Dr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health
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Welcome to the huberman la podcast, where we discussed science and science space tools for everyday life. I'm under huberman in and am a professor of neurobiology and optimal gy at stanford school of medicine. today.

My guest is doctor Justin sonenberg. Doctor sonenberg is a professor of microbiology and immo logy at stanford school of medicine and one of the world's leading experts on the gut microbiome. The gut microbiome is the existence of trillions of little microorganism throughout your gut.

And by your gut, I don't just mean your stomach, I mean your entire digestive track. Turns out we also have a microbial that exists in our nose in any other location in which our body interfaces with the outside world. In fact, there is a microbial on your skin, and I might seem kind of intrusive or kind of disgusting to have all these little microorganism.

They can be immensely beneficial for our health, meaning our hormonal health, our brain health and our immune system function. Doctor's sonnier teaches us about the gut microbiome, how it's organized, special meaning which microbiota live, where he teaches us about these incredible things called crips and meshes, which are little caves within our digestive track that certain microbiota take residents and at that premier real ee state, they're able to do incredible things to support our health. He also talks about the things that we can all do to support our microbial in order for our microbiome, to support our brain and body health.

Doctor song co. Runs his laboratory with his spouse, doctor ericka sonne g. And together they've also written a terrific and highly informative book called the good gut, taking control of your weight, your mood and your long term health.

Even though that book was written a few years back, the information still holds up very nicely. And today he also builds on that information, informing us about recent studies that, for instance, point to the important role of fermented foods and the role of fiber in supporting a healthy gut microbiome. So if you heard about they got microbial, or even if you haven't today, you're going to hear about IT from one of the world's leading experts.

He makes IT immensely clear as to what IT is, how IT functions and how to support IT for your brain and body health. During today's discussion, we don't just talk about nutrition. We also talk about the impact of behaviors and the microbial behaviour, such as who you touch, who you kiss, who you hug, whether not you interact with or avoid animals, whether you are those animals belong to you, or whether or if he belonged to somebody else.

If all that sounds a little bit bizarre, you'll soon understand that your microbial is constantly being modified by the behavioral interactions, the nutritional interactions, and indeed your mood and internal reactions to the outside world. This is an incredible system. Everyone has one.

Everyone should know how that works, and everyone should know how to optimize IT. And today, you're going to learn all of that from doctors on emg. Before we begin, i'd like to emphasize that this podcast is separate from my teaching and research.

Stanford IT is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, i'd like to thank the sponsors of today's podcast. Our first sponsor is athletic Greens. Athletic Greens is in all in one of vitamin, mineral probiotic drink.

I've been taking athletic Greens since two thousand and twelve, so i'm delighted that their sponsor in the podcast, the reason I started taking athletic Greens and the reason I still take athletic Greens once or twice a day, is that IT helps me cover all of my basic nutritional need to make up for any deficiencies that I might have. In addition, IT has probiotics, which are vital for microbial om health. I've done a couple of episodes now on the so called gut microbiome and the ways in which the microbiome interacts with your immune system, with your brain to regulate mood, and essentially with every biological system relevant to health throughout your brain and body.

With deleted Greens, I get the vitals I need, the minerals I need and the probiotic to support my microbes. If you'd like to try athletic Greens, you can go to let the Greens dot com slash huberman in and claim a special offer. They'll give you five free travel packs plus a year supply of vitamin d 3k two。

A ton of data now showing that vitamin three is essential for various aspects of our brain and body health. Even if we're getting a lot of sunshine, many of us are still deficient in vitamin d three and k two is also important because IT regulates things like cardiovascular function, calcium in the body and so on. Again, go to athletic Green dot com huberman in to claim the special offer of the five free travel packs and the year supply of vitamin three k two.

Today's episode also brought to us by element. Element is an electoral light drink that has everything you need and nothing you don't. That means the exact ratios of electrolier ts are an element, and those are sodium, magnesium and potassium. But IT has no sugar.

I talk many times before in this podcast about the key role of hydration and electoral lights for nerve cell function, neuron function, as well as the function of all the cells and all the tissues in organ systems of the body. If we have sodium anisim in patasse I an present in the proper ratio, all of those cells functioned properly and all our bodily systems can be optimized. If the electronics are not present in the hydration is low, we simply can't think as well as we would otherwise.

Our mood is off, hormonal systems go off, our ability to get in the physical action, to engage in in dance and strength and all sorts of other things is diminished. So with element, you can make sure that you're staying on top of your hydration and that you're getting the proper ratio of electoral lights. If you d like to try element, you can go to drink element that's element t dot com slash huberman and you'll get a free element sample pack with your purchase.

They're all delicious. So again, if you want to try element, you can go to element, element t docomo slash human. Today's episode is also brought to us by waking up, waking up as a meditation APP that includes hundreds of meditation programs, mindfulness trainings, yoga eda sessions and n sdr non sleep depressed protocols.

I started using the waking up up a few years ago because even though i've been doing regular meditation since my teens, and I started doing yoga ea about a decade ago, my dad mentioned to me that he had found an APP turned out to be the waking up APP, which could teach you meditations of different durations, and that had a lot of different types of meditations to place the bringing body into different states, and that he liked IT very much. So I gave the waking up up a try, and I too found IT to be extremely useful, because sometimes I only have a few minutes to meditate, other times I have longer to meditate. And indeed, I love the fact that I can explore different types of meditation to bring about different levels of understanding about consciousness, but also to place my brain and body into lots of different kinds of states, depending on which meditation I do.

I also love that the waking up up has lots of different types of yoga eda sessions. Those who you don't know, yogananda is a process of lying very still, but keeping an active mind. It's very different than most meditations.

And there's excEllent scientific data to show that yoga ea and something similar to IT called non sleep depressed or n sdr, can greatly restore levels of cognitive and physical energy even, which is to a short ten minute session. If you'd like to try the waking up, you can go to waking up dot com slash huberman and access a free thirty day trial. Again, that's waking up dot com slash huberman to access a free thirty day trial. And now for my discussion with doctor Justin swanberg. Justin, thanks so much for being here.

Great to be here. Yeah.

I am a true novice when IT comes to the microbiome. So i'd like to start off with a really basic question. What is the microbial? I imagine lots of little bugs running around in my gut and I don't quite like the image of that. But i'm aware that our microbes um can be good for us, but we can also have an unhealthy microbiome. So if I were to look at the microbes at the scale that I could see the meaningful things, what would that look like and what's gone on in there?

Yeah I mean, the essentially you're correct. I mean, we have all of these little microorganism running around in our gut, I think not just to start off with clarifying terminology um microbiome microbiota quiet often referred to our used to referred to our microbial community interchangeably. And i'll probably switch between those two terms today. The other important thing to realize is that these microbes are um not just in our gut p but they're all over our body there in our nose, they're in our mouse, they're on our skin and um so basically anywhere that the environment can get to uh in our body, which includes insider digestive tract of courses and colonize with with microbes and um the vast majority of these are in our distal gut in our collen and so this is the gut microbiota get microbiome and um the density of this community is astounding.

I mean IT really is a if you get down to the scale of um you know being able to see microbes, uh you know you start off with a zoomed out view and you see something that looks like, you know fecal material that I just inside the the gut and you zoom in and you start to know get to the microscopic level and see the microbes they are just packed, you side decide and and its a super dense bacteria community, almost like a um bio film. You know something that just made up of microbes to the point where um I thought that you know around thirty percent of final matter is microbes, thirty to fifty percent. So you know it's it's an incredibly dense microbial community.

We're talking of trillions of microbial cells and all those microbial cells if you start to get to know them and and see who they are um break out in the gut probably to um hundreds to a thousands species, depending upon how you define uh, microbial species. And then most of these are bacteria um but there are a lot of other life forms there. There are R K A which are little microbes that are bacteria like, but they're they're different.

Um there are uh U K riots. So you know um we commonly think of u carriole in the god is you know something like uh a parasite. But um there are you Carry ots.

There are fungi. There are also little viruses. There are these bacteria ages that in fact bacterial cells and so um and and those actually outnumber the bacteria like ten to one. So they're just everywhere there they kill bacteria um and so there there's these really interesting predator prey interactions. But overall, it's just a really dense, complex dynamic ecosystem. And and so you know where we're talking about the human as a single species, but we're also thinking of the human as this complex, integrated ecosystem of hundreds of thousands of species interacting and concert to do all the fantastic things that we know happened in the human body.

amazing. So we've got a lot of car go may be where the car?

Yes no yeah I mean, there there have been people that have liked and humans to just a really elaborate culturing flask for microbes and that we've actually been designed over the course of evolution um designed to just um efficiently propagate this microbial culture from person to person, from generation to generation. So it's a different way of thinking of the human body.

Interesting, I believe that our P H or the V P H of our digestive system varies as you descend, as you go from mouth to, you know, to throat and stomach. And you said that most of the microbiota in the distal common are there distinct forms of microbiota along the length of the of the digestive track and within these other interfaces with the outside world.

totally. Yeah so IT starts like with our teeth and in our mouth and saliva. There's a oral um these microbial species are very different than the ones you find in the digestive track.

There are usually um built to deal with oxygen very well there. You know in an area that is exposed to a lot of oxygen, of course, see different nutrients than, for instance, colonic bacteria would see. And they grow quite often in in mats that live in on teeth.

So they're very structured in terms of um and not moving around a lot. So they they're very fairly stationary as you move down the digester track. There are microbes in our soft us and our stomach, but those are those communities are are not very dense and actually not very well studied.

We know of a very um there's a very famous stomach bacteria known as helicopters, acker pilli, which um can cause steam closers and cause gastro cancer and some some um you know less frequent situations, but um you this is um a uh very different um different set of microbes. They have to be adapted to a different environment in the study, especially incredibly active environment, but also very different in terms of their ability to interact with other microbes just because the communities are less dense, their less dynamic, there's less nutrients that stay there and passage through the community. So the a lot of times those communities are reliant upon neutrons, arrive from the host as opposed to neutral, arrive from our diet.

As you move down out of the stomach into the small and testing, you start to see these communities, which are the ones that are becoming more well studied. Um small and test that is still a bit of a black box just because it's hard to access. And so there's some really cool technologies out there for using, for instance, capsules to do sapling as the capsule passes through the digestive tracks so that we have a Better idea of what's going on in the small and teston.

And then you get to the coin. And this is the community that is so incredibly densely packed i'm doing a tone that there's a tono metaphoric activity happening there and um a bunch of interaction with the host. And that's the study, that's the community that's really the best studied.

Part of the reason for that is because stool is so easy to obtain compare difference in something in the stomach or small in teston. And that stall is fairly representative. We know from studies that have been done using colonography. And so far, school is fairly representative of what's happening in the command. So um then super exciting community, but also the best study just because it's the the easiest to access in the lower digestive track.

Very interesting. I imagine these microbiota have to get in there at some point. Are microbial to scene in newborn's um in other words, where do they come from? And there I ask him what direction they enter the body yeah or is IT from multiple directions?

Yeah yeah great questions. So you know one of the burning questions that we can come back to at the into this is where does our microbiota from? Because IT is this kind of know existential question in the field like where where is this community assembling from and the the reason that is such an interesting question is that um you know a few days when it's in the whom IT that's actually a sterile environment.

There have been some studies that have looked at um whether there are microbes in the woman and microbes colonizing the feast at that point. There's some debate about this but overall IT looks like that's not a big part of the equation of my robo colonization. And um so each time an infant is born, it's this new ecosystem.

