Welcome to the Huberman Lab Podcast,
where we discuss science
and science-based tools for everyday life.
I’m Andrew Huberman,
and I’m a professor of neurobiology and ophthalmology
at Stanford School of Medicine.
Today, we are going to discuss the gut and the brain,
and we are going to discuss how your gut
influences your brain and your brain influences your gut.
As many of you probably know,
there is a phenomenon called your gut feeling,
which tends to be something that you seem to know
without really knowing how you know it.
That’s one version of the gut feeling.
The other is that you sense something
in your actual gut, in your body,
and that that somehow drives you to think or feel
or act in a particular way,
maybe to move towards something
or to move away from something.
Now, today, we aren’t going to focus so much
on the psychology of gut feelings,
but on the biology of gut feelings
and how the gut and brain interact,
because indeed, your gut is communicating to your brain
both directly by way of neurons, nerve cells,
and indirectly by changing the chemistry of your body,
which permeates up to your brain
and impacts various aspects of brain function.
But it works in the other direction too.
Your brain is influencing your entire gut,
and when I say entire gut, I don’t just mean your stomach,
I mean your entire digestive tract.
Your brain is impacting things
like how quickly your food is digesting,
the chemistry of your gut.
If you happen to be stressed or not stressed,
whether or not you are under a particular social challenge
or whether or not you’re particularly happy
will in fact adjust the chemistry of your gut,
and the chemistry of your gut in turn
will change the way that your brain works.
I’ll put all that together for you
in the context of what we call the gut microbiome.
The gut microbiome are the trillions of little bacteria
that live all the way along your digestive tract
and that strongly impact the way
that your entire body works at the level of metabolism,
immune system, and brain function.
And of course, we will discuss tools,
things that you can do in order to maintain
or improve your gut health.
Because as you’ll also soon see,
gut health is immensely important
for all aspects of our wellbeing,
at the level of our brain, at the level of our body.
And there are simple, actionable things that we can all do
in order to optimize our gut health
in ways that optimize
our overall nervous system functioning.
So we will be sure to review those today.
This episode also serves as a bit of a primer
for our guest episode that’s coming up next week
with Dr. Justin Sonnenberg from Stanford University.
Dr. Sonnenberg is a world expert in the gut microbiome.
And so we will dive really deep into the gut microbiome
in all its complexity.
We’ll make it all very simple for you.
We will also talk about actionable tools in that episode.
This episode is a standalone episode,
so you’ll get a lot of information and tools.
But if you have the opportunity to see this episode first,
I think it will serve as a nice primer
for the conversation with Dr. Sonnenberg.
Before we begin, I’d like to emphasize that this podcast
is separate from my teaching and research roles at Stanford.
It is however, part of my desire and effort
to bring zero cost to consumer information about science
and science related tools to the general public.
In keeping with that theme,
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I’ve done a couple of episodes now
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Okay, let’s talk about the gut and the brain
and how your gut and your brain communicate
in both directions.
Because as I mentioned before,
your gut is communicating all the time with your brain
and your brain is communicating all the time with your gut.
And so the two are in this ongoing dance with one another
that ordinarily is below your conscious detection,
although you’re probably familiar with the experience
of every once in a while getting a stomach ache
or of eating something that doesn’t agree with you
or conversely eating something
that you find particularly delicious.
And that sensation or that experience rather
being a whole body experience.
Your mind is excited about what you’re eating or just ate.
Your gut is excited about what you’re eating or just ate.
And it seems to be a kind of unified perception
of both brain and body.
Today, we’re going to talk about how that comes about
in the negative sense,
like when you meet someone you really dislike
or when you have a stomach ache and in the positive sense,
when you interact with somebody that you really, really like
and you’d like to spend more time with them, for instance,
or when you eat something that you really, really like
and you’d like to spend more time with that food,
so to speak.
Now, the gut and the brain represent
what we call a biological circuit,
meaning they include different stations.
So station A communicates with station B,
which communicates with station C and so on.
And as I mentioned earlier, it is bi-directional.
It’s a two-way street between gut and brain.
I want to make the important point at the outset
that when I say the word gut, when I refer to the gut,
I’m not just referring to the stomach.
Most of us think that the gut equates to the stomach
because we think of having a gut or not having a gut
or having a gut feeling of some sort.
But in the context of gut brain signaling
and the related microbiome,
the gut includes the entire digestive tract.
That’s right, from start to finish,
the entire digestive tract.
So much so that today we’re going to talk about,
for instance, the presence of neurons, nerve cells,
that reside in your gut,
that communicate to specific locations in the brain
and cause the release of specific neurochemicals,
such as the neurochemical dopamine or serotonin,
that can motivate you to seek more of a particular food
or type of interaction or behavior,
or to avoid particular foods, interactions, and behaviors.
And some of those neurons, many of those neurons, in fact,
reside in your intestines, not in your stomach.
They can be in the small intestine or the large intestine.
In fact, you actually have taste receptors
and neurons located all along your digestive tract.
You have neurons that are located
all along your digestive tract,
and they are communicating to your brain
to impact what you think, what you feel, and what you do.
Okay, so for the gut brain axis,
we need to deal with the brain part,
and then we need to deal with the gut part.
Let’s just quickly talk about the brain part,
because there, the word brain is also a bit of a misnomer,
in that when we say the gut brain axis,
it does include the brain,
but includes a lot of other things as well.
So as many of you probably know by now,
if you’re listeners of this podcast,
and if you don’t, that’s fine,
your nervous system includes your brain
and your spinal cord,
and those together constitute
what’s called the central nervous system.
Your neural retinas,
which are the lining the back of your eyes
and are the light sensing portion of your eyes,
are also part of your central nervous system.
So actually your eyes are part of your brain,
they’re the only parts of your brain
that are outside the cranial vault.
So your retinas, your brain proper,
and your spinal cord make up the central nervous system.
The other parts of your nervous system
constitute what’s called the peripheral nervous system,
which are the components of your nervous system
that reside outside the retinas, brain, and spinal cord.
Now, this is very important
because today we’re going to talk a lot about
how the gut communicates with the brain,
and it does that by way
of peripheral nervous system components,
meaning nerve cells that reside in the gut
and elsewhere in the body that communicate to the brain
and cross into the central nervous system
to influence what you think and what you feel, okay?
So that’s the nervous system part
of what we call the gut-brain axis.
Brain, again, just being a shorthand
for including all the elements I just described.
Gut, as you now know,
includes all the elements of the digestive tract.
Let’s talk about the architecture
or the structure of the gut of your digestive system.
Now, not surprisingly, your digestive system,
aka your gut, begins at your mouth and ends at your anus.
And all along its length,
there are a series of sphincters
that cut off certain chambers of the digestive tract
from the other chambers.
Now, also along this tube that we call the digestive tract,
there’s great variation in the degree of acidity
or pH, as it’s sometimes called.
That variation in acidity turns out to give rise
to different little microenvironments
in which particular microbiota, microbacteria,
can thrive or fail to thrive.
And so the way I’d like you to think
about the digestive tract,
this gut component of the gut-brain axis,
is that it’s not just one component.
It’s not just your stomach with a particular acidity
and a bunch of microorganisms that work particularly well
to make you feel good
and make your digestive pathways work well.
It’s a series of chambers, little microenvironments,
in which particular microbiota thrive
and other microbiota do not.
And certain behaviors that you undertake
and certain experiences that you have
will adjust those microenvironments
in ways that make particular microbiota, certain bacteria,
more likely to thrive and others less likely to thrive.
We’ll talk about how that was set up for you early in life.
Actually, from the moment that you came into the world,
that microbiome was being established.
It was actually strongly impacted,
depending on whether or not you were born by C-section
or by vaginal birth.
And it was strongly impacted by who handled you
when you came into the world.
Literally the hands that were on you,
how much skin contact you had,
whether or not you were a preemie baby or not,
whether or not you had pets at home,
whether or not you were allowed to play in the dirt,
whether or not you were allowed to eat snails,
or whether or not you were kept
in a very antiseptic environment.
All of those experiences
shaped these little microenvironments
and shaped what constitutes best or worst
for those microenvironments, okay?
So you have this long tube that we call the digestive tract
and it’s very, very long.
In fact, if we were to splay it out,
we were to take all the curves and turns
out of the intestine, we would find that it is very long.
It’s approximately nine meters long.
Now the structure of that digestive tract
turns out to be very important
in terms of gut brain signaling.
Once again, it’s a tube and the hollow of that tube
is called the lumen, L-U-M-E-N.
But the walls of the tube are not necessarily smooth,
at least not for significant portions
of the digestive tract.
For much of the digestive tract,
there are bumps and grooves that look very much
like the folds in the brain,
but these bumps and grooves are made up of other tissues.
They’re made up of what’s called a mucosal lining.
So there’s a lot of mucus there.
And if we were to look really closely,
what we would find is that there are little hairy
like cellular processes that we call microvilli
that are able to push things along the digestive tract.
The microbiota reside everywhere along the lumen
of the digestive tract, starting at the mouth
and all the way to the other end.
And they reside within those microvilli
and they reside within the lumen.
And if we were to look really closely
at the bumps and grooves along the digestive tract,
what we would find is that there are little niches,
little areas in which particular things
can grow and reside best.
Now that might sound kind of gross,
but it actually is a good thing,
especially what’s growing and residing there
are microbacterial organisms that are good for your gut
and that signal good things to your brain.
And we will talk about what that signaling looks like
and how that’s done and accomplished in just a few moments.
But I want you to get a clear mental picture of your gut,
something that we don’t often see.
And often when we think about the gut,
again, we just think about the hollow of the stomach,
food going in there and getting digested,
but it’s far more complex
and actually far more interesting than that.
Now I’ve been referring to the gut microbiome
and to the microbiota and these bacteria.
Let me define those terms a little bit more specifically
just to avoid any confusion.
The microbiota are the actual bacteria.
The microbiome is used to refer to the bacteria,
but also all the genes that those bacteria make
because it turns out that they make some important genes
that actually impact all of us.
You have loads and loads of these little microbiota,
In fact, right now you are carrying with you
about two to three kilograms.
So that’s more than six pounds of these microbiota,
And if we were to look at them under a microscope,
what we would see is
these are relatively simple little organisms.
Some remain stationary.
So they might plop down into the mucosal lining
or they might hang out on a particular microvilli
or they might be in one of those little niches
and others can move about.
But they basically fill the entire lumen.
They surround and kind of coat the surface
of the microvilli and they’re tucked up
into any of those little niches
that are available to them to tuck into.
If you were to take the head of a pin
and look at it under the microscope,
you could fit many, many hundreds,
if not thousands or more of these little microbacteria.
And the reason I say many, many thousands or more,
I’m giving a kind of broad range there,
is that they do vary in size.
And again, they vary as to whether or not they can move
or they don’t move.
