to really understand on a granular level, the science of why. So we go like, oh yeah, okay, I get to take probiotics, whatever, you know, take prebiotics, whatever. But you actually give us the

science of why. So that's the urolithin story. Let's talk about resveratrol and SIRT1. Yeah. Work, work, work, work. I don't know. I could drink that much wine and you'd die. You'd die. But basically, it's been shown to help with cardiovascular disease, but also maybe impacting the brain and metabolism, maybe even more than the heart. So how can this resveratrol compound that comes from grapes... And by the way, I don't think we can get it from red wine. I think that's going to cause problems. And you talk about it in your book.

I'm like, don't drink so much. So we can get into the alcohol story. But I think the key is the phytochemical. So talk about how resveratrol can be used to help or treat and prevent neurogenic metabolic diseases and how it relates to the gut microbiome? Well, again, I think resveratrol is a very poorly absorbed compound. And again, we've known that for years. And so David Sinclair is a friend and we've through the years talked about his love of resveratrol and mine, and he loves pharmacologic doses of it.

But what's really cool about resveratrol is that it is a it's a signaling molecule and it literally activates SIRT1. And it's a really good way to come full circle of uncoupling mitochondria as well. But it literally tells, it tells, it repairs DNA breaks. It actually fosters the production of short chain fatty acids like butyrate. And the more we look at the downstream effects of resveratrol activated by the microbiome, we're beginning to see, okay, well, why is it that, we've, the middle guy that allows resveratrol to work is the microbiome, making it an absorbable compound. And that's what none of us knew until really the microbiome project got finished. Amazing. It's quite amazing.

I mean, I think the other thing that, you know, I want to dive into, because I mean, we could talk for hours and I don't, unfortunately we both have work to do. We have other jobs, patients and all that. But I think, you know, the other issue is sort of the microbiome and the brain and mood. And you talk about, you know, major depression is a big issue and depression is the biggest cause of disability in this country. And how the microbiome of people who are depressed is different. And in 2022, there was a study of microbiomes of over a thousand people with depression, and they found changes in about 13 bacteria. And these bacteria are known to produce various neurotransmitters. So can you kind of unpack that for us and just give us a little taste of the mood, brain, gut, microbiome connection.

Yeah, I guess, you know, I suppose we should have known this. But again, now that we're being able to look at individual bacteria and the compounds that they produce, you're right. Brand new studies in the last year or so have shown that depressed individuals have a depressive microbiome. And you can constitute these particular abnormal species. What's really interesting is, let me step back one. We've known that glyphosate, which is a lovely weed killer, was actually patented as an antibiotic. And one of the recent findings about glyphosate is that glyphosate targets the tryptophan pathway bacteria in our gut.

Now, why should that be interesting is because tryptophan makes 5-HTP, makes serotonin, which, and GABA for that matter. And so glyphosate? And now we know, well, you can say, oh, well, glyphosate's bad for you. But wait a minute. Glyphosate is after the bacteria that are essential for our mood. Yeah, I think that's okay steven yeah it's like what have we done yeah yeah it's true it's the unintentional side effects that happen from things we think we're trying to do good oh weed killer great herbicide we need it blah blah blah but but these this is you know people say oh glyphosate cancer this not maybe

okay there's been some you know lawsuits that have been oh, glyphosate cancer, this and that. Maybe, okay, there's been some, you know, lawsuits that have been successful around non-Hodgkin's lymphoma, I guess, if you douse yourself in it. But what's really striking me about glyphosate in really small amounts, it wipes out your microbiome. It doesn't take a lot. It's not like you have to, like, drink Roundup in order to actually mess yourself up. It literally is in small amounts. And that has led to maybe an increasing epidemic of low microbial diversity that we're seeing and an increase of all these chronic diseases, including psychiatric disorders, which could be really from this sort of altered microbiome, in part from glyphosate.

I mean, there's a million other reasons, obviously, xenobiotics and other toxins and other things that are really, really important. I think, you know, the thing I want to sort of dive into a little bit more is cancer, because people don't think about cancer and your microbiome. But there was a, Charis Eng, who was the head of the Genomics Research Center at Cleveland Clinic when I got there, she was so happy to see me. She said, what took you so long to get here? And I'm like, well, I don't know. I didn't, I didn't want to, I didn't really want to go to Cleveland Clinic, but they dragged me over there. And, and she just told me about all her research on the microbiome and breast cancer. And I was like, fascinating. And they were really, this is like, you know, some Russian lab, you know,

trying to do some research. This is like Cleveland Clinic and they're, they're digging into this. Dan Hazen, you know, digging into the microbiome and heart disease. Clinic, and they're digging into this. Stan Hazen is digging into the microbiome in heart disease. And so can you talk about how the microbiome determines not only a risk of cancer, but also how we respond to certain immunotherapy drugs that are now basically some of the best drugs we have against cancer. But if your microbiome's not right, the drugs don't work. Right. Yeah. You know, a number of years ago now, there was a, there was a paper, and I'm sure you're aware of that looked at the tongue scrapings of people with pancreatic cancer and the oral microbiome. And there was a very strong correlation between the oral microbiome and predicting pancreatic cancer.

And people go, wow, this is great. Now we'll have a diagnostic test and we'll just scrape people's tongues and we'll know who's at risk for pancreatic cancer. And then people went, wait a minute, what does that have to do with cancer? Well, now, of course, we go, wow, there is, like I talk about in the book, there is a colon cancer microbiome. There's an ovarian cancer microbiome. There's a breast cancer microbiome. There's a pancreatic cancer microbiome. There's a lung cancer microbiome that is distinct to those cancers.

