Hi.
Good morning.
See, there were people there who said
hi, and those people said good morning.
Because in health optimization medicine
and practice, as you heard yesterday,
hi is always a four letter word.
Today we're talking about the
enderic microbiota gut brain
axis in the context of health
optimization medicine and practice.
Now, I'd like to disclose that I'm the
founder of both of these organizations,
Health Optimization Medicine and
Practice, which is a non profit.
We teach physicians health optimization
medicine and non physician healthcare
practitioners health optimization
practice on how to do health optimization.
And The products off descriptions LLC,
which is now held a company held by
smarter, not harder is actually to help
clinicians deal with more acute symptoms.
During a patient or client
care for example, anxiousness
and sleeplessness and pain.
And we are essentially the
main donors to Home Hope.
So that's a disclosure for me.
The general schema of everything
that we talk about is this,
is a enteric microbiota with
a bidirectional communication
with the gut and a bidirectional
communication with the organs.
So it's enteric microbiota
gut organ communication.
I actually created this slide
because I was made to lecture
on enteric microbiota gut lung.
Access during the beginning of
COVID and as you can see here there
is the common theme is that all of
these organs actually have malt.
And I don't mean whiskey because
in health optimization, we
have better drugs and alcohol.
So MALT stands for what?
Mucosa associated lymphoid tissue, right?
So you could see here whereas before
the other systems we should thought were
sterile, like the ureters, et cetera,
and placenta, they actually have a,
Microbiota now, as we have found out.
So after this lecture, you will be
able to discuss knowledgeably about
the fundamental structure functions
and new perspectives of the M.
G.
B.
Axis enumerate the bidirectional
communication pathways of the E.
M.
G.
B.
Axis mentally formed a framework.
Of HomeHope and its fundamental
role in caring for the EMGB
axis as a practitioner.
Be familiar with the technique of
detection and correction of imbalance
of HomeHope versus diagnosis and
treatment of disease of illness
medicine as applied to the EMGB axis.
Discuss knowledgeably about
the enteric microbiota brain
interactions, neuroinflammation,
and identify what's missing in
today's research on the EMGB axis.
And be up to date with the latest
developments in the EMGB axis.
Now, let's take the first part
of this, is the structure,
functions, and new perspectives.
You guys already can always Google
the structure and function, right?
What I'd like you to remember
from this section are really
the perspectives that you should
carry when you are in the clinic.
Let's take a look at a quick structure.
Many of you have more expertise
than I have in this area.
This is distribution of
microbial communities by weight.
As you can see, 78 percent
is in the GI tract.
And here's the distribution.
On the right side of the slide, where you
could see where the colon has 10 to the
11, jejunum 10 squared, and 10 to the 8.
So you could see where the
distributions are of the gut microbiota.
Now the important thing here is
to visualize it in several layers.
The gut microbiota actually
pre process all of your food.
Now, that's a key term here, is it pre
processes everything that you swallow
they try to pre process even non
edible things that you try to swallow.
So here after they pre process it
and it passes through the liver.
That's When you take an oral drug the
liver tries to either activate or detoxify
it however the drug is configured and
then those raw materials are now then fed
to the brain to the heart, the adipose
tissue, the muscle, kidneys, and so on.
All right, so the new perspective is the
enteric microbiota is a post natal organ.
Okay it's an organ that actually
appears and grows after birth, right?
It's seeded usually in spontaneous vaginal
delivery through the vaginal canal.
And as early as 2006, there
were already some publications
that is the forgotten organ.
Now, don't forget microbiota
is not foreign to you, right?
It is part of what grows in
you as an organ, except that it
only grows after you're born.
So here's a more recent, this is
2019 article, a representation
of the gut micro biota in terms
of prenatal, infancy, childhood,
adolescence, adulthood, and aging.
And you could see here on the lower
part what they're actually doing
right in helping to contribute.
Doing now of course the second part
that, that's your enteric microbiota.
Remember in, in old textbooks,
we just say gut-brain axis.
That's already old, right?
You have to specify enteric
microbiota, gut brain axis, right?
In order to be more specific, that the
microbiota itself is an organ in the body.
Now the gut is actually
a brain in itself, right?
It has the lumen, of course the
like the ventricles in the brain.
Myenteric plasters, which
is the main nervous.
system of the brain, which
we call actually the enteric
nervous system, right?
And then there's semicosal
plexus, and then the mesentery.
This is an old book that
actually popularized the idea
that it's the second brain.
For many people, in fact, it is the first
brain because evolutionarily, the brain is
actually a later development in evolution.
You had the gut first.
So the functions would be nutrient
absorption and immune defense, right?
And you could see here underneath
the intestinal lining, there
is the payers patches, right?
And there is the M cell or the micro
fold cell that proceeds it and of
course there's a lymphoid tissue
underneath and this is called the
induction path induction patch, right?
This is where most of the immune
system actually interacts with anything
that's in the gut lumen, right?
Now the new perspective that I'd
like you to take home with you is
that it's the largest immune organ.
When you were in med school,
it was a bone marrow, right?
But we have, in the last 15 years, we now
know it's the largest immune organ, right?
And you could see here the
distribution and with apologies
for those who love Ayn Rand, who is
GALT gut associated lymphoid tissue.
This makes up 70% of
the immune system now.
Let's go to the brain the third part
of the axis the brain we we we should
always take a look that we have two
brains and a single body, right?
Let's take a look at
the second brain first.
