What We Got Wrong About the Gut Microbiome (And What's Actually Right)

But I think to see the microbiome as a master translator in our bodies that translates whatever goes on around us, comes into the diet, and which comes to us through our mind, because that goes down to the microbes as well. The microbes translate this information into the body's own language. And if that translation has an end result of a pro-inflammatory neurodegenerative message, then that's where the disease comes in.

Welcome, Emmeren, to the podcast again. It's good to have you back.

Thanks for inviting me, Mark. It's a pleasure, honor.

Well, it's fun. It's fun to talk about poop, which is my favorite subject. They used to call me Dr. See Every Poop when I was at Canyon Ranch because I used to look at stool tests all the time and I wanted to see stool tests on every patient. But you were, you're an MD, you're a gastroenterologist, you're a scientist. You've been studying the microbiome for a long time. And, you know, you've written a book about it that we talked about on a previous podcast, which I recommend people listen to, The Mind-Gut Connection, a really powerful book. This is sort of a 10th anniversary edition that's come out, How Hidden conversations within our bodies impact our mood, our choices, and overall health. And I think, you know, science has finally caught up with this simple idea that what's happening in your gut is affecting every single system in your body and is related to almost every disease you can think of, whether it's depression or dementia, whether it's cancer or heart disease, whether it's diabetes or multiple sclerosis, everything in some way or another has a tie back to the microbiome in the gut. And even, you know, this whole new nutritional metabolic psychiatry field has emerged since then. I think systems biology is now coming more into the forefront of understanding the body as this complex network of systems, not this structured organ-based medicine that we have that's based on specialties that has nothing to do with actually how the body works. It's just an artifact of Vesalius dissecting the body. So now we're kind of in this field of like, well, what do we know about the microbiome now?

What can we do to assess it properly?

And how do we actually treat people focused on the microbiome? And a lot of your work is about this in your new book, which is really an incredible manual. It's more like a practice manual called The Mayer Model: Optimize Your Health and Wellness with the Brain-Gut Connection. It's out now. It's a really good practical application of this and understanding how we can bring our healthy microbiome back into gear. So maybe we can start out by having you kind of frame Just the scope of the problem. Again, how big is the problem of the microbiome in health and chronic disease in 2026, particularly in America?

Yeah, I would say, I mean, just building on what you elegantly summarized, that we're changing our view of looking at these interacting systems. It's not just the microbiome, it's not a particular microorganism, it's really the system in which these elements interact with each other. I think that So I've kind of, from the initial enthusiasm, well, I would say from the initial skepticism 10 years ago when these first papers came out about how in mouse models, how changes in the microbiome can alter emotion-like behavior, which I questioned because we'd done decades of research on these brain-gut interactions without the microbiome and had a pretty good idea of how they work. So I went from my initial skepticism to jumped on the bandwagon, was totally enthusiastic. This is going to explain everything and we can cure all our chronic non-contagious diseases with manipulating the microbiome. And I've kind of come back to a much more careful view of this, that the microbiome is a— we have a lot of evidence from animal studies that there is a causal relationship between what the microbes actually do and what the result is. We don't have that evidence, the same evidence in humans, unfortunately. We still have to rely on correlations, epidemiological correlations. And so I like to keep my skepticism in terms of, can we actually deal with this, with our health crisis, just focusing on the microbiome? Can we just tell people to take this or this probiotic or symbiotic. I just don't think it's as simple as that. And the reason I'm saying this is because if you look at reality, there's so many people, like topic of longevity, a lot of people live into their— become centenarians, live into their hundreds. If you look at these personalities, I doubt seriously that they paid attention to any of these things that we're now—

No.

propagating from exercise to the healthy diet. There's also good evidence that many of the negative factors like traumatic stress by changing the microbiome has this long-term effect because a lot of these centenarians, actually Holocaust survivors, have gone through the most severe early life stress.

Yeah.

Based on a simple model, you would say. So, What can we do? I mean, it's just coming back to your question. The interventions haven't really changed that much. This is one thing when I wrote this anniversary edition and reread the book from 10 years ago, there hasn't really been that many novel, if any, practical recommendations that we can give based on the science. We know a lot more about the system now, but the mostly effective interventions are basically lifestyle and diet.

Yeah.

That's kind of a paradox. And I don't know if that will change, if we ever will come to, I mean, it's kind of another topic we can talk about that I mentioned in the anniversary edition. There's this new field in science of these bioengineered probiotics, which basically you can interfere with specific functions in the body. We don't really have those yet in hand for clinical use.

Like custom probiotics for particular conditions.

Yeah, for particular conditions. Like, there would be one for obesity, one for inflammatory bowel disease. It's theoretically possible that that will happen. I've been involved in some of this research towards both the estrogen recycling but also the inflammatory bowel disease applications. Yeah, we're not there yet and we don't have any clinical trials that show that this actually works.

