Full episode transcript (beware of typos!) below:
Nick Jikomes
Professor Emeran Mayer, thank you for joining me.
Emeran Mayer 2:32
Well, thanks. Thanks for inviting me. It's a pleasure to be on your podcast.
Nick Jikomes 2:36
Yeah, we are excited to have you this is going to be a really interesting set of topics, I think, can you tell everyone just to start, who you are, what you do and what your new book is about?
Emeran Mayer 2:48
So, um, I've been a professor at UCLA for many years, decades. And I'm a gastroenterologist by training and a neuroscientist in my research part of sort of combined gastroenterology with neuroscience in studying the brain gut interactions of brain gut microbiome interactions. And yeah, so I've been interested in this topic my entire career, initially, prior to the microbiome science exploding. But this is just I've just added that component not to my long standing research and concepts about the importance of that system. So yeah, and I've just just about to publish my second book, the gut immune connection. The first one was the mind gut connection, which was sort of at the beginning of, of our interest in linking the microbiome with the brain and the nervous system and psychiatric diseases. Now, the new book is, takes it's a significant step further, I mean, a lot has happened in those five years in terms of the science goes, but also I take, secrete this concept of the the One Health concept that essentially the the health of our, of our gut, our gut microbiome, our brain is part of the health of the soil microbiome, the health of the plants and ultimately the health of the planet. So it takes a much more global perspective on this.
Nick Jikomes 4:45
Yeah, I think this is this is a fascinating area that I've been hearing a lot more coverage of in the media and in the research world. This idea that the health of our gut and our microbiome is linked to what our immune system is doing is linked to what our brain doing. And it seems like a fascinating area that I actually don't know too much about. One of the basic things I wanted to ask you about in the beginning, has to do with setting up the problem in some sense. So it certainly seems like people are basically getting unhealthier with time, when you look at things like obesity rates, and different metabolic diseases like diabetes, for example. It seems like these things are going up. And I'm pretty sure that they've been going up for a long time. But can you give us a sense for some of the statistics here? How, how have things like obesity and diabetes and related issues changed over the past few decades? And what kind of healthcare burden is actually there right now?
Emeran Mayer 5:47
Yeah, so you have to be correct. I mean, we, as a population, we have gotten sicker. The what the health care system, or really the disease care system is done. It's, it's been very successful in keeping us from dying. So our life expectancy and longevity, you know, has been increasing, but only with the help of massive interventions to have, you know, pharmaceuticals, and seems now you know, with metabolic diseases that almost 100% of men over 60, you know, should be on a statin based on the criteria that have been established. So it's almost become the norm, that there were metabolically unhealthy when it came when we age. And sort of people have been obsessed, really, with the longevity aspect, you know, it's always been celebrated. That longevity has increased our society, everybody now has friends or relatives who have lived in their hundreds, which was, you know, when I grew up, kind of unthinkable, really. But if you, if you really look at the cost of that accomplishment, it's, it's tremendous. And it's, you know, it means good business for the pharmaceutical industry, and also for the healthcare industry, which is, as I said, it's a disease care industry very good in, in keeping people alive and doing all kinds of ever increasing, increasingly expensive tests. But ultimately, it's not making us healthier, and another players vote to, I would say, physical health and, and mental health. So we have a, you know, a mental health epidemic with, you know, increasing suicide rates, amongst younger people. increase in depression, depression is projected to be one of the main with the main health issue in the next couple of decades. Substance abuse, addiction is is obviously, more people than most other diseases. And then we have this, this epidemic of what's been called these chronic non infectious diseases, which include, you know, all the metabolic diseases and the consequences cardiovascular disease, some forms of cancer, like colon cancer, neurodegenerative diseases, and those, those diseases are, it's kind of interesting, they're really not separate from each other. You know, we we, in the medical system, we tried to divide them up into all these categories that sent people are sent to different experts. You know, for colon cancer, you go to the gastroenterologist for Alzheimer's disease, you go to a to a neurologist. But in reality, when you look at it, I mean, they're all linked together. So the the metabolic derangements that have happened. And I would say, you could say in the last, you know, plus minus 75 years since World War Two really does, if you look at the curves have been an increase in in all these diseases, some faster than others, some of the most rapid ones. And part of that increase has been influenced by the changing definition. So like autism spectrum, for example, has had a dramatic increase in the last, you know, 4050 years, but it also has undergone different definitions and classification. So it's hard to say what the actual rate of increases and some of these diseases have increased, like Parkinson's and Alzheimer's disease, the sort of blamed on the issue increasing age and increasing life expectancy. But in reality, you know, it's not a necessary consequence of getting older that you have an increased risk for Alzheimer's disease. It's, it's, again, the the metabolic arrangements that people live with, that makes that more likely that more and more people develop those diseases. And yeah, I would say, you know, it's an epidemic of chronic diseases that we are experiencing, it's this has been overshadowed clearly by the pandemic, and much more acute and,
you know, visible problem that we have been incredibly the medical system incredibly effective and coming up with a solution with with the vaccinations. But again, I mean, those, those pandemics, so in some ways you can link them to the, to this chronic disease epidemic as well, because people that have any of those chronic diseases have been more vulnerable to develop a more severe course of the COVID-19 infection and are more likely to develop the, like the long COVID complication. And a disproportionate number of people did have more these comorbid conditions, suitable comorbid conditions, which I really, you know, is hiding the fact that the this this network of interconnected diseases, and the reason it's important is because the reason these diseases are interconnected with each other, his dramatic change in lifestyle that has occurred since World War Two, and particularly the diet, you know, so something not just diet is interactions of other factors as well, like decreased exercise, you know, chemicals in our environment, and many other things. But I think diet has received the most attention in this and, you know, we can talk about this, how that links, these increasing diseases with each other, but also, you know, with, with our lifestyle, so,
Nick Jikomes 12:32
so, so there's this chronic disease epidemic, and there's many different chronic diseases that have been going up over time. It sounds to me that there's a few different things I'm hearing here, it's almost like a perfect storm of various things where our lifestyles are, in general, leading to an increase in various chronic diseases, that's obviously bad, because nobody wants a disease of any kind. But a chronic disease is also one, by definition that you're going to be living with for a long time. And it seems to me the, there's also a problem there, which is, these things are sort of slowly developing. So they're almost less noticeable as an epidemic. It's not something like COVID, where, you know, one day, we all of a sudden, more or less have this brand new problem that was right in front of us, but the sort of chronic diseases have slowly crept up steadily over time. And in some ways, you almost don't even notice that we're in the middle of such an epidemic
Emeran Mayer 13:31
Sandin, you know, and end up being normalized, like, you know, you notice, for example, so, you know, with with obesity, for example, you know, if you look at images from the, you know, from the from the 50s in the US and images today, you know, it's it's obviously apparent that people the averages has greatly increased the in obesity rates, and it's been normalized, because, you know, the media want to want to be want to send a message that it's, they don't want to exclude anybody with obesity. So like, now in the news, in the advertisements, you always see obese people, you know, as even with the pharmaceutical ads, you know, that promote, like statins or medications for high blood pressure, or blood lipids, or diabetes. You don't see you know, slim people that are always obese, and it's, it's almost show like the new normal and I think it's a very dangerous trend. You know, the media want to be politically correct. You don't want to discriminate anybody with obesity. I don't care about the cosmetic aspect of obesity. As a physician and scientists, I care about the metabolic implications and that should not be normalized, you know, It's just not.
Nick Jikomes 15:02
So I actually have, I have heard people in the media make claims, in some cases directly that, you know, being overweight or obese is not actually unhealthy. So can I just want you to be very clear, is that true at all.