It has glial cells, 500 million neurons,
14 neurotransmitters that are identified
and produces 50 percent of all dopamine
and 95 percent of all serotonin.
Now, remember, these are not for the
brain in the central nervous system.
This is for its own use.
As a brain in itself, right?
So it's time for you to forget
the fact that, oh, are these
going to be used by the brain?
No, this is going to be used
by your second brain, right?
It is a brain in itself.
So these are its own neurotransmitters.
These are what it produces for
itself in order to function.
That's why I said it requires a
really, a shift in perspective
to treat it as a brain, right?
The other brain actually has
about 86 billion neurons.
And for those of you who are
curious, really 65 billion of those.
are contained in your cerebellum,
so you have really only very
few that are in your neocortex.
Now the the finding, of course this
was in, I think 2012, is that there's
a glymphatic system in the brain.
We used to think that there was no
lymphatic system in the brain at all,
and it turns out that the glial cells
actually form a perilymphatic space
or a perivascular space around the
blood vessels and actually cleans out
your brain, especially during sleep.
So this is a Nobel worthy development
that they actually saw that there is the
brain has actually a lymphatic system.
Now, the structure of the brain all of
us talk about the blood brain barrier as
if it were the only barrier of the brain.
It is not, right?
There are barriers at the surface of the
brain the arachnoid barrier There's a
blood CSF barrier closer to the cavities
of your brain called the ventricles.
And of course, there's
the blood brain barrier.
So all of these are actually significant
in what we're discussing today.
So when someone says blood brain
barrier, do you mean just the blood
brain barrier or do you mean the blood
cerebrospinal fluid barrier or the
barrier at the surface of the brain?
These are very important
distinctions to make.
Now the function of the brain is for
cognition and emotional regulation.
And is actually interesting.
Psychedelic research find the ego
exists in the default mode network.
This is a network that looks
like a butterfly like this.
It's composed of the posterior
cingulate gyrus, the prefrontal
cortex, angular gyri.
And you can see here that you should
keep in mind, we're talking about,
gut microbiota here, and the thing
that you could think about is your
ego is actually getting controlled
by your gut microbiota sometimes.
The other thing is that the brain circuit
for spirituality has been identified
and it's the periaqueductal gray.
And for those of you who administer
anesthesia at one point or the
other, this is an opiate rich
center that gets you high.
And so there is your brain circuit for
spirituality, and it's also in the brain.
And so this is also being
affected by your microbiota.
I wonder if anyone here would
sequence the gut microbiota of
highly spiritual people and see
what they get in terms of organisms.
Now, then the new perspective that
I'd like you to go home with is that
the brain is not immune privileged.
It has a neuro immune system.
You guys are actually
very familiar with this.
This is the capture, rolling,
activation, adhesion, this is all
white blood cell activity, right?
And it actually can insinuate itself into
the neurons via the perivascular space.
You could see here there's a
neuroimmune crosstalk, right?
There's a healthy brain
and the diseased brain.
You could see in the diseased brain
or the unhealthy brain, right?
There's a reactive astrocyte
and activated microglia.
Remember that astrocytes are just,
what, special types of microglia.
So let's take a look at the
bidirectional communication
in the tripartite axis, right?
So there's neural, endocrine,
immune, metabolite signaling,
and vesicular, right?
Here you have the neural mechanism.
Here's the the neural mainly
mediated as we as is often
referenced as a vagus nerve, right?
And then the endocrine is via the
HPA axis with a cortisol affecting,
gut motility, the immune system with
the cytokines metabolite signaling.
And one more here's the bi
directional communication.
We all know about the vagus nerve
vagus actually slows down intestinal
motility, and that's a signal.
But what you should not forget is they're
communicating with the enteric neurons.
That's important.
We all think it's just
coming from the brain.
Your second brain is actually
communicating with your first brain
in terms of its own enteric neurons.
Okay.
Now there's a bidirectional
communication via the endocrine system.
You have the hypothalamo pit axis, of
course, the cortisol release and so on.
And those actually report basically
affect your microbiota and what your
microbiota do actually produce metabolites
that then are sent back to the brain.
If you take a look here you have
your we only think again this is
what I'm going to emphasize here.
You always think that it's
coming from the brain.
But the gut itself has its
own enteroendocrine cells.
It means it produces its own hormones,
like GLP 1, PYY, CCK, these are all
enteroendocrine hormones that are produced
by the enteroendocrine cells in the gut.
As I said earlier this is
a separate brain in itself.
So it has its own neurohormones, it
has its own hormones that affect it and
that affect the first brain in itself.
The third is bi directional
communication using the immune system.
Of course, here are the
immune cells, right?
They produce the inflammatory cytokines
and they affect the brain if they are
inflammatory cytokines, of course,
then you will begin to have something
like neuro inflammation, right?
It says here that the LPS
activates an inflammatory response.
You all are familiar with LPS.
And one of the things I'd like to say
here is that cardiologists like to
put down to basically bring down your
low density lipoproteins, but your
low density lipoproteins are actually
responsible for mopping up the the LPS.
In your system.
So there is a certain amount.
If you push it way too low, your patient
will actually be in a chronic state
of inflammation because what the LPS
could not be cleared out properly.
Now.
Metabolite signaling, you know that
the colonic bacteria, for example,
produces short chain fatty acids, right?
And and short chain fatty acids,
as you will see in later slides,
actually is responsible for the
behavior of your blood brain barrier.
And among your short chain fatty
acids the most prominent one that
you know about is butyrate, right?
