Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew huberman, and I'm a professor of neurobiology and Ophthalmology at Stanford school of medicine. Today. We are going to discuss the gut and the brain. And we are going to discuss how your gut influences your brain and your brain influences your gut. As many of you probably know. There's a phenomenon called your gut feeling which tends to be something.
You seem to know without really knowing how, you know it, that's one version of the gut feeling. The other is that you sent something in your actual gut in your body and that that somehow drives you to think, or feel or act in a particular way, maybe to move towards something or to move away from something. Now today. We are going to focus so much on the psychology of gut feelings, but on the biology of gut feelings and how the gut and brain interact. Because indeed.
A gut is communicating to your brain. Both directly by way of neurons nerve cells and indirectly by changing the chemistry of your body, which permeates up to your brain and impacts various aspects of brain function, but it works in the other direction to your brain is influencing your entire gut. And when I say entire gut, I don't just mean your stomach. I mean, your entire digestive tract, your brain is impacting things like how quickly your food is digesting, the chemistry of your gut if you haven't be stressed or not.
Whether or not you are under a particular social challenge, or whether or not you're particularly happy will, in fact, adjust the chemistry of your gut and the chemistry of your gut in turn will change the way that your brain works. I'll put all that together for you in the context of what we call the gut microbiome, the gut microbiome are the trillions of little bacteria that live all the way along your digestive tract. And that strongly impact, the way that your entire body works at the level of metabolism immune system.
Oh, and brain function. And of course, we will discuss tools things that you can do in order to maintain or improve your gut health because as you'll also soon, see, gut health is immensely important for all aspects of our well-being at the level of our brain at the level of our body. And there are simple actionable things that we can all do in order to optimize our gut health in ways that optimize our overall nervous system functioning. So we will be sure to review those today this
Sold also serves as a bit of a primer for our guest episode. That's coming up next week with dr. Justin Sonnenberg from Stanford University. Dr. Sonnenberg is a world expert in the gut microbiome. And so, we will dive really deep into the gut microbiome in all its complexity will make it all very simple for you. We will also talk about actionable Tools in that episode. This episode is a standalone episode. So you'll get a lot of information and tools, but if you have the opportunity to see this episode first, I think it will serve as a nice primer.
R4 the conversation with dr. Sonnenberg before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at 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 an all-in-one vitamin mineral, probiotic drink. I've been using athletic greens, which is now called a G1 since
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Munich 8 in both directions because as I mentioned before, your gut is communicating all the time with your brain and your brain is communicating all the time with your gut. And so the two are in this ongoing dance with one. Another that ordinarily is below your conscious detection. Although you're probably familiar with the experience of every, once in a while, getting a stomachache or eating something that doesn't agree with you or conversely, eating something that you find particularly delicious and that sensation or that.
It's rather being a whole body experience. Your mind is excited about what you're eating, or just ate your gut is excited about what you're eating or just ate. And it seems to be a kind of unified perception of both brain and body. Today. We're going to talk about how that comes about in the negative sense. Like, you know, when you meet someone you really dislike when you have a stomach ache and in the positive sense, when you interact with somebody that you really really like and you'd like to spend more time with them for instance where when you eat something that you really, really like
And you'd like to spend more time with that food. So to speak. Now, the gut and the Brain represent, what we call a biological circuit meaning, they include different stations. So station, a communicates with station B, which communicates with station C and so on. And as I mentioned earlier, it is bi-directional. It's a two-way street between gut and brain. I want to make the important point at the outset that when I say the word gut when I refer to the gut I'm not just referring to the stomach.
Most of us think that the gut equates to the stomach because we think of having a gut or not having a gut or having a gut feeling of some sort, but in the context of gut-brain signaling and the related microbiome, the gut includes the entire digestive tract. That's right. From start to finish the entire digestive tract so much. So that today we're going to talk about, for instance. The presence of neurons nerve cells that reside in your gut.
That communicates a specific locations in the brain and cause the release of specific neural chemicals such as the neurochemical dopamine or serotonin that can motivate you to seek more of a particular food or type of interaction or behavior or to avoid particular Foods, interactions and behaviors, and some of those neurons many of those neurons. In fact, reside, in your intestines knot in your stomach. They can be in the small intestine or the large intestine. In fact, you actually have taste.
Receptors and neurons located, all along your digestive tract, you have neurons that are located all along your digestive tract and they are communicating to your brain to impact. What you think, what you feel and what you do. Okay. So for the gut brain axis, we need to deal with the brain part and then we need to deal with the gut part. Let's just quickly talk about the brain part because there the word brain is also a bit of a misnomer in that when we say the gut brain axis. It does include the brain, but includes a lot of other things as well.
So as many of you probably know by now, if your listeners of this podcast and if you don't that's fine, your nervous system includes your brain and your spinal cord and those together constitute what is called the central nervous system. Your neural retinas, which are the lining, the back of your eyes and are the light. Sensing portion of your eyes are also part of your central nervous system. So actually your eyes are part of your brain. They're the only parts of your brain that are outside the cranium.
Vault. So your retinas, your brain proper and your spinal cord. Make up the central nervous system the other parts of your nervous system constitute. What's called the peripheral nervous system, which are the components of your nervous system that reside outside the retinas brain and spinal cord. Now, this is very important because today we're going to talk a lot about how the gut communicates with the brain and it does that by way of peripheral nervous. System components, meaning nerve cells that reside in the gut and
The body that communicate to the brain and cross into the central nervous system to influence what you think and what you feel. Okay. So that's the nervous system part of what we call the gut brain axis brain. Again, just being a shorthand for including all the elements. I just described gut as you now know, includes all the elements of the digestive tract. Let's talk about the architecture, or the structure of the gut of your digestive system, not surprisingly, your digestive system.
System, AKA your gut begins at your mouth and ends at your anus and all along its length. There are series of sphincters that cut off certain chambers of the digestive tract from the other Chambers. Now, also along this tube that we call the digestive tract. There is great variation in the degree of acidity or pH, as it's sometimes called that variation and acidity turns out to give rise to different little micro environment.
Armaments in which particular microbiota micro bacteria can Thrive or fail to thrive. And so the way I'd like you to think about the digestive tract, this gut component of the gut brain axis is that it's not just one component. It's not just your stomach with a particular acidity and a bunch of microorganisms that work particularly well to make you feel good. And if you make your digestive Pathways work, well, it's a series of Chambers little micro environment.
It's in which particular microbiota Thrive and other microbiota do not and certain behaviors that you Undertake and certain experiences that you have will adjust those micro environments in ways that make particular microbiota, certain bacteria, more likely to thrive and others less likely to thrive. We'll talk about how that was set up for you early in life. Actually from the moment that you came into the world that microbiome was being established. It was actually strongly impacted.
Depending on whether or not you were born by C-section or by vaginal birth. And it was strongly impacted by who handled you, when you came into the world. Literally the hands that were on you. How much skin contact you had whether or not you were a preemie baby or not, whether or not you had pets at home whether or not you are allowed to play in the dirt whether or not you're allowed to eat snails or whether or not you were kept in a very antiseptic environment. All of those experiences shaped these little micro environments and shaped what constitutes best or worst for those micro environment.
It's okay. So you have this long tube that we call the digestive tract and it's very very long. In fact, if we were to splay it out. We were to take all the curves and turns out of the intestine we would find that. It is very long. It's approximately nine meters long. Now the structure of that digestive tract turns out to be very important in terms of gut-brain signaling.
Once again, it's a tube and the Halo of that tube is called the Lumen L. Um, Iain, but the walls of the tube are not necessarily smooth. At least, not for significant portions of the digestive tract for much of the digestive tract. There are bumps and grooves. That look, very much like the folds in the brain, but these bumps and grooves are made up of other tissues. They're made up of what's called a mucosal lining. So, there's a lot of mucus there. And if we were to look really closely, what we would find is that
Their little hairy like cellular processes that we call microvilli that are able to push things along the digestive tract.
The microbiota reside everywhere, along the Lumen of the digestive tract, starting at the mouth, and all the way to the other end, and they reside within those microvilli and they reside within the Lumen. And if we were to look really closely at the bumps and grooves along the digestive tract, what we would find is that there are little niches little areas in which particular things can grow. And reside best might sound kind of gross, but it
Actually is a good thing, especially what's growing? And residing, there are micro bacterial organisms that are good for your gut and that signal, good things to your brain. And we will talk about what that signaling looks like and how that's done and accomplished in just a few moments, but I want you to get a clear mental picture of your gut. Something that we don't often see. And often when we think about the gut again, we just think about the Halo of the stomach food, going in there and getting digested, but it's far more complex and actually far more interesting than that. Now I've been referring
Into the gut microbiome and to the microbiota. And these bacteria. Let me Define those terms a little bit more specifically, just to avoid any confusion. The microbiota are the actual bacteria. The microbiome is used to refer to the bacteria, but also all the genes that those bacteria make, because it turns out that they make some important genes that actually impact all of
us.
You have loads and loads of these little micro biota these bacteria. In fact, right now. You are carrying with you about 2 to 3 Kg. So that's more than six pounds of these microbiota, these bacteria. And if we were to look at them under a microscope, what we would see is these are relatively simple little organisms, some remain stationary. So they might plop down into the mucosal lining or they might hang out on a particular microvilli, or they might be in one of those little niches.
And others can move about. But they basically fill the entire Lumen, they surround and kind of coat the surface of the microvilli and they're tucked up into any of those little niches that are available to them to tuck into. If you were to take the head of a pin and look at it under the microscope. You could fit many many hundreds, if not thousands or more of these little micro bacteria. And the reason I say many, many thousands.
Or more. I'm giving up the kind of broad range. There is that they do vary in size. And again they vary as to whether not they can move or they don't move. Now. They're constantly turning over in your gut. Meaning they're being born so to speak and they're dying off and some will stay there for very long periods of time within your gut and others will get excreted about 60% of your stool as unpleasant as that might be to think about is made up of live and dead micro bacteria.