Emeran Mayer 15:22
And it's, it's not true. I mean, there's not 100% link between obesity and metabolic disease. So example. Many Asian populations like in China, you know, I have people who have metabolic syndrome, but are not obese. And that's a particularly dangerous situation, because you don't even have any external warning signals, something's going wrong. But in general, I think in, in the US population. And I often say this, when I give a talk, you know, somewhere in the country, we're like, in the middle of the country, where you see more obese people than on the coasts, I often tell the audience, you know, 40%, in this room probably have a metabolic disturbance. Maybe not full blown metabolic syndrome, but you're on the way towards that. And with all its implications for higher risk of chronic disease, so I would say, in Western populations in the US, there's just there's a pretty good correlation between obesity, definitely, once it gets to, I mean, overweight is a sort of a heterogeneous group of people, as many healthy people that are somewhat overweight. But in general, people who develop like, type two diabetes, or metabolic syndrome are overweight and obese.
Nick Jikomes 16:50
One of the things I want to talk about upfront too, is hunger and food intake. It's simultaneously something that everyone's very familiar with, because we all get hungry, and we all eat, but at the same time, there's a lot more going on there than probably meets the eye for most people. So as a neuroscientist, what is hunger at a high level? And how is it actually regulated by certain key parts of the brain and body in a normal, healthy individual?
Emeran Mayer 17:19
Yes, so hunger is a sensation, you know, a basic emotion that makes sure that we fulfill the metabolic needs of the body. And normally this has been is fairly tightly regulated. That you know, there's there's a, there's a release of a hormone in the stomach called ghrelin, that stimulates appetite, and makes people want to eat, it's really the only hormone produced in the GI tract, it stimulates appetite, all the other ones are actually counterregulatory. So they create satiety to make you stop eating. There's also insulin, you know, increase insulin levels will stimulate appetite or even craving. But in terms of if you say with a with a GI tract, so grayling gets to the brain gets into reward areas stimulates the release of dopamine, which is a motivational neurotransmitter, and that stimulates ingestive behavior. In a normal situation, a healthy individual that triggers that, you know, food intake, food intake, will go down through this into the small intestine, into large intestine and in the, you know, so the end of the small intestine. And then there's a series of cells in the GI tract that have hormones that are called anorexigenic hormones. So they, they turn off the appetite and the hunger and they're stored there in you know, what we call endocrine cells and through endocrine cells in the in the gut, and the being released when they come in contact with food that you ingest. They get into the bloodstream but also act on the vagus nerve and then send a signal to the brain and they counteract the the orexigenic signals like grehlin or insulin. So it's it's an it's a feedback loop that normally works really well. So if you've, you know, have a associating meals, you appetite will turn off. And what we have learned that these cells in the gut that produce these anorexigenic signals is satiety signals they have receptors on the surface that respond to signals from the microbes, such as, you know, short chain fatty acids or secondary bile acids and several other metabolites. So the micros play a big role in this. And, you know, not by coincidence, changes in the microbial composition and abundance has been identified in people with obesity and people with, you know, what's been called food addiction. Essentially, what is craving for food becomes independent of the metabolic needs. So there's uncoupling between the metabolic needs of the body that need to need to be satiated. And appetite and craving is a hallmark of the current obesity epidemic.
Nick Jikomes 20:55
So it sounds like the gut and the brain communicate through multiple channels, one of them is through the nervous system directly. So something like the vagus nerve is directly connecting the central nervous system and the gut to determine you know, what's going on in the gut at any given moment. There's also an endocrine connection. So there's hormones that get released from the gut, into the bloodstream that go up to the brain. And in general, we can think about those as being either pro hunger or pro satiety signals. So something like ghrelin is basically going through the blood up to the brain and telling the brain okay, we need food orchestrate behavior accordingly. And then there's counteracting signals that do the opposite.
Emeran Mayer 21:40
Yeah, and then there's, you know, these, these inhibitory mechanisms that that normally would control a healthy food intake are compromised. A because, you know, microbes can play a role in in excessively stimulating these. notion said it's in not sufficiently stimulating these enter endocrine cells. But it's also a component which has to do with with democracy playing a role in generating this system wide immune activation, and these immune mediators have been shown to decrease the sensitivity of receptors for some of these satiety hormones. So not only is there an alteration at the gut level, and its interaction routine, microbial signals entered to come within cells. But there's also an alteration at the at the brain level in the hypothalamus, that these hypothalamic receptors do not respond as well, to the satiety hormones. So the
Nick Jikomes 22:59
microbiome can actually impact the immune system, it's not surprising that the immune system would be tied to the microbiome since our immune system is supposed to be basically communicating, detecting what microbes are doing in the body, but this can actually have a downstream impact on how our body's responding to its own hunger signals.
Emeran Mayer 23:19
Absolutely, and I think this is what sort of been evolving. So, this integrated relationship between you know, the diet that influences microbial composition, then the signaling of the microbes with our hormonal cells in the gut is tidy containing society, hormone containing cells, the interaction of the microbes with the immune system in the gut was 70% of the immune system of our immune system cells are located in the gut just microns away from you know, from from from the, from the microbes in the center of the gut. And, and then that that influencing our appetite and hunger regulating centers within in the hypothalamus and and kind of uncoupling So, one thing that happens you know, in a situation like food addictions are normally our craving for food and our behavior, motivated behavior to seek seek out, you know, pasty foods is, is is is always constrained by this natural barrier of the systems that we talked about. If it becomes uncoupled, then the, the cortical centers you know, basically become unrestrained and food intake is now driven by totally different motivations by you know, by memories of food and by All the stuff that we see in advertisements, which creates these images and memories that then drove her food intake not based on metabolic needs, but based on, you know, cortical, not on hypothalamic mechanisms, but on, on, you know, cortical and emotional centers within the brain.
Nick Jikomes 25:22
Is this the distinction between what they call homeostatic versus hedonic regulation?
Emeran Mayer 25:30
Yeah, absolutely. So that's a hallmark of, of food addiction. So some people have a problem calling this really an addiction. But I think it has many features, that this behavior that you can compare to, to other situations of substance abuse and addictive behavior. But this is one of the hallmarks that the hedonic component becomes dominant, and the homeostatic one is overridden by by these hedonic impulses.
Nick Jikomes 26:06
So in simple terms, food intake, that's regulated homeostatic Lee is sort of like the natural baseline way that hunger is regulated, you're eating because you actually feel hungry, because you actually have not eaten in a while, whereas the hedonic component is eating something, because you remember that it tastes really good, and you just want that pleasure on of eating it.
Emeran Mayer 26:29
Yeah, and a good example, I mean, you know, I, I've been on a lot of sort of mountaineering adventures, and, you know, like, long distance hiking, and would you notice that, you know, after a couple of days, you you, you switch completely to the homeostatic mechanism of food intake, because there's no possibility, like, you can't take all yours snacks and power bars to last you, you know, for four weeks on your hike. So you essentially, just eat for your homeostatic needs, and which is actually very little, you know, and, and you're not craving for food, you're, you're focused on your, on your hiking experience, and a physical performance. And even though you need more, you, you're burning more calories, you don't have that craving for food all the time, it just completely switches. And I think, what we, what we see in our modern world, it's the opposite, you know, that we, we spent so much time sitting in so many people in front of the TV for or in front of their iPhones, which is all time that, you know, does does not really require the or it's not influenced by the homeostatic needs of the body that the minimal that so anything that people do is what they see on the commercial. You know, they get up in the middle of evening TV and go to the fridge and eat something, not for homeostatic needs, but because they saw that appealing advertisement on TV so that that's a that's a good, you know, practical example.
Nick Jikomes 28:26
So backing up a little bit to the microbiome, what is the microbiome? Is it just the full set of microbes that live inside of us?
