Is a leaky gut really the root of your ailments? Here’s the science.

Episode Transcript
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Kate Scarlata MPH, RDN (00:19):
Thank you.
The Gut Health Podcast willempower you with a fascinating
scientific connection betweenyour brain, food and the gut.
Come join us.
We welcome you.

Dr. Megan Riehl (00:34):
Hello friends, and welcome to the Gut Health
Podcast, where we talk about allthings related to your gut and
well-being.
We are your hosts.
I'm Dr Megan Riehl, a GIpsychologist.

And I'm Kate Scarlatta, a GI dietitian.
Today we have a veryinteresting and some may say,
provocative topic, and that is"leaky gut.
In the scientific community weoften refer to leaky gut as
intestinal permeability, butwhen the gut does have enhanced
intestinal permeability, there'sdownstream effects.

(01:09):
Things can leak through the gutundigested food, microbes,
toxins and this actually maylead to health problems, maybe
systemic inflammation.
So today we have a very amazingguest, dr Alessio Fasano, and
Megan, will you introduce ourguest?

I sure will.
Dr Alessio Fasano is aworld-renowned expert in celiac
disease, autoimmunity and thegut microbiome.
He is the W Allen Walker Chairof Pediatric Gastroenterology,
Hepatology and Nutrition,director of the Mucosal
Immunology and Biology ResearchCenter and Director of the

(01:49):
Center for Celiac Research andTreatment, all at the Mass
General Brigham.
He's also Professor ofPediatrics at Harvard Medical
School and Professor ofNutrition at the Harvard TH Chan
School of Public Health.
As founder of one of the firstceliac centers in the US in 1996
, Dr.
Fasano has been a leader inresearch, education and advocacy

(02:13):
for advancing awareness ofceliac disease and other
gluten-related disorders.
In collaboration with others,his research focuses on
developing an alternativetherapeutic treatment and
finding a way to prevent celiacdisease from developing.
With more than 450peer-reviewed publications, he
is widely sought after andshares his expertise with many

(02:35):
organizations and institutions.
He has authored two books thatour audience may be very
interested in Gluten Freedom andGut Feelings the Microbiome of
Our Health, with co-author SusieFlaherty, published by MIT
Press.
Welcome, Dr.
Fasano.

All right.
So, Dr.
Fasano, we always start ourepisodes with a little myth
busting.
So do you have a myth you wouldlike to bust in regards to
leaky gut or gut health ingeneral?

Alessio Fasano, MD (03:06):
If you believe that you are not an
Olympian because you have theleaky gut, or that you would not
win a Nobel Prize because yourgut leaks, yes, that's a myth
that needs to be busted.
Meaning the leaky gut.
The term is that, by the way, Idon't like.
I like.
Loss of better function orincreased gut permeability is

(03:28):
indeed involved in manyconditions, but cannot be
responsible why the electionswent that way this year, for
example.

That's perfect.
So all right, let's dive intothat.
Can you explain this term ofleaky gut in simple terms?
And is it a medicallyrecognized condition, being you
know, is the leaky gut the sameas leaky gut syndrome?
Is there such thing?

All right, so let's explain first the term
and then we will go to thedetails.
Leaky gut or loss of barrierfunction implies, as a concept,
the fact that we have barriersthat divide us against the
external environment.
The most obvious that we seeall the time is our skin right

(04:14):
so that stuff doesn't come inour body, because we have the
skin.
The most complex, the moststudied and probably the most
sophisticated barrier that wehave, because it's the largest
interface with the environment,is the intestine.
An adult's intestinal surfaceis spread on the ground with a

(04:37):
double tennis court.
That would be seven timesroughly.
What is the interface with theskin?
Just to quantify that, it's notthe only one, again, but it's
the most studied for all thesereasons.
When I was in training so bothof you were not born yet- I
might have been.
We were thought that thesebarriers to be efficient, should

(05:01):
be static, like a sort of wallthat divides the external world
from our body, so that we wouldbe protected from the
inadvertent and uncontrolledpassage of the stuff that you
were mentioning, you know,toxins, endotoxins, junk, in
other words that comes from theenvironment.
Now, coming to the intestine,but this applies to all mucosas,

(05:23):
also the airways.
The entire layer of theintestine is scored by
single-layer cells, just thesingle-layer cells that are
cemented that was the conceptthat was told to us between them
, so that nothing comes throughother than in through the cells,
what we call technically thetranscellular pathway.