Yeah. I mean, that's the challenge. You know what I often say, the absence of evidence is not the evidence of absence. And I think, you know, the fact that we haven't really had funding, which is the problem for a systematic approach to treating gut issues, is a problem. And it leads to kind of a gap in the scientific literature where you've got a whole group of physicians who are using the clues in the science because there's a lot of clues. There's a lot of things pointing what works and what's helpful, whether it's prebiotics or probiotics or polyphenols or treating SIBO or fungal overgrowth or gut repair. I mean, there's a lot of sort of animal data, there's some human data, but it's not in a systematic randomized controlled trial. And that's really just an artifact of our really screwed up scientific paradigm, which is funded mostly by pharma and for things that you will make a lot of money from. But restoring gut health and gut function is not necessarily something you're going to make a lot of money from. So it's been done by a group of physicians in functional medicine. We have a whole system that we've developed that's based on a framework called the 5R program, essentially to reset the gut, which is remove the bad stuff, like whether it's allergens or bad bugs or SIBO or parasites, replace what's missing. It could be digestive enzymes or hydrochloric acid, prebiotics, and then, you know, reinoculate, which is probiotics. And then of course repair, which is Providing things to help soothe the gut, whether it's vitamin D or vitamin A or omega-3 fats or various kinds of things like glutamine that might be helpful. And then, we help restore the nervous system by helping with relaxation techniques and various kinds of nervous system reset. And, it's not been scientifically validated, but it's something that's been used clinically by thousands and thousands and thousands of patients. And, it seems to work even when we don't completely understand what's happening in the microbiome. I've experienced that quite a bit where I've had recently had a patient with severe SIBO, bloating, distension, constipation, pain, neurocognitive symptoms, fatigue, brain fog. And, I basically treated her with 3 antibiotics because she had sulfur gas, hydrogen gas, methane gas. And then, I treated her with herbs to help keep things calmed down after. And I gave her basically some things to help her rebuild her microbiome, the probiotics and so forth. And she's doing amazing. I think for those people suffering with issues, and it's, by the way, you can have gut problems and have no gut issues. That's a big thing I want to talk to you about. But if you do, there's usually a way to get through it. And typical gastroenterology doesn't really focus on it. So I'd love your perspective on that and how you think about, you know, kind of bridging that gap.

Yeah, I find that what you just said is really interesting. So if you had talked to me 10 years ago or 15 years ago, I would have said, this is, you know, I don't believe it. It has to be evidence-based. We have come to so many breakthroughs in medicine with the traditional model and the randomized controlled trials. And in the meantime, I've sort of changed the view. So one is I feel there's a lot of affinity I feel with the functional medicine approach. And I've gotten invited to meetings which always has surprised me in the beginning because I've not talked that pleasantly about functional medicine, but it has changed. The second one is there's this whole historical evidence-based body of evidence from these ancient healing traditions. So if people kept something like turmeric, for example, over several thousand years as a remedy and an anti-inflammatory compound, it can't be wrong. I mean, people would not be that stupid to take something that has absolutely no effect or no benefit. And there's many of these examples. So that historical evidence for me is also one point that I sort of realized and also realizing the shortcomings of randomized controlled trials. Clearly, having done many of these studies and having seen That, I mean, the heterogeneity of people, that's kind of one of the big problems. I mean, yeah, in inbred mice, you can do a randomized controlled trial.

Yeah.

100% positive.

Right, right. But, humans are not all inbred identically genetically and they all have different backgrounds and different genetics and different microbiomes and different lifestyles. And it's definitely a problem. And I think, you know, that's a fundamental flaw in the scientific model that we're using. And we don't know how to create N-of-1 studies, which is basically what the NIH now says is the highest level of evidence, which is, you know, if you have a single person, you can use them as their own control before and after treatment and measure the changes or outcomes. And that's a validated measure. And then since we call those anecdotes, but actually if they're systematically done, They actually tell you a lot of information.

Yeah, it's kind of, I find that interesting for myself that I would ever, but being a hardcore scientist, I've always been open to, I have my own hypotheses and if they're not confirmed by reality, then I abandon them or move on to better hypotheses. And that's sort of been happening with this dealing with chronic diseases. Our paradigms and our reductionistic hypotheses just don't work for them.

Bloating, gas, irregularity are often brushed off as minor issues, but they can really interfere with your quality of life. I see this all the time with patients who feel uncomfortable after meals, worried about digestion when they travel, or frustrated that nothing they've tried actually works. That's one reason I continue to recommend Seed. Their DS-01 daily symbiotic was designed differently from most probiotics in the market. Many probiotics don't survive digestion, but DS-01 uses a capsule-in-capsule delivery system designed to help the strains survive and reach your colon colon where they can actually do their job. It's a 24-strain probiotic and prebiotic clinically shown to improve regularity, reduce bloating, and alleviate gas. And what impressed me most is the level of scientific rigor behind the product, which is what led me to join Seed's clinical board. Go to seed.com/hyman and use the code 25HYMAN to get 25% off your first month. That's seed.com/hyman and use the code 25HYMAN.