Now, they’re constantly turning over in your gut,
meaning they’re being born, so to speak,
and they’re dying off.
And some will stay there for very long periods of time
within your gut and others will get excreted.
About 60% of your stool,
as unpleasant as that might be to think about,
is made up of live and dead microbacteria.
So you’re constantly making
and excreting these microbacteria.
And which microbacteria you make
and how many stay inside your gut and how many leave,
meaning how many are excreted,
depends a lot on the chemistry of your gut
and depends very strongly on the foods that you eat
and the foods that you do not eat.
Now, just because what we eat
strongly influences our microbiome,
meaning our microbacteria,
does not mean that there are not other influences
on what constitutes our microbiome.
Our microbiome is also made up by microbacteria
that access our digestive tract through our mouth,
through breathing, through kissing,
and through skin contact.
In fact, one of the major determinants of our microbiome
is who we interact with
and the environment that we happen to be in.
And that actually includes
whether or not we interact with animals.
In a little bit, I’ll talk about some data
as to whether or not you grew up in a home that had animals,
whether or not you grew up in a home,
whether or not there was a lot of social contact,
meaning skin contact,
or whether or not you grew up in a more animal-sparse,
and how that shapes your microbiome.
But the simple point is
that what you eat influences your microbiome,
but also what you do, what you think, and what you feel.
And many of the little microbacteria
that get into your digestive tract
do so by way of social interactions.
In fact, if you ask a neurobiologist
what the role of the microbiome is,
they’ll tell you almost certainly
that it’s there to impact brain function.
But if you have friends that are microbiologists,
such as I do, they’ll tell you,
well, maybe the brain and nervous system
are there to support the microbiome.
It’s the other way around.
You have all these little microorganisms
that are taking residence in our body.
They don’t really know what they’re doing as far as we know.
We don’t know that they have a consciousness or they don’t.
We can’t rule that out, but it seems pretty unlikely.
Nonetheless, they are taking advantage
of the different environments
all along your digestive tract.
They are taking advantage
of the sorts of social interactions.
For instance, the people you talk to
and that breathe on you,
the people that you shake hands with,
the people that you kiss or don’t kiss,
the people that you happen
to be romantically involved with or not,
your dog, your cat, your lizard, your rat,
whatever pet you happen to own is impacting your microbiome.
There’s absolutely no question about that.
So hopefully now you have some sense
of the architecture of the digestive pathway
and you have some sense of the trillions
of little micro bacteria that are living all along
the different components of that digestive pathway.
But what we haven’t talked about yet
and what I’d like to talk about now
is what those little microbiota are actually doing
in your digestive tract.
In addition to just living there
for their own intents and purposes,
they are contributing, for instance, to your digestion.
Many of the genes that those microbiota make
are genes that are involved in fermentation
and genes that are involved in digestion
of particular types of nutrients.
And in a little bit,
we will talk about how what you eat
can actually change the enzymes
that those microbiome components make.
Enzymes largely being things
that are responsible for digestion.
They catalyze other sorts of cellular events,
but in the context of the digestive pathway,
we’re talking about enzymes that help digest your food.
So those microbiota are indeed helping you in many ways.
And if you lack certain microbiota that can help you digest,
it stands to reason that you would have challenges
digesting certain types of foods.
The other amazing thing that these microbiota do
is they change the way that your brain functions
by way of metabolizing or facilitating the metabolism
of particular neurotransmitters.
So one of the ways that having certain microbiota
present in your gut can improve your mood
or degrade your mood, for instance,
is by way of certain microbiota being converted into
or facilitating the conversion of chemicals such as GABA.
GABA is what we call an inhibitory neurotransmitter.
It’s involved in suppressing the action of other neurons.
And that might sound like a bad thing,
but all types of sedatives, for instance, alcohol,
and a lot of neurons that naturally make GABA
can help quiet certain circuits in the brain.
For instance, circuits responsible for anxiety.
In people who have epilepsy,
the GABAergic neurons as they’re called
can often be disrupted in their signaling,
meaning they’re not cranking out as much GABA.
And therefore the excitatory neurons,
which typically release other molecules like glutamate
can engage in what’s called runaway excitation.
And that can give us rise to seizures.
So the simple message here is that the microbiota
by way of making neurochemicals
can influence the way that your brain functions.
So you want to support those microbiota
and we will give you tools to support those microbiota.
But the takeaway at this point is that those microbiota
are making things locally to help digest food.
Other microbiota are helping to make
certain neurotransmitters like GABA.
And we’ll also talk about dopamine and serotonin.
And so the very specific microbiota that reside in your gut
have a profound influence
on many, many biological functions,
especially immune system function,
brain function, and digestion.
So that should give you a fairly complete picture
of your gut microbiome.
Now I’d like to talk about how your microbiome
and your brain communicate,
or more accurately how your microbiome
and the rest of your nervous system communicate.
Neurons, which simply means nerve cells,
are the cells that do most of the heavy lifting
in your nervous system.
There are of course other cell types
that are important, glial cells, for instance,
very, very important cell types.
You have endothelial cells,
which are responsible for blood flow,
pericytes and other types of cells.
But the neurons are really doing most of the heavy lifting
for most of the things we think about
in terms of nervous system function.
You have neurons in your gut
and that should not surprise you.
Neurons reside in your brain, your spinal cord, your eyes,
in fact, all over your body.
And you’ve got them in your heart
and you’ve got them in your lungs
and you’ve got them in your spleen
and they connect to all the different organs
and tissues of your body.
So that’s not surprising that you have neurons in your gut.
What is surprising, however,
is the presence of particular types of neurons
that reside near or in the mucosal lining
just next to that lumen of the gut
and that are paying attention,
and I’ll explain what I mean by paying attention,
to the components of the gut,
both the nutrients and the microbiota,
and thereby can send signals up to the brain
by way of a long wire that we call an axon
and can communicate what the chemistry
and what the nutritional quality
and what the other aspects of the environment
are at the gut at a given location up to the brain
in ways that can influence the brain to, for instance,
seek out more of a particular food.
Let me give you a sort of action-based picture of this.
Let’s say, like most people, you enjoy sweet foods.
I don’t particularly enjoy sweet foods,
but there are a few that I like.
I’m a sucker for a really good dark chocolate
or really good ice cream,
or I got this thing for donuts that seems to just not quit,
although I don’t tend to indulge it very often.
I do like them.
If I eat that particular food,
obviously digestion starts in the mouth,
there are enzymes there, it gets chewed up,
the food goes down into the gut.
These neurons are activated,
meaning that causes the neurons to be electrically active
when particular components,
certain nutrients in those foods are present.
And for the cell types,
or I should say the neuron types that matter here,
the nutrients that really trigger their activation
are sugar, fatty acids, and amino acids.
Now, these particular neurons
have the name enteroendocrine cells,
but more recently they’ve been defined as neuropod cells.
Neuropod cells were discovered by Diego Bohorquez’s lab
at Duke University.
This is a phenomenal set of discoveries
made mostly in the last 10 years.
These neuropod cells, as I mentioned,
are activated by sugar, fatty acids, or amino acids,
but have a particularly strong activation to sugars.
They do seem to be part of the sweet sensing system.
And even though I’m focusing on this particular example,
they represent a really nice example
of how a particular set of nerve cells in our gut
is collecting information about what is there
at a particular location in the gut
and sending that information up to our brain.
Now they do that by way of a nerve pathway
called the vagus nerve.
The vagus nerve is part of the peripheral nervous system.
And the vagus nerve is a little bit complex to describe
if you’re just listening to this.
If you’re watching this,
I’ll try and use my hands as a diagram,
but really the best thing to do
if you really want to learn neuroanatomy
is to just imagine it in your mind as best you can.
And if you can track down a picture of it, terrific.
But here’s how it works.
Neurons have a cell body that we call a soma.
That’s where all the DNA are contained.
That’s where a lot of the operating machinery
of the cells are contained
and a lot of the instructions for that cell of what to be
and how to operate are contained.
The cell bodies of these neurons or the relevant neurons
are actually up near the neck.
So you can think of them as kind of a clump of grapes
because cell bodies tend to be round or ovalish.
And then they send a process that we call an axon
in one direction out to the gut.
And they’ll send another process up into the brain.
And that little cluster near the neck that’s relevant here
is called the nodose ganglion, N-O-D-O-S-E.
The nodose ganglion is a little cluster of neurons
on either side of the neck.
It has a process that goes out to the gut
and a process that goes up into the brain.
And again, these are just one component
of the so-called vagus nerve.
The vagus nerve has many, many branches,
not just to the gut.
There are also branches to the liver,
branches to the lungs, branches to the heart,
branches to the larynx, and even to the spleen
and other areas of the body that are important.
But right now we’re just concentrating on the neurons
that are in the gut that signal up to the brain.
And what the Bohorkes lab has shown
is that these neuropod cells are part of this network.
They’re sensing several different nutrients,
but in particular, when they send sugar,
they send signals in the form of electrical firing
up to the brain in ways that trigger activation
of other brain stations that cause you to seek out
more of that particular food.
Now, this brings us to some classic experiments
that at least to me are incredible.
And these are highly reproducible findings
showing for instance, that even if you bypass taste
by infusing sweet liquid or putting sweet foods
into the gut and people can never taste them
with their mouth, people will seek out more
of that particular food.
And if you give them the option to have a sweet food
infused into their gut or a bitter food infused
into their gut or a sweet versus sour
or a more sweet versus less sweet food,
people have a selective preference for sweet foods
even if they can’t taste them.
Now, this is important to understand
in the context of gut brain signaling,
because we always think that we like sweet foods
because of the way they taste.
And indeed that’s still true,
but much of what we consider the great taste of a sweet food
also has to do with a gut sensation
that is below our conscious detection.
How do we know that?
Well, the Bohorkes lab has performed experiments
using modern methods and their classic experiments
showing that animals and humans will actively seek out
more of a particular sweet food
even if it bypasses this taste system.
And the reverse is also true.
There have been experiments done in animals and in humans
that have allowed animals or humans to select
and eat sweet foods, and indeed that’s what they do
if they’re given the option.
And yet to somehow eliminate the activation
of these neurons within the gut that can sense sweet foods.
Now, there are a couple of different ways
that those experiments have been done.
In classic experiments that date back to the 80s,
this was done by what’s called sub diaphragmatic vagotomy.
So this means cutting off the branch of the vagus
that innervates the gut below the diaphragm
so that the other organs can still function
because the vagus is very important.
But basically cutting off the sweet sensing in the gut,
still giving people the opportunity
to taste sweet foods with their mouth.
And they don’t actively seek out
quite as much of the sweet food
when they don’t have this gut sensing mechanism
that we now know to be dependent on these neuropod cells.
More recent experiments involve selective silencing
of these neuropod cells.
And there’ve been a lot of different derivations
of this sort of thing.
But the takeaway from it is that our experience of
and our desire for particular foods
has everything to do with how those foods taste.