(05:43):
Because the other differencebetween you know, the epithelial
cells in the gut compared toother interfaces like the skin.
We want some stuff to come in,nutrients, otherwise we'll die
right, but only under specificcircumstances and after being
digested, because we have aspecific way to bring the stuff
in.
Nothing else was supposed tocome through.

(06:04):
This concept was fueled by one,the idea that again we should
be otherwise.
We don't want harmful stuff tocome through.
Two, because the resolution ofour microscopy at that time,
even electromicroscopy,suggested that the two
neighboring cells, you knowmembranes were fused.

(06:26):
Given the concept of the cement.
And this was until the late 70s, early 80s, when a Japanese
group said uh-uh, there's nocement there.
There are doors, most of thetime closed, that technically
they called tile junctions.
They are very complexstructures made by hundreds of

(06:47):
proteins with a lot offunctional redundancy.
That, in biological terms,means it's something important
where you have redundancy, youhave backup, so to speak, that
eventually control thetrafficking of stuff from the
lumen into our body.
Now, the concept of door meansthat they can be open and

(07:10):
therefore they introduce theconcept of plasticity, so
dynamic structure that can forthfrom the outside world or not.
If you allow me a comparison ofhow.
Let's say that you know theseare the front door of your house
, okay, most of the time.
Let's say that you know theseare through the front door of
your house, okay, most of thetime it's closed.

(07:31):
If somebody rings, you know thedoor, you open the door to let
the people go in, but you knowwhen they're in, you close the
door and that's the way thatthey are supposed to work.
If you forget the door open andyou go to sleep at night, then
the chance exists that somebodythat is inappropriately
qualified to come to your houseit does, and that is the concept
of a leaky gut.

(07:52):
Coming to leaky gut syndrome,that does not exist in my book,
but of course you know this ismy personal opinion, because you
know that would imply there isa specific entity that created
the problem.
Now we know much more of thebiology why this stuff opened
for too long, how this happened,what are the mechanisms and so

(08:14):
on and so forth.
So there are conditions inwhich you lose the barrier
function for a specific reasonthat you know.
I'm assuming we're going to goa little bit more in details,
but they are not part of asyndrome, because the word
syndrome means we don't know themechanism, we don't know the
reasoning, and that's not whatis the case right now.

hat science has evolved.
It just makes me think of allthese people making a million
dollars on leaky gut syndromeprotocols.

And products to fix it.

Correct so that's fix it Correct.
So that's the thing.

There's no quick fix with any of this,
doesn't exist, but you knowagain, the more that we learn
about the process, the more weknow what can be done eventually
to mitigate the problem.

That's right.
That's right.
So tell us a little bit aboutthe role of this intestinal
barrier, right?
So tell us a little bit aboutthe role of this intestinal
barrier You've started to talkabout this and how does its
dysfunction contribute to otherhealth issues?

Yeah, you know I want to make a disclaimer
before that we go through thedetails.
The disclaimer here is that youknow, in general this is a
hidden topic, as you mentionedat the beginning of the show,
because, you know, because itpolarized people.
It's like the political lifethat we live nowadays in the
United States.
There are believers andnon-believers.
The believers they're all inand they believe that, again,

(09:35):
everything under the sun andthat's the reason why I made
that provocative myth at thebeginning is due to the fact
that our intestine leaks.
The non-believers said this isa totally voodoo, junk kind of
science.
Of course the truth issomewhere in the middle.