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Yeah. So there's one simple story that, you know, I tell patients, you know, there's a lot of beneficial molecules. The microbes generate metabolites from our diet and from whatever we ingest. And, but there's, so there's a lot of compounds that cause inflammation or low-grade immune. So when I talk inflammation, I always prefer low-grade immune activation because you don't get the same inflammation as you get in inflammatory bowel disease. It's not something that you necessarily see on an endoscope or on a biopsy. But at the same time, the microbes produce these beneficial molecules. And so far, our view is limited on this. So these short-chain fatty acids, mainly butyrate, that have an anti-inflammatory effect and many other health benefits at the gut level and throughout the body and in the brain as well. So the balance between these harmful substances that get into our system and these anti-inflammatory molecules, I think ultimately determines the health condition of your organ. My main interest has been on the brain. So in theory, you could do some unhealthy things and have all these chemicals in your diet. But if you eat a highly diverse diet that's highly diverse in fruits and vegetables, you will generate sufficient amounts of anti-inflammatory molecules that counterbalance these negative effects. So you'll never have just a pure positive influence on the brain from your diet. It will always be a mix.

Oh, yeah.

And I think it is that balance. So that's one thing. The second explanation is the microbiome sits at this interface between what we call the exposome, the world around us, and our immune system, microns away from all these immune cells. One mistake that's being made in this communication would trigger a lethal inflammatory reaction. It's amazing that that does not happen normally. So there's many protective mechanisms. But I think to see the microbiome as the master translator in our bodies that translates whatever goes on around us, comes into the diet, and which comes to us through our mind because that goes down to the microbes as well.

Yeah.

The microbes translate this information into the body's own language. And if that translation has an end result of a pro-inflammatory neurodegenerative message, then that's where the disease comes in. So I wouldn't say it's as— people have always said, microbiome is another organ. I like to see it as a master translator, which is able to speaks the same language as the molecules, these biological molecules that our brain uses and our nervous system uses, our immune system uses, and the microbes. I mean, they're all similar, so they all speak the same language, but you need that translation, this translational step in between to tell the body how it should respond.

So, it's almost like the gut microbiome is a transducer from the world to your body that then changes what happens across all your physiology. In other words, the, the, what you eat, your lifestyle, toxins, infections, all that is affecting your gut microbiome. And that in turn is affecting every biological system in your body, regulating it, changing it, modifying it. And, and both from the short-chain fatty acids that get absorbed, but also the microbial metabolites.

Yeah.

Stan Hazen at Cleveland Clinic, I asked him once, how many of the blood metabolites that are existing in the blood, and there's maybe 6,000, how many of those are from the microbiome? And he's like, I think a third or half. I don't know if that's true, if there's any evidence to that, but is that true?

That is true. And, you know, the problem is we don't know, for most of these, we don't really know with the exceptions of TMAO, for example, that, you know, the San Hazen example, or certain tryptophan metabolites. like kynurenine. For most of them, we actually don't know or we only know it in a reductionistic way. So people have used one of these metabolites, put them on a cell culture and see what happens or into a mouse model. But that's not how these metabolites act. They all interact with each other. It's again, the systems biology concept comes in. It's a whole network of these what you may call potentially harmful metabolites and the beneficial metabolites that constantly interact and compute the outcome. And, the outcome in general in a healthy person is always positive, which is amazing.

Yeah.

I mean, considering what we put into our bodies and are exposed to in the environment now with the microplastic, it's absolutely amazing to me the resilience of that system. So, The engineers of evolution have done a masterful job. That's true.

That's true. But I think we've really hardened microbiomes in the 21st century. We have increasing rates of C-sections, lack of breastfeeding, and early antibiotic use, increasing toxic load, increasing food sensitivities. I mean, food additives, emulsifiers, and other things that destroy the microbiome. And then we end up with poor diets, low fiber, ultra-processed food, and the list goes on, stress, and all of this is affecting the microbiome directly.

If I can comment on this, so yeah, the system is masterfully designed over millions of years or billions of years, I would say. The last 100 years have created a mismatch of that system with the microbes that have adapted, they're rapidly adapting to all these environmental changes. Because with their millions of genes, they're much better in doing this, but our bodies have not. The immune system has not been able to catch up with this. Nothing has prepared our immune system for what we are experiencing today. And so there's now this mismatch between the microbial world that is adapted to what we put in and feed it and expose it to, and our much more conservative human biology, you know, that, so this response of inflammation is basically a response to the system doesn't recognize this dramatically changed microbiome world. You know, it's, even though it may not necessarily be harmful to us, but that there's now, the immune system rings the alarm bell because what it sees that these microbes now There's fewer of them, there's more pathological molecules, fewer beneficial protective molecules. And yeah, I mean, I like this concept, the mismatch that has occurred in the last 100 years, that that's in some ways the main problem that we're facing. And how are we going to deal with this ultimately? I'm not exactly sure. We can try all kinds of things we do right now, but— Unless we change the environmental situation, which I doubt we will, you know, it's hard to say how we, 100 years from now, what this looks like.

Yeah.