Emeran Mayer 28:37
It's the full set of microbes plus their genetic information, basically, that function. So if you want to be really strict with the definition, so the microbiota are the players, the individual microbes, and, you know, that includes bacterium and viruses and fungi, with the bacteria being the most. And then the other two groups, we haven't really studied that well. But all three groups of microorganisms interact with each other. The microbiome is if you ask is, you know, hundreds and millions of genetic information that microbes have, which essentially, is representative for the functional capabilities that they have many of which we don't, most of which we don't really understand yet. But so microbiome is both in the individual players, but also their products or their metabolites or their functions that they exert. And it's it's a very complex system. I think we're just really at the beginning of unraveling the complexity and as I mentioned, the interactions for example of viruses most of which are phages, that that feed on the microbes, so the the The relative abundances of microbes are partially influenced by your virome. But, you know, what, how many viruses and what type you have? And it's quite possible that, you know, quite likely actually, that in 510 years, we will focus primarily on these on these viruses, you know, as in terms of implicating them in in, in some of the diseases that right now are sort of counted as, as microbiome related, or is bacteria related?
Nick Jikomes 30:35
So what are some of the major examples of, say, components of our diet that are broken down not by our own cells, but by micro organisms? And then on the flip side of that, what are some examples of metabolites that these organisms are producing that are doing very impactful things in our own bodies?
Emeran Mayer 30:57
So, um, I mean, the main domain principle is that, you know, microbes. And I have to have to admit some, I'm not an expert on the Veyron. So I can tell you that exactly. You know, I mean, obviously, the viruses feed on the microbe. So they're not really clear news. But in general, we have this interaction of the food that we eat with the mic with the microbiome, it's the main influence. And it's the components in the food that that cannot be absorbed by our small intestine. But that go down to towards the end of the small intestine, the ileum, and into the colon, were then broken down or metabolized by microbes into smaller, you know, smaller components, short chain fatty acids, being sort of one of the most often talked about with these metabolites, because we know that they have a lot of beneficial effects on on the gut and, and on the body and on the immune system. And then there's another group of molecules called poly phenols. So very large. I mean, they used to get a lot of attention some time ago as antioxidants, because people found if you put these, these large molecules into test tubes, they haven't an antioxidant effect on cells on cultured cells. And, or if they're injected into into animals, the same thing. But in the meantime, we know that most of them just like fiber, is the two large molecules who don't have the mechanisms, the enzymes in the, in the proximal small intestine to break them down and absorb them. So they all go down. And microbes have the ability to break down these poly phenols into smaller components and phenolic compounds, which can then be absorbed. So both of these major plant based food components, the fiber and the poly phenols have sort of a similar function. So they, they escape our absorption, so they don't get shortcut into our metabolism. And they have a beneficial effect on the microbes on the composition on the diversity. But also, then the microbes turn them into molecules that are absorbable and have health benefits for us. The fiber of components, so at this point, better understood than many of these phenolic compounds. But there's pretty good evidence that you know, phenolic compounds, once absorbed play a role, either as antioxidants, but also other anti inflammatory functions like for, for example, at the at the brain level. So the main connection between, you know, food, the microbes, and the metabolites in in our health is sort of this, this chain of events. And I always say, you know, the healthiest diet is one that's essentially targeted at the microbes, if you see a little bit extreme to say that, but I think it's pretty correct, that if you only eat to the benefit of your microbes, you do the best thing for your body as at the same time.
Nick Jikomes 34:36
So basically, these microbes are breaking down stuff that we can absorb or break down on our own. And in so doing, that they produce compounds that we actually can absorb and, and use and can have benefits in different ways.
Emeran Mayer 34:50
Yeah, and and the way this developed an evolution, you know, fruit of our ancestors hunter gatherers. You know, was, was very high in these absorbable comfort components, you know, it was, it was certainly unprocessed, cooking became the first major way of processing food. Fermentation became another way of doing this. But our ancestors in order to get enough calories, they were totally relying on this mechanism on their microbes to break down these plant based foods and turn them into short chain fatty acids and provide energy for the for the body. Today, you know, we're in a very different situation, everything is ultra processed, everything gets rapidly absorbed in the first part of that small intestine to do a genome. And, you know, one of the one of the reasons for our obesity epidemic is exactly that, how the food has changed from something that originally that our bodies were specialized in breaking down, having broken down by the microbes, to something that's rapidly absorbed instantaneously, when we, you know, when we eat it, sugar is the best example, you know that a vast amount of our calories are, come from this rapidly absorbed sugar, not just sugar that we add to, you know, to our coffee, with our cereals, the sugar, that high fructose corn syrup, that's ubiquitous in our foods. So yeah, this completely changing, you know, the way we ingest from something that was originally, we developed this, this unique symbiosis with the microbes, to keep us alive and keep us fed, we've abandoned that system, and we've completely switched it to the other one, and now we are neglecting the, you know, the microbial ecosystem. With its own negative consequences,
Nick Jikomes 37:04
I actually didn't realize, I actually had not realized that about processed foods or processed food doesn't simply mean food that contains things that we don't find a nature or contain something artificial, it actually means that the food itself and what it does contain, is absorbed earlier on in the digestive process, much more so than what you know, our hunter gatherer ancestors would have been,
Emeran Mayer 37:29
absolutely take a good example, you know, that often maligned bread intake, you know, if, if you look at some of the you know, like the ancient cereals, it's now becoming popular again, certainly in Europe that you get combined these these breads made out of, you know, ancient cereals. And, and, and not from, from, from from the processed wheat. So, this is a good example of the, the original breads, which has so much fiber in them, because of these, these grains is, you know, ancient grains, that there was a lot of that red that goes to the microbes, you know, I don't know if we can say half of it or but, but then you take wonderbread, which is still advertised as being advertised on, on TV have recently seen this, it's amazing that this still happens. Hawaiian bread, which is white, totally devoid of any fiber, ultra processed spread, which will all be absorbed immediately when you when you need it, you know, and nothing goes further downstream.
Nick Jikomes 38:44
So it's fair to say, is it fair to say that highly processed food, when you eat highly processed food, you are effectively starving your microbiome? That's
Emeran Mayer 38:53
that's correctly said yeah, this is exactly that. And this is something that I think what we have seen in the last 75 years increasingly with, you know, with industrial food production, I mean, starting with the kind of seeds and plants that we use, so the potatoes, you know, are now optimized not based on their fiber content, like sweet potatoes that are essential part of the Okinawan healthy diet, which is a lot of fiber and goes down to the microbes to the French fried potatoes that are you know, just ideal for making French fries. And that is the mostly consumed form now, in the in the US, for example. So and there's many examples, that is a wide variety of, of grains and plants has been reduced dramatically based on the interests of you know, these these these big food products. As in companies that and that have conditioned the taste preferences of children. You know, and sort of this is still something I think we, we see now changes in this. So it's a good thing that people, everybody talks about gut health. And so, you know, fiber is becoming sort of a major topic of this conversation. But it starts really way upstream, it starts with the selection of, of seeds and plants that are being used to make the food that we, you know, that we consume. And I always see this, you know, when I travel in Europe, that then in some countries, they they've made this, they've gone back much faster, to using some of these old ingredients, much less selected, much less Ultra processed than, than in the US.
Nick Jikomes 41:03
So, you know, if you're eating, the diet that you're eating can influence the composition of your microbiome, if you're eating a bad diet, whatever Exactly. That means, that can have bad consequences for your microbiome. I want to talk about at least one more way that we negatively impact our microbiome, and then I want to switch to how we can actually build it back up, potentially. So I want to talk about antibiotics. Antibiotics are obviously much more prevalent today than they have been historically. So what is the effect of antibiotics that are common on our microbiome? And what do we know is going on there?
