How Early Life Experiences Profoundly Impact the Gut-Brain Dialogue - An Interview With Dr. Emeran Mayer

What follows is a transcript for the podcast Gut Brain - Dr. Emeran Mayer - Neuroscience.

Topics within the interview include the following: 

• The profound link between our gut and brain, and its impact on our emotions, thoughts, and behavior and mental disorders.
• Explore how early life experiences shape the mind-gut connection and impact long-term physical and mental health.
• The crucial role of the gut microbiome in maintaining optimal physical and mental well-being.
• Exploring the effects of diet on gut health and its implications for our mental and emotional states.
• Investigating the bidirectional relationship between stress and gut health, along with practical strategies to manage stress for overall well-being.

Dr. Greg Kelly: Hi. This is Dr. Greg Kelly, Senior Director of Product Development at Qualia, and today I'll be the host of this episode of Collective Insights. Today, we have with us world renowned gastroenterologist, neuroscientist, and bestselling author of the Mind-Gut Connection and The Gut-Immune Connection, Dr. Emeran Mayer. Dr. Mayer is one of the pioneers and leading researchers in the bidirectional communication within the brain-gut microbiome system. This has wide-ranging applications in both intestinal and brain disorders. Dr. Mayer, welcome to the show today.

Dr. Emeran Mayer: Nice to be on the show, Greg. It's a pleasure to be here.

Dr. Greg Kelly:  Great. Well, I've read your book and reread it recently, so I'm excited to share what you have with our audience. So I want to just jump right in. There's a lot to cover today, and your experience is so vast. I think when I've looked on PubMed, there's more than 200 citations with your name, so we have a lot to cover for our audience. So with that, one of the things I wanted to start off is just how our gut microbiome is shaped both during pregnancy and early life, and then the impact that has not only on the gut microbiome, but the brain. So can we start there?

How Early Life Experiences Shape the Gut-Brain Dialogue

Dr. Emeran Mayer: Yeah. So when I wrote my book, which is now the first book more than six years ago, the main emphasis was on the early colonization of the infants got with the maternal microbiota and the metabolites. So when the baby went through the birth canal, the exposure to vaginal fluids and also some fecal fluids provided that first inoculation. This is a period where the very early phase of the microbiome where there's no such thing as what we now call colonization resistance, so whatever the gut is exposed to in terms of microbes will stay there.

In the meantime, we know a lot more. This early programming really starts during pregnancies. So the fetus doesn't have any microbes living in it. There was some controversy about this, but I think we've come to the conclusion now, but there's the maternal microbiome, and that is influenced by a lot of things that the mother is going through being metabolic health, diet, obesity, stress, any other chronic illness that will all affect the maternal microbiome, and we know a lot about this. The metabolites that are being produced and the low-grade inflammation that's happening in the gut of, for example, obese mother will cross the placenta and reach the fetal brain and has a major influence on brain development.

Then during birth, as I said, is the exposure to the maternal microbiome. The very good studies that have shown that, for example, chronic stress or I should also include in this, very importantly, antibiotic exposure of the mother. So in animal models, we know that even a one-time exposure of a pregnant mother has an influence on the maternal microbiome, which is transferred onto the baby.

Then in the postnatal phase, there's clearly an important influence of the mother as well. There are these human milk oligosaccharides. These are very large molecules in breast milk, and these molecules are not really designed as nutrition for the baby, but there's such large molecules that can't be absorbed in small intestine. They migrate down into the colon and are a major factor, again, in shaping the baby's microbiome. So the duration of breastfeeding has an important influence on the baby's development.

In summary, why do we have all these different steps of programming? There's many examples of that that nature really aims to program the optimal, the most adaptable phenotype and the most appropriate phenotype for a world that the mother has been experiencing. So nature assumes that that's going to be the same for the infant. If it's a very stressful environment, then the child is equipped primarily for a stressful world, and it all worked really well.

In the past, it was highly adaptive. It has led to the reproductive success of humans, but in the meantime because the environment has changed so dramatically in terms of the diet, the health of the mother, affecting differentially women from different socioeconomic backgrounds, just some of these influences are very negative, very high infant mortality, for example, in African Americans. So all this has changed and that has affected the health of the infant's microbiome and the earliest influence with these metabolites of the mother affect brain development. So the entire brain-gut microbiome interactions is programed both on the brain side and on the microbiome side by these early influences. So very important phase of development.

The Language of Gut Microbes

Dr. Greg Kelly: Well, you use a term in your first book, microbe speak. So the way I would think of this, and I know I'm oversimplifying this drastically, would be similar to us learning human language, that early experiences when our brain's most plastic and the best opportunity to learn and be able to speak as a native in multiple languages. After that window is closed, for many of us, it becomes a lot more difficult. So the way I think of it, and you can certainly correct me if I'm wrong, is that the microbe speak, what our gut microbiome is going to speak natively to our brain is just disproportionately largely affected both in that prenatal birth and that early infancy period. So the more we can do to set the stage to have great communication, the better we are.