Well, we have to take care of our microbiomes. And I think there's a whole, I mean, a whole evolution of this research that's pointing to more specific personalized probiotics, prebiotic foods, the role of polyphenols, all the colorful plant compounds that help fertilize the gut, fermented foods as an intervention. And so there's a lot of things that you can do. to really take care of your microbiome. I think most of us don't think about, oh, how am I going to care for my microbiome? They go, oh, I'm going to exercise for my muscles and I'm going to make sure I sleep and I don't eat too much sugar or whatever for my health. But people don't think, oh, there's this whole organ in there that I really need to pay attention to and I really need to take care of. So if people haven't thought of that, they need to. And when they think of it, I'd love you to sort of walk through your model. The mayor model that you developed of how to really take care of your microbiome in a microbiome-unfriendly world. That's what we live in.

So, I think the first thing we have to realize that, you know, I've created these pillars that all influence healthy longevity and health. And, at the center of this flower is the brain-gut microbiome system, this complex system, bidirectional communication, from the brain to the gut, to the microbes and back, which I would consider the main homeostatic organ in our system, in our body. So the first thing is we have to realize that. The second one, we have to realize that the influences, which are the petals of the flower that influence that end result of homeostasis, the weight of these petals varies between different individuals. It's very personalized. So, I mean, The pedals, so these influences are food is one of the most important ones, exercise, mindfulness, resilience, community, connectivity, connections, purpose, and sleep. So, these 7 influences, they all have variable influences in different individuals. So, in some person, it may be diet plays 100%, causes 100% of the variance of the end result of homeostasis and balance. And somebody else's diet may play 20%. They may be on a very unhealthy diet, may not exercise, but have a very strong sense of community and both socially and spiritually, and that compensates for this. So I think the main thing to realize is we're not all the same in terms of the importance of these influences. And so we have to design, every person has to design, they have to look at themselves or their healthcare practitioner has to look at what pattern does this individual fit in and then focus on building up the things that are the most important in that person. So would I tell somebody, You know, with metabolic syndrome, is obese, doesn't exercise, probably would want to work on all of these pedals slowly. And that's what I propose in this Maya Model book. Do it gradually. There's no, you know, you don't have to do this or you can't do it within a week. You have to gradually work on all these challenges. And ultimately, you will feel that you become in charge of your health and your overall resilience and balance, and you will decrease the risk of developing chronic diseases. So, I mean, the first is buying into the model, this 7-pillar model. Other people have proposed similar kinds of models as well. We have to get away from one thing that if you meditate 5 hours a day and do nothing else for your health, it's not going to help you. Monks don't live into their hundreds. They usually, I've always looked at this when I was trekking in the Himalayas. Yeah, you don't see people that live into their hundreds. That's not their goal anyway.

Yeah.

But now our goal is healthy longevity. I mean, I think society has finally recognized that this is probably the most important goal, healthy longevity without billions of pharmaceutical products keeping us alive. And for that, I think you need to have a whole program. I think that functional medicine also proposes that. You don't say to somebody, you just have to take that one supplement and we'll take care of it. So I would say all of these things will be reflected in a change in the microbiome, which is interesting. So you would think, so why does sleep affect the microbiome or a sense of purpose or sense of community? But studies have shown that it's reflected in a healthier microbiome characterized by generally increased diversity and richness and increased number of anti-inflammatory-producing organisms. Yeah, this is my main insight in the last 10 years, I think coming from mind-gut connection to this holistic program where the microbiome still plays a central role, but it's sort of a readout, which is a good thing. So when we do stool tests, and I think we are getting better in interpreting these stool tests, I still think we're not there where we want to be ultimately that we have a readout and with a predictive value, are you at high risk for Alzheimer's or when you do this in your 20s or 30s, but we will get there. I think that technology is advancing and also AI, how to interpret these, you know, massive amounts of data you can get out of the microbiome. Yeah, I would say the microbiome is an excellent readout, better than most of the other components or organs in our body.

I mean, I think it's quite an interesting model you're talking about because you're saying basically you You are understanding now that outside influences, our thoughts, our feelings, experiences, all these things affect the microbiome, exercise, stress, sleep. It's bidirectional though, because also the microbiome affects all those things. So, it's kind of this conversation that's going on all the time between the microbiome and the brain. And, I think, I remember when we were trained in medical school, you're a little bit older than I am, I think, but we learned that irritable bowel was a functional bowel disease and it was it was, we joked that it was super tentorial, meaning it was all in your head. And that we identified that people were anxious and that was why they had this problem. And we kind of blamed them in a way because, you know, it's your fault. You're just anxious. That's why you have these digestive symptoms. But I remember a paper, I think it was in JAMA many years ago where they, I forget the scientist, but he was talking about the other direction that the enteric nervous system and the leaky gut and the dysbiosis and the inflammation in the gut was sending signals back up to the brain when there's a dysregulated microbiome to cause brain dysfunctions, whether it's mood issues, behavior issues, attention issues, autism spectrum issues, all of it is affected. And so I think your model is really important because it's sort of both top-down and bottom-up.