Like everything.

Correct.
And again, I'm not trying todemonize the functional medicine
folks.
They are the one that took theforefront, you know, on this
topic.
Actually they had the argumentto understand that there was
such a thing.
The more evidence-basedmedicine took a long, long time
to get there, but now they areon its common ground.

(10:12):
So we know that this stuffexists, you know, and we start
to understand why that existsand under which circumstances.
So if you look at thepathogenesis of any disease of
humankind, until we resolve thehuman genome project, we were
convinced that there are onlytwo things, two elements that

(10:33):
were necessary, sufficient todevelop these diseases.
One, genetics who you aregenetically speaking, what kind
of predisposition you have todevelop any given disease.
And then environmental factorsthat eventually will put your
genetic predisposition you haveto develop any given disease.
And then environmental factorsthat eventually will put you
know your genetic predispositionto motion, to develop any given
condition.
And again, you know this was acorollary that we had until

(10:58):
probably, I would say, themid-70s.
You know there was an epochalchange of our destiny as human
beings.
You know, for almost twomillion years of our evolution
we mostly got sick and died ofinfections.
That's been our destiny.
Until again the mid-70s, when,you know, we start to understand

(11:19):
the basics of this, you knowinfectious diseases, and we
start to develop remedies likesanitizers of water, antibiotics
, vaccines and so on and soforth.
And where we deployed thesemeasures particularly the
Western hemisphere, increasingWestern lifestyle we saw these
diseases plummeting.
So rheumatic fever, tb, measles, rubella, just went almost to

(11:42):
zero.
But during the same period wehad this increase, exponential
increase, on non-infectedchronic inflammatory diseases
like neurodegenerative disease,like Parkinson's, dementia and
Alzheimer's, orneurodevelopmental diseases like
autism, autoimmunity, cancer,metabolic disorders and so on
and so forth.
That led us to pose about thesetwo pillars to be necessary and

(12:07):
sufficient, because again weinterpret this phenomenon that
of course you can't blamegenetics, that takes generations
to have these changes and thismaterialized in a matter of 23
years.
So the same generation saw thisexplosion of chronic
inflammatory disease.
So we concluded we haven'tchanged the environment too fast
for us for that.
That was our conclusion.

(12:29):
But there was another morepositive, optimistic reading of
the phenomenon.
We were convinced that if I'mborn with the genes for breast
cancer or Alzheimer, that's mydestiny, can't do anything about
it.
But this epidemiologicalobservation that originally was
called the IGene hypothesis andnow being revisited.
It's not called that anymore.

(12:50):
It taught us another lesson IfI'm born with these genes, it's
not my destiny that I will getthat disease.
If I do, it do not depend on mylifestyle.
In other words, I will play mygenetic cards.
Understanding what we've beendoing wrong by embracing the
lifestyle like the Westernlifestyle will give us a hint of

(13:10):
what's going on, and that leadsa huge amount of efforts to say
what else is at play, and threeother elements surface.
This is a long way to answeryour question.
These two worlds are normallysegregated by barriers.
You've got to lose thatsegregation in order that they
have to interact.
So, in other words, theseelements from the environment

(13:31):
need to be seen by our genes,particularly the ones that
control the immune system, inorder to develop a problem.
The fourth element, becausewe're talking about chronic
inflammatory diseases, is thatan immune system becomes
hyper-religion.
And, last but not least, theecosystem that we have in our
body, particularly in the gut,what we call the microbiome, is

(13:57):
also involved.
So, with that understanding,the more we've been studying the
critical leading gut world, themore we realize, no matter what
kind of disease you see,because all five pillars are
necessarily sufficient.
You've got to have lots ofbarrier function, some shape or
form, in order to develop theseproblems, because you got to
have increased antigentrafficking or endotoxin
trafficking that will lead tothe beginning of that march from
genetic misposition to being aoutcome.