It also has to do as you probably know with their texture
and the sensation of those foods in our mouth
and even indeed how they go down our throat
sometimes can be very pleasing or very unpleasant.
And it also has to do with this subconscious processing
of taste that occurs in the gut itself.
And again, when I say gut, I don’t just mean in the stomach.
There are actually neurons, neuropod cells
further down your digestive tract
which are signaling to your brain
about the presence of sweet foods
as well as foods such as amino acid rich foods
or foods that are rich in particular types of fatty acids
signaling up to your brain
and causing you to seek out more of those foods
or to consume more of those foods.
Now you’re probably asking, what is the signal?
How does it actually make me want more of those foods
without me realizing it?
Well, it does that by adjusting the release
of particular neuromodulators.
For those of you that are not familiar
these are similar to neurotransmitters
but they tend to act more broadly.
They tend to impact many more neurons all at once.
And they go by names like dopamine, serotonin,
acetylcholine, epinephrine, and so forth.
Sometimes people refer to those as neurotransmitters.
Technically they are neuromodulators.
I’ll refer to them almost always as neuromodulators.
The neuropod cells signal by way
of a particular branch of the vagus
through that no-dose ganglion that we talked about before
and through a number of different stations in the brainstem
eventually cause the release of the neuromodulator dopamine.
Dopamine is often associated
with a sense of pleasure and reward,
but it is more appropriately thought of
as a neuromodulator that impacts motivation,
craving, and pursuit.
It tends to put us into modes of action,
not necessarily running and moving through space,
although it can do that too.
But in the context of feeding,
it tends to make us look around more,
chew more, reach for things more,
and seek out more of whatever it is
that’s giving us that sensation of delight or satisfaction.
And again, that sense of delight and satisfaction
you might experience only consciously
as the way that something tastes on your mouth,
but it actually is caused again
by both the sensations in your mouth,
but also by the activation of these neuropod cells.
So this is an incredible system of gut-brain signaling,
and it is but one system of gut-brain signaling.
It turns out it’s the system that we know the most about
at this point in time.
There are other components of gut-brain signaling
that we’ll talk about in a moment.
For instance, the serotonin system.
But in terms of examples of gut-brain signaling
for which we know a lot of the individual elements
and how they work,
I think this neuropod neuron sensing of sweet foods,
fatty acids, and amino acids in the gut
and communicating that up to the brain
by way of the vagus and causing us to seek out
more of the foods that deliver those nutrients
is an incredible pathway that really delineates the beauty
and the power of this gut-brain axis.
Let me talk about timescales.
Here, I’m talking about a particular type of neuron
that is signaling up to the brain using electrical signals
to cause us to want to seek out
a particular category of foods.
That’s happening relatively fast
compared to the hormone pathways of the gut,
which also involve neurons.
So your gut is also communicating to your brain
by way of neurons, nerve cells.
But some of those nerve cells also release hormones,
and those hormones go by names like CCK,
glucagon-like peptide one, PYY, et cetera.
A good example of a hormone pathway
or what’s sometimes called a hormone peptide pathway
that is similar to the pathway I’ve talked about before,
but a little bit slower is the ghrelin pathway.
Ghrelin, G-H-R-E-L-I-N, increases with fasting.
So the longer it’s been since you’ve eaten,
or if you’re just eating very little food
compared to your caloric needs,
ghrelin levels are going to go up in your bloodstream,
and they go up because of processes
that include processes within the gut
and include the nervous system.
So it’s a slow pathway driving you
to seek out food generally.
As far as we know, the ghrelin system is not partial
to seeking out of sweet foods or fatty foods or so on.
Ghrelin increases the longer it’s been
since you’ve eaten sufficient calories,
and it stimulates a feeling of you wanting to seek out food.
Well, how does it do that?
It does that, again,
by impacting neural circuits within the brain,
neural circuits that include
what we call the brainstem autonomic centers.
So it tends to make you feel alert
and quite, we say, high levels of autonomic arousal.
If you haven’t eaten in a while,
you might think that you just get really exhausted, right?
Because we all hear that food is energy
and caloric energy is what we need to burn,
but you actually have a lot of energy stored in your body
that you would be able to use if you really needed energy.
But typically we haven’t eaten in a while,
we start to get agitated,
and we get agitated by way of release
of the neuromodulator epinephrine,
which causes us to look around more,
move around more and seek out food.
That all occurs in brainstem autonomic centers
and in the hypothalamus.
We did an entire episode on feeding behavior
and metabolism as well,
and you can find those episodes at hubermanlab.com.
So I don’t want to go into a lot of detail
about hypothalamic and brainstem centers,
but there’s a particular area of the brain
called the nucleus of the solitary tract,
the NST as it’s called,
that’s very strongly impacted by these circulating hormones
and tends to drive us toward feeding behavior.
So the important point here is that we have a fast system
that is paying attention to the nutrients in our gut
or the absence of nutrients in our gut
and stimulating us to seek out food
or to stop eating certain foods.
And we have a slower hormone related system
that also originates in the gut and impacts the brain,
but all of those converge on neural circuits for feeding.
The neural circuits for feeding
include things like the arcuate nucleus, the hypothalamus,
they include a bunch of other neurochemicals,
but the point is that you’ve got a fast route
and a slow route to drive you to eat more or eat less,
to seek out food and consume it,
or to stop eating and to essentially kickstart
the satiety mechanisms as they’re called.
And those are operating in parallel.
It’s not like one happens first and stops then the other,
they’re always operating in parallel.
And I bring this up because there’s a bigger theme here,
which we see over and over again in biology,
which is the concept of parallel pathways.
You’ve always got multiple accelerators
and multiple brakes on a system.
It’s very, very rare to have just one accelerator
and one brake on the system.
And this will become important later
when we talk about tools for optimizing your gut microbiome
for healthy eating and for healthy digestion
and for healthy brain function.
I want to take a moment and talk about
glucagon-like peptide one, which is also called GLP-1.
GLP-1 is made by neurons in the gut
and by neurons in the brain.
This is a fairly recent discovery, but it’s an important one.
GLP-1 tends to inhibit feeding and tends to reduce appetite.
There are a number of drugs released on the market now.
GLP-1, for instance, goes by the name semaglutide,
which is essentially a GLP-1 agonist.
It causes the release of more GLP-1.
It’s being used to treat type two diabetes,
which is insulin resistant diabetes.
This is different than type one diabetes
where people don’t actually make insulin.
It’s also being used as a drug to reduce obesity.
And it seems pretty effective,
at least in certain populations.
There are certain foods and substances that increase GLP-1.
I’ve talked about a few of these on the podcast.
One that I’m a particular fan of for entirely other reasons
is yerba mate tea can stimulate the release of GLP-1.
In South America, it’s often used as an appetite suppressant,
probably in large part because of its effects
on GLP-1 release, but probably also
because it does contain caffeine,
which is a bit of a stimulant,
which also can be involved in lipolysis,
which is the utilization of fat stores
for energy and so forth.
A brief mention about yerba mate.
There are some reports out there
that yerba mate can increase certain types of cancers.
The data that I’ve seen on this is that it tends to relate
to whether or not those are smoked versions
of the yerba mate tea, the amount of consumption,
and the debate is still out.
So I invite you to look at those papers.
You can search for those online.
Nonetheless, yerba mate is one source of GLP-1 stimulation.
Semaglutide is another source.
It also can be stimulated by various foods,
nuts, avocados, eggs, and so forth.
Certain high-fiber complex grains will also stimulate GLP-1.
I raise this as not necessarily a route
that you want to take in order to reduce food intake.
I don’t even know that that’s your goal,
but that GLP-1 is another one of these
gut-to-brain signaling mechanisms that adjust appetite
that is dependent on diet,
depends on what you eat or drink,
and that the GLP-1 pathway does seem particularly sensitive
to the constituents of diet.
There’s at least one quality study I was able to find
showing that the ketogenic diet, for instance,
which almost always involves ingestion
of very low levels of carbohydrate, can increase GLP-1.
Although, as I mentioned before,
there are other foods that fall outside the range
of what we would consider ketogenic
that can also stimulate GLP-1.
And as I mentioned, there are prescription drugs
There are other ones as well now that stimulate GLP-1.
So how does GLP-1 reduce appetite?
It does that in part by changing the activity of neurons
in the hypothalamus,
this cluster of neurons just above the roof of our mouth
that themselves make GLP-1
and that cause the activation of motor circuits
for reaching, chewing,
all the things that we associate with feeding behavior.
So I use GLP-1 as an example of a pathway
that you might choose to tap into
by ingestion of Yerba Mate
or by ingestion of the foods I mentioned,
or if it’s something that interests you, ketogenic diet.
But I also mention it simply because
it’s another beautiful example
of how our hormone pathway
can impact the activity of brain circuits
that are directly involved in a particular behavior.
So yet another example of how gut is communicating to brain
in order to change what we think we want
or to change what our actual behaviors are.
So the next time you find yourself reaching for food
or you find yourself wanting a particular sweet thing
or fatty thing or something that contains
a lot of amino acids, a protein-rich food,
keep in mind that that’s not just about
the taste of the food.
And it’s not even necessarily about the nutrients
that you need or don’t need, it could be,
but it’s also about the subconscious signaling
that’s coming from your body all the time.
Waves of hormones, waves of nerve cell signals,
electrical signals that are changing the way
that your brain works.
And this raises for me a memory of the episode
that I did with Dr. Robert Sapolsky,
who’s a world expert colleague of mine at Stanford,
who is expert on things like hormones and behavior.
But we got into the topic of free will,
which is a bit of a barbed wire topic.
As many of you know,
it gets into the realm of philosophy, et cetera.
And we were kind of batting back and forth the idea.
I was saying, well, I think there’s free will
and can’t there certainly be free will
or certainly the idea that we can avoid certain choices.
And Robert was saying, no.
In fact, he said, nah,
he doesn’t believe that we have any free will.
He thinks that events in our brain are determined
by biological events that are below our conscious detection
and that occur seconds to milliseconds
before we make decisions or assessments.
And therefore we just can’t control what we do,
what we think and what we feel.
And at the time I sort of didn’t buy it.
I thought, I don’t know.
I just, I guess I really wanted to believe in free will.
And to some extent I still do.
But as we talk about how these neurons in our gut
and these hormones in our gut are influencing our brain
and the decisions that we are making
at the level of circuits like the hypothalamus
and the nucleus of the solitary tract,
these are areas of the brain way below our frontal cortex
and our conscious perception.
I think these are examples that really fall in favor
of what Dr. Sapolsky was arguing,
which is that events that are happening within our body
are actually changing the way our brain works.
So we might think that we want the cupcake.
We might think that we don’t need to eat something
or do need to eat something.
And that is entirely on the basis of prior knowledge
and decision-making that we’re making with our head.