It's like an island rising up out of the ocean that has no species on IT and suddenly there is this like rush for you, this open territory and and so you know we know that infants go through this really complex process microbiota assembly over the first days, weeks, months, years of life and then you know you get into um switching to solid food two to three years of age. Um there are some changes in um childhood, adolescence, working into adult od but that first you know um zero to uh one year is a super dynamic time with really um kind of stereotypical developmental changes. And they got microbiota that appeared to um have the possibility of going wrong and causing problems for infants in some instances.

But you know if you step away from that extreme side of things going wrong, they're also where a lot of different trajectories that developmental process can take, because our microbiota so valuable and so plastic. And those trajectories can be affected by all sorts of factors in early life. So an example is whether an infant is born by c section or born vaccinated.

We know from um beautiful work has been done in the field that uh infants that are born by sea section actually have a um got microbiota that looks more like human skin than IT does like either the that the birth canal, the vagina microbiota or um the mother's um store microbiota babies that are born through the birth canal have initial colonization vag inal microbes and of school microbes es from their mother and so just these first days, whether were born by c section or through or through natural childbirth, you got microbiome looks very different and then compound on top of that, whether your breast fed or formula fed, whether your family has a pet or doesn't have a pet, whether you're exposed to antibiotics. There are all these factors that really can change that developmental process and really change your microbial identity eventually in life. The reason that this is um that the field is playing, paying really close attention in this instead ying this right now is because we know from animal studies that depending upon the microbes that you get early in life, you can send the immune system or metabolic of an organism or other parts, their biology in totally different developmental trajectory.

So what microbes are colonized with early in life can really change your biology. And we can come back to that later. But I we you know getting back to that original question of where your microbes s come from, you think, because you're born through your mother's birth canal, are exposed to her skin microbes, that a lot of your microbes would come from your mother.

But IT actually turns out that, you know, we can certainly detect that signalling, certainly see maternal microbes in the infant, but there are a lot of microbes that are coming from other places, uh, surfaces, other people, perhaps other caregivers, but perhaps h strangers as well. So we acquire our microbes from A A variety of sources. The first ones are are from our mom, from our caregivers, from the hospital. But then we add to that tremendously over the first year of life.

incredible. You even said pets. So if a kid in if there's a dog in the home or a parakeet in the home that clearly they have a microbiome also and potentially the child is deriving microbial to species from from those pads.

exactly yeah and so know the best studies that have been done have just looked at pets in the household as a factor and whether that changes um you know the group of infants that have a pet to look slightly different than the group of infants that don't have a pet and then the question is what what is the pet doing to change those microbes?

And some of IT is probably actually contributing direct members of the microbiota actually know we I have a dog, that dog occasionally will look my off without me like paying attention, you know and that's probably introducing microbes. Es um we also know that um you know pezare are down in the dirt there you know outside there, you there, they're being exposed to a lot of environmental. And so just um you know pet serving, as I can do, IT for a bunch of microbes that we wouldn't otherwise come in contact with as as a possibility as well.

Well, we will return to a pattern, in particular your dog and amazing dog. By the way, I met your dog just the other day, and I had to forced myself. I had to pride myself away from hevens. When what is your dog?

I lupis str.

路易 pastore。 How appropriate. Amazing dog with a personality on that dog.

The issue that I, I think a lot of people are probably wondering is what what is a healthy microbes and what is IT? What is IT supporting? We hear that you need a healthy microbiome to support the immune system, tablet sm, or even the good brain access.

How do we define a healthy versus as a unhealthy microbiome? Some people might know the unhealthy microbiome as a disciple. Sis is the word that I encounter in the literature.

But given that there are so many species of microbiota, and given that, I think we probably each have a signal sub pattern of microbiota, how do we define healthy versus unhealthy microbiota? Is there a test for this? Later i'll talk about technologies for testing microbiota.

there. A lot of companies now, a lot of people setting two samples in the mail. Never look at the postal service the same way again. But there is out there and it's getting analyzed.

So how should I think about this? I can think about things like heart rate, art rate, variability of BMI, all sorts of meat, rics of health. How should I think about the microbiota? How do I know if my microbiome healthy or unhealthy? Yeah it's it's a .

million dollar question right now in the field and there's a lot of different ways of thinking about that. I can talk about some of those, but I would say, you know um there are sessions at conferences, their review articles being commissioned. There are all sorts of kind of thought pieces about this right now, like what is a healthy microbial or what are the features that define IT.

And you know I think before diving into this, the important thing to to realize is it's a complex topic. Um context matters a lot. What's healthy for one person or one population may not be healthy for another personal population.

And um the microbiota is um malual you know it's plastic IT changes um our human biology, which I think is you know how we think about health quite often B M I and you know long gravity, reproductive success, how do you want to define IT? It's certainly um can accommodate a variety of configurations of god microbiota. And we don't have um you is really hard to untangle um all of the different factors of what what could be you very healthy versus a little bit less healthy.

So so I will say that there is no single answer to this, but there are some really important considerations. And um perhaps the best way to start talking about this is to go back to um the inception of the human microbial on project, which was this um program that that N H started to invested a lot of money in two thousand and eight, two thousand and nine for um really um propelling the um field of got microban om research that was becoming evident at that point that this was not just a curiosity of human biology, that I was really important for our health. And they had all this wonderful sequencing technology from the human genome sequencing project, and with the human genome completed that point, they started turning that technology to sequencing or got microbes.

And you know it's important to contextualize the amount of information that they're trying to um document. The you collective genome of our got microbes is on the order of um one hundred to five hundred times larger than our human genome. So it's just in terms of the number gene, so it's just this vast number of of genes.

And then if you start getting into some of the fine variation, it's know scales by ten to hundred four. So really a huge amount of information they are trying to document and and the and so it's so uh, I was a wonderful investment and that continues to pay dividends to this day. Um but one of their goals of that project was try to define what a healthy microbiome is versus a disease microbiome. Different context. And so they started um enrolling a bunch of healthy people and a bunch of people with, for instance, and flamma bad disease and other diseases.

Um and and the idea was let's let's document those microbiome, what microbes are there, what genes are there and then we can start to get a sense of what what are the commonalities of the the healthy people and and what know how how can that go wrong in these different disease states and um you know they they there were some answers from that but you um through those studies we really started to get the image that there is a tremendous individuality and then get and um and so it's it's really hard to um start drawing um conclusions after initial pass of that project of what is a healthy microbiome. But the other thing that we started to realize at the same time, there were studies going on documenting the got microbial of traditional populations of humans, hundred gathers rural agricultural populations and um those studies were really mind blowing from the perspective of all these people are healthy. They're living very different lifestyles and their microbial doesn't look anything like a healthy american microbial.

So does that mean that the healthy american microbiome is healthy, but only in the context of living in the united states and consuming what's consumed here? Or is IT that there is a superior microbial signature somewhere in our history or currently in the world?

Yeah you know I think that's that's kind of a big question right now. I think you know um there's a great quote from the genki that says nothing in biology makes sense to accept in the light of evolution and of these traditional populations are all modern people are living on the planet now but their lifestyle does represent um uh you know the the closest approximation to how our ancestors um early humans lived and and so those microbiome and now we know from sequencing of po faces the microbiome of these traditional populations is representative more representative of the microbiome that we evolved with that that potentially shaped our human genome.

And so one possibility is that in the industrialized world we have a different microbial from traditional populations. And that microbiome is well adapted to our style and therefore healthy in the context of an industrialized society. And there probably are elements of that that are true um but another possibility is that this is a microbiome that's gone off the rails that he is um you know determination in the face of antibiotic use and um um all the problems associated with industrial ized diet, western diet and that even though the human microbiome um project documented the microbes mm of healthy people, healthy americans, that what they really may have been documenting there is a perturbed microbiota that's uh really prety disposing people to a variety of inflammatory and metal bolic diseases.

He reminds me of the as a nearby logic was weed in the in the landscape of so called critical periods where early life environment very strongly shapes the the brain. And so many studies were done on animals raised in traditional cages with water bottles and food, maybe a few other animals of the same species. And then people came along and to wait. Normally these species in the wild would have things like, things to climb over and things to go through. And you provide those very basic elements, and also on the architecture of neural circuit looks very different. And you realized you, you are studying at a private condition um and earlier you actually referred to, if I understood correctly, to critical periods for got microban ome development um is IT fair to say that there are critical periods, meaning if my let's say my let's emit at me if my if my got microban was this biotic IT was off um early in life. Can I rescue that through proper conditions and exercise or is there are some sort of fixed pattern that's gonna hard for me to escape from?

Yeah there's a big field that's emerging now that um you know we refer to this kind of reprogramming that get microbiome, I think if we want to conceptualized humans as this aggregate human bial biology, um you know most people have heard of crisper in the ability to potentially change our human genome in ways that correct genetic problems.

That's a wonderful technology and has kind of put on the table no genetic engineering for curing disease, but it's much easier to change that microbes for a problem just because that that community is is malarious. Um the issue that I think um we're seeing in the field is that uh microbiome, quite often, whether they are diseased or healthy existence, stable states, they kind of ten towards this um well that has gravity to IT in in a way biological gravity where um it's really hard to dislodge the community from that state. So even individuals, for instance, that get an biotics um you know you uh take oral antibiotics s the community takes a huge set, know that bunch of microbes die, the composition changes and you know that represents a period of vulnerability where pathogens can come in and take over in cause disease.

But if that doesn't happen, the microbiota kind of worse its way back to something that is not exactly like but similar to the prana biotic treatment. Uh we know with the yet tary protocols um quite often you'll see uh really rapid change to the got microbial and then this is almost like a memory where IT snaps back to this, something that's very similar to the original state, even though the diet remains different. And so there's this incredible what we refer to as resilience if they got microbiome and resistance to change or at least resistance to establishing a new stable state. So that doesn't mean it's hopeless to change an unhealthy microbial to uh uh healthy microbiome but IT does mean that we need to think carefully about um you know restructuring these communities in ways where we achieve a new stable state that will resist the microbial community getting pulled back to that original state.

And one of the really kind of simplest and nicest examples um of this is uh an experiment that um we performed a with with mice where we you know we're feeding mice a Normal mouse diet um a lot of nutrient there for the gut microbiota things like dietary fiber and um we switch those mice, half the mice to A A low fiber diet and we are basically asking the question that you know, if you switched to kind of a western like diet, low fiber, higher fat diet, what happens to the get microbiota and we saw the microbiota change at lost diversity. IT was very similar to what we see in um in the difference between industrialized and traditional populations. But when we brought back a healthy diet, a lot of the microbes returned no is fairly know there there was this kind of memory where IT went back to very similar to its original state.

The difference is that when we put the mice on a low fiber, high fat diet and then keep them on that for multiple generations, um we saw this progressive deterioration over the course of generations wear by the fourth generation. The good microban was a know a fraction of what I originally was. Let's say, thirty percent of the species, only main something like seventy percent of the species have gone extinct, appear to have gone extinct.

We then put those mice back onto a high fibre diet and we didn't see recovery. So in that case, it's um um a situation where a new stable state has been achieved. Um in that case, it's probably because those don't actually have access to the microbes that we've lost and we actually know that we did a the control experiment of a mice on a high fiber diet for four generations.

They maintain all their microbe if we take those four generation mice with all the diversity and do a recal transplant into the mice that had lost their microbes but had been returned to a high fiber diet, all of the diversity was reconstituted so IT was, um you know so your question of like how do we establish new stable states? How do we get back to a healthy microbiology, have taken a lot of antibiotics or have a determinate microbiota? It's probably a combination of having access to the right microbes.