Dr. Emeran Mayer: Yeah, and that microbiome speak, as I explained in my first book, it was something, is really ancient because the microbes have been around for billions of years of the dominant life form on earth. They inhabited oceans of the world by themselves without any animals around. They've accumulated millions of genes, many of which we don't really know yet what they do, but many of them are the basis for this language. So they learn the language to communicate with each other primarily. In evolution, ultimately, we humans have adopted the same language first in our gut, in our enteric nervous system. So the neurotransmitters that are there are the same words that the microbes used to have used for a long time. Then from the enteric nervous system, the same words were transferred to the brain.

So there's two kinds of programming. There's this longtime evolutionary programming, and then there's individual programming based on the mother's experiences and what she hands over to the infant. One thing I should say, there's also the postnatal period. So this is where breastfeeding comes in. So I think science and medicine is really focused on the nutrition aspect of breastfeeding, but there's also something in breast milk, which are these human milk oligosaccharides, very large molecules, complex carbohydrates that cannot be absorbed in the small intestine. So they're targeted then. They move down unabsorbed into the colon, the end of the small intestine, and they play a major role in the postnatal programming in nurturing of the microbiome.

So the longer that source, that supply of human milk oligosaccharide lasts, the more profound that influences. There's many influences that probably go into these human milk oligosaccharides, genetic on the one side and probably environmental on the other side. Really, a chronically stressed mother probably produces a different combination of these molecules than somebody who's not chronically stressed. It is amazing when you think about how sophisticated this programming has been designed by evolution.

Dr. Greg Kelly: Would it be fair to use the term prebiotic for the human milk oligosaccharides?

Dr. Emeran Mayer: Yeah.

Dr. Greg Kelly: So I think the way I think of it, and I think you mentioned this specifically in your book, this is food in breast milk for our gut microbiota, not food for the baby.

Dr. Emeran Mayer: Exactly. Exactly. You also mentioned something earlier about the Yanomami. So I've had this experience, very fortunate, I think it was in the first year of medical school during a semester break that I was invited to participate in a documentary film expedition to the Orinoco River in Venezuela. So we lived with the Yanomami, more or less uncontacted tribe of the Yanomami for some six weeks and observed and filmed everything. Unfortunately, my medical knowledge was minimal at the time. The microbiome science did not exist.

So I was just a astute observer, not somebody who had something in mind that I wanted to see. One thing that was obvious in terms of this early development is ... So I witnessed one of these births of a Yanomami baby in the middle of the night where the woman squatted in the middle of the village square and had a banana leaf under her separating that baby from the dirt of the village square. So that baby was exposed from day one, from minute one to an enormous number of microbes from the animals that were running around there, the pet animals that the Yanomami children had.

So that was one, clearly very different from the sterile environments of delivery rooms in the US where the mothers are treated with prophylactic antibiotics. So none of this existed there. The second thing was they're hunter gatherers. So the women run around most of the day collecting food, mainly plant-based food in the forest, and they always carry their infants with them. They have this contraption that they always have these babies from day one with the mothers also, again, exposed to all kinds of things in the jungle, running around in the jungle, but also, this period lasts two years. So they nursed them for two years before they gradually transfer them to bananas and platanos. So a very different early phase of that postnatal programming.

It's obvious from all the things that I told you now about the Yanomami, when they studied their gut microbiome, it turned out they had the most diverse and rich microbial composition ecosystem of anybody in the world for both in terms of their largely plant-based diet as adults. They do eat some animals, but not in abundance as we do, but also because of this cruel process really of early programming.

So in retrospect, I wish I could go back there. I just learned that my friend and somebody I admire tremendously, Dr. Martin Blazer, has actually just gone back there with his wife Gloria Dominguez and just came out of the jungle today because they revisited them. Also, this may be pertinent for this conversation, but I followed this whole Yanomami story closely. In Brazil, they're threatened by extinction, and in Brazil, they're completely dependent on government support with food support. There's malnourished children, and words in Venezuela based on what Dr. Blazer told me, they seem to be pretty much intact. They live the way they have.

So it shows you how this lifestyle and this early life exposure has been so beneficial for the ones living in on the Venezuelan side of the border as opposed to the likely extinction on the other side of the border of the same people.

