The Mind and The Gut - with Dr. Emeran Mayer | The Empowering Neurologist EP. 24

Hello everyone, I'm Dr. David Perlmutter and you are watching the Empowering Neurologist program. Today we're going to talk about the mind-gut connection, you know, this connection that people talk about between what goes on in the gut and what goes on in the brain affecting cognition, affecting even mood. And our guest is Dr. Emery Mayer. He's the author of this incredible new book, that you'll be seeing very, very soon called The Mind-Gut Connection. I first had the opportunity to meet with Dr. Mayer as he was one of our guest speakers at last year's International Microbiome Symposium that we held here in Florida. He is a gastroenterologist, but he's also a neuroscientist, and he's a professor, professor in the departments of medicine, physiology, and psychiatry at the David Geffen School of Medicine at UCLA. He is the executive director of the Oppenheimer Family Center for Neurobiology of Stress, again at UCLA, and he's one of the pioneers and leading researchers in the role of what are called mind-body interactions in health and chronic disease. His scientific contributions in the United States, both nationally as well as even international communities, in the broad area of basic and translational enteric neurobiology and wide-ranging applications in clinical GI diseases and disorders are virtually unparalleled. He is— he's published more than 300 scientific papers and co-edited 3 books. His most recent work has focused on the role of gut microbes, the microbiome being what we're talking about here, and how the microbiome, meaning the gut microbes and their DNA and their metabolic products, how they influence the brain, the role of food, how food addiction comes into play in this discussion, and even obesity. He has a longstanding interest in ancient healing traditions and affords them a level of respect that we typically don't see in Western medicine. He wrote and co-produced the award-winning documentary In Search of Balance. He's been interviewed on National Public Radio, public television, and many other national and international media outlets, including the Los Angeles Times, Atlantic Magazine. And he also did a really compelling TEDx talk at UCLA on the mysterious origin of gut feelings that was done back in 2015. So, we're going to talk today about this really wonderful new book and learn what Dr. Emery Mayer is up to at this, at this time. So I'm really delighted, Dr. Merit, to have this opportunity to speak with you today, and we're very, very excited about your new book coming out, The Mind-Gut Connection. I have to say, who knew? But, you know, the beginning of your book starts by you almost having to validate this notion that things in the gut influence the brain. Why has there been over the years such a pushback between us getting our arms around this relationship between the gut and the brain?

Well, first of all, it's great to be on the show. To answer your question, I mean, this pushback continues to exist really within the medical community and amongst many gastroenterologists. I think there's been a slow acceptance of this concept that the brain actually is an important part of the digestive system and that the brain-gut axis is equally relevant as specific things that gastroenterologists have focused just at the gut level. Why the pushback? I mean, you know, you could use this often-used story of Descartes, the Cartesian split, that science has— that medicine is primarily focused on the body and has left the brain to religion and psychologists, and that anything that happens in at the brain level, still a very prevalent concept for gastroenterologists and for some patients, is psychological.

So why did a guy— what's a nice guy like you doing in the brain? In other words, how does a gastroenterologist suddenly become interested in the effects of the gut on the brain? What happened?

Well, it wasn't suddenly. So, you know, this is a long story. I mean, I tried to condense this down into the key points. Before I decided to go into medical school, my main interest was in psychology. I was a big fan of Freudian and Jungian. I mean, this was really something I find really fascinating. Then in medical school, when I had to find a thesis advisor, I was searching. It was very hard, as kind of described within the book. I ended up in the Physiological Institute of Munich where a very prominent investigator was looking at the connections between the brain and the heart, mainly the regulation of coronary blood flow and myocardial perfusion, differential perfusion during stress. And that was exactly what I wanted to do. But then, you know, I did a clinical rotation at the Mass General in the summer and in gastroenterology, and that convinced me that The clinical field of gastroenterology was more interesting to me at the time than cardiology. So that's how I ended up with GI. And the best example at the time in GI was really the functional GI disorders, which were a puzzle to the medical community and which matched very well with my brain-heart experience. And so I essentially applied the same viewpoint, same— Yeah. concepts on the GI tract. What did change then that, you know, with the heart, the main action is really from the brain to the heart. With the GI tract, it became pretty obvious very soon that it goes in both directions. So the brain influences the gut and the gut sends back signals to the brain. So it's a very integrated circular system. It's not— one way or the other, you know. So that— so, I'm glad I made this transition into the field of gastroenterology. And we have some interactions now at UCLA with cardiologists who are paying a lot of attention to that same topic now as well. So, I mean, there's a slow paradigm shift, I think, within medicine.