And there, you have seen studies
where low butyrate actually is very
much associated with colon cancer.
When I lecture to my students, I tell
them that if you're looking for a colonic
surgeon, you should ask your colon surgeon
what the primary fuel is of colonocytes.
If he says glucose, you should
ditch him and find another one.
A, these are very simple tests.
Ask what's the primary fuel your GI,
what the primary fuel of your enterocytes
are, if he says glucose, ditch him,
or ask your cardiologist what the
primary fuel of the heart cells are,
and if he says glucose, ditch him.
If you ask your neurologist,
what's the primary fuel of the
brain at rest, if he says glucose.
Fire him.
These are basic or fundamental things
that we all should know, right?
Both doctors and practitioners
should be very aware of what
fuels your fundamental cells.
So it's the neural, it's the vagus
nervous system, endocrine is the
hypothalamic pituitary axis and the entero
endocrine system then there's immune
signaling, metabolite signaling, right?
And then, the last one,
actually Um, is by what's called
bacterial membrane vesicles are
often outer membrane vesicles.
So that the, again, the communication
is bidirectional that the bacteria
actually produce membrane vesicles that
can then fuse with your enterocytes.
And it may contain
anything it can contain.
It may contain RNA.
In fact the Nobel award for this
was showing it containing RNA.
So for those of you who get
questions about COVID vaccine, right?
That it actually has RNA and it's
being incorporated in the system.
Evolution has been doing this for
us thousands of years in our gut.
So that's just something
for you guys to think about.
Now, here's what I was telling
you about, the bidirectional
communication in the EMGB axis, right?
This was in 2013, and he says,
Recently interkingdom crosstalk
was demonstrated between humans and
bacteria through fecal microRNAs.
What, why is that significant?
Because interspecies talk
is not allowed, right?
It's just like reproducing between a
hippopotamus and a swallow, for example.
But now we find that they
actually communicate, right?
And we talk back and forth
with them through RNA.
They alter our epigenome, and
guess what, and therefore they
will alter our behavior as well.
So the way to look at it is
what I term as a holobion.
We are basically an
assemblage of organisms.
We are a network of organisms that
are all communicating with each other.
We cross a species in order
to talk to each other, right?
So human cells, human microbiota
food, fungi, and other viruses, they
are all in a network within our body
as an ecosystem, and they all talk
to each other by different means.
And the last means that was just
shown was actually by membrane
vesicles, which was forbidden.
This form of communication
between species was forbidden by
biology, by dogma a long time ago.
Finally this is 20 19 article.
They're finally using the term holobiont
in the microbiota gut brain axis
articles that you will find out there.
Now, the third part would be an
introduction to home hope for those of
you who weren't here yesterday and then
how to detect and correcting balances in
the enteric microbiota got brain access.
And then the.
Uh, Entire microbiota brain interaction.
The interaction between
the two organs, right?
And then a neural inflammation
and illness medicine versus health
organization, medicine and practice.
This is a very simple way to display what
we do in health optimization medicine.
In illness medicine, essentially
you look for disease markers
like FBS or HBA1C, right?
And then you basically correlate
that with some disease and
you do disease management.
So it's very simple.
Here we do diagnosis and treatment
and that's a clinical practice.
Of illness medicine is to
diagnose and treat diseases.
However with the advent of technology,
we now know how to look inside the cell.
And by looking at it, we see that
actually there are about four drivers
that precede the disease markers, right?
These are genes symbiotic
partners, environment, and time.
For genes, you have the various types
of the nuclear DNA, mitochondrial
DNA, nucleic acids, your symbiotic
partners, your mitochondria, which are
endosymbionts, bacteria that live inside
your cells, your gut microbiota, which
are your exosymbionts, bacteria that live
outside of your cells, your environment,
like the direct and indirect signals from
environment for example light, can be
photo toxic to you and then evolutionary
and circadian time and all of these gears
actually produce metabolites that can
be then detected and corrected, right?
And you can detect and correct
metabolite imbalances, and that's
what we do at Health Optimization
Medicine as a clinical practice is
to detect and correct imbalances.
We really don't do disease, we set
the diseases aside and make sure
we take care of your fundamental
self first in terms of its balance.
If you want to check for the
health markers and adjust the
metabolome itself, then use the
science of clinical metabolomics.
If you want to affect the DNA, we're
too old for CRISPR Cas9 technology.
Trust me.
I tried.
I bought a CRISPR Cas9 lab for
myself and was unsuccessful.
All I was able to do was develop a
glowing Saccharomyces bouillardii.
But anyway if you want to affect the DNA,
then there's the science of epigenetics.
Then if you want to affect the
mitochondria and gut microbiota, you
use the sciences of bioenergetics
and the gut immune system.
And if you want to affect the direct
and indirect signals from environment,
use a science called the exposome.
Exposome, which is the sum total of
your exposure to everything, right?
And my favorite example here is that
if a mother drinks during a pregnancy,
then there's exposure to alcohol, right?
And now you know why we look at this
history when we're trying to figure out
whether or not we have a fetal alcohol
syndrome or an adult that was Exhibited
fetal alcohol syndrome as a child.
If you are looking to change the
evolutionary and circadian time,
you use the sciences of evolutionary
medicine and chronobiology.
Take a look at the Ohms here, right?
Metabolome mitochondrial metabolome,
got microbiome, epigenome so the
cell danger response, a metabolome
for evolutionary medicine and in
chronobiology, we have the chronobiome
and then you have the exposome.