You're constantly making and excreting these micro bacteria, and which microbacteria you make, and how many stay inside your gut and how many leave meaning? How many are excreted, Depends a lot on the chemistry of your gut and Depends very strongly on the foods that you eat and the foods that you do not eat. Now, just because what we eat strongly influences our microbiome, meaning our micro bacteria does not
Mean, that there are not other influences on what constitutes our microbiome. Our microbiome is also made up by micro bacteria that access our digestive tract through our mouth, through breathing through kissing and through skin contact. In fact, one of the major determinants of our microbiome is who we interact with and the environment that we happen to be in and that actually includes whether or not we interact with animals.
In a little bit. I'll talk about some data as to whether or not you grew up in a home that had animals whether or not you grew up in the home whether or not there was a lot of social contact meeting skin contact or whether, or not you grew up in a more animal sparse contact sparse environment and how that shapes your microbiome. But the simple point is that what you eat influences your microbiome, but also, what you do, what you think and what you feel, and many of the little micro bacteria that get into your digestive tract.
Do so by way of social interactions. In fact, if you ask a neurobiologist what the role of the microbiome is, they'll tell you almost certainly that it's there to impact brain function. But if you have friends that are microbiologists, such as I do, they'll tell you, well. Well, maybe the brain and nervous system are there to support the microbiome. It's the other way around. You have all these little micro organisms that are taking residents in our body. They don't really
Know what they're doing as far as we know. We don't know that they have a Consciousness or they don't we can't rule that out, but it seems pretty unlikely. Nonetheless. They are taking advantage of the different environments. All along your digestive tract. They are taking advantage of the sorts of social interactions. For instance, the people, you talk to in that breathe on you, the people that you shake hands with the people that you kiss or don't. Kiss the people that you happen to be romantically involved with, or not your dog, your cat, your lizard, your rat, whatever. Pet you happen to own is
Impacting your microbiome. There's absolutely no question about that. So, hopefully now you have some sense of the architecture of the digestive pathway and you have some sense of the trillions of little micro bacteria that are living all along the different components of that digestive pathway, but what we haven't talked about yet and what I'd like to talk about now is what those little microbiota are actually doing in your digestive tract, in addition to just living there for their own intents and purposes. They are contributing.
Instance to your digestion, many of the genes that those microbiota make our genes that are involved in fermentation and genes that are involved in digestion, a particular types of nutrients and in the little bit we will talk about how what you eat can actually change the enzymes that those microbiome components. Make enzymes, largely being things that are responsible for digestion. They catalyze other sorts of cellular events, but in the context of the digestive pathway, we're talking about
About enzymes that help digest your food. So those microbiota are indeed helping you in many ways. And if you lack certain microbiota that can help you digest, it stands to reason that you would have challenges digesting certain types of foods. The other amazing thing that these microbiota do is they change the way that your brain functions by way of metabolizing, or facilitating the metabolism of particular neurotransmitters. So, one of the ways that having certain microbiota present in your gut can
Move your mood or degrade. Your mood, for instance is by way of certain microbiota being converted into or facilitating, the conversion of chemicals such as Gabba. Gabba is an what we call an inhibitory neurotransmitter. It's involved in suppressing, the action of other neurons, and that might sound like a bad thing, but all types of sedatives, for instance, alcohol. And a lot of neurons that naturally make Gap.
Ava can help quiet certain circuits in the brain for instance circuits, responsible for anxiety. In people who have epilepsy the gabaergic neurons as they're called, can often be disrupted in their signaling meaning. They're not cranking out as much Gaba and therefore, the excitatory neurons, which typically release other molecules like glutamate can engage in what's called Runaway excitation and that can give his rise to seizures. So the simple message here. Is that the microbiota by way of
Taking neurochemicals can influence the way that your brain functions. So you want to support those microbiota and we will give you tools to support those microbiota, but the takeaway at this point is that those microbiota are making things locally to help digest food, other microbiota are helping to make certain neurotransmitters like Gaba. And we'll also talk about dopamine and serotonin. And so, the very specific microbiota that reside in your gut, have a profound influence on many, many biological.
Logical functions, especially immune system function, brain function and digestion. So that should give you a fairly complete picture of your gut microbiome. Now, I'd like to talk about how your microbiome and your brain communicate or more accurately, how your microbiome and the rest of your nervous system, communicate neurons, which simply means nerve cells. Are the cells that do most of the heavy lifting in your nervous system. There are, of course, other cell types that are important glial cells. For instance. Very, very,
All types, you have endothelial cells which are responsible for blood flow, parasites and other types of cells, but the neurons are really doing most of the heavy lifting for most of the things we think about in terms of nervous system function, you have neurons in your gut and that should not surprise you neurons. Reside in your brain or spinal cord, your eyes, in fact, all over your body and you've got them on your heart and in your heart and you've got them in your lungs and you've got them in your
your spleen and they connect to all the different organs and tissues of your body. So that's not surprising that you have neurons in your gut. What is surprising. However, is the presence of particular types of neurons that reside near or in the mucosal lining just next to that Lumen of the gut and that are paying attention. And I'll explain what I mean by paying attention to the components of the gut, both the nutrients and the microbiota.
And thereby can send signals up to the brain by way of a long wire that we call an axon.
And can communicate what the chemistry and what the nutritional quality and what the other aspects of the environment are at the gut at a given location up to the brain in ways that can influence the brain to, for instance, seek out more of a particular food. Let me give you a sort of action based picture of this. Let's say, like most people, you enjoy sweet Foods. I don't particularly enjoy sweet foods, but there are a few that I like I'm a sucker for a really good dark chocolate or
Really good ice cream. Or I got this thing for donuts. That seems to just not quit. Although, I don't tend to indulge it very often. I do like them. If I eat that particular food, obviously digestion starts in the mouth. There are enzymes there. It gets chewed up. The food goes down into the gut. These neurons are activated. Meaning that causes the neurons to be electrically active. When particular component, certain nutrients in those foods are present and
for the cell types, or I should say the neuron types that matter here, the nutrients that really trigger their activation, our sugar fatty acids, and amino acids. Now, these particular neurons have the name, enter 0, Endocrine cells, but more recently, they've been defined as neuro pod cells. Neuro pod, cells were discovered by Diego bojorquez Lab at Duke University. This is a phenomenal set of discoveries made mostly in the last 10 years.
These neuro pod cells as I mention are activated by Sugar fatty acids, or amino acids, but have a particularly strong activation Two Sugars. They do seem to be part of the sweet sensing system. And even though I'm focusing on this particular example, they represent a really nice example of how a particular set of nerve cells. In our gut is collecting information about what is there at a particular location in the gut and sending that information up to our brain?
They do that by way of a nerve pathway called the vagus nerve. The vagus nerve is part of the peripheral nervous system and the vagus nerve is a little bit complex to describe. If you're just listening to this. If you're watching this, I'll try and use my hands as a diagram. But really the best thing to do. If you want really want to learn neuroanatomy is to just imagine it in your mind as best you can and if you can track down a picture of it. Terrific but here's how it works. Neurons, have a cell body that we call a Soma. That's where all the DNA.
Are contained. That's where a lot of the operating Machinery of the cells are contained. And a lot of the instructions for that cell of what to be and how to operate are contained. The cell bodies of these neurons are the relevant neurons are actually up near the neck so you can think of them as kind of a clump of grapes because cell bodies tend to be round or oval ish. And then they send a process that we call an axon in One Direction out to the gut.
And they'll send another process up into the brain and that little cluster near the neck. That's relevant here is called the NoDoz ganglion and OD o SE. The NoDoz ganglion is low cluster of neurons on either side of the neck. It has a process that goes out to the gut and a process that goes up into the brain. And again, these are just one component of the so-called vagus nerve.
The vagus nerve has many, many branches. Not just to the gut. They're also branches to the liver branches, to the lungs, branches to the heart, branches, to the larynx, and even to the spleen, and, and other areas of the body that are important. But right now we're just concentrating on the neurons that are in the gut that signal up to the brain. And what the pork is lab has shown is that these neuro pod cells are part of this network. They're sensing several different nutrients, but in particular when they sent sugar, they
Send signals in the form of electrical firing up to the brain in ways that trigger activation of other brain stations that cause you to seek out more of that particular food. Now this brings us to some classic experiments that at least to me are incredible and these are highly reproducible findings. Showing for instance that even if you bypassed taste by infusing sweet liquid, or putting sweet Foods,
Into the gut and people can never taste them with their mouth. People will seek out more of that particular food. And if you give them the option to have a sweet food infused into their gut or a bitter food, infused into their gut or a sweet vs. Sour or a more sweet versus less sweet food. People have a selective preference for sweet Foods, even if they can't taste them. Now, this is important to understand in the context of gut brain signal.
Because we always think that we like sweet Foods because of the way they taste and indeed that's still true. But much of what we consider, the Great Taste of a sweet food also has to do with a gut Sensation that is below our conscious detection. How do we know that? Well, the bojorquez lab has performed experiments using modern methods and their classic experiments showing that animals. And humans will actively seek out more of a particular sweet food, even if it bypasses this
Taste system. And the reverse is also true. There have been experiments done in animals and in humans that have allowed animals or humans to select and eat sweet foods. And indeed. That's what they do if they're given the option.
And yet to somehow eliminate the activation of these neurons within the gut that can sense. Sweet Foods. Now, there are a couple different ways that those experiments have been done in classic experiments, the date back to the 80s. This was done by what's called sub diaphragmatic vagotomy. So be this means cutting off the branch of the vagus that innervates the gut below the diaphragm so that the other organs can still function because the Vegas is very important, but basically cutting off, the sweet sensing in the gut still giving people the
Opportunity to taste sweet foods with their mouth and they don't actively seek out quite as much of the sweet food when they don't have this gut sensing mechanism, that we now know to be dependent on these neuro pod, sells more recent experiments involve selective, silencing of these neuro pod cells, and there been a lot of different derivations of this sort of thing, but the take away from it, is that our experience of and our desire for particular Foods has everything to do with how those Foods taste. It also has to do as you probably know, with their
Sure and The Sensation of those Foods in our mouths and even indeed how they go down. Our throat. Sometimes can be very pleasing or very unpleasant. And it also has to do with this subconscious processing of taste that occurs in the gut itself. And again, when I say got, I don't just mean in the stomach there, actually neurons, neuro pod cells, further down your digestive tract, which are signaling to your brain about the presence of sweet Foods as well as foods such as
As amino acid, rich foods, or foods, that are rich in particular types, of fatty acids, signaling up to your brain and causing you to seek out more of those Foods or to consume more of those Foods. Now, you're probably asking what is the signal? How does it actually make me want more of those foods without me realizing it? What does that by adjusting? The release of particular neuromodulators? For those of you that are not familiar with neuromodulators. These are similar to neurotransmitters, but they tend to act more broadly. They tend to act.