Well, when I read that in your book, I was very taken by the fact that 3rd-year medical students have to create a— defend a thesis, basically, and that your proposal about, you know, this interaction was, I think, by the person who was overseeing this, I think that he rejected your ideas and told you that wasn't going to lead anywhere.

Well, this was for the, yeah, for the initial proposal. Once I've worked in that lab, you know, so, I mean, I worked there for 4 years, so it was really in a basic science department. Which prolonged my medical studies. But that lab was fully on board with that. But it was hard to find a person. And, you know, so many people I talked to said, oh, you know, this can't really be studied scientifically. We all know it's part of medicine, but you can't do a thesis on that. And so—

But how incredible it is that all of that science has been sort of rewritten now that we understand the influence of the gut microbiota in terms of changing mood, in terms of influencing behavior. And I wonder if you could just give us a quick overview in terms of the various channels by which the gut microbiota are influencing the brain.

Yeah, so there's channels, again, that mediate this bidirectional communication. So from the brain to the gut and the microbes that live in it, I would say the most important channel is the autonomic nervous system. I always highlight this one example of that during stress where we activate the sympathetic nervous system, there's not just release of norepinephrine into our blood affecting the heart, but research has shown that there's a release, pretty hefty release, into the gut lumen. So what does it do there? When these findings were first discovered, Same thing for serotonin here in our center. Serotonin was that molecule and people ignored it and the research was not pursued. This was like 20 years ago. Now we know that microbes have receptors for serotonin, dynorphin, norepinephrine, all the, what we used to call the gut hormones. So the same chemicals that our body uses to communicate with between different organs and the brain. Our brain influences the release of those in the gut. They affect the microbial behavior, the gene expression. So that's one channel.

I have to stop you right there because that's really profound, and I want to make sure that our viewers catch that, that these receptors for neurotransmitters that we're all hyped up about being in the brain, that are the target of pharmaceutical manipulation are, in fact, also on the cell surfaces of various organisms living in the gut, and that these same chemicals are being used to modify bacterial behavior, probably more metabolic behavior, obviously, but that these are the same chemicals that we all like to talk about.

Absolutely. And, you know, so this is sort of fascinating to me because, I mean, I came to UCLA as a like before my GI fellowship to actually study these peptide molecules. They used to be called gut peptides before we realized they're not just limited to the gut but in the brain there. And now we know that they're also— that the microbes use them. So it's kind of the universal language of our entire organism. And it's ironic or interesting that The microbes are really the ones that developed this language billions of years ago as a means of communicating with each other. And then during evolution, they gradually were adopted probably by something that's called lateral gene transfer so that these microorganisms could transfer these genes into primitive animals. And then in the animals where they were first in the GI tract, they gradually made it up into the brain. So the reason that we now have this completely integrated system, which the brain and its emotions affect the behavior of these microbes and change their behavior, change what they produce, which then affects us again, is— I think for me it's the most profound, you know, and the most satisfying aspect of my research. We've really come full circle, studying this some 40 years ago. You know, in these peptides when they were extracted from tons of pig intestine, because we didn't have the sophisticated ways that we have today, to what we understand today, you know, I find that absolutely fascinating.

We all think back about the work of Dr. Candace Pert, Molecules of Emotion, and, you know, remember the groundwork that she put forward forth for our understanding the role of these mediators, these signaling molecules, in modulating mood, etc. But now you bring just a whole new level of complexity in a good way to what, you know, their history and what really may be going on. Probably 3 years ago now, I heard you lecture at Harvard and you were presenting your data of your study where you had provided— there were 36 women, I believe, and you provided one group with a probiotic-enriched yogurt and followed them over a 4-week period of time and then measured them in terms of— you did some functional imaging of their brains, as I recall. That was a very, very profound result that you achieved. And I remember I asked you about that, and we didn't know each other at that point, but I came up after and asked you about it. You were so humble. You said, well, you know, We need to do more research in the future. But I want to revisit that now that a few years have elapsed and just again indicate to you that the notion that manipulating somebody's food in terms of its probiotic content had— that it had a significant effect on their perception of the world, basically, in terms of anxiety through the pathways that were changed. That's a pretty intense bit of science that I think a lot of people might have a tough time really embracing. But now that a few years have elapsed since you published, what are you thinking retrospectively about that study that you did?