So these are the seven pillars of health
optimization medicine and practice.
Unfortunately, this is not taught to
us in medical schools yet but we hope
that by doing this and educating a
lot more people, we can get to where
we want to be in terms of health
in this country and in the world.
Let's define health.
If you ask any person, especially
a doctor, to define health, they
wouldn't have any definition of health.
I like a more clinically actionable
definition of health, and this is, you
can take this with you, A plus B plus
C is the absence of disease, which is
illness medicine, and the balance between
anabolism and catabolism according
to the cycle of life of the organism.
And we don't do root causes of disease.
There's only one root cause of health,
and it's the maintenance of balance
between anabolism and catabolism, right?
And I hope someone now here knows
the answer to my question yesterday.
Is inflammation anabolic or catabolic?
I'm not going to answer that for you.
So it means that just because you're
not sick doesn't mean you're healthy.
It only means that you're not sick, right?
And optimization Now it's defined as
neotenizing your metabolic subnetworks
to values that it had when you
were between 21 to 30 years old, or
use evolutionarily derived values.
And neotenizing means making young.
When your patient or client comes
to you and says, Oh, but this value
is normal that's normal for the age.
But what we try to do, or what we do, is
actually to move your values to the values
you had between 21 and 30 the golden
age for having children then her dog
actually did this in hormone balancing.
He uses a mean value of 25 plus
minus two standard visions.
United States, by the way,
uses 30 for hormone, right?
Gordon his median value is he takes a
median value between age 20 to 30, and I
use the 50th to 75th percentile at age 21
to 30, or and I use evolutionarily derived
values, for example, for vitamin D.
Vitamin D values, as I see in this country
the range, reference range is way too low.
We do not use illness medicine range of
values, lab values are cut of values
they are survival values and are not
optimal values and normal is not optimal.
Now the practice is very simple.
You measure the levels of metabolites, you
compare them to the optimal ranges, not
the normal ranges, and you balance using
two major techniques, which is network
wide range shifting and ratio correction.
Network wide range shifting
brings the concept of network.
Everything is networked in the body.
If you touch one node,
everything else is moves.
The other one is ratio correction.
For example, if you are looking at
omega 3, omega 6 balance, then you
should correct this by correcting
the ratio and not correcting a
single value in those metabolites.
So this is a visual summary
of home hope balancing.
We all know that oxidative stress
leads to all of these diseases.
It's not only oxidative stress, right?
There's also the nitrogen
stress, the RNS, right?
Which is used by the body really
to kill viruses instantly.
And so here it is, there's a
redox balance and redox signaling.
So we're after balancing, there's can
see here the mitochondrial homeostasis
metabolism inflammation on the other side.
And then if you take a look, this is
the yin yang of inflammation, right?
For if you have , imbalanced redox.
Then your NF kappa B transcription
factor gets activated.
And immediately produces your pro
inflammatory cytokines, right?
There's NF kappa B activation,
your body knows what to do.
Yeah, we're not dumb organisms.
We evolved over time.
We have our own mechanisms of
healing and protecting ourselves.
We should take a look at what we're doing
first before we actually go gung ho and
do different things to the body by shoving
all sorts of things to it, we should know
what the body is doing evolutionarily
before you start changing things.
The NRF2 system produces anti
inflammatory cytokines, and
this is the yin yang balance of
inflammation and anti inflammation.
Many of you like turmeric, is
a very common way to decrease
total body inflammation.
Because it is a direct
activator of the NRF2 system.
Now, here's your pro inflammatory,
anti inflammatory balance.
You you can do a cytokine testing
if you like to, or if your patient
is rich enough to have this done.
Again, you take a look at the
balance of your inflammatory
and anti inflammatory cytokines.
In homo balancing, this is
like the center of what we do.
We optimize the resolution of
the cell danger response, right?
There is cell danger response
consists of four major parts.
Oxidative stress, which you could
see can be the trigger is like
your reactive oxygen species or
reactive nitrogen species, right?
And then your amplifier would be
the inflammation by your cytokines.
And then there's innate
immunity, the activation of,
say, your macrophages, right?
And then there's the endoplasmic
reticular stress response.
As I said yesterday, you guys
must be very familiar with this.
This is unfolded protein response.
This is elucidated over two decades ago.
And you guys should be
experts on this by now.
This acute physical, biological,
and psychological threat induces
the cell danger response, right?
And so does chronic physical
chemical, and biological threat.
Acute threats usually you can resolve
it by ourselves, but the chronic
threats are the ones that produce
chronic diseases like diabetes
or clinical cognitive decline.
So I asked ChatGPT-4, I said, are
there any vitamins, mineral, cofactors
and hormones that dampen and or
quell the cell danger response?
And he says, vitamin DCE, A, mineral,
zinc, magnesium, selenium, cofactor, coq,
10 a LA, and a D plus hormones, melatonin,
cortisol, testosterone, and others.
Omega-3 fats and polyphenols, right?
But should you give everything if
your patient is, or client is in
a cell dangerous response mode?
Of course not.
What we do in health optimization
medicine is actually we measure, right?
So we measure the levels of antioxidants,
vitamins, C, A, alpha lipoic acid.
Those are measurable right now by
clinical metabolomic testing, right?
So before giving any of that stuff.
Just because you have chat GPT 4
doesn't mean you should just inundate
your patient with all the supplements.
Measure and see whether or
not they need them, right?
If your patient is in actual anti
oxidative stress, then they are warranted
to the levels your tests are showing.