Emeran Mayer 41:41
Yeah, so antibiotics are given in this is very part of the problem. I mean, that definitely the most effective therapy that you know, modern medicine is ever developed. So millions of lives have been saved because of antibiotics. But the principle of antibiotics is that you did you declare war on a particular pathogen on a particular strain of a, of a microbe like Rico strain of E. coli, for example. But at the same time, being willing to take the collateral damage on all the other microbial strains that you have in your, in your in your gut. So it's a very, you know, is this were warfare, it would be cluster bombs on civilian areas, just as a catch one terrorists. So this is a comparison. And they had, they've had a detrimental effect, you know, what, in proportion to how much the excessive use of antibiotics, what negative effect they that this has had, compared to the poor diet, I couldn't give you a number for that. It's where the interaction but so the there the shocking numbers, you know, that the children by the age of two have received, received between five and 10 doses of broad spectrum antibiotics, generally? Well, for two reasons, generally, because of overly worried mothers that take their infants to to the pediatrician when they have a bad cold. And, you know, this is something has to be done, you know, might I need an antibiotic? I've seen this many times, you know, the mothers. I mean, friends have come to me, they can make a prescription for an antibiotic. The other one is
that, you know, we have used antibiotics, for example, during the whole day, is the time of delivery. So women get prophylactic antibiotics in the delivery room to prevent serious infections, which do happen in some women. But so life already starts for the infant coming out the birth canal, being exposed to antibiotics, because these antibiotics have affected the maternal microbiome, which first comes in contact with the with the infant. So yeah, antibiotics, particularly early in life, because the development or the the programming of the microbiome happens during the first three years of life. And it's obviously the worst time to use these broad spectrum antibiotics, you know, for, for for non indications. So, now these viral diseases obviously are affected by
Nick Jikomes 44:51
Yeah, no, I mean, I think we probably all have examples in our life. I certainly can think of some where, you know, someone has a cold which is caused by a virus and the To go to the doctor and demand an antibiotic, and they typically get it, just because it's probably irritating for the doctor to keep hearing it,
Emeran Mayer 45:07
it took me to get it. And what was also interesting is, you know, some kids get better, and it's free, more placebo effect. Because, you know, we do know that antibiotics do not affect viruses, you know. So, if you take an antibiotic and believe this is really powerful, you will, you will feel better, you know, there's no question. So.
Nick Jikomes 45:30
And I did want to say, you mentioned, the idea of the microbiome getting set up very early on, before birth and during birth, can you talk a little bit more about how that initial microbiome is normally established in a young child? And then also any, are there any clear links between antibiotics early in life alterations, the microbiome, and then you know, childhood obesity or other metabolic issues?
Emeran Mayer 45:58
Yeah, so this is a complicated topic, because this programming is quite complex. So it starts, I mean, you could almost go back to the situation, you know, before the child is born, because the microbiome of the mother will produce metabolites and signaling molecules and inflammatory substances that affect the developing fetus. So there's already an exposure to microbial to the microbial world. Even though the the the fetus is does not have its own microbiome has been controversial, but most likely not. It is already exposed to microbial products from from the from the mother, and that may play a big role in diseases like autism spectrum, you know, which starts really in utero, then when, when the infant is is born, it goes through the birth canal, with least still in the majority of women. And it comes in contact with a sort of a mixture of microbes from the the intestinal tract of the mother, you know, from from from the rectum and end of China. And that's the first inoculation of this sterile environment, still got the environment of the of the newborn. there that is influenced by we notice mainly from animal experiments, is influenced if the mother has taken antibiotic, because then that affects the mother's vaginal microbiome and the intestinal, but also, if the mother is chronically stressed, so there's fascinating studies that have shown that their chronic stress in in mice changes dimensional microbiome. And so the the newborn mice get inoculated by different microbial population then in non stressed mice. So the antibiotic exposure, the mother and the stress level of the mother have a major influence in this early inoculation, then it continues, so breast milk has molecules in it does human milk oligosaccharides it's another category of these molecules that are too big to be absorbed by the small intestine. And so in evolution, they were designed not for nutrition for the newborn, but targeted at at the microbiome, Edie evolving microbiome, these human milk oligosaccharides are influenced again, by the diet and the genetics of the mother. multiple connections, you know, between the mother and this, this development of the infant microbiome. So C sections which have become increasingly popular in some parts of the world, I think in Italy and Brazil, leading that trend, up to 60% of women, I think undergo C sections, C section deliveries. And that has been shown that you know, a C section delivered baby will have an increased risk for developing asthma for example, and, and obesity, even though the microbiome normalizes so if you take an infant that was born by C section and one by you know vaginally delivered after a year, their microbiome composition looks very similar. You know, there's sort of a dance, but the the programming that has happened during those during that First Year has occurred and it takes, for example, the immune system in a different direction. Because during that first year, it's not just the microbiome, it's also the immune system interaction with these microbes. So just the fact that, you know, after a year, we have the same you, you could trivialize it and say, it's not such a big deal, because, you know, after a year, both types of Davies are, you know, basically have the same microbiome, that that's not correct, because that year of altered microbial immune interaction will leave a memory and will leave a less competent immune system that manifests later in life, you know, with autoimmune diseases and, and allergies. And then, so the other one is, you know, formula feeding versus breastfeeding. I've sort of learned this, had had no idea about this. So in
100 years ago, you know, for wealthy people, women didn't want to breastfeed, and actually hired nannies to breastfeed the their, their their children. Or, you know, formula feeding did happen in many parts of Africa. So this was sold as a as a good substitute for, for breastfeeding. So that also leaves a big trace on a negative trace on the microbiome, because it did not get these molecules, these human milk oligosaccharides, they were essential in setting up the ecosystem of of the adult microbiome. So there's a lot of things that then we talked about the antibiotics that interfere with that process. And so yeah, it's it's something that has not, I think, has not received enough attention by pediatricians and by OB GYN physicians. And by young mothers, how important that early phase is. So it's not just, you know, getting enough nutrients to the baby, and calories. It's really nurturing the microbiome and optimizing this this programming face for later in life. And all these factors combined, that we have interfered with in the modern world, probably play a big role in our current health problems, from obesity to autoimmune disease, this too. So the autoimmune disease is, you know, in addition to all the metabolic complications are another manifestation of a compromised microbiome.
Nick Jikomes 52:50
One of the things that I'm interested in learning about here is, my understanding is that there are some striking experiments in rodents and experimental animals where maybe you sort of wipe out the microbiome using broad spectrum antibiotics. And then you actually replace that animal's microbiome with that from another animal. Are there any striking examples where that kind of microbiome transplantation is sufficient to either induce or cure some kind of disease?