Impact many more neurons all at once and they go by names like dopamine serotonin acetylcholine epinephrine and so forth. Sometimes people refer to those as neurotransmitters, technically, they are neuromodulators. I'll refer to them. Almost always is neuromodulators the neuro pod sells signal by way of a particular branch of the vagus through that NoDoz ganglion that we talked about before and through a number of different stations in the brainstem eventually cause the release of the
Our dopamine dopamine is often associated with a sense of pleasure and reward but it is more appropriately. Thought of as a neuromodulator that impacts motivation, craving and pursuit. It tends to put us into modes of action. Not necessarily running and moving through space. Although it can do that too. But in the context of feeding, it tends to make us look around, more chew more, reach for things, more and seek out, more of whatever it is. That's giving us that sensation of delight.
Satisfaction. And again, that sense of delight and satisfaction, you might experience only consciously as the way, that something tastes on your mouth, but it actually is caused Again by both the sensations in your mouth, but also by the activation of these neuro pot cells. So this is an incredible system of gut-brain signaling and it is, but one system of gut-brain signaling. It turns out it's the system that we know the most about at this point in time. There are other components of got brain signaling that we'll talk about in a moment.
For instance, the serotonin system, but in terms of examples of gut-brain signaling for which we know a lot of the individual elements and how they work. I think this neuro pod, neuron sensing of sweet Foods, fatty acids, and amino acids in the gut and communicating that up to the brain by way of the Vegas and causing us to seek out, more of the foods that deliver those nutrients is an incredible pathway that really delineates the Beauty and the power of this gut-brain axis.
Let me talk about timescales here. I'm talking about a particular type of neuron. That is signaling to up to the brain using electrical signals to cause us to want to seek out a particular category of
foods
that's happening. Relatively fast compared to the hormone Pathways of the gut which also involve neurons. So your gut is also communicating to your brain by way of neurons nerve cells, but some of those nerve cells. Also release hormones and those hormones go.
Names, like cck, glucagon-like peptide, 1py Etc, a good example of a hormone pathway or what's sometimes called a hormone peptide pathway, that is similar to the pathway of talked about before. But a little bit slower is the ghrelin pathway ghrelin, GH reli. N increases with fasting. So the longer it's been since you've eaten or if you're just eating very little food compared to your claw.
Eric needs ghrelin levels are going to go up in your bloodstream and they go up because of processes that include processes within the gut and include the nervous system. So it's a slow pathway driving you to seek out food. Generally as far as we know, the ghrelin system is not partial to seeking out of sweet Foods or fatty foods or so on.
Ghrelin increases the longer. It's been since you've eaten sufficient calories and it stimulates a feeling of you wanting to seek out food while how does it do that? It does that again by impacting neural circuits within the brain? Neural circuits that include what we call the brain stem autonomic Center. So it tends to make you feel alert. And quite we say, high levels of autonomic arousal. If you haven't eaten in a while, you might think that you just get really exhausted, right? Because we all hear that food is energy.
And caloric energy is what we need to burn. But you actually have a lot of energy stored in your body that you would be able to use if you really needed energy, but typically we haven't eaten in a while we start to get agitated and we get agitated by way of release of the neuromodulator epinephrine, which causes us to look around more move around more and seek out food that all occurs in brainstem autonomic centers. And in the hypothalamus, we did an entire episode on feeding behavior and Metabolism as well. And you can find those episodes.
Huberman lab.com. So I don't want to go into a lot of detail about hypothalamic and brainstem centers, but there's a particular area of the brain called. The nucleus of the solitary tract. The NST is it's called that's very strongly impacted by the circulating hormones and tends to drive us toward feeding Behavior. So the important Point here is that we have a fast system that is paying attention to the nutrients in our gut or the absence of nutrients in our gut and stimulating us to seek out food or to stop eating certain foods, and we have a slower hormone-related.
System that also originates in the gut and impacts the brain. But all of those Converge on neural circuits. For feeding the neural circuits for feeding include things like the arcuate nucleus of the hypothalamus. They include a bunch of other neurochemicals. But the point is that you've got a fast route and a slow route to drive you to eat more or eat less right to seek out food and consume it or to stop eating to essentially Kickstart the satiety mechanisms as they're called.
And those are operating in parallel. It's not like one happens first, then stops than the other. They're always operating in parallel. And I bring this up because there's a bigger theme here which we see over and over again in biology, which is the concept of parallel Pathways. You've always got multiple accelerators and multiple breaks on a system. It's very, very rare to have just one accelerator in one break on the system. And this will become important later when we talk about tools for optimizing your gut microbiome for healthy eating and for healthy digestion, and for healthy brain function. I want to take a moment and talk about
Agon, like peptide one, which is also called glp-1, glp-1 is made by neurons in the gut, and by neurons in the brain. This is a fairly recent discovery, but it's an important one. Glp-1 tends to inhibit, feeding and tends to reduce appetite. There are a number of drugs released on the market. Now 1 for instance, goes by the name. Some
Igloo tide, which is essentially an glp-1 agonists. It causes the release of more glp-1. It's being used to treat. Type 2 diabetes, which is insulin resistant, diabetes. This is different than type 1 diabetes, where people don't actually make insulin. It's also being used as a drug to reduce obesity and it seems pretty effective at least in certain populations. There are certain foods and substances that increase glp-1. I've talked about a few of these on the podcast, one that I
Particular fan of for entirely other reasons is yerba. Mate. Tea can stimulate the release of glp-1 in South America. It's often used as an appetite suppressant, probably in large part because of its effects, on glp-1 release, but probably also because it does contain caffeine which is a bit of a, stimulant, which also can be involved in lipolysis, which is the utilization of fat stores for energy and so forth.
A brief mention about yerba mate. There are some reports out there that yerba mate can increase certain types of cancers. The data that I've seen on this is that it tends to relate to whether or not those are smoked versions of the Yerba mate tea, the amount of consumption and the debate is still out. So I invite you to look at those papers. You can search for those online.
Nonetheless yerba mate is one source of glp-1 stimulation. Some Igloo tide is another source. It also can be stimulated by various Foods nuts, avocados eggs, and so forth. Certain high fiber, complex grains will also stimulate glp-1. I raise this as not necessarily a route that you want to take in order to reduce food intake. I don't even know that that's your goal. But that glp-1 is
Another one of these gut to brain signaling mechanisms that adjust appetite, that is dependent on diet, depends on what you eat or drink and that the glp-1 pathway does seem particularly sensitive to the constituents of diet. There's at least one quality study. I was able to find showing that the ketogenic diet, for instance, which almost always involves ingestion of very low levels of carbohydrate can increase glp-1, although, as I mentioned before, there are other foods that fall outside the
Inch of what we would consider ketogenic that can also stimulate glp-1. And as I mentioned their prescription drugs, like someone glue tied their other ones as well. Now that stimulate glp-1. So how does glp-1 reduce appetite it? Does that in part by changing the activity of neurons in the hypothalamus this cluster of neurons just above the roof of our mouth that themselves, make glp-1 and that caused the activation of motor circuits for reaching chewing, all the things that we associate with feeding.
Yer. So I use glp-1 as an example of a pathway that you might choose to tap into by ingestion of yerba mate, or by ingestion of the foods I mentioned. Or if it's something that interests, you ketogenic diet, but I also mention it simply because it's an another beautiful example of how a hormone pathway can impact the activity of brain circuits that are directly involved in a particular Behavior. So yet another example of how gut is communicating to brain in order to change what we think we want or to change, what our actual
Behaviors are. So the next time you find yourself reaching for food, or you find yourself, wanting a particular sweet thing or fatty thing or something that contains a lot of amino acids, a protein rich food. Keep in mind that that's not just about the taste of the food and it's not even necessarily about the nutrients that you need or don't need. It could be. But it's also about the subconscious signaling that's coming from your body all the time. Waves of hormones, waves of nerve cell signals electrical.
Electrical signals that are changing the way that your your brain works and this raises for me, a memory of the episode that I did with. Dr. Robert sapolsky, who's a world expert colleague of mine. At Stanford, who is expert on things like hormones and behavior, but we got into the topic of Free Will, which is a bit of a barbed wire topic as many of, you know, it gets into the realm of philosophy, etcetera and we were kind of batting back and forth. The idea I was saying, well, I think there's free will and can't there.
Certainly be free will or or certainly the the idea that we can avoid certain choices. And Robert was saying, No, in fact, he said nah, he doesn't believe that we have any free will. He thinks that events in our brains are determined by biological events that are below our conscious detection and that occur S 2 milliseconds before we make decisions or assessments and therefore we just can't control what we do, what we think and what we feel and at the time
I sort of didn't buy it. I thought, I don't know. I just I guess I really wanted to believe in Free Will and to some extent, I still do. But as we talked about how these neurons and our gut, and these hormones in our gut are influencing our brain, and the decisions that we are making at the level of circuits, like the hypothalamus, and the nucleus of the solitary tract. These are areas of the brain way below our frontal cortex, and our conscious perception. Think these are examples that really fall in favor of what doctor sapolsky was arguing, which is that
Events that are happening within our body are actually changing the way our brain works. We might think that we want the cupcake. We might think that we don't need to eat something or do need to eat something and that is entirely on the basis of prior knowledge and decision-making that we're making with our head. But in fact, it's very clear to me based on the work from the bojorquez lab classic work over the years, dating back to the 80s and indeed back to the 50s that we'll talk about in a moment that our body is shaping the decisions that our brain is making
We're not aware of it at all. Now the good news, is that whether or not you believe in free will or not the simple knowledge. That this whole process is happening can perhaps be a benefit to you. You can perhaps leverage it to get some insight and understanding and perhaps even a wedge into your own behavior. You might think I think I want that particular food or I think I want to avoid that particular food, but actually, that's not a decision that I'm making on a purely. Rational basis has a lot to do with what my gut is telling my brain. So we've largely
I'm talking about chemical communication between the gut and the Brain chemical because even though these neuro pod cells are communicating with the brain, by way of electrical activity, what we call Action, potentials. And in neural language we call those spikes spikes of action, potentials.