And we can talk about what that access looks like. They may look like therapy euros in the future. There are a lot of companies working on creating cocktails of healthy microbes, but IT will be a combination of access to the right microbes and um nurturing those microbes with the the proper diet. Very interesting.

This multi generational study reminds you of something that I was told the early in my training, which was that IT takes a long time for a trade to evolve, but not a long time for traits to evolve exactly, which generally is true of human behavior too. Although IT depends, we can all do Better. None the last very interest.

So I have a puzzle, a bit of a canon um around this notion of species of microbes to so the. If the PH of the accident is differs along the digestive track, but is more less fixed for a given location, right? I mean, less sometimes is really off.

The PH of the stomach is within a particular range in the the the interest and so forth. And certain microbiota thrive in at a given station, a given location along the the digestive track. And the PH is fixed more less.

I'm trying to figure out what what, what is allowing certain microbiota to stay in a given location? Why don't think my grade up or down? So are they PH sensitive? And that's what what they're selecting for along the track. And um i'm also trying to figure out how these changes in food so robustly changed the microbial. It's the way describe IT almost makes a sound like food is the the variable that's going to dictate the quality of the microbial, although i'm sure there are other factors as well.

And then in the back of my mind, I don't know that I want to ask this question, but I really want to ask this question, which is, where are they in there exactly? And why don't they all get flushed out, right? Um if thirty percent of a final matter is microbiota um then where are they living? Are they in? Are they along the the original and the little microbe I of the in testing and what are they attaching to and interacting with? We know there are neurons in there, we know especially within the stomach, there is a lot of work now being done on get neons and how they signal to the brain and so forth, but who are they talking to in terms of the the host cells? And um because if it's just from food, I imagine that they're in there having their good time or or not and then some are getting flushed out or not.

But how do they actually stay in there? Who are they attaching to? What are they talking about? What are they doing for fun?

Yeah ah super interesting. So um i'll come back to the attachment question and kind of like why they don't get washed out because this is super fascinating question. And um you know I think you're you're um initial point of like the the kind of regional differences in what's happening in terms of physiology. Biochemistry along the length of the gut is really interesting. They're certainly is a PH gradient along the length of the got there is um actually by carbonate that secreted into the small and testing to try to neutralize stomach acid.

There are also as bio that created um that creates A A different chemical environment in their bio loving bacteria that kind of live in that region of the gut um and then you know there there is an a nutrient gradient just because as food leaves a stomach IT um a lot of the simple nutrition are absorbed. And so you might see microbes in the small and test and for instance, that are Better at consuming simple sugars. But you won't find many micro bes in the colum like that because all the simple sugars have been depleted at that point.

Um and then the immune system is a big factor as well and the immune system is incredibly active in the small and testing. In the small and testing. Is this really interesting chAllenge for the host because it's a tissue that's been you know it's purposes mainly absorbed.

And so there has to be flow of um a lot of things know a lot of neutrons from the luminous contents into home sales. And so that means the barrier can be as sportif ed. And so the immune system is incredibly active in the small and testing to make sure that microbes aren't getting so close.

And if they arent getting close, there's a response to them to put them back in their right location. Um so there's no and then know along this whole kind of architecture of the gut, there's the launch udal gradients um things like like P H and so forth. And and I should say that you know P H starts to drop again in the Colin because a lot of those microbes are commenting things in producing assets.

And so you actually end up with uh you know the the P H starting to drop, not as lose a stomach, but starting to drop again if there's a lot of fermentation happening in the coin. In addition, you also have a gradient from the host surface epithelium out to the the middle of the gut. And that is likely the the key for what is retained in the gut and how the community isn't washed out.

So lining the gut, we have epithelial cells in the small in test and they're largely absorptive. Um in the coin, there's a lot of mucus production and we also see this in the small in testing. And this mucus lining is this um substance that we secrete largely made of carbon hydrate actually and the purpose of that is to keep microbes in the right spot and to allow nutrients and water to be absorbed in the testing and large and testing.

And so it's a mesh work that is supposed to keep out large things like bacteria, let in small things like like nutrient. That milk layer is IT turns over more slowly than illuminate contents passing by. And so if a microbe learns to hold on to that mucus layer, IT can actually resist the flow of the the contents of the gun.

And so there there's many microbes in the gun that are not just good at attaching to milk as, but also good at nimble, on IT, at eating IT. And you know, there are these bacteria like across I musi mucus loving. It's one of its main things that does is actually eat mucus in the guta that's its life style.

And and so there's you know an incredible um gradient of activity from the host tissue working away out to the middle of what's amazing is some microbes actually do penetrate pass the mucus. And there are these invaders instance in the in testing on as crips actually where the stem cells live that produced the epithelium. And there are microbial communities that conform in those craps.

And we don't know completely what their function is, but we've done some studies that appear to indicate that if you can localize to egypt, you've hit the jackpot as a microbe for being able to maintain dominance in the gut. So if you sit in the clipt and something similar to you, another micros similar to you comes into the guy, you can actually exclude that microbe. And the thinking is that I can't find a spot to resist being washed out of the gut. So there probably are these little nitches close to host tissue in the mucus that are absolutely essential for um for resisting getting washed out with the with the flow of all the contents.

incredible. That raises a question about two things that are reasonably popular.

One is this notion of classes um from either direction people will consume things by mouth to try and cleans their digestive tract there's a long history of this not recommending that they're differ opinions on whether not this is good or bad and the other is fasting or time restricted feeding uh the reason that I asked about time starched feeding as my understanding is that after a prolonged od of fasting there some auto absorbtion or digestion of one's own digestive track that then gets renewed in others. Ds, you're testing and stomach start eating. Its on lining to some extent in the absence of food.

So what do we know about cleanses? Oh, and then I suppose there's classes from the other direction to right which less popular but i've never run this statistic expert. I um but I certainly exist out there. What's the idea about classes and fasting as IT relates to the health or the dispirited is of the microbiota know there hasn't .

been a lot of high quality science in this area, so it's really hard to conclude whether these are good, good for health. There are bad for health. I think the the fasting we're in a really interesting situation in the industrialized world because we have so many problems associated with our digestive tract, and that probably has to do with our highly processed diet and perhaps having a microbiota that's fairly perturbed as well.

And so know um whether doing things like this are good or bad, it's really hard to define because we may be starting off in a fairly bad state anyway. There are so many diseases that we're dealing with meta lic syndrome, inflammatory bell disease, that just put a massive portion of the population in a very different category than people that are thinking about how do I maintain health, how do I live along life um from starting off and what we consider a fairly healthy state. And so things like you know fasting um and and a lot of other therapies that have been developed in the field. Um you know I think kito generic diet may be kind of in this category as well. There can be tremendous benefits in terms of um their impact in the context of meta lic syndrome and for people that are battling um you know eating a continual bad diet or something like that.

So I ended hearts, I think one of the one of the reasons for the popularity of inter mint and passing time circuit feeding and sort of what do they call them now exclusion diets where you entirely exclude me or entirely exclude plants or whatever, this is the that adhere and is sometimes easier in the all or none um as nobile as we think that there's a go no go circuitry. It's harder to make a decisions nuances decisions often about food than IT is to just eliminate entire categories of food. Not eating for many people is easier than eating smaller portions yes yeah ah so some .

of that I think .

is neurobiological and psychological. absolutely.

And we've had, you know gaston neology fellows in our lab that come in. And we kind of I think that kind of slice through the new ones of all this. There's a very simple recipe and really well accepted kind of broad definition of what a healthy diet is of the the meditation ian diet, plant based diet um is you know there's just a ton of data that um particularly people of european ancestry.

But there's A A pretty broad acceptance that if you eat mostly plants for most people, that's going to be very healthy to the point where a wonderful colleague of our Christopher gardener whose study diet um his whole life trying to establish what a healthy diet is in people was giving advice as i'm giving advice to die tian, who was trying to get all the rules of like what what he should be recommending to um people that he deals with are interested in a healthy diet and he said, so the number one i'm going to say plant based fiber is probably super important and that should be you know very high on list and SHE goes on a number two and he said, stop he said if people do number one well, you don't need to know any other rules. I mean, it's basically like if you can have a high fiber plant based diet. Um for most people at least you know talking about the bucket of people that are already in a healthy state, you don't really need to think about other things because you can eat too much me.

You can eat too many sweets. You've already eaten a huge amount of plant based fiber, your gut is full, you're not gonna be hungry um and and I kind of takes care of worrying about what should I eat? What what should I just eat a ton of whole plan, you know whole grain, legumes, vegetables, fruit, that that high fiber based.

not high, completely exclude meat and fish.

He and he was saying, like, you know, people can add their own spins on this but I I think that the the main rule just start off with, you know kind gets back to to Michael Collins, montreal, you know, um eat food not too much, mostly plants.

You know, I think if you stick with kind of these simple rules and don't over think, like, should I have this? Can I eat eggs? Can I eat, you know, just kind of stick to these simple rules that makes a very approached. But I agreed like so these gastroenterology feels that we've had in our labs say that they it's really hard.

We kind of say to them, why won't you give this dietary advice? It's really well known and they just said, well, it's it's really hard to get people to change their diet unless you're doing either a uh go no go sort of thing like or eliminating something. So you know carrots are giving you problems, don't care its and that's a very simple, easy instruction to follow but um doesn't really deal with the root problem of why can't you eat carrots because you should be able to eat carrots.

Most people can eat carrots and um and so I so I think that you know there we um yeah we we when we when we're thinking about things like fasting and you know all these different dietary regimes and lenses that the people do, um we we have to step back for a moment and say, okay, what are really the the big high level rules that we should take home and then if you are experiencing problems and you want to think about how to deal with them, it's good to go to an evidence based method where there's actually dated to back IT up. The the data in the field really shows that with like fasting, particularly if you go to like animals, that hyper nature are things like that where there's really extended fast, you actually have um a microbial to come up that uh that blooms in the absence of of food coming in through diet that's really good at at eating mucus. So you have um no bacteria that that specialized in eating nutrients to rise from the host because there's no other nutrients to live on.

Now whether this is good or bad we don't know, but IT IT seems like the you know consumption of mucus in access is a problem from the standpoint of microbes getting too close to host tissue and exciting information, which is what we see an animal models. When we deprive of dietary fiber, we see these mucus utilizes, become abundant and inflammatory markers start to come on. So so fasting short term might be fine probably.

Um you know there's definitely benefits that are seen medically um in terms of what that means for a long term health from the standpoint in the get microbiota would say we don't have the answer to that yet in terms of the you know the classes and the flashes and all this uh personally I I think it's a terrible idea. I mean, we know that like if you know and studies that are being done now to reprogrammed to get microbiota, to install a completely new microbial community, the first step is to wash away the resident microbial community that's there. So if you're in the process of acquiring a really good microbiota and you know how to do that, the flushing everything out is great.

Um otherwise what is happening is your kind of leaving rebuilding of the community to chance, like what is IT. And so um you know what what microbes are going to colonize who's gonna up space after you do this flesh clans and um you know that I think it's A A little bit like playing russian reality. You may end up with A A good microbial community and there afterwards you may not you certainly want to pay close attention to what you're eating while you're doing the reconstitution of the community after you do something like that, 对 吧？

Thank you for that. I know a lot of people are interested in these kinds of elimination diets and intermet and fasting flash time structure. Fear seems to be getting some traction, in part because at some level, we are all doing this when we sleep.