Dr. Greg Kelly: Wow. Tragic. Before we move on to the next thing, I just want to summarize and make sure I have this generally correct, but the general idea at this point among people in your field would be that early lifestyle, so pre-pregnancy, pregnancy, delivery, the first two years is critical for almost shaping the gut microbiome in a way that says, "Okay. This is the environment you're going to live in and we want to make sure you are appropriately exposed so you can be optimized for that particular environment." The modern environment is vastly different, so we get a vastly different gut microbiota, essentially range of languages that speaks and communicates.

I know I saw one study, I believe it was small, seven people, a few children, a few adults, and I don't know if it was the Yanomami, but they put them into an indigenous area and measured skin, gut, and maybe there was another microbiome they measured. The children were much more plastic. These were children coming from a Western environment, but the skin was the most plastic to change. The gut was the least plastic and the adults were far less plastic. I think, at least the way I think about it is our gut microbiomes, as I live in California, was born near the Boston area, were optimized for that particular environment. I'm unlikely ever to have the microbiome of a indigenous Yanomami, and that's okay. Mine can do a good job, but there's windows of plasticity. For an adult, as you mentioned, breastfeeding is one of the best ways to shape the gut microbiota to thrive.

Dr. Emeran Mayer: No, this is correct. One thing I do want to mention also ... So our human genes change very slowly. It takes thousands of years before they change. The microbiota can change rapidly to any environmental change. So as long as the Yanomami live in the jungle, they will maintain that diverse and rich microbial ecosystem. When some of them have gone to Caracas to the capital and they become obese and they develop the same diseases that we have, the microbiome of these people rapidly changes in a way to adapt to this new lifestyle. There's even indications that within 48 hours it can adapt. What can't adapt is our gut and our immune system and our metabolic system.

So you get this mismatch between the microbes that were ideally adapted to that original lifestyle and to the original human makeup of these people. When they go into a different environment, the microbes rapidly adapt. Our genes do not adapt, this big mismatch, which leads to immune activation and all these chronic diseases.

Exploring Neurotransmitters That Are Used in Gut-Brain Communication

Dr. Greg Kelly: Wow. Okay. Well, we had touched a bit on microbe speak and you had mentioned that they were speaking between themselves long before our brain reducing these compounds. So can we talk a bit about some of these compounds that are used for the gut microbiome brain communication?

Dr. Emeran Mayer: Yes. There's obviously thousands of metabolites. So when we look at this like an untargeted metabolite analysis will give thousands of compounds, many of which we don't know what they do. So research has focused on the ones that have homology with human neurotransmitters, for example. There's tryptophan, there's serotonin, there's the indoles, there's GABA, this inhibitory neurotransmitter. So there's many substances that are almost identical to the human neurotransmitters that are produced in the gut.

If these compounds or how many of these compounds make it to the brain is questionable, particularly, do they make it to the brain in a concentration that's required to stimulate the receptor systems for these compounds in the brain? They do act locally in the gut on the enteric nervous system, which is in some ways also homologous to our central nervous system, and they can influence contractions, secretions, all the gut functions.

They can also communicate on sensory nerve fibers of the vagus nerve, which goes down to the gut, innovates different cell types in the gut that contain hormones like the satiety hormones. The vagus nerve is always in contact with them. They also innovate cells, the main storage houses or factories for serotonin. The vagus nerve is right there and has receptors. When these hormonal cells release their content, it acts on the vagus nerve on different branches of vagus nerve, which then are carried up into the brain stem high up into the brain.

There's an active field of research, for example, how these complicated vagal signaling really influences functions at the brain stem level and then high up into the cortical system. It's not that one substance really causes one particular emotion. It's a simplistic way of saying it. It's always, in this area, multiple components interact with each other to create some pattern which then results in a particular brain response.

Dr. Greg Kelly: Sorry to interrupt. I think of it was Candace Pert, had the molecules of emotion or however, but the way I often interpreted that was it was like a soup or stew. There was all these together and that particular recipe was going to create a response. So thinking only of serotonin or only one ingredient in the soup is maybe misplaced. It's the whole meal of all these interacting things.

Dr. Emeran Mayer: There are situations particularly right now with the new medications for type two diabetes that also they're being used primarily for weight loss that essentially mimics the signals that come from these gut cells containing satiety hormones. So the satiety hormones in the gut, their release is greatly influenced by the microbes, by the metabolites, by short-term fatty acids, by secondary bile acids. So they have a big say in that, how much of that satiety signal reaches the brain.

So in our society, obviously, we're after patentable targets and mechanisms. So this particular mechanism, obviously, is quite dominant. These new drugs seem to be working well without many side effects, at least at the moment. So that's a little bit of an exception that some molecules dominate other influences, but in general, I think it's a combinatorial way of communicating that you don't use one messenger.