Spike's have a commission potentials. Meaning those neural signals cause the release of chemicals in the brain like dopamine.
So it's chemical transmission.
Similarly hormones, even though they act more slowly or moms, like neuropeptide y like cck, like ghrelin, they are signaling chemically, they're moving through the body. They're going in there affecting the chemical output of different cells and they're changing the chemistry of those cells in the chemistry of the cells. Those cells talk to so that gives us one particular category of signaling from gut to brain, which is chemical signaling. But of course, there are other forms of signals and those
Under the category of mechanical signaling. You're probably familiar with this. If you've ever eaten a very large meal or consumed, a lot of fluid, you experienced that as distention of the gut and that doesn't just have to be distention of the stomach, but distension of your intestines as well that distension is registered by neurons. That reside in your gut, the signals go up to your brain and communicate with areas of the brain that are responsible for suppressing further consumption of food and or fluid and
Under certain circumstances can also be associated with the activation of neural circuits that cause vomiting or the desire to vomit. So if ever you've eaten too much or you've eaten something that doesn't agree with you, that information is communicated by way of meccano sensors that sense the mechanics of your gut, possibly also the chemistry of your gut but mostly the mechanics of your gut signal up to the brain and activate brain centers that are involved in stopping the eating behavior and activation.
Of an area of the brain stem. That is affectionately for referred to as the vomit Center among neuroanatomists. This is a area that more appropriately is called the chemoreceptor trigger Zone. The ctz or area post trauma and neurons in this area, actually will trigger the vomiting reflex. So the way that the gut and the Brain communicate is both chemical and mechanical and it can be both for sake of increasing certain types of behavior. Today. We're talking mainly about feeding.
Havior up until now anyway, but also ceasing to eat closing your mouth, moving away from food, turning away from food, all behaviors, that were familiar with anytime. We feel kind of sick on the basis of activation of this, meccano sensor for gastric distress. So we've got chemical signaling and mechanical signaling. And I also want to emphasize that we have direct and indirect signaling from the gut to the brain. Direct signaling is the kind of signaling of the sort. I've been talking about mainly a
up until now, which is neurons in the gut communicating with neurons in the brain stem that communicate with neurons in the hypothalamus. And of course, those are also going to interact with neurons of the prefrontal cortex, which is the area of the brain involved in decision-making. The you know, I think it was the shrimp that made me sick. I'm going to I just don't want any more of that or I'm never going back to that restaurant again, because after I ate there about an hour later, I started feeling really not. Well, I felt, you know, kind of feverish but my gut didn't feel well, my digestion was really
Off all of that kind of information is handled in the prefrontal cortex at a conscious level, but the immediate decision to stop eating, or to eat more of something to move towards something or away from it. That's made by neural circuits that reside at the, we would say, the subconscious layout level, but what we really mean is below the level of the neocortex below, the cortex means, essentially below our level of conscious awareness. So we talked about two types of information within the gut that are communicated to the brain chemical information. Meaning information about the
Giants that happen to be there and mechanical information, distention of the god or lack of distension and so forth. And we talked about how these neuro pod cells can signal the release of dopamine and circuits within the brain to cause you to seek out more of something. Now, in a very logically consistent way, dopamine is also involved in the whole business of vomiting. You might think. Well, that doesn't make any sense. I thought dopamine was always a good thing. It's involved in motivation and reward etcetera, but turns out that area push Strummer. This vomit Center.
And the brain stem is chock-a-block full of dopamine receptors. And if dopamine levels, go too high. It can actually trigger vomiting. And this, we see in the context of various drugs, that are used to treat things, like Parkinson's, Parkinson's is a deficiency in dopamine or a lack of dopamine neurons. Typically, the causes a resting Tremor difficulty in movement, because dopamines also associated with a lot of the neural circuits for movement, many drugs that are used to treat Parkinson's like l-dopa increased levels.
Has of dopamine so much or at least activate dopamine receptors to such a great degree in certain areas of the brain that they can cause activation of things like the trigger to vomit. Now. This should also make sense in the natural context of you, Gorge yourself with food, Gorge yourself with food, gorgeous off with food the neurons in your gut. That respond to that are simply detecting the presence of nutrients, but they don't really make decisions themselves. They don't know to stop eating.
Brain knows to stop eating or to eject that food. And so it's a wonderful thing that those neurons are communicating with areas of the brain. Not just that stimulate consuming more food, but that are communicating with areas of the brain. For instance area, post trauma that when dopamine levels, get too high cause us to either stop eating that food or in the case of vomiting to eject that food. So I raise this, not to give you a kind of disgusting counterexample to what we call a
Negative behaviors the things that we like to do more of but simply to give you a sense of just how strongly even these reflexes that we think of as feeling sick and vomiting or the desire to seek out, more food are really being controlled by a kind of push pull system by parallel Pathways that are arriving from our gut and the same neural. Chemicals. In this case dopamine are being used to create two opposite type behaviors. One Behavior to consume more one Behavior to get rid of everything you've already consumed. So our brain is actually sensitive.
Of to the amount of signaling coming from our gut, not just the path, by which that signal arrives. Our brain is very carefully, paying attention to whether or not the levels of dopamine that are being triggered are within a normal range for typical eating Behavior or whether or not we've gorged ourselves to the point where enough already. Now, of course, mechanical signals will also play into area Plus drama and into the vomiting reflex. If we have a very distended gut, we feel lousy, it just it actually can.
Hurt very badly and we will have the desire to vomit, but where we will just simply vomit, mechanical and chemical signals are always arriving in parallel. They never work in unison. And so now we have chemical signals mechanical, signals and a now I'd like to talk about direct and indirect signals because almost everything I've talked about and up until now our direct signals a neural pathway that converges in the brain to create a particular feeling thought or behavior, but there are also indirect
And that's what takes us back to the gut microbiome and to these little microbiota. And to just give you the take away message at the front here. And then I'll give you a little more detail as to how it comes about. You have neurotransmitters in your brain and in your spinal cord and in your eyes and in your peripheral nervous system, they cause the activation or the suppression of nerve activity, meaning they either electrically activate, other nerve cells or they cause other nerve cells to be less electrically active and they do that by way of
Neurotransmitters, but as it turns out, the gut microbiota are capable of influencing metabolic events. And in some cases are capable of synthesizing neurotransmitters themselves. So what that means is that these little bugs, these little micro biota that our Cargo in your gut, this six pounds of cargo, they actually can make neural chemicals that can pass into the bloodstream, and into your brain and actually impact the other cells of your body and brain indirectly. So, without involving these, very intricate nerve pathways.
We've been talking about. In other words, the foods you eat the environment of your gut, microbiome can actually create the chemical substrates that allow your brain to feel one way or the other to feel great or to feel lousy to seek out more of a particular type of behavior or to avoid that behavior and that would constitute indirect signaling. So, I've been talking a lot about the structure and function of the gut to brain pathway focusing, mainly on feeding behaviors. And in some cases, avoiding feeding or
even ejecting food from the digestive tract. I'd like to drill a little bit deeper into this indirect signaling pathway from the gut to the brain because it Bridges us nicely from neuronal signals in the gut to the brain. Hormonal signals from the gut to the brain to what also includes the microbiome, which is what we started talking about at the beginning of the episode.
They mention a couple of minutes ago.
Certain gut microbiota can actually synthesize certain neurotransmitters that can go impact the brain. And we actually have some knowledge about which microbiota can synthesize particular neurotransmitters. For instance. The neuromodulator dopamine can be synthesized by or from bacillus and Sriracha. Now, these are just names of microbiota. I don't expect that. Any of you would necessarily recognize them. These aren't the sorts of things that you necessarily would run out and buy to get more dopamine, but the
Is that particular gut microbiota can create dopamine in our gut that can get into our bloodstream and can generally change. The our Baseline levels of dopamine within the brain and other areas of the body. I mentioned Baseline levels of dopamine because as I talked about on an episode all about dopamine, but I'll just repeat the basics here. Now, we have Baseline levels of neurotransmitters or neuromodulators that act as sort of the level of the tide. The oh
Overall level. And then we can have peaks of dopamine that are created by behaviors, or, by ingestion of particular Foods, or drugs, Etc. So bacillus and Sarah Tia tend to increase our Baseline levels of dopamine. So if it turns out that we are creating the right gut microbiome environment, that these particular gut microbiota can thrive in. Well, then our Baseline levels of dopamine will be elevated and in general that leads to enhancement of mood.
Similarly, there are other gut microbiota, for instance, candida streptococcus, various enterococcus. These always have these with kind of strange, and not. So, attractive names, at least to me is a neurobiologist, nonetheless, those particular microbiota support the production of, or can even be metabolized into serotonin, which is a neuromodulator associated with mood, with social interactions with a huge number of different types of
Events and behaviors again these gut microbiota, when present and allowed to thrive in our gut will increase our overall levels of Serotonin and riding on top of that. Level of Serotonin will be the serotonin. That's specifically released in response to certain behaviors. I really want to drive home this point of baselines and Peaks the Baseline level of Serotonin might set our overall mood whether or not we wake up feeling pretty good or
Really lousy, if our serotonin levels happen to be very, very low whether or not we tend to be in it kind of a calm space or whether or not we tend to be somewhat irritable. But then of course, individual events as we go about our day, maybe a compliment that we get or maybe somebody says something irritating to us, whatever it may be, will also influence levels of Serotonin but those serotonin events are going to be related to events at particular, neural circuits in the brain and this is an important topic because I think that a lot of people here quite accurately
90 to 95 percent of our serotonin is manufactured in the gut, and indeed that's true. It's manufactured from the sorts of microbiota that I just described and there are many, many experiments now mostly in animal models, but also some in humans that show that if the gut microbiome is deficient, in some way to these particular bacteria, that serotonin levels, drop and people's mood suffers, maybe even their immune system functions, maybe even exacerbates certain psychiatric illnesses.