And it's sort of, I mean, I would say, I hate to use that expression, trendy, but if you look at science, I mean, it's more and more moving into this direction of systems biology. And we also do it in our own research. I mean, analyzing these complex datasets with data from brain imaging and behavioral and blood values and the microbiome values and diet. You put all this into a pot and then you have sophisticated AI techniques work with this data, which you cannot as a human brain comprehend in a similar way. So this is, I think, is happening in many areas, this overabundance of data that we can generate and gather. But we haven't really been able to do the best way in interpreting it and making, creating action items based on individual patterns. So there could be pattern 1 in one patient and pattern 2 in another patient. And there's always attempts to do this in a simplistic way. Like many of my colleagues, we strongly believe that AI will make the breakthrough in this.

Let's talk about that because I think what you're speaking to is something really important because there's, you know, there's probably 40 trillion cells of bacteria in your gut. There's probably 102 or more times as much DNA from bacteria in your gut as your own DNA. It's constantly making proteins and metabolites. There's thousands of metabolites in your blood from the microbiome. It's almost incomprehensible. Like the average doctor can look at a panel of blood tests.

It's, you know, 20, 30, 50, 100 maybe.

But when you're talking about thousands, it's just hard to process all that. And so you're talking about an era that we're entering where AI is going to help us understand the complexity of human biology. And I would really love to hear you kind of talk a little bit more about how this is going to affect our thinking about the microbiome and how it's going to affect the clinical practice of medicine around chronic illness and how chronic illness and the microbiome are so connected.

I think it will dramatically change the way we look at the microbiome. I still, even though the stool tests have gotten a lot better and some companies use AI to interpret them or put them into context of published data, but I think ultimately we will come up with conclusions that are way beyond what we're talking about now. This whole, still, I mean, the current approach that look at these microbiome tests and you look at which ones are outliers from a normal pattern, and then you focus on these 3 or 4 organisms and you create a probiotic or a prebiotic cocktail that will strengthen those. I personally think that that will kind of disappear, really. I think we will have footprints, we'll get footprints of people, and then we compare this with tens of thousands of people, and we'll see that these footprints are recurring in different populations, and we can connect them to dietary lifestyle patterns. I mean, this is, I think it's going to happen over the next 5 years. We're sort of confronted with this ourselves. We have these these massive datasets. And collecting the data is one thing, but then really grinding them through this analytical mill is still an unresolved issue. So that's definitely going to happen. I think guidelines will follow from that. I mean, the current guidelines, they often focus just on diet. If you look at what happened in IBD first, there was a recommendation of a fiber-poor diet being beneficial for patients with Crohn's disease. Now, we have pretty good evidence that a Mediterranean-style diet is the best anti-inflammatory intervention you can do if you don't have strictures and stenosis.

Yeah.

So, I think we will get much more rational recommendations. And also what I see, like at UCLA, so if somebody comes, complex patient with IBS, they're not just going to get a dietary recommendation or a probiotic recommendation. They also get a behavioral assessment. And then if, like many people that make it to a university clinic, they have The strong brain component being early life trauma, anxiety disorder, depression. It depends on the population, but in the most severe patient populations in IBS, you can't deal with the issue just with a dietary change or with an antibiotic. You have to embed this in a holistic approach and you need the You need the experienced practitioners in these areas, gut-focused psychologists, gut CBT, gut hypnosis, kind of specialized people. So I think it's already changing the system when I look at what happened at UCLA since when I started there, we first started a clinic like this, a holistic clinic, but it took a long time. It took like almost 40 years before this is now becoming an official program of our GI division. And it's happening at other universities as well, in other settings as well. So I think we're moving for some— and I shouldn't just say it's important for IBS. I mean, same situation in inflammatory bowel diseases, where we get quite a few people that do not respond satisfactorily to biologic to biologics where increasing the dose of the medication is not going to do it, but you have to identify mechanisms in which the brain basically drives the inflammatory condition in the gut in addition to what goes on in the gut.

It's quite an exciting time for the microbiome, I would say. I think we're learning so much. I want to kind of dive into another part of the conversation, which is about longevity and aging and what happens to our microbiome as we get older. And there seems to be some interesting literature around, and you've discussed this, around the microbiome and Parkinson's and Alzheimer's. And the question is, how do we think about the aging microbiome? In hallmarks of aging now, which is sort of the features of aging, it seems to be one of the things that goes bad. And it seems like it's a modifiable risk factor. You know, we've looked at really exceptionally healthy older adults and centenarians and their microbiomes. I wonder if they're different. So maybe you can talk about some of the aspects of longevity and the aging microbiome and how it, how, how we need to think about that.