Remember that is there is a syndrome
called AIS, anti oxidant induced.
stress.
If you give way too many antioxidants,
your system will go haywire.
It will go the other way, right?
And why is this?
For example, if you enlarge the
pool of your antioxidant vitamin
E, that's a very large pool.
And remember, they're in a cycle.
Whatever is next in the
cycle is still a small pool.
So when you're looking at increasing
your antioxidant pool, for example,
take a look at your antioxidant
regeneration pathway, right?
Because all of those are involved.
What you're going to do is
simply pool the vitamin E and
what it has reduced in its pool.
And then a smaller pool is waiting
to actually do the recycling for it.
And that's the reason why many
studies on, for example, Oh,
selenium and vitamin E failed in
80, 000 cohort for prostate cancer.
If you don't measure this stuff
before giving them it you are
doing a wrong protocol, right?
And then the imbalance of enteric
microbiota It's called dysbiosis,
of course, you know this, and you
can detect and correct, for example,
malabsorption and bacterial dysbiosis
types of metabolites, right?
You know how to do that, and you could
do your recommended supplementation
and dosing with prebiotics,
probiotics, parabiotics, post-biotic,
symbiotics high fiber diets.
As I say in my lectures, the
fastest diminishing macronutrient
in the human diet is fiber, right?
Lifestyle adjustments like meal timing
all of us usually sacrifice our meal
timing in order to do our work or to
have our extracurricular activities.
So let's take a look at the entire
microbiota and the blood-brain
barrier that you can see here.
The role of short chain fatty acids.
As you can see, short chain fatty
acids you have to have the levels
such that they actually promote the
strengthen the blood brain barrier.
It has an anti-inflammatory effect.
It's neuroprotective, it
regulates the microglia.
Some of the SFCAs can actually cross
the blood brain barrier, right?
And it's an area of ongoing research,
and it can serve as an energy source of
in the brain, such as it's the primary
energy source for your colonocytes.
When you're supplementing, for example,
the short chain fatty acids directly and
not via a high fiber diet modification or
prebiotic probiotic modification, then you
make, you should make sure that the short
chain fatty acid actually is s enteric
coated enough to actually get uncoated
or dissolved in your colon, right?
Otherwise it's basically useless.
Now the enteric microbiota and
brain neurotransmitters, as you
can see here essentially the
neurotransmitters SCF FAs and BDNF.
So the neurotransmitters, serotonin,
90 percent of serotonin is produced
in the gut, but remember serotonin
is not produced it's not, doesn't
cross the blood brain barrier.
So the serotonin in the brain
is produced by the brain itself.
You have your tryptophan.
There's a large neutral amino acid
transporter that actually transports
tryptophan and creates its own serotonin.
So this serotonin is actually produced
for the use of the gut itself, right?
And then dopamine Some bacteria
can produce dopamine and they
can have the systemic effects.
We don't know whether or not the
cross is a blood brain barrier.
I suspect it doesn't.
GABA, of course, is a notoriously huge
molecule it does not cross a blood
brain barrier in a classic sense.
And therefore it has to be synthesized
from scratch via the glutamine from your
diet, which becomes glutamate in the
brain and then gets converted into gaba.
Now, certain strains of lactobacilli and
bifidobacteria can actually produce gaba.
And then norepinephrine is
also produced by gut bacteria.
So again, the main perspective here, even
if you don't remember any of this, is
that the gut is itself a second brain.
It has its own neurotransmitters,
it has its own hormones, and
you should respect it as that.
So the enteric microbiota effects on BDNF.
You have BDNF upregulation, stress
response, if you have stress induced
changes in your gut, it will actually
decrease your BDNF and for inflammation,
of course, gut microbiota can
modulate systemic inflammation, which
can in turn influence BDNF levels.
What if you're.
Patient or client complains
that he or she is so poor could
not buy all the prebiotics and
probiotics that you recommend.
One of the biggest things that
you could do is actually exercise.
It can raise your BDNF by about 60 percent
and beats any the results of any SSRI that
you could give out there for depression.
That is if you could
push them to exercise.
Your microbe associated
molecular patterns, right?
And then you have damps damage
associated molecular patterns.
You guys are familiar with those, right?
Those are all terminology pumps and damps.
And you could see here that
microbiota actually modulate
your neuro immune function and.
Implications of the modulation of
neuroimmune function, actually altered gut
microbiota can lead to increased levels
of pro inflammatory cytokines, right?
When you look at immunity, when a
patient presents to you or a client
presents to you, for example, with
lupus or some autoimmune system, don't
look immediately for autoimmune causes.
Look right away at the gut health.
What can you do immediately for
your patient or client is actually
to clean up the gut, seal it up,
and make sure that, the microbiota
are appropriately replenished.
Autoimmunity neuro degeneration.
They're implicated in neuroinflammatory
aspects of Alzheimer's and Parkinson's.
I have a few of these patients and one
of the first things that I do really is
to clean up the gut and decrease total
body inflammation because an inflammation
in the gut will already give you a
clue that the brain is also inflamed.
Question again, how does one
take care of gut dysbiosis?
Dietary changes like prebiotic foods,
probiotic foods, low sugar and low fat
supplements probiotics, digestive enzymes,
glutamine, berberine, caprylic acid, zinc,
carnosine, curcumin, lifestyle changes.
Stress management, physical exercise,
adequate sleep medical treatments, right?
If antibiotics are warranted, I
prefer to use natural antibiotics
and antifungals, right?
