00:00[upbeat music] - Welcome to
00:00the Huberman Lab Podcast
00:01where we discuss science and science-based tools
00:09I'm Andrew Huberman,
00:10and I'm a professor of neurobiology and ophthalmology
00:12at Stanford School of Medicine.
00:14Today, we are going to discuss the gut and the brain,
00:17and we are going to discuss how your gut
00:20influences your brain and your brain influences your gut.
00:24As many of you probably know,
00:25there is a phenomenon called your gut feeling,
00:28which tends to be something that you seem to know
00:31without really knowing how you know it.
00:33That's one version of the gut feeling.
00:35The other is that you sense something in your actual gut,
00:39in your body, and that somehow drives you
00:43to think or feel or act in a particular way,
00:46maybe to move towards something
00:48or to move away from something.
00:50Now, today, we aren't going to focus so much
00:52on the psychology of gut feelings
00:54but on the biology of gut feelings
00:57and how the gut and brain interact.
00:59Because indeed your gut is communicating to your brain
01:01both directly by way of neurons, nerve cells,
01:05and indirectly by changing the chemistry of your body,
01:08which permeates up to your brain
01:10and impacts various aspects of brain function.
01:12But it works in the other direction, too.
01:14Your brain is influencing your entire gut.
01:18And when I say entire gut, I don't just mean your stomach,
01:20I mean, your entire digestive tract.
01:22Your brain is impacting things
01:23like how quickly your food is digesting,
01:26the chemistry of your gut,
01:28if you happen to be stressed or not stressed.
01:30Whether or not you are under a particular social challenge
01:33or whether or not you're particularly happy
01:35will in fact adjust the chemistry of your gut
01:38and the chemistry of your gut in turn
01:40will change the way that your brain works.
01:42I'll put all that together for you
01:44in the context of what we call the gut microbiome.
01:47The gut microbiome are the trillions of little bacteria
01:50that live all the way along your digestive tract
01:54and that strongly impact the way that your entire body works
01:57at the level of metabolism,
01:59immune system, and brain function.
02:01And of course, we will discuss to tools,
02:03things that you can do in order to maintain
02:06or improve your gut health.
02:08Because as you'll also soon see,
02:10gut health is immensely important
02:13for all aspects of our wellbeing
02:15at the level of our brain,
02:16at the level of our body,
02:18And there are simple, actionable things that we can all do
02:21in order to optimize our gut health
02:23in ways that optimize
02:24our overall nervous system functioning.
02:26So we will be sure to review those today.
02:29This episode also serves as a bit of a primer
02:32for our guest episode that's coming up next week
02:35with Dr. Justin Sonnenburg from Stanford University.
02:38Dr. Sonnenburg is a world expert in the gut microbiome
02:42and so we will dive really deep into the gut microbiome
02:45in all its complexity.
02:47We'll make it all very simple for you.
02:49We will also talk about actionable tools in that episode.
02:51This episode is a standalone episode,
02:53so you'll get a lot of information and tools,
02:55but if you have the opportunity to see this episode first,
02:58I think it will serve as a nice primer for the conversation
03:01with Dr. Sonnenburg.
03:03I'd like to emphasize that this podcast
03:05is separate from my teaching and research roles at Stanford.
03:08It is however, part of my desire and effort
03:10to bring zero cost to consumer information
03:12about science and science-related tools
03:14to the general public.
03:15In keeping with that theme,
03:16I'd like to thank the sponsors of today's podcast.
03:19Our first sponsor is Athletic Greens.
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03:26I've been using Athletic Greens,
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04:05for my gut microbiome.
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06:56Okay, let's talk about the gut and the brain
06:58and how your gut and your brain
06:59communicate in both directions.
07:02Because as I mentioned before,
07:03your gut is communicating all the time
07:06with your brain and your brain is communicating all the time
07:10And so the two are in this ongoing dance with one another,
07:14that ordinarily is below your conscious detection
07:17although you're probably familiar with the experience
07:19of every once in a while getting a stomach ache
07:21or of eating something that doesn't agree with you,
07:23or conversely eating something
07:25that you find particularly delicious
07:27and that sensation or that experience rather
07:30being a whole body experience.
07:32Your mind is excited about what you're eating or just ate,
07:35your gut is excited about what you're eating or just ate,
07:39and it seems to be a kind of unified perception
07:42of both brain and body.
07:44Today, we're going to talk about how that comes about
07:46in the negative sense.
07:47Like, you know, when you meet someone you really dislike
07:50or when you have a stomach ache,
07:51and in the positive sense,
07:52when you interact with somebody
07:53that you really, really like
07:54and you'd like to spend more time with them, for instance,
07:57or when you eat something
07:58that you really, really like
07:59and you'd like to spend more time with that food,
08:03Now, the gut and the brain represent what we call
08:06a biological circuit,
08:08meaning they include different stations.
08:10So station A communicates with station B,
08:13which communicates with station C, and so on.
08:16And as I mentioned earlier, it is bidirectional.
08:17It's a two-way street between gut and brain.
08:21I want to make the important point at the outset
08:24that when I say the word gut,
08:25when I refer to the gut,
08:27I am not just referring to the stomach.
08:30Most of us think that the gut equates to the stomach
08:33because we think of having a gut or not having a gut
08:37or having a gut feeling of some sort.
08:39But in the context of gut-brain signaling
08:43and the related microbiome,
08:45the gut includes the entire digestive tract.
08:49That's right, from start to finish
08:51the entire digestive tract
08:53so much so that today we're going to talk about,
08:55for instance, the presence of neurons, nerve cells,
08:58that reside in your gut
09:00that communicate to specific locations in the brain
09:03and cause the release of specific neurochemicals,
09:06such as the neurochemical dopamine or serotonin,
09:09that can motivate you to seek more of a particular food
09:12or type of interaction or behavior,
09:15or to avoid particular foods, interactions, and behaviors.
09:18And some of those neurons, many of those neurons, in fact,
09:21reside in your intestines, not in your stomach.
09:24They can be in the small intestine or the large intestine.
09:27In fact, you actually have taste receptors and neurons
09:31located all along your digestive tract.
09:33You have neurons that are located
09:35all along your digestive tract
09:36and they are communicating to your brain
09:39to impact what you think, what you feel, and what you do.
09:42Okay, so for the gut-brain axis,
09:44we need to deal with the brain part
09:45and then we need to deal with the gut part.
09:48Let's just quickly talk about the brain part
09:49because there the word brain is also a bit of a misnomer
09:53in that when we say the gut-brain axis,
09:55it does include the brain
09:57but includes a lot of other things as well.
10:00So as many of you probably know by now,
10:02if you're listeners of this podcast,
10:04and if you don't, that's fine,
10:06your nervous system includes your brain
10:09and your spinal cord
10:10and those together constitute
10:11what's called the central nervous system.
10:14Your neural retinas,
10:15which are lining the back of your eyes
10:18and are the light sensing portion of your eyes
10:22are also part of your central nervous system.
10:25So actually your eyes are part of your brain.
10:27They're the only parts of your brain
10:28that are outside the cranial vault.
10:31So your retinas, your brain proper,
10:34and your spinal cord make up the central nervous system.
10:36The other parts of your nervous system constitute
10:38what's called the peripheral nervous system,
10:40which are the components of your nervous system
10:42that reside outside the retinas, brain, and spinal cord.
10:46Now, this is very important
10:47because today we're going to talk a lot
10:49about how the gut communicates with the brain.
10:52And it does that by way
10:53of peripheral nervous system components,
10:57meaning nerve cells that reside in the gut
10:59and elsewhere in the body that communicate to the brain
11:03and cross into the central nervous system
11:05to influence what you think and what you feel, okay?
11:08So that's the nervous system part of what we call
11:13brain, again, just being a shorthand
11:14for including all the elements I just described.
11:17Gut, as you now know,
11:19includes all the elements of the digestive tract.
11:21Let's talk about the architecture or the structure
11:24of the gut of your digestive system.
11:27Now, not surprisingly your digestive system,
11:30aka your gut, begins at your mouth and ends at your anus.
11:34And all along its length,
11:35there are a series of sphincters
11:38that cut off certain chambers of the digestive tract
11:41from the other chambers.
11:43Now, also along this tube that we call the digestive tract,
11:47there's great variation in the degree of acidity,
11:51or pH as it's sometimes called.
11:54That variation in acidity turns out to give rise
11:58to different little microenvironments
12:00in which particular microbiota, microbacteria,
12:04can thrive or fail to thrive.
12:07And so the way I'd like you to think
12:09about the digestive tract,
12:10this gut component of the gut-brain axis,
12:13is that it's not just one component.
12:15It's not just your stomach with a particular acidity
12:18and a bunch of microorganisms
12:20that work particularly well
12:22to make you feel good
12:23and make your digestive pathways work well.
12:27It's a series of chambers, little microenvironments,
12:30in which particular microbiota thrive
12:33and other microbiota do not.
12:35And certain behaviors that you undertake
12:38and certain experiences that you have
12:40will adjust those microenvironments in ways
12:43that make particular microbiota, certain bacteria,
12:46more likely to thrive and others less likely to thrive.
12:50We'll talk about how that was set up for you early in life.
12:53Actually from the moment that you came into the world,
12:55that microbiome was being established.
12:57It was actually strongly impacted
13:00depending on whether or not you were born by C-section
13:02or by vaginal birth.
13:05And it was strongly impacted by who handled you
13:07when you came into the world,
13:08literally the hands that were on you.
13:10How much skin contact you had,
13:12whether or not you were a preemie baby or not,
13:14whether or not you had pets at home,
13:16whether or not you were allowed to play in the dirt,
13:17whether or not you were allowed to eat snails
13:19or whether or not you were kept
13:20in a very antiseptic environment.
13:22All of those experiences
13:23shaped these little microenvironments
13:26and shaped what constitutes best or worst
13:29for those microenvironments, okay?
13:30So you have this long tube that we call the digestive tract
13:34and it's very, very long.
13:36In fact, if we were to splay it out,
13:38we were to take all the curves and turns
13:40out of the intestine, we would find that it is very long.
13:43It's approximately nine meters long.
13:46Now, the structure of that digestive tract
13:48turns out to be very important
13:50in terms of gut-brain signaling.
13:53Once again, it's a tube and the hollow of that tube
13:56is called the lumen, L-U-M-E-N.
13:59But the walls of the tube are not necessarily smooth,
14:02at least not for significant portions
14:04of the digestive tract.
14:06For much of the digestive tract,
14:09there are bumps and grooves that look very much
14:11like the folds in the brain,
14:13but these bumps and grooves are made up of other tissues.
14:16They're made up of what's called a mucosal lining,
14:17so there's a lot of mucus there.
14:20And if we were to look really closely,
14:22what we'd find is that there are
14:23little hairy-like cellular processes
14:27that we call microvilli
14:29that are able to push things along the digestive tract.
14:34The microbiota reside everywhere along the lumen
14:38of the digestive tract,
14:40starting at the mouth and all the way to the other end.
14:43And they reside within those microvilli
14:45and they reside within the lumen.
14:48And if we were to look really closely
14:51at the bumps and grooves along the digestive tract,
14:54what we would find is that there are little niches,
14:57little areas in which particular things
14:59can grow and reside best.
15:02Now, that might sound kind of gross,
15:03but it actually is a good thing,
15:05especially what's growing and residing there
15:08are microbacterial organisms that are good for your gut
15:12and that signal good things to your brain.
15:14And we will talk about what that signaling looks like
15:16and how that's done and accomplished in just a few moments.
15:19But I want you to get a clear mental picture of your gut,
15:22something that we don't often see.
15:23And often when we think about the gut,
15:25again, we just think about the hollow of the stomach,
15:27food going in there, and getting digested,
15:29but it's far more complex
15:31and actually far more interesting than that.