It's fascinating.
I'm just taking it all in andthinking about how gut health
then.
It is so broad, it affects allof us.
It affects every cell in ourbody and you've just beautifully
demonstrated that with thisexplanation of the cells in our
body.

I know it's almost like you have to
like pause and just take it allin.
I felt like both Megan and Iwere just like sitting here like
just contemplating everythingthat you said.
And it's not just one thing,but there's a lot of factors
here and many of them aremodifiable with lifestyle.
You know.
You do see, just I saw apicture from the 1970s.

(15:00):
It was from old orchard beach,Maine and I showed the picture
to my husband just last nightand I said what looks different?
And not everyone was fat.
I mean, it was so obvious instriking in this particular
picture.
So you know that lots going onthat's affecting that's right.

So now you struck another note here,
because when we're trying tofigure out what we've been doing
wrong by increasing lifestylethat is conducive of this
chronic inflammatory diseases,so what have we been doing wrong
in the Western atmosphere?
So the last three elements, bythe way that we didn't know, gut

(15:41):
permeability, the immune systemthe become hyper belligerent
and the microbiome.
They're highly interconnected.
So typical example if you havean imbalance of microbiome, that
is the strongest stimulus tohave your intestine leak, and if
your intestine leak, yourmicrobiome goes off balance.
And now we know, and I don'thave to elaborate too much about

(16:03):
that the microbiome reallydictated our destiny, because
with only 24,000 genes or 28,000genes, whatever, it is that
reasoning that we had when wedid the Human Genome Project one
gene, one protein, one diseaseis out the window.
So it's all epigenetics andit's the microbiome to decide if
, when, why and how some genesare put in motion, that we start

(16:25):
that march from geneticallydisposition to clinical outcome.
And therefore the reading ofall this is because we change
that friendly relationship withthe microbiome that we have this
surge of chronic inflammatorydisease.
These genes that put our riskfor those conditions has been
always there but never been putin motion and now it seems to be

(16:47):
that because of the fact thatwe're not taking good care of
our microbiome talk about guthealth, including the microbiome
that's the reason why we're introuble, and all this stuff that
we can do when we embrace aworsened lifestyle can affect
negatively the microbiome andtherefore our clinical destiny.
Yeah, c-section versus vaginaldelivery, but that's one episode

(17:10):
in my life.
You know antibiotics.
Yeah, I can take three or fourantibiotics a year, but I eat
three or four times a day.
So probably the most impactfulreason why we got in this mess
is because we radically changedour nutrition.
And this will go back to whatyou're saying, kate.
In the 70s everybody was on thelean side and now we have, just

(17:34):
in pediatrics, 30-40% of childobesity and these are the kids
that bring comorbidities.
When I was in training again, Ihad never seen a kid with
hypertension or fatty liver orcardiovascular diseases, and now
we see this in clinic.
That was unconceivable.
All type two diabetesunconceivable.

I just think of growing up in the 70s
TV dinners, the Betty Crockercake mixes, everything was out
of a box growing up and then Ithink, okay, that I was creating
like probably the worstmicrobiome, and then I had three
kids and they got a piece ofthat you know.
So you see the generation youknow, and antibiotics were like

(18:20):
candy.
I mean, I was on antibioticsall the time, all the time as a
kid, so you can see how you canhave generational effects and
this problem get bigger andbigger and bigger.
I want to just comment on sothe intestinal permeability I
want to make sure I got thisright for our listeners is a big

(18:42):
piece to the advent of thesechronic diseases that we're
seeing.
Like that has to be there.
Is that what you were sayingearlier?

That's right .

That is a part of this picture.

That's right .
But again, it's one of the fivepillars that you got to have to
have these problems.
And the point of why I focus onmicrobiome and therefore
nutrition is because of all thestuff that you know can bring
you to a quote-unquote leaky gut.
This biosis is the strongeststimulus that can happen to you.