And fecal microbiota transplants those
have been in the news over five years ago.
These are the classes of what
actions you can think about for your
patient or client, dietary changes,
supplements, lifestyle changes, and if
if warranted, any medical treatments.
So you know, this is
just a simple diagram.
You already know what this means.
Probiotics are healthful
microbial living cells.
Parabiotics are dead or
inactivated probiotics.
And then prebiotics are chemical
agents that have the ability
to stimulate probiotics.
Postbiotics are beneficial
metabolites of probiotics.
Prebiotics and modulation of
the microbiota gout brain axis.
So that's how this is from this
paper and that's how I'd like you to
remember the gut is, it's not as a gut,
but microbiota gout brain axis, gut
associated lymphoid tissue, because
that's where most of the problems of your
patients or clients will be coming from.
Think of it as really an immune system.
And as I say to my guys in health
optimization medicine, your immune
system is responsible for your defense.
And if you look at the United
States, the Department of
Defense has the biggest budget.
Energy budget of the body is also
the biggest for its immune system.
Alright, so again there's the imbalance
of the gut immune system, you have a leaky
gut you guys are very familiar with this.
As you can see here there are
factors that can cause decreased
permeability, like propionate,
butyrate, oligosaccharides, fiber.
Increased with propionate,
glucose, fructose.
So always have that balancing principle
in mind when you're looking at the gut or
the brain or any other part of the body,
and if there is too little permeability,
then you cannot absorb anything, right?
It's too much, then you have
what's called a leaky gut.
So what you have in here is you
achieve a balance between an optimal
type of permeability for your client.
And this is very individual.
Because the lifestyle, the diet of your
clients usually stay in one place and
then it's usually very steady, it's
continuously very fatty, and you guys know
that the most difficult thing to change in
any client or patient is behavior, right?
So you have to follow their behavior
for a while, while adjusting
the permeability of their gut.
It's not a one size fits all thing when
you're looking at the client, right?
So the, and then you could measure,
calprotectin, EPX, fecal secretory
IgA, the butyrate, pionate, acetate
take a look at those levels and
determine appropriate supplementation.
Now you could do your elimination
diets, your glutamine, probiotics,
digestive enzymes, et cetera.
One of the things that induces
leaky gut actually from stress
is post operative patients.
when you're dealing with a post operative
case, and they usually just dump the
patients in the recovery room and give
them nothing by way of any support.
And when you receive the patient
is in severe leaky gut and
complaining of other problems.
So what you can do there is to
recommend six grams off of glutamine
in a liter of water to be sipped by
the patient in a while in the OR,
especially if intestinal surgery, right?
And that actually keeps the patient
in positive nitrogen balance, right?
And that will make sure that
your intestinal permeability
is not harmed that much.
It will say any surgery to the
body is still stressful, right?
How does one take care of
the leaky gut syndrome?
So you don't need me for this
anymore, you just need to chat GPT 4.
Dietary changes like the elimination
diet, high fiber foods, probiotic
rich foods, supplements, probiotics
glutamine, digestive enzymes, omega 3s,
zinc, collagen or bone broth, right?
Vitamin D, turmeric, lifestyle changes,
stress management, if they need to
divorce their husbands or wives, right?
Adequate sleep, right?
If the partner is snoring, it's
been shown that for each snore the
cortisol level rises in your partner.
each snore that your partner makes,
your cortisol actually rises.
You may be in love, but
you are sleep divorced.
And then regular exercise, which is
one of the most difficult things to
get your clients to do, unless they're
actually younger and seeking a mate.
Now medical treatments,
as I said, only if needed.
Antibiotics, antifungals,
anti inflammatories, right?
And what I want you to note
here is simply the classes.
Dietary changes, supplements,
lifestyle changes, medical treatments.
, we're looking at brain balance when you go
take a look at neuroinflammation, right?
It's a balance of micro, microglia.
They're either activated or inactivated.
Arresting microglia will have
a regular phagocytic function.
They will have steady state monitoring.
Remember, this is an immune system.
They're soldiers.
They're sentinels.
They monitor their environment, even
if you consider them as brain cells.
They serve as the immune function.
And then there's the activated
microglia, which now produces
your pro inflammatory cytokines.
And you can see here there's an
active function, neural injury.
I went quickly through a slide earlier
that showed the cell danger response.
Now, what I wanted to emphasize
there is the following.
There are only eight ways by which
a cell, a fundamental cell, can
respond to stress evolutionarily.
All the other ways that it responds are
actually due to the specialized functions.
And that's what we actually
teach in our online module on
evolutionary medicine, is the cell
danger response metabolome, right?
There are only eight of those, and if
you could actually resolve those eight
different steps, you actually have already
resolved the cell danger response that
the the stress is putting out, and you
have quelled it, and you're Patient
or client would start feeling better.
All right.
Now, here's a cell with
no neuro inflammation.
There is an oval for inflammasome
unless you've been living under a rock.
You.
All know what an inflammasome ear
is, the most famous one of course
is the NLRP3 inflammasome, right?
This is the staging area
for your inflammation.
As you can see, everything
is nice and neat and clean.
And when you look at the gut, you should
always think about the brain, right?
Because they have the same
fundamental structures.
You have your bloodstream, you have your
endothelium and you could see that The
lymphoid tissues are underneath the gut,
whereas in the brain, your glial system
actually serves as the immune system.
So always think of these two in
parallel, especially if you're.
patients or clients are exhibiting
brain fog at the same time, right?