However, a lot of people take that to mean that the serotonin of the brain, all comes from the gut or mostly comes from the gut, that's not the case. It's still the case that you have neurons in the brain that are responsible for releasing their serotonin directly in response to certain things like social touch or through other types of positive social experiences. So we've got
Gut microbiota that can literally be turned into dopamine and raise our Baseline levels of dopamine. We've got gut microbiota. That can literally raise our Baseline levels of Serotonin and indeed, there are other gut microbiota like, lactobacillus or biffo dekhti bifidobacterium. Scuse me hard complex names to pronounce bifidobacterium, that can give rise to increases in Gaba levels. This inhibitory neurotransmitter that can act as a little bit of a mild sedative can reduce irritability.
Etc, but that's just the Baseline. The kind of Tide of those neuromodulators. Again. I want to emphasize that we still have neural circuits within the brain and body that are specifically releasing in a very potent way, dopamine serotonin and Gaba. So the two things act in concert, even though the gut and the brain are acting both in parallel and directly influencing one another. It is a powerful synergistic effect, and there are now hundreds of studies, maybe even thousands by this point.
Aunt, mostly performed an animal models typically mice, but also some studies in humans that show that creating the correct environment for these gut microbiota to thrive, really does enhance mood and well-being and that when our gut microbiome is not healthy, that it really can deplete our mood and sense of well-being. Now, there are two major phases to creating a healthy gut microbiome, one, you can control and the other
Is less under your control. I get into this in a lot of detail in the episode with dr. Sonnenberg, which is coming out immediately after this one, the following Monday that is. But for now, I want to just capture a few of the main points about the early establishment of the gut microbiome.
It turns out that the
environment that we are exposed to the things that come into contact with our skin and digestive tract, and any other mucosal lining even the urethra, the nasal passages. Any opening to the outside world that brings in circuit, excuse me, certain microbiota in the first three years of life is going to have a profound impact on the overall menu of microbiota that we will be able to carry within our body. And it really does seem
Getting exposure to and building a diverse microbiome in those. First three years is critical. There is a lot of speculation and some data. As to cesarean delivered babies, having less diverse microbiomes compared to vaginally delivered babies. There have been attempts. Although not conclusive attempts to link that to the, the presence of autism spectrum disorders, which at least, by some statistics, seem to be of higher probability in cesarean deliveries, although there are
Are other studies that refute that, and I want to make that clear?
However, it's clear that babies do not get much if any exposure to microbiota inside of the womb, maybe a little bit, but not much. But that is during the birth process, and then the days and weeks immediately after they arrived in the world, that their gut microbiome has established that those gut microbiota, take residents within the gut, so it will depend on whether or not they were breastfed or bottle-fed. It will depend on whether or not they were exposed to a household pet or not, whether or not they were held by.
Caregivers or just buy one whether or not they were a preemie baby. And we're contained in a particularly restrictive environment in order to encourage their further development before. They could be brought home or not. I don't want to give the picture that if you were isolated, or you were delivered by C-section that you're somehow doomed, have a poor microbiome, that simply not the case. However, it is the case that the more diversity of microbiota that one can create early in life is really helpful for it.
Long-term outcomes in terms of brain to got signaling got to brain signaling. And for sake of of the immune system. There are some decent studies showing that if children are exposed to a lot of antibiotic treatment early in life that can be very detrimental to establishment of a healthy gut microbiome. And fortunately, that re-establishing a healthy gut microbiome can help rescue some of those deficits. So doctors, nowadays are much more cautious.
About the prescription of antibiotic drugs to children in their early years. Not just up to three years, but extending out to, you know, five and seven and ten years and even in adults. They're very, very careful about that or they ought to be one reason, is the existence or say, the proliferation of antibiotic-resistant bacteria that are becoming more common in hospitals and elsewhere, and that can cause serious problems. But in addition to that, because of this understanding that the gut microbiome is influencing
And actually creating neurotransmitters that can impact mood, and mental health, impact, immune health and so on. As I mentioned earlier, there are hundreds, if not thousands of studies emphasizing the key role of the microbiome on brain, health psychiatric, Health, Etc. I want to just highlight a few of those studies. And in particular, some recent studies that come from Labs that have been working on this sort of thing for a very long time. One of the more exciting studies comes from the work of malraux cost. Amati Oles lab, which is at Baylor College of Medicine.
Listen Morrow's lab has been working on Mouse models of autism spectrum disorder for a long time and looking at social behavior using a mouse model for a long time. And they've been able to identify particular types of microbiota that when they take resonance in, the gut can help offset some of the symptoms of autism at least the symptoms of autism that exist in these Mouse models. Okay. So again, this is not human work. This is work being done.
Done a mouse models. For the simple reason that you can do these kinds of manipulations where basically they took mice that were in germ, free environments, or non germ-free environments, or they expose my stew. Particular microbiota and not other microbiota and they discovered that a particular microbiota called el rotary it, sell period re u t erri treatment with L router, eat corrects the social deficits present in these autism models, and it does so by way of activating.
Our old friend, the vagus nerve but not simply because the vagus nerve triggers the release of dopamine, but it turns out that this particular gut microbiota prudery can correct the social deficits in this autism spectrum disorder model. It does that by way of a vagal nerve pathway that stimulates both dopamine release an oxytocin release. And they establish, this really mechanistically by showing for instance. If you get rid of the oxytocin receptor, you don't see this rescue. Now, those are Mouse models. So we have to take those with the appropriate grain of salt, but they're really
a exciting and they come to us in parallel with other studies that are being done taking the microbiomes of people who have one condition or lack of condition and putting it into people who have one condition or another condition. Let me explain what I mean by that the early discovery of the gut microbiome and its potential to impact Health was not in the context of the gut to brain pathway, but rather it was in the context of colitis, this dates back to studies in the
He's whereby people with very severe intractable colitis for which no other treatment was going to work received fecal transplants. So yes, that's exactly as it sounds taking the stool of healthy people who do not have Colitis. Transplanting those stools into the lower digestive tract of people who do have Colitis and they saw a significant Improvement. If not Rescue of the colitis, that was one of the first indications, that something within stool of all things could actually rescue.
Another individual from disease, which sounds kind of wild and crazy and may even sound disgusting to some of you. But as I mentioned at the beginning of the episode, almost 60% of stool is live or dead bacteria microbiota, and it really opened up this entire field of exploring how different microbiota much might have therapeutic effects and indeed that has been shown to be the case also in fecal transplants for certain psychiatric.
This has
these are still ongoing studies. They vary in quality. It's these are hard studies to do, for all sorts of reasons, getting the appropriate patient populations getting agreement etcetera, making sure that everything is handled properly. But what this involves is fecal transplants from individuals, that lack a particular psychiatric condition or metabolic condition into people who have a particular, metabolic condition and there has been tremendous success. In some cases, one of the more
Powerful and Salient examples is for obesity. There's some people for which even if they ingest very low numbers of calories, even if they go on a liquid protein, diet simply can't lose weight. Is they're somewhat rare disorders, but these are people that would either. Do I get gastric, bypass surgery. Some people are now getting these fecal transplants from people that have healthy healthy weight and they take the stool from them. They put it into lower digestive tract and they can see substantial.
Mint in weight loss and people that were otherwise unable to do that in some cases. Actually, they can start eating relatively normal levels of food and still lose weight. So, pretty remarkable, and that tells us there's something in these microbiota. That's really powerful. Now, how those effects are generated is in clear one idea, is that it's impacting the metabolomic components of the metabolism. Almost certainly that's going to be the case. Another idea is that it's impacting neurotransmitters, which change behavior and food choices within the
Brain, although, as I mentioned some of these people are already eating very little food to begin with. So that's a little bit harder of an argument to create. There are also some somewhat famous examples now of how fecal transplants can lead to negative outcomes, but those negative outcomes further underscore the power of the microbiome in impacting bodily health.
One key example of this, for instance is transfer of fecal matter into another person in order to treat something like colitis and it effectively does that but if the donor of the of the stool of the fecal matter happen to be obese or have some other metabolic syndrome, it's been observed that the recipient can also develop that metabolic syndrome simply by way of receiving that donors particular microbiota. So these microbial
But I can create positive outcomes or they can create negative outcomes. Most of us, of course, are not interested in or pursuing fecal transplants. Most people are interested in just creating a healthy gut microbiome environment for sake of immune system and brain function. And we will talk about how to do that in just a few minutes, but I just want to further underscore the power of the microbiota in shaping brain chemistry, and in shaping things like mood or other aspects of mental health that typically, we don't associate with our gut.
There are several studies published in recent years one that I'll just highlight now first author, it's Tanya Nguyen and g. Uy e, n, the title of the paper is Association of loneliness, and wisdom with gut microbial, diversity and composition an exploratory study. So interesting study looked at 184, community-dwelling of a adults, excuse me, ranging from, 28 to 97 years old, they explored
Whether or not having enhanced microbial diversity, somehow related to these variables that they refer to as loneliness and wisdom. They used a number of different tests to evaluate those. Those are common tests in the psychology literature and not so much in the biology literature. But nonetheless, there are ways of measuring things like loneliness, and wisdom wisdom. In this case, being that the opposite of loneliness, at least in the context of this study and what they found was the more microbial diversity, the more
First ones microbiome was the lower incidence of loneliness and they did this by taking fecal samples profiling them for RNA. So essentially doing Gene sequencing of the stool of these individuals getting ratings of how lonely or not lonely. They felt and correlating those. And that's just, but one study, I point it out because it's particularly recent and it like it was particularly. Well done. There is another study that I'll just refer you to. This was a study published in 2020 and scientific reports. The title of the study is emotional well-being and
And gut microbiome profiles by in Tarot type. What I particularly like about this study is that they were able to correlate the presence of certain microbiota with feelings of subjective, well-being and lack of or presence of depressive
symptoms.
