Our Episode

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 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 to 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 Sonnenburg
from Stanford University.

Dr.

Sonnenburg 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.

Sonnenburg.

Before we begin,
I’d like to emphasize that this podcast
is separate from my teaching
and research roles at Stanford.

It is however, part of
my desire and effort
to bring zero cost to consumer information
about science and science-related tools
to the general public.

In keeping with that theme,
I’d like to thank the
sponsors of today’s podcast.

Our first sponsor is Athletic Greens.

Athletic Greens is an all-in-one
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I’ve been using Athletic Greens,
which is now called AG1, since 2012
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The reason I started
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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, you know, 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 bidirectional.

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 am 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 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’d 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 as 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, these bacteria.

In fact, right now you
are carrying with you
about two to three kilograms,
so that’s more than six pounds,
of these microbiota, these bacteria.

And if we were to look at
them under a microscope,
what we would see
is these are relatively
simple little organisms.

Some remain stationary
so they might plop down
into the mucosal lining
or they might hang out on
a particular microvilli
or they might be in one
of those little niches,
and others can move about,
but they basically fill the entire lumen.

They surround and kind of coat the surface
of the microvilli and they’re tucked up
into any of those little niches
that are available to them
to tuck into.

If you were to take the head of a pin
and look at it under the microscope,
you could fit many, many hundreds,
if not thousands or more of
these little 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 the 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,
contact sparse environment
and how that shapes your microbiome.

But the simple point is that what you eat
influences your microbiome,
but also what you do,
what you think, and what you feel,
and many of the low 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
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 microbacteria 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 all 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 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 cell, 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 on your
heart and 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 neuro 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 are watching this,
I’ll try and use my hands as a diagram
but really the best thing to do
if you want really want
to learn neuroanatomy
is to just imagine it in
your mind as best you can
and if you can track down
a picture of it, terrific,
but here’s how it works.

Neurons have a cell body
that we call a soma,
that’s where all the DNA are contained.

That’s where a lot of
the operating machinery
of the cells are contained
and a lot of the
instructions for that cell
of what to be and how to
operate are contained.

The cell bodies of these
neurons or the relevant neurons
are actually up near the neck.

So you can think of them
as a clump of grapes,
’cause cell bodies tend
to be round or oval-ish.

And then they send a
process that we call an axon
in one direction out to the gut
and they’ll send another
process up into the brain.

And that little cluster near the neck
that’s relevant here is called
the 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 Bohorquez lab has shown
is that these neuropod
cells are part of network.

They’re sensing several
different nutrients,
but in particular, when they sense 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 Bohorquez lab
has performed experiments
using modern methods and
they’re classic experiments
showing that animals and humans
will actively seek out more
of a particular sweet food
even if it bypasses this taste system.

And the reverse is also true.

There have been experiments
done in animals and in humans
that have allowed animals or humans
to select and eat sweet foods,
and indeed that’s what they do
if they’re given the option.

And yet to somehow eliminate
the activation of these neurons
within the gut that can sense sweet foods.

Now, there are a couple different ways
that those experiments ave been done.

In classic experiments
that date back to the ’80s,
this was done by what’s called
subdiaphragmatic vagotomy.

So this means cutting off
the branch of the vagus
that enervates 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 have 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 with neuromodulators,
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 nodose ganglion
that we talked about before
and through a number of different stations
in the brain stem,
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 1, 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 brain
stem autonomic center.

So it tends to make you feel alert
and quite, we say, high
levels of autonomic arousal.

If you haven’t eaten in a while,
you might think that you just
get really exhausted, right?

Because we all hear that food is energy
and caloric energy is
what we need to burn,
but you actually have a lot
of energy stored in your body
that you would be able to use
if you really needed energy.

But typically if we
haven’t eaten in a while,
we start to get agitated
and we get agitated by way 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 brain
stem 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
brains stem 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 of the hypothalamus,
they include a bunch of
other neurochemicals,
but the point is that
you’ve got a fast route
and a slow route to drive
you to eat more or eat less,
right, to seek out food and
consume it or to stop eating,
to essentially kickstart
the satiety mechanisms
as they’re called,
and those are operating in parallel.

It’s not like one happens first
then stops 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
health healthy digestion
and for healthy brain function.

I want to take a moment and talk
about glucagon-like peptide 1,
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,
one for instance goes
by the name semaglutide,
which is essentially an GLP-1 agonist.

It causes the release of more GLP-1.

It’s being used to treat type II diabetes,
which is insulin resistant diabetes.

This is different than type I 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 effect 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 adjusts 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, like semaglutide,
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 a hormone pathway
can impact the activity
of brain circuits that
are directly involved
in a particular behavior.

So yet another example of how
gut is communicating to brain
in order to change what we think we want
or to change what our
actual behaviors are.

So the next time you find
yourself reaching for food,
or you find yourself wanting
a particular sweet thing
or fatty thing or something that contains
a lot of amino acids,
a protein rich food,
keep in mind that that’s not just
about the taste of the food,
and it’s not even necessarily
about the nutrients
that you need or don’t need.

It could be,
but it’s also about this
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.

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 Bohorquez 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.

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
distension of the gut
and that doesn’t just have to
be distension of the stomach,
but distension of your intestines as well.

That distension is registered by neurons
that reside in your gut,
the signals go up to your brain,
and communicate with areas of the brain
that are responsible for suppressing
further consumption of food and/or fluid,
and, under certain circumstances,
can also be associated with the activation
of neural circuits that cause vomiting
or the desire to vomit.