Yeah, I mean, I think it's still— it's kind of a paradigm-shifting study because up to that point, and quite honestly, up to now, there's this very little data in humans that has indicated that some of these spectacular experiments that have been published from mice, from gnotobiotic mice, and that, you know, changes in the gut microbiota with antibiotics, probiotics, or growing up, you know, without the bacteria would have profound effects on emotional behaviors and feeding behaviors. It still remains the best, or the only study really that has demonstrated this in humans. We're pursuing this on multiple levels in new studies, and I have to say, if it hadn't been for this study, I mean, I was a big skeptic of the mouse studies, not in terms of their scientific validity, but in terms of their relevance for complex human behavior and emotions. Right. I'm still a skeptic of that.

How do you know if a mouse is depressed, basically?

Yeah, and the kind of behaviors that are being used in the laboratory to assume this is, you know, related to human depression or human anxiety or autism with all the complex symptoms, I think it's difficult. But since we found this in healthy women, you know, that changed the course of my research because we've now launched every single study that we do longitudinally and long-term studies, studies with evaluating the effect of cognitive behavioral therapy, mindfulness-based stress reduction. We now always look at the microbes and the metabolites that they produce and do these interventions change their behavior. So that study had this profound, you know, career-shifting influence on me, and I'm delighted we did it. Believe it or not, I mean, the company that provided the probiotic had pursued me for years if you wanted to do something like that. And I always said, we have too much going on, you know, we have NIH-funded studies, I can't spend a year or two doing this kind of work, because I didn't Well,

I want you to know that that study didn't just change your trajectory, but there are many of us who were highly influenced by the results of that study. And it really was a paradigm shifter for us because it was an interventional trial in humans that you, you know, you actually demonstrated graphically on the imaging studies the changes that happened. That's a big aha moment when you look at Changing someone's food that is enriched with probiotics and seeing changes in brain functionality, that's, no pun intended, it's a lot to swallow, a lot to get your arms around. So, I mean, there are, there have been a very few studies using Lactobacillus helveticus and Bifidobacterium longum strain-specific and seeing some changes in humans, but I would agree that we're really at a very nascent stage in our understanding of what specific organisms may do, and even more primitive place that we are in terms of ever even considering intervention or therapeutic utilization of probiotics. But we're starting to see some, at least, anecdotes in terms of people changing their diets, adding more prebiotics. And, you know, you talk about it in your book, and you talk— we'll get to that, what your dietary recommendations are. Yeah. So, I think you're building on some pretty sound information that's now been generated.

And, you know, I mean, you have to realize we're in the very beginning of this field. So, I mean, the concept of, you know, that has been coined by some investigators in this field, like, about psychobiotics, I think the concept in itself is interesting and may have some validity. far away from having those kind of molecules or organisms. But since we're able to change the genetic makeup, so we can change microbial production of GABA, for example, or serotonin precursor tryptophan, it creates a very intriguing— Potential. totally new way of treating serious brain disorders. And I mean, not that I'm totally without reservations for these kind of approaches because it's like you're messing with a very complex ecology. It's sort of introducing like a new species in Australia like the rabbits and then later you realize this was a disastrous thing to do. I sort of trust more into changing your diet and changing the prebiotics, how you feed the existing. But these attempts are ongoing to manipulate microbes to do specific things. They could produce insulin, they could produce serotonin, like your own antidepressant, in a more physiological way. Big caveat, if you do this to one organism, what does it do to the ecology of the system? With unintended consequences?