Most of us are needing when will we sleep anyway. And adJusting the numbers seems more accessible for a lot of people. But we have a lot of colleagues at stanford to I know happen to follow that regimen um or a time instructive feeding regime, but um also who's follow the most traditional meal spacing as well. Of course, the one of the things that I wonder about as we talk about primarily plant based with some, what do you say the poland thing was that was eat mostly plants, and then maybe some meat, but not too much, yeah.

or not much. Eat food mostly plants. Not too got IT. Sorry, eat food.

Not too much. Mostly playing, you know, just A I hear this again again. I know um there are number of people who do seem to do well on a lower carbon hydrate, um even some people who are report feeling much Better on a like really strictly almost meet organ only diet and the only reason I raise this is not I don't participate I think i'm an a morning of those omnivores that out there um I do eat some meat um and I do eat plants as well.

But the reason I raise this is that earlier you are talking about communities that may have microbiota are healthier than ours or at least different than hours. And there are communities in the world that that subsist largely on animal products, or for which unprocessed animal products are considered the richest nutrient foods in those communities. Protein is very scarce, and ancestrally protein was more scarce.

So eggs and meat and things that sort. So could there be a genetic component? In other words, if we fast forward ten years, and we actually can make sense of all the human genome stuff, are we gonna find that someone who has a skin and avian, uh, roots, or somebody who has south american roots, or somebody had descended from a different tribe, will do Better on one particularly diverse s another. And thereby where I should say in parallel with that, that they're got microbiome will have different signatures that are so you're microbes on might thrive on plants and mind might thrive on organ meets. And as I say this, i'm not a big consumer of organ mets have just playing .

this out for the sake of example yeah I yeah great um so um a few notes uh the first one has to do with the carbohydrates and restriction of carbo hydrates. And some people feeling healthier when they they cut the my guesses is this is this is my theory to be tested um that people feel Better cutting carbohydrate out because the diet that we eat in the united states and industrialized countries, the carbohydrate are largely crap.

Their process there is like stage simple sugar um it's things that contribute to glass mic index. It's the sugars that that we eat. They make IT to our small in testing, they get chopped up and simple sugars absorbed into our bloodstream.

And we have a ton of glucose then coursing through our veins which we know is bad and can lead to things like diabetes. Um if the couple the carbo hydrates that were in our diet were complex carbon hydrates dialect ary fiber. And we like to refer to the subset of dietary fiber that the microbiota can actually access as microbiota accessible carbo hydrates.

And the reason that we like that term as that has the word carbo hydrate in IT. And it's um to point out that not all carbs are bad. It's just there are bad carbs or carbs that are bad if you consume them in too high quantity, things like you uh, table sugar and simple starches.

But there are good carbs as well in these microbiota cessions carbo hydrate are the complex ones that we can't digest and fuel I got microbiota I got microbiota confirm them. And um so the you know I think I think um we probably all would be Better off with less of the carbs that were typically served, but most of us and probably the vast majority of us would be Better off by consuming a lot more cards that were complex that were microbiota cessions. Um and i'll come back to why that's important.

In terms of our biology, there are some mechanisms that are known as to why those complex carbon hydrates are so important for our health, for most of us. Um I think this aspect of human genetic adaptation to diet is super interesting. And then layer on top of that got microbial adaptation to diet, which is another layer of this that um is also fascinating. It's very clear that over very short birds of time, humans can adapt to differences in their diet, lack tae persistently.

Kind of the classic example of this just over the past ten thousand years um humans you know certain groups of humans have adapted to being able to consume dairy um by taking this enzi lack taste that Normally just expressed in most the world's population early in life to be be able to metabolize actos in breast milk um by extending the expression of that throughout life, now you can consume milk for your whole life and so that is an example of specific populations of humans, human genome genetically adapting to die in a very short credit time and this there are other examples of this and undoubted this has happened um throughout the world to various aspects of diet. So certainly um it's important to remember that there will be um different diets Better Better for different groups based on what genes you you harboring and have in your in your human genome. The other aspect on top of that is that um you know there there are um good examples of the gut microbiome adapting to cultural differences in diet.

And the classic example of this is the degradation of seaweed. So we know that most americans, if you eat sushi in and there's norry there, you you eat um some of this the seaweed IT has a dietary fiber in IT. Notice the poor for in that poor friend will shoot through most of us untransformed in nerd substance. You know it'll do other things like retain water and service kind of something like saulus not be for mental at a high level. Um if somebody from southeast asia that's always consumed um seaweed and is part of a culture that consumed seaweed is.

They have a good microbe that can now metabolite poor form and so there are these very specific gene transfer events where the genes for breaking down poor friend have been imported into the micro bio of many people in south east asia to um you know, we can think of IT is helping digest poor form, but it's really just a microbe that's found a ish, found a way to make a living in the gut by consuming something that's common in the diet there. So there are these different layers, are human genetic adaptations, and there are microbiome ditties that are cultural and and based on people's geographic c location um but you know that there is no escaping the fact that for much of human evolution, the vast majority of people, people that are on this planet, had ancestors that were hundred gathers force ging consuming huge quantities of plant material just because that's that's what was there and so one of the groups that we study, the hadds one hundred gathers in africa. Um and I I should take a moment just to say that you know um our research and and research of many people in our field and other field to rely on study of indigenous communities and it's really important to um think of these communities as um you know are equals their modern people on the planet.

They have interesting lifestyles that are informative with regard to certain aspects of of human biology, but in many cases they also are um leading a vulnerable existence. And so we really take great care in our research programme. And it's important for people to realize that these populations take partner research because they're wonderful research partners and we need to be mindful of kind of thinking about how um yeah both we talk about them and use our data that that has um been game through their um generous contribution to our research program.

The holds one hundred gathers is estimated consume on the order of one hundred to one hundred fifty grams of dietary fiber per day. And that, in start, contrast to the typical american that consumes about fifteen grams. So somewhere ten, seven to ten fold decrease in the main nutrient that feds are got microbiome in the american diet.

The the hadza are a, 嗯， you know, one example. There are different, many different form ging populations, but the vast majority of these populations consume huge amounts of dietary fiber because plants are the reliable, consistent sources. You know, if you, as a hundred gather, go on a hunt, usually that hunt is unsuccessful.

You know, I think the data that no one out of twenty to thirty hunts are successful in ending actually big game for the hot zh. They have you birds that they shoot and small animals, but quite often, day after day, they're relying upon berries, tubers, baobab fruit. Now they're y're relying on the plans in their environment.

And actually you um you go to the data and look at what their food food preferences are. Their food preferences are actually meet and honey. So they don't eat a high fibre diet because they love fiber.

They eat a high fiber diet because that's what's available and consistent for them to to survive. But you know, our brains are wired for chord density. And so if you took a hot zen, put them in a restaurant in the united states, they would make the same crappy decisions that we make. Because we, you know, all want sugar and fat and calories. It's how our brain is wired.

And protein and fat are essential for brain development as far as we know, right? So so IT sounds like that the heart, I hope i'm pronouncing that correctly, you said, would prefer to eat, meet and honey. But they do. They happen to consume a lot of plant fiber as a consequence of what's available.

The one of the questions I I have is that relates to all of this is IT IT sounds to me like there is no question from the pool vegan all the way to the extreme opposite which should be pure meat diet um that avoiding proceed foods is a good idea. We're heavily proceed foods in general and I mean not that you the occasional consumption is is necessarily bad, but whether not one is thinking about one maco neutral profiles or another IT sounds like consuming process fd is just a bad for the microbiome. Can we say that categorically first? Okay, yes, what I know.

So your low car person, your zero car person, your extreme vegan, no meat, whether not you're all meat, organ meat. Sounds to me as if a the number one thing, maybe even there I say above crisis, A A point about plans. So i'm not in chAllenge because gardener on nutrition, I would be way outside the lame lines to do that.

But is that to avoiding processed foods? yes. Is paramo. yeah.

And I think that's completely compatible with what chrystal her is saying. He was saying if you put prioritize getting a huge amount of of whole plant based food with a lot of fiber first, you're not going to have room for reading a lot of processes. So yeah, so it's kind of the same as avoiding processed.

So I think that those are exactly the same rule. And I I think that the year exactly right and we can break down what you know. There's a lot of data White different components of process food are so bad for us and so bad for our microbial and I can talk about a few examples of that.

But the flip side of this is this mechanism of, you know and again, thinking about the spectrum of a plant based diet vers a meat based diet. Um you know there is uh a lot of data to tell us that a meter a key to genre or high fat diet may have big benefits in terms of short term meta lic health. That's typically how people think about that diet.

Um there's also a lot of heart disease. It's linked with that as well. There's good literature for that, which is something to for people to to look at and be aware of the plant based diet.

If you're reading a bunch of complex um you know fibers that feature got microbiota, you're got microbiota produces these substances called short chain fatty acids, things like mutate and it's known that these short chain fatty acids play really essential components both in terms of fuel in colonizes, enforcing the barrier, keeping inflation tion law, regulating the immunity stem regulating metabolism. And so know a lot of people think of dietary fiber. Is this in nerd substances passes through, makes us feel full maybe for a little bit, but we get hungry afterwards right away.

If you're eating a lot of fiber that's feeding, you're got microbiota. You're got microbiota just producing this vast array of fermentation and products that then get absorbed into our bloodstream and have all of these tremendous skating effects that appear to be largely beneficial on our biology. And so to think about that paradise of simple carbs versus complex carbs.

In the case of simple carbs, you end up with hyborian sugar. Know something that will Spike your instant, and you have all kinds of weird metal bolic effects. In the case of complex carbon hydrate, you end up with very low blood sugar because most of those have low gye mic index and a bunch of short chain fat acts that are having regulatory rules.

So so just to round out that that topic, I think there is a reason to think that you know maybe not appropriate for absolutely everyone out there. But I think the vast majority of people, particularly given the statistics of what we know people eat in the united states and the industrialized countries, most people would reap tremendous health benefits from eating more whole plant based dietary fiber. Now proceed foods, I think, is this other dimension where you have all of these weird chemicals, artificial sweeteners, weird fat um you know a lot of refined simple nutrient, the simple neutral ts we've talked about.

But we know that for instant artificial sweeteners can have a massive negative impact on the gut microbial and can lead us towards metal bolic syndrome. Me actually there's been beautiful work out of the wiseman institute on this. And then a motifs, these compounds that are put in processed foods to help them maintain shelf stabilities so things don't separate.

And so um you know all the the moisture content is retained appropriately. Um many of these are known to disrupt the milk layer. And as soon as you start disrupting that barrier that can lead you in the direction of inflation tion and in animal models, we know that can lead towards meta lic syndrome as well. So there's there is a components of process food that are, when studied in isolation, known to have a direct negative impact on get biology in the they .

mention of artificial sweeteners is interesting. I confess it's a third rail on social talking about artificial sweeteners. There two camps, IT seems, or at least two camps, one that say artificial sweet tens are not detrimental at all. Another that says the very detrimental, mainly based on the mouse studies and then their people in the middle that are, I put myself in that category out drink the occasion that so I don't consume them in large volume, but I was in the middle, however. And so I just throw that out there because I know immediately people are jumping on that.