(19:13):
Of course, if you take, youknow, non-steroidal
anti-inflammatory drug that willleak your gut, or it's, if you
are, you know, eventually arestressed, your gut can leak and
so on and so forth.
But you know I can make anyargument that all this stuff
will affect your microbiomania.
So maybe that directly willaffect gut leakness, but maybe
it all translated and transducedby the microbiome dysbiosis.

And so is there any biomarkers used in
clinical practice to help assess?
I know there are some that are,you know, used in clinical
practice to help assess.
I know there are some that areused in research settings,
zonulin being one of them.
No, patients really don't haveany way to assess for this.

The honest answer is no.
However, I want to make alittle disclaimer here.
For many, many years in theresearch setting, we use very
complex and sophisticatedmeasures of gut permeability,
like the double sugar test, thelateral mannitol test.
It is very cumbersome and notdoable under clinical practice.

(20:17):
Then you mentioned zonulin.
Just for the benefit of thepeople that are listening, just
what the heck is zonulin?
You know if, going back to theparallel of your tight junction,
this spacing between cellsbeing a door, zonulin is the key
.
So in other words, it's whathappened at that door.
And if you produce too muchzonulin, that's been, you know,

(20:37):
associated by almost more than1,000 papers now since they
scored this molecule by ourgroup, like 20 years ago, to a
variety of chronic inflammatorydiseases.
So all this to say, yeah, thatis a common denominator what the
people in science have beendoing to manage your gut
permeability in the humansetting.

(20:58):
I don't care about the animals,because that cannot be that
important, of course, becauseyou can do it with an animal
model, something that probablyis not doable with humans.
Over the years there have beenthree biomarkers that surface
that are very meaningful to us.
One is zonulin.
That is, again, if I producetoo much.
I know that my intestine leaksbecause you know I opened these

(21:22):
doors.
But you know what Many of us.
They have a leaky gut and theydon't have any consequences.
All depends how long the gutleaks and, as I said, the
intestine and any other barrieris built to be open at some
point, not for too long.
So it's not important just toknow is my door open?

(21:43):
The next question is who camethrough the door?
Do I have a smuggler or youknow a robber guy that came
through?
And the biomarker for that?
Because most of theinflammation not all, but most
of the inflammation is caused byendotoxins.
In other words, you know stuffthat comes from the bacteria in

(22:03):
the gut.
The second biomarker thatpeople use is what we call the
LPS.
That is an endotoxinlipopolysaccharide.
LPS is binding protein.
So now I'll answer the secondquestion.
One the zone is up.
My door is open.
LPS binding protein is up.
A bad guy came through the door.
And then the third biomarkerthat people they use in research

(22:26):
is what we call Soluble CD14.
That is a biomarker is tellingme, because of all this, my
immune system is fighting andit's generating inflammation.
So, bottom line, back to theparallel my door is open, a bad
guy came through and he'sstealing my stuff because I know
that it's been stolen.
There is now an effort to bringthis to clinic, for example in

(22:52):
Europe.
In Germany, where functionalmedicine doctors are a sizable
number of healthcareprofessionals, the zone assays
use routine in clinic.
Some companies here.
They start to offer zonulintesting here, sometimes by
itself, sometimes in combinationwith the microbiome analysis,

(23:15):
so they too test together as guthealth kind of testing.
Are these ready for prime time?
Probably not, but you know,once this validation will become
more and more substantiated, Iwill anticipate that.
You know again and I see thisin my clinical practice A lot of
people that come there withthese results.

(23:36):
I say can you?
tell me, what that means.
So there are companies that youknow in a name that they are
cashing on this already, right.

But it's just not ready.

Yeah, and what do you tell those patients?
Because we see it too, andespecially my anxious patients
where they don't feel good.
They don't feel good andthey're desperate and they will
spend whatever money they couldfind to try and understand
what's going on.
They read the word leaky gut onsome report and they say I have

(24:05):
this, Dr.
Fasano, it's here.
What do you say to them?
That's based in science andthat gives them some hope on
where do we go from here.
That's right.