And the question is, did they cause the cancer or are they facilitating the cancer? And that answer is not there yet. But like you mentioned, we know that certain patients are going to respond better to chemotherapy if we actually do targeted antibiotics to change the microbiome. And other people aren't going to. And it's this whole personalized medicine. But we're now going, holy cow, why didn't we realize that there is this microbial component to cancer? And again, I'm not saying cause and effect, but they're there. And we certainly owe it to ourselves to figure out, well, okay,

what part are they playing in this? Yeah, this story is definitely being unpacked. We're not quite there yet. But, you know, our friend Will Lee talked about his mother who had stage four uterine cancer and did her microbiome test and found low acromantia or no acromantia. And he did some research and showed that, geez, people did not respond to these checkpoint inhibitors in immunotherapy, which are great at advancing cancer, if they didn't have acromantia. It's like, wait a minute. How come this powerful drug doesn't work if you don't have this one little lowly bacteria? But literally, we are just uncovering how powerful these microbes are in regulating so many aspects of our health or response to therapies.

And I think he was able to give her these polyphenols that we talked about and boost her acromantia. And she got the immunotherapy again and was cured of stage four cancer. It worked. Yeah. Yeah. So think about that. A probiotic or polyphenols curing stage four cancer in conjunction with a drug that wasn't working before.

That's kind of radical shit. Yeah. And, you know, you brought one other thing, which is actually a good segue. You brought up xenobiotics and so xenobiotics are all these uh environmental toxins these endocrine disruptors plastics petrochemical products like bpa pcbs pfas comp everything all the phthalates phthalates all the crap all this awful stuff yeah when you and i write about this in the book when you look at these super old people's microbiomes you know 95 and above and they're thriving they have a microbiome that eats

xenobiotics oh wow yeah and you go well son of a gun and they go and people go well wait a minute xenobiotics look you can engineer bacteria they eat oil spills for goodness sakes they just want that's right they're just looking for carbon atoms right that's right that's right so yeah and one of the hallmarks of these guys besides the fact that they make urolithin a is that their microbiome eats xenobiotics and it's like well of course now do we know which microbes do that and where can i where can i buy yeah or what do i need to eat to grow them do we know well you see that's what's really kind of fun about all this uh because i never heard this before and i think i just the

reason i say it's important is because we're we we doing the best we still can't eliminate our exposure to these compounds they're everywhere and they're in us. And so if we can take some kind of probiotic to offset the harm from the xenobiotics, I want that. We now believe that food poisoning starts the whole process. So you, and eating is part of it. You know, 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 traveler's diarrhea. Or we get food poisoning or whatever. We start to explore the world of food. But 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 food poisoning, the CDTV toxin, 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 watched those. And they always say-

I like the loss. I used to watch loss, which was kind of like Survivor. It's a little bit different. There a little more there's a little more raunchiness story with survivor you're just kind of trying trying to make it to a road somewhere but um the point was that he he always this this guy on the survivor show would always say if the water's not moving don't drink it if the water is 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. So you're almost saying it's like an autoimmune disease of the nerves of the gut that develops that kind of sluggish. So this is a kind of a 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 IBS. They think of IBD or inflammatory bowel disease, but they don't think of, you know, irritable bowel being autoimmune. The interesting thing about contrasting IBD to IBS. So the antibody that we discovered is an auto antibody 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 vinculin that we discovered is directly related to the pathophysiology we can make rats have ibs just by giving them this toxin uh and so that that's very uh cool because it allows us to study new drugs and new therapies coming in not so cool for the rats though so this is fascinating so you were saying there are different kinds of bacteria. Can you explain, you know, what are the kinds of bacteria and then, and then what type of food poisoning? Is it any, like if you get Giardia or if you get Salmonella, Shigella, Campylobacter or Entamoeba or like, you know, what, what are, are the kinds that typically cause the problem? Well, the four horsemen of the apocalypse of IBS are Campylobacter, Salmonella, Shigella, and some E. coli, food poisoning type of E. coli,

pathogenic E. coli. Giardia can do it too. It turns out it has vinculin in its structure. And so maybe that's how you get the antibodies from Giardia. The viruses are less likely to precipitate IBS. So the four horsemen, Campylobacter salmonella, Shigella, and E. coli. So that's, and it occurs about, starts to occur about three months after you get sick. Patients will remember. Some don't remember, and they'll say, well, you know, 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. I have heard that story so many times, you know, I went to Thailand or India or, you know, Jamaica and like, and sort of tripped the whole thing going.

Yeah. Or the taco truck in Venice. Yeah. So a lot of possibilities. Wow. So, so this explains like 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? Well, so based on culturing the bowel, we've been able to isolate that 60% of IBS is SIBO. The other 40% is a mixed bag. So, for example, and you probably talk about this now, Ehlers-Danlos 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 Ehlers-Danlos syndrome or POTS, or some of them are celiac that we've missed. Some of them are food sensitivities. Some of them are histamine sensitivity. 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. So let's pause there for a minute, because 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 CFO, small intestinal fungal overgrowth. You know, and 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 like a quacky alternative concept. But it seems to be, you know, now understood as potentially playing a role in some of these cases. Can you talk about the, the current understanding of this and actually some of the treatment and then I'll sort of loop the loop back to the, how do we start to treat and think about IBS differently? Yeah. I mean, Satish Rao, Dr. Satish Rao 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 been seeing this fungal overgrowth. That doesn't mean you shoot somebody in the gut with a shotgun. No, shotgun sequencing means we sequence every single piece of DNA we can find and then characterize it and 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 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. Chase it by doing stool cultures or? Well, chase it. It could be by stool, but if you want to find small intestinal fungal overgrowth,

you got to get into the small intestine and that's really- Sampling. You have to have endoscopy and all of that. That's how Dr. Rao identifies it. Yeah. And any particular species of fungus or is it sort of a broad array? 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, Malassezia 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. Yeah, no, I definitely have seen that on cultures.