But in fact, it’s very clear to me based on the work
from the Bohork’s lab, classic work over the years,
dating back to the 80s and indeed back to the 50s
that we’ll talk about in a moment,
that our body is shaping the decisions
that our brain is making and we’re not aware of it at all.
Now, the good news is that whether or not you believe
in free will or not, the simple knowledge
that this whole process is happening
can perhaps be a benefit to you.
You can perhaps leverage it to get some insight
and understanding and perhaps even a wedge
into your own behavior.
You might think, ah, I think I want that particular food
or I think I want to avoid that particular food,
but actually that’s not a decision that I’m making
on a purely rational basis.
It has a lot to do with what my gut is telling my brain.
So we’ve largely been talking about chemical communication
between the gut and the brain.
Chemical because even though these neuropod cells
are communicating with the brain
by way of electrical activity,
what we call action potentials,
and in neural language, we call those spikes,
spikes of action potentials.
Spikes of action potentials, meaning those neural signals,
cause the release of chemicals in the brain like dopamine.
So it’s chemical transmission.
Similarly, hormones, even though they act more slowly,
hormones like neuropeptide Y, like CCK, like ghrelin,
they are signaling chemically.
They’re moving through the body,
they’re going in there affecting the chemical output
of different cells,
and they’re changing the chemistry of those cells
and the chemistry of the cells that those cells talk to.
So that gives us one particular category of signaling
from gut to brain, which is chemical signaling.
But of course, there are other forms of signals,
and those fall under the category of mechanical signaling.
You’re probably familiar with this.
If you’ve ever eaten a very large meal
or consumed a lot of fluid,
you experience that as distention of the gut,
and that doesn’t just have to be distention of the stomach,
but distention of your intestines as well.
That distention is registered by neurons
that reside in your gut.
The signals go up to your brain
and communicate with areas of the brain
that are responsible for suppressing further consumption
of food and or fluid.
And under certain circumstances,
can also be associated with the activation
of neural circuits that cause vomiting
or the desire to vomit.
So if ever you’ve eaten too much,
or you’ve eaten something that doesn’t agree with you,
that information is communicated by way of mechanosensors
that sense the mechanics of your gut,
possibly also the chemistry of your gut,
but mostly the mechanics of your gut,
signal up to the brain and activate brain centers
that are involved in stopping the eating behavior
and activation of an area of the brainstem
that is affectionately referred to as the vomit center
This is a area that more appropriately
is called the chemoreceptor trigger zone,
the CTZ or area post-strema,
and neurons in this area actually will trigger
the vomiting reflex.
So the way that the gut and the brain communicate
is both chemical and mechanical,
and it can be both for sake of increasing
certain types of behavior,
today we’re talking mainly about feeding behavior
up until now anyway,
but also ceasing to eat, closing your mouth,
moving away from food, turning away from food,
all behaviors that we’re familiar with
anytime we feel kind of sick on the basis of activation
of this mechanosensor for gastric distress.
So we’ve got chemical signaling and mechanical signaling,
and I also want to emphasize
that we have direct and indirect signaling
from the gut to the brain.
Direct signaling is the kind of signaling
of the sort I’ve been talking about mainly up until now,
which is neurons in the gut
communicating with neurons in the brainstem
that communicate with neurons in the hypothalamus,
and of course, those are also going to interact
with neurons of the prefrontal cortex,
which is the area of your brain involved in decision-making,
the, you know, I think it was the shrimp that made me sick,
I just don’t want any more of that,
or I’m never going back to that restaurant again
because after I ate there about an hour later,
I started feeling really not well.
I felt, you know, kind of feverish,
but my gut didn’t feel well, my digestion was really off.
All of that kind of information is handled
in the prefrontal cortex at a conscious level,
but the immediate decision to stop eating
or to eat more of something,
to move towards something or away from it,
that’s made by neural circuits that reside at the,
we would say the subconscious level,
but what we really mean
is below the level of the neocortex.
Below the cortex means essentially
below our level of conscious awareness.
So we talked about two types of information within the gut
that are communicated to the brain,
chemical information, meaning information
about the nutrients that happen to be there
and mechanical information,
distention of the gut or lack of distention and so forth.
And we talked about how these neuropod cells
can signal the release of dopamine
in circuits within the brain
to cause you to seek out more of something.
Now, in a very logically consistent way,
dopamine is also involved in the whole business of vomiting.
You might think, well, that doesn’t make any sense.
I thought dopamine was always a good thing.
It’s involved in motivation and reward, et cetera.
But it turns out the areopostrema,
this vomit center and the brainstem
is chock-a-block full of dopamine receptors.
And if dopamine levels go too high,
it can actually trigger vomiting.
And this we see in the context of various drugs
that are used to treat things like Parkinson’s.
Parkinson’s is a deficiency in dopamine
or a lack of dopamine neurons,
typically that causes a resting tremor,
difficulty in movement,
because dopamine is also associated
with a lot of the neural circuits for movement.
Many drugs that are used to treat Parkinson’s like L-DOPA
increase levels of dopamine so much
or at least activate dopamine receptors
to such a great degree in certain areas of the brain
that they can cause activation of things
like the trigger to vomit.
Now, this should also make sense in the natural context
of if you gorge yourself with food,
gorge yourself with food, gorge yourself with food,
the neurons in your gut that respond to that
are simply detecting the presence of nutrients,
but they don’t really make decisions themselves.
They don’t know to stop eating.
Your brain knows to stop eating or to eject that food.
And so it’s a wonderful thing
that those neurons are communicating
with areas of the brain,
not just that stimulate consuming more food,
but that are communicating with areas of the brain,
for instance, areopostrema,
that when dopamine levels get too high,
cause us to either stop eating that food
or in the case of vomiting to eject that food.
So I raise this not to give you a kind of a disgusting
counterexample to what we call appetitive behaviors,
the things that we like to do more of,
but simply to give you a sense of just how strongly
even these reflexes that we think of
as feeling sick and vomiting
or the desire to seek out more food
are really being controlled by a kind of push pull system,
by parallel pathways that are arriving from our gut.
And the same neurochemicals in this case,
dopamine are being used
to create two opposite type behaviors,
one behavior to consume more,
one behavior to get rid of everything
you’ve already consumed.
So our brain is actually sensitive
to the amount of signaling coming from our gut,
not just the path by which that signal arrives.
Our brain is very carefully paying attention
to whether or not the levels of dopamine
that are being triggered are within a normal range
for typical eating behavior
or whether or not we’ve gorged ourselves
to the point where enough already.
Now, of course, mechanical signals will also play
into areopostrema and into the vomiting reflex.
If we have a very distended gut, we feel lousy.
It just, it actually can hurt very badly
and we will have the desire to vomit
or we will just simply vomit.
So mechanical and chemical signals
are always arriving in parallel.
They never work in unison.
And so now we have chemical signals, mechanical signals.
And now I’d like to talk about direct and indirect signals
because almost everything I’ve talked about up until now
are direct signals, a neural pathway
that converges in the brain
to create a particular feeling, thought, or behavior,
but there are also indirect pathways.
And that’s what takes us back to the gut microbiome
and to these little microbiota.
And to just give you the takeaway message at the front here,
and then I’ll give you a little more detail
as to how it comes about.
You have neurotransmitters in your brain
and in your spinal cord and in your eyes
and in your peripheral nervous system.
They cause the activation or the suppression
of nerve activity, meaning they either
electrically activate other nerve cells
or they cause other nerve cells
to be less electrically active.
And they do that by way of neurotransmitters.
But as it turns out, the gut microbiota
are capable of influencing metabolic events.
And in some cases are capable
of synthesizing neurotransmitters themselves.
So what that means is that these little bugs,
these little microbiota that are cargo in your gut,
the six pounds of cargo,
they actually can make neurochemicals
that can pass into the bloodstream and into your brain
and actually impact the other cells
of your body and brain indirectly.
So without involving these very intricate nerve pathways
that we’ve been talking about.
In other words, the foods you eat,
the environment of your gut microbiome
can actually create the chemical substrates
that allow your brain to feel one way or the other,
to feel great or to feel lousy,
to seek out more of a particular type of behavior
or to avoid that behavior.
And that would constitute indirect signaling.
So I’ve been talking a lot about the structure
and function of the gut to brain pathway,
focusing mainly on feeding behaviors
and in some cases avoiding feeding
or even ejecting food from the digestive tract.
I’d like to drill a little bit deeper
into this indirect signaling pathway
from the gut to the brain,
because it bridges us nicely from neuronal signals
in the gut to the brain,
hormonal signals from the gut to the brain,
to what also includes the microbiome,
which is what we started talking about
at the beginning of the episode.
As I mentioned a couple of minutes ago,
certain gut microbiota can actually synthesize
certain neurotransmitters that can go impact the brain.
And we actually have some knowledge
about which microbiota can synthesize
For instance, the neuromodulator dopamine
can be synthesized by or from bacillus and ceratia.
Now, these are just names of microbiota.
I don’t expect that any of you
would necessarily recognize them.
These aren’t the sorts of things
that you necessarily would have run out and buy
to get more dopamine.
But the point is that particular gut microbiota
can create dopamine in our gut
that can get into our bloodstream
and can generally change our baseline levels of dopamine
within the brain and other areas of the body.
I mentioned baseline levels of dopamine
because as I talked about on an episode all about dopamine,
but I’ll just repeat the basics here now,
we have baseline levels of neurotransmitters
or neuromodulators that act as sort of
the level of the tide, the overall level,
and then we can have peaks of dopamine
that are created by behaviors
or by ingestion of particular foods or drugs, et cetera.
So bacillus and ceratia tend to increase
our baseline levels of dopamine.
So if it turns out that we are creating
the right gut microbiome environment
that these particular gut microbiota can thrive in,
well, then our baseline levels of dopamine will be elevated.
And in general, that leads to enhancement of mood.
Similarly, there are other gut microbiota,
for instance, candida, streptococcus, various enterococcus.
These always have these kind of strange
and not so attractive names,
at least to me as a neurobiologist.
Nonetheless, those particular microbiota
support the production of,
or can even be metabolized into serotonin,
which is a neuromodulator associated with mood,
with social interactions,
with a huge number of different
types of events and behaviors.
Again, these gut microbiota, when present
and allowed to thrive in our gut,
will increase our overall levels of serotonin.
And riding on top of that level of serotonin
will be the serotonin that’s specifically released
in response to certain behaviors.
And I really want to drive home this point
of baselines and peaks.
The baseline level of serotonin might set our overall mood,
whether or not we wake up feeling pretty good
or really lousy if our serotonin levels
happen to be very, very low.
Whether or not we tend to be in a kind of a calm space
or whether or not we tend to be somewhat irritable.
But then of course, individual events
as we go about our day,
maybe a compliment that we get,
or maybe somebody says something irritating to us,
whatever it may be,
will also influence levels of serotonin.
