How to Enhance Your Gut Microbiome for Brain & Overall Health

[upbeat music] - 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.

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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.