They did high-throughput Gene, sequencing of the microbiomes of individual. So that meant measuring, the microbiota figuring out which microbiota were present how diverse their microbiome was in general, gut microbiome. Diversity is a good thing and
Then to correlate that with What's called the PA n a.s., Score PA nasd and for positive effect, negative effect schedule. This is a test that my lab is used extensively than other labs, use to evaluate mood and well-being. And they Define what we're what were called, three enterotypes, three different categories of people that ate very different diets that tended to fall into categories of having more or fewer emotional symptoms that were negative or more, if you were emotional Signum symptoms that were
Positive and whether or not they tend to be more depressed anxious or have more stress related, behaviors, Etc. And what they were able to derive from this study was some strong indications about what types of things we should ingest in our diet, maybe even certain things that we should avoid, but certainly the types of things that we should ingest that can enhance mood and well-being and can tend to shift people away from more depressive like anxiety and stress related symptoms before we get into what the particular food items worth at least.
Themselves to a healthy microbiome. I want to raise a bigger and perhaps more important issue, which is what is a healthy microbiome. I think if you asked any number of world experts, and I certainly ask this of doctor Sonnenberg. What is a healthy microbiome? They're all going to tell you. It's a micro biome that has a lot of diversity. That includes a lot of different types of bacteria that make sense it, because it logically would include the bacteria that produce Gaba, and dopamine, and serotonin, and that support the immune system and do a number of different.
Things, but is it simply the case that adding microbiota diversity is always a good thing. Well, that doesn't seem to be the case.
Probiotics and prebiotics, both of which can enhance microbial. Diversity, can improve mood digestion, immune system, and so on, that's been established, but it's mainly been established in the context of post antibiotic treatment or people that are recovering from illness or people that have been very stressed or have been dealing with all sorts of challenges, mental or physical. And they are an attempt to replenish the gut microbiome. However, it's
also clear that excessive microbiota brought about by excessive intake of probiotics can lead to things. Like brain fog. There's actually some good studies that point to the fact that certain metabolites of the microbiome, certain chemicals produced in the gut. And in in the body can actually lead to brain fog States. This is thought to come about through the lactate Pathways of the gut that can then impact the brain if you want to look more into this issue of whether or not
Probiotics taken in excess, perhaps can lead to brain fog. I'd encourage you to look at a particular paper. There is a paper published in clinical and translational gastroenterology. And the title of the paper is brain, fogginess, gas and bloating. A link between sibo probiotics and metabolic acidosis. It was published in 2018. We can provide a link to this study and there are several other studies in the references that point to the fact that in some cases, excessive intake of protein.
Alex and excessive proliferation of gut microbiota. Can actually be problematic. I mention this not to confuse you but because it is confusing out there. We all would think that just increasing microbial diversity is always a good thing but there are thresholds Beyond which excessive microbial diversity might be problematic. I think everyone agrees that having too few microbial species living in US is not a good idea. Now, none of that answers the question.
Is that I think everyone really wants answers to which our, what should we do? What should we not do to improve our gut microbiome? I mean, clearly we can't time travel back to when we were 20, 23 years old and get a dog. If we didn't have a dog, get breastfed, if we weren't breastfed be delivered, vaginally as opposed to, by C-section. If we didn't have that opportunity, we just can't time travel and do that all of us. However, should be seeking to improve the conditions of our gut microbiome, because of the critical ways in which
It impacts the rest of our brain, and bodily health. So what should we do? What should we do? Clearly? We know that stress can negatively impact the gut microbiome. However, some forms of stress that can quote unquote, negatively impact, the microbiome include fasting long periods of fast, which makes sense because a lot of microbiota need food in order to thrive. In fact, many if not, all of them do at some point.
There are other questions such as should we eat particular foods and how often should we eat those Foods? We've all been told that fiber is incredibly important because of the presence of Prebiotic fiber which can essentially feed the microbiome, but is fiber really necessary and how necessary is it to encourage a healthy microbiome. Clearly. There are a number of people following relatively low fiber diet such as ketogenic diets, and those can have in some cases, anti-inflammatory effects and can
Some times also improve certain microbiota species. So it can all be rather confusing and for that matter. I asked our resident expert. Dr. Justin Sonnenberg at Stanford all of these questions and he answers them. Very systematically in the episode that comes out after this one, but I don't want to withhold anything from you. So I'll just give a very top Contour version of those answers. And then you'll get more in-depth answers. During that episode. I asked about fasting. And the reason I asked about fasting is that
Years ago, I was at a meeting as part of the Pew, bios, biomedical Scholars meeting and one of the other few biomedical Scholars is an expert in gut microbiome. And I said, hey are probiotics good for the microbiome. And if so, which one should I take? And his answer was very interesting. He said, you know, in certain cases they can be, especially if you're traveling or you're stressed, but it turns out that that particular bacteria that they put in most probiotics, don't actually
We replenish the microbiota that you need most. And I thought oh, well, why don't they make ones that replenish the microbiota that you need most? And his answer was, well, they don't replenish those but they replenish other ones that then in turn encouraged the development of the microbiota that you do want. Once you start eating the appropriate Foods. So they change the environment, which makes the environment better. Which indirectly supports the proliferation of quote unquote, good microbiota. Okay, so that was a somewhat convoluted.
Dancer, but I did appreciate his answer. Then. I asked him about fasting. I said, well, a lot of people are getting interested in intermittent fasting. Now, people are spending a significant portion of each 24-hour cycle. Avoiding food for sake of time, restricted feeding. What does that do to the gut microbiome? Does it make it healthier? Does it make it unhealthy? ER? Well, my colleague from Yale and dr. Sonnenberg both confirmed that during periods of fasting, especially prolonged periods of fasting. We actually start to digest away much of our digestive tract. Now, the whole thing doesn't start too.
Pierre. But there's thinning of the mucosal lining or at least disruption the mucosal lining. A lot of the microbiota species can start to die off. And so it was surprising to me. But nonetheless, interesting that fasting may actually cause A disruption to certain healthy elements of the gut microbiome. But again, there's a caveat. The caveat is that when people eat after a period of fast, there may be a compensatory proliferation, meaning an increase in healthy gut.
Microbiota, so you start to get the picture that fasting is neither good nor bad. You start to get the picture that particular diets, meaning certain restriction, diets, or macro, nutrient, Rich diets may not be good or bad for the microbiome. And yet there are some answers that arrive to us from dr. Sonnenberg, but from other experts in the field, that there are certain foods and certain things that we can ingest, which definitely enhance the microbiome and make it healthier than it.
Were we to not ingest those Foods. So next I'd like to talk about what I think is a really pioneering and important study in this area. This is a study that was carried out by the Sonnenberg lab in collaboration with Chris gardeners lab also at Stanford where they compared to General types of diets in humans diets that were fiber-rich, which has been proposed time and time again to enhance microphone biodiversity and to enhance gut-brain signaling even and to enhance the
the immune system, perhaps and diets that were enriched in so-called low sugar. Fermented foods before I dive into that study and what the conclusions were, because they are very interesting and very actionable for all of us. I do want to touch on probiotics because I want to avoid confusion.
It is not the case that ingestion of probiotics will always lead to brain fog. I want to make that clear, it is the case that ingestion of probiotics, even if those probiotics don't directly contain, the microbiota species. That one is trying to proliferate can be useful for improving microbial diversity. In general. It seems that maintaining a healthy gut microbiome involves ingesting, certain types of foods. We will talk about those in a moment.
But perhaps also augmenting, the microbiota system through prebiotics or probiotics at a fairly low level on a consistent basis. So these are not high dose probiotics except under conditions of dysbiosis. Where, for instance, if somebody has done a round of antibiotics and they need to replenish their gut microbiome, there are foods and their appeal form and powder form, prebiotics, and probiotics that can be very useful or in cases where people.
Have been very stressed or are undergoing excessive travel or have shifted their diet, radically. Maybe that's due to travel maybe that's due to illness. Maybe that's due to stress. But when there are a number of different converging events that are stressing or depleting microbial diversity. That's when at least, I believe it can be useful to support the gut microbiome, through the ingestion of quality probiotics or prebiotics. So it would be under conditions where people are.
A store their system is generally stressed for environmental or illness related reasons that it might be useful to lean towards higher doses of prebiotics and probiotics than one might normally use. But that under normal conditions, that one would focus on quality nutrients through diet, and focus on ingestion of probiotics, at a fairly low to moderate level and or prebiotics at a fairly low to moderate level.
Just seems like the logical approach based on the experts that I've spoken to, but certainly, if your doctor prescribes or suggest that you take high levels of probiotics, for any reason, you should definitely pay attention to your physician and you should, obviously pay attention your physician. In any case you should never add or remove anything from your nutritional plan or supplementation plan without conduct Consulting a physician. So what should we do in order to maximize the health of our gut brain axis? As it's called? How should we support the diversity of the good?
Biota that help us create all these neurotransmitters that we want improve our immune system function and so on and so forth. Well, some of that is going to be through the basics when I say the basics, I mean the foundational things that really set us up for overall health. So this is going to be getting deep sleep of sufficient duration, 80 plus percent of the time. I mean, if you could get a hundred percent of the time, that'd be great. But very few people accomplish that it's going to be proper hydration. It's going to be proper.
Social interactions. It's going to be proper nutrition and we'll talk more about nutrition and moment. It's going to be limiting, excessive prolonged stressors or stress. And indeed, we've done episodes about just about all of those things, but certainly about stress. We have an episode of the human loud podcast that you can find at huberman lab.com. All about mastering stress. How to avoid long periods of intense stress? What to do to offset those?
Given that stress can disrupt the microbiome, whether or not you're fasting or not. Those tools ought to be useful. Now, in what I consider to be a landmark study exploring, the relationship between the gut microbiome food intake, and overall health is this paper from Justin Sonnenberg slab and Chris Gardner's lab. Both of which are at Stanford and the paper entitled gut microbiota targeted diets modulate human immune status was published in the journal cell.
Which is among the three top journals, perhaps in the world nature science and sell really being the Apex journals for overall science and especially for biomedical Sciences. Now, this is very interesting study. It was done on humans. There were two major groups, one group of humans was instructed to increase the amount of fiber in their diet. And in fact eight a high fiber diet, the other group was instructed to eat a high, fermented food diet now.