So, Megan, you're already at the next step.
So let's say that this stuff isvalidated and some people they
believe that it is to the pointthat they're using the clinical
practice.
So the reality of the story isthat we are at the verge of a
revolution of how we practicemedicine.
The early doctors were healersand they were all focused on the

(24:34):
patients.
Then evidence-based medicinesaid oh no, we don't look at the
patient, we look at the organ,we look at the specific piece of
the car here and we lost trackof what is the reality of the
story because we made theassumption okay, if I have
breast cancer, we're anhomogeneous population.
That's not true.
How you reach that finaldestination can be different

(24:59):
from one individual to others.
In other words, what I'm sayingnow, the focus is back on the
individual versus personalizedmedicine, the future, and to do
that then you need to put thiskind of testing in perspective
what that means for yourpatients.
One key element when we do thiskind of measurements, let's say
you know I do the zonulin testsand my intestine leaks, and

(25:20):
then I do my microbiome testing,and what was in dysbiosis, you
know, will require thatcapability to standardize and
validate all this testing in thecontext of a complexity that we
stretched in the surface justnow.
Let me explain what I mean forthat People believe, some people

(25:42):
believe that there's a normalmicrobiome.
There is no such thing.
It's like to say what is thenormal length of my hair?
Everybody has a differentlength.
It's not that it's normal ornot.
It's very subjective.
The microbiome is verypersonalized.
It has to fit with our genome.
So each of us, they have adifferent microbiome.

(26:04):
What we have in common, though,is the results of the genetic
and macrobial interaction,because we all have to have,
let's say, the glucose levelwithin a certain range, right?
So, metabolically, we havesimilarities, but how that
metabolic state is reached isvery personal from one person to
another.
Once we got that and this willrequire huge data, ai modeling

(26:27):
and so on and so forth that weare already doing this research.
So it's coming.
Then, and only then, I can havean intelligible answer to the
individual.
Because, megan, to answer yourquestion, if we want to be
honest with these people andthey say you know I am here,
where I'm going, I cannot tellyou if you don't tell me where

(26:48):
are you coming from?
How did you start your journey.
So the future is going to be weall will have our genome done
when we're born.
We all will have our microbiomedone when we start this journey
of life on the face of earth.
And we will see the dynamicover time where we introduce
baby food and all my yards, andevery single time that we got

(27:09):
sick we would do that again.
And now we model and I said youknow what you were supposed to
be left?
And now you're right, I need tobring you back to left.
Then I can answer your question, what I can do about it.
Can I give you some prebioticsso I can feed the good guy to

(27:30):
help you to go back to left?
Should I give you probiotics?
Which one Depends on which oneyou lost?
Should I give you postbiotic orsymbiotic or whatever?
The reality of the story is thatuntil we reach that level of
sophistication, common senseneeds to be shared and say
listen, lifestyle will help youto bring this back.

(27:52):
There you go so good, exercise,control the stress, good
nutrition.
As I told you, this is going tobe instrumental.
That will provide the naturalsource of prebiotics symbiotic,
postbiotic, all-night-yards,probiototic and so on and so
forth sleep, hygiene, respect tothe environment.

(28:13):
So some of that are under ourcontrol and we should take
ownership of that and some wouldnot.
What is the caveat of what Ijust said, megan?
A lot of people will push backbecause people they don't want
to work on goals.
I have headaches.

(28:37):
Give me a pill.
I'm obese.
Give me my famous GLP-1receptor agonist so that I can
lose 20 pounds without workingtoward that goal.
There is no such a thing.