Emeran Mayer 53:25
Yeah, up to date, it's there's only one disease where this is really clearly been demonstrated to be effective. And this is a particular form of post and post antibiotic complications, C. difficile colitis, or some people sort of after a course of antibiotic wipe out their their microbiome and developing and develop life threatening colon inflammation or colitis that's been typically been treated with certain antibiotics. But it's been found that a fecal microbial transplant is the best short term and long term treatment for this condition. And probably the reason that this works, and that this is the only disease where this where this works, is because you have already wiped out your own microbial ecosystem through this process of developing this colitis. So now, when you come in with a transplant, it can start from from scratch. And basically, it will go back to your original design of your ecosystem. So there is a transition phase where the donor of this transplant, you know, these microbes will dominate your own ecosystem composition. But this transition phase, you'll basically return to your own original programmed microbiome. So the the blueprint so even though your microbiome has to wiped out by the antibiotic associated colitis, the Blueprint was not destroyed. And the gut rebuilds that same population, after a while. This has not been successful in many other diseases. So it's been tried in. In obesity, it's been tried in, in inflammatory bowel disease, in tried in some psychiatric diseases. And it's not happening because all of these, it's also been tried in autism spectrum. And I'll say something about this in a minute. In all these other diseases, you don't have this initial complete destruction of the of the ecosystem. So you have something you have a bad microbiome, a compromised microbiome, but it's still, that system is still resilient enough to to exclude any newcomer to settle in that. So this is called colonization resistance. So it's it will not allow any newcomer from a transplant to set foot and stay there. There's one. So this is the current state of the knowledge, this interesting example of studies with autism spectrum disorder, we're a sort of modified technique has been used. So using an initial application of a broad spectrum antibiotic to knock down as much as possible the the autistic microbiome, and then doing a series, multiple transplants over time, to week to recolonize. It and that has been shown to be both largely in uncontrolled studies. So this is the big question mark. But it's been shown to change both the improve the symptoms, both the mental, but also the GI symptoms of these kids. But also, it's been shown to change the microbial ecosystem composition. And even after fall off after one year, I think it was one or two years, these benefits we're still seeing. So this would almost indicate that that is a way that you can add at least over a period of a couple of years. influence and change and correct is this alter microbiome of characteristic of autism spectrum, children, I think in the future, people are working on techniques. And there could be molecular biology or gene manipulation, to overcome this conversation resistant resistance so that you have microbes that are identical to normal gut microbes, but where you manipulate the genes, so they can overcome the this colonization resistance or the ecosystem. That would have obviously, huge potentials for the treatment of many diseases, you know, both psychiatry, and in metabolic diseases, the risk of something like that is always
you know, this, this called colonization, resistance has a good reason why we have that because we wouldn't want anytime we have an enteric infection, that these pathogens can settle in our microbiome and stay there. So you want you want a system that's, it's almost like the custom system. You know, in a, in a country, you don't want anybody to come in uncontrolled and settle there. You want to have some, some close regulation of that process. If you if you miss with that process that evolution has established, there's always the risk that you know, this code going the other direction.
Nick Jikomes 59:05
So it sounds like we normally have a kind of baseline microbiome with a certain population composition, that our body will have a tendency to always go back to. And there's actually this, you're mentioning this concept of colonization resistance. So, you know, the microbiome that's native to our body is going to want to prevent other microbes from just getting in there. Does that have implications for how we think about things like probiotics, and their ability to actually change our microbiome? And, you know, can you start talking about probiotics generally, do they actually work most of the time? Do the products out there have the right bacteria in them? What What should people know about that?
Emeran Mayer 59:45
Yeah, so your first part of the question is easier to answer. So, these probiotics, in general, for the majority of people do not overcome colonization resistance. So after 24 to 48 hours, you take a dose of a probiotic, it's gone from your from your gut, it does not, it does not change your originally programmed ecosystem. There's some exceptions. So in some people they actually are allowed to colonize. I don't know what the factors are, and I can't really give you a detailed explanation for that. But in general, it's it, it is important, if you, if you believe in probiotics, you would have to take them on a regular basis. It may also be possible that some, so there's obviously multiples strains and species of probiotics. You know, humans started to develop fermented foods sex some of these 40,000 years ago, not for health reasons, but for reasons to preserve food, you know, and allow them to travel long distances and colonize other parts of the world. So 40,000 years, that's long enough for our own microbiome and our own genes to adapt to that exposure. So it's, it's quite possible that many of the strains that are part of naturally fermented foods, be it you know, fermented vegetables, fish, dairy products, so anything else are allowed, you know, do not have the problem of colonization resistance. I, again, I can't give you an an, an answer. And I didn't even know if that has been studied with all these different strains. But it's certainly for me personally, a, a reason why I recommend to patients, if you believe in probiotics, consume them with with naturally fermented foods, if you have access to them. There was a study, interesting study, kind of controversial, was was received a lot of criticism and suspicion came out of the Weitzman Institute in in Tel Aviv, where they found that after an antibiotic course, people, they got a cocktail of probiotics. In some of them, it took longer to reconstitute the pre antibiotic, microbial ecosystem, the healthy ecosystem, then the ones that did not get the the probiotic cocktail, so that it would actually delay or compete with the natural with the natural microbes to come back. If that's,
Nick Jikomes 1:02:46
you know,
Emeran Mayer 1:02:47
obviously, this ran to a lot of opposition from all the probiotic manufacturers. I do not know what that field stands for, I have not seen a a reversal or just these findings being refuted, but it's certainly something to keep in mind. So, most importantly, I would say, if you believe in probiotics, and you take them, and you notice, a significant benefit for you, you may either be somebody with these microbes are allowed to settle in your gut. Or or you have been taking them on a regular basis, you know, and not just for a few weeks, and then stop taking them because they will not have a long term effect in the future. Well, then he asked me the question, so which are these probiotics and it's obviously hundreds being promoted on the internet and and by by companies, each one is sort of celebrate as the most potent and most evidence based? Well, the evidence is very, very limited. You know, the kind of rigor that that we apply to new medications, for example, you know, randomized control trials, phase one, two, and three, for the great majority of probiotics has never happened, and probably will never happen. It's too expensive. And I think a lot of the people that companies that sell these products would be afraid that it would show that you know, there's no benefit compared to placebo group. So they, these studies are not being done. I've I've been involved a couple of times. In a process for, you know, scientists developed showed animal studies would just had a major effect on on brain health and depression like behavior, then, you know, these were industry sponsored preclinical studies. Then there was sort of a big plan to do Worldwide randomized control trials, phase two or phase three. And I've seen this twice now, different companies, those studies were cancelled in the last minute. And, you know, no reason is given. But my feeling is, the main reason is the risk of having negative results was too high to justify the expensive hundreds of millions of dollars for for trials like that, or it would show the negative thing in any would kill this compound for, you know, for any commercial purposes.
Nick Jikomes 1:05:35
Yeah, I mean, I can just imagine the, you know, marketing teams at these companies right now, it's like, you already have the one animal study that seems to show something positive, you can just point to that, and you can
Emeran Mayer 1:05:47
say, does, it's evidence based is science based, and, you know, that's what everybody's using. And I think there may be another, you know, there may be a whole other series of probiotics on the horizon, and we see some of those. So for example, I've interacted with a group in in Canada, that developed a bio engineered micro microbial strain that that produces short chain fatty acids in high amounts, and they were able to knock out the gene that is responsible for this condensation resistance. So these, these microbes would actually settle in the gut, and have a much more profound effect on you know, the ecosystem. Another one would be, you know, beneficial microbes that are high short chain fatty acid or like butyrate producers, that or, you know, producers, for example of GABA, this is a neurotransmitter that could have anxiolytic effects. This company's microbes have already been engineered and have undergone some testing. Some of them are on on the market, like for short chain fatty acid producers, but others, like the GABA producing has not made it into any commercial application. Because probably they, you know, there were concerns about either do you reach high enough concentrations in the in the brain from microbial produce kava or so I think there will be new, a new generation of probiotics, how popular there will be with public, like genetically engineered microbes in your gut. So obviously, a lot of resistance to that concept. And so, but we'll have to see that there is enough, you know, startup companies are working in that, in that space that we'll see some of these.
Nick Jikomes 1:08:01
So you mentioned briefly that some people might be unusual, and their guts may be more readily colonize Abul by certain microbes. How much variation is there from person to person and microbiome composition? Is there a lot of variability? And how easily changeable? Or tunable? Might that composition be from person to person?
Emeran Mayer 1:08:24
Yeah, so there's a there's a huge very variability into individual variability. So if you compare it with genetic, you know, variability, which I mean, we're so similar to each other, and even to a mouse next to us, but in terms of the microbes, particularly if you go down to the strain level, so if you, you know, the different classifications of taxa of microbes if you started at the highest level. So almost everybody has like three main taxa, Firmicutes, Spectre, Adidas, and and in the third group of microbes, every almost everybody has those. If you go down another level, to the species, you'll see that this similarity will go way down. And if you go to the strain level, it's been estimated that only 10% are shared by individuals with each other. So depends a lot of at what level you look at. Ultimately, it depends on the strains, because if you think about ecoli, the species of Ecoli you know, the strains that are deadly Enterotoxigenic ecoli, and there is strains that are commensals, so highly beneficial to our microbial composition. So I think I mean, many of the early studies and the majority is have stopped at best at the species level. and many of them didn't go deeper than the genus level. And so the results that came out of these studies is kind of misleading. You know, it's, I think with, with, with the more sophisticated techniques that we use today, you know, meta genomic analysis or transcriptomic analysis, you get a much finer grain of differentiating, you know, different players and different products generate within within the microbiome. And it's, so we the second part of your question was, how, maybe you want to repeat it, change it?