15:33Now, I've been referring to the gut microbiome
15:35and to the microbiota and these bacteria.
15:38Let me define those terms a little bit more specifically
15:40just to avoid any confusion.
15:43The microbiota are the actual bacteria.
15:46The microbiome is used to refer to the bacteria
15:50but also all the genes as bacteria make,
15:52because it turns out that they make some important genes
15:54that actually impact all of us.
15:58You have loads and loads
16:00of these little microbiota, these bacteria.
16:03In fact, right now you are carrying with you
16:06about two to three kilograms,
16:08so that's more than six pounds,
16:10of these microbiota, these bacteria.
16:13And if we were to look at them under a microscope,
16:15is these are relatively simple little organisms.
16:18Some remain stationary so they might plop down
16:21into the mucosal lining
16:22or they might hang out on a particular microvilli
16:25or they might be in one of those little niches,
16:28and others can move about,
16:30but they basically fill the entire lumen.
16:33They surround and kind of coat the surface
16:36of the microvilli and they're tucked up
16:38into any of those little niches that are available to them
16:44If you were to take the head of a pin
16:46and look at it under the microscope,
16:49you could fit many, many hundreds,
16:50if not thousands or more of these little microbacteria.
16:55And the reason I say many, many thousands or more,
16:58I'm giving a kind of broad range there,
17:00is that they do vary in size
17:02and, again, they vary as to whether or not they can move
17:05Now, they're constantly turning over in your gut,
17:08meaning they're being born so to speak
17:10and they're dying off.
17:12And some will stay there
17:14for very long periods of time within your gut
17:16and others will get excreted.
17:18About 60% of your stool,
17:20as unpleasant as that might be to think about,
17:23is made up of live and dead microbacteria.
17:27So you're constantly making
17:29and excreting these microbacteria.
17:32And which microbacteria you make
17:35and how many stay inside your gut and how many leave,
17:39meaning how many are excreted,
17:42depends a lot on the chemistry of your gut
17:45and depends very strongly on the foods that you eat
17:48and the foods that you do not eat.
17:50Now, just because what we eat strongly influences
17:53our microbiome, meaning our microbacteria,
17:56does not mean that there are not other influences
18:00on what constitutes our microbiome.
18:03Our microbiome is also made up by microbacteria
18:07that access our digestive tract through our mouth,
18:10through breathing, through kissing,
18:13and through skin contact.
18:16In fact, one of the major determinants of our microbiome
18:19is who we interact with
18:21and the environment that we happen to be in.
18:24And that actually includes whether or not
18:25we interact with animals.
18:27In a little bit, I'll talk about some data
18:30as to whether or not you grew up in a home that had animals,
18:33whether or not you grew up in the home,
18:34whether or not there was a lot of social contact,
18:36meaning skin contact,
18:38or whether or not you grew up
18:39in a more animal sparse, contact sparse environment
18:43and how that shapes your microbiome.
18:45But the simple point is that what you eat
18:48influences your microbiome, but also what you do,
18:51what you think, and what you feel,
18:52and many of the low microbacteria
18:55that get into your digestive tract
18:57do so by way of social interactions.
18:59In fact, if you ask a neurobiologist
19:02what the role of the microbiome is,
19:04they'll tell you almost certainly
19:06that it's there to impact brain function.
19:10But if you have friends that are microbiologists,
19:14such as I do, they'll tell you,
19:17well, maybe the brain and nervous system are there
19:19to support the microbiome.
19:21It's the other way around.
19:22You have all these little microorganisms
19:24that are taking residence in our body.
19:26They don't really know what they're doing as far as we know.
19:29We don't know that they have consciousness or they don't.
19:31We can't rule that out, but it seems pretty unlikely.
19:33Nonetheless, they are taking advantage
19:36of the different environments
19:38all along your digestive tract.
19:39They are taking advantage
19:41of the sorts of social interactions,
19:43for instance, the people you talk to
19:44and that breathe on you,
19:46the people that you shake hands with,
19:48the people that you kiss or don't kiss,
19:50the people that you happen to be
19:51romantically involved with or not,
19:52your dog, your cat, your lizard, your rat,
19:54whatever pet you happen to own is impacting your microbiome.
19:59There's absolutely no question about that.
20:01So hopefully now you have some sense of the architecture
20:03of the digestive pathway
20:05and you have some sense of the trillions
20:08of little microbacteria that are living
20:10all along the different components
20:12of that digestive pathway.
20:14But what we haven't talked about yet,
20:15and what I'd like to talk about now,
20:17is what those little microbiota are actually doing
20:21in your digestive tract.
20:23In addition to just living there
20:24for their own intents and purposes,
20:26they are contributing, for instance, to your digestion.
20:29Many of the genes that those microbiota make
20:32are genes that are involved in fermentation
20:35and genes that are involved in digestion
20:37of particular types of nutrients.
20:40And in a little bit, we will talk
20:41about how what you eat can actually change the enzymes
20:46that those microbiome components make,
20:49enzymes largely being things
20:50that are responsible for digestion.
20:52They catalyze other sorts of cellular events
20:54but in the context of the digestive pathway,
20:56we're talking about enzymes that help digest your food.
20:59So those microbiota are indeed helping you in many ways.
21:02And if you lack certain microbiota
21:04that can help you digest,
21:06it stands to reason that you would have challenges
21:07digesting certain types of foods.
21:09The other amazing thing that these microbiota do
21:13is they change the way that your brain functions
21:16by way of metabolizing or facilitating
21:20the metabolism of particular neurotransmitters.
21:23So one of the ways that having certain microbiota present
21:25in your gut can improve your mood or degrade your mood,
21:29for instance, is by way of certain microbiota
21:34being converted into or facilitating the conversion
21:38of chemicals, such as GABA.
21:41GABA is what we call an inhibitory neurotransmitter.
21:44It's involved in suppressing the action
21:48And that might sound like a bad thing,
21:50but all types of sedatives, for instance,
21:54alcohol, and a lot of neurons that naturally make GABA
21:57can help quiet certain circuits in the brain,
21:59for instance, circuits responsible for anxiety.
22:03In people who have epilepsy,
22:05the GABAergic neurons, as they're called,
22:07can all often be disrupted in their signaling,
22:10meaning they're not cranking out as much GABA
22:12and therefore the excitatory neurons,
22:15which typically release other molecules like glutamate
22:17can engage in what's called runaway excitation
22:20and that can give rise to seizures.
22:23So the simple message here is that the microbiota
22:26by way of making neurochemicals
22:28can influence the way that your brain functions.
22:31So you want to support those microbiota
22:33and we will give you tools to support those microbiota.
22:36But the takeaway at this point
22:39is that those microbiota are making things locally
22:41to help digest food.
22:43Other microbiota are helping to make
22:46certain neurotransmitters like GABA,
22:48and we'll also talk about dopamine and serotonin.
22:50And so the very specific microbiota that reside in your gut
22:54have a profound influence
22:56on many, many biological functions,
22:58especially immune system function,
23:01brain function, and digestion.
23:03So that should give you a fairly complete picture
23:05of your gut microbiome.
23:08Now I'd like to talk about how your microbiome
23:10and your brain communicate,
23:12or more accurately, how your microbiome
23:14and the rest of your nervous system communicate.
23:16Neurons, which simply means nerve cells,
23:19are the cells that do most of the heavy lifting
23:22in your nervous system.
23:23There are of course other cell types that are important.
23:25Glial cell, for instance, very, very important cell types.
23:28You have endothelial cells,
23:29which are responsible for blood flow,
23:31pericytes and other types of cells,
23:33but the neurons are really doing most of the heavy lifting
23:36for most of the things we think about
23:38in terms of nervous system function.
23:41You have neurons in your gut
23:44and that should not surprise you.
23:47Neurons reside in your brain, your spinal cord, your eyes,
23:49in fact, all over your body,
23:51and you've got them on your heart and in your heart,
23:54and you've got them in your lungs,
23:56and you've got them in your spleen,
23:58and they connect to all the different organs
24:00and tissues of your body.
24:02So that's not surprising that you have neurons in your gut.
24:05What is surprising, however,
24:07is the presence of particular types of neurons
24:09that reside near or in the mucosal lining
24:13just next to that lumen of the gut
24:16and that are paying attention,
24:18and I'll explain what I mean by paying attention,
24:20to the components of the gut, both the nutrients
24:26and thereby can send signals
24:29up to the brain by way of a long wire
24:33that we call an axon, and can communicate
24:37what the chemistry and what the nutritional quality
24:42and what the other aspects of the environment are at the gut
24:44at a given location up to the brain
24:47in ways that can influence the brain to, for instance,
24:49seek out more of a particular food.
24:52Let me give you a sort of action-based picture of this.
24:55Let's say like most people, you enjoy sweet foods.
24:59I don't particularly enjoy sweet foods
25:00but there are a few that I like.
25:01I'm a sucker for a really good dark chocolate
25:05or really good ice cream
25:07or I got this thing for donuts
25:09that seems to just not quit
25:10although I don't tend to indulge it very often,
25:15If I eat that particular food,
25:17obviously digestion starts in the mouth.
25:19There are enzymes there, it gets chewed up,
25:21the food goes down into the gut.
25:23These neurons are activated,
25:27meaning that causes the neurons to be electrically active
25:30when particular components,
25:32certain nutrients in those foods are present.
25:35And for the cell types,
25:37or I should say the neuron types that matter here,
25:40the nutrients that really trigger their activation
25:43are sugar, fatty acids,
25:48Now, these particular neurons
25:50have the name enteroendocrine cells
25:53but more recently they've been defined as neuropod cells.
25:57Neuropod cells were discovered
25:58by Diego Bohorquez's lab at Duke University.
26:02This is a phenomenal set of discoveries
26:03made mostly in the last 10 years.
26:06These neuropod cells, as I mentioned,
26:08are activated by sugar, fatty acids, or amino acids,
26:12but have a particularly strong activation to sugars.
26:17They do seem to be part of the sweet sensing system.
26:20And even though I'm focusing on this particular example,
26:22they represent a really nice example
26:25of how a particular set of neuro cells in our gut
26:29is collecting information about what is there
26:31at a particular location in the gut,
26:33and sending that information up to our brain.
26:36Now, they do that by way of a nerve pathway
26:39called the vagus nerve.
26:40The vagus nerve is part of the peripheral nervous system.
26:43And the vagus nerve is a little bit complex to describe
26:46if you're just listening to this.
26:48If you are watching this,
26:49I'll try and use my hands as a diagram
26:51but really the best thing to do
26:53if you want really want to learn neuroanatomy
26:55is to just imagine it in your mind as best you can
26:58and if you can track down a picture of it, terrific,
26:59but here's how it works.
27:01Neurons have a cell body that we call a soma,
27:04that's where all the DNA are contained.
27:07That's where a lot of the operating machinery
27:09of the cells are contained
27:11and a lot of the instructions for that cell
27:13of what to be and how to operate are contained.
27:16The cell bodies of these neurons or the relevant neurons
27:20are actually up near the neck.
27:22So you can think of them as a clump of grapes,
27:25'cause cell bodies tend to be round or oval-ish.
27:28And then they send a process that we call an axon
27:32in one direction out to the gut
27:36and they'll send another process up into the brain.
27:40And that little cluster near the neck
27:42that's relevant here is called
27:43the nodose ganglion, N-O-D-O-S-E.
27:47The nodose ganglion is a little cluster of neurons
27:50on either side of the neck.
27:51It has a process that goes out to the gut
27:53and a process that goes up into the brain.
27:55And again, these are just one component
27:57of the so-called vagus nerve.
28:00The vagus nerve has many, many branches,
28:02not just to the gut.