So if ever you’ve eaten too
much or you’ve eaten something
that doesn’t agree with you,
that information is communicated
by way of 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 brain stem
that is affectionately referred to
as the vomit center among neuroanatomists.

This is a area that more appropriately
is called the chemoreceptor
trigger zone, the CTZ,
or area postrema
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 brain stem
that communicate with
neurons in the hypothalamus.

And, of course, those are
also going to interact
with neurons of the prefrontal cortex
which is the area of a brain
involved in decision making
the, you know, I think it was
the shrimp that made me sick.

I’m going to, I just don’t
want any more of that.

Or I’m never going back
to that restaurant again
because after I ate there
about an hour later,
I started feeling really not well.

I felt, you know, kind of feverish,
but my gut didn’t feel well,
my digestion was really off.

All of that kind of information
is handled in the prefrontal
cortex at a conscious level,
but the immediate decision to stop eating
or to eat more of something
to move towards something
or away from it, that’s
made by neural circuits
that reside at the, we would say,
the subconscious 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 and circuits
within the brain to cause you
to seek out more of something.

Now, in a very logically consistent way,
dopamine is also involved in
the whole business of vomiting.

You might think, well, that
doesn’t make any sense.

I thought dopamine was
always a good thing.

It’s involved in moderation
and reward, et cetera.

But it turns out the area postrema,
this vomit center in the brain stem,
is chockablock 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’s 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, area postrema,
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 area postrema
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.

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 particular
neurotransmitters.

For instance, the neuromodulator dopamine
can be synthesized
by or from bacillus and serratia.

Now, these are just names of microbiota.

I don’t expect that any of you
would necessarily recognize them.

These aren’t the sorts of
things that you necessarily
would run out and buy
to get more dopamine.

But the 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 transmitters 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 serratia 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,
streptococus, 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 it 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
neurocircuits 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.

Sonnenburg,
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 have 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 that 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’ll 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 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. reuteri,
it’s L.

R-E-U-T-E-R-I.

Treatment with L. reuteri
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. reuteri 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 establish this
really mechanistically
by showing, for instance,
if you get rid of the oxytocin receptor,
you don’t see this rescue.

Now, those are mouse models
so we have to take those with
the appropriate grain of salt,
but they’re really 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 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’s some people for
which even if they ingest
very low numbers of calories,
even if they go on a liquid protein diet,
simply can’t lose weight.

These are somewhat rare disorders
but these are people that would
either 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 is Tonya 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 point it 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 by Enterotype”.

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 to 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 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 ask
this of Dr.

Sonnenburg,
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
microbiotal 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
microbiotal diversity
is always a good thing
but there are thresholds
beyond which excessive
microbiotal 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 fasts,
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,
anti-inflammatory
effects 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 Sonnenburg 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 ones 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 restrictive 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.

Sonnenburg
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 the 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 arrive to us
from Dr.

Sonnenburg, 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 Sonnenburg 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
microbiotal 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
microbiotal 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 a 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 or stress.

And indeed we’ve done episodes about,
just about all of those things
but certainly about stress
we have an episode of
the 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 Sonnenburg’s
lab and Chris Gardner’s lab,
both of which are at Stanford.

And the paper entitled “Gut
Microbiome-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 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.

You know, 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
microbiotal 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 do
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 decrease 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?

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 of microbiota.

And likewise, if you consume yogurt
that has a lot of sugar or
other components added to it,
it’s not going to have
the same positive effect
on the microbiome,
at least that’s the prediction
given some of the relationship
between the sorts of
microbiota that live in sugar
versus plain type yogurts.

They gave people the option of consuming
any number of different
low-sugar fermented food.

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, six ounce servings,
or six, 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 follow up
work that’s being done,
sounds like a terrific idea
if you want to improve your gut microbiome
for all the great reasons
that one would want to,
brain-body health, reduced
inflammation, and on and on,
well then you definitely want to focus
on fermented foods that
you enjoy consuming.

So for you if that’s kefir,
or for you that’s plain yogurt,
or for you that’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.

Sonnenburg,
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.

There 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,
and 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’s 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 foods
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 post doc,
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 to 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 Sonnenburg and Gardner paper,
they make a quite good point,
which is that the increase in fiber intake
that led to the increase in
carbohydrate active enzymes,
these CAZymes 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 microbiotal 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 Bohorquez’s 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 now, 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 nodose 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.

And 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 sweet presence
of real sweetener versus
artificial sweetener
in humans as well,
although that still remains
to be determined empirically.

So I’d like to just briefly
recap what I’ve covered today.

I started off by talking about
the structure and function
of the gut-brain axis.

I described the basic
structure and function
of the digestive pathway,
and how that digestive pathway
harbors microbiotal 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 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 or restrictive
in terms of macronutrient intake,
how those may or may
not improve the health
of gut microbiome.

And the basic takeaway was
that because 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 emphasized the fact
that for most people,
ingesting high quality non-processed foods
that includes some prebiotic fiber
but also that includes 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 jetlagged,
you’re traveling
excessively for any reason,
or working excessively,
you’re not getting enough sleep,
or your diet is radically
changed from normal.

And we talked about how
increasing the amount of fiber
in your diet might be
useful for increasing
fiber digesting enzymes
and the assimilation
of fibrous foods
but that it’s really the
ingestion of fermented foods
and, in fact, getting anywhere from 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 Sonnenburg
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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