Nick Jikomes 1:10:45
Yeah. Like how changeable? Is it based on what you've said, so far? It's sort of sounding like, it's relatively difficult to change the composition of the microbiome unless you do something relatively drastic, like go on a broad spectrum antibiotic.
Emeran Mayer 1:11:02
Yeah, so this is something that has really changed his concept over time. We know, for example, there's a certain bandwidth that it's changeable. So you know, we can't, if you compare our gut microbiome with that of the remnants of hunter gatherers in, in, in Africa, the hosta, or what's the Yanomami on you, or Norco? You know, our diversity and richness is way down, and will continue to decrease based on these lifestyle changes in modern societies that we talked about earlier. But that doesn't mean that, you know, we're doomed on this downhill course of our gut microbiome and health, there's a certain bandwidth, I think this is how people currently conceptualize this certain bandwidth that we can either improve it, but not get to the level of our ancestors. But we certainly is much leeway to make it even worse. So the it is it is changeable. And that the change happens can be intergenerational. So if one, for example, it's been shown in animals, if, if one generation of animals is fed a low fiber diet, and microbial diversity goes down the offspring, if the offspring again, is fed a, such a diet, you will go further down. If you try to intervene, after the first generation, you may be able to bring it back to its original richness and diversity. But after the second generation, that's no longer possible. And I think we may be seeing, it's always hard to extrapolate from mouse studies to human situation, but we may be seeing something similar, that there has been this progressive decrease in the health of the gut my, you know, microbiome system that will not be able to reverse that completely. But certainly, we can stop further decline. And we can, you know, we can go up a certain level within the bandwidth of variability. Certainly, there's studies have shown rapid response to dietary changes from, you know, carnivore to do vegan, very dramatic change of the both the individual microbial abundances, but also the metabolites that they produce. And this is in the in the in the short term. But if these people would go back to their original diet, it would switch back to the, you know, to their original composition. So there is definitely, I mean, the good news is, and that's really important for me in our recommendations for healthy diets. The good news is you can stop further deterioration, you can improve the situation over its current baseline. If there is a possibility, then over generations to rebuild it. That's I don't think that's known yet. I have not seen that. And that may be different in humans, and then then in mice. But there's certainly reason for optimism and the justification for a aggressive campaign for, you know, got microbial friendly diets and restoration of the ecosystem.
Nick Jikomes 1:14:49
So So there definitely is some response of the microbiome to the diet we're eating. I did want to ask you about different diets. So on the one hand, Our diet, like must obviously impact our metabolic health and things like microbiome composition. On the other hand, you know, dieting is a very frustrating and annoying topic to a scientist, I think and to a lot of people, because you know, every week, there's a new diet book out that claims to be the best diet for whatever. And a lot of it is clearly, you know, garbage mixed in with partial truth mixed in with actual factual statements. So it's very difficult even for an educated person to make heads or tails of the whole dieting industry and what they can can follow. Good advice for. So can you talk a little bit about a couple different popular areas of dieting, and whether or not there's any clear evidence that they impact things like the microbiome, the one I want to ask you about first, because it's related to the stories you're telling us from your mountaineering adventures, is intermittent fasting. So it started to sound like you were saying that the body can sort of switch modes or regimes of metabolism, and be less anchored in the hedonic signals that we're getting in the modern world and go back to mostly paying attention to homeostatic hunger signals, if you just sort of remove yourself from having food all over the place. So does that tie into intermittent fasting and whether or not that can actually have benefits on our health?
Emeran Mayer 1:16:30
Yeah, so you know, intermittent fasting has received a lot of attention recently. I personally like to sort of break this up into the truly intermittent fasting and the time restricted eating because I think there are, is a significant difference between those two. So with, with time restricted eating, which is a technique that I think is, is practical, is realistic, almost everybody can do this, where you don't limit the amount of food they eat, but you compress the feeding time, the eating time, into eight hours or or less, if you can, and leave the gods empty for 16 hours. This it does not have theoretical and preclinical reasons or evidence to support that. So one is, if you go to a D, let's say your 16 hours of non eating a big portion that happens during asleep, so at least, you know, half half of that happens during asleep. And so you switch the whole physiology of your GI tract, you switch the contraction patterns from one of peristalsis and mixing and grinding to a regular, almost like clockwork MC sequence, that every 90 minutes, you have a big contract with sewing in the esophagus, going all the way down to the end of your intestine. And that wave is used to be called the housekeeper of the gods, we didn't really know when this first was detected. This, this was like when I started my career in this field that this was first reported by investigators at the Mayo Clinic. So to say it was thought to clean the GI tract of all debris and undigestible food, but that's probably not the main function of it. If you imagine the microbes living in these different communities all along the gut, it puts them back into the right place and it regulates the abundance in different parts of the gut, like in the small intestine, you want to have a very low concentration of these microbes in the proximal small intestine and little bit high in the distal and highest in the colon. So what is wav does, it puts everybody back into place, it's almost like cleaning up at the end of, of a busy day, you know, in a, in a in a restaurant. That seems to be a very important part of regulating the, you know, the ecosystem. And there's different different parts. These ecosystems are regionally specialized, you know, you don't have the same ecosystem all the way through you got different in the small intestine, just so small intestine, large intestine. So that's that's one thing it also this wave affects the secretion affects blood flow. But it also has been shown to affect the, the what's called the geography of the microbes towards your, your gut lining and the cells that make up your gut lining and your immune cells. So during the fasting you have a greater distance So there's less of that signaling that goes from the microbes to the rest of the body, then, you know, during during the feeding time, so both in terms of the ecosystem localization, relative abundances, and the geography of the microbes, to your in relationship to your gut lining is altered during this, you know, non eating phase. And we've almost abandoned this in our modern lifestyle, you know, snacking in front of the TV, till midnight or after midnight. And then having snacking throughout the day, the whole food bar industry is essentially a way of eliminating that, that mechanism, that regulatory mechanism from our, because the minute you put something in your mouth, it will stop that that cleaning process.
So this is and I would say, you know, it is very convincing mouse experiments that mice could be fed to a very unhealthy what's called cafeteria diet, on which they would gain weight and develop metabolic disturbances. If they are fed ad libitum, they can have access to the food all the time. But Windows switch to this time restricted eating, they can consume the same diet, but will not sure these negative consequences. So I think it's something so we've tried to snow and family during the pandemic, during the stay home phase. It's something that's takes some discipline, not to, you know, snack or have you a glass of wine in the evening after dinner. But after a while, it sort of becomes a pre natural state. And it definitely on our self experiment has shown, you know, beneficial effects on pretty significant loss of weight. Now, there are several studies out now there's a lot of studies in animals, which are all positive. So few studies out in humans, some of which are positive, others are a negative did not show a benefit. So the final word on that is still out. So this is all about time restricted eating. Now, if you go to intermittent fasting, obviously a much more difficult thing to do for the average person on this use spiritually motivated, or, you know, have a very high discipline.
Nick Jikomes 1:22:40
So would this be intermittent fasting without be having multiple days where you're not eating in a row?