You might think, oh, the thyroid.
No, it may just be a simple
neuroinflammation from
a gut dysbiosis, right?
Don't jump into conclusions
immediately that your patients need
any of these big guns right away.
Now, see here, take a look at
neuro inflammation, they will occur
almost at the same time if you don't
address the inflammation of the gut.
inflammation of the gut usually
occurs first because that is
what is exposed to food, right?
External elements.
So the body has to fight what it doesn't
want inside and actually allow what
it wants to get inside, and you could
see here is a total inflammation.
And when I say inflammation, not
the traditional mosquito bite
inflammation should come to your mind.
It is, it should be what's
called molecular inflammation.
What you should think about is that there
is heavy reactive oxygen species load.
Your NF kappa B is activated.
Your cytokines are being produced.
That's the kind of inflammation
that should be in your head.
We're no longer in the 1940s,
where you have to look at
microscopes to do that, right?
We deal with metabolites now.
And you could see in the brain itself,
you could see that the Euglia cells
are the ones responding as your
lymphoid tissue in the brain and the
alter your neurotransmitters, right?
Chat GPT 4, like what can be done to
dampen or quell inflammasome activity?
It says here.
Natural compounds like curcumin and
resveratrol lifestyle and diet like
fasting and caloric restriction and
anti inflammatory diet, microbiota
modulation, probiotics and prebiotics
fecal microbiota transplant, I've had
cases where I actually had to send or
accompany clients in Germany for adult
fecal microbiota transplant for C.
diff, severe C.
diff in adulthood.
And epigenetic modulation
metabolomic approaches, which is
what we actually do in HomeHope.
So not all neuroinflammation is bad.
Your gut, there's a certain optimal
form of leakiness in the gut.
There's also an optimal form of
inflammation that's optimal to the brain.
So on low inflammation.
There is immune to brain communication
with immune surveillance.
There is the, it's involved in
development, memory, and learning.
Transient inflammation is involved
with injury and induced remodeling.
And this is called eustress.
This is eu inflammation.
And for those who are
stoics here, eudaimonia.
Anyway negative aspects of
neuroinflammation, as you can see.
These are high inflammatory states.
And again, when you think of
inflammation, think molecular, right?
Your mitochondria are highly
stressed out, they will put
out a lot of reactive species.
They will induce your cytokine production.
Those will activate your NF KB.
They'll induce your cytokine production,
and then you will have all the downstream
effects of molecular inflammation alright.
Now, what's wrong with this picture?
Can anyone tell me what's
wrong with this picture?
Microbiota and gut brain axis.
Implications for a new
therapeutic design in CNS.
This was just published in 2022.
So this is beautiful, right?
microbial metabolite entry,
altered receptor activity, altered
neurotransmission, the pathways that we
discussed, immune, neuroendocrine, enteric
nervous system, circulatory system,
vagus, secretions, peptides, gut hormones.
Very nicely done, right?
And then up there you have your
neurodegenerative diseases like
MS Parkinson's, Alzheimer's, brain
tumors, and then neurodevelopmental
and neuropsychiatric disorders like
autism and depression and anxiety
and stress and schizophrenia.
They immediately proceed
to disease, right?
Many of your clients or patients will not
be having these things beforehand, right?
These things come as a consequence
of what happens beforehand.
So if you could catch that for
them beforehand or prevent that
beforehand, why would you not do
it if you already have the tools
and the products to do it, right?
So it's not always about disease.
It's time to think of health first.
So when you see a client, you
set aside what their diagnoses
are, and take a look at what the
fundamental or basic cell is doing.
Is the mitochondria all right?
Is the cytoplasm okay?
Are the cell membranes okay?
Is there very fast oxidation
of the cell membranes?
Is there any indication that the
DNA, nuclear DNA is oxidizing?
Very rapidly.
You could see all of those in a
fundamental cell and all cells
of body have that, except, of
course, for mature red blood cells,
which don't have mitochondria.
So you could see here that diet, genetics,
and epigenetics, mode of delivery,
environment, drugs, and exercise affect
the enteric microbiota gut brain axis,
and it will affect the behavior, food
intake, cognitive behavior, stress,
social interaction, fear, and as I said
earlier, it can affect your enlightenment.
Because it affects your
default mode network.
It can affect your spirituality, because
it affects your periaqueductal gray.
Take care of this organ that grows
after you're born, or after your
patients or clients are born.
Let me just show you the difference
in care between illness medicine and
health optimization medicine on the
enteric microbiota gut brain axis, right?
The first one is a diagnosed disease.
In illness medicine, you have
anxiety, depression, multiple
sclerosis, Parkinson's, Alzheimer's.
Whereas what we do is we
just detect imbalances.
We use metabolomic tests to detect
imbalances in vitamin, mineral cofactors,
carbohydrate, protein, fat, hormone,
metabolism, exposure to toxins, etc.
And then use the enteric microbiota.
Your goal there is to achieve eubiosis.
For us, we want to correct imbalances
with supplementation, diet, exercise,
sleep, and other lifestyle advice, right?
For illness medicine, you
want to seal the leaky gut.
And for us, we want to resolve
the enteric neuroinflammation.
Neuroinflammation is not
only in the brain, guys.
Remember that you have a second
brain, and therefore, you have
an enteric neuroinflammation.
All right?
Don't forget these things.
When you remember this become very
fundamental to your care because you
will remember immediately what to do
with your patients or clients, right?