And, you know, 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 also I can tell because they might have other fungal symptoms. They might, you know, 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 kind of a yeasty kind of situation going on. But I think it's important that it's been identified. And going back to kind of the treatment of that, how would that normally be treated? 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. Yeah, sometimes you can take what we used to call amphoterrible, which was a horrible first-generation antifungal, but it's not absorbed. So if you take it orally, it's not absorbed and that can be effective. Exactly. Yeah. Oh, yeah. And then in terms of the bacterial stuff, you talked about these three different bacteria, right? You've got methane-producing, hydrogen-producing, sulfide-producing, and they all are a little bit different. You said the methane producers are not really bacteria, they're archaea, but for simplicity's sake, let's call them bacteria.

I don't think most people know what archaea is. It's arcane, right? It's arcane. What is your approach to starting to kind of differentiate these? And then how do you determine what the right treatment is for a patient and can kind of guide us through what to do, both in terms of lifestyle, diet, any kind of supplements that might be helpful and medication? Yeah. So first of all, we helped develop the first three gas breath tests. So just full disclosure, 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 Escherichia coli, the non-pathogenic one, and Klebsiella pneumoniae. Those two characters, when they come

into town, everybody leaves 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. 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 methanogen 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 kid 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 sulfide is 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 have 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. Yeah, yeah, yeah. Go through the treatments because they can be real different. And this is important to understand for people because, you know, 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. Pimenton developed, the tests for anti-CDTB and anti-viculin

antibodies are really important. And then the breath test that allows you to look at hydrogens, methane, and sulfur. So can you talk about what are the different treatments for each of these? Yeah. So, I mean, if I have an IBS 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 because you could get into further trouble with these antibodies going higher. So I universally do that. Like prophylaxis, like what? Like Zifaxan? I give Zifaxan 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 test in all of our patients. And if it's hydrogen, and we all know rifaximin got FDA approved for IBS with diarrhea,

on the basis that IBS 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, it looks like. And that's basically Pepto-Bismol.

Yeah, Pepto-Bismol. Yeah. 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? We haven't sorted out or had time to sort out the different diet approaches, but I envision smarter people in 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 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 low FODMAP indefinitely and FODMAP is like fermentable oligosaccharides that yeah fermentable oligosaccharides, monosaccharides, etc. And basically, it's too restrictive. But you've probably, most people have probably read about 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 it's, you know, you don't want to be the person at the table just because you have IBS that spends 10 minutes with the, you know, trying to explain your dietary restrictions on a low FODMAP diet. So, you know, that's part of the reason we want our IBS patients to feel as normal and as socially non-isolated as possible.

And that's part of it. What is a low fermentation diet? So it's basically 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 to 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 up. So anyway.

It's interesting, you know, the typical dietary recommendation when I was in medical school for IBS was more fiber, like Metamucil, basically. What you're saying is that you want to restrict soluble fibers that are digestible. And low-fiber diets seem to be, you know, 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, how can you

navigate that? Well, you know, 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 it's colon health and all this stuff for 20 years. How many, how much have we heard about colon health and all this stuff for 20 years how many how much have we heard about colon health and fiber a lot and what have we what have we got now uh we've got colon cancer happening in the 40s 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 i'm 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. And for a healthy person whose

microbiome is healthy, no problem. But not for these patients with these microbial conditions. 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 the 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. Well, I can answer that 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, you know,

being cataclysmic. It's getting rid of the E. coli and the Klebsiella and SIBO. That allows the regular bacteria to reflourish, repopulate and take over again for a period of time. But remember, the problem is those cleaning waves are not working. So it is possibly going to come back. It depends how badly damaged. And that's where that antibody comes in. Because if the antivinculin, which is that autoantibody for the autoimmune disease of IBS, is very high, the neuropathy is more high or more intense, and you're going to relapse or reoccur more frequently. So that's where we're 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 because that's 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, you know, 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. So this is something that's a chronic condition that has to be kind of continually retreated in some ways. Is that what you're saying? 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. More and more as I've studied the microbiome and the gut-brain connection, I've moved from more general, when I first started in my clinic, for more generalized suggestions based on someone's individually telling me what their diet is and essentially what they're doing, to a very highly personalized plan. And some of that is based on some fascinating research that has come up around things like yo-yo dieting that he's shown that in some animal studies that um and the science was very nicely done that there's almost a there's almost a for one of a better word like a fat memory in in mice that were overweight that is recorded in the microbiome so it has taught me that each person is so different and that I

have to think about them more in terms of what they're eating, what their symptoms are, what their makeup might be. And so I first obtain a proper history, ask them what they think they should be eating and what they are eating. And often in that history taking, I'll uncover something that is a startling, most often something startling that they didn't realize. And I've talked about some of those examples in the book where they may be eating something that they perceive to be somewhat healthy, part of a diet, part of a cultural diet, whatever it is, and they actually either packing in sugar that they didn't know about, something that is obviously driving the gut in the wrong direction or driving dysbiosis. So what's an example of that?