But those serotonin events are going to be related to events
at particular neural circuits in the brain.
And this is an important topic
because I think that a lot of people hear quite accurately,
oh, 90 to 95% of our serotonin is manufactured in the gut.
And indeed that’s true.
It’s manufactured from the sorts of microbiota
that I just described.
And there are many, many experiments now,
mostly in animal models,
but also some in humans that show
that if the gut microbiome is deficient in some way
to these particular bacteria,
that serotonin levels drop and people’s mood suffers,
maybe even their immune system functions,
maybe even exacerbates certain psychiatric illnesses.
However, a lot of people take that to mean
that the serotonin of the brain all comes from the gut
or mostly comes from the gut.
That’s not the case.
It’s still the case that you have neurons in the brain
that are responsible for releasing serotonin directly
in response to certain things like social touch
or through other types of positive social experiences.
So we’ve got gut microbiota
that can literally be turned into dopamine
and raise our baseline levels of dopamine.
We’ve got gut microbiota that can literally
raise our baseline levels of serotonin.
And indeed there are other gut microbiota
like lactobacillus or bifidobacterium, excuse me,
hard complex names to pronounce.
Bifidobacterium that can give rise to increases
in GABA levels, this inhibitory neurotransmitter
that can act as a little bit of a mild sedative,
can reduce irritability, et cetera.
But that’s just the baseline,
the kind of tide of those neuromodulators.
Again, I want to emphasize that we still have neural circuits
within the brain and body that are specifically releasing
in a very potent way, dopamine, serotonin, and GABA.
So the two things act in concert.
Even though the gut and the brain are acting
both in parallel and directly influencing one another,
it is a powerful synergistic effect.
And there are now hundreds of studies,
maybe even thousands by this point,
mostly performed in animal models, typically mice,
but also some studies in humans that show
that creating the correct environment
for these gut microbiota to thrive
really does enhance mood and wellbeing.
And that when our gut microbiome is not healthy,
that it really can deplete our mood and sense of wellbeing.
Now, there are two major phases
to creating a healthy gut microbiome.
One you can control,
and the other one is less under your control.
I get into this in a lot of detail
in the episode with Dr. Sonnenberg,
which is coming out immediately after this one,
the following Monday, that is.
But for now, I want to just capture a few of the main points
about the early establishment of the gut microbiome.
It turns out that the environment that we are exposed to,
the things that come into contact with our skin
and digestive tract and any other mucosal lining,
even the urethra, the nasal passages,
any opening to the outside world
that brings in certain, excuse me,
certain microbiota in the first three years of life
is going to have a profound impact
on the overall menu of microbiota
that we will be able to carry within our body.
And it really does seem that getting exposure to
and building a diverse microbiome
in those first three years is critical.
There’s a lot of speculation and some data
as to cesarean delivered babies
having less diverse microbiomes
compared to vaginally delivered babies.
There’ve been attempts, although not conclusive attempts,
to link that to the presence of autism spectrum disorders,
which at least by some statistics
seem to be of higher probability in cesarean deliveries,
although there are other studies that refute that,
and I want to make that clear.
However, it’s clear that babies do not get much,
if any, exposure to microbiota inside of the womb,
maybe a little bit, but not much,
but it is during the birth process
and in the days and weeks immediately after
they arrive in the world
that their gut microbiome is established,
that those gut microbiota take residence within the gut.
So it will depend on whether or not
they were breastfed or bottle-fed.
It will depend on whether or not
they were exposed to a household pet or not,
whether or not they were held by multiple caregivers
or just by one, whether or not they were a preemie baby
and were contained in a particularly restrictive environment
in order to encourage their further development
before they could be brought home or not.
I don’t want to give the picture
that if you were isolated or you were delivered by C-section
that you’re somehow doomed to have a poor microbiome.
That’s simply not the case.
However, it is the case that the more diversity
of microbiota that one can create early in life
is really helpful for long-term outcomes
in terms of brain to gut signaling, gut to brain signaling,
and for sake of the immune system.
There are some decent studies showing that
if children are exposed to a lot of antibiotic treatment
early in life, that can be very detrimental
to establishment of a healthy gut microbiome.
And fortunately, that reestablishing
a healthy gut microbiome can help rescue
some of those deficits.
So doctors nowadays are much more cautious
about the prescription of antibiotic drugs
to children in their early years,
not just up to three years, but extending out to,
you know, five and seven and 10 years.
And even in adults, they’re very, very careful about that
or they ought to be.
One reason is the existence or I would say the proliferation
of antibiotic resistant bacteria
that are becoming more common in hospitals and elsewhere,
and that can cause serious problems.
But in addition to that, because of this understanding
that the gut microbiome is influencing
and actually creating neurotransmitters
that can impact mood and mental health,
impact immune health, and so on.
As I mentioned earlier, there are hundreds,
if not thousands of studies,
emphasizing the key role of the microbiome
on brain health, psychiatric health, et cetera.
I want to just highlight a few of those studies.
And in particular, some recent studies that come from labs
that have been working on this sort of thing
for a very long time.
One of the more exciting studies comes from the work
of Mauro Costa Mattioli’s lab,
which is at Baylor College of Medicine.
Mauro’s lab has been working on mouse models
of autism spectrum disorder for a long time
and looking at social behavior using a mouse model
for a long time.
And they’ve been able to identify particular types
of microbiota that when they take resonance in the gut
can help offset some of the symptoms of autism,
at least the symptoms of autism
that exist in these mouse models.
Okay, so again, this is not human work.
This is work being done on mouse models
for the simple reason that you can do these kinds
of manipulations where basically they took mice
that were in germ-free environments
or non-germ-free environments,
or they exposed mice to particular microbiota
and not other microbiota.
And they discovered that a particular microbiota
called L. ruteri, it’s L period, R-E-U-T-E-R-I.
Treatment with L. ruteri corrects the social deficits
present in these autism models.
And it does so by way of activating our old friend,
the vagus nerve, but not simply because the vagus nerve
triggers the release of dopamine,
but it turns out that this particular gut microbiota,
L. ruteri, can correct the social deficits
in this autism spectrum disorder model.
It does that by way of a vagal nerve pathway
that stimulates both dopamine release and oxytocin release.
And they established this really mechanistically
by showing, for instance,
if you get rid of the oxytocin receptor,
you don’t see this rescue.
Now those are mouse models,
so we have to take those with the appropriate grain of salt,
but they’re really exciting.
And they come to us in parallel with other studies
that are being done, taking the microbiomes of people
who have one condition or lack of condition
and putting it into people who have one condition
or another condition.
Let me explain what I mean by that.
The early discovery of the gut microbiome
and its potential to impact health
was not in the context of the gut to brain pathway,
but rather it was in the context of colitis.
This dates back to studies in the 50s,
whereby people with very severe intractable colitis
for which no other treatment was going to work
received fecal transplants.
So yes, that’s exactly as it sounds.
Taking the stool of healthy people
who do not have colitis,
transplanting those stools into the lower digestive tract
of people who do have colitis,
and they saw a significant improvement
if not rescue of the colitis.
That was one of the first indications
that something within stool of all things
could actually rescue another individual from disease,
which sounds kind of wild and crazy
and may even sound disgusting to some of you.
But as I mentioned at the beginning of the episode,
almost 60% of stool is live or dead bacteria, microbiota.
And it really opened up this entire field
of exploring how different microbiota
might have therapeutic effects.
And indeed that has been shown to be the case
also in fecal transplants for certain psychiatric illnesses.
These are still ongoing studies.
They vary in quality.
These are hard studies to do for all sorts of reasons,
getting the appropriate patient populations,
getting agreement, et cetera,
making sure that everything’s handled properly.
But what this involves is fecal transplants
from individuals that lack a particular
psychiatric condition or metabolic condition
into people who have a particular metabolic condition.
And there has been tremendous success in some cases.
One of the more powerful and salient examples
is for obesity.
There are some people for which,
even if they ingest very low numbers of calories,
even if they go on a liquid protein diet,
simply can’t lose weight.
These are somewhat rare disorders,
but these are people that would either do,
get gastric bypass surgery.
Some people are now getting these fecal transplants
from people that have healthy weight
and they take the stool from them.
They put it into lower digestive tract
and they can see substantial improvement in weight loss
in people that were otherwise unable to do that.
In some cases, actually,
they can start eating relatively normal levels of food
and still lose weight.
So pretty remarkable.
And that tells us there’s something in these microbiota
that’s really powerful.
Now, how those effects are generated isn’t clear.
One idea is that it’s impacting the metabolome,
components of the metabolism.
Almost certainly, that’s going to be the case.
Another idea is that it’s impacting neurotransmitters,
which change behavior and food choices within the brain.
Although, as I mentioned,
some of these people are already eating
very little food to begin with.
So that’s a little bit harder of an argument to create.
There are also some somewhat famous examples now
of how fecal transplants can lead to negative outcomes.
But those negative outcomes further underscore
the power of the microbiome in impacting bodily health.
One key example of this, for instance,
is transfer of fecal matter into another person
in order to treat something like colitis.
And it effectively does that.
But if the donor of the stool of the fecal matter
happened to be obese or have some other metabolic syndrome,
it’s been observed that the recipient
can also develop that metabolic syndrome
simply by way of receiving
that donor’s particular microbiota.
So these microbiota can create positive outcomes
or they can create negative outcomes.
Now, most of us, of course, are not interested in
or pursuing fecal transplants.
Most people are interested
in just creating a healthy gut microbiome environment
for sake of immune system and brain function.
And we will talk about how to do that
in just a few minutes.
But I just want to further underscore
the power of the microbiota in shaping brain chemistry
and in shaping things like mood
or other aspects of mental health
that typically we don’t associate with our gut.
There are several studies published in recent years.
One that I’ll just highlight now, first author,
it’s Tanya Nguyen, N-G-U-Y-E-N.
The title of the paper is
Association of Loneliness and Wisdom
with Gut Microbial Diversity and Composition,
an exploratory study.
It’s an interesting study,
looked at 184 community dwelling adults, excuse me,
ranging from 28 to 97 years old.
They explored whether or not
having enhanced microbial diversity
somehow related to these variables
that they refer to as loneliness and wisdom.
They used a number of different tests to evaluate those.
Those are common tests in the psychology literature,
not so much in the biology literature,
but nonetheless, there are ways of measuring
things like loneliness and wisdom.
Wisdom, in this case, being the opposite of loneliness,
at least in the context of this study.
And what they found was the more microbial diversity,
the more diverse one’s microbiome was,
the lower incidence of loneliness.
And they did this by taking fecal samples,
profiling them for RNA,
so essentially doing gene sequencing of the stool
of these individuals,
getting ratings of how lonely or not lonely they felt
and correlating those.
And that’s just but one study.
I pointed out because it’s particularly recent
and it looked like it was particularly well done.
There is another study that I’ll just refer you to.