Yeah. So the initial studies were done, you know, on, on selected populations, like in, in homes for older people. Um, and, you know, there was a confusion of how much the change in the microbiome, the decrease in diversity and richness was actually a consequence of this dramatically changed lifestyle in these retirement homes or nursing homes, both in terms of diet, particularly in terms of diet, but also in terms of loss of purpose and loss of social interactions. But we know in the meantime that that's one factor and many aging microbiome studies have been affected by this that have not been controlled for factors other than age. So we know that, I mean, the microbiome diversity is fairly well maintained through age from midlife to age. There are changes. If you compare microbiomes from different people, they become more different. So, a more individualized pattern evolves. There's a decrease in certain microbes that play a role, for example, in bile acid metabolism in the gut. So, I think we're slowly getting a fairly good picture in somebody that is a healthy centenarian. It's not the simple explanation that we gave like 10 years ago, just a decrease in diversity, and that's why they're more prone to develop diseases. It's really— it's a much more nuanced What's happening then? I think there's dramatic changes in these factors that we talked about earlier, these pedals that influence the microbiome. The exercise obviously goes down pretty dramatically in the majority of people. Food, unless you can afford to have your 30 different plants and vegetables a week delivered to you, will decrease in variety. So this decrease in diversity and this decreased prevalence of the beneficial microbes is definitely a risk factor for the manifestation of many of these diseases that come with older age. But we have to realize these diseases like Alzheimer's and Parkinson's, they start at the microbiome level in our 40s. There's more and more studies that are showing that you can actually predict changes based on microbiome negative changes much earlier in life. But then, when the microbiome goes down in its main functions, the disease actually then becomes apparent. You could probably, it's sort of a good way of identifying where we can intervene. So, we can intervene at midlife in patients at high risk that have absolutely no symptoms, but we can see some signs on the microbiome level that indicate don't guarantee, but indicate that this person's at high risk. But we can certainly, once the first signs and symptoms of the neurological disease, and I've talked particularly about Parkinson's and Alzheimer's, to really aggressively reverse the changes that are going on within the gut microbiome. I would say at that age, probably diet is more successful, more practical than than some of the other changes, but also just connectivity, purpose. I mean, all these things. I think that so many elderly people, we have this epidemic of loneliness, which is definitely, it's reflected at the gut microbiome level as well. That's kind of the intriguing thing. It's like this, you have this mirror inside of you. The better we get in identifying the subtle changes, that reflect environmental influences, the better we'll be in preventing them and treating them aggressively. If you have the full-blown disease, I don't think you need to do a microbiome test. It's not going to change somebody who has full-blown Parkinson's disease with all the neurological symptoms. It's not going to make a difference. Same with Alzheimer's. In Alzheimer's disease, it's almost like the opposite. You know, you want— there's evidence that a keto diet is actually beneficial because it has anti-inflammatory effects on the brain in somebody who is, you know—

Yeah, yeah, I've seen that. I've treated patients with Alzheimer's and they use keto diets and it has been remarkable to see the way it impacts them. And I think the question I would have for you is now sort of we think about taking care of our microbiome and the aging microbiome is a thing. In terms of contributing to acceleration of aging through increasing more of a sterile inflammation in the body and affecting every other system. Let's kind of walk through practical steps because you mentioned the 30 plants. I think that's important. I think I want to talk about the specifics with you of what you actually recommend to people so that they can keep their microbiomes healthy as they age.

Yeah, it's actually not too different from What I would recommend to all my patients, and I mean, it's kind of, sometimes it's kind of embarrassing to say that. So with all this fancy science that we have and all these subtypes and personalizing diet, that the approach is fairly standard, the overall approach. It has to be sort of standard concept of like the 30 or 35 plants and vegetables has to be adapted to the taste preferences.

Yeah.

Because food has to be enjoyable. A major function of food on our health is the enjoyment and the pleasure. It's closely linked to the centers within the brain. So I would say, you know, start with a breakfast bowl that has many of the ingredients, seeds and oats and chia seeds, fruits, fermented foods in it. So, you can easily come up with 5 to 10 ingredients that you add a spoonful to that morning bowl that you have rather than just have your yogurt with blueberries. I think more than ever, you want to avoid the ultra-processed foods.

Yeah.

Eliminate them from your diet.

I often say that food is medicine, but there's another part of the conversation we don't talk about enough.

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And the reason is that the science is there that it damages your microbiome. So if you, you know, 60% of our diet is ultra-processed food, that is directly damaging our microbiome and it's increasing what we call leaky gut because of some of the emulsifiers and other additives. So, it's not— and artificial sweeteners affect the microbiome. So, people think, oh, it doesn't matter, but it's such a big deal that I think if people could do one thing is swap out ultra-processed food for real food and eat a lot of plants, right?

Yeah. And then, I mean, just to make it practical, you can create salads, not the typical lettuce salads that now get a bad rap because of this These infectious diseases.

Cyclospora, yeah.

So, we've experimented this at home. You can easily add 10 different vegetables to a salad, to a complex salad that— so, if you start your morning like this and end your day with a salad like this, you actually already fulfill these criteria and you avoid the ultra-processed foods, particularly sugary stuff. I mean, we still don't know exactly with the ultra-processed foods. I mean, There is this controversy about this concept that it's too loose and not— and some people say it's all the sugar, but that's definitely not all of it because—

No, no.

Like all the chemicals, they don't even know what they are. They're printed on the label. It's kind of amazing. Like on an airline, you look at this thing with your so-called pretzels. The pretzels are the minor part of this.

And if it's a minute package, unless it's got simple ingredients that you recognize is definitely not good for you. Do you focus a lot on prebiotic foods for people? Because I think, you know, I think there's more and more data on prebiotics and polyphenols rather than probiotics as a benefit because that really changes over time the composition of your microbiome. Whereas probiotics, it sort of just gives you something additional, but it doesn't really sort of shape the bugs that are growing in there.