Sure. So, for example, I speak about her in the book. I had a patient who was pregnant and had a healthy pregnancy and was eating a lot of her favorite spice, which is a Korean spice called gochujang. But when you get the straw pot version, there's a very high, some of those preservatives, but there's a very high sugar level in that. And she was just adding this to her healthy foods, her vegetables and her lean proteins and stuff. But she was consuming a larger amount of it because she sort of was craving it during the pregnancy. And so some of what we had to do is really peel back on that and figure out

other ways we could do that. Either we created a sauce that, you know, worked on a little recipe that would give her the flavors for that, but take away the unhealthy ingredients. So, you know, sometimes it's little things like that. All right. So talk about how specifically the studies recently have shown that diet can have a profound impact on our mental health, things like ADD, depression, anxiety, sleep issues, dementia, OCD. I mean, we don't think of, for example, OCD as being diet related or ADD as being diet related, but how are these linkages being discovered in the science now? Because I've been witnessing them for decades as a clinician and I've been waiting for the science to catch up and it's kind of catching up. So what have you found? You know,

you're at the, you know, Harvard Medical School. This is not some fringe idea. This is now mainstream. So talk about what these studies show and how we can learn about how these things are all connected. Sure. So, you know, the basis of how I describe a lot of it is around the gut microbiome and how, and I'm sure your audience is very familiar with just how information gets formed and things like that. The way that it works with examples of things like, let's take anxiety, and I will speak about that because it's what my clients are coming in most commonly with right now the uncertainty the fear loss of jobs quarantine you know restrictions changing and going back the next day is really creating an immense immense amount of anxiety and what the studies have shown is that there's

certain things that so the way that i is that there's certain things that, so the way that I look at it is the things that you, in terms of food that you need to embrace and the things that you need to avoid. And the things that seem to worsen anxiety include foods with gluten in them. And it's not necessarily people who have celiac disease or non-celiac glucose sensitivity, but there seems to be a correlation in the studies around the level of anxiety and consuming gluten. So things that are positive are the use of things like turmeric with black pepper. But what makes the gluten become a problem?

What is the mechanism? Has anybody figured that out? So we think that from what the studies have shown, that it's that there's some sort of disruption that occurs in the microbiome that leads to dysbiosis in individuals who have anxiety. So I've had patients who can tolerate gluten,

but if I were to give a general recommendation to someone based on what we've learned, we try to have them avoid it. With the turmeric and black pepper, we know that curcumin and turmeric is activated by the piperine in black pepper, and it actually increases the absorption by a significant percent.

And a study also showed that where omega-3s are involved, that can enhance the absorption. So this combination and the work that's been done on omega-3s in both anxiety and depression, for example, there was a study of medical students done that looked at treatment of anxiety using omega-3s. And we've heard about omega-3s, and people know about using it for mood, but it targets anxiety as well. And the combination of turmeric, black pepper, as well as omega-3s, and I'm talking mostly about food sources of omega-3s.

Some people do take supplements, and it's perfectly fine. Actually, it's quite powerful for lowering anxiety levels. So those right there are things, you know, that people should move toward. So maybe like a sardine curry with a little black pepper. Exactly, exactly, you know, or, you know, some sort of like really fancy glaze that you put on salmon, you know and it could be oven roasted it could be baked and you know using all the healthy oils and to make a left you know as well as some other things so so that that's you know that those would be a good a good way to go and with you know the studies of depression the the there's

there's been trials that were done using folate and mucal folate decades ago by some of my mentors at Mass General. But, you know, adding them in as leafy greens are thought to be helpful. And so there's a real logical way in which adding, you know, simple recommendations that we make about fruits and vegetables, adding that fiber back into your diet actually drives down any type of inflammation in the gut. And therefore, with the gut-brain connection, lowers any type of potential neuroinflammation. The thing that many, many people, and I think I'm more aware of these types of things now, is that serotonin, the happy hormone, 90% or more of the serotonin receptors are in the gut. So it really does make a difference what you eat,

because if you're eating poorly, those serotonin receptors are going to be affected. And the passage of serotonin in a healthy way back and forth, it all depends on what's being transported via the vagus nerve to the brain. And by eating the poor foods and creating dysbiosis in your gut, you're driving the mechanism in the wrong direction for you. So one of the things you said, which I want to back up on, which is so important, you kind of glossed over it,

which is this whole idea of neuroinflammation. Now, when your joint hurts, you get arthritis, it's inflammation in the joint, it hurts. If you have a sore throat, is inflammation in your throat, it hurts. You get arthritis. It's inflammation in the joint. It hurts. If you have a sore throat, is inflammation in your throat, it hurts. If your brain's inflamed, it doesn't hurt, but it shows up as depression, anxiety, ADD, dementia, OCD, whatever, right? Autism. These are all inflammatory diseases of the brain. And what you're saying is that a lot of the source of the inflammation comes from imbalances in the microbiome, in the bacteria in the gut, what you call dysbiosis, which is the difference between symbiosis, which is a nice balance with your gut flora, which is dysbiosis,

which is really bad bugs that are growing that drive inflammation. And when you're eating different foods, you're feeding different bugs. And that may be how the mechanism of this works with mental health. Is that what you're saying? Exactly. So a few different things. And thank you for backing up on the neuroinflammation

because it is such an important point. I'll give you an example of a patient. So a gastroenterologist referred me a patient who was having severe panic for the first time at a stage in life that you wouldn't expect someone to develop anxiety and panic disorders going by the DSM-5 TR criteria. And as I took a history and spent time with him, it turns out that his actual, even though he was presenting with the panic to me, what was distressing him was his irritable bowel. He was very uncomfortable. He had developed

these symptoms over time. And as we took, you know, found out more information, he had moved to a new job, highly stressed, eating very few meals at home, eating either in the afternoon from the vending machine, eating lunch out, getting takeout, and getting fast food on the way home. From being a relatively, you know, relatively healthy weight, and from being someone who was eating, I would say, probably three, from what I remember, three to five meals at home in the evenings, his diet had changed over the period of 18 months. He developed discomfort in his bowel. He, you know, had lots of diarrhea and constipation, but he presented to me with panic. And rather than do that, as we tried to figure out the details and placed him on the proper diet,

these symptoms, it took time, but these symptoms abated over time. So much so that he didn't need clonazepam or Xanax or acetyine for his symptoms of panic. So you're saying you fixed his gut and that fixed his anxiety and his panic attacks. Exactly. But you and I went to medical school. We're old enough that we went to medical school. And we were taught that there's something called functional bowel disease or irritable bowel syndrome, which we had a pejorative way of talking about as a supratentorial phenomena, which in English means it's all in your head.