It's really this issue of truly
understanding that our health ismultifactorial.
And you are so right that Ihave patients that have been
diagnosed with IBS they wouldrather have cancer and say this
is the treatment.
You go through thischemotherapy and ideally we will

(29:06):
get this in remission andonward with your life.
You will go, and I'm not jokingwhen I say that I've literally
had patients say they wouldrather have a chronic illness.
That will respond ideally,again with hope and prayer and
science and they will be cured.
And when we're talking leakygut and we're talking many of

(29:27):
these other issues, there is nocure.
There is a understanding,appreciation and time devoted to
living a lifestyle that isgoing to incorporate the
expertise of lots of people thatcan help you get to where
you're hoping to get with yourhealth.

Yeah, now, both for leaky gut and IBS.
It's not true that there isnothing that we can do about it,
because now we understand muchmore than we understand before.
Let's take IBS as a typicalexample.
We don't call that IBS anymore,by the way, because IBS means
irritable.
So there's something that isnot right Bowel that has

(30:09):
happened in the intestineSyndrome.
I have no freaking clue what isgoing on.
Now it's not called thisanymore IBS.
Why?
Because this is thequintessential example of
miscommunication between the gutand the brain, what we call the
gut-brain axis.
That, megan, this isn't a smashof what you do for a living, I
guess.
So you know, a while ago I reada book that is called Gluten

(30:33):
Freedom.
That has to do with gluten inyour health and so on and so
forth, and I put a quote inthere that I didn't have any
idea that was going to be aquote that would go on the
shirts when I said you know, thegut is not like Las Vegas.
What happened to the gutdoesn't stay in the gut, meaning
it is a battlefield, but theconsequences can spread

(30:54):
everywhere in your body, and thegut-brain-access communication
is one of the examples of how weare highly interconnected and
how we miss the boat if we don'ttake this in the context of the
complexity, how we interactwith the different pieces of our
body and different systems toreally achieve a specific goal.

(31:15):
Now, IBS is nothing else thanthis motility in my gut, because
this communication between thegut and the brain cannot
coordinate that kind of motilityand therefore it's
multifactorial.
Can be due to dysbiosis, forexample, small intestine battery
overgrowth can be one reasonwhy you have IBS.

(31:36):
It can be because, of course,you have a threshold of stress
that's very low and thereforethis will translate in
communication through thevaginal nerve.
That will mess up your motilityand therefore you create the
condition of IBS, you can do aninfection, and I can go on and
on and on.
So the key element is to try tounderstand which three I have to

(31:59):
bark to in order to fix the IBS.
Again.
We don't call that anymore.
So that's fixable, providedthat we have an understanding,
and I am very sympathetic withyour patients.
They say you know what muchbetter chronic conditions that
have a target.
So I'm giving me a drug and Iwill fix it.
Tell me there's not much I cando about it.
Because that's verydebilitating.

(32:20):
I understand that.
But some people resolve IBSwith biofeedback because it's
stress-relieving.
Other people then they fix byfixing SIBO, and I can go on and
on and on, or by doing anelimination diet because it's
driven by gluten, whatever.
So it's all a question that howcan I put people out of this

(32:41):
pot that I put in there becauseI don't know exactly what's
going on with them?
That's the essence of the story.

It's interesting I think of like IBS
and IBD and just talking alittle bit about nutrition and
the need for personalization,because there's been some
interesting studies looking atinflammatory bowel disease and
in a small subset of thoseindividuals, when they consume
fructans, which are found inwheat barley rye the same gluten
foods which are found in wheatbarley rye the gluten, same

(33:10):
gluten foods it stimulatesthere's inflammatory markers.
And in IBS, when we look at someof the recent data done out of
UMichigan, in the people thatresponded to a low FODMAP diet
they found adding FODMAPs backincited immune activation,
created a dysbiosis with LPS.
You know they measured for LPS,they had this immune activation

(33:35):
and colonic barrier dysfunctionwas measured as well.
But not everyone that has IBSneeds a low FODMAP diet or
benefits and not everyone withIBD is sensitive to fructans.
And so you know these one sizefits all recommendations or I
feel, for patients that are like, okay, my diet's lousy, I got

(33:56):
to eat more fiber, and they goout and buy like a bunch of
whole wheat bread and feelmiserable.
And it's finding the rightfoods too that'll work for your
body, based on this very complexsystem and the individual
nature of it, right, the gutmicrobiome being so different
person to person.