But I will just mention there's some recent data out of the ago board has lab at duke versa that the neurons that live in the gutty coast of these neurologic ells can actually distinguish between artificial and um true sweet sugar versus artificial uh swetnams. The extent different patterns of neural signals up to the brain and the brain circuitry seems strongly impacted so I think as the data emerge we're hearing more and more of these artificial sweet tener either or problematic or at least are signaling different events in in the gut. I do want to make sure that we distinguish uh artificial sweetness ers from non chloric plant based swetnams. Um and this is based on the mistake that i've made over and over again on the podcast, where i'll just kind of lump artificial sweet nes um into one big category and say and then i'll mention stevia, so what about plant the sweeteners that are not artificial? They weren't manufactured in a laboratory like sacring or super lose or expert in what do we know anything about plant based non Clark sweet tensor low collor ch swetnams very little you .

know a lot of those have um a lot more bank for the buck there. They are incredibly suit. So IT takes a really small amount for them to trigger a huge amount of sweden. And um and so it's depending upon the mechanism of action by which these um sweeteners that are not sugar or impacting our biology IT may be that those are actually um you know less negative or more healthy than um the ones that are artificial just because IT requires less of them in the food for us to perceive that sweet test IT may also be that because there I don't think that everything is that natural is Better necessarily than things that are artificial but IT may be that because of um you know kind of evolutionary exposure to these compounds in our diet. Historically, there are I think, traditional populations that use these, for instance to sweden, um you sweeten different foods um that our bodies just kind of know how to deal with those compounds Better than the ones that are sthetic. Um but I think the this study is telling to be done.

do you actively avoid artificial sweeteners suk illos aspera in schon?

You personally yeah you know so I I do I I avoid them but i'm not I you know um so um I worked closely with my wife eras you know we do we run the lab together and we um you know wrote this book the good gut where we kind of document our journey in changing our lifestyle, dietary habits, choices we make based on the research as we've gotten to know IT in to get microbiota past fifteen.

And you know I think that one of the lessons that we've learned is that just uh doing things in moderation makes that a lot um easier and doing things slowly makes IT a lot easier. And so so there are very few rules that I have that are harder, fast. I'm a pretty flexible heater.

I don't believe that having artificial you having a diet coke um well you know somehow cascine into some terrible disease or something like that. I tried to avoid them. I don't really like the flavor of them. I'm supersensitive to the the nuances of the flavor even with the new stevia moggi sides from one fruit t and stuff like that, I just really the flavors are really heard for me to deal with. But um so so but I also in this journey of changing our diet, like when we started off in microban on research, I was in the habit of you know in the afternoon having a sweet a nothing or a cookie or something like that and when we started to realize that we know we should be eating less sweet since eating more diet ary fiber, this was an incredibly difficult change for me to make. I was just wired to kind of crave .

this classic scientist, scientist. Love the pastry in the afternoon, in the coffee. yeah.

And then the old days that used to be a cigarette too. When I started my training, a lot of people still smoke. Yeah right.

And he was only during my post doctor training that they eliminate smoking on campuses. And productivity took a took a trough for a while. And until these people developed other tools to uh to focus their .

attention exactly. So there there is this kind of like need, and then once you have an in grain behavior and maybe things that are addictive, that becomes incredibly difficult to break that habit. And um and so I would say you know gradually over the course of like you know five or more years, we have um migrated our diet away from sweet foods to um things that are are less sweet um and it's you know it's been a journey. It's been a slow process um but we've gotten to the point now where we've just retrained our pallets and it's amazing how this happens now where i'll have something that you know is something that I would have used to have like daily and it's unpalatable. I like I just can't deal with the sweetness of IT and and so I avoid I certainly avoid artificial sweet tender, but I also avoid just sweet things in general that have sugar in them just because they now that, you know, is originally I was made, I was trying to be disciplines and trying to change my diet, but now they just don't .

taste good to me. Like why I completely lost my appetite for sugar at the turn of the last year, and I don't know how to explain IT, but the way I even though I don't have an mechanistic explanation, I I say I like sweet people. I don't like sweet food anymore.

I just don't. I have not lost my appetite for fatty foods. I love cheese and a certain meats for me.

I blame my argentinian. I is is I gravitate towards them. But in any case, avoiding process foods, probably avoiding sugars. And muslims are these kinds of things for people listening or watching. We're not setting up strict guidelines that we're just bouncing around the ah the carnival that is the microbial and a nutrition because I think that these we hear this everywhere eat this, don't eat that or this is best for microbiome, worst for microbial.

But I hearing fiber again and again, so were going to come back to fiber, but I want to make sure that we close the hatch on this issue of fasting and cleansing. Based on your answer earlier, IT sounds to me like IT is not necessary to do a cleans or fast prior to an attempt to repopulate the microbes. In other words, if I want to make my microbiome healthier, IT sounds like I don't have to try and flush all the the current microbiology of their first.

Is that correct? Yeah you know it's a very good question and I don't mean to suggest that those things are known to be terrible or I would just say like this, you know the studies haven't been done and to me, wiping out this microbial community um unless it's done with like some sort, unless it's done in an informed way and we don't really have the information for how that would be done IT just seems like um you playing a littery a little bit.

And so so I think I don't want to say that those that may be that when the study is done, those are to be amazing, but I just don't think we have the data to know yet. So it's somewhat of an arbitrary thing. Um if somebody you know out there feels way Better when they do this and are not experiencing problems with the then maybe it's the right thing for them.

But I certainly can can say that it's something great to do. I can't imagine a future where um as the microbiome gets incorporated into this emerging paradigm, precision health, you go into a clinic, somebody types your microbial and says, oh, there's a this huge, massive m configuration. You have all these in grafted bacteria that live that a residence and you're got microbiome that are sending out molecules that are not good for your health.

IT would be good if we do a master y programing of IT. The way that we do that is we flush your gut and we actually give a light and biotic treatment to try to kill everything that's there. And then we repopulate with this other conception of microbes that we've studied and no or healthy, no or compatible with your human genome, and can be reinforced with a diet that we know is good for you will install those microbes, will help you, along in the diet to know so you know, how to nourish those microbes.

And that will be the way that will reconfigure. You got microbiome. So, you know, I can't imagine a future where that sort of flushing or cleaning is part of something for repopulating the guy. But right now, that seems a little half ked to me.

Yes, great. I'd love to talk about fiber and fermented foods because you and Chris had a really what I think is a really interesting, exciting paper at the end of last year about comparing um the inflameth um so inflammatory markers of people who ate a certain count of fiber, certain amount of of these fermented foods.

This study is amazing for several reasons, but almost as amazing is how diverse the interpretation of this study was in the media. If ever there was a study that was um kind of hy jacked by different priority schemes out there, and it's this study. So you performed the study with Chris and your post docks and graduate students and staff.

What are the major conclusions and what sorts of directives, if any, emerged from this study? And i'll just press this again by saying if I wasn't clear, some news reports said, ah this means fiber is not important and then others said, this means for mental foods and fiber are important and others said fermented foods are the thing and the only thing IT was all over the place and one of the reasons for doing this podd cast at all is so that we can go straight to the people who perform the work. And even though i'm not certainly not expert in microbes and give you the opportunity to share with me and me to ask the kinds of questions that have zero agenda, I do like sour crowd.

I do drink the occasional computes A. I do like low sugar, not so sweet forms of fermented foods. So I will be delighted if fermented foods are good for me, but I have no stake in the fermented food industry.

Yeah yeah yeah yeah yeah great. Um yeah wonderful. And and an important note there is, is the one you point IT out that this is an incredible collaboration with Christopher diners lab and you know a bunch of people Erica sonnenburg help lead the study and and then tones of like you are saying, postdoc staff and um other people at at stanford and wonderful participants that were part of this study. So a huge team effort.

Um let me take before I dive into that study, let me take a step back because I think the reason that we did this study and and kind of Christopher her's group and in our group as as started to pursue this line of of looking at dietary an interventions and how they impact our microbiome, how they impact human biology, goes back to this kind of epiphone y that we we had while studying. They get microban um because I think when we started studying at at stanford we are thinking about IT as a kind of newly appreciated aspect of our biology almost like um finding an organ that we didn't know as there and starting to think about like all the drug targets that were there. Can we go in with small molecule drugs and think of ways to manipulate this community to humiliate disease? And this is largely the mindset of western medicine and largely born out of the area of infectious disease.

You wait for an infection to start a bacteria infection you treat with antibiotics and you that the way medicine is practice and that's become less successful over time as we moved into this era of inflaming western diseases and um you know with the exception of the the current pandemic that sweeping the world, largely moved out of the era of infectious diseases, at least infectious bacteria diseases, that this paradigm of waiting for diseases to appear and come into the clinic um is not really very effective in the context of inflaming western diseases. Ottawa mune diseases, meta lic syndrome, heart diseases and inflammatory disease. You know the list goes on and on and um and so we started to think a lot about like how can we get out in front of this?

How can we think about like preventive ways of dealing with this crisis of metal bolic and inflammatory diseases? And this tremendous, beautiful body of literature started to come forward in the field about ten years ago that shows that the gut microbes ome is absolutely critical to modulating our immune status. So if you change the microbiome.

You can fundamentally change how the immune system Operates. And we know that the immune system is at the basis of a lot of these diseases flament ory chronic diseases. And so IT IT brought up this possibility.

That may be the fact that we're not nurturing this community well enough, maybe the fact that it's um deteriorated over time um due to all of the things that go along with an industrial ized lifestyle, antibiotics and so forth. Um maybe we have a microbiome right now in the industrialized world that is setting our immune system at a sap point, simmering information that's driving us towards ease and flaming diseases. And wouldn't IT be wonderful if we could figure out how to um uh use diet specifically, but just kind of learn the rules of how to reconfigure both the composition and function of argot microbiome.

So that information was different in our bodies so that each one of us was less likely to go on and to develop in flamm disease, leading to Better, you know long novy and health over the course of our life. And so we we were you know study this in actually in mouse models and realizing that um you know we really needed to start doing human studies, we needed to um start studying microbiome humans and because we are studying diet, we knew that this was something we could go in and do right away. We didn't have to apply for F, D, A approval for a drug before we could do a human study.

We could just start doing human diet. Ary interventions launch totally monitoring the immune system and the microbial, and starting to put the pieces together of what is that in diet that can change our microbiome a healthy way, help us to find what a healthy microbiome is and monitor the immune system in great detail. And so there are really two critical components of this in addition to our microbial expertise.

One was Christopher gardeners group. Um we wanted to do these human studies but were absolutely terrified of humans. We work with mice.

Humans are terrifying in many ways themselves.

That that's true you .

know of four housing of course.

Yes yeah sadly just for that portion of the population the um so Christopher group were there are masters are working with human populations and then the other wonderful thing that we have a stanford is this human immo monitoring center um run by mark Davis and holden maker. They started this beautiful center for allowing people to do imminent logy in humans. Critical element because a lot of the mouse studies don't translate well to humans.

So if you can do the studies in humans, uh, similar to how we are thinking about the microbiome, you learn something that you know is relevant to humans. And so having that immune profiling capability where we can monitor, you know hundreds to thousands different parameters in the immune system, longitude and people from a blood draw, and not just know if C R P goes up of inter lu and six goes upper down, but to be able to see all these facets of the immune system changing concert as we're changing the microbial with that was really a key component of this. And so our flagship study, supported by wonderful donors. Um so this actually isn't in funded by typical foundations and national institutes of healthy was funded by philanthropy. We wanted to understand if we put people on a high fiber diet um how would that affect their microbiome immune system and if we put them on a hydrometer food diet, diet rich and live microbes and all the metabolizes that um are present from fermentation and foods, how would that change microbiome immune system?

Could you give us some examples of what those diets look like? And were you changing their bases al diet? Or were you just adding things on top of what they were already eating?