But maybe it's actually something else. Maybe it's an infradiaphragmatic phenomena, meaning it's below your diaphragm or in your stomach. And yet as psychiatrists, how much did you learn about the gut? Zero, right? Exactly. As well as nutrition. These are not things that

where we've made the connections yet. There are treatments for depression, like vagal nerve stimulation. You know, there are things that actively target the vagus nerve that will help to treat depression. So we sort of know some of the science around it, but we haven't put this in. And some of it goes back to something you said at the beginning, Mark. You know, going back to my story of the Dunkin' Donuts coffee, from there I just began to have more of an open mind around these questions. And I didn't know when I tried to help him evolve and change his diet that it would work. Part of it was trying to see if it would.

And this was also someone who had developed these symptoms, also in the context of that poor diet. He had not early on in his life, you know, for want of a better name for the syndromes, that was what his gastroenterologist called it. But as that evolved and he ate healthy and it did take time, it seemed like he can cause a better bacteria to grow. And, you know, some of that really kicked in. So, so I do feel that that root cause part of it may take time, but we just have to figure out where it is. Well, this whole gut connection is so fascinating because what you're saying is the type of food we eat changes the type of bacteria. How do you do that? And why is it important that we focus on that sure so so you know if you

if you take um if you take a typical um you know the standard american diet that unfortunately is the diet used as the point of comparison in a lot of nutrition studies um you know it's it's generally here are some here are some fun facts um a lot of fast food French fries have sugar in them. We know that sugar is fine. And gluten. And gluten. I don't even know this story, but I had this patient who was like,

went to get some French fries at a fast food place. And it's like, you know, I want to make sure the French fries don't have any wheat in them. And they're like, oh, no, no, no. They don't have any wheat. We just dip them in gluten and then we fry them. So there you go.

So since it's absolutely true, they have a lot of stuff that we don't realize is in them because you just thinking it's a, it's a potato. But no, it's, it's, it's very, very far from that. And it's made through a whole process of extrusion to make it a truly processed food. But the point being that it's a simple thing where you think, Oh, I'll just, you know, I'll, I'll get some dinner on the way home as that particular patient was doing.

But there's so many added just, you know, I'll get some dinner on the way home as that particular patient was doing. But there's so many added just bad ingredients in foods that you don't realize. So, you know, you're familiar with sort of the added sugars and savory foods, salad dressings, ketchup, you know, fruited yogurts and stuff. That's just one element of it. Then there's the added gluten in people who are gluten sensitive. Then, you know, it's the unhealthy fats that you don't realize are there. You know, the last time I checked, there was 61 other names for sugar. I think there's 250. I'm sure there are. By now, I'm sure there are. And so I will, you know, teach people to just think about four grams of sugars, one teaspoon,

look at the food label, see what's in it. Because any of those poor foods that are the foods to avoid are the things that are going to disrupt those gut bacteria. So basically, the imbalance is going to be the bad bacteria having a party. And the good guys are not doing well because they're being overrun. And that imbalance is what leads to the leaky gut or the intestinal permeability. And, you know, that's when it really starts to back up and also then causing your inflammation. Well, you know, this is music to my ears

because 20 years ago, I remember having conversations with physicians talking about intestinal permeability and dysbiosis and leaky gut and gluten. And they just looked at me like I was from Mars, like I was some kind of quack. They didn't know what he was talking about. I'm like, all I know is what I'm seeing. And I see when patients change their diet, when we fix their gut, they get better from all sorts of things. And your work is so important because we've had on the podcast a psychiatrist

who's talked about metabolic psychiatry, which is a role of sugar and insulin, but you're taking all this down into the gut. And there's an incredible bunch of studies that were looked at by psychiatrist, Stephanie Chung and her colleagues that looked at gut health and depression. And they found that people with major depressive disorder had about 50 different types of species in their gut microbiome that were different from the control groups that didn't have depression. And a lot of recent research shows that these bacterial species are associated with high quality of life, are often depleted in people who are depressed. And bacteria that cause inflammation are found in a lot higher numbers in people who have depression. So can you talk about what these studies showed and the connection between this inflammation

and depression? Because I mean, I saw a study recently that just made me crazy, which was using TNF alpha blockers for depression, which are these powerful drugs that cost 50,000 a year. They're used for autoimmune disease to shut off inflammation. I'm like, why not deal with the source, which is the gut? So talk about what these studies show and how this connection exists between inflammation and depression. So the more that we learn about the gut, the more that we realize there might actually be certain specific bacteria that are involved with the positive drive of depression versus

the negative drive. I want to actually mention a study, and the reason I'm talking about it is that it's linked to this in the sense of how people don't realize the impact of certain gut bacteria and a food mechanism that can help you. A study that looked at yo-yo dieting, and this becomes significant because my patients who come in who've gained the weight from, say, medication, don't know how to get off it, and they might start to lose weight, and then they gain it back. And the sort of yo-yo piece of dieting has also happened with, say, reality TV shows, and people don't realize that there could actually be a mechanism in the gut.