Yeah. And coming back to this, I mean, these 30, you know, fruits and vegetables. So, from Most vegetables and I mean also for some of the fruits, fiber is obviously a very important component, a health-promoting component because microbes are masters. I mean, they love the fiber because they break it down to their own food, main food source, but they also convert it into these short-chain fatty acids again. From a lot of the fruits, you get the polyphenols and that's a group that sort of been, I would say, mislabeled or misrepresented in terms of calling them antioxidants because it's a very interesting part of our diet, just like fiber.

Yeah.

It's not absorbed in our small intestine. The molecules are too big, so it has to be broken down the same, but the polyphenols are broken down by the gut microbiome into smaller molecules, which are then both again food for the microbes and are absorbed as health-promoting phenols and phenolic compounds that circulate in the body. So, and there's some very good studies. People always forget that, you know, with some polyphenols like flavonols, for example, there's the studies that reach all the way from molecular studies showing that they foster Vasodilatation of small blood vessels both in the heart and in the brain, increase nitric oxygen production with the vasodilator. And so, we know the mechanism how they actually protect these organs, both the brain and the health. And, we have clinical outcome data from pretty well-designed clinical trials. This is an exception. So, I think this is often It's often swept under the carpet that people say, yeah, the antioxidants. Yeah, it's good to have antioxidants. It's something much bigger than that. You know, it's—

Yeah, they're kind of, I call them biological response modifiers. They basically are signals or chemical signals that regulate all sorts of systems in your body. And I think we co-evolved with all these plants that do all these things for us, particularly our microbiome. And, you know, we have to feed ourselves, but we also have to feed the microbiome. And I think the focus on more prebiotic foods, more fermented foods, more polyphenols, these are things that are different than just like taking a probiotic that I think people really could learn about. And I think you could probably cover this in your book, right? The Mayer Model and talk about these various aspects of how to optimize your diet for your microbiome.

Yeah. And I always emphasize this point. You know, it's actually quite easy to find the right diet. If you identify a diet that's beneficial for your microbiome, for the diversity and the health and the richness of your microbes, that's the best diet for you as well because we have lived with these organisms for millions of years. Our ancestors, pre-human ancestors done that as well. So, yeah, I always say the general advice is eat what's best for your microbes. And the 2 main categories that pop up are definitely Fiber, prebiotics, and polyphenols. I mean, there's obviously many of these other vitamins and micronutrients that you can add in, but the main workhorse are really these 3 groups of ingredients.

So there's the fiber, the polyphenols, and the prebiotics. I'm sort of not clear of the third thing. It was prebiotics and polyphenols, and then the third part, which Yeah.

I mean, so, I mean, the third thing that I recommend from the diet is, you know, naturally fermented foods. And the reason I'm saying this because, you know, people always talk about, you know, yeah, I mean, when did people start eating yogurts? But there's thousands of years history of our ancestors fermenting food products in order to preserve them, not for their own health. So, our immune system and our gut had enough time to adapt genetically to these fermented foods. Again, the larger the variety of these fermented food components is, the better we think. I mean, the variety is always sort of a key component in the recommendations. It's not just what you eat, it's what variety you eat and how often do you eat it.

Yeah. And I think, you know, you're saying more specific. The, there's a lot of specific foods that you can eat that are helpful. And I, you know, I try to cook these and eat them regularly. One is like garlic, onions, shallots, leeks are great prebiotic foods, asparagus, dandelion greens, beans, lentils, chickpeas, oats, barley, cooked potatoes that are cooled, rice or pasta that's cooled, makes it more resistant to starch, green bananas. There's a whole bunch of these that are really great. I think there's also polyphenols. Like I know, for example, cranberry, pomegranate, green tea, and a lot of the colorful compounds really help a lot. And those I've used myself personally to help my own microbiome. And I see a change from it.

Have you ever had a microbiome— I'm sure you had multiple stool microbiome tests done.

Yeah, yeah. Oh, yeah. I've had them. And they definitely mod— they change and they shift in response to what I'm eating and my overall health. So, I think, you know, the bottom line is it's hard to change your microbiome through probiotics. But, if you use the fermented foods, the prebiotics, and the polyphenols, you're naturally going to be growing a better garden essentially inside your gut. And I think it's a really empowering thing to sort of start to think about when you're eating to actually use the science around what your microbiome likes to eat to feed them as well as yourself.

And it's not rocket science. It's actually fairly straight. Once you accept that concept, it's not rocket science. And it's It needs to be pleasurable. Like, I mean, I always emphasize this, you know, if you go to Mediterranean countries, I mean, they love their food. They don't eat it because it's healthy, you know. Yeah, yeah.

They eat it because it's good. It tastes good, right?