Emeran Mayer 1:22:46
Yeah, and you know, people have used different patterns. So some people go on one week fast. So just water during a one week fasts, or some go into two days, two days a week, one day a week, one fasting day, I, I just think, you know, being at work, like most people are, it's just like, you can do this for the length of a clinical trial for a four week period. But there's evidence and many of these techniques, you know, if you look at them, after a year, will not be sustained. And obviously, you lose, then it's particularly bad because people lose weight on these dietary interventions, then if you stop it, you know, many have this yo yo effect, where then the weight increases above your, your baseline weight, even so you make things even worse. So but I think, you know, if you have the discipline, if your leave monastic life, you know, at the fasting is very, very important thing for because it does affect the brain and your mind and consciousness. But for the the average person, I just don't think that these techniques are, are realistic. You know,
Nick Jikomes 1:24:09
what, what do people tend to report if they go on a multi day fast? I've heard that, you know, usually the first day or two, you basically get very irritable, and you're probably not fun to be around. But then after that, you have other kinds of mental and behavioral changes.
Emeran Mayer 1:24:27
Yeah, so people say that, you know, they feel better, they have more energy, they have fat, they've lost their brain fog, improved their concentration, so many positive things. And, you know, that could be attributed. So what happens during this fasting is that you switch your main metabolic mode to a state of ketosis. So you're burning ketone bodies instead of sugar for your energy and ketone bodies, you know, from your fat stores. And so typically, you know, when people go on a ketogenic diet to actually eat, try to live primarily on, on animal products, fats and protein. But fasting, essentially forces the body to do something very similar, you know, without ingesting unhealthy aspects of a diet, which I think the, you know, most of these animals are particularly if you consume them in high amounts. So, if you look at it this way, you know, even the, and this is just really from self experimentation, I have to say, having seen the study, so, if you got intermittent fasting, during that, during that 16 hour, not having food in your stomach, and politically, if you exercise you get up in the morning, you exercise on an empty stomach, you will have a certain degree of ketosis and burning ketone bodies instead of sugar because there's no you know, interested carbohydrates that you can burn. So, if you extend that period by having your first meal of the day, which is typically at 11, or noon, being of, of plant based fats and protein, you know, without carbs, so these will be seeds. And yeah, I mean, this will be mainly seeds, different types of seeds, and then you can actually expand that, that time of ketosis. So this is where we'll switch to. So we are actually on on a ketogenic mode for for more than the, you know, the 16 hours, we'll pray on that mode for 20 hours a day. And, I mean, again, we've not done a study on this, I've never seen a study on this, but from what I know, I would imagine that this is probably the best way that you can use this ketosis principle for your own health without, at the same time eating a healthy diet, because you know, you've your second big meal should be a highly varied PLANT BASE diet with multiple, you know, fiber, providing vegetables and, and through so yeah, for me, personally, I'm against the ketogenic diet, for many reasons, environmental, but also health wise, but I think utilizing that principle of a, of a switching to a ketogenic mode, during this intermittent and not intermittent fasting, time, restricted eating is probably a good thing.
Nick Jikomes 1:28:10
So just to summarize, intermittent fasting, much harder to implement, just because it's not as practical, you have to go multiple days without eating. But what you're effectively doing with intermittent fasting is putting your body into a state of ketosis, which is the same thing that people achieve when they go on this ketogenic diet that's high in animal fat and protein. And the difference between that and the time restricted feeding, is that if you're doing time restricted feeding, you just have to pick a start time and a stop time every day, and stick to it. 16 hours without food, but it sounded like it really has to be 16 hours without anything except water. Not even like a glass of wine or a glass of juice. Is that accurate?
Emeran Mayer 1:28:52
Yeah. And that's that's the hard part. You know, it's not most people have their dinner, you know, by seven, eight at the latest. And they don't really feel like they want to have another meal but the snacking and, and the alcohol that that's that's the hardest part of so essentially change your lifestyle, you know, and we're sort of come up with this idea that you don't have to do this 100% Because if you travel you know, if you go to a Mediterranean country, you go to Argentina, you don't want to live like that for these two weeks that you're traveling there because you're missing out on the best part of their culture. You know, eating out to restaurants 11 at night but at home, you know related if you can easily build this into your work schedule. It's it's something you know, it's it's something feasible without making a religion we also found you know, when we invite friends over, obviously you don't say after eight o'clock There's no, there's not a glass of wine or cans of beer. So you don't have to be religious about this, you know, you should be religious for most of the time, but don't sacrifice your social life for your enjoyment of other things because of that.
Nick Jikomes 1:30:17
Yeah, I think that's good advice, you know, during the workweek, when you're at home, and you're not traveling or whatever, you know, stick to something, but at, you know, you can let you can let things slip beyond that, as long as you're doing it. Some of the time. You mentioned the Mediterranean diet effectively, or the Mediterranean culture. And I did want to ask you about the so called Mediterranean diet, is that because you hear that's one of the ones that you hear about all the time? Is that even really a thing? And if so, what is the composition of that diet? And is there any evidence of any positive health benefits of that type of diet?
Emeran Mayer 1:30:52
Yes, so, you know, what it is, I mean, it started with his early studies, famous paper by Ancel key, or report there was solicited by the, I think, the Rockefeller Foundation, where he studied people in in Crete, in the, I think it was in the early 60s. And this was obviously a very different situation of, of, you know, kind of low income people who could not afford a lot of meat. So they had a diet that was was high in vegetables and fruits, which were cheaper easily available, with some meat, usually goat meat and, and some poultry. And when he compared the the health outcomes of people in Crete with other populations in Europe, they, they signed this cross sectional, epidemiological studies, you know, significant health benefits. Now, this could have been confounded by a lot of different factors. And obviously, that diet in the early 60s, and Crete is not what you get today, when you travel in Italy, or Spain, or if you go to an Italian restaurant. And we just been dramatically changed. So I usually say, the health benefits of a traditional Mediterranean diet, which is more similar to, you know, high and could behind fat and plant fats, olive oil, primarily seeds and nuts and different types of seasonal vegetables and, and fruits, and low in in red meat and dairy products. But, and there's now many cross sectional epidemiological case control studies that have been done and have confirmed that that not only just seems to be beneficial, or has a decreased risk for morbidities, cardiovascular disease, psychiatric, like depression, metabolic disease, so the evidence for that is pretty strong. I mean, these are not large, most of these are not longitudinal studies, most of them are not, will not allow you to say anything about the causality that clearly these health outcomes were weren't directly caused by their diet. But significant circumstantial evidence that it's the case. And so there's a few recent studies that have actually looked at an intervention. So with a control group and following individuals up for for a while, and some of these studies have really proven that people on this diet both have a favorable microbiome profile and metabolites and lower inflammatory markers in the brain, lower metabolites that we know play a role in the pathophysiology of many brain disorders. And that so they looked at frailty and cognitive decline in these people, and it had a positive effect on those as well and those clinical outcomes. So I would say that and there are studies going on in you know, early Alzheimer's disease and Parkinson's disease in many both medical and psychiatric diseases. And my guess is they will in generally confirm the benefits of that diet. And yeah, so, but for many of the other studies, the evidence is much less strong, mainly because there haven't been many studies done in that same rigorous way. So there's smaller studies that shows certain benefits for the ketogenic diet in terms of metabolic regulation. Yeah, clearly, if you go on a four week ketogenic diet, you will improve your hemoglobin a one C, you will, you know, improve system systemic immune activation. But if you do this for four year or longer, it will have negative does positive effects will be overshadowed by negative effects, because you're essentially starving your, your gut microbiome, you know, and is that which we know is an unhealthy thing.
Nick Jikomes 1:35:49
So switching gears a little bit, your latest book is about the interaction between the gut and the immune system. Is that accurate?
Emeran Mayer 1:35:59
Um, this this new book coming out? Yeah.