A study that was done and published in Cell sometime this year showed that in particular lean mice and mice that had gained weight, they identified that certain gut bacteria were driving this. And it was almost, for want of a more elegant word, like a fat memory coded in the gut. Then they found that if they fed back proper and certain antioxidants that those, the inflammation caused by this gut memory improved. And I think that what is so cool about this is it's one of those studies that directly showed a mechanism where antioxidants worked in a positive way. And I think that for me, it goes back to the Stephanie Chung study and those that have shown the multiple bacterial species, a quality of life factor,

a lowering of depression. And, you know, I think I appreciate what you've been saying all throughout this conversation, Mark, because going into this, you know, I think that I didn't, when I said at the beginning, you know, the illness that I had didn't lead to the book. It was because I wasn't sure that there was a book. I had been doing the work. But it was some of the work that got more publicity that led to my writing the book. Because I knew the science was there. And what this did for me is it pushed me to look at, like you were saying, you know, 700 references condensed to over 550

because there was science behind it. And sometimes, you know, we get pushed to the side as complementary, alternative, or soft science, but there's real data behind it. And I think that the more we can explain that to people and have them try things that, you know, it's not going to harm someone unless you have an allergy to try a different diet and to use these mechanisms to feel better. And we can be highly specific in some of these situations. because if you're looking at trying a drug that's very expensive or that has potential risky side effects, the bar is a lot higher than saying, why don't you stop eating sugar and gluten

and eat some vegetables and fiber and fix your gut? And the evidence is there. We may not have large randomized trials, but we have a lot of evidence, like you said, and the kinds of studies that are done now are just so compelling and so beautifully done. And I remember one of the studies I looked at was the SMILES trial, which looked at just swapping out people's normal processed food diet with more whole foods. And it was as good as antidepressant, right? Exactly. It was as good as antidepressant and they added in counseling and coaching. So you had, you know, you followed this diet and then they also had someone check in with you and ask you some questions and see how you were doing. So, you know, a lot of, say, weight

loss programs have built-in coaching now because there's this almost contact part and accountability part that is very helpful to people. There was a great trial done by my colleagues in Australia and I think that you know one of the things that we're trying to do more of is really larger human trials. The difficulty is that how to capture some of the actual food that people eat becomes a little bit of a challenge and so you know I think that we're... Because we're not lab rats.

You can't just lock us away and feed us the same diet. Feed us the same diet, exactly. Free-living humans are hard to study. It's hard to study. It's different if you're prescribing, you know, if you're doing a pharmaceutical trial. And, you know, there's also a lot more funding that goes to pharmaceutical trials and very little incentive that goes to nutritional trials and very little incentive that goes to nutritional science and nutrition epidemiology studies um that there's definitely a difference

and so um you know i do think that with the studies we've looked at even if the numbers are smaller we've looked at the science and tried to to pull out for people facts that will be digestible to them that they can actually take home and say, well, I can try to do that. And at the end of the day, you know, I think we can always find a study that's pro one thing on the same day, a study that's against the same thing. It's how we interpret it for people and show them the balance of what has worked. And that's where clinical, you know, like you said, so many, the many patients that you've treated, that's where clinical, you know, like you said, with so many patients that you've treated, that's where the clinical piece also becomes so important. Tell me about the moment you sort of began to connect to the nutrition piece and then the microbiome, because you really

have gone deep into these areas and far more than most physicians. Yeah, that's, you know, actually tied into my cancer research quite a bit. So my research was focused on mitochondria, which are elements within the microbiome. These are archaea. Archaea are the precursor to modern bacteria. So somewhere around 4 billion years ago, 3.5 billion years ago on planet Earth, we see the emergence of the archaea. And then within half a billion years afterwards, we start to see more modern versions of the bacteria that thrive and create most of the biodiversity. But one of those archaea bacteria were absorbed into a more complex methane-producing bacteria some billions of years ago, it seems, in the fossil record to create the first mitochondria.

And at the moment that we had a functional mitochondria, it changed the way that energy was produced in the cell. And so my research in chemotherapy was around maximizing the signaling system out of mitochondria. So how do these ancient bacteria that live and thrive within our human cells create all of the energy for ourselves and create a network of communication within ourselves? How do they communicate back to something as complex as our genome or our pathways of enzymatic function so that was my area of research and i didn't think of them as microbiome i thought of them very much and i think i was really trained to believe that they were part of the human cell and they were just like this little organelle inside the human cell nobody told me they were my client nobody told me they look like bacteria if you look at them under a microscope they look like little bacteria and they're actually, they have different DNA actually than your whole DNA.

They have their own genome, which isn't taught to us either. Like we're not taught, you know, maybe I hope that med school students today are, but certainly in my generation of physicians, we were not taught at all the fact that mitochondria have their own genome and that they are archaea makes them very unique. Like the new stuff around genomics is fascinating around this. I don't want to go down that rabbit hole, I guess. But, you know, this was the entry point to when I started a nutrition center

and started seeing people not responding to health food regimens that had been proven out for 40 years from the likes of Colin Campbell and Esselstyn at the Cleveland Clinic. And, you know, I was applying, you know, master's level of information that these guys had produced over the years to my patients and seeing them fail. I was seeing them actually get worse, not better on things like kale. And so I was trying to figure out why kale could cause an inflammatory reaction. And it took me a while to believe that the patient was actually eating the kale.

Like I thought, well, maybe they ran out and ate a Twinkie at the same time. Like I really blamed the patient for a long time before I developed enough relationship to find out that I really trusted them and actually came to realize they were eating healthier than I was. And so in that journey, we had to start asking really tough questions about what does kale look like today to find out that it's devoid of alkaloids, the medicine within the food, to find out that it's actually got an abnormal ratio of soluble, insoluble fibers compared to kale 20 years ago, to find out that it's laced with a chemical called glyphosate. A roundup was a big aha moment for me. And so that was the journey into, you know, realizing that we were going to have to look

deeper than just a nutrition protocol and start asking tough questions about the food, which immediately took us into soil. And so- Yeah, wait a minute. That's powerful. I just got to unpack that. So you're basically saying that you realize that your patients were eating what you thought was good food. They weren't responding to it. And so you traced back to what the quality of the food was and what it was missing compared to decades ago when we had better soil.