Both groups started off not having eaten a lot of fiber or a lot of fermented foods and we're told to increase the amount of either fiber or fermented foods that they were ingesting over a four-week ramp up period and that was to avoid any major gastric distress. It turns out that if you're not already accustomed to eating a lot of fiber, increasing the amount of fiber dramatically can cause some gastric distress, but if you ease into it over time, as we'll see there's a mechanism behind this which was unveiled in this study, but if you ease into it over time,
Then the system can tolerate it, likewise. Hi, fermented foods can be readily tolerated. If there's a ramp up phase of ingesting, maybe one serving a day, then maybe two servings and ramping up in this case, as high as six servings per day. However, after this ramp up period, the group assigned to the high fiber condition, maintained, high fiber intake for six weeks and the high fermented food group, maintained High, fermented food intake, 46.
Weeks after which they went off, either the high fiber or the high, fermented food diet and there was a four-week follow-up period during which they gradually returned to Baseline throughout the study, their gut microbiome was evaluated for the diversity of gut microbiota. And there were also a number of measures of immune system function, in particular, measures of the so-called inflammatory on the immune system has a lot of different molecules involved. I did a whole episode about the immune system if you're interested in learning what some of those molecules
Our various cytokines and signaling molecules that reflect either High inflammation States or reduced inflammation states in the brain and body. You're welcome to check out that episode. It's also a huberman lab.com. Regardless, in this study. They explored the sorts of immune markers that were expressed in either of the two groups and compared those, the basic takeaway of this paper. Was that contrary to what they predicted, the high fiber diet did not lead to
To increase microbiota diversity, at least, not in all cases. And that was somewhat. Surprising the idea is that Prebiotic fiber and a lot of the material in fruits and vegetables and Grains and so forth are supposed to support microbial diversity and the proliferation of existing microbiota. And that is not what they observed. Although. I want to be very clear and pointing out that the results do not indicate. That fiber is not useful for
Overall, but it does point to the fact that increasing fiber intake did not increase micro biodiversity, which in general, as I mentioned before, is associated with improvements in microbiota function, health and overall well-being. Now, the high fermented food diet. Condition was very interesting. It resulted in increased microbiome diversity, and decrease inflammatory signals and activity. So there was a twofer. Basically, by ingesting High fermented foods.
At Fair abundance, right, you know, four to six servings or more per day is a lot of fermented food intake will talk about what some of those Foods were but the outcome was very positive. It was a clear increase in microbiome diversity, and decreased inflammatory signals. So things like interleukin 6 a number of other interleukins and cytokines that are associated with increased inflammation in the brain and body were reduced significantly. Now, let's talk a little bit about this notion of know.
Of servings Etc, one somewhat minor point of the study, but I think is useful in terms of an act, taking an actionable stance with this, is that the number of servings of fermented foods, was not as strong. A predictor of improvements in the inflammatory, meaning, reduced inflammation, and improvements in micro biodiversity as was the duration of time that the individuals were ingesting fermented foods. In other words, the longer that one is consistently.
In fermented foods on a daily basis. The better the outcomes in terms of the gut microbiome and for reducing inflammation. So I think that's an important point and I make that point especially because for a lot of people, even if you do this ramp up Phase 6 servings per day of fermented foods, can seem like quite a lot. So what are these fermented foods right? I think many of us are familiar with certain Cheese's and being fermented and beer being fermented. And kombucha is fermented in this study. They focus specifically
On low sugar, fermented foods. So this would be plain yogurt in some cases kimchi or sauerkraut and important consideration. However, is that it needs to contain what are called live active cultures, which means they're actually have to be microbiota that are alive inside the sauerkraut. One way, you know, whether or not that's happening is if you purchase sauerkraut or pickles or kimchi from a jar or container that's on the non-refrigerated Shelf of the
Anon refrigerated section of your grocery store. It is not going to contain live active cultures of microbiota and likewise. If you consume yogurt that has a lot of sugar or other components added to it. It's not going to have the same positive effect on the microbiome. At least that's the prediction. Given some of the relationship between the sorts of microbiota that live in sugared versus plain type. Yogurts. They gave people the option of consuming any number of different low-sugar fermented food, so that
And that could be sauerkraut, kimchi, things like Kefir natto in Japan. They consume natto, which is a fermented food. Beer, wasn't a, not one of the fermented foods. That was included in the fermented food list. And when we say six servings per day, that is indeed 6. 6 ounce servings or 6-4 2-6 out servings. It was not 6 servings of what's listed on the package. So that again, that turns out to be a fair amount of fermented foods. How should you gauge whether
Or not, you're getting enough of this. Well, if you decide to take on this protocol of ingesting, more fermented foods, which at least, by my read of this study and some of the follow-up work that's being done. Sounds like a terrific idea. If you want to improve your gut microbiome, for all the great reasons, that one would want to brain body Health, reduced inflammation and on and on. Well, then you definitely want to focus on fermented foods that you enjoy consuming. So for you, if that's kefir or for you that's plain yogurt or for you that sauerkraut.
Which happens to be my personal favorite. Then you want to make sure that it's going to be something that you are going to enjoy ingesting quite a lot of and that you're going to be okay with ingesting. Probably throughout the day. Now if people follow different meal schedules, of course, but this does require not just eating all the fermented foods just before bedtime or it one meal. I suppose you could do that, but in general, it's going to work best in terms of limiting, gastric distress by spreading it out throughout the day. I also want to mention brine
Brian, is the liquid that surrounds sauerkraut. It's that very salty fluid, and that contains a lot of active live cultures. And they did include, or they allowed people to include brine in this, in the study and in discussions with dr. Sonnenberg, which will go into in more detail on the episode that comes out next week. We talked a lot about the particular value. That Brian might hold in terms of bringing about micro biodiversity because of the
- of live cultures that it contains. I do want to focus for a moment on the high fiber condition, because there were some interesting observations about the people that were placed into that condition. First of all, increasing the amount of fiber definitely increased, the number of enzymes that can be used to digest fiber. This is in keeping with this idea of this ramp up phase where accumulation of more fiber intake can over time lead to less, gastric distress, but also to more utilization
enough fiber, which overall should be a good thing. So while they didn't observe an increase in immune system function or an increase in micro biodiversity, there was an increase in these fiber digesting enzymes. They also observed what they called personalized immune responses. There were some subgroups within the high fiber group that had interesting changes in terms of their reactions to, or I should say their inflammatory m-meaning, the inflammatory markers, they expressed as well as their microbiota diversity.
So there are essentially three groups, one group actually showed an increase in inflammatory markers, that was quite surprising, and probably not wonderful for the message. That fiber is always good for us. But that was a small cohort within the fiber, intake group, another group and still another group both showed reductions in Baseline microbiota diversity, although to varying degrees. So I don't want to paint the picture. That fiber is bad but fiber, certainly did not have the positive effects.
On microbiota diversity that the high fermented food, diet did. So my read of this study, and I think the stance that many others have taken as a consequence of these data is that we should be increasing our fermented food intake that that simply a good thing to do in order to support our gut microbiome and to reduce inflammatory signals in our brain and body. And there are a number of different ways to do that. I mentioned some of the particular Foods, however, any time you're talking about ingesting, fermented foods, especially the high quality.
Ones that come from the refrigerated section of the grocery store or that end that have low sugar content. Etc. We do have to be considerate of cost because certain things like kombuchas, for instance can be quite costly. I should also mention some kombuchas actually contain alcohol. Some do not or contain very little amounts of alcohol. One way to avoid the high cost of fermented foods while still being able to accumulate a lot of fermented food intake is to Simply make those fermented foods yourself. This is something that
We started exploring and experimenting with in our home, one simple way to do. This is to just make your own sauerkraut. It involves very few ingredients. It basically involves cabbage, water and salt, but there's a specific process that you need to follow in order to create these large volumes of sauerkraut at home using that low cost method. The best resource that I know of, in order to follow a great recipe to make homemade. Sauerkraut would be the recipe for homemade sauerkraut that's contained in. Tim Ferriss has booked the
Our Chef, there's an excellent protocol. There. It involves chopping up the Cabbage, putting into a bowl, mashing it up with your hands, which can be fun, putting water in there. Some salt, covering it, and then keeping it in a particular environment. And then routinely, scraping off some of the material from the surface, you have to do that in order to make sure that you're not getting a micro microbes and things growing in it that are bad for you. So you definitely want to pay careful attention to the protocol, but that's a very very low cost way of generating lots and lots of
Of fermented food. So you don't go broke trying to improve your microbiome. The other thing that you can do, if you're really obsessed with kombucha or something like that, to avoid the high cost of Kombucha, is there are ways that you can get the scoby, which basically allows you to make your own kombucha at home. I've never tried this, but when I was a postdoc, There Was An undergraduate in the lab, I think. Well, I won't out him but he's now gone on to medical school and I think he's past his residency in his and is a practicing doctor, but nonetheless, he was always making kombucha at home. He told
Was exceedingly, easy, but then again, he had a number of other skills and attributes that made me think that he could do pretty much anything with these. Whereas I tend to struggle with even basic cooking. So maybe if you're feeling a little more adventurous, you could explore making your own kombucha, but there are a number of different protocols and recipes out there for making your own low sugar. Fermented foods. So you needn't run out and buy fresh sauerkraut all the time. I should also mention for those of you that are interested in getting your fermented intake from pickles jar.
And pickles. Rarely if ever contain ferment. Mostly, they're just soaked in vinegar, water, and with some spices, but there are some that contain ferment. You actually have to look for that on the container. And I don't know maybe someone out there knows how to make natto and knows how to make kimchi. Well and things of that sort. It certainly is the case based on the data. From the study, that ingesting more servings of fermented food per day, ought to be beneficial for our gut microbiome. And since this is an episode not just about gut microbiome, but got brain health, I should mention
That one form of signaling between the gut microbiome and the Brain, which we did not discuss and I'll just touch on briefly is that when the inflammatory um, or the genes and markers of inflammation are kept in a healthy range. There's an active signaling of that immune system status to the brain. There's an intermediate cell type that communicates immune status to the brain, and that cell type is the microglial cell to type of Glee. Has the name suggests when
There's a lot of inflammation in the body, these microglia actually get activated and can start eating away at various components of the brain and nervous system. And I don't mean massive eating away. They're not going to digest the whole brain, but these microglia are sort of the resident macrophages of the brain, macrophages are in the periphery and they gobble up debris and things of that sort. The microglia on a regular basis are eating up debris that accumulates across waking cycles and in response to micro damage of the brain that occurs on a daily.