Well, I think the broad strokes have to do with changes in microbial diversity. I mean, I think that's a common theme that's pervasive throughout the literature these days, is that there are health consequences associated with loss of microbial diversity, both in humans as well as laboratory animals. That said, you know, your colleagues Sonnenburgs recently published a report showing a fairly dramatic drop in laboratory animals that were inoculated with human microbiota, a drop in the diversity when their availability of metabolizable fiber was compromised. In other words, when they had a reduction in the— of fiber, basically prebiotic fiber available to them, they lost their diversity. But what they showed, I thought was really fascinating, was when they resumed higher levels of prebiotic fiber, a carbohydrate, That the diversity increased again, not to its former level. But what was even more compelling was the fact that generation after generation, when they kept giving them the low carbohydrate, the low metabolizable carbohydrate diet, less fiber, that the recoverability became less and less, and they continued to lose diversity. You know, when you, when you look at a study like that, an animal study, then you walk around a public place like an airport and look at humans, you begin to get a sense that, you know, really what's going on globally is we're losing our microbial diversity. And as such, as you talked about the very beginning of your book, we are losing our adaptability to environmental changes. So, you know, we talk about food and we'll get there in just a moment. But, you know, let's just segue into in a little bit, you're going to, you know, at the end of your book, you talked about sort of the paleo ideas. But how important is food if we're paying attention to our diversity of our microbiota?

Very important. So that is— there's no question. So, I mean, I have to preface, you know, I'm not a dietary expert per se. So I'm not— and also, my book was not written about, you know, promoting a particular diet. It's I'm in some ways looking more at the general picture of— and so one thing that we do know is that diet plays a major role. I mean, there's clearly the microbial composition, the architecture is programmed early on in life. It probably starts even prenatally, definitely during birth, and then through breast milk, through human breast milk and the metabolites and also the— Yeah. Microbial organisms that are transmitted during breastfeeding play a big role, and then the environment of the household. So by age 3, if you look at children from, you know, one of the pivotal studies that was done on this of natives, primal people living in the jungle of the Orinoco, as opposed to North American cities. So even in these infants, there was already before they started their regular diet, there were made profound differences, including the loss of diversity And so a lot of things happen early on. I think once we've grown up, our system is much more stable, but what it maintains is this adaptability. So it can— and that was the best thing for humans, that, you know, we can go through famines, we can— where we have no access to meat, we can live without any meat for years without serious consequences. On the other hand, we can be on a high-fat, high-meat diet. So it's incredibly adaptable. I think that's the uniqueness. And it's totally consistent with this concept of diversity, which goes along with resilience. And so the best, from a microbiome standpoint, the best composition is one of, from the early beginning, of great diversity. So, So, if these individuals— I mean, just the fact that humans can have these very different diets that are being recommended and not having major side effects or, you know, develop diseases is actually quite remarkable. I think the only exception to that is what's happened in the North American diet. I think that our microbes and our brain-gut axis are not— Yeah. adapted to handle. I mean, so that's the one exception, I think, in evolution, probably that—

Well, you know, we are seeing publications coming out now that really are beginning to correlate the differences in the diversity and even looking at things like Firmicutes-Bacteroidetes ratios, etc., in comparing various diets, whether a person is vegan, you know, an omnivore, or Or what are various other diets? Yeah. So the real question is, is the microbiome adapting to that diet in a positive way, or does the microbiome reflect issues that may ultimately prove negative for that individual? I mean, we know that the microbiome changes quite readily based upon diet, but at the same time, we know that the microbiome influences our food choices. So, who's in charge here? It's really quite compelling information.

Yeah, and I think we have become more vulnerable. I mean, this is one thing that, you know, becomes obvious once you sort of look into this. And for me, it's been helpful to get towards the diet through the microbiome because that's sort of really the angle that— I mean, it's kind of ironic as a gastroenterologist, you're really not trained in dietary aspects.

It is ironic, isn't it? I love that.