So because it's hard .

to change people's die, it's have to trust that they actually do IT. They're not sneaking and totally .

yeah and so so we um and you know we've started the center for human microbial studies at stanford for doing a lot of these studies and a portion of the studies we do focus on supplements, pro biotics, uh microbes delivered in pill form prebiotics which are um purified forms of fiber and in those cases we actually can have placebo groups um because you know it's it's more like a drug study and um we don't change people's diet so we can just administer this on top of what they are doing.

So in a way, they're a lot more controlled, but it's not food. When you start doing food studies, you can't do a placebo group because people know what they're heading. And the other problem is that it's really hard to just change one thing because as soon as you start adding something, people usually eliminate something else.

The idea was to basically give these people simple instructions for, in the case of the high fiber diet, just increasing plant based fiber. So can you eat more whole grains, more logins, more vegetables, nuts? Get the fiber up in the range of, you know from fifty to twenty grams per day, up to over forty grams per day. So can you kind of double or more the amount of fiber, the U E. Per day, knowing that that would have a tremendous impact on a lot of other facts of their um diet. They um eat less um uh meat, animal base protein, less animal base fats as a product of this um you know I will say that getting back to the know Christmas rule for a healthy diet, um a lot of the macro neutral changes that we saw in their diet were consistent with um healthy changes in the less saturated that less animal base protein, more plant base protein. So a lot of changes that are known to be beneficial kind of came in concert with just telling people eat a high fiber diet, high plant based fiber diet.

Um the people that were eating the high from mental food uh diet, um they were instructed to basically eat um you know foods you could buy at a grocery store that were naturally fermented and contain live microbe and so this largely consist of yoga uh key for uh power crowd kim chi, um you know some fermented vegetables um kind of brain for mental vegetables, les pickles, things like that but but they do you know one of the things that I think is a pitfall in in choosing from mental foods is know you can go down the can food dial and there's a huge section of pickles and jars that are can those are not formatted foods. Those are are cucumbers that they've put in a seac acid in vinegar to reconstitute that fermented flavor. But there's no live microbes involved in that and even shower crowds in the can food tile, even if they were naturally for mental quite often and they're not quite often, they're just bind um in in vinegar. But even if they are naturally commented, all of the microbes are killed prior to canning or during the process of canning and if you want so what we use for the study and if you want to have live from mental foods that contain life microbes, you need to buy those out of the um the refrigerated section essentially.

And really glad you pointed this out because you can find out our crowd on the non governmental, non refrigerated shelf that is indeed non informative. A lot of fermented foods that available in the us can be high in sugar. So where is there any instruction as to, you know, getting people to make sure that they were consuming yo gurt that weren't loaded with sugar? Or or did you let them just select for the stuff in the cold, the cold section that is fermented?

No super important point. We we instructed people to eat non sweetened yogurt. Um the if I think a huge pitfall in the areas you can have a yogurt loaded with bacteria kind of the base of what's healthy and then a ton of like artificial flavors and sugar loaded on top of that manufacturer put a ton of sugar in after the fact that kind of mask the sour taste instrumented foods, which is hard for some people to become a customer to when we were switching to more fermented foods, our daughters were Young at that point.

We would take you know plain yoga, which um they didn't like just kind of meat. Um we would mix them like a little maple syrup or honey just a little bit and gradually we reduce that over time to the point where um their palot just that now they just really like playing yogurt. But IT is you know I think getting used to that sour flavor is is difficult, but people really should try to stay away from those fermented foods that are loaded to the sugar. And that's what we instructed people in the study.

And beer was not included. Number of people that asked when I I did brief thing on social media about this study and hopeful ly, I got IT right. And I think I did but people just ask about beer. I'm not a drinker so um for me beer has no appeal anyway but beer is fermented correct um but where they instructed to avoid de beer or to drink beer.

you just to go with their Normal dietary habits, but that did not count as affirmative food and and compute I can have small amounts of alcohol in IT um but um you know um we yeah cambodia actually was one of the major things that people drink during the are consumed during the fermented food phase and um the you know that the deal with um with a beers that there may be beneficial properties of the microbial communities and naturally for mental beer, but most the beer that we buy again and filtered and there's no live microbes there. So very different than if you you know size in IT off of your home brew and drink IT. Probably if you buy .

IT in the store, I will get to the results study in one. But I say A A lot of people show away from the high quality for mental foods because they can be quite costly. I just refer people to a resource in tim phrase book the four hour chef.

He actually gives an excEllent recipe for making own sour crop, which basically um involves cabbage and water and salt. But you have to do IT properly because you can grow some um not necessarily lethal, but somewhat dangerous bacteria if you don't scrape off the top layer properly. But he gives beautiful instructions for how to do this in vat.

We've started doing this at home. Now actually we get them, which is a ceramic c that and you can see you can make large amounts of truly fermented sour crowd just from cabbage, water and salt. If you're willing to follow the protocol, and if you're interested in science, that protocol looks a lot like what you'll do for most of your graduate career.

He said, maybe some sequences too. So anyway, just to refer people do a source that's very low cost yeah compared to buying the high quality for mental with even compute as. For somebody you know like five dollars a bottle no only this much. And if you consume liquid way I consume them that's kind just the big the start so yeah um and but .

you if you can get your hands on a scope e ambushes, another one that's super simple can grow your own. You you can just make your own and it's super easy to do. I make IT.

I constantly have a bad can boucher going at home and IT just know this is a scope of sibiu tic community of bacteria east that you you know, you brute, you add sugar to IT and you put the scope in and you wait a week or two depending upon the temperature, and you then you just, you know, move the scope over to a new batch and you're old. What the scope was in his cambodia. And it's it's wonderful.

I love I would love IT if members is ready and suit, start to make their own comb chi and sarka. I been having so much one. I don't do IT, but you know, it's done in our home.

I don't go on anywhere near the food production and is for everyone's benefit. So how much fermented food and then uh, where they consuming and because you mention the number of grams, approximately of a fiber and uh but was IT in serving answers how many times a day? Early day.

late day, right? Yeah so the we had A A wonderful dietician instructing people for this uh her name's delhi. Approval and SHE really was the key and is the key for many of our studies for getting people to eat differently. And um you know the general instructions for people to eat as much experimented food as possible, more as Better.

And the the reason is that with this initial study, we really wanted to maximize our chance of seeing a signal if there was something biological going on with the idea that if we you know the dose was excessive and not easily achievable by a lot of people, the end we can go back and and say, okay, this this is the point of which we lose the biological signal um but people um during the height of the intervention phase, the intervention phase was six weeks um during the height of that were up over six savings on average per day of formated foods so kind of two surfings at each meal and the uh you know answers are way to ze IT really depends on what the fermented food was and we just told them to stick to what was the recommended dose on the the package that they were. They were buying for a cambodge. I'd be like a sixty eight on glass um sour crowd like a half cup or something like that and sing with yoga.

great. So what what were the results?

Yeah so the results um I sounded us in a way, but then thinking more deeply and it'll be evident even after I explaining IT in the context of this conversation, likely why we saw the results we saw um the results were astounding because um our hypotheses sis going into this was that the high fiber diet was going to give the massive signal. We know that this is the big deficiency in the western diet.

Um we uh all the male studies have told us that high fiber really leads to a much healthier microbiota can lead to positive changes in the immune system and in fact, even when we had a limited we had wonderful donor support but still limited amount of money when we started this study, my lab was really very eager to do the high fiber um part of this really well and Christopher, kind of how to twist our arms to do the fermented food side of IT. And we thought that was kind of corky and neat like live microbes should be exciting. Like let's try IT.

So we put that in and IT turns out that we were very thankful that he twisted arms because I was that um hydro mental food ARM that really gave us the big signal. Even though our hypothesis was that the hype ber was going to lead to more shortening fatty assets produced in the gut, a more diverse microbiota um less inflation tion in the immune system, we didn't see that across the cohorts. We actually saw very individualized responses to the dietary fiber and all come back to what those responses were.

The the big signal really was in the fermented food group we saw all the things that you would hope to see in a western microbiota and western human. We saw this increase in microbiota diversity over the course of the six weeks while they were consuming the fermented foods. Um and we can always say that um higher diversity is Better when IT comes to our microbial communities.

We know their cases, for instance, bacteria, vaccines, is where higher diversity is actually indicative of a disease state um but we um knowing the context of the gut and for people living in the industrialized world, higher diversity is generally Better. We know that there's a spectrum of diversity. People with higher diversity, generally your heart healthier.

If you can push your diversity higher, you're in Better shape. And so we saw that increase in diversity. And then the major question is what happened to the immune system as these people were increasing their good microbial diversity through the fermented foods. Um we so we did the um this massive immune profiling and we see you know a couple dozen immune markers and film tory markers decrease over the course of the study.

So we we we measured these at multiple time points without the course of the study and there's kind of the stepwise reduction in things like in lucan six and um you h interlude twelve, a variety of kind of famous and flamma mediators. Um and then even if you go into the immune cells and you start looking at their signaling cades, we see that those signaling cades are less tiv ated at the end of the study compared to the beginning of the study, indicating an an attacking ation of inflation tion. So so kind of exactly what we would hypothesize would lead to less propensity for inflaming disease over time.

That's A A huge extension of a very short study in how and so the complete protocol, I think, was fourteen to seventeen weeks or something like that. The actual intervention phase consisted of a four week ramp and then a six week maintenance period. So the intervention itself was ten weeks, but there were six weeks of really kind of hard core high levels of a fiber or formated foods.

Yeah and I glad you have mention the rain up because my experience with um for mental food is that you IT can be beneficial to give the system an opportunity to actually I mean you consume a bull of sour crowd some can be the worst day and night of your life but you will you'll know you did you just leave IT at that and so you want to kind of acumen to IT I met the point now where people some I think this is gross.

But after I exercise them in sweating a lot, I like the saul tints of actually drink the the liquid that that this our crowd has been stewing in and I get i'd like to think that I consume some fermentation that way at salty and access kind of a post training of replacement. But if I had done that six months ago, straight ed off, I think I would have been pretty rough for my sister. I started taking little bits of IT and then .

adding at each day, totally. And so both with a fermented foods in the fibre, it's well known that that this kind of gradual ramping is a really important way of eating bloating another kind of digestive discomfort that can happen when your microbiome reconfigures and starts for mental more and changing community number. So um you should take that ramp at your own pace if something seems to be going wrong.

Just kind of level last stay there know we did this in a very delicate way to get people up to the height dose the um brian question just a um attention here for a second. Um that was actually one of the products that we um had people used in the formated food phase. There's actually product called gut shots, which is just the brian from that they've marketed.

Um we actually now studying IT in the lab. I just actually before this came from a lab meeting where A G I fellow in my lab is actually putting gut shots, specialized, got microbe or fronted um uh fermentation microbes removed or present in demise and looking at changes in their mucosal immune system. So we're studying this in detail now because this is it's a rich source of lactic and a bunch of other interesting metabolites.

I love that my weird behavior in advert tly being studied at stanford medicine. I wanted to spend this thing about the good shots. Those are are sold at as as a drink.

There is also just for certain listeners and different budgets that can be very expensive. If you really think about some of them are exceedingly expensive. But when I described before with making your own kampuchea is not quite brining, but the homemade sour crowd.

And that protocol is out. There is a mention in tim's book, the four hour chef and you get a lot of the brining from from that and Normal endless amount. Um a cautionary note.

I once went into the refrigeration and saw something similar to get shot. IT wasn't got shot and I drank the whole to advance bottle and realized that IT was twenty four services ings. And that's where I got my initial experience with what IT is to not do a ramp up phase and do not recommend doing that. Some of these is very potent. IT seems that you can consume, you know.

even a half an out and I mean very point from the standpoint information, but also very sault. So there's a lot of effects.