This was a study published in 2020 in Scientific Reports.
The title of the study is
Emotional Wellbeing and Gut Microbiome Profiles
What I particularly like about this study
is that they were able to correlate the presence
of certain microbiota
with feelings of subjective wellbeing
and lack of or presence of depressive symptoms.
They did high throughput gene sequencing
of the microbiomes of individuals.
So that meant measuring the microbiota,
figuring out which microbiota were present,
how diverse their microbiome was in general.
Gut microbiome diversity is a good thing.
And then to correlate that with what’s called
the PANAS score.
PANAS stands for positive affect, negative affect schedule.
This is a test that my lab has used extensively
that other labs use to evaluate mood and wellbeing.
And they defined what were called three enterotypes,
three different categories of people
that ate very different diets
that tended to fall into categories
of having more or fewer emotional symptoms
that were negative or more or fewer emotional symptoms
that were positive,
and whether or not they tend to be more depressed, anxious,
or have more stress-related behaviors, et cetera.
And what they were able to derive from this study
was some strong indications
about what types of things we should ingest in our diet,
maybe even certain things that we should avoid,
but certainly the types of things that we should ingest
that can enhance mood and wellbeing
and can tend to shift people away
from more depressive-like anxiety
and stress-related symptoms.
Before we get into what the particular food items were
that lend themselves to a healthy microbiome,
I want to raise a bigger
and perhaps more important issue,
which is what is a healthy microbiome?
I think if you asked any number of world experts,
and I certainly asked this of Dr. Sonnenberg,
what is a healthy microbiome?
They’re all going to tell you it’s a microbiome
that has a lot of diversity,
that includes a lot of different types of bacteria.
And that makes sense
because it logically would include the bacteria
that produce GABA and dopamine and serotonin
and that support the immune system
and do a number of different things.
But is it simply the case
that adding microbiota diversity is always a good thing?
Well, that doesn’t seem to be the case.
Probiotics and prebiotics,
both of which can enhance microbiota diversity,
can improve mood digestion, immune system, and so on.
That’s been established,
but it’s mainly been established
in the context of post-antibiotic treatment
or people that are recovering from illness
or people that have been very stressed
or have been dealing with all sorts of challenges,
mental or physical,
and they are an attempt to replenish the gut microbiome.
However, it’s also clear
that excessive microbiota brought about
by excessive intake of probiotics
can lead to things like brain fog.
There’s actually some good studies
that point to the fact that certain metabolites
of the microbiome,
certain chemicals produced in the gut and in the body
can actually lead to brain fog states.
This is thought to come about
through the lactate pathways of the gut
that can then impact the brain.
If you want to look more into this issue
of whether or not probiotics taken in excess, perhaps,
can lead to brain fog,
I’d encourage you to look at a particular paper.
This is a paper published
in Clinical and Translational Gastroenterology,
and the title of the paper
is Brain Fogginess, Gas, and Bloating,
A Link Between SIBO, Probiotics, and Metabolic Acidosis.
It was published in 2018.
We can provide a link to this study.
And there are several other studies in the references
that point to the fact that, in some cases,
excessive intake of probiotics
and excessive proliferation of gut microbiota
can actually be problematic.
I mention this not to confuse you,
but because it is confusing out there.
We all would think that just increasing microbiota diversity
is always a good thing,
but there are thresholds beyond
which excessive microbiota diversity might be problematic.
I think everyone agrees
that having too few microbial species living in us
is not a good idea.
Now, none of that answers the questions
that I think everyone really wants answers to,
which are, what should we do,
what should we not do to improve our gut microbiome?
I mean, clearly, we can’t time travel back
to when we were zero to three years old
and get a dog if we didn’t have a dog,
get breastfed if we weren’t breastfed,
be delivered vaginally as opposed to by C-section
if we didn’t have that opportunity.
We just can’t time travel and do that.
All of us, however, should be seeking
to improve the conditions of our gut microbiome
because of the critical ways
in which it impacts the rest of our brain and bodily health.
So what should we do?
What shouldn’t we do?
Clearly, we know that stress
can negatively impact the gut microbiome.
However, some forms of stress
that can quote unquote negatively impact the microbiome
include fasting, long periods of fast,
which makes sense because a lot of microbiota need food
in order to thrive.
In fact, many, if not all of them do at some point.
There are other questions such as,
should we eat particular foods
and how often should we eat those foods?
We’ve all been told that fiber is incredibly important
because of the presence of prebiotic fiber,
which can essentially feed the microbiome,
but is fiber really necessary
and how necessary is it to encourage
a healthy microbiome?
Clearly, there are a number of people
following relatively low fiber diets,
such as ketogenic diets,
and those can have, in some cases,
and can sometimes also improve certain microbiota species.
So it can all be rather confusing.
And for that matter, I asked our resident expert,
Dr. Justin Sonnenberg at Stanford, all of these questions,
and he answers them very systematically
in the episode that comes out after this one.
But I don’t want to withhold anything from you,
so I’ll just give a very top contour version
of those answers,
and then you’ll get more in-depth answers
during that episode.
I asked about fasting.
And the reason I asked about fasting
is that years ago, I was at a meeting
as part of the Pew Biomedical Scholars meeting,
and one of the other Pew Biomedical Scholars
was an expert in gut microbiome.
And I said, hey, are probiotics good for the microbiome?
And if so, which one should I take?
And his answer was very interesting.
He said, you know, in certain cases they can be,
especially if you’re traveling or you’re stressed,
but it turns out that the particular bacteria
that they put in most probiotics
don’t actually replenish the microbiota that you need most.
And I thought, oh, well, why don’t they make ones
that replenish the microbiota that you need most?
And his answer was, well, they don’t replenish those,
but they replenish other ones
that then in turn encourage the development
of the microbiota that you do want
once you start eating the appropriate foods.
So they change the environment,
which makes the environment better,
which indirectly supports the proliferation
of quote-unquote good microbiota.
Okay, so that was a somewhat convoluted answer,
but I did appreciate his answer.
Then I asked him about fasting.
I said, well, a lot of people are getting interested
in intermittent fasting now.
People are spending a significant portion
of each 24-hour cycle avoiding food
for sake of time-restricted feeding.
What does that do to the gut microbiome?
Does it make it healthier or does it make it unhealthier?
Well, my colleague from Yale and Dr. Sonnenberg
both confirmed that during periods of fasting,
especially prolonged periods of fasting,
we actually start to digest away
much of our digestive tract.
Now, the whole thing doesn’t start to disappear,
but there’s thinning of the mucosal lining
or at least disruption of the mucosal lining.
A lot of the microbiota species can start to die off.
And so it was surprising to me,
but nonetheless interesting that fasting
may actually cause a disruption
to certain healthy elements of the gut microbiome.
But again, there’s a caveat.
The caveat is that when people eat after a period of fast,
there may be a compensatory proliferation,
meaning an increase in healthy gut microbiota.
So you start to get the picture
that fasting is neither good nor bad.
You start to get the picture that particular diets,
meaning certain restriction diets
or macronutrient-rich diets
may not be good or bad for the microbiome.
And yet there are some answers that arrived to us
from Dr. Sonnenberg, but from other experts in the field,
that there are certain foods
and certain things that we can ingest
which definitely enhance the microbiome
and make it healthier than it would be
were we to not ingest those foods.
So next I’d like to talk about
what I think is a really pioneering
and important study in this area.
This is a study that was carried out by the Sonnenberg lab
in collaboration with Chris Gardner’s lab,
also at Stanford,
where they compared two general types of diets in humans,
diets that were fiber-rich,
which has been proposed time and time again
to enhance microbiota diversity
and to enhance gut-brain signaling even
and to enhance the immune system, perhaps,
and diets that were enriched
in so-called low-sugar fermented foods.
Before I dive into that study
and what the conclusions were,
because they are very interesting
and very actionable for all of us,
I do want to touch on probiotics
because I want to avoid confusion.
It is not the case that ingestion of probiotics
will always lead to brain fog.
I want to make that clear.
It is the case that ingestion of probiotics,
even if those probiotics don’t directly contain
the microbiota species that one is trying to proliferate,
can be useful for improving microbiota diversity.
In general, it seems that maintaining
a healthy gut microbiome involves ingesting
certain types of foods,
and we’ll talk about those in a moment,
but perhaps also augmenting the microbiota system
through prebiotics or probiotics
at a fairly low level on a consistent basis.
So these are not high-dose probiotics,
except under conditions of dysbiosis,
where, for instance,
if somebody has done a round of antibiotics
and they need to replenish their gut microbiome,
there are foods and there are pill form
and powder form prebiotics and probiotics
that can be very useful.
Or in cases where people have been very stressed
or are undergoing excessive travel
or have shifted their diet radically,
maybe that’s due to travel,
maybe that’s due to illness,
maybe that’s due to stress,
but when there are a number of different converging events
that are stressing or depleting microbiota diversity,
that’s when, at least I believe,
it can be useful to support the gut microbiome
through the ingestion of quality probiotics or prebiotics.
So it would be under conditions
where people are stressed
or their system is generally stressed
for environmental or illness-related reasons
that it might be useful to lean towards higher doses
of prebiotics or probiotics than one might normally use,
but that under normal conditions
that one would focus on quality nutrients
through diet and focus on ingestion of probiotics
at a fairly low to moderate level
and or prebiotics at a fairly low to moderate level.
That just seems like the logical approach
based on the experts that I’ve spoken to,
but certainly if your doctor prescribes
or suggests that you take high levels of probiotics
for any reason,
you should definitely pay attention to your physician
and you should obviously pay attention to your physician
in any case, you should never add or remove anything
from your nutritional plan or supplementation plan
without consulting a physician.
So what should we do in order to maximize the health
of our gut brain axis as it’s called?
How should we support the diversity of the good microbiota
that help us create all these neurotransmitters
that we want, improve our immune system function
and so on and so forth?
Well, some of that is going to be through the basics.
When I say the basics,
I mean the foundational things
that really set us up for overall health.
So this is going to be getting deep sleep
of sufficient duration, 80 plus percent of the time.
I mean, if you could get a hundred percent of the time,
that’d be great, but very few people accomplish that.
It’s going to be proper hydration.
It’s going to be proper social interactions.
It’s going to be proper nutrition.
And we’ll talk more about nutrition in a moment.
It’s going to be limiting excessive prolonged stressors
And indeed we’ve done episodes
about just about all of those things,
but certainly about stress.
We have an episode of the Huberman Lab podcast
that you can find at hubermanlab.com
all about mastering stress,
how to avoid long periods of intense stress,
what to do to offset those.
Given that stress can disrupt the microbiome,
whether or not you’re fasting or not,
those tools ought to be useful.
Now, in what I consider to be a landmark study
exploring the relationship between the gut microbiome,
food intake and overall health
is this paper from Justin Sonnenberg’s lab
and Chris Gardner’s lab, both of which are at Stanford.