28:03There are also branches to the liver,
28:06branches to the lungs,
28:07branches to the heart, branches to the larynx,
28:10and even to the spleen,
28:11and other areas of the body that are important.
28:14But right now we're just concentrating on the neurons
28:16that are in the gut that signal up to the brain.
28:19And what the Bohorquez lab has shown
28:22is that these neuropod cells are part of network.
28:25They're sensing several different nutrients,
28:28but in particular, when they sense sugar,
28:30they send signals in the form of electrical firing
28:34up to the brain in ways that trigger activation
28:37of other brain stations that cause you to seek out more
28:40of that particular food.
28:43Now, this brings us to some classic experiments
28:45that at least to me are incredible.
28:48And these are highly reproducible findings
28:50showing, for instance,
28:52that even if you bypass taste
28:54by infusing sweet liquid
28:57or putting sweet foods into the gut,
29:01and people can never taste them with their mouth,
29:04people will seek out more of that particular food.
29:07And if you give them the option
29:09to have a sweet food infused into their gut
29:13or a bitter food infused into their gut
29:16or a sweet versus sour,
29:19or a more sweet versus less sweet food,
29:21people have a selective preference for sweet foods
29:25even if they can't taste them.
29:27Now, this is important to understand
29:28in the context of gut-brain signaling
29:30because we always think that we like sweet foods
29:33because of the way they taste.
29:34And indeed that's still true,
29:37but much of what we consider the great taste of a sweet food
29:41also has to do with a gut sensation
29:43that is below our conscious detection.
29:46How do we know that?
29:47Well, the Bohorquez lab has performed experiments
29:51using modern methods and they're classic experiments
29:53showing that animals and humans
29:55will actively seek out more of a particular sweet food
29:58even if it bypasses this taste system.
30:01And the reverse is also true.
30:04There have been experiments done in animals and in humans
30:07that have allowed animals or humans
30:09to select and eat sweet foods,
30:11and indeed that's what they do if they're given the option.
30:16And yet to somehow eliminate the activation of these neurons
30:20within the gut that can sense sweet foods.
30:23Now, there are a couple different ways
30:24that those experiments ave been done.
30:26In classic experiments that date back to the '80s,
30:29this was done by what's called subdiaphragmatic vagotomy.
30:32So this means cutting off the branch of the vagus
30:34that enervates the gut below the diaphragm
30:37so that the other organs can still function
30:38because the vagus is very important,
30:40but basically cutting off the sweet sensing in the gut,
30:43still giving people the opportunity to taste sweet foods
30:46and they don't actively seek out
30:48quite as much of the sweet food
30:50when they don't have this gut sensing mechanism
30:52that we now know to be dependent on these neuropod cells.
30:57More recent experiments involve selective silencing
30:59of these neuropod cells.
31:01And there have been a lot of different derivations
31:02of this sort of thing,
31:03but the takeaway from it is that our experience of
31:07and our desire for particular foods
31:09has everything to do with how those foods taste.
31:11It also has to do, as you probably know,
31:13with their texture and the sensation of those foods
31:17in our mouth, and even indeed how they go down our throat
31:20sometimes can be very pleasing or very unpleasant.
31:24And it also has to do with this subconscious processing
31:28of taste that occurs in the gut itself.
31:31And again, when I say gut, I don't just mean in the stomach.
31:34There are actually neurons, neuropod cells,
31:37further down your digestive tract
31:39which are signaling to your brain
31:40about the presence of sweet foods,
31:42as well as foods such as amino acid rich foods
31:46or foods that are rich in particular types of fatty acids
31:49signaling up to your brain
31:51and causing you to seek out more of those foods
31:54or to consume more of those foods.
31:57Now, you're probably asking, what is the signal?
31:59How does it actually make me want more of those foods
32:01without me realizing it?
32:03Well, it does that by adjusting the release
32:05of particular neuromodulators.
32:07For those of you that are not familiar with neuromodulators,
32:10these are similar to neurotransmitters,
32:11but they tend to act more broadly.
32:13They tend to impact many more neurons all at once
32:16and they go by names like dopamine, serotonin,
32:19acetylcholine, epinephrine, and so forth.
32:21Sometimes people refer to those as neurotransmitters.
32:24Technically they are neuromodulators.
32:25I'll refer to them almost always as neuromodulators.
32:28The neuropod cells signal by way
32:31of a particular branch of the vagus
32:33through that nodose ganglion that we talked about before
32:36and through a number of different stations
32:40eventually cause the release of the neuromodulator dopamine.
32:46Dopamine is often associated
32:48with a sense of pleasure and reward
32:49but it is more appropriately thought of as a neuromodulator
32:53that impacts motivation, craving, and pursuit.
32:55It tends to put us into modes of action,
32:57not necessarily running and moving through space,
33:00although it can do that too, but in the context of feeding,
33:03it tends to make us look around more,
33:07chew more, reach for things more,
33:09and seek out more of whatever it is
33:10that's giving us that sensation
33:13of delight or satisfaction.
33:15And again, that sense of delight and satisfaction,
33:18you might experience only consciously
33:21as the way that something tastes on your mouth
33:23but it actually is caused again
33:25by both the sensations in your mouth
33:27but also by the activation of these neuropod cells.
33:31So this is an incredible system of gut-brain signaling,
33:34and it is but one system of gut-brain signaling.
33:36It turns out it's the system that we know the most about
33:39at this point in time.
33:41There are other components of gut-brain signaling
33:43that we'll talk about in a moment, for instance,
33:44the serotonin system.
33:46But in terms of examples of gut-brain signaling
33:49for which we know a lot of the individual elements
33:52I think this neuropod, neuron sensing of sweet foods,
33:57fatty acids, and amino acids in the gut
33:59and communicating that up to the brain
34:02by way of the vagus and causing us
34:04to seek out more of the foods
34:05that deliver those nutrients is an incredible pathway
34:08that really delineates the beauty and the power
34:11of this gut-brain axis.
34:13Let me talk about timescales.
34:14Here I'm talking about a particular type of neuron
34:17that is signaling up to the brain using electrical signals
34:20to cause us to want to seek out
34:23a particular category of foods.
34:26That's happening relatively fast
34:28compared to the hormone pathways of the gut
34:31which also involve neurons.
34:32So your gut is also communicating to your brain
34:35by way of neurons, nerve cells.
34:38But some of those nerve cells also release hormones.
34:41And those hormones go by names like CCK,
34:44glucagon-like peptide 1, PYY, et cetera.
34:49A good example of a hormone pathway,
34:51or what's sometimes called a hormone peptide pathway,
34:54that is similar to the pathway I've talked about before
34:58but a little bit slower is the ghrelin pathway.
35:01Ghrelin, G-H-R-E-L-I-N,
35:04increases with fasting.
35:07So the longer it's been since you've eaten,
35:10or if you're just eating very little food
35:12compared to your caloric needs,
35:14ghrelin levels are going to go up in your bloodstream
35:16and they go up because of processes
35:18that include processes within the gut
35:21and include the nervous system.
35:22So it's a slow pathway driving you
35:24to seek out food generally.
35:27As far as we know, the ghrelin system is not partial
35:30to seeking out of sweet foods or fatty foods or so on.
35:35Ghrelin increases the longer it's been
35:38since you've eaten sufficient calories
35:40and it stimulates a feeling of you wanting to seek out food.
35:44Well, how does it do that?
35:46It does that again by impacting neural circuits
35:48within the brain, neural circuits that include
35:50what we call the brain stem autonomic center.
35:52So it tends to make you feel alert
35:54and quite, we say, high levels of autonomic arousal.
35:58If you haven't eaten in a while,
35:59you might think that you just get really exhausted, right?
36:02Because we all hear that food is energy
36:03and caloric energy is what we need to burn,
36:05but you actually have a lot of energy stored in your body
36:08that you would be able to use
36:10if you really needed energy.
36:12But typically if we haven't eaten in a while,
36:14we start to get agitated
36:15and we get agitated by way way of release
36:17of the neuromodulator epinephrine,
36:20which causes us to look around more, move around more,
36:25That all occurs in brain stem autonomic centers
36:27and in the hypothalamus.
36:28We did an entire episode on feeding behavior
36:30and metabolism as well
36:32and you can find those episodes at hubermanlab.com
36:34so I don't want to go into a lot of detail
36:36about hypothalamic and brains stem centers.
36:38But there's a particular area of the brain
36:40called the nucleus of the solitary tract,
36:43the NST as it's called, that's very strongly impacted
36:46by these circulating hormones
36:48and tends to drive us toward feeding behavior.
36:50So the important point here is that we have a fast system
36:53that is paying attention to the nutrients in our gut
36:56or the absence of nutrients in our gut,
36:57and stimulating us to seek out food
36:59or to stop eating certain foods,
37:01and we have a slower hormone-related system
37:04that also originates in the gut and impacts the brain.
37:07But all of those converge on neural circuits for feeding.
37:12The neural circuits for feeding
37:13include things like the arcuate nucleus of the hypothalamus,
37:15they include a bunch of other neurochemicals,
37:18but the point is that you've got a fast route
37:20and a slow route to drive you to eat more or eat less,
37:24right, to seek out food and consume it or to stop eating,
37:28to essentially kickstart the satiety mechanisms
37:33and those are operating in parallel.
37:35It's not like one happens first
37:37then stops then the other.
37:38They're always operating in parallel.
37:39And I bring this up because there's a bigger theme here
37:42which we see over and over again in biology,
37:44which is the concept of parallel pathways.
37:46You've always got multiple accelerators and multiple brakes
37:50It's very, very rare to have just one accelerator
37:52and one brake on the system.
37:53And this will become important later
37:54when we talk about tools for optimizing your gut microbiome
37:58for healthy eating and for health healthy digestion
38:00and for healthy brain function.
38:02I want to take a moment and talk
38:03about glucagon-like peptide 1,
38:05which is also called GLP-1.
38:09GLP-1 is made by neurons in the gut
38:13and by neurons in the brain.
38:15This is a fairly recent discovery
38:18but it's an important one.
38:20GLP-1 tends to inhibit feeding
38:24and tends to reduce appetite.
38:27There are a number of drugs released on the market now,
38:31one for instance goes by the name semaglutide,
38:34which is essentially an GLP-1 agonist.
38:38It causes the release of more GLP-1.
38:40It's being used to treat type II diabetes,
38:42which is insulin resistant diabetes.
38:44This is different than type I diabetes
38:46where people don't actually make insulin.
38:48It's also being used as a drug to reduce obesity.
38:54And it seems pretty effective
38:55at least in certain populations.
38:57There are certain foods and substances that increase GLP-1.
39:01I've talked about a few of these on the podcast.
39:03One that I'm a particular fan of for entirely other reasons
39:06is yerba mate tea can stimulate the release of GLP-1.
39:10In South America, it's often used
39:12as an appetite suppressant,
39:13probably in large part
39:14because of its effect on GLP-1 release,
39:17but probably also because it does contain caffeine,
39:20which is a bit of a stimulant,
39:21which also can be involved in lipolysis,
39:23which is the utilization of fat stores
39:24for energy and so forth.
39:27A brief mention about yerba mate.
39:29There are some reports out there that yerba mate
39:32can increase certain types of cancers.
39:35The data that I've seen on this
39:37is that it tends to relate to whether or not
39:39those are smoked versions of the yerba mate tea,
39:42the amount of consumption,
39:44and the debate is still out.
39:45So I invite you to look at those papers.
39:47You can search for those online.
39:50Nonetheless, yerba mate is one source of GLP-1 stimulation.
39:55Semaglutide is another source.
39:56It also can be stimulated by various foods, nuts,
39:59avocados, eggs, and so forth.
40:01Certain high fiber complex grains
40:04will also stimulate GLP-1.