Yeah I don't do what I do, at least not at the outset. And but so that is an experienced morning. So they did this as I recall, there was a swap condition or there was a halt condition.

So you did controllers right wasn't just comparing groups. You had individuals who were initially in one group of the other um moved to a different group. Well stop and then return.

Yeah we actually just did to stop and follow them during a wash your face. And I the ideal situation for um dict arian interventions like this are to do um cross over studies as you're suggesting. We've recently completed a key to geneva, the international. Not yet, but Christopher, between a lot of these data, there's a paper vision right now. So if you go to Christa gardeners um to IT twitter feed, you'll be able to find him reporting some of the the early results of of this study.

Give us a little bit of was there just give us you want to tell us which one but was there a superior condition of either mediterannean versus key to generic?

So um so I should the meta lic effects of these um it's a beautiful study. I should let his group comment on that. The microbial to data we actually are just generating now.

So the study that his his group is put together from this is largely independent of the microbial tic data. And now we're doing a more in deep analysis, and i'll have more to say about that the future, but that return to that. But but it's a super exciting study because IT is one of these where people eat a certain way.

And what's really beautiful about this is we even got food delivered for part of the um intervention. So we had complete control over what they at least had available to eat. Um and then the second phase, they um they um make the food on their own and then we cross over and do the same thing.

And so that's really like the um if you have a good enough budget, the right way to do a study like this for this. We didn't have the um the timer or or money to do across over, but we did do a wash out face where people we didn't make them stop eating whatever if they were enjoying up. But we monitored and there was some certification where there was a decrease and fiber from mental food. And we can see, for instance, diversity start to a platoon reverse in many of these people. So there does appear to be like a need for maintenance of the intervention to maintain the perceived health benefits that we were measuring.

great. Um we will provide a link to the study in the caption and thank you for that. Very clear and through description um from the one of the investigators involved in the study that is great to go direct to the source anecdotally were their improvements in mood, in um resistance to called an infection um during the course of the study.

And this is a kind of a pre lude to wear. I'm headed next which is there is a tremendous amount of interest in the so called good brain access. But also, I want to make sure that we talk about how these microbe in the conditions they are establishing in the gut, are creating positive or negative health effects, I mean, actually based how signals get out of the gut.

So so did people. I certainly notice that when I an more formatted foods, or there's probiotics in some in drink cyd summer, of what that I feel code and quote air quotes, completely subject, I feel Better. I wish there was an objective measure of feeling Better, but I seem to think more clearly, sleep Better, mood at that.

And I know i'm not alone in that and people at any time I ve taken harsh antibiotics, I feel worse. But then again, i'm usually taking them because i'm feeling bad about something else. I don't take them just because so did people say they were feeling Better in any way. If so, what did you observe? And again, we're highlighting these .

as antic data. Yeah to know we as as part of this effort um to look at how dietary interventions uh affect our our health and well being in so forth microbiome omean system um we uh interact with a lot of people who have like read our book or you know kind of have become microbial and have implemented a lot of these changes in their personal life and I hear the same thing that that you are saying and that you know tons of people say they have more energy, they think more clearly, they sleep Better.

Their family is nice to each other like the number of crazy things and it's really hard done couple like is this because you know these people have taken charge now what they are eating and just feel Better in general for being in control of kind of what they're doing? Or is there this cascade set of effects that are actually, you know, impacting you kind of eminent from the gut brain access? And and so we actually implemented a bunch of questionnaire and even a cognitive test to try to get in some of this.

And and I should say you know that the list of this goes on and on, their people who claim that their completion improves and that there, you know allergies and there's probably all sorts of ripple effects. If you can affect your information, you we know that you can affect your cognition. We know that you can affect your, you know, your your skin and and information that's occurring on your skin.

So so I really think that there is a basis for a lot of those animals that may just be hard to see in a short study and in um a small you know a small cohort of people of a so creative time. But we didn't really see significant things associated with cognition and modes and know all of the things that that um we were testing for which um yeah there there could be a variety of explanations for that. You know we also have um a standardized um uh store measure that people use. And there was a kind of less constipation, Better bow movements over the course of both of these interventions. So IT did seem like ballot habits improved, which a lot of times can lead to Better moods, but that we weren't able to to mission that .

the classic psychoanalysts would have A A field day. With that, what sorts of interesting things did you observe in the fiber e group? Because it's clear that, that group yield at some unexpected findings in both directions that things you expected to see you didn't see as to the same implats you did in the fermented food group. But i'm guessing you also saw some very interesting things in the fibre group .

totally yeah so um so we started looking at the data more detail when we didn't see the cohorn wide um response. And um one of the things we observed is that in measuring all these immune parameters, there appeared to be three different groups of kind of immune responses that we are seeing, one group that got overall lesson flaming and then two other groups that kind of had a mixed result, partly more inflammatory, partly less inflammatory in all these markers that we are looking at.

And when we started digg into like what um aspect of the the biology of those people dictated or predicted which group they fell into, the really interesting part is the people with the highest diversity got microbiome to start the study were the ones that were most likely to have the um decreases and information. And so the you know data seem to be telling us that if you start off with a diverse microbiota, maybe one that's the equipped to degrade a wide variety of of dietary fiber, you're more likely to respond positively to IT. If you have a very depleted got microbiome, you're not as likely to be able to respond IT.

And thinking back to that experiment that we talked about before with a multi generational loss of fibre for mental microbe in in mice that were fed A A western diet um IT IT may be that um many of us in the industrialized world have a microbial that's so depleted now that even if we consume a high fiber diet, at least for a short period of time, we don't have the right micro bes and got to degrade that fiber. And this has actually been observed by other groups. Beautiful study out of university of minnesota looking at immigrants coming to the united states and within nine months but certainly over the course of years, immigrants that come here lose um uh a lot of the diversity and there are got microblog m but a lot of the fiber degrading capacity and there get microbiome too.

So I could be that over time, this becomes a one way street and it's hard for us to recover um the the microbes that that actually can degrade the fiber. And I think that this probably intersects with sAnitation and our environment in the fact that we don't have access to new microbes that might help us degrade the fiber that we actually, um you know, have lost these microbes. And there in some ways irrecoverable without deliberate reintroduction of fibre degrading microbes .

I could call from childhood were kids that would eat dirt yeah and snails and that this sounds totally disgusting. But you know kids covered with mod and know that maybe not so much anymore and and certainly during the pane dem mic there's been a lot more um use of these hand anodic ers that prior to that people seem pretty spooked about but then obviously that they prioritize them um so I do you well, you have children do do you encourage them to to when they were Young, did you encourage them to interact with pets and dirt and of stuff in the environment provided that stuff wasn't toxic?

exactly. So this is really you know it's it's a continual um cost benefit analysis. I think the I will say that with the pandemic now and um certainly just with infectious diseases in general, it's really important to be aware of you know the the possibility for compromising your health through the spread of germs and so that that is just you know hand washing is important in we have to be careful with you know um the spread of germs.

But I do think that um you know the the santiago of our environment um has gone to overboard with you know um various things being impregnable, ted with Annie otis shopping carts and things like that and tooth brushes and you know it's it's like antibiotics and and um you know things for killing micro bes or are everywhere. And when we were raising, when our daughters were Young and we are making these decisions, calculations that we would make or really um one um how likely are they to encounter a disease causing micro b if we've been out on a hike or in our garden, just kind of working in the dirt, whatever, maybe it's not as important to wash your hands before you have lunch even if there's a little bit of dirt on them. If you've been in a public playground where maybe there's um other kids with germs or maybe even chemicals like pesticides and an urban des that are being used um IT, maybe it's more important than to wash your hands.

You know certainly if you've been in the grocery store on the subway, probably good idea to wash your hands. But I so I think you really need to think about kind of the the context of IT and um exposure to microbes from the environment is likely an important part of um educating our immune stem in keeping the proper baLance in our immune stem. And it's just a matter of figuring out the right way to do that safely. And IT may be that the fermented food result that we saw is a way of tapping into the same pathways, kind of an tal exposure to microbes that safe.

interesting, like to touch on how signals get from the gut to the rest of the body. And we pride, don't have time to go into all the systems that benefit from having a diverse microbial or healthy microbial um but we talked about the immune system um there's active signaling in transport from the god all along its line, as far as I know, into the bloodstream, into other organs and tissues. So for the immune system.

Um IT seems straight forward um to produce the the amount or number of inflammatory side of kinds like I six and so forth, maybe increased the anti employ tory sa kinds like alton um and others but we know there's a got brain access and neurons that literally talk to in both directions between brain and gut. But let's say I eating my fermented foods, i'm doing all the right things and I, my god, is diverse and i've all the good goods at all the right places. How is IT that that the fact that those microbiota thriving is conveyed to the rest of the body because they're in they're doing their thing.

And I don't know that they have a mind, but they probably not thinking of taking care of me, Andrew, but I get feel Better or I might get sick less often or combat any honest more quickly. How is that actually happening? I mean is is that that the microbiota stay restricted to the the gut, but the signaling molecules are all downstream um in a downstream way or are making good or bad things happen? Or is there is some sort of direct recognition at the body level or there's cells in the body that are responding to oh that got microban is healthy and therefore I can make more of the good stuff and .

less of the bad stuff you speak yeah great that um you're writing super complex. There's a huge array of ways that our body perceives um both the microbes and the molecules that they produce in our gut. And the molecules they produce are of course the product of what microbes are there and then what they receive as of meta lic inputs, what we're eating and what other microbes are present in the environment providing molecules to them.

So you know this is complex matrix, but we you know that um probably the the simplest place to start is just the immune system we have um in immune system that you know the vast majority of mean cells in our body are located in our gut just because they're such A A dense population of microbes there that have you know there um we consider them um beneficial microbes, but they're only beneficial if they're in the right spot in the gut as soon as they miss localize. We know that they can become opportunistic pathogens. And so the immune system really playing an important role to keep with them in place.

IT is essential for this system not moving into a disease space. The immune system has a variety of ways of of monitoring what microbes are there. There are actually specialize structures in the gut um notice pie pie patches that actually take up microbes.

They they actually allow microbes to transit into this population of immune cells in a very controlled way, so that that set of immune cells becomes educated as to what microbes are just on the other side of the barrier. So like a water patrol, exactly. Yes, they bring them in, you know singer them and then um you know have have kind of this um you know set of responses ready to go if needed.

Uh there there are other cells known as dendritic c cells, special types that actually send uh long arms, these processes out into the lumina they got and do the same thing, take up microbes, bring them back in and sample them um in addition to these direct sampling mechanisms, the cells that land the gut have a uh huge ray of receptors, specialized proteins that perceive patterns that the molecular patterns that the microbes make. So things like toxin, like pop sacrist um just the cell wall of the um bacteria, we have specialized receptors that recognize those if those signals become too profound or if they're perceived in the wrong place that can stimulate and inflaming response. There's all these ways of kind of monitoring the membership and where IT is and how close IT is.

But then there's this whole other set of um ways of perceiving meta lic activity in what's happening and they get you mention before this direct um you know these cell types um express taste receptors in the gut and have ways of sampling dietary components. There are the same types of um analogous cells in or got that are perceiving metabolites produced by the microbiota so that um our bodies can perceive what sort of metabolite activity is going on. And then you know in addition to that, there is this tremendous, tremendously important interact nervous system that's um sending signals back to the praying, dictating things like a mortality.