And the paper entitled
Gut Microbiota-Targeted Diets Modulate Human Immune Status
was published in the journal Cell,
which is among the three top journals,
perhaps in the world, Nature Science and Cell,
really being the apex journals for overall science
and especially for biomedical sciences.
Now, this is a very interesting study.
It was done on humans.
There were two major groups.
One group of humans was instructed
to increase the amount of fiber in their diet.
And in fact, ate a high fiber diet.
The other group was instructed
to eat a high fermented food diet.
Now, both groups started off
not having eaten a lot of fiber or a lot of fermented foods,
and were told to increase the amount of either fiber
or fermented foods that they were ingesting
over a four-week ramp up period.
And that was to avoid any major gastric distress.
It turns out that if you’re not already accustomed
to eating a lot of fiber,
increasing your amount of fiber dramatically
can cause some gastric distress.
But if you ease into it over time, as we’ll see,
there’s a mechanism behind this,
which was unveiled in this study.
But if you ease into it over time,
then the system can tolerate it.
Likewise, high fermented foods can be readily tolerated
if there’s a ramp up phase of ingesting
maybe one serving a day, then maybe two servings,
and ramping up, in this case,
as high as six servings per day.
However, after this ramp up period,
the group assigned to the high fiber condition
maintained high fiber intake for six weeks,
and the high fermented food group
maintained high fermented food intake for six weeks,
after which they went off either the high fiber
or the high fermented food diet,
and there was a four-week follow-up period
during which they gradually returned to baseline.
Throughout the study, their gut microbiome
was evaluated for the diversity of gut microbiota,
and there were also a number of measures
of immune system function,
in particular, measures of the so-called inflammatome.
The immune system has a lot of different molecules involved.
I did a whole episode about the immune system.
If you’re interested in learning
what some of those molecules are,
various cytokines and signaling molecules
that reflect either high inflammation states
or reduced inflammation states in the brain and body,
you’re welcome to check out that episode.
It’s also at hubermanlab.com.
Regardless, in this study,
they explored the sorts of immune markers
that were expressed in either of the two groups
and compared those.
The basic takeaway of this paper
was that contrary to what they predicted,
the high fiber diet did not lead
to increased microbiota diversity,
at least not in all cases,
and that was somewhat surprising.
The idea is that prebiotic fiber
and a lot of the material in fruits and vegetables
and grains and so forth
are supposed to support microbiota diversity
and the proliferation of existing microbiota,
and that is not what they observed,
although I want to be very clear in pointing out
that the results did not indicate
that fiber is not useful for health overall,
but it does point to the fact
that increasing fiber intake
did not increase microbiota diversity,
which in general, as I mentioned before,
is associated with improvements in microbiota function,
health, and overall wellbeing.
Now, the high fermented food diet condition
was very interesting.
It resulted in increased microbiome diversity
and decreased inflammatory signals and activity.
So there was a twofer.
Basically, by ingesting high fermented foods
in fair abundance, right,
you know, four to six servings or more per day
is a lot of fermented food intake.
We’ll talk about what some of those foods were,
but the outcome was very positive.
There was a clear increase in microbiome diversity
and decreased inflammatory signals.
So things like interleukin-6,
a number of other interleukins and cytokines
that are associated with increased inflammation
in the brain and body were reduced significantly.
Now, let’s talk a little bit about this notion
of number of servings, et cetera.
One somewhat minor point of the study,
but I think is useful in terms of
taking an actionable stance with this,
is that the number of servings of fermented foods
was not as strong a predictor of improvements
in the inflammatome, meaning reduced inflammation,
and improvements in microbiota diversity,
as was the duration of time
that the individuals were ingesting fermented foods.
In other words, the longer that one
is consistently ingesting fermented foods on a daily basis,
the better the outcomes in terms of the gut microbiome
and for reducing inflammation.
So I think that’s an important point.
And I make that point,
especially because for a lot of people,
even if you do this ramp up phase,
six servings per day of fermented foods
can seem like quite a lot.
So what are these fermented foods, right?
I think many of us are familiar with certain cheeses
and being fermented and beer being fermented
and kombucha is fermented.
In this study, they focus specifically
on low sugar fermented foods.
So this would be plain yogurt,
in some cases, kimchi or sauerkraut.
An important consideration, however,
is that it needs to contain
what are called live active cultures,
which means there actually have to be microbiota
that are alive inside the sauerkraut.
One way you know whether or not that’s happening
is if you purchase sauerkraut or pickles or kimchi
from a jar or a container
that’s on the non-refrigerated shelf,
or the non-refrigerated section of your grocery store,
it is not going to contain live active cultures
And likewise, if you consume yogurt
that has a lot of sugar or other components added to it,
it’s not going to have the same positive effect
on the microbiome, at least that’s the prediction,
given some of the relationship
between the sorts of microbiota that live in sugar
versus plain type yogurts.
They gave people the option of consuming
any number of different low sugar fermented foods
so that again, that could be sauerkraut, kimchi,
things like kefir, natto.
In Japan, they consume natto, which is a fermented food.
Beer was not one of the fermented foods
that was included in the fermented food list.
And when we say six servings per day,
that is indeed six ounce servings
or four to six ounce servings.
It was not six servings of what’s listed on the package.
So again, that turns out to be
a fair amount of fermented foods.
How should you gauge
whether or not you’re getting enough of this?
Well, if you decide to take on this protocol
of ingesting more fermented foods,
which at least by my read of this study
and some of the followup work that’s being done,
sounds like a terrific idea.
If you want to improve your gut microbiome
for all the great reasons that one would want to,
brain, body health, reduced inflammation and on and on,
well then you definitely want to focus on fermented foods
that you enjoy consuming.
So for you, if that’s kefir or for you that’s plain yogurt
or for you that’s sauerkraut,
which happens to be my personal favorite,
then you want to make sure that it’s going to be something
that you are going to enjoy ingesting quite a lot of
and that you’re going to be okay with ingesting
probably throughout the day.
Now people follow different meal schedules, of course,
but this does require not just eating
all the fermented foods just before bedtime or at one meal.
I suppose you could do that,
but in general, it’s going to work best
in terms of limiting gastric distress
by spreading it out throughout the day.
I also want to mention brine.
Brine is the liquid that surrounds sauerkraut.
It’s that very salty fluid.
And that contains a lot of active live cultures.
And they did include,
or they allowed people to include brine in this study.
And in discussions with Dr. Sonnenberg,
which we’ll go into in more detail on the episode
that comes out next week,
we talk a lot about the particular value
that brine might hold in terms of bringing about
microbiota diversity because of the richness
of live cultures that it contains.
I do want to focus for a moment on the high fiber condition
because there were some interesting observations
about the people that were placed into that condition.
First of all, increasing the amount of fiber
definitely increased the number of enzymes
that can be used to digest fiber.
This is in keeping with this idea of this ramp up phase
where accumulation of more fiber intake
can over time lead to less gastric distress,
but also to more utilization of fiber,
which overall should be a good thing.
So while they didn’t observe an increase
in immune system function
or an increase in microbiota diversity,
there was an increase in these fiber digesting enzymes.
They also observed what they called
personalized immune responses.
These were some subgroups within the high fiber group
that had interesting changes in terms of their reactions to,
or I should say their inflammatome,
meaning the inflammatory markers they expressed
as well as their microbiota diversity.
So there were essentially three groups.
One group actually showed an increase
in inflammatory markers, so that was quite surprising
and probably not wonderful for the message
that fiber is always good for us,
but that was a small cohort within the fiber intake group.
Another group and still another group
both showed reductions in baseline microbiota diversity,
although to varying degrees.
So I don’t want to paint the picture that fiber is bad,
but fiber certainly did not have the positive effects
on microbiota diversity
that the high fermented food diet did.
So my read of this study,
and I think the stance that many others have taken
as a consequence of these data
is that we should be increasing our fermented food intake,
that that’s simply a good thing to do
in order to support our gut microbiome
and to reduce inflammatory signals in our brain and body.
And there are a number of different ways to do that.
I mentioned some of the particular foods.
However, anytime you’re talking
about ingesting fermented foods,
especially the high quality ones
that come from the refrigerated section of the grocery store
or that end that have low sugar content, et cetera,
we do have to be considerate of cost
because certain things like kombuchas, for instance,
can be quite costly.
I should also mention some kombuchas
actually contain alcohol, some do not,
or contain very little amounts of alcohol.
One way to avoid the high cost of fermented foods
while still being able to accumulate
a lot of fermented food intake
is to simply make those fermented foods yourself.
And this is something that we’ve started exploring
and experimenting with in our home.
One simple way to do this
is to just make your own sauerkraut.
It involves very few ingredients.
It basically involves cabbage, water, and salt,
but there’s a specific process that you need to follow
in order to create these large volumes of sauerkraut at home
using that low cost method.
The best resource that I know of
in order to follow a great recipe
to make homemade sauerkraut
would be the recipe for homemade sauerkraut
that’s contained in Tim Ferriss’ book,
The 4-Hour Chef.
There’s an excellent protocol there.
It involves chopping up the cabbage,
putting into a bowl, mashing it up with your hands,
which can be fun, putting water in there,
some salt, covering it,
and then keeping it in a particular environment,
and then routinely scraping off
some of the material from the surface.
You have to do that in order to make sure
that you’re not getting microbes and things growing in it
that are bad for you.
So you definitely want to pay careful attention
to the protocol,
but that’s a very, very low cost way
of generating lots and lots of fermented food
so you don’t go broke trying to improve your microbiome.
The other thing that you can do
if you’re really obsessed with kombucha
or something like that to avoid the high cost of kombucha
is there are ways that you can get the SCOBY,
which basically allows you to make your own kombucha at home.
I’ve never tried this, but when I was a postdoc,
there was an undergraduate in the lab,
I think, well, I won’t out him,
but he’s now gone on to medical school,
and I think he’s passed his residency
and is a practicing doctor,
but nonetheless, he was always making kombucha at home.
He told me it was exceedingly easy,
but then again, he had a number of other skills
and attributes that made me think
that he could do pretty much anything with ease,
whereas I tend to struggle with even basic cooking.
So maybe if you’re feeling a little more adventurous,
you could explore making your own kombucha,
but there are a number of different protocols
and recipes out there
for making your own low sugar fermented foods.
So you needn’t run out and buy fresh sauerkraut
all the time.
I should also mention for those of you
that are interested in getting your fermented intake
from pickles, jarred pickles rarely,
if ever, contain ferment.
Mostly they’re just soaked in vinegar water
and with some spices,
but there are some that contain ferment.
You actually have to look for that on the container.
And I don’t know, maybe someone out there
knows how to make natto and knows how to make kimchi well
and things of that sort.
It certainly is the case based on the data from the study
that ingesting more servings of fermented food per day
ought to be beneficial for our gut microbiome.