Dr. Greg Kelly: Just for our audience, the satiety drugs that Dr. Mayer is speaking of, I believe would be the GLP-1 agonist that have been widely now starting to be embraced for obesity management. So the other thing I thought that ... One of your studies, it was ... I'll read the title so our audience will know it, but Cognitive Behavioral Therapy for Irritable Bowel Syndrome Induces Bidirectional Alterations in the Brain-Gut Microbiome Axis associated with Gastrointestinal Symptom Improvement. So I'd like to talk a little bit about that, but serotonin was one of the things that I believe in that study predicted the response to the cognitive behavioral therapy, and by that I mean the serotonin the gut microbiota was making.

A Study: Brain-Gut Microbiome Axis Associated With Gastrointestinal Symptom Improvement

Dr. Emeran Mayer: That was an interesting study because it ... So we looked at brain mechanisms, we looked at subjective symptoms, and we looked at the gut microbiome. So cognitive behavioral therapy, we know it influences the brain. It doesn't influence directly the gut microbes, obviously. So both the response of the brain to cognitive behavioral therapy could be influenced by the exposure to microbial signals, so that could predict who will respond. Not everybody responded to this therapy.

When we compared the responders with the non-responders, there were certain microbial features, including the serotonin levels that were greater in the responders that predicted a responder status. Then there was also an interesting thing. When we looked at the responders, their microbial composition changed with successful cognitive behavioral therapy. So there was this bidirectional signals. We thought this would really be a long sought after causal relationship that gives you the causal relationship between microbes and the brain.

It gave us partially. We really thought that this influence was in a bidirectional way, but it definitely was a proof of concept that if you change something at the brain level, it will affect or the response to that is predicted by the gut microbiome. Also, if you respond to it, your microbes will change. Not only the brain will change, but also your microbes will change.

It's the first wave. Another study ongoing that hopefully will clarify this further, but it's these attempts to really develop translationally relevant or relevant translations of the many mechanistic animal studies that we have. So most impressive research comes out of these mouse studies where you can manipulate everything from the homogeneity of the mice that are being examined to the environment, to the food, to the exposure to the stressor or to some interventions. So all these things we can't really do in humans. So it's been very difficult to actually translate the findings that are so intriguing and so many people have jumped ahead and said, "Okay. When one of these mouse studies comes out, we can say, okay, the microbiome plays significant role in autism spectrum."

At this point, this is mainly determined from these mouse studies and this will change over time. I think it's also a funding situation. A lot more money goes into these animal studies than into human studies. The human studies, because you need large number of subjects, are much more expensive to do than mouse studies where can see an effect on very small sample size.

Dr. Greg Kelly: I think the other thing too that complicates this field is that, one, the brain is crazy complicated, but if we start talking about the gut microbiota, I think you mentioned in your book, there's roughly a thousand different species of gut bacteria that most of us will have, and they're making, as you just mentioned, tens of thousands, if not hundreds of thousands of metabolites, including all the neurotransmitters that our audience would've heard of, the serotonins, the GABA, the dopamine, acetylcholine, but all kinds of other things that are intermediate between that.

All of this is constantly bidirectionally, as you just mentioned in your study. You change something in the brain, it changes then the macrobiotic portfolio in the gut, so to speak, but the metabolites as well, you change something there, it also shapes the brain. So it just makes it ... I can't even imagine how complicated to come up with things other than saying, "Okay. We see this pattern and this pattern gives us this thing that we may then infer," but I think often what I see in influencers are that generally is they'll see something and oversimplify it to the point where it's lost really all of its predictive value.

Dr. Emeran Mayer: This is a big problem in this field. I didn't know this being completely isolated in my scientific world and clinical world, but ever since I've expanded into the more public domain and the social media, you encounter what a lot of the influencers do. As I said, they pick one study published in Nature in a mouse model or in a zebrafish and expanded inappropriately to a human conclusion, which is very exciting, and that this is what people would like to read, but it's just not the way that we gain further knowledge and really develop actionable interventions.

Dr. Greg Kelly: Well, I guess going back to my language analogy, it's not that there's 10 different languages that the gut microbiome is speaking. It's dialects within dialects, within languages that shifts as soon as we change our environment. So I think I tend to try to think in complex systems like an ecosystem, we'll hopefully talk a bit more about that, but the nice thing about thinking in that systems approach, you don't have to micromanage a system to get it to respond well. In many ways, it's making sure it has the right resources and leaving alone to do its job. It'll figure out a lot of the rest.

I think that's what you mentioned in the early work with shaping our gut microbiota. That gives us whatever our most unique ecosystem and the one we're probably going to be best adapted to. If we do a lot of things that indigenous people would've done to thrive in their world, it'll set our gut ecosystem up to thrive even in our world.