Nick Jikomes 1:36:03
So is there anything you want to say about that book? And what's inside of it that people might find interesting, given all the things that we've touched on here?
Emeran Mayer 1:36:12
Yeah, so it's, it's clearly building on my first book, The mind gut connection. But it takes it so a lot of things have happened in those five years science wise. And it's sort of really focused on this phenomenon that, you know, that diet influences our microbiome, which then has an effect on how the microbiome interacts with our immune gut based immune system, and how they got basic immune system then sense inflammatory signals throughout the body, to other organs, all our other organs, the liver, the colon, the, the brain, the heart. And how those, you know, those immune signals together with other chemical signals from the microbes play a major role in, in, in many of these diseases, I focus again on on brain diseases, calling the kind of Alzheimer's Parkinson's autism spectrum, but mentioned that you know, how closely these these links that we see to other disorders, like cardiovascular and metabolic and cancer, but I'm not going to detail all these. So at the core of this concept is that the microbes diverse microbiome, plays a big role in generating and maintaining the barrier between the microbes and immune system in the gut. Initially inform of the mucous layer that in many microbes interact with specialized cells in the gut, Scar blood cells produce this mucus, which is the first layer of insulation, and then the guards epithelial layer, second line, and how a compromised dietary compromised gut microbiome leads progressively to a compromised insulation between microbes and the immune system. So that's where the problem starts. That compromised microbiome could come from either the poor diet, many examples for the standard American diet, you know, high in sugar, high and ultra processed foods high and low in fiber. High in animal based fats. But there's also another factor that plays a big role, which is the descending influences from the brain. So chronic stress, you know, what's called Aloe stasis, chronic engagement of the stress system in the brain has very similar effects on this on this barrier, you know, it increases the permeability of the leakiness of this gut barrier, the mucous layer and the epithelial layer. So, in our modern lifestyle, we have unfortunately, a combination of both the chronic stress increase in chronic stress levels and and, you know, the worsening of the diet, which interact and obviously create a the worst possible scenario. And we see you know, we have increasing rates of depression. On the one side, we have this increased rate of poor digestive health, but they they converge on something that is a common denominator. Then also another thing that I come up then from this with this recommendation, a healthy diet is one that keeps in mind, first of all, the health of your gut microbiome. So which means You know, largely plant based food. The other one is that when you select your diet, you have to ask three questions. What do you eat? When you eat it, and where does the food come from? Because there's a lot of changes in the way in a modern industrial agriculture has changed food production, and we will see even worse things coming down the pipeline with aquaponics you know, vegetables and fruits grown in water and along and soil. So there's no longer an exposure to the microbes in the soil, which play a big role in stimulating the health promoting molecules, these polyphenols in the plants. And then also the impact of your diet on not just on, you know, soil health, but also on environmental health with major impact that the constantly increasing consumption of, of animal products with this has on deforestation and monocultures and use of pesticides and herbicides. So it's it takes it from the microbes and microbial health, all the way to soil health, and planetary health and constant I like to call the One Health concept.
Nick Jikomes 1:41:27
So we've touched on it a little bit, but one of the last things I want to ask you is to what extent and how all of your research and all of your studies over the past few years, past few decades, has influenced your own dieting habits, what do you have, like a basic routine and set of rules that you follow in terms of time restricted eating and the composition of your diet, whether it's more plant based or animal based? I think you've you've sort of hinted at it along the way. But can you summarize for everyone? How you approach dieting and how you think about your strategies?
Emeran Mayer 1:42:03
Yeah, and I've had a pretty dramatic change in my dietary habits from when I was a student living primarily on on animal products, you know, both and you know, growing up in, in Munich, in southern Germany, this was certainly not the health, the place for the non foods healthiest diet. And maybe not as much processed meats, as you would get here. But certainly, you know, I was mainly thriving and completely unconscious, I have to say this, were the most important thing, I was really living the way that a large number of people live without having thoughts, and a conscious awareness of, you know, this whole topic that we have been talking about, you know, where does this food come from? It's grown. So then I had some, I was not trained as a gastroenterologist in any aspect of diet or nutrition, and not a single hour. When, in my research, my early research was always the brain gut interaction, not really with the microbes, and with the role of food in this in this process. But when I wrote my first book, this was the eureka moment really, when I went through all this literature, and once you start thinking about the microbes, you cannot avoid getting deep into the diet and into nutrition. And with the first book that was not as extreme as it was the second time. Because in the meantime, you know, through the promotional my book, I got to know and got to speak, got invited to many places that as a regular gastroenterologists that would have never encountered before audiences questions like the ones we're having right now. You know, in my early career, I would have not had this conversation with you. And, you know, I've met people like in regenerative organic agriculture, really understanding what that means and how important organic is become in a situation where you recommend a largely plant based diet so if it's, if it's not organically grown you you in consumes a vast amount of pesticides and chemicals that are now used to grow these foods. So my awareness is kept increasing about paying attention to it. So today we've switched to you know, a, a largely plant based diet. I mean, the only meat sources is fish once a week and chicken once a week. All the rest is, is plant based. Lots of varied fruits and vegetables and also paying a lot of attentions are paying a lot of attention on the labels of food, which in the past, I've not really done that much. And also going beyond that, finding out places that sell food that has been grown in a regenerative organic way, or at least in an in an organic way, in an environmentally friendly way. How far away is this being produced? I don't, you know, we used to, just to make sure that we get our blueberries, eat them all year coming from places like Chile. And so we don't do this anymore. So we, you know, have adjusted this to many to locally grown products, which means seasonally adjusted. So it's it's a long process, I don't know, you know, suddenly on the, in Southern California, there's a lot of consciousness about all these things now. And there's a lot of, you know, in the media, I don't know how widespread that kind of process is really in the general US population. It's, it's very prevalent in Europe, I think. People ask a lot of these questions. So a pretty large portion of the population is, is sensitized to ask this, you know, many of these questions. But it's, it's not, it's not simple. I mean, you have to dedicate part of your attentional capacity to food that before you were just, you know, when you buy a hamburger obsoleted, there's no need to think about it, what this doesn't work comes from and how many trees have been cut down to, you know, have cheap food for cheap soybeans, for the cows that are going to this hamburger. So once you develop this, so this has happened to us?
And I think it will, it will increase you know, it's not, it's not a static thing, I think it's a constant learning process. And the good sides are I see progress. So at least in Southern California, and the audience's that I interact with, I hope the award will spread, you know, throughout throughout the country and throughout the world. And it's certainly something that I've dedicated a lot of energy with my books, for example, which are equally a call to action for, you know, environmental health as are for gut health and gut microbial health.
Nick Jikomes 1:47:46
All right, well, this is a fascinating area. And it sounds like it's a fast moving area of research. So you're gonna have to write a new book every five years. But very excited to see your new book come out. So remind everyone one more time, the name of your old book, the name and name of the new one.
Emeran Mayer 1:48:03
So the old one is the mind gut connection. And the new one is the gut immune connection. And as I said, you know, the second one builds on some of the concepts of the first one, but with a lot more new science and taking it beyond the gut, into the soil, plant health, planetary health and environment. So I'm, it sort of reflects me on process of growth in this area. And I am really excited that this you know, quite honestly, in the beginning, when I thought about writing a second book, The main question was, is there enough space in a very crowded field now of, you know, self declared microbiome gut health experts, published books. And so once I came up with this, with this concept of the One Health idea, you know, that really energized me and I think something came out that is, is very novel to a lot of people have not really seen in concentrated in one book.
Nick Jikomes 1:49:13
Actually, excellent. Well, this is a fascinating area. I'll link to it in the episode description for everyone to find easily. Professor Emmer in there. Thank you for joining us,
Emeran Mayer 1:49:22
Nick. It was a pleasure. Thanks a lot really enjoyed it
Unknown Speaker 1:49:25
as well.
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