40:06I raise this as not necessarily a route
40:09that you want to take in order to reduce food intake.
40:12I don't even know that that's your goal.
40:14But that GLP-1 is another one
40:18of these gut-to-brain signaling mechanisms
40:20that adjusts appetite that is dependent on diet,
40:24depends on what you eat or drink,
40:26and that the GLP-1 pathway
40:28does seem particularly sensitive
40:30to the constituents of diet.
40:32There's at least one quality study
40:34I was able to find showing
40:35that the ketogenic diet for instance,
40:37which almost always involves ingestion
40:40of very low levels of carbohydrate
40:44Although, as I mentioned before,
40:45there are other foods that fall
40:46outside the range of what we would consider ketogenic
40:49that can also stimulate GLP-1,
40:51there are prescription drugs, like semaglutide,
40:54there are other ones as well now,
40:55that stimulate GLP-1.
40:57So how does GLP-1 reduce appetite?
40:59It does that, in part, by changing the activity of neurons
41:02in the hypothalamus,
41:03this cluster of neurons just above the roof of our mouth,
41:06that themselves make GLP-1
41:09and that cause the activation of motor circuits
41:12for reaching, chewing, all the things
41:15that we associate with feeding behavior.
41:18So I use GLP-1 as an example of a pathway
41:20that you might choose to tap into
41:22by ingestion of yerba mate
41:23or by ingestion of the foods I mentioned,
41:25or if it's something that interests you, ketogenic diet.
41:28But I also mention it simply
41:30because it's another beautiful example
41:32of how a hormone pathway can impact the activity
41:35of brain circuits that are directly involved
41:37in a particular behavior.
41:39So yet another example of how gut is communicating to brain
41:43in order to change what we think we want
41:46or to change what our actual behaviors are.
41:49So the next time you find yourself reaching for food,
41:51or you find yourself wanting a particular sweet thing
41:55or fatty thing or something that contains
41:58a lot of amino acids,
41:59a protein rich food,
42:01keep in mind that that's not just
42:03about the taste of the food,
42:04and it's not even necessarily about the nutrients
42:06that you need or don't need.
42:09but it's also about this subconscious signaling
42:11that's coming from your body all the time,
42:13waves of hormones, waves of nerve cell signals,
42:17electrical signals that are changing the way
42:19that your brain works.
42:21And this raises for me
42:23a memory of the episode that I did with Dr. Robert Sapolsky,
42:27who's a world expert colleague of mine at Stanford,
42:30who is expert on things like hormones and behavior.
42:34But we got into the topic of free will,
42:36which is a bit of a barbed wire topic
42:38as many of you know.
42:39It gets into the realm of philosophy, et cetera.
42:41And we were kind of batting back and forth
42:43the idea, I was saying, \"Well, I think there's free will,
42:46and can't there certainly be free will
42:48or certainly the idea that we can avoid certain choices?\"
42:53And Robert was saying, \"No.\"
42:55In fact, he said, \"Nah,\" he doesn't believe
42:58that we have any free will.
42:59He thinks that events in our brain are determined
43:03by biological events that are below our conscious detection
43:06and that occur seconds to milliseconds
43:09before we make decisions or assessments
43:11and, therefore, we just can't control what we do,
43:14what we think, and what we feel.
43:16And at the time I sort of didn't buy it.
43:19I thought, I don't know.
43:20I just, I guess I really wanted to believe in free will.
43:23And to some extent I still do
43:25but as we talk about how these neurons in our gut
43:27and these hormones in our gut are influencing our brain
43:30and the decisions that we are making,
43:32at the level of circuits, like the hypothalamus
43:34and the nucleus of the solitary tract,
43:36these are areas of the brain way below our frontal cortex
43:39and our conscious perception.
43:42Think these are examples that really fall
43:43in favor of what Dr. Sapolsky was arguing,
43:46which is that events that are happening within our body
43:49are actually changing the way our brain works.
43:51So we might think that we want the cupcake.
43:53We might think that we don't need to eat something
43:56or do need to eat something
43:58and that is entirely on the basis of prior knowledge
44:01and decision-making that we're making with our head,
44:04it's very clear to me based on the work
44:07from the Bohorquez lab,
44:08classic work over the years dating back to the '80s,
44:11and indeed back to the '50s
44:12that we'll talk about in a moment,
44:13that our body is shaping the decisions
44:16that our brain is making and we're not aware of it at all.
44:19Now, the good news is that whether or not you believe
44:21in free will or not, the simple knowledge
44:24that this whole process is happening
44:26can perhaps be a benefit to you.
44:27You can perhaps leverage it to get some insight
44:31and understanding and perhaps even a wedge
44:32into your own behavior.
44:33You might think, ah, I think I want that particular food,
44:37or I think I want to avoid that particular food,
44:39but actually that's not a decision
44:41that I'm making on a purely rational basis.
44:44Has a lot to do with what my gut is telling my brain.
44:47So we've largely been talking about chemical communication
44:50between the gut and the brain.
44:51Chemical because even though these neuropod cells
44:55are communicating with the brain
44:57by way of electrical activity,
44:59what we call action potentials,
45:00and in neural language we call those spikes,
45:03spikes of action potentials,
45:06spikes of action potentials,
45:09meaning those neural signals,
45:10cause the release of chemicals in the brain like dopamine.
45:15So it's chemical transmission.
45:18Similarly, hormones, even though they act more slowly,
45:21hormones like neuropeptide Y like CCK, like ghrelin,
45:26they are signaling chemically.
45:28They're moving through the body,
45:30they're going in there affecting the chemical output
45:34and they're changing the chemistry of those cells
45:35and the chemistry of the cells that those cells talk to.
45:38So that gives us one particular category of signaling
45:41from gut to brain, which is chemical signaling.
45:44But of course there are other forms of signals
45:47and those fall under the category of mechanical signaling.
45:51You're probably familiar with this.
45:52If you've ever eaten a very large meal
45:54or consumed a lot of fluid,
45:56you experience that as distension of the gut
45:59and that doesn't just have to be distension of the stomach,
46:02but distension of your intestines as well.
46:06That distension is registered by neurons
46:08that reside in your gut,
46:09the signals go up to your brain,
46:11and communicate with areas of the brain
46:12that are responsible for suppressing
46:14further consumption of food and/or fluid,
46:17and, under certain circumstances,
46:20can also be associated with the activation
46:22of neural circuits that cause vomiting
46:24or the desire to vomit.
46:26So if ever you've eaten too much or you've eaten something
46:28that doesn't agree with you,
46:30that information is communicated
46:32by way of mechanosensors
46:33that sense the mechanics of your gut,
46:36possibly also the chemistry of your gut,
46:37but mostly the mechanics of your gut,
46:40signal up to the brain,
46:41and activate brain centers that are involved
46:43in stopping the eating behavior,
46:46and activation of an area of the brain stem
46:50that is affectionately referred to
46:52as the vomit center among neuroanatomists.
46:55This is a area that more appropriately
46:57is called the chemoreceptor trigger zone, the CTZ,
47:02and neurons in this area actually will trigger
47:04the vomiting reflex.
47:06So the way that the gut and the brain communicate
47:10is both chemical and mechanical,
47:12and it can be both for sake
47:13of increasing certain types of behavior.
47:16Today, we're talking mainly about feeding behavior
47:20but also ceasing to eat, closing your mouth,
47:24moving away from food, turning away from food,
47:26all behaviors that we're familiar with
47:28anytime we feel kind of sick
47:29on the basis of activation of this mechanosensor
47:33for gastric distress.
47:35So we've got chemical signaling and mechanical signaling.
47:38And I also want to emphasize that we have
47:40direct and indirect signaling from the gut to the brain.
47:44Direct signaling is the kind of signaling
47:46of the sort I've been talking about mainly up until now,
47:48which is neurons in the gut
47:51communicating with neurons in the brain stem
47:53that communicate with neurons in the hypothalamus.
47:55And, of course, those are also going to interact
47:57with neurons of the prefrontal cortex
47:59which is the area of a brain involved in decision making
48:01the, you know, I think it was the shrimp that made me sick.
48:05I'm going to, I just don't want any more of that.
48:07Or I'm never going back to that restaurant again
48:10because after I ate there about an hour later,
48:13I started feeling really not well.
48:14I felt, you know, kind of feverish,
48:15but my gut didn't feel well,
48:17my digestion was really off.
48:19All of that kind of information
48:20is handled in the prefrontal cortex at a conscious level,
48:23but the immediate decision to stop eating
48:26or to eat more of something to move towards something
48:28or away from it, that's made by neural circuits
48:30that reside at the, we would say,
48:32the subconscious level
48:34but what we really mean is below the level of the neocortex.
48:36Below the cortex means essentially below our level
48:39of conscious awareness.
48:41So we talked about two types of information within the gut
48:43that are communicated to the brain,
48:45chemical information, meaning information
48:47about the nutrients that happen to be there,
48:49and mechanical information,
48:49distention of the gut or lack of distention and so forth.
48:53And we talked about how these neuropod cells
48:55can signal the release of dopamine and circuits
48:57within the brain to cause you to seek out more of something.
49:00Now, in a very logically consistent way,
49:04dopamine is also involved in the whole business of vomiting.
49:08You might think, well, that doesn't make any sense.
49:10I thought dopamine was always a good thing.
49:12It's involved in moderation and reward, et cetera.
49:14But it turns out the area postrema,
49:16this vomit center in the brain stem,
49:19is chockablock full of dopamine receptors.
49:22And if dopamine levels go too high,
49:24it can actually trigger vomiting.
49:26And this we see in the context of various drugs
49:29that are used to treat things like Parkinson's.
49:31Parkinson's is a deficiency in dopamine
49:34or a lack of dopamine neurons typically
49:36that causes a resting tremor,
49:37difficulty in movement,
49:38because dopamine's also associated
49:40with a lot of the neural circuits for movement.
49:43Many drugs that are used to treat Parkinson's
49:46like L-DOPA increase levels of dopamine so much,
49:49or at least activate dopamine receptors
49:52to such a great degree in certain areas of the brain
49:55that they can cause activation of things
49:58like the trigger to vomit.
50:01Now, this should also make sense in the natural context
50:04of if you gorge yourself with food,
50:05gorge yourself with food, gorge yourself with food,
50:08the neurons in your gut that respond to that
50:11are simply detecting the presence of nutrients
50:13but they don't really make decisions themselves.
50:16They don't know to stop eating.
50:18Your brain knows to stop eating or to eject that food.
50:21And so it's a wonderful thing that those neurons
50:23are communicating with areas of the brain
50:25not just that stimulate consuming more food
50:27but that are communicating with areas of the brain,
50:31for instance, area postrema,
50:32that when dopamine levels get too high,
50:35cause us to either stop eating that food
50:38or in the case of vomiting to eject that food.
50:41So I raise this not to give you
50:44a kind of a disgusting counterexample
50:46to what we call appetitive behaviors,
50:49the things that we like to do more of,
50:51but simply to give you a sense of just how strongly
50:54even these reflexes that we think of
50:56as feeling sick and vomiting
50:58or the desire to seek out more food
51:00are really being controlled by a kind of push-pull system,
51:03by parallel pathways that are arriving from our gut
51:05and the same neurochemicals, in this case dopamine,
51:08are being used to create two opposite type behaviors,
51:12one behavior to consume more,
51:13one behavior to get rid of everything
51:15you've already consumed.
51:16So our brain is actually sensitive
51:18to the amount of signaling coming from our gut
51:21not just the path by which that signal arrives.
51:25Our brain is very carefully paying attention
51:28to whether or not the levels of dopamine
51:30that are being triggered are within a normal range
51:32for typical eating behavior
51:34or whether or not we've gorged ourselves
51:35to the point where enough already.