How to Setup Our Gut Ecosystem to Thrive

Dr. Emeran Mayer: The thing is if you could go back and, obviously, it's not never going to happen, but if you could go back, and there've been a few examples of anthropologists who lived with the Yanomami, one actually, forgot his name, married a Yanomami woman and lived there and had children and lived with them for a while. Then most likely, his gut microbes adapted to that lifestyle, but the issue is there's also this extinction of strains and species that has happened in our world.

So for this anthropologist, my guess, and I don't know if he ever did his microbiome analysis, that he didn't even have some of the strains anymore because he had grown up in, I think, somewhere in the US, forgot which city, but growing up and being born and having gone through all this, well, we talked about this early programming, he didn't even have a lot of these microbes anymore that Yanomami had. So even for him living this lifestyle would not restore a Yanomami-type microbiome because it just doesn't have all the players.

Dr. Greg Kelly: I think my understanding is that like any ecosystem, once the organisms have staked out their niche, they're hard to displace. They've adjusted to that. They both will compete for the space and the food supply. So it's hard for then a new thing to take up residents there.

Dr. Emeran Mayer: It's a phenomenon called colonization resistance, which is a good thing, obviously, because otherwise, our microbiome would constantly change when we travel, whatever. On the other hand, it's become a major obstacle with these attempts to do fecal microbial transplants for human diseases. So that approach works well. As you know for C. difficile colitis, most of the native ecosystem has been wiped out. So there's no colonization resistance left, but it doesn't work for most of the other diseases where it's been tried because even though these diseases may have a compromised microbiome, it's still a pretty stable ecosystem that will not let others come in and take over.

Dr. Greg Kelly: Well, one of the things that I wanted to make sure we covered because when I was in practice, I had somewhat more of a mind-body slant to how I saw things. One of the things that I really appreciated about your book is it seemed like in your experience having worked with many patients over the years, that you had evolved to a similar, maybe already had it, but I wanted to just give a quote for our audience and then use that to piggyback into something.
So the quote that caught my eye was, "I've seen many patients with complex, seemingly unexplainable symptoms, and one of the important lessons I've learned is to listen to their stories." So I was wondering if you could share a bit more about that because the stories patients told me when I was in practice often were incredible clues to help them improve their situation.

The Science Behind the Mind-Gut Connection

Dr. Emeran Mayer: I would say I've been incredibly thankful to my patients for providing me this information that basically has been dismissed by many of my colleagues that do not have that perspective. Some of these stories seem outlandish that from a typical medical perspective, you wouldn't think this makes any sense, but some simple things. For example, this question that I've always used, "Have you had a happy childhood?" which so many of my colleagues think they don't want to get into early life experiences because it gets into sexual abuse and they don't know how to deal with it. Sexual abuse is a very small portion of these early life experiences.

If you ask that non-compromising question, "Have you had a happy childhood?" I would say two-thirds of my patients, they either would give an answer right away or they would think for a minute and say, "Actually, when I think about it, no, I did not." Then that opens up stories and situations that we know in the meantime from research play an important role, also things about what's going on in their current relationship, in their current lives, which is also a very common reason why people would make a decision to see me at this point. They're stuck with a frustrating work situation, difficulties with their partner, recently got divorced.

So there's many of these stories that would not come up in a typical medical history taking or it would just be on the social factors, but not really as a key to understand what's going on with this patient.

Another one, for example, a lot of people would come to me with this problem that they have food intolerances, that the symptoms flare up when they eat anything. Well, what I've learned is if you ask the right questions, often typical story ... I think I mentioned this in my book as well. So the business executive downtown LA that when he eats his lunch in his office where he knows where the bathroom is, he has absolutely no problems. He never has any GI side effects. If he has to go to a business meeting to a restaurant that he's not familiar with and he doesn't know where the bathroom is, he will develop his symptoms already driving to that restaurant.

So this fear of foods or this projection what may happen, it's also called catastrophizing or prediction error. There's many reasons for that, but this is a very important concept. For example, cognitive behavioral therapy deals with that prediction error. That gets rid of this exaggerated negative prediction of what's going to happen. So it's not the food sensitivity of that person, it's really the calculations that his brain makes what's going to happen in relation to food.

So these are just a couple of examples, but there's many that I would say have a repertoire of five to maximally 10 questions that lets me go through everything else without getting distracted, and I get a very good snapshot of what's going on, what's driving the symptoms of that patient.

Dr. Greg Kelly: I just think, at least from reading your book, but even now more talking to you in this conversation, it just strikes me like, "Wow, this is amazing. He's just not treating the symptoms, he's treating the person," and the person's stories and things that are then subsequently impacting it. So that's brilliant.