Which is kind of amazing. But so, you know, some of us have gotten into through the back door, through the microbiome now. And if you just think about that, we start out even as infants having grown up in a US city with this greatly compromised diversity and adaptability. And then we're confronted with an onslaught of unprecedented changes in our food supply. And I'm not just talking about the different composition of macronutrients, but it's the chemicals that go into processed food, the emulsifiers, the artificial sweeteners, the colors. There's a lot of things being added. And also, like, you know, along the lines of your expertise in terms of gluten, I mean, the amount of gluten that's being added to all kinds of foods as a You know, to help to change the taste or consistency or palatability. Yeah, I mean, you have to expect that some bad things are going to happen. So you start out with a diminished diversity and then you add things to it, feed the microbiome things that it's never encountered in evolution before. So I think That's the worrisome thing. And I think many of the diseases that are popping up, like obesity, metabolic syndrome, degenerative brain diseases— I mean, some of these diseases have not changed so dramatically as obesity, but they are increasing, not just because the population gets older. And you've pointed this out in your own books elegantly, that— You know, we sort of— it's just slowly starting that people look at, like, Alzheimer's disease as an inflammatory disease of the brain. And inflammation clearly is one thing that, you know, starts at the gut level to a big degree. So I think those pieces are slowly coming together. But To me, it's been amazing to really understand what is the North American diet. And I personally put less emphasis necessarily on the components, if you increase your carbs or decrease your fat or, you know, whatever. It's how it's been modified and without people realizing it, what they're ingesting, you know.

Well, for our viewers, I would encourage you to look back through our interviews. Several weeks ago, we interviewed Dr. Stephanie Seneff from MIT. And she was talking about some fairly dramatic changes that are occurring in the microbiome as a consequence of levels of glyphosate, the active ingredient in Roundup. Yeah, that's it. In our food. So there are a lot of things. But getting back to just the idea that here you are at this stage of the game as a gastroenterologist paying attention to food, that's great. I mean, that's, that's a mark of completion that is so, so exciting. You do mention the paleo kind of idea, paleo movement. And, you know, basically, that is sort of an attempt by people to emulate what our ancestors may have eaten. Why do you— why do you go to that place? What's the validity here?

So that's a very interesting story. Also, you know, point out in my book that during college, I had the— this, you know, unusual opportunity to become part of a documentary film team to go to various places, faraway places, usually living with primal people. So, you know, I went for 6 weeks to the Yanomami at the Orinoco River within the Amazon rainforest, another time to the Asmat people in Irian Jaya in Indonesia. The most interesting example to me has been the Yanomami because we now have data from these same tribes about their microbiome. And so when I met the researcher that led this study, the sort of pivotal study really, I couldn't believe that somebody would have studied those natives that really live a very primal, prehistoric lifestyle. lifestyle, the untouched ones. And we lived in their village for 6 weeks and observed, saw them hunting, saw what they eat and how they ate. And so now I've come back to these and dug out my old diary and the film clips, like all the information we had. So this was like, you know, 40 years ago. And I found it absolutely fascinating. And so a couple of things are important about this. You know, these people, they die from various causes certainly earlier than we in the West do. They don't become 90 or 100 years old. They have accidents, they fight a lot of wars, but they seem to be, at least what you see in a 6-week period, very healthy. We never saw a sick person. We saw sick people once they've moved to a missionary compound, got all kinds of skin diseases, allergies, obesity. So like we saw it right in front of us, that going from that lifestyle that they had for thousands of years to just in the same area moving close to a Western-type environment, you know, a lot of diseases popped up. So without glorifying this this primal lifestyle, you know, it showed, it certainly has health benefits for people in that age group. And so we saw closely what they ate. I mean, they spent a lot of time running around, a lot of exercise, tremendous amount of exercise. They eat a relatively small amount of animal protein that they, you know, they shoot birds and monkeys and fish. And a lot of plant-based foods. I mean, they grow, I don't know how many species of different plants and tubers and collect things.

But high-fiber plants.

That's the key thing. It's the key thing. So I think the reason that they have this very high diversity, I think it's like fourfold higher than, you know, in the West, is this enormous amount of natural fibers. very different types. It's not just one food item, it's probably hundreds of different things they pick up in the jungle. There may be lots of antioxidants as well, lots of other benefits as well, but the high fiber is clearly the main thing. I couldn't tell you, I mean, I know you've interviewed people and you personally have written about this, about the importance of fat, the fat content in health. What we have seen and what I've read up afterwards, so the animals that they shoot and catch obviously are wild animals, almost without fat. So this particular, you know, prehistoric culture has very low fat intake, animal fat intake, very high fiber intake. And lots of physical activity. I think those 3 are probably the most relevant components for one type of healthy diet.