51:37Now, of course, mechanical signals
51:40will also play into area postrema
51:43and into the vomiting reflex.
51:45If we have a very distended gut,
51:47It just, it actually can hurt very badly,
51:49and we will have the desire to vomit,
51:51or we will just simply vomit.
51:54Mechanical and chemical signals
51:56are always arriving in parallel.
51:58They never work in unison.
52:00And so now we have chemical signals, mechanical signals,
52:04and now I'd like to talk about direct and indirect signals
52:07because almost everything I've talked about up until now
52:10are direct signals, a neural pathway that converges
52:13in the brain to create a particular feeling,
52:14thought, or behavior,
52:15but there are also indirect pathways.
52:18And that's what takes us back to the gut microbiome
52:21and to these little microbiota.
52:22And to just give you the takeaway message at the front here
52:26and then I'll give you a little more detail
52:28as to how it comes about,
52:30you have neurotransmitters in your brain
52:33and in your spinal cord and in your eyes
52:35and in your peripheral nervous system.
52:37They cause the activation or the suppression
52:41meaning they either electrically activate other nerve cells
52:44or they cause other nerve cells
52:45to be less electrically active.
52:46And they do that by way of neurotransmitters.
52:50But as it turns out,
52:51the gut microbiota are capable
52:53of influencing metabolic events
52:55and in some cases are capable
52:57of synthesizing neurotransmitters themselves.
53:00So what that means is that these little bugs,
53:02these little microbiota that are cargo in your gut,
53:05the six pounds of cargo,
53:06they actually can make neurochemicals
53:08that can pass into the bloodstream
53:10and into your brain and actually impact
53:12the other cells of your body and brain indirectly,
53:15so without involving these very intricate nerve pathways
53:18that we've been talking about.
53:19In other words, the foods you eat,
53:23the environment of your gut microbiome,
53:25can actually create the chemical substrates
53:27that allow your brain to feel one way or the other,
53:30to feel great or to feel lousy,
53:32to seek out more of a particular type of behavior
53:34or to avoid that behavior.
53:36And that would constitute indirect signaling.
53:38So I've been talking a lot about the structure and function
53:41of the gut-to-brain pathway,
53:43focusing mainly on feeding behaviors
53:45and in some cases avoiding feeding or even ejecting food
53:49from the digestive tract,
53:51I'd like to drill a little bit deeper
53:52into this indirect signaling pathway
53:55from the gut to the brain
53:56because it bridges us nicely from neuronal signals
54:00in the gut to the brain,
54:01hormonal signals from the gut to the brain,
54:04to what also includes the microbiome,
54:06which is what we started talking about
54:08at the beginning of the episode.
54:10As I mentioned a couple of minutes ago,
54:14certain gut microbiota can actually synthesize
54:17certain neurotransmitters that can go impact the brain.
54:19And we actually have some knowledge about which microbiota
54:22can synthesize particular neurotransmitters.
54:25For instance, the neuromodulator dopamine
54:29by or from bacillus and serratia.
54:34Now, these are just names of microbiota.
54:36I don't expect that any of you
54:37would necessarily recognize them.
54:39These aren't the sorts of things that you necessarily
54:40would run out and buy to get more dopamine.
54:43But the point is that particular gut microbiota
54:47can create dopamine in our gut
54:49that can get into our bloodstream
54:51and can generally change our baseline levels of dopamine
54:55within the brain and other areas of the body.
54:58I mentioned baseline levels of dopamine
55:00because as I talked about on an episode all about dopamine
55:03but I'll just repeat the basics here now,
55:07we have baseline levels
55:08of transmitters or neuromodulators
55:10that act as sort of the level of the tide,
55:14and then we can have peaks of dopamine
55:16that are created by behaviors
55:18or by ingestion of particular foods or drugs, et cetera.
55:21So bacillus and serratia tend to increase
55:25our baseline levels of dopamine.
55:28So if it turns out that we are creating
55:30the right gut microbiome environment
55:33that these particular gut microbiota can thrive in,
55:38well, then our baseline levels of dopamine will be elevated
55:41and in general, that leads to enhancement of mood.
55:44Similarly, there are other gut microbiota,
55:48for instance, candida, streptococus, various enterococcus,
55:53these always have these kind of strange
55:54and not so attractive names, at least to me
55:57as a neurobiologist.
55:58Nonetheless, those particular microbiota
56:01support the production of or can even be metabolized
56:05into serotonin, which is a neuromodulator
56:08associated with mood, with social interactions,
56:12with a huge number of different types
56:14of events and behaviors.
56:15Again, these gut microbiota when present
56:20and allowed to thrive in our gut
56:22will increase our overall levels of serotonin
56:25and riding on top of that level of serotonin
56:29will be the serotonin that's specifically released
56:31in response to certain behaviors.
56:33And I really want to drive home this point
56:35of baselines and peaks.
56:37The baseline level of serotonin might set our overall mood,
56:40whether or not we wake up feeling pretty good
56:42or really lousy if our serotonin levels
56:45happen to be very, very low,
56:47whether or not we tend to be in a kind of a calm space
56:50or whether or not we tend to be somewhat irritable.
56:52But then of course individual events as we go about our day,
56:56maybe a compliment that we get
56:57or maybe somebody says something irritating to us,
56:59whatever it may be will also influence levels of serotonin,
57:02but those serotonin events are going to be related
57:05to events at particular neural circuits in the brain.
57:08And this is an important topic
57:10because I think that a lot of people hear quite accurately,
57:14oh, 90 to 95% of our serotonin is manufactured in the gut.
57:18And indeed that's true.
57:19It's manufactured from the sorts of microbiota
57:21that I just described.
57:23And there are many, many experiments now,
57:25mostly in animal models,
57:26but also some in humans that show that if the gut microbiome
57:30is deficient in some way to these particular bacteria,
57:34that serotonin levels drop and people's mood suffers,
57:37maybe even their immune system functions,
57:39maybe even it exacerbates certain psychiatric illnesses.
57:43However, a lot of people take that to mean
57:45that the serotonin of the brain all comes from the gut
57:50or mostly comes from the gut.
57:51That's not the case.
57:52It's still the case that you have neurons in the brain
57:54that are responsible for releasing serotonin
57:57directly in response to certain things like social touch
58:00or through other types of positive social experiences.
58:04So we've got gut microbiota
58:07that can literally be turned into dopamine
58:10and raise our baseline levels of dopamine.
58:11We've got gut microbiota
58:13that can literally raise our baseline levels of serotonin.
58:16And indeed there are other gut microbiota like lactobacillus
58:19or bifidobacterium, excuse me,
58:23hard complex names to pronounce,
58:26bifidobacterium that can give rise
58:29to increases in GABA levels,
58:30this inhibitory neurotransmitter
58:32that can act as a little bit of a mild sedative,
58:34can reduce irritability, et cetera,
58:37but that's just the baseline,
58:38the kind of tide of those neuromodulators.
58:41Again, I want to emphasize that we still have
58:42neurocircuits within the brain and body
58:44that are specifically releasing in a very potent way
58:47dopamine, serotonin, and GABA.
58:50So the two things act in concert.
58:52Even though the gut and the brain are acting
58:54both in parallel and directly influencing one another,
58:59it is a powerful synergistic effect.
59:01And there are now hundreds of studies,
59:04maybe even thousands by this point,
59:06mostly performed in animal models,
59:09typically mice, but also some studies in humans
59:12that show that creating the correct environment
59:15for these gut microbiota to thrive
59:17really does enhance mood and wellbeing.
59:20And that when our gut microbiome is not healthy,
59:25that it really can deplete our mood and sense of wellbeing.
59:28Now, there are two major phases
59:31to creating a healthy gut microbiome.
59:33One you can control and the other one
59:36is less under your control.
59:38I get into this in a lot of detail
59:40in the episode with Dr. Sonnenburg,
59:42which is coming out immediately after this one,
59:46the following Monday, that is.
59:48But for now I want to just capture a few of the main points
59:52about the early establishment of the gut microbiome.
59:56It turns out that the environment
59:59that we are exposed to,
01:00:01the things that come into contact with our skin
01:00:02and digestive tract and any other mucosal lining,
01:00:05even the urethra, the nasal passages,
01:00:08any opening to the outside world
01:00:11that brings in certain, excuse me,
01:00:13certain microbiota in the first three years of life
01:00:17is going to have a profound impact
01:00:20on the overall menu of microbiota
01:00:22that we will be able to carry within our body.
01:00:27And it really does seem that getting exposure to
01:00:30and building a diverse microbiome
01:00:32in those first three years is critical.
01:00:34There's a lot of speculation and some data
01:00:37as to cesarean delivered babies
01:00:40having less diverse microbiomes
01:00:43compared to vaginally delivered babies.
01:00:44There have been attempts,
01:00:45although not conclusive attempts,
01:00:48to link that to the presence of autism spectrum disorders,
01:00:51which at least by some statistics
01:00:53seem to be of higher probability in cesarean deliveries
01:00:57although there are other studies that refute that,
01:01:00and I want to make that clear.
01:01:03However, it's clear that babies do not get much,
01:01:06if any, exposure to microbiota inside of the womb,
01:01:10maybe a little bit, but not much.
01:01:11But that is during the birth process
01:01:13and in the days and weeks immediately after
01:01:17they arrive in the world that their gut microbiome
01:01:19is established, that those gut microbiota
01:01:22take residence within the gut.
01:01:24So it will depend on whether or not they were breastfed
01:01:27It'll depend on whether or not they were exposed
01:01:29to a household pet or not,
01:01:30whether or not they were held by multiple caregivers
01:01:34whether or not they were a preemie baby
01:01:36and were contained in a particularly restrictive environment
01:01:39in order to encourage their further development
01:01:41before they could be brought home or not.
01:01:43I don't want to give the picture that if you were isolated
01:01:46or you were delivered by C-section,
01:01:48that you're somehow doomed to have a poor microbiome.
01:01:50That's simply not the case.
01:01:52However, it is the case that the more diversity
01:01:55of microbiota that one can create early in life
01:02:00is really helpful for long-term outcomes
01:02:03in terms of brain-to-gut signaling,
01:02:06gut-to-brain signaling,
01:02:07and for sake of the immune system.
01:02:11There are some decent studies showing
01:02:14that if children are exposed
01:02:16to a lot of antibiotic treatment early in life,
01:02:19that can be very detrimental to establishment
01:02:21of a healthy gut microbiome.
01:02:23And fortunately that reestablishing a healthy gut microbiome
01:02:27can help rescue some of those deficits.
01:02:29So doctors nowadays are much more cautious
01:02:32about the prescription of antibiotic drugs to children
01:02:36in their early years, not just up to three years,
01:02:38but extending out to five and seven and 10 years.
01:02:41And even in adults, they're very, very careful about that,
01:02:44or they ought to be.
01:02:46One reason is the existence, or I would say,
01:02:49the proliferation of antibiotic-resistant bacteria
01:02:52that are becoming more common in hospitals and elsewhere
01:02:55and that can cause serious problems.
01:02:57But in addition to that,
01:02:58because of this understanding that the gut microbiome
01:03:00is influencing and actually creating neurotransmitters
01:03:04that can impact mood and mental health,
01:03:06impact immune health, and so on.
01:03:08As I mentioned earlier, there are hundreds
01:03:09if not thousands of studies emphasizing the key role
01:03:12of the microbiome on brain health,
01:03:15psychiatric health, et cetera.
01:03:18I want to just highlight a few of those studies
01:03:20and in particular, some recent studies that come from labs
01:03:23that have been working on this sort of thing
01:03:25for a very long time.
01:03:26One of the more exciting studies comes from the work
01:03:28of Mauro Costa-Mattioli's lab,
01:03:31which is at Baylor College of Medicine.