Dr. Emeran Mayer: Some of these stories, I have to say, I guess as a physician you're not supposed to really get involved emotionally, but I've heard some of the most amazing stories from patients that I wish they had written them all down, but could write a book about that. I selected a few for the Mind-Gut Connection. Then what happened after that, new patients came to me with the book in hand and they would say, "I'm patient so-and-so on page 55 of your book. Can you tell me more about it?" So that became a very typical scenario.

How Emotions Impact Gut Microbiota

Dr. Greg Kelly: Good. I think just for our audience, the main key thing, at least, I took away from your book was just, again, this idea that we could store emotions in our gut almost from early life experiences, maybe more recent things ongoing now, and that when we often think of emotions, we're thinking of our heart racing and other things, but anything we're feeling, our gut microbiota is feeling because we share our common language.

Dr. Emeran Mayer: That topic is also a fascinating topic. There's two prominent people that have influenced my thinking a lot, and I respect them tremendously, Antonio Damasio and Bart Craig, a PhD scientist who spent his entire career on the biology of emotions and regions in the brain, the circuits in the brain. So the concept that came out of this is that every emotional experience has two components. One is the sensing, the emotional feeling, conscious awareness, and the other one is the emotion. Emotion means movement or the action that your body does, your autonomic nervous system implements.

So every time you have an emotion, you have that emotional, this autonomic nervous system part to it, which essentially sends down signals to the gut, to other organs as well, to the heart, but the gut is particularly interesting in this respect, and in the gut, the microbes. So the microbes get that signal as well. We know that, for example, one autonomic nervous system mediator neurotransmitter, norepinephrine, can act on microbes directly, changing their gene expression, their behavior. So every time you have this emotion, not only do you change your gut function and the environment in which the microbes live in, but you also directly talk to the microbes.

Then the gut and the microbes with the metabolites send signals back to the brain either through the vagus nerve or through the circulation. That combined experience, the emotion, the action part, and the emotional feeling part, that's for both of these investigators and myself as well, believe that information is stored in these video clips in the brain or within the brain-gut system. Whenever you make a decision later based on your gut feelings, your brain somehow can access that information instantaneously as opposed to making a rational decision using your prefrontal cortex, which is a much slower process.

Now, that theory has not been proven experimentally. I'm not exactly sure how you would do it in humans, but I think it makes a lot of sense and it's obviously compatible with what we currently think about computers and rapid access to information without a slow system like a prefrontal cortex. What our modern computers and AI is doing is much more similar, I think, to this biological rapid access to stored information. The database of that is vast, starts probably during delivery. The first experiences of the baby's brain and microbiome are probably stored there already.

Dr. Greg Kelly: I know one of the things you touched on, and I think the field is seeing more and more of this, is that not only then can our emotions shape the gut and our responses, but they may be influencing, maybe not causing, but subtly nudging us in some of our behaviors. Could you talk a bit more about some of the behaviors? I know a lot of it's based on animals, but the gut microbiota seems to really strongly influence.

Dr. Emeran Mayer: With the behaviors, this is one of those areas where it's hard to really find the correct translation because these experimental setups are so focused on ... They isolate everything else except that observed behavior. There's so many other things that happen in a human situation like that and so many different influences from memory and from genetics. So there's one example, coming back to the GLP-1, to the satiety hormone. So as I said, the microbes play a big role in influencing the release of that hormone, and that hormone, obviously, shuts down our hunger feelings and changes the behavior, you stop eating. So that's a good example where that mechanism is pretty strongly maintained.

With the other one, the appetite hormone ghrelin, I've followed that area as well. If ghrelin release is in any way influenced by microbes, wouldn't surprise me. More complex behavior like the fight and flight response, I don't know if it would make sense for the microbes to play a role in this because that fight and flight response is triggered in response to external influences. So it makes much more sense that the brain takes over that part of it.

Complex emotions, anger, fear, love, affection, I would not be surprised if there's a role of the microbes, which we currently have not ... Very difficult experiments to do in humans as you can imagine, but I would not be surprised that ... There's a connection. People have written about this. So food intake and social connections, so when humans discovered a fire and developed cooking, it was always a communal affair, which is still present in many Mediterranean countries, and that's part of the health of that diet. So this interaction of these social influences of feeling well in a social setting and reinforcing that social behavior, it's quite possible.

I think that microbes do this in some form or other. You could almost, say, speculate. People that go on a Mediterranean diet, largely plant-based, that they are more prone to have these social behaviors than carnivores, for example. That's a pure speculation, but it would make sense. There's clearly, in evolutionary terms, a link between social behavior, food intake, and the microbial composition in that setting.