And it's, you know, it's observational information, but, you know, in my writings about eating animals and eating fat, I really am so careful to characterize the fact that these are not factory-farmed animals high in omega-6, Treated with antibiotics and sprayed with who knows what.

That's—

And that we're not loading the plate with animal products. And it's, you know, 3 to 5— it's the size of basically a deck of cards each day in terms of your protein consumption. But I think that overall, the types of protein people derive, or by eating plants, not just the protein, but by eating rather animals that are produced is very threatening in our society. And, you know, when people say, well, vegetarians have better risk relation to certain disease entities here in America, there may be some good merit because I think by and large the meat that's available to us here, you know, 70% of the antibiotics used in America are going into raising cattle, making them fat. As you know, Dr. Martin Blaser, his book Missing Microbes was very eloquent about— Yeah. You know, his contention that one of the causes of obesity is just the fact that people are so exposed to antibiotics, and antibiotics directly lead to obesity. We've known that since the late 1950s. It's why they're used so aggressively in raising animals. The other thing you mentioned I thought was very important as well, and that is that the culture that you observed was anything but sedentary. And you know, they're up doing stuff all day long, and we really aren't. I recently interviewed. Oddly enough, I have the book right here. Dr. Kelly Starrett and his his book there it is called Deskbound, and you know talking about the fact that we spend eight, ten, twelve hours a day sitting on our rear ends, and that wasn't what our Paleolithic hunter ancestor hunter gatherer ancestors did. They were out doing stuff. So I think it's it's very important because I'm certain that everything you and I have talked about food. Diversity of the microbiome and physical activity have huge epigenetic implications in terms of modulating our own genome. So, go ahead.

It's just one comment. I mean, you know, you've also been a big proponent of the importance of low-grade inflammation. I mean, it seems like this is really becoming the common currency for most chronic illnesses. And when you think about it, What's most beneficial for your health is anything that you do or eat or consume that decreases this inflammatory potential. So exercise, clearly, a very important variable in that, and various food components equally important. So, you know, the high fiber clearly has also this anti-inflammatory effect. Yeah. It may well be at the end, once this is sort of more widely accepted in the medical community, that we realize that many of these processed foods and the way they're made and what's in them might be more relevant for our health than exactly the composition of what we eat. That's kind of— I mean, I can't prove this, but from my understanding, I think— Anything that sort of aims at reducing this inflammatory potential in our body. And then we know multiple channels of communications to the brain through the vagus nerve, through circulating cytokines, other inflammatory molecules can stimulate inflammatory processes within the brain. So I think there's sort of these— what I've found, there's more of these global concepts evolving And certainly I do it in my own lifestyle. Um, I, I don't focus on one thing. I look at this as we're a complicated machine, we're an ecosystem. We have to be, you know, engineers, as I write about, engineers of our ecosystem management. And multiple things contribute to the optimal functioning of this ecosystem and increase diversity.

Well, I think it's a very, uh, great place for us to end today, and that is that After your 40 years and my 35 years of exploration and wondering what this is all about, we come to the conclusion— who knew— that food probably matters most. So, and yet, you know, it's so disenchanting how little is expended in terms of bringing that information in medical training. You know, many medical schools don't get any nutritional training whatsoever. And yet look what we're talking about now, that the most leverageable aspect of our decision-making tree is the food that we choose to eat. And whether it's the macronutrients or micronutrients or the additives, who knows? But I think, you know, the global picture— you were a very big proponent at the end of your book about the simple word organic. You mentioned it several times. And now I see, you know, why you say that. And And we're all in. So congratulations on the new book. I am certain it's going to be very, very successful. And I sure enjoyed chatting with you today.

Thanks very much. Really enjoyed it myself.

Okay. Talk soon.

Okay. Bye-bye.

I really enjoyed that. Dr. Maier is an amazing individual doing so much work and really breaking down these barriers that have kind of restricted Western science, Western research, and Western clinicians From embracing the notion that there is this profound relationship between what goes on in the gut and, for example, our mood, and understanding that the foods we eat have a role to play in changing the microbes and their function in the gut. And this has a huge effect on mood and cognition as well. So thanks for joining us. I'm Dr. David Perlmutter. Thank you.