01:03:33Mauro's lab has been working on mouse models
01:03:36of autism spectrum disorder for a long time,
01:03:39and looking at social behavior
01:03:41using a mouse model for a long time.
01:03:43And they've been able to identify
01:03:46particular types of microbiota
01:03:49that when they take resonance in the gut
01:03:52can help offset some of the symptoms of autism,
01:03:56at least the symptoms of autism
01:03:57that exist in these mouse models, okay?
01:03:59So again, this is not human work.
01:04:01This is work being done on mouse models
01:04:03for the simple reason that you can do
01:04:04these kinds of manipulations,
01:04:06where basically they took mice
01:04:07that were in germ free-environments
01:04:09or non-germ-free environments,
01:04:11or they exposed mice to particular microbiota
01:04:14and not other microbiota
01:04:15and they discovered that a particular microbiota
01:04:18called L. reuteri,
01:04:19it's L. R-E-U-T-E-R-I.
01:04:24Treatment with L. reuteri corrects the social deficits
01:04:28present in these autism models
01:04:30and it does so by way of activating our old friend
01:04:34but not simply because the vagus nerve
01:04:36triggers the release of dopamine,
01:04:38but it turns out that this particular gut microbiota
01:04:41L. reuteri can correct the social deficits
01:04:43in this autism spectrum disorder model.
01:04:45It does that by way of a vagal nerve pathway
01:04:48that stimulates both dopamine release and oxytocin release.
01:04:51And they establish this really mechanistically
01:04:53by showing, for instance,
01:04:53if you get rid of the oxytocin receptor,
01:04:55you don't see this rescue.
01:04:57Now, those are mouse models
01:04:58so we have to take those with the appropriate grain of salt,
01:05:01but they're really exciting.
01:05:02And they come to us in parallel with other studies
01:05:06that are being done,
01:05:07taking the microbiomes of people
01:05:11who have one condition or lack of condition,
01:05:13and putting it into people who have one condition
01:05:16or another condition.
01:05:17Let me explain what I mean by that.
01:05:20The early discovery of the gut microbiome
01:05:22and its potential to impact health
01:05:25was not in the context of the gut-to-brain pathway
01:05:28but rather it was in the context of colitis.
01:05:30This dates back to studies in the '50s,
01:05:33whereby people with very severe intractable colitis
01:05:36for which no other treatment was going to work
01:05:39received fecal transplants.
01:05:40So yes, that's exactly as it sounds.
01:05:42Taking the stool of healthy people who do not have colitis,
01:05:46transplanting those stools into the lower digestive tract
01:05:49of people who do have colitis,
01:05:51and they saw significant improvement,
01:05:53if not rescue of the colitis.
01:05:55That was one of the first indications
01:05:57that something within stool, of all things,
01:06:00could actually rescue another individual from disease,
01:06:04which sounds kind of wild and crazy,
01:06:07and may even sound disgusting to some of you,
01:06:09but as I mentioned at the beginning of the episode,
01:06:12almost 60% of stool is live or dead bacteria,
01:06:17microbiota, and it really opened up this entire field
01:06:21of exploring how different microbiota
01:06:23might have therapeutic effects.
01:06:26And indeed, that has been shown to be the case
01:06:28also in fecal transplants for certain psychiatric illnesses.
01:06:32These are still ongoing studies.
01:06:35They vary in quality.
01:06:37These are hard studies to do for all sorts of reasons,
01:06:40getting the appropriate patient populations,
01:06:42getting agreement, et cetera,
01:06:44making sure that everything's handled properly.
01:06:46But what this involves is fecal transplants
01:06:49from individuals that lack
01:06:51a particular psychiatric condition
01:06:53or metabolic condition into people
01:06:55who have a particular metabolic condition
01:06:58and there has been tremendous success in some cases.
01:07:00One of the more powerful and salient examples
01:07:04There's some people for which even if they ingest
01:07:06very low numbers of calories,
01:07:09even if they go on a liquid protein diet,
01:07:11simply can't lose weight.
01:07:13These are somewhat rare disorders
01:07:14but these are people that would
01:07:16either get gastric bypass surgery.
01:07:18Some people are now getting these fecal transplants
01:07:20from people that have
01:07:23healthy weight and they take the stool from them,
01:07:28they put it into lower digestive tract,
01:07:30and they can see substantial improvement in weight loss
01:07:34in people that were otherwise unable to do that.
01:07:36In some cases, actually they can start eating
01:07:39relatively normal levels of food and still lose weight.
01:07:41So pretty remarkable
01:07:42and that tells us there's something in these microbiota
01:07:44that's really powerful.
01:07:45Now, how those effects are generated isn't clear.
01:07:49One idea is that it's impacting the metabolome,
01:07:53components of the metabolism,
01:07:54almost certainly that's going to be the case.
01:07:56Another idea is that it's impacting neurotransmitters
01:07:59which change behavior and food choices within the brain.
01:08:02Although, as I mentioned, some of these people
01:08:03are already eating very little food to begin with
01:08:06so that's a little bit harder of an argument to create.
01:08:10There are also some somewhat famous examples now
01:08:13of how fecal transplants can lead to negative outcomes.
01:08:17But those negative outcomes further underscore
01:08:19the power of the microbiome in impacting bodily health.
01:08:24One key example of this, for instance,
01:08:26is transfer of fecal matter into another person
01:08:31in order to treat something like colitis
01:08:33and it effectively does that,
01:08:35but if the donor of the stool, of the fecal matter
01:08:40happened to be obese or have some other metabolic syndrome,
01:08:43it's been observed that the recipient
01:08:45can also develop that metabolic syndrome
01:08:47simply by way of receiving
01:08:50that donor's particular microbiota.
01:08:53So these microbiota can create positive outcomes
01:08:55or they can create negative outcomes.
01:08:57Now, most of us of course, are not interested in
01:09:00or pursuing fecal transplants.
01:09:01Most people are interested in just creating
01:09:03a healthy gut microbiome environment
01:09:05for sake of immune system and brain function.
01:09:07And we will talk about how to do that in just a few minutes.
01:09:10But I just want to further underscore
01:09:13the power of the microbiota in shaping brain chemistry
01:09:17and in shaping things like mood
01:09:20or other aspects of mental health
01:09:21that typically we don't associate with our gut.
01:09:24There are several studies published in recent years,
01:09:26one that I'll just highlight now,
01:09:28first author is Tonya Nguyen, N-G-U-Y-E-N.
01:09:32The title of the paper is
01:09:33\"Association of Loneliness and Wisdom
01:09:36with Gut Microbial Diversity and Composition,
01:09:38an Exploratory Study\".
01:09:40It's an interesting study.
01:09:41Looked at 184 community dwelling adults, excuse me,
01:09:46ranging from 28 to 97 years old.
01:09:49They explored whether or not
01:09:52having enhanced microbial diversity
01:09:54somehow related to these variables
01:09:56that they refer to as loneliness and wisdom.
01:09:58They used a number of different tests to evaluate those.
01:10:02Those are common tests in the psychology literature,
01:10:04not so much in the biology literature,
01:10:06but nonetheless, there are ways of measuring things
01:10:08like loneliness and wisdom,
01:10:12wisdom in this case, being the opposite of loneliness,
01:10:16at least in the context of this study.
01:10:18And what they found was the more microbial diversity,
01:10:20the more diverse one's microbiome was,
01:10:22the lower incidence of loneliness.
01:10:25And they did this by taking fecal samples,
01:10:28profiling them for RNA.
01:10:29So essentially doing gene sequencing of the stool
01:10:31of these individuals,
01:10:32getting ratings of how lonely or not lonely they felt,
01:10:35and correlating those.
01:10:37And that's just but one study.
01:10:38I point it out because it's particularly recent
01:10:41and it looked like it was particularly well done.
01:10:43There is another study that I'll just refer you to.
01:10:45This was a study published in 2020 in \"Scientific Reports\".
01:10:49The title of the study is \"Emotional Wellbeing
01:10:51and Gut Microbiome Profiles by Enterotype\".
01:10:54What I particularly like about this study
01:10:55is that they were able to correlate the presence
01:10:57of certain microbiota with feelings of subjective wellbeing
01:11:02and lack of or presence of depressive symptoms.
01:11:06They did high-throughput gene sequencing
01:11:08of the microbiomes of individuals.
01:11:10So that meant measuring the microbiota,
01:11:13figuring out which microbiota were present,
01:11:15how diverse their microbiome was in general.
01:11:18Gut microbiome diversity is a good thing.
01:11:20And then to correlate that with what's called
01:11:26PANAS stands for positive affect negative affect schedule.
01:11:29This is a test that my lab has used extensively,
01:11:31that other labs to use to evaluate mood and wellbeing.
01:11:34And they defined what were called three enterotypes,
01:11:38three different categories of people
01:11:40that ate very different diets
01:11:42that tended to fall into categories of having more
01:11:44or fewer emotional symptoms that were negative
01:11:48or more fewer emotional symptoms that were positive
01:11:52and whether or not they tend to be more depressed, anxious,
01:11:55or have more stress-related behaviors, et cetera.
01:11:57And what they were able to derive from this study
01:12:01was some strong indications about what types of things
01:12:04we should ingest in our diet,
01:12:05maybe even certain things that we should avoid,
01:12:07but certainly the types of things that we should ingest,
01:12:10that can enhance mood and wellbeing
01:12:12and can tend to shift people away
01:12:14from more depressive-like anxiety
01:12:16and stress-related symptoms.
01:12:18Before we get into what the particular food items were
01:12:20that lend themselves to a healthy microbiome,
01:12:23I want to raise a bigger and perhaps more important issue,
01:12:25which is what is a healthy microbiome.
01:12:29I think if you asked any number of world experts,
01:12:32and I certainly ask this of Dr. Sonnenburg,
01:12:33what is a healthy microbiome,
01:12:35they're all going to tell you
01:12:36it's a microbiome that has a lot of diversity,
01:12:38that includes a lot of different types of bacteria.
01:12:41And that makes sense
01:12:43because it logically would include the bacteria
01:12:46that produce GABA and dopamine and serotonin,
01:12:48and that support the immune system,
01:12:50and do a number of different things.
01:12:51But is it simply the case that adding microbiota diversity
01:12:56is always a good thing?
01:12:58Well, that doesn't seem to be the case.
01:13:02Probiotics and prebiotics,
01:13:04both of which can enhance microbiotal diversity,
01:13:07can improve mood, digestion, immune system, and so on.
01:13:10That's been established but it's mainly been established
01:13:12in the context of post-antibiotic treatment
01:13:15or people that are recovering from illness
01:13:17or people that have been very stressed
01:13:20or have been dealing with all sorts of challenges,
01:13:24mental or physical,
01:13:25and they are an attempt to replenish the gut microbiome.
01:13:28However, it's also clear
01:13:32that excessive microbiota
01:13:35brought about by excessive intake of probiotics
01:13:38can lead to things like brain fog.
01:13:40There's actually some good studies that point to the fact
01:13:42that certain metabolites of the microbiome,
01:13:46certain chemicals produced in the gut
01:13:48and in the body can actually lead to brain fog states.
01:13:51This is thought to come about through the lactate pathways
01:13:55of the gut that can then impact the brain.
01:13:58If you want to look more into this issue
01:14:00of whether or not probiotics taken in excess perhaps
01:14:04can lead to brain fog,
01:14:06I'd encourage you to look at a particular paper.
01:14:08This is a paper published
01:14:09in \"Clinical and Translational Gastroenterology\".
01:14:12And the title of the paper
01:14:13is \"Brain Fogginess, Gas, and Bloating,
01:14:15a Link Between SIBO Probiotics and Metabolic Acidosis\".