Dr. Greg Kelly: You had mentioned earlier, one, we know that what we eat has a drastic ability to change the ecosystem. They got ecosystem. You've mentioned a couple times during this conversation were things in the environment. So it would make sense that shared food, shared environment, we would be maybe not speaking the exact same microbiome language, but it would be more common and so that it would bring us closer together. So I think-

Dr. Emeran Mayer: Coming back again to the Yanomami, it's a very social lifestyle, always the family extremely close ties. They eat together. The fathers play with their infants. To what degree that is influenced by their unique microbiome that is so diverse and rich and has players in it that we don't have anymore? If you ask the likelihood of that, I would say it's more likely than not that this plays a role.

Dr. Greg Kelly: Good. Now, a couple things I wanted to get to before we run out of time. One is I've seen a few different people in your field. It's more speculation, but as an example, if we fed our gut microbiota more resistant starch, one, we would expect that the populations that can consume that and then the ones that can be cross-fed because of them would grow in abundance, and that then they may actually make us crave more resistant starch, again, through that bidirectional. Is there growing support for that type of idea that the gut microbiota strongly may influence foods that we would crave, but specifically to directly feed them?

Dr. Emeran Mayer: This was brought up in a review article where somebody received a lot of attention and it was really mainly speculative, I would say this. I think there's some animal data from flies, from an animal, a fly. I've not seen this really corroborated, but certainly, that, again, would make sense. So with a healthy diet, you build an ecosystem. As you said, it's different experts that break down the food and then the next level that process the food, that initial microbes, the keystone species have pre-processed, and that such a diverse microsystem would then crave for the kind of food to maintain it.

Unfortunately, when you look at what has happened in the American diet world, that's really not happened. So if anything, we're craving for food that's genetically programmed, like high caloric density food, sugar and fat. I'm not sure. I think this is more or less, say, genetically programmed phenomenon. Even if the microbes don't like it and they don't like it because they decrease in their diversity and all kinds of diseases develop, I don't think they can override that genetic drive that when you see something sugary, your rational mind shuts off because the basic evolutionary conserved instinct to get as much as you can when you can override it.

The Effects of Diet on Gut Health and its Implications For Our Mental and Emotional States

Dr. Greg Kelly: Good. Well, in the time we have left, I wanted to focus more now on translational. You've had a lot of experience working with people. I know in your book there was certain foods in the gut health or Gut-Mind Connection that you mentioned that we might want to consider consuming glass or avoiding. Can you talk a bit about some of those foods or food additives in your experience that might not be great ideas for us?

Dr. Emeran Mayer: So this has become somewhat generally accepted knowledge now that a Mediterranean style, traditional Mediterranean style diet is optimal for its benefits, not just for a healthy individual, but also in terms of being partially therapeutic for many of these brain-gut microbiome diseases.

So there's really nothing magic about this diet. It's 75% plant-based. The plants and the vegetables and the fruit should be composed of a large variety of foods, not just eating tomatoes, but there's also the other component that comes from the fruits, the polyphenols, these large molecular structures that in the past have been referred to as antioxidants, but that's actually the least part that they do in terms of their health promotion. They also act as prebiotics because they can't be absorbed intact and the microbes both feed on them, but also transform them into smaller molecules that are then absorbed and go through have health benefits throughout the body, brain, and heart, which has been confirmed in human studies.

There's also all the nuts and seeds, essentially also a component that has a lot of these polyphenols, but also the healthy fatty acids. Then there's the olive oil, the extra virgin olive oil, also rich in polyphenols. To what degree each of these components is essential to create this health benefit of this dietary style or pattern? I don't think it really has been determined. It's similar to what we talked about earlier. It's probably a combinatorial effect of all of these in addition to the intense social interactions that the Mediterranean countries have around food intake, which maybe ... There's a lot of talk recent recently about social isolation, the pandemic of social isolation in the US and what health consequences that has.

So the Mediterranean lifestyle is a way to provide both these social interactions, and the foods that we know have multiple aspects of health promotion. It's not the modern Italian diet. So if you think if you go to an Italian restaurant every week that that is necessarily a health-promoting activity because the modern Italian diet and Greek diet and French diet have all moved away from a very small intake of red meat and have moved much more to the American style, high fat, high red meat, higher processed food style. So really, if you look at the elements that I mentioned, and you can find similar elements, for example, in traditional Asian cuisines, probably almost identical in their effectiveness. So I would say it's a very simple guideline.

So I've just recently written this recipe book. It's not my forte to write recipe books as an investigator, but I've been asked so many times by patients. It's a very simple way of highlighting these components and then the practical application, what kind of food should you eat in order to get these components that I told you. It's not rocket science. The science in this field is rocket science, but to apply it to maximize your health benefits is not rocket science. I think we know a lot about this now.