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That's right. And if you eat this way, you can make delicious food. I just, I think about just, you know, being more deliberate and also just being aware of all the things that harm your microbiome. And I think it's important to be aware that, you know, eating ultra-processed food, you know, a lot of different kind of medications, exposures to environmental toxins. All these things will affect your microbiome stress, your relationships, your connections, amount of exercise. All the things you talk about in the MAIRE model are all things that modify the microbiome in one way or the other. And the levers are there. I think, you know, I'd just like to close by asking you, you know, this is sort of a general conversation about creating a healthy microbiome, but, you know, I find it as a target and very, very specific target In order to treat a lot of conditions that are medical conditions using the microbiome as a direct kind of doorway to many, many health conditions, whether it's autoimmunity or allergy or asthma or fibromyalgia, or even things like migraines. Or you talk about the estrobolone, which is, you know, basically the estrogen metabolism in the microbiome. We didn't get into that too much, but that affects women's hormones. So treating the gut can often be a doorway to many, many different problems across many, many different specialties. And I wonder sort of how you think about that and where the sort of evidence is on that right now.

It is amazing. I'm still amazed about that. And as a sort of a physician and scientist, it's kind of against my nature to say there's this string theory of health and diet that explains everything. But I think the microbiome has that quality that you could use it as a— and I keep emphasizing its connections to the brain and the gut. I mean, the gut is an amazing organ, has all these components in it, immune component, hormone component, the nervous system component, and the microbes know exactly how to communicate with these systems within our gut. So, I would say it doesn't surprise me once you understand that it has so many influences on particularly the immune system when you think about almost all the immune cells travel through the gut and reach their distant destinations like what happened during COVID COVID doesn't start in the gut, but the immune cells that are in your lungs have a connection to their past when they did their migration through the gut-based immune system. And so even in— and the same with the brain. So many cells that end up in the brain have a history of encounters with the microbiome. I think we have to be careful not to come up with simplistic conclusions. Now we know everything. But I think we have to acknowledge that we've discovered unexpectedly a system in our bodies that is doing, is almost like rivaling the brain in terms In terms of its complexity and its influences on—

It is. I mean, I think we're kind of in the— it's a new sort of era in medicine, I think, where I think the microbiome has kind of shaken some of the foundational principles of traditional medicine, which is specialty and organ-focused, and sort of understands how now the gut is related to every system in the body, and the body's a network, and the microbiome is part of the network. And, We really have to think more about network and systems approaches to treating disease rather than this reductionist model. And I think, you know, what I've found over the years being a doctor and seeing patients is that when I focus on gut health with people across the spectrum of diseases, whether it's someone with Parkinson's or allergies or migraines or PMS or you name it, autoimmune disease, that people will get better, that people really do improve. And, you know, I've seen over and over in a way that's pretty striking. And I think, you know, the methods are still being worked out and we're still at the beginning of this era, but it doesn't mean that we can't apply these principles clinically, practically, because they're very low risk generally. They're very effective often. And, you know, there's not a lot of downside to eating healthier and managing some of those things, taking some prebiotics and probiotics. It's kind of low risk and the yield is quite high. So I think It's kind of an exciting moment. So, how do you see this field going over the next 10 years?

And just to wrap up.

I think there's going to be bigger breakthroughs in terms of practical applications than have happened during the last 10 years. I think this is— the science is still accelerating. I think the acceptance by practitioners, I mean, you see the increased popularity of functional medicine, Even for traditionally trained physicians, this keeps increasing for that very reason. And so I think there's going to be, I mean, there's very strong headwinds ahead. We're going to be facing, I mean, the next 10 years, it's hard to imagine actually what this world is going to look like from all these multi-crisis we're experiencing. which also will affect food production and environmental exposure, heat, and all kinds of things. But I think there will be a new era of holistic, I hate to use this old-fashioned term, but holistic medicine, medical practice that takes into account now all these insights that we get from digesting and integrating all these different pieces of information. I think people hopefully, you know, we see some efforts at that with the MAHA movement. I mean, that's something that you couldn't expect 10 years ago, you know, that something like this would happen.

Which, sorry, which movement is that?

The MAHA, the M-A-H-A.

Oh, MAHA, MAHA. Yeah, yeah, yeah. Make America Healthy Again. Okay.

In my opinion, this doesn't go far enough. You know, there's still a lot of loopholes in it that will not do it. But it's definitely something, something like this could happen. Imagine what will happen the next 10 years, you know.

Yeah, that's true. It's an exciting moment with the convergence of systems medicine, with AI, with changes in health policy, people awakening up to the fact that we're in a different era. I think it's quite exciting. And I think your work is such a key part of it and you really contribute so much to the field. I definitely encourage everybody listening to get your first book, which is an updated edition, The Mind-Gut Connection, and also the new book, which is The Mayer Model, available everywhere you can get your books. And, The Mayer Model is really about practical applications, a beautiful book. It's well-designed and it's easy to use. And, I think that it covers 7 pillars really helping your microbiome: food, exercise, mindfulness, resilience, community purpose, sleep, and talks about how you can focus on the right diet, very specific things we talked about even in more detail.

Yeah.

And, and, uh, and I think it'll help everybody listening to develop a healthier microbiome, which is really the key to good health. And I think many ancient healing systems have figured this out a long time ago, but we're finally figuring that out in the West. So thank you so much for your work and your contribution and your new book. And, uh, I can't wait to see what's going to happen in the next 10 years.

Thanks for having me on your show. Greatly appreciate it, Mark.

Check it out here.