And since this is an episode, not just about gut microbiome,
but gut brain health,
I should mention that one form of signaling
between the gut microbiome and the brain,
which we did not discuss, and I’ll just touch on briefly,
is that when the inflammatome
or the genes and markers of inflammation
are kept in a healthy range,
there’s an active signaling
of that immune system status to the brain.
There’s an intermediate cell type
that communicates immune status to the brain.
And that cell type is the microglial cell.
It’s a type of glia, as the name suggests.
When there’s a lot of inflammation in the body,
these microglia actually get activated
and can start eating away at various components
of the brain and nervous system.
And I don’t mean massive eating away.
They’re not going to digest the whole brain,
but these microglia are sort of the resident macrophages
of the brain.
Macrophages are in the periphery
and they gobble up debris and things of that sort.
The microglia on a regular basis are eating up debris
that accumulates across waking cycles
and in response to micro damage of the brain
that occurs on a daily basis.
So they have a lot of important basic everyday,
what we call housekeeping functions.
But when there’s a lot of inflammation in the body,
when there’s a massive immune response,
the microglia can be hyperactivated.
And that’s thought to lead to any number
of different cognitive defects or challenges,
thinking, or maybe even some forms
of neurodegeneration over time.
Although that last point is more of a hypothesis
than a well tamped down fact at this point.
There’s still a lot of investigation to be done in humans.
The animal data, however, are very, very strong
that when the immune system is activated
or chronically activated or hyperactivated,
that neural tissue, meaning brain tissue
and other central nervous system tissue can suffer.
So there are a lot of reasons to want
to not just improve microbiome diversity,
but to also improve immune system function
and to limit the number of inflammatory markers
that are present in the body because of the way
those inflammatory markers can signal
deleterious events in the brain.
And while eating fermented foods
and making your own fermented foods
and buying high quality fermented foods
might seem like an inconvenience,
I would say that from the perspective
of cost benefit or effort benefit,
it’s actually quite a good situation
where if you can just ramp up the number of fermented foods
or servings of fermented foods that you’re eating per day
over a period of a few weeks
so that you’re tolerating that well,
that ought to have a very positive effect
on your microbiome diversity
and indeed on gut brain function.
And I’ll be the last to suggest
that people completely forego on fiber.
I think there’s some debate out there
as to how much fiber we need
and whether or not certain forms of fiber
are better than others.
I’m not going to get into that debate.
It’s barbed wire enough without me injecting
my own views into that debate.
But I think there’s ample evidence
to support the fact that for most people,
ingesting a fair amount of fiber is going to be a good idea.
I would just say that make sure that you’re also
ingesting a fair amount of fermented foods.
And along the lines of fiber
in an accompanying article published in Cell,
which was sort of a, what we call a news and views piece
about the Sonnenberg and Gardner paper,
they make a quite good point,
which is that the increase in fiber intake
that led to this increase in carbohydrate active enzymes,
these C-A-Z zymes, as they’re called,
these are enzymes that help digest fiber,
quote, indicating an enhanced capacity for the microbiome
to degrade complex carbohydrates present in fibrous foods.
So in other words, eating more fiber and fibrous foods
allowed for an increase in these enzymes
that allow you to eat still more fibrous foods
or to better digest fibrous foods
that are coming in through other sources.
So there is at least one utility for increasing fiber,
even though it’s separate from the gut microbiota diversity
and reducing inflammation.
And I’d be remiss if I didn’t touch on some of the data
and controversy about artificial sweeteners
and the gut microbiome.
I want to be very clear that what I’m about to tell you
has only been established in animal models,
in a mouse model, at least to my knowledge.
What the studies have shown, and there were several,
but one published in the journal Nature a few years back
is the one that got the most amount of attention,
is that animals that consume large amounts
of artificial sweeteners, in particular,
things like saccharin or sucralose,
show disruptions in their gut microbiome.
I’m not aware of any studies in humans
that show the equivalent effect,
and I’m not aware of any studies in humans
that show the equivalent effect
for things like plant-based low-calorie sweeteners,
things like stevia, monk fruit, and things of that sort.
And at least by my exploration,
I couldn’t find any data specifically related
to the sweetener aspartame.
So right now it’s somewhat controversial,
and actually this is kind of a third rail topic out there
when one group will come out saying
that artificial sweeteners are bad
because they disrupt the gut microbiome.
The response generally from a number of people as well,
that’s only been shown in animal models,
and indeed that’s true.
So right now I don’t think that there’s a strong case
one way or the other.
I think that people should basically ask themselves
whether or not they like artificial sweeteners or not,
whether or not they’re willing to risk it or not,
and obviously that’s an individual choice.
I also want to point out a recent study
from Diego Borges’ lab, which actually shows, however,
that neurons in the gut, those neuropod cells,
are actually capable of distinguishing
between real sugars and artificial sweeteners.
This is a really interesting body of work.
It was published just recently, I should say, February 2022.
The title of the paper is
the preference for sugar over sweetener
depends on a gut sensor cell.
And to make a long story short,
what they showed was there’s a category of neuropod cells
that recognize sugar in the gut
and signal that information
about the presence of sugar in the gut to the brain
via the pathways we talked about before,
the no-dose ganglia, the vagus, dopamine, et cetera, et cetera.
Interestingly, the very same category of neurons
can respond to artificial sweeteners
and signal that information to the brain,
but the pattern of signaling and indeed the signature pattern
that is conveyed to the brain and received by the brain
is actually quite a bit different
when these same neurons are responding
to artificial sweeteners versus actual sugar.
This is very interesting because what it means
is first of all, that neurons have incredible specificity
in terms of what they are signaling
from the gut to the brain.
And it also means that there may be a particular signal
that the brain receives that says,
I’m receiving some intake of food or drink that tastes sweet
but doesn’t actually offer much nutrients
in the direction of sweetness,
meaning that it doesn’t have calories despite being sweet.
Now, again, this is all subconscious processing.
And like with the previous studies,
we were just discussing about artificial sweeteners
generally and the gut microbiome generally,
it’s unclear how this relates to humans
at this point in time.
But given the similarity of cellular processes
and molecular processes at the level of gut brain in mice,
I think it stands to reason that these neuropod cells
very likely are capable of signaling presence
of real sweetener versus artificial sweetener
in humans as well,
although that still remains to be determined empirically.
So I’d like to just briefly recap what I’ve covered today.
I started off by talking about the structure and function
of the gut brain axis.
I described the basic structure and function
of the digestive pathway
and how that digestive pathway harbors microbiota species,
meaning many, many little bacteria
that can signal all sorts of things
to the rest of the brain and body.
And indeed, we talked about the various ways
that they do that.
We talked about direct pathways,
literally nerve networks that extend from the gut
up to the brain and from the brain back to the gut.
And we talked about indirect pathways,
how some of the gut microbiota
can actually synthesize neurotransmitters
that get out into the bloodstream, can impact the body,
can impact the immune system,
and can get into the brain
and act as neurotransmitters in the brain,
just as would neurotransmitters
that originate from within the brain.
We also talked about what constitutes
a healthy versus unhealthy microbiome.
And it’s very clear that having a diverse microbiome
is healthier than having a non-diverse microbiome.
But as I pointed out,
there’s still a lot of questions
as to exactly what microbiota species you want to enhance
and which ones you want to suppress in the gut
in order to achieve the best gut-brain axis function.
We talked about how things like fasting
might impact the microbiome
and how some of that might be a little bit counterintuitive
based on some of the other positive effects of fasting.
Or if we’re not just discussing fasting,
some other types of somewhat restrictive diets,
either restrictive in time
in terms of macronutrient intake,
how those may or may not improve
the health of the gut microbiome.
And the basic takeaway was that
because we don’t know exactly
how specific diets impact the gut microbiome,
and we don’t know how fasting
either promotes or degrades the microbiome,
we really can’t say whether or not
they are improving or degrading the microbiome at this time.
However, it is clear that stress,
in particular chronic stress,
can disrupt the gut microbiome.
It’s also clear, of course,
that antibiotics can disrupt the gut microbiome.
And that brings us to the topic
of prebiotics and probiotics.
And I emphasize the fact that for most people,
ingesting high quality non-processed foods
that include some prebiotic fiber,
but also that include some probiotics
will probably be healthy,
but not excessive levels of probiotics.
High levels of supplemented probiotics
of the sort that would come in a probiotic pill
or even prescription probiotics
would probably lend themselves best
to when people were under severe chronic stress
or had just come off a serious round
or an ongoing or repeated rounds of antibiotics.
That does not mean that ingesting probiotics
in any form or any kind is not good.
It just means that the very high dose probiotics,
again, typically found in prescription form
or capsule pill form,
probably are best reserved to cases
where, of course, your doctor prescribes them.
You should always follow your doctor’s advice.
But in cases where perhaps you are jet lagged,
you’re traveling excessively for any reason
or working excessively, you’re not getting enough sleep,
or your diet has radically changed from normal.
And we talked about how increasing the amount of fiber
in your diet might be useful
for increasing fiber digesting enzymes
and the assimilation of fibrous foods,
but that it’s really the ingestion of fermented foods.
And in fact, getting anywhere from four
or even up to six servings a day of fermented foods
can be immensely beneficial
for reducing inflammatory markers in the body
and for improving microbiota diversity all along the gut
and thereby improving signaling
and outcomes along the gut-brain axis.
So we went all the way from structure to function
to the four kinds of signaling,
mechanical, chemical, indirect-direct,
probiotics, fiber, and fermented foods.
And I tossed in a little bit at the end there
also about ways that you can make
your own fermented foods at home
in order to try and offset some of the costs.
Also, it’s just kind of fun to do.
And some of those actually taste quite good.
I’ve actually found that the fermented sauerkraut
that we’re making at home actually rivals the sauerkraut
that you can buy out of the refrigerated section
at the grocery store.
And I am by no means a skilled cook or chef
and basically have no culinary skill whatsoever.
So if I can do it, you can do it.
I hope you found this information useful
and perhaps also actionable.
One of my motivations for doing this episode was,
again, as a primer for the episode
with Dr. Justin Sonnenberg,
where we go really deep into the gut microbiome,
less so into the gut-brain axis,
but really deep into the gut microbiome,
what it is, what it does, what it doesn’t do,
and some of the emerging findings from his lab
that are yet to be published.
And I also was excited to do this episode
because I think many of us have heard
about the gut microbiome.
We hear about these bacteria that live in our gut.
We hear about the gut-brain axis
or that 90% or more of the serotonin
that we make is made in our gut.
We hear about the gut as a second brain and so forth.
But I think for many people,
they don’t really have a clear picture
of what the gut microbiome is
and the pathways and mechanisms
by which it can signal to the brain
and to the other parts of the body.
So I hope that today’s information
at least improved the clarity around that topic
and leaves you with a more vivid picture
of this incredible system that is our gut-brain axis.
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