And that it had lower levels of fiber and lower levels of nutrients and had lower levels of other compounds. It even had higher levels of compounds like glyphosate, which I really were going to get into with you about it. So you just sort of connected the dots. And that is a moment when I guess you realize that you can't just go to the grocery store. You have to go to the farm. That's right.

That's right. Yeah. And at that moment, this was like 2012, you know, we were studying those soil, we were starting to study soil and we found a family of molecules that are vast and variety, each species of bacteria and fungi are capable of making 10 to 15 variants of these carbon molecules. And they happen to look a lot like the chemotherapy I used to develop that was disrupting and changing mitochondrial metabolism. And so I suddenly realized that the soil could potentially hold, you know, highly intelligent medicinal qualities to it, which that ultimately really proved that not only do we have issues

with our farming industry in regards to its productive quality, we had perhaps a deficiency at the soil level of medicines that had never been discovered before. And, you know, I'd always had this vision and I was dealing with plant medicine. I was doing biome and A extractions and all that. And then, you know, fast forward in my clinic and I'm trying to use, you know, herbal extracts. And I was investigating homeopathy. I was investigating, you know, herbal medicine and all this stuff. So I was starting to really welcome in all this stuff, only to find out that 4 find out that 4,000 years of looking at the plants for medicine might've missed a deeper

story that the microbiome of the soils were capable of producing even a more, a higher level of intelligence within my, within the cellular systems of communication, nutrient delivery and the like. So that was the closing point of, you know, where I really pivoted at that point. And I started a biotech lab at

that moment to start studying soil and the possibility of a whole medicinal capacity to soil. And so that's what we do now. We produce out of Virginia soil compounds that carry these carbon molecules. Okay. This is really a radical idea. I just want to pause and emphasize this because we know about the rainforest and we hear about the medicinal plants and all the medicines that come out of the rainforest. And nobody thinks of dirt or soil being a reservoir of compounds that have utility in human health. And yet we know there are a lot of things in soil that have produced medicines. A lot of medicines do come from the soil. And what we're finding is that we're driving the extinction of our soil. So we don't think about, oh, the destruction of the rainforest, the destruction

of the soil. We're not really talking about that. There are a few people like us, but it's really not out there in people's consciousness that soil is actually so critical for human life on the planet, not just to produce food, but as a reservoir of all these compounds. So take us down that road and tell us what kinds of things specifically you find in the soil that people don't know about that are so beneficial and helpful that we've discovered. Yeah, you know, we could spend hours on that in a lot of different directions, but to focus it in on these carbon molecules for a moment, because I think it's a profound new concept of medicine in general.

Not only is it a novel source coming from soil, but it totally changed my whole perspective on what we should be doing as physicians or a pharmaceutical industry, which is instead of trying to micromanage a single pathway. So something like NRF2 is commonly talked about. So NRF2 is a pathway that regulates a bunch of our oxidant antioxidant relationship to the world around us. And inflammation cascades can be really disruptive when NRF2 is affected and things like this. So we align with that as a pharmaceutical industry and say, okay, we want to find things that upregulate or downgrade NRF2. And we try to find man-made chemicals that we can patent and change that pathway.

From the nutraceutical world and dietary supplement world, we say, okay, we want a tendency to kick the allopathic medicine mindset off the stool and then sit right back up on the same stool and simply offer a different toolbox to do the same reductive kind of effort towards changing biology or micromanaging the NRF2 pathway with this beet extract instead of with that pharmaceutical drug. But in the end, we're failing to realize that the NRF2 pathway is perturbed for a reason upstream. And so we tend to be very reductionist in our mindsets, and we tend to focus on symptoms as the problem rather than an upstream phenomenon. And so these carbon molecules, when I saw them, were very unique because i had studied extensively redox chemistry and mitochondria which are oxygen-based compounds that allow for the release and exchange of hydrogen and therefore electrons and so redox chemistry intracellularly is mainly produced by the mitochondria and they allow for trafficking of information. So it literally works as a liquid circuit board inside your cell system

to coordinate cellular behavior at complex levels. And that redox chemistry is a wireless communication network between the systems, between cells even. They have to go through gap junctions because they can't go into the extracellular space because the extracellular space is too variable in its osmolality, its pH, it's all of these different things that can destroy that domino effect of oxygen-based redox chemistry. What I found in 2000—

Hold on, hold on, hold on. Before you go to the next thing, I just want to unpack that for people because it was a mouthful. So what you're basically saying is there is inside your cells a balance between antioxidants and things that are free radicals or oxidants. And that balance is critical to health. And when it's out of balance, it changes all the chemical signaling in your body that can lead towards disease. Did I get that right?

Spot on, yeah. So redox is a reduction of words of reduction and oxidation. So oxidation is the pulling away of an electron from the environment and reduction is an addition of electron. And so by moving electrons between reductants and oxidants, you can get a stream of electricity. And so to create a wireless network of communication at the cellular level, you want to pass electrons. And the oxygen molecules that are produced by the mitochondria,

when they produce a single molecule of ATP, which is kind of the fuel that we're purportedly running on, the ATP production in its byproducts is producing a bunch of 15 different variants of these oxygen compounds. There are things like ozone, hydroperoxide, O2H, which is kind of the opposite of H2O and all of this. And so very unique oxygen-containing molecules. The issue or the limitations of intracellular mitochondrial-based redox chemistry is that every one of those oxygen-based molecules only lasts for about a millionth of a second. And so they are down in the quantum physics realm of communication. If you try to take that quantum environment outside of the cell into like a soil

system or into your gut lining, you lose the capacity of that domino effect or electron potential because you can't maintain a consistent current. So what we found in soil was these large carbon molecules with the right side of the molecule looking a lot like the redox chemistry that I used for my chemotherapy. So the idea that this big carbon backbone would be produced by bacteria and fungi to stabilize redox chemistry in extracellular environments was super exciting. It really, it was just massive goosebump moment when my colleague and I were going through this white paper on dirt. I didn't know anybody knew anything about dirt, let alone an ID page,