01:14:19It was published in 2018.
01:14:20We can provide a link to this study.
01:14:22And there are several other studies in the references
01:14:25that point to the fact that in some cases,
01:14:29excessive intake of probiotics and excessive proliferation
01:14:32of gut microbiota can actually be problematic.
01:14:36I mention this not to confuse you
01:14:37but because it is confusing out there.
01:14:41We all would think that just increasing
01:14:42microbiotal diversity is always a good thing
01:14:45but there are thresholds
01:14:47beyond which excessive microbiotal diversity
01:14:50might be problematic.
01:14:52I think everyone agrees that having
01:14:54too few microbial species living in us is not a good idea.
01:14:59Now, none of that answers the questions
01:15:01that I think everyone really wants answers to,
01:15:03which are, what should we do,
01:15:06what should we not do to improve our gut microbiome?
01:15:09I mean, clearly we can't time travel back
01:15:11to when we were zero to three years old
01:15:14and get a dog if we didn't have a dog,
01:15:16get breastfed if we weren't breastfed,
01:15:18be delivered vaginally as opposed to by C-section
01:15:21if we didn't have that opportunity.
01:15:23We just can't time travel and do that.
01:15:25All of us, however, should be seeking to improve
01:15:27the conditions of our gut microbiome
01:15:29because of the critical ways in which it impacts
01:15:32the rest of our brain and bodily health.
01:15:34So what should we do, what shouldn't we do?
01:15:36Clearly we know that stress can negatively impact
01:15:39the gut microbiome.
01:15:41However, some forms of stress that can quote unquote
01:15:44negatively impact the microbiome
01:15:45include fasting, long periods of fasts,
01:15:48which makes sense because a lot of microbiota need food
01:15:51in order to thrive.
01:15:52In fact, many if not all of them do at some point.
01:15:57There are other questions
01:15:58such as should we eat particular foods
01:16:01and how often should we eat those foods?
01:16:02We've all been told that fiber is incredibly important
01:16:05because of the presence of prebiotic fiber,
01:16:08which can essentially feed the microbiome,
01:16:11but is fiber really necessary
01:16:15and how necessary is it to encourage a healthy microbiome?
01:16:17Clearly, there are a number of people
01:16:19following relatively low fiber diets,
01:16:21such as ketogenic diets,
01:16:22and those can have, in some cases,
01:16:25anti-inflammatory effects and can sometimes
01:16:28also improve certain microbiota species.
01:16:31So it can all be rather confusing.
01:16:32And for that matter, I asked our resident expert,
01:16:35Dr. Justin Sonnenburg at Stanford,
01:16:38all of these questions.
01:16:39And he answers them very systematically
01:16:41in the episode that comes out after this one.
01:16:45But I don't want to withhold anything from you
01:16:46so I'll just give a very top contour version
01:16:49of those answers and then you'll get more in-depth answers
01:16:52during that episode.
01:16:54I asked about fasting.
01:16:55And the reason I asked about fasting is that years ago,
01:16:57I was at a meeting as part
01:16:59of the Pew Biomedical Scholars Meeting
01:17:02and one of the other Pew Biomedical Scholars
01:17:05was an expert in gut microbiome
01:17:07and I said, \"Hey, are probiotics good for the microbiome?
01:17:11And if so, which ones should I take?\"
01:17:14And his answer was very interesting.
01:17:15He said, \"You know, in certain cases they can be,
01:17:18especially if you're traveling or you're stressed,
01:17:21but it turns out that the particular bacteria
01:17:24that they put in most probiotics
01:17:26don't actually replenish the microbiota that you need most.\"
01:17:30And I thought, \"Oh, well, why don't they make ones
01:17:32that replenish the microbiota that you need most?\"
01:17:35And his answer was, \"Well, they don't replenish those
01:17:39but they replenish other ones
01:17:41that then in turn encourage the development
01:17:44of the microbiota that you do want
01:17:46once you start eating the appropriate foods.
01:17:47So they change the environment
01:17:49which makes the environment better,
01:17:50which indirectly supports the proliferation
01:17:53of quote unquote good microbiota.\"
01:17:55Okay, so that was a somewhat convoluted answer
01:17:57but I did appreciate his answer.
01:17:59Then I asked him about fasting.
01:18:00I said, \"Well, a lot of people are getting interested
01:18:02in intermittent fasting now.
01:18:04People are spending a significant portion
01:18:06of each 24-hour cycle avoiding food
01:18:08for sake of time restrictive feeding.
01:18:10What does that do to the gut microbiome?
01:18:11Does it make it healthier or does it make it unhealthier?\"
01:18:14Well, my colleague from Yale and Dr. Sonnenburg
01:18:17both confirmed that during periods of fasting,
01:18:20especially prolonged periods of fasting,
01:18:22we actually start to digest away
01:18:23much of our digestive tract.
01:18:26Now, the whole thing doesn't start to disappear
01:18:28but there's thinning of the mucosal lining
01:18:29or the least disruption of the mucosal lining.
01:18:31A lot of the microbiota species can start to die off.
01:18:35And so it was surprising to me, but nonetheless interesting
01:18:38that fasting may actually cause a disruption
01:18:42to certain healthy elements of the gut microbiome.
01:18:46But again, there's a caveat.
01:18:47The caveat is that when people eat after a period of fast,
01:18:52there may be a compensatory proliferation,
01:18:55meaning an increase in healthy gut microbiota.
01:18:58So you start to get the picture
01:18:59that fasting is neither good nor bad.
01:19:02You start to get the picture that particular diets,
01:19:04meaning certain restriction diets
01:19:07or macronutrient-rich diets may not be good or bad
01:19:10for the microbiome.
01:19:11And yet there are some answers that arrive to us
01:19:15from Dr. Sonnenburg, but from other experts in the field,
01:19:18that there are certain foods
01:19:20and certain things that we can ingest
01:19:22which definitely enhance the microbiome
01:19:25and make it healthier than it would be
01:19:27were we to not ingest those foods.
01:19:30So next I'd like to talk about what I think
01:19:32is a really pioneering and important study in this area.
01:19:35This is a study that was carried out by the Sonnenburg lab
01:19:38in collaboration with Chris Gardner's lab, also at Stanford,
01:19:42where they compared two general types of diets in humans,
01:19:47diets that were fiber rich,
01:19:49which has been proposed time and time again
01:19:51to enhance microbiota diversity
01:19:54and to enhance gut-brain signaling even
01:19:56and to enhance the immune system perhaps,
01:19:59and diets that were enriched
01:20:01in so-called low-sugar fermented foods.
01:20:04Before I dive into that study and what the conclusions were
01:20:06because they are very interesting
01:20:08and very actionable for all of us,
01:20:10I do want to touch on probiotics
01:20:12because I want to avoid confusion.
01:20:15It is not the case that ingestion of probiotics
01:20:18will always lead to brain fog.
01:20:20I want to make that clear.
01:20:21It is the case that ingestion of probiotics,
01:20:24even if those probiotics don't directly contain
01:20:28the microbiota species that one is trying to proliferate,
01:20:31can be useful for improving microbiotal diversity.
01:20:35In general, it seems that maintaining
01:20:38a healthy gut microbiome
01:20:40involves ingesting certain types of foods,
01:20:42and we'll talk about those in a moment,
01:20:45but perhaps also augmenting the microbiota system
01:20:50through prebiotics or probiotics at a fairly low level
01:20:53on a consistent basis.
01:20:54So these are not high dose probiotics
01:20:56except under conditions of dysbiosis
01:21:00where, for instance, if somebody has done
01:21:02a round of antibiotics and they need to replenish
01:21:05their gut microbiome,
01:21:07there are foods and there are pill form
01:21:09and powder form prebiotics and probiotics
01:21:11that can be very useful.
01:21:14Or in cases where people have been very stressed
01:21:17or are undergoing excessive travel
01:21:19or have shifted their diet radically,
01:21:22maybe that's due to travel,
01:21:23maybe that's due to illness,
01:21:24maybe that's due to stress.
01:21:26But when there are a number of different converging events
01:21:28that are stressing or depleting microbiotal diversity,
01:21:33that's when at least I believe it can be useful
01:21:36to support the gut microbiome
01:21:37through the ingestion of quality probiotics or prebiotics.
01:21:42So it would be under conditions where people are stressed
01:21:45or their system is generally stressed
01:21:47for environmental or illness-related reasons
01:21:50that it might be useful to lean towards higher doses
01:21:54of prebiotics or probiotics than one might normally use
01:21:57but that under normal conditions,
01:21:59that one would focus on quality nutrients
01:22:03through diet and focus on ingestion of probiotics
01:22:08at a fairly low to moderate level,
01:22:11and/or prebiotics at a fairly low to moderate level.
01:22:15That just seems like the logical approach
01:22:16based on the experts that I've spoken to.
01:22:19But certainly if your doctor prescribes
01:22:22or suggests that you take high levels of probiotics
01:22:25you should definitely pay attention to your physician,
01:22:27and you should obviously pay attention to your physician
01:22:30You should never add or remove anything
01:22:32from your nutritional plan or supplementation plan
01:22:35without consulting a physician.
01:22:37So what should we do in order to maximize the health
01:22:39of our gut-brain axis as it's called?
01:22:42How should we support the diversity of the good microbiota
01:22:45that help us create all these neurotransmitters
01:22:47that we want, improve our immune system function,
01:22:52and so on and so forth?
01:22:53Well, some of that is going to be through the basics.
01:22:57When I say the basics,
01:22:58I mean the foundational things that really set us up
01:23:01for overall health.
01:23:02So this is going to be getting deep sleep
01:23:05of sufficient duration 80 plus percent of the time.
01:23:09I mean, if you could get a hundred percent of the time,
01:23:10that'd be great but very few people accomplish that.
01:23:12It's going to be proper hydration.
01:23:14It's going to be proper social interactions.
01:23:16It's going to be proper nutrition.
01:23:17And we'll talk more about nutrition in a moment.
01:23:19It's going to be limiting
01:23:20excessive, prolonged stressors or stress.
01:23:24And indeed we've done episodes about,
01:23:26just about all of those things
01:23:27but certainly about stress
01:23:29we have an episode of the Huberman Lab Podcast
01:23:31that you can find at hubermanlab.com
01:23:32all about mastering stress,
01:23:33how to avoid long periods of intense stress,
01:23:37what to do to offset those.
01:23:40Given that stress can disrupt the microbiome,
01:23:43whether or not you're fasting or not,
01:23:45those tools ought to be useful.
01:23:48Now, in what I consider to be a landmark study
01:23:51exploring the relationship between the gut microbiome,
01:23:54food intake, and overall health is this paper
01:23:58from Justin Sonnenburg's lab and Chris Gardner's lab,
01:24:01both of which are at Stanford.
01:24:03And the paper entitled \"Gut Microbiome-Targeted Diets
01:24:06Modulate Human Immune Status\"
01:24:08was published in the journal \"Cell\",
01:24:09which is among the three top journals perhaps in the world,
01:24:12\"Nature\", \"Science\", and \"Cell\"
01:24:13really being the apex journals for overall science,
01:24:18and especially for biomedical sciences.
01:24:21Now, this is a very interesting study.
01:24:23It was done on humans. There were two major groups.
01:24:26One group of humans was instructed to increase
01:24:29the amount of fiber in their diet
01:24:30and in fact ate a high fiber diet.
01:24:33The other group was instructed to eat
01:24:35a high fermented food diet.
01:24:38Now, both groups started off not having eaten
01:24:42a lot of fiber or a lot of fermented foods
01:24:45and were told to increase the amount of either fiber
01:24:47or fermented foods that they were ingesting
01:24:49over a four-week ramp up period
01:24:51and that was to avoid any major gastric distress.