Dr. Greg Kelly: One of the things I liked about part of your emphasis in the book, that ecological thinking in terms of the gut ecosystem. So that's how I tend to think of it too. Let's think like a ecologist or think like a farmer maybe might be a simpler analogy, but you mentioned keystone species. So I think most of our audience would know in something like Yellowstone National Park where they reintroduce the wolves, the keystone species that completely reshaped the ecosystem over several years. I know in your field I see that idea of keystone species come out over and over again that, yes, there's a thousand different species, but there's some that are the keystone species and the food they thrive on may be more represented in a traditional Mediterranean diet because of the prebiotic-like compounds or prebiotic compounds, but also the polyphenols that I think of as more prebiotic-like, but also are things that some keystone species thrive on.

Dr. Emeran Mayer: Absolutely. This is what makes the practical application so easy that you just have to provide these kind of foods and the system will respond to it. You don't have to engineer one particular microbe. You say, "Okay. I don't have enough of that particular species," or that if you provide the right food, that species, if it's still there, if it's extinct already, obviously, it won't come back, but there's something, for example, with a recent study with a probiotic intervention where they found fermented foods. So people that ate a lot of fermented foods, they found that they showed the greatest effect on diversity and health of the ecosystem and decrease of inflammatory markers.

The most interesting part of this was that the microbes that were now detected in the gut of these people that ate more fermented food were not the microbes that came with the fermented food, but that food intake promoted the appearance of microbes that were not there before. The investigators could not answer the question where they came from, were they present in very low amounts already in the gut or did they come from the outside, and did this food intervention, dietary intervention facilitate the migration of these microbes into the gut. So that's a good example when you do a relatively general intervention that it would facilitate the growth of the ecosystem and its diversity and it's benefit.

I think that's probably true about a lot of things. Then there are differences. I'm very interested in this ecology concept as well. I just come back from a trip to a meeting in Sao Paolo and they organized a one-eek excursion to this Pantanal area of Brazil in the middle of Southern Brazil. This is an area with the highest diversity of life on the planet, but it's also heavily contested by agricultural interests to turn it into corn and soy production monocultures.

So you see when you drive there, only separate by maybe half a mile, the jungle on one side and these endless fields of corn. Obviously in that corn field, there's nothing left of any ecosystem because it's not only the monoculture, it's also they're being sprayed with glyphosate and herbicides and pesticides. So any diversity has been eliminated. Then you go into the jungle site where some of these farmers actually develop ecotourism, and you see this amazing variety of animals from jaguars to caimans, both in the water and in the air, the birds, which is phenomenal. So that gives a good explanation of these extremes. I don't think our guts are in the condition as extreme as these monocultures of corn, but it's in the direction like that that we have been moving both in our outside ecology, macro ecology, and also in our internal ecology.

Dr. Greg Kelly: Well, I think that's a great place to leave it off. Again, thank you for being here and for our audience. A couple of the things I will personally take away is just this understanding that our gut's flexible. It's speaking with our brain. The exact language mine's speaking might be slightly different than yours, but we're sharing the same words, neurotransmitters, and that some of the things that we can do to make a big impact are both operating on the brain end like you said in some of the stories you shared, but then also paying attention to what we eat because we need nourishment, but so does our gut microbiota. So with that, if there's anything else you'd like to share with our audience, Dr. Mayer.

Dr. Emeran Mayer: So just want to mention a couple of things, which make me very excited. I have to say I've really been as excited in my career. So there's three things that are happening in the next couple of months. So one is, as I said, we're coming out with this recipe book called The Interconnected Plate. The second one is the paperback version of The Mind-Gut Connection comes out on a new title, The Mind-Gut Immune Connection, and really presenting as a sequel to the first one because some people ... This concept of the mind is still, I think, the most interesting to people.

The third one is I'm also in the early stages of developing a masterclass on this topic. So I've been invited to be part of that. So very exciting. I think there's going to ... Oh, forgot the last thing. So there will also be a documentary, a PBS documentary in December on the same topic. So this year is definitely the year to get the message out to the lay public.

Dr. Greg Kelly: That's fantastic. For our audience, what's the best way if they want to follow you, learn more about what you're doing?

Dr. Emeran Mayer: Really, the simplest way is to go to my website, emeranmayer.com, and that gives you options, sign up for the newsletter. There's taking look at the whole library of podcasts and Instagram posts and our newsletter. So that's very the simplest way of doing it.

Dr. Greg Kelly: Great. For the listeners, I know we're launching a book club here come up shortly. I'm not sure where this will air in that, but yours is the second book that we're covering.

Dr. Emeran Mayer: Oh, great.

Dr. Greg Kelly: So we'll be also sharing it with our audience that way. So again, thank you for being with us today.

Dr. Emeran Mayer: Thank you. It was a great conversation. Really enjoyed it.