They said, so they have a lot of important basic everyday, what we call housekeeping functions, but when there's a lot of inflammation in the body, when there's a massive immune response, the microglia can be hyperactivated. And that's thought to lead to any number of different cognitive defects or challenges thinking, or maybe even some forms of neurodegeneration over time. Although, that last point is more of a hypothesis than a. Well, tamped down fact, at this point. There's still a lot of Investigation to be done in humans. The animal data. However are very, very
Strong, that when the immune system is activated or chronically activated or hyperactivated, that neural tissue, meaning brain tissue and other central nervous system tissue can suffer. So there are a lot of reasons to want to not just improve microbiome diversity, but to also improve immune system function, and to limit the number of inflammatory markers that are present in the body because of the way, those inflammatory markers can signal deleterious events in the brain and while eating fermented foods and making your own firm,
That foods and buying high quality fermented foods. Might seem like an inconvenience. I would say, that from the perspective of cost benefit or effort benefit. It's actually quite a good situation where if you can just ramped up the number of fermented foods that or servings of fermented foods that you're eating per day, over a period of a few weeks. So that you're tolerating that, well, that ought to have a very positive effect on your microbiome, diversity, and indeed on gut brain function, and I'll be the last to suggest that people completely
Leaf or go on fiber. I think there's some debate out there as to how much fiber we need and whether or not certain forms of fiber better than others. I'm not going to get into that debate. It's barbed wire enough without me injecting, my own views into that debate, but I think there's ample evidence to support the fact that for most people ingesting, a fair amount of fiber is going to be a good idea. I would just say that make sure that you're also ingesting a fair amount of fermented foods and along the lines of fiber in an accompanying article published in cell which
Of a what we call a News and Views piece about the Sonnenberg and Gardner paper. They make a quite good point, which is that the increase in fiber intake that led to this increase in carbohydrates, active enzymes, these CA Z zaimes, as they're called. These are enzymes. That help digest. Fiber, quote indicating an enhanced capacity for the microbiome to degrade complex, carbohydrates present in fibrous Foods. So in other words, eating more fiber,
Or and fibrous Foods allowed for an increase. In these enzymes that allow you to eat, still more fibrous Foods or to better digest fibrous foods that are coming in through other sources. So there is at least one, utility for increasing fiber, even though it's separate from the gut microbiota, diversity and reducing inflammation. And I'd be remiss if I didn't touch on some of the data and controversy about artificial sweeteners and the gut microbiome. I want to be very clear that what I'm about to tell you has only been established in animal.
I was in a mouse model at least to my knowledge. What the Studies have shown it? And there were several but one published in the journal Nature a few years back is the one that got the most amount of attention is that animals that consume large amounts of artificial sweeteners in particular things like saccharine or sucralose show disruptions in their gut microbiome. I'm not aware of any studies in humans that show the equivalent effect and I'm not aware of any studies in humans that show, the equivalent effect for things like plant-based low-calorie sweeteners, things like stevia.
Monk fruit and things of that sort. And at least by my exploration, I couldn't find any data specifically related to the sweetener aspartame. So, right now it's somewhat controversial and actually, this is kind of a third rail topic out there. When one group will come out saying that artificial sweeteners are bad because they disrupt the gut microbiome, the response generally from a number of people as well. That's only been shown in animal models and indeed that's true. So right now I don't think that there's a strong case one way or the other. I think that
Bullshit basically ask themselves whether or not they like artificial sweeteners or not, whether or not they're willing to risk it or not. And obviously, that's an individual choice. I also want to point out a recent study from Diego bojorquez lab, which actually shows, however, that neurons in the gut, those neuro pod cells are actually capable of distinguishing between real sugars and artificial sweeteners. This is a really interesting body of work. It was published just snap just recently.
I should say February, 20, 22. The title of the paper is the preference for sugar over. Sweetener depends on a gut sensor cell. And to make a long story short. What they showed was, there's a category of neuro pod cells that recognize sugar in the gut and signal that information about the presence of sugar in the gut to the brain. Via the pathways, we talked about before, the NoDoz ganglia, the Vegas dopamine etcetera, Etc. Interestingly the very same category of neurons can respond to
Artificial sweeteners and signal that information to the brain, but the pattern of signaling and indeed the signature pattern, that is conveyed to the brain and received by the brain, is actually quite a bit different when these same neurons are responding to artificial sweeteners versus actual sugar. This is very interesting because what it means is first of all that neurons have incredible specificity in terms of what they are signaling from the gut to the brain.
And it also means that there may be a particular signal that the brain receives that says I'm receiving some intake of food or drink that tastes sweet but doesn't actually offer much nutrients in the direction of sweetness. Meaning that it doesn't have calories despite being sweet. Now again, this is all subconscious processing and like with the previous studies. We were just discussing about artificial sweeteners, generally in the gut microbiome. Generally. It's unclear how this relates to Human.
At this point in time, but given the similarity of cellular processes and molecular processes at the level of gut-brain in mice. I think it stands to reason that these neuro pot cells, very likely are capable of signaling sweet presence of real sweetener versus artificial sweetener in humans as well. Although that Still Remains to be determined empirically, so I'd like to just briefly recap what I've covered today. I started off by talking about the structure and function of the gut brain axis. I described the basic structure and function of the digestive.
Way and how that digestive pathway, Harbors microbiota, species, meaning many many little bacteria that can signal all sorts of things to the rest of the brain and body. And indeed, we talked about the various ways that they do that. We talked about direct Pathways literally nerve networks. That extend from the gut up to the brain and from the brain back to the gut and we talked about indirect Pathways how some of the gut microbiota can actually synthesize neurotransmitters that get out into the bloodstream. Can
The body can impact the immune system and can get into the brain and act as neurotransmitters in the brain, just as would neurotransmitters that originated from within the brain. Also talked about what constitutes a healthy versus unhealthy microbiome. And it's very clear that having a diverse microbiome is healthier than having a non-diverse microbiome. But as I pointed out, there's still a lot of questions as to exactly what microbiota species you want to enhance.
And which ones you want to suppress in the gut in order to achieve the best, gut-brain axis function, we talked about how things like fasting, might impact the microbiome and how some of that might be a little bit counterintuitive, based on some of the other positive effects of fasting. Or if we're not just discussing fasting, some other types of somewhat restrictive diets, either restrictive in time or restrictive, in terms of macronutrient intake, how those may or may not improve the health of gut microbiome, and the basic takeaway. Was that because
Don't know exactly how specific diets impact the gut microbiome and we don't know how fasting either promote or degrades the microbiome. We really can't say whether or not they are improving or degrading the microbiome at this time. However, it is clear that stress, in particular, chronic stress can disrupt the gut microbiome. It's also clear, of course, the antibiotics can disrupt the gut microbiome and that brings us to the topic of prebiotics and probiotics. And I emphasize the fact that for most people in
testing high-quality on processed foods that include some Prebiotic fiber but also that include some probiotics will probably be healthy, but not excessive levels of probiotics high levels of supplemented probiotics of the sort that would come in a probiotic pill or even prescription probiotics would probably lend themselves best to when people were under severe. Chronic stress or had just come off a serious round or an ongoing or repeated rounds of antibiotics. That does not mean that ingesting.
In any form or any kind is not good. It just means that the very high dose probiotics. Again, typically found in prescription for more poor capsule pill form. Probably our best reserved, two cases. Where, of course your doctor prescribes them. You should always follow your doctor's advice but in cases where perhaps you are jet-lagged, you're traveling excessively for any reason or working excessively. You're not getting enough sleep or your diet is radically changed from normal and we talked about how increasing the amount of fiber in your diet.
Might be useful for increasing fiber, digesting enzymes and the assimilation of fibrous foods, but that it's really the ingestion of fermented foods. And in fact, getting anywhere from, for even up to six servings a day of fermented foods, can be immensely beneficial for reducing inflammatory markers in the body and for improving microbiota. Diversity all along the gut and thereby improving signaling and outcomes along the gut brain axis. So, we went all the way.
From structure to function, to the four kinds of signaling mechanical chemical, in direct, direct probiotics, fiber, and fermented foods, and I tossed in a little bit at the end. They're also about ways that you can make your own fermented foods at home in order to try and offset some of the costs. Also. It's just kind of fun to do and some of those actually tastes quite good. I've actually found that the fermented sauerkraut that we're making at home, actually Rivals the sauerkraut that you can buy out of the refrigerated section on the grocery store.
And I am by no means a skilled cook or Chef or and basically have no culinary skill whatsoever. So if I can do it, you can do it. I hope you found this information useful and perhaps also actionable one of my motivations for doing this episode was again, as a primer for the episode with dr. Justin Sonnenberg where we go, really deep into the gut microbiome less. So into the gut brain axis, but really deep into the gut microbiome. What it is, what it does, what it doesn't do. And some of the emerging findings from his lab that
Yet to be published. And I also was excited to do this episode because I think many of us have heard about the gut microbiome. We hear about these bacteria that live in our gut. We hear about the gut brain Axis or that 90% or more of the serotonin that we make is made in our gut. We heard about the gut, is a second brain and so forth, but I think for many people, they don't really have a clear picture of what the gut microbiome is, and the pathways and mechanisms by which it can signal to the brain into the other parts of the body. So, I hope that today
Has information, at least improved, the clarity around that topic and leaves you with a more Vivid picture of this incredible system. That is our gut brain axis. If you're enjoying and or learning from this podcast, please subscribe to our YouTube channel. That's a terrific. Zero cost way to support us. In addition, please subscribe to the podcast on Spotify and apple and on Apple, you can leave us up to a five star review on YouTube. We have a comment section, please. Of course, give us feedback and comments, but please also make suggestions about top.
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