01:24:54It turns out that if you're not already accustomed
01:24:56to eating a lot of fiber,
01:24:57increasing your amount of fiber dramatically
01:25:00can cause some gastric distress
01:25:02but if you ease into it over time, as we'll see,
01:25:04there's a mechanism behind this,
01:25:05which was unveiled in this study,
01:25:08but if you ease into it over time,
01:25:09then the system can tolerate it.
01:25:11Likewise high fermented foods
01:25:14can be readily tolerated
01:25:16if there's a ramp up phase of ingesting
01:25:18maybe one serving a day,
01:25:19then maybe two servings, and ramping up in this case
01:25:23as high as six servings per day.
01:25:26However, after this ramp up period,
01:25:29the group assigned to the high fiber condition
01:25:32maintained high fiber intake for six weeks
01:25:34and the high fermented food group maintained
01:25:37high fermented food intake for six weeks
01:25:40after which they went off
01:25:42either the high fiber or the high fermented food diet
01:25:45and there was a four-week follow up period
01:25:47during which they gradually returned to baseline.
01:25:50Throughout the study their gut microbiome was evaluated
01:25:53for the diversity of gut microbiota.
01:25:56And there were also a number of measures
01:25:58of immune system function,
01:25:59in particular measures of the so-called inflammatome.
01:26:03The immune system has a lot of different molecules involved.
01:26:05I did a whole episode about the immune system
01:26:07if you're interested in learning
01:26:08what some of those molecules are,
01:26:09various cytokines and signaling molecules
01:26:12that reflect either high inflammation states
01:26:14or reduced inflammation states in the brain and body.
01:26:17You're welcome to check that episode.
01:26:19It's also at hubermanlab.com.
01:26:21Regardless, in this study,
01:26:24they explored the sorts of immune markers
01:26:27that were expressed in either of the two groups
01:26:29and compared those.
01:26:30The basic takeaway of this paper
01:26:32was that contrary to what they predicted,
01:26:37the high fiber diet did not lead
01:26:39to increased microbiota diversity,
01:26:41at least not in all cases.
01:26:43And that was somewhat surprising.
01:26:45You know, the idea is that prebiotic fiber
01:26:48and a lot of the material in fruits and vegetables
01:26:50and grains and so forth
01:26:52are supposed to support microbiotal diversity
01:26:56and the proliferation of existing microbiota.
01:26:59And that is not what they observed,
01:27:01although I want to be very clear in pointing out
01:27:03that the results do not indicate that fiber
01:27:06is not useful for health overall,
01:27:10but it does point to the fact that increasing fiber intake
01:27:13did not increase microbiota diversity,
01:27:15which in general, as I mentioned before,
01:27:17is associated with improvements in microbiota function,
01:27:21health, and overall wellbeing.
01:27:24Now, the high fermented food diet condition
01:27:27was very interesting.
01:27:28It resulted in increased microbiome diversity
01:27:31and decrease inflammatory signals and activity.
01:27:35So there was a twofer.
01:27:36Basically by ingesting high fermented foods
01:27:40in fair abundance, right?
01:27:41You know, four to six servings or more per day
01:27:43is a lot of fermented food intake.
01:27:46We'll talk about what some of those foods were.
01:27:48But the outcome was very positive.
01:27:50There was a clear increase in microbiome diversity
01:27:53and decreased inflammatory signals.
01:27:56So things like interleukin-6,
01:27:58a number of other interleukins and cytokines
01:28:00that are associated with increased inflammation
01:28:03in the brain and body were reduced significantly.
01:28:06Now, let's talk a little bit about this notion
01:28:08of number of servings, et cetera.
01:28:10One somewhat minor point of the study,
01:28:14but I think is useful in terms
01:28:15of taking an actionable stance with this
01:28:18is that the number of servings of fermented foods
01:28:21was not as strong a predictor of improvements
01:28:25in the inflammatome, meaning reduced inflammation
01:28:28and improvements in microbiota diversity,
01:28:31as was the duration of time that the individuals
01:28:34were ingesting fermented foods.
01:28:36In other words, the longer that one
01:28:38is consistently ingesting fermented foods on a daily basis,
01:28:41the better the outcomes in terms of the gut microbiome
01:28:44and for reducing inflammation.
01:28:46So I think that's an important point.
01:28:48And I make that point,
01:28:49especially because for a lot of people,
01:28:52even if you do this ramp up phase,
01:28:53six servings per day of fermented foods
01:28:55can seem like quite a lot.
01:28:57So what are these fermented foods?
01:28:59I think many of us are familiar with certain cheeses
01:29:03and being fermented and beer being fermented
01:29:05and kombucha is fermented.
01:29:07In this study, they focus specifically
01:29:09on low-sugar fermented foods.
01:29:11So this would be plain yogurt,
01:29:14in some cases, kimchi or sauerkraut.
01:29:17An important consideration, however,
01:29:19is that it needs to contain
01:29:21what are called live active cultures,
01:29:23which means there actually have to be microbiota
01:29:26that are alive inside the sauerkraut.
01:29:28One way you know whether or not that's happening
01:29:30is if you purchase sauerkraut or pickles or kimchi
01:29:34from a jar or a container
01:29:35that's on the non-refrigerated shelf
01:29:38or the non-refrigerated section of your grocery store,
01:29:41it is not going to contain
01:29:43live active cultures of microbiota.
01:29:46And likewise, if you consume yogurt
01:29:49that has a lot of sugar or other components added to it,
01:29:53it's not going to have the same positive effect
01:29:55on the microbiome,
01:29:56at least that's the prediction
01:29:57given some of the relationship
01:29:59between the sorts of microbiota that live in sugar
01:30:02versus plain type yogurts.
01:30:04They gave people the option of consuming
01:30:06any number of different low-sugar fermented food.
01:30:08So that again that could be sauerkraut, kimchi,
01:30:10things like kefir, natto.
01:30:13In Japan, they consume natto which is a fermented food.
01:30:17Beer was not one of the fermented foods
01:30:20that was included in the fermented food list.
01:30:22And when we say six servings per day,
01:30:25that is indeed six, six ounce servings,
01:30:29or six, four to six ounce servings.
01:30:31It was not six servings of what's listed on the package.
01:30:34So again, that turns out to be a fair amount
01:30:37of fermented foods.
01:30:38How should you gauge
01:30:39whether or not you're getting enough of this?
01:30:40Well, if you decide to take on this protocol
01:30:43of ingesting more fermented foods,
01:30:44which at least by my read of this study
01:30:47and some of the follow up work that's being done,
01:30:49sounds like a terrific idea
01:30:50if you want to improve your gut microbiome
01:30:52for all the great reasons that one would want to,
01:30:55brain-body health, reduced inflammation, and on and on,
01:30:59well then you definitely want to focus
01:31:01on fermented foods that you enjoy consuming.
01:31:04So for you if that's kefir,
01:31:06or for you that's plain yogurt,
01:31:07or for you that's sauerkraut,
01:31:09which happens to be my personal favorite,
01:31:12then you want to make sure that it's going to be something
01:31:14that you are going to enjoy ingesting quite a lot of
01:31:17and that you're going to be okay with ingesting
01:31:20probably throughout the day.
01:31:21Now, people follow different meal schedules, of course,
01:31:24but this does require not just eating
01:31:26all the fermented foods just before bedtime or at one meal.
01:31:30I suppose you could do that,
01:31:31but in general, it's going to work best in terms
01:31:33of limiting gastric distress
01:31:35by spreading it out throughout the day.
01:31:37I also want to mention brine.
01:31:39Brine is the liquid that surrounds sauerkraut.
01:31:43It's that very salty fluid.
01:31:46And that contains a lot of active live cultures.
01:31:49And they did include or they allowed people to include
01:31:53brine in this study.
01:31:55And in discussions with Dr. Sonnenburg,
01:31:57which we'll go into in more detail on the episode
01:32:01that comes out next week,
01:32:02we talk a lot about the particular value
01:32:04that brine might hold
01:32:05in terms of bringing about microbiota diversity
01:32:08because of the richness of live cultures that it contains.
01:32:12I do want to focus for a moment on the high fiber condition
01:32:14because there were some interesting observations
01:32:16about the people that were placed into that condition.
01:32:18First of all, increasing the amount of fiber
01:32:23definitely increased the number of enzymes
01:32:26that can be used to digest fiber.
01:32:29This is in keeping with this idea of this ramp up phase
01:32:32where accumulation of more fiber intake
01:32:35can over time lead to less gastric distress
01:32:37but also to more utilization of fiber
01:32:39which overall should be a good thing.
01:32:41So while they didn't observe an increase
01:32:43in immune system function
01:32:45or an increase in microbiota diversity,
01:32:47there was an increase in these fiber digesting enzymes.
01:32:51They also observed what they called
01:32:53personalized immune responses.
01:32:55There were some subgroups within the high fiber group
01:32:58that had interesting changes in terms
01:33:00of their reactions to, or I should say their inflammatome,
01:33:05meaning the inflammatory markers they expressed,
01:33:06as well as their microbiota diversity.
01:33:09So there were essentially three groups.
01:33:11One group actually showed an increase
01:33:12in inflammatory markers.
01:33:14So that was quite surprising
01:33:15and probably not wonderful for the message
01:33:19that fiber is always good for us
01:33:21but that was a small cohort within the fiber intake group.
01:33:25Another group and still another group,
01:33:28both showed reductions in baseline microbiota diversity
01:33:31although to varying degrees.
01:33:34So I don't want to paint the picture that fiber is bad
01:33:36but fiber certainly did not have the positive effects
01:33:39on microbiota diversity
01:33:40that the high fermented food diet did.
01:33:43So my read of this study,
01:33:44and I think the stance that many others have taken
01:33:47as a consequence of these data,
01:33:49is that we should be increasing our fermented food intake,
01:33:52that that's simply a good thing to do in order to support
01:33:55our gut microbiome and to reduce inflammatory signals
01:33:58in our brain and body.
01:34:00And there are a number of different ways to do that.
01:34:02I mentioned some of the particular foods.
01:34:04However, anytime you're talking
01:34:05about ingesting fermented foods,
01:34:07especially the high quality ones
01:34:09that come from the refrigerated section
01:34:10of the grocery store,
01:34:13and that have low sugar content, et cetera,
01:34:16we do have to be considerate of cost
01:34:18because certain things like kombuchas, for instance,
01:34:20can be quite costly.
01:34:22I should also mention some kombuchas
01:34:23actually contain alcohol, some do not,
01:34:26or contain very little amounts of alcohol.
01:34:30One way to avoid the high cost of fermented foods
01:34:32while still being able to accumulate
01:34:34a lot of fermented food intake
01:34:35is to simply make those fermented foods yourself.
01:34:38And this is something that we've started exploring
01:34:40and experimenting with in our home.
01:34:42One simple way to do this
01:34:43is to just make your own sauerkraut.
01:34:45It involves very few ingredients.
01:34:47It basically involves cabbage, water, and salt,
01:34:50but there's a specific process that you need to follow
01:34:52in order to create these large volumes of sauerkraut at home
01:34:56using that low cost method.
01:34:58The best resource that I know of
01:35:00in order to follow a great recipe
01:35:03to make homemade sauerkraut would be the recipe
01:35:06for homemade sauerkraut that's contained
01:35:07in Tim Ferriss's book, \"The 4-Hour Chef\".
01:35:09There's an excellent protocol there.
01:35:11It involves chopping up the cabbage, putting into a bowl,
01:35:13mashing it up with your hands,
01:35:16which can be fun,
01:35:18putting water in there, some salt, covering it,
01:35:19and then keeping it in a particular environment,
01:35:22and then routinely scraping off
01:35:23some of the material from the surface.