white paper on soil science. I was blown away, paging through this thing, this molecule, goosebump moment of not only is there medicine in the soil, it could be so much more stable and deliverable as a medicinal kind of effect than our oxygen compounds and those that would affect it. The exciting thing about redox chemistry, again, is it resets our concept of a medicinal. Instead of trying to affect a single pathway, in fact, instead of trying to do anything to a human body, for example, all you're trying to do is reconnect the communication system so that the cells can communicate. And when cells have uninterrupted information, they become healing machines. They know how to mobilize stem cells if they're too damaged to repair. They know how to repair themselves at a faster rate. They know

which proteins are missing. And so that was the excitement. And as we started putting this into cancer cells and neurons and proximal renal tubules in our lab, we were immediately seeing things we had never seen before. And this was a cumulative experience of like over 120 years between the scientists that were involved and everything else of basic science, looking under microscopes, John Gilday, PhD, you know, UVA, you know, master of microscopy and cell biology. He was seeing things that never happened before under the microscope. And it was because for the very first time, we were not treating human cells and health and disease as if it was an isolated event. We were bringing in a biologic compound of communication network made by bacteria and fungi

and introducing it to a petri dish. For the first time, we were watching biology happen in the context of an ecosystem. And the last 10 years, you know, journey has just been mind-blowing to find out how powerful we are as healing machines when endowed with with the communication network that's up and running so how are you using the soil science that you learned and this this these microbes in the soil that actually regulate these pathways how is that linked up to human health directly yeah make it a little practical how do how do we actually see this in real life so the first thing that we did was study uh gut lining because we had come john gilday had done a lot of work uh around um

you know deep reading and understanding of glyphosate which is the roundup you know active compound herbicide most ubiquitous chemical that we spray in the world over four billion pounds a year now into our soil systems water system around around the world. And so this molecule was ever-present in his mind. And one of the main things that this molecule was becoming recognized to be capable of was destroying barriers. And so it could break down the gut barrier. It could break down the blood-brain barrier, kidney tubules. And this would lead to a leaky sieve event and the chronic inflammation in the population. And so, of course, the debut in 1976, and then the spraying directly of wheat in 1992, and then the GMO crop, a Roundup Ready genetic modification in 1996,

you can see that the uptick in chronic disease, autoimmune disease, inflammatory conditions of neurologic degenerative conditions, all of these upticking with every introduction. And the ground zero seemed to be in this protein destruction of the tight junctions. These are the Velcro-like proteins. As soon as we put this one- That's what people call leaky gut, right? Leaky gut, leaky brain, you know, leaky kidneys, you know, and the symptoms tend to be, you know, bloating, poor digestion, poor energy level, fatigue after meals, cravings, poor sex drive, poor sleep quality, brain fog, you you know short-term memory loss and then inflammatory conditions of vascular disease diabetes metabolic collapse opc all that are is

set up by the breakdown of the single protein which is so interesting that ground zero is like you know boiled down simply the velcro that holds all of those cells together is called tight junctions and as soon as we put this communication network back in, we saw something extraordinary happening, which was cells knew how to lace themselves back together. So we could destroy a gut membrane, small intestine, or colon immediately. Within six minutes of roundup, you've got massive leak going on. But if you gave it back a wireless communication network made by the microbiome, those cells would lace themselves right back up into a cohesive, coherent, highly protective barrier. Subsequently, we've shown

this on the blood-brain barrier. We've shown that the relationship between the gut and the brain injury is very interlaced. If you give Roundup and gluten, for example, to the brain barrier directly, it doesn't do much. But if you first give gluten and round up to the gut lining then the blood barrier blows apart and so it's so interesting to see how this cascade of putting this chemical round up into our food system set us up for this breakdown in these different barrier systems and it's so beautiful that here is the chemical that we're destroying planet earth soils with and yet she planted as an antidote to this chemical, these compounds within her soil 60 million years ago. And that's how we extract these

carbon molecules. So we go to a fossil layer of soil in the Southwest United States, and we then bring that to our labs. We crush that into nanoparticles, and we go through a multi-stage process to liberate small carbon molecules and get hydrogen to bond to the oxygens again and get a redox effect and when that system of communication from fossil soils goes back in to a modern human experience it's unbelievable you know what can happen and again it's not because the compound's doing anything it's because the human cell is capable of that and when it's grounded in the intelligence of soil when it's grounded in the intelligence of soil, when it's grounded in the intelligence of nature. And so that's been the journey towards this, you know, extraordinary realization that

if we don't fix the agricultural industry, we're going to fail. So now our biotech company with all of its supplements are channeling all of our profits back into root cause solutions. And one of those being our nonprofit, which is an awareness and education effort to allow chemical farmers to realize that they're actually the most potent members of change for the transformation of human health. And this is poignant because they are facing the highest levels of chronic disease in the world. The last 90 miles of the Mississippi River that collects some 80% of the roundup in our environment is cancer alleys. We see farmers with third time, fifth time cancers of different organ systems. Their children are affected by ADHD and autism and brain defects.

And I've seen just the most horrific stories of tragic human health on these farms as we've been filming over the years in these environments. And so you can only imagine how devastating it is to, I give these talks out with PowerPoint presentations, literally in farm fields. And so it'll go dark while I'm showing a part. And these farm families are just riveted, sitting around on bales of hay, listening to this story, realizing that their children's diseases

that they're treating and their own cancer is coming from the very chemicals they have to handle every single day. Thanks for listening today. If you love this podcast, please share it with your friends and family. Leave a comment on your own best practices on how you upgrade your health and subscribe wherever you get your podcasts. And follow me on all social media channels at Dr. Mark Hyman.

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