Oh, I'm not only dealing
with neuroinflammation here.
I'm also dealing with
brain inflammation, right?
Because they will tend to
co occur after a while.
In the brain, you treat the
disease like with drugs, right?
So for Parkinson's, for example, and
in the brain, you resolve the CNS
neuroinflammation, which includes
achieving eubiosis and sealing the gut.
Now for those of you who have
Parkinson's patients or are Parkinson's
clients, you already know that the
Parkinson's is now considered to
have, a dual etiologic pathways.
One is actually via the gut.
And the other one is central.
you could see now that we are
seeing the gut brain connection
even in the diseases themselves.
HomeHope, take care of the needs of the
fundamental cell in its network first,
and the rest will follow, because disease
is managed, but health is optimized.
Managing means that, you're only
there until the disease resolves,
but health, you're there every day.
And my favorite question here from
an audience one time is asking
me whether or not we could bank.
We could bank exercise.
Actually, you can't.
And just that's just like
health optimization, right?
So the order of use of balancing agents,
the first line will be your bioidenticals
and bioactives, like bioidentical
hormones, bioactive nutrients.
An example here would be using
methylcobalamin instead of cyanocobalamin.
Cobalamin is an artifact of manufacture
cyanide is an artifact of manufacture
in cyanocobalamin, Second line would
be phytocyticals, fungicyticals,
bacteria, like your probiotics phages.
And the third line would be xenobiotics.
And why do I put drugs last, even
if I'm trained in pharmacology?
is because Almost all the drugs that We
have out there have never been encountered
by the body in evolution, and the
body doesn't know what to do with it.
But it knows what to do with your
hormones, nutrients, and other
things that it actually uses to
heal itself or to balance itself.
So use those first, and use the big guns
later, because you know when you start
to use a synthetic antibiotic, you're
going to bomb your gut microbiota organ.
So this is the balancing very simple,
you measure the levels of your
vitamins, minerals, cofactors toxins
and neurotransmitters and so on, and
then you give them measured supplements.
So the era of asking me whether or not
vitamin E is good for you is over, right?
You can measure all of
those things and they can be
measured at a reasonable price.
The latest developments we
have in this particular areas.
The doudna herself is now in the game.
She's she's Nobel Laureate
in the CRISPR Cas9 team.
Technology, right?
And watch out guys.
She's ready to tackle gut microbiota
on changing the genome according to what
you want them to produce, whether or not,
are we going to have non GMO microbiota?
I have no idea, but, she's already
expressed her Interest in the game.
They found that there's a dedicated
cytoplasmic container that collects exo
Somal, DNA, away from the melian nucleus.
And it's a new organelle . It's
called the Exclusome.
So you now know that we have
another organelle in the cell, and
it's called the Exclusome, right?
And the latest developments in the
brain a new kind of cell shakes
up neuroscience and we continually
find newer and newer cells, right?
The specialized astrocytes
mediate glutamatergic glia
transmission in the CNS.
So if the new organelle is called the
exclusome, this is called the what?
This is called the
glutamatergic astrocytes.
Astrocytes are not supposed to
produce any neurohormones, but this
one produces actually glutamate.
All right.
So the latest developments in the
enteric microbiota gut brain axis,
Kieran yesterday was discussing, how you
develop drugs and how you do test various
types of microbiota in the SHIME system.
Now they're going ahead rather
than using the SHIME system.
What I want you to see here is that one.
And term that I'd like you
to remember is organoids.
You're now, they're now using intestinal
organoids and brain organoids to
test what particular microbiota
are producing what particular
metabolites that will affect the brain.
And this is big news.
This is a totally different
way of doing things now.
We've been doing things
forever via the SHIME system.
So the latest developments in AI I created
this chatbot for us who actually do not
like to memorize things and just like to
seek things out this is what's coming we
intend to give this to our practitioners
health optimization medicine.
And health organization practice
practitioners initially, right?
This is what to do if orotic acid is high.
And I threw in a few books in there
and KB stands for knowledge base.
And this is what it came up with
after looking at the books that
I put in there, if orotic acid
is high, it may be indicative of
abnormalities in our gene in metabolism.
And then I actually placed in a separate
window, the chat GPT response itself.
As you can see, your, if your books are
in here, the professional books, the
response is a lot more professional.
To your liking, ChatGTP is a slightly,
a little bit more general, but can
provide you insights as to the other
things that you may want to investigate.
So this tool will be available hopefully
next year to our practitioners.
And a lot of AI are actually already
being used now for the gut microbiota and
development of more of newer probiotics.
Okay.
Here's our summary this is my ending
slide, here is all the things that we
talked about, the enteric microbiota
gut brain axis the ways by which
they communicate what can go wrong
with the communication is usually
mediation by inflammation, right?
And so the ability of
brain to influence intestinal
microbiota, that's one way down.
And the ability of microbiota is to go
the other way up in a bidirectional way.
Don't forget that the classic
things that you learned about have
their counterparts in the gut,
like the vagus has the enteric gut.
Nervous system, right?
The HPA axis has your
enteroendocrine system, right?
So think of it really as another brain
that actually has its own functions.
It's what's gives you your butterflies in
your stomach, right when you're nervous or
when you're about to divorce your spouse.
So when homeHope takes care of the
needs of the fundamental cell and its
networks first, and the rest will follow.
Remember, the disease is managed,
health is optimized, and I encourage
you to optimize the health of
your patients or clients rather
than managing their disease.
Thank you very much.
This is my last slide.