Do I get rid of what's in here? Do I move IT along quickly? What what actually is is happening? Do I need to interact with immune cells? So there is this really complex array of of um interactions between the different call types and then a lot of the cells that are in the gut perceiving all of these signals, a lot of the immune cells can actually get up and leave, they can know get into the blood cycle through and then home to other regions of the um mucosal surfaces so that mu costal services are are um educated broadly against what's um what's passing through that.

So there's there's a variety of ways of cells communicating and then a lot of the molecules that the microbiota makes can actually make their way into the bloodstream directly. And so you know the um the array of molecules are still being defined. We're trying to figure out um what all these chemicals are.

We've mention the short chain fatty assets, but those are just the tip, the iceberg. They're really interesting compounds like you know indore derivatives and finals and you know derived from a mino assets meta lizer by microbes taken up into the bloodstream. And then we further metabolite these, they become kind of co micropower metabolizes. And then they can go on and bind to different receptors throughout our body anywhere a bloodstream has access to and start to trigger signaling.

Caskets is not known whether not any of those molecules are small enough to cross the blood brain barrier because the hypothesis uh and the current thinking is that um neurotransmitter is manufactured in the gut and signaling along the gut brain access literally neurons talking back and forth electrically from brain to gut and got to in is what regulate things like mood, or at least in animal models.

And there are some emerging human study's improvement of symptoms in autism spectrum disorders may be even an add. What i'm basically saying here is there there is some evidence emerging that improving the gut microbes can improve outcomes in psychiatric and developmental disorders. But what you're telling me is that the that the microbiota themselves are manufacturing chemicals that can make into the blood streaming.

Therefore, i'm asking if those chemicals can move from the blood streaming into the brain directly. IT may not be a gut brain access via neons. IT actually could just be sept of serotonin into the brain and or see to calling into .

the brain for matter totally yeah and you know the the the the biology of most of these molecules is not well understood, but certainly in like server final flu that's been analyzed it's you can perceive these microbial metabolic they are .

there the answers of them are getting across .

the but so really interesting thing is I think a lot of these molecules are um if they are experienced hanging of doses are um toxic or have toxic properties. We know that um a lot of these metabolic, they make the way into the bloodstream, eventually are excluded through the kidneys and neuron. So actually we can monitor the metabolic that's going on in your gut by actually looking at the metabolic are present in your eun, because those many of those originated in your gott from your gut microbes. But people with kidney disease whose kidney's um filtering processes not functioning properly, actually build up high levels of many of these metabolites into the bloodstream. And um that can lead to more these molecules making IT across the blood brain barrier and in fact some of the um transporters in the kidney that are responsible for shuttling these molecules out in the urn are also found at the blood brain barrier for shuttling the molecules back into the bloodstream if they do get across and and we know that like mental fog is a big one of the big symptoms of kidding disease potentially because a lot of these metabolizes accumulating blood and then make their way across the blood brain barrier into the central of system.

amazing. I'm glad you mention mental fog a few years back there reports are in some science fc reports and as a consequence in in the media that excessive and take a probe of pill form probiotics could create mental fog. I don't if that ever took and and IT raises a general question about um piller m pro biotics.

I took them for a few years just thinking that would be good for my got microban I switch to the fermented food thing largely as a consequences ve the work that you and Chris published but what what's the thought about prox for for the typical person that's not recovering from a round of antibiotics or that has been described them? Um i've heard that the species of microbiota, that the proferred might not be the species that we want to proliferate. But I ve also heard that maybe that doesn't matter.

So what's your general things? They can be quite expensive also. I know i've been hanging about expensive today, but I always want to take into account that people are showing up to the table with a variety of budgets and you know probably are one of the more expensive supplements out there you can quickly get into the several hundreds of dollars per month if you're getting the court and best quality ones, if they're got actually causing brain fog, then yeah, I D want to use them no.

completely. And there's a turn of snake oil out there. I mean, there's just people know that they you know I think the a many of these companies are aware that they can pray off of people's spheres and get a lot of money from them with absolutely no data to back up their probiotic is doing anything.

Uh, so I think the the first thing to say is bier beer because it's a supplement market, is largely unregulated and that means that there are a lot of bad products out there and a lot of products that um even though they are not intended to be bad, just don't have great quality control. There been several studies that have taken off the uh over the counter, just kind of off the shelf probiotics surveyed what's in there based on sequencing and shown that they what is in there does not match what's on the label. So then that's true of many .

supplements and unfortunately, supplement companies. This is something we get into on the podcast a lot. There are reputable brands and they go through a lot of work to to get things right. And there are many that just for whatever reason, that just doesn't .

match what's this exactly. And so there are um uh places the probability companies can send their product to have IT independently validated. So you want to look for that sort of validation on on a product. There are also are names that are just very well known. And um you know it's A.

You know their reputations are on the line, so they probably invest a little bit more in quality control and maybe some of the other less or no names um but you know there's a huge range of um data on pro biotics. And I think you the the thing that we kind of recommend is, you know um try to find good products and then experiment for yourself and see if you can find something that works for you. I know people who have experienced constipation and um you know I don't want to change their diet and I found a probiotic that helps them with that um if you can find that right makes great you know that that's wonderful.

Um I would say that the the data right now is not um overwhelmingly positive for what pro biotics do to the microbiota. So there have been some nice studies looking at the impact of probiotics on recovery after antibiotic treatment and IT appears to slow down the recovery of the micros microbiota um and uh some other studies that have um where where the the big signal isn't seen, as you might hope, with a proof that supposed to treat a different disease. There have been made analysis that do suggest in certain instances recovery from um uh anode ocs that there even though that may cause your microbial to recover more slowly, that IT may actually prevent the real disease recovery from viral areas.

Robotics may help. But because there are such a huge range of products and because each person is their own little paper and IT comes to the microbiome, it's really hard to know um whether there are great products for a given indication. 那 really good advice that i've heard is try to find um uh a study that supports and you know a really well design study。 And this is very hard for people who aren't scientists to. But so you know if you're experiencing a medical problem or want to consult the doctor, um the you know that that might be helpful. But finding a study where a specific robotic has successfully done whatever IT is you're looking for and then sticking with that probiotic is really the best recipe for as as a place to start in the space.

I think. And what about prebiotic ics? Is there are a number of reasons why I can imagine that prebiotic would be beneficial um which is essentially is your pushing the fibre system, which we talked a lot .

about today. Yeah yeah absolutely. Um 疫苗 的 the studies that have been done on prebiotics that it's really kind of of a mixed bag of results。 There have been studies done with um purified fibers where you actually see microbiology, versy, plumet over the course of the study because um you get a very specific bloom in a small number of bacteria that are good at using that one type of fiber, and that's at the expense of all the other microbes that are in the gut.

And so um so it's really hard to replicate with purified fiber what you d get, for instance, inside a salad bar in terms of the array of complex carbo hydrates that you would be exposing your microbiota two. And I think the kind of um uh 我 我 broad view of this in the field is that consuming a broad variety of plants is and and all the the diverse fiber that comes with that is probably Better in Fostering diversity in your microbiota。 Then purified fibers.

Now there are um again a lot of people who benefit from purified fibers either for G M motility um or or for other aspects of of G I health problems that y've been experiencing. Again, I think it's a type of thing you have to um try to find the thing that that's right for you. But there um there also are studies that suggest that if you layer rapidly for mental um fibers on top of a western diet, you actually can um result in weird metabolism happening in your liver because you have this incredibly rapid formation of fiber along with a lot of fat.

I'm coming into the system, at least that's the that's the theory. And in a mouse study that was published a few years ago, they actually see that a subset, the mice develop a pata ua carson oma when they're vea of hydas crew biona liver cancer on top of on top of a western diet. So whether that's representative of human biology we don't know. But um you pi fied fibers are definitely very different um both in terms of the diversity of structures but also in terms of how rapidly they're fermented in the gut because um you know if you are eating plants, the complex structures, they're really slow the microbes down in terms of fermentation and you end up with a slow rate of over the length of your Colin as opposed to this big burst confirmation that can happen if you eat something that is highly soluble in and easily accessed by the microbes.

interesting. So I guess is that fair to come back to this idea trying to avoid process foods, the highly palatable foods, they are all sometimes super highly palatable foods they are now called that are packed with hidden sugars and also fires um sounds like some fibre is good um and despite the outcome of the study, you identify that if you have the property microbiota, you will background and one will respond even Better to the fiber, maybe a longer ran up but face for those folks. And then the fermented foods because is no reason why you can do both. And as we talked about before, a lot of commented, foods have fiber, so you can kill two birds with one stone totally.

And IT could be that the diversity increased, that we saw the hydro mental food group could be something that would aid the high fiber group. And so now we're planning another study coming up where we're doing high fiber, hyper mental food and then fiber plus fermented food just to see if there's a cinna justice .

effect that I want in role. Seriously, although I guess i'm bias because I sort of nowhere you're trying to well, is that blood draws .

that used to measure .

the inflammation. And i'm incredibly grateful this was a area biology that despite having learned lot about three papers and going to talks and and reading articles in the media, has remained somewhat mysterious to me until today. You've given us a very vivid picture of how this system works.

Where can people find out more about the work that you're doing? We can certainly provide links and you and and your wife who go on your lab, you have a book on this topic. So could you talk about the book where we can not learn more about the song in berg lab in the work at that your doing um maybe people even trying to roll in some of these .

studies yeah fantastic. I would be great if we could get people to enroll where I was looking for um for you willing participants um yeah so uh american my wife and I wrote a book called the good gut and um that that really was a um response to how we were changing our lives in response to to being in the field, being very family with the research, seeing that a lot of our friends that weren't studying to got microbes on, but we're very well informed.

Many of them scientists were not doing the same things we were doing. And IT was very clear that he was just the lack of information funneling out of the field to other people. And so we wanted to um make that accessible to people who are not microbial scientists.

There's also a really interesting story. We are at a uh conference site that just has scientific conferences all summer long, week after week after week, different fields. And so it's people that work there that are just dealing with these new groups coming in week after week and the week.

We are there for a microbiome ference uh people um uh the work in the dining comments came up to us. They said, what group is this? This is weird. And like, what's weird? They said we can keep the salad bar stocked and IT was just IT was very clear that nobody was doing what we were doing until we would go to a microbiome conference and then everybody was doing the same stuff that we were doing and so um so anyway, we wrote this book to talk about a personal journey and kind of the science in the field and um yeah just um lay a foundation for people if they want to start thinking about these changes.

And then you know in terms of um kind of connecting with our research, certainly there's the center for human microbial studies at stanford, which is kind of our home base for doing a lot of these dietary interventions. We list the studies there, give more information on what we're doing and then we have a lab website to that people can go to and read more about our research. Um yeah but um we're and we're always looking for participants for our studies.

great. Well, we will provide links to all of those sources. And I just want to say thank you so much for sharing with us your knowledge for the incredible work that you and era, your wife and and Chris do and and are continuing to do.

I think this is an area that when I started my training, I heard a little bit about microbiota and I was just saw those are people that work on infectious disease. And like all the bads, it's it's interesting and really a important that people realized that that that we're Carrying all this vital cargo and we need to take care of the cargo so we can take care of us. So thank you so much for your time and for the work you do. And I hope we can do IT again.

Thanks, Andrew. This was a great conversation. terrific.

Thank you for joining me today for my discussion with doctor Justin sonntag, all about the good microbiome, how to optimize you got microbes um for health. Please check out the sonenberg lab web page that sonenberg spell S O N N E N B U R G L A B. Not stanford.

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