Yeah, before then I answer, I have to make a
disclaimer.
Besides to be professor ofpediatrics, I'm also professor
of nutrition, so I'm a littlebit biased here.
But precision nutrition, in myhumble opinion, is going to be
the future to solve or toameliorate at least many of
these issues.
So you made the right example.
Let's say IBD, for example.

(34:36):
We know that if you're newlydiagnosed with IBD, most of the
time we don't use steroidsanymore to put the IBD under
control.
We use an elemental diet.
It's as efficacious as thesteroids but no side effects,
not sustainable because it'sawful, but you know at least to
take control until I will kickin with biological or anything

(34:59):
else that can eventually do thetrick.
That's very telling to me thatthe mucobomb composition and
function and the antigentrafficking big time.
They have a role in creating aninflammatory situation.
If I'm genetically predisposedto IBD, there are some people,
for example, that you know theyhave seizures.
They don't respond to ananti-epileptic drug.

(35:20):
Then if they go specific dietsthey control it.
So meaning that eventually inthis subgroup of individuals
there are some stuff that youknow.
We change the GABA levels andall that and eventually
subsidize.
You know the problem there, andI can go on and on and on.
I have the biased vision thatonce we understand the basic of

(35:43):
these chronic inflammatorydiseases, why we develop them
inflammatory diseases, why wedevelop them, what kind of the
element that this triangulationbetween my immune system, the
gut permeability ie leaky gutand the microbiome is at play, I
can customize the nutritionintervention that can substitute
any drug that you can imagine,because think about IBD, for

(36:03):
example, the drug that we usenow I treat in the consequence
inflammation Now.
Now the reason why I haveinflammation.
It's like that.
I have pneumonia and I takeTylenol.
Of course the fever will goaway.
I'm testing the consequencefever Now, the reason why I have
fever.
Unless I already get thepneumonia with antibodies, that

(36:24):
will stay there.

Right, so the conversation.

That's right we are going after are going
after the consequences, not thecause.
Changing my nutrition that willchange my microbiome, that will
change my antigen traffickingand give a break to my immune
system so I don't have thechronic inflammation, will be
the future of the personalizednutrition and food as medicine,
so to speak.

(36:48):
Of course that approach doesn'thave too many friends because
you don't make too much moneyout of it.

I know you can't sell it as a drug.

So drug companies are not very pleased
to hear that song.

That's where the conversation of prevention
starts to come in.

You know, Kate, what you were saying.
This has been amazing because,at least at my age, I've seen
this change.
Generation speaking, my motherused to cook from scratch.
We live in the fast lane oflife and we were raised with the
boxes that we see onadvertisement there as an

(37:26):
efficient and logical way to dostuff.
And now we understand thatwe're paying consequences.
My wishful thinking is that oneof the things that was a bad
habit when I was growing up wassmoking.
You know, if you didn't smokeyou were a loser.
Thankfully I was a loserbecause I never smoked in my
life.
But look what happened insingle generation, maybe two

(37:49):
generations.
Now it's the opposite.
If you see somebody smokes,it's kind of weird, but the vast
majority don't smoke.
It took an educational campaignto explain that.
That was a remarkable bet foryou.
A bet for what?
One single disease lung cancer.
But bad for what?
One single disease lung cancer.
If we will go back to the notionthat eating well will take care

(38:20):
of a variety of chronicinflammatory diseases, that will
change completely the landscape.
If I can give an example,during COVID I had the blessing
to have my grandchild born, mydaughter and my son-in-law very
busy.
I was busy as well because Iwas every day in the hospital
and so on and so forth.
Time came that, you know, thislittle fellow that was four or
five months old has to be, youknow, introduced to baby food.

(38:44):
And my wife and I said we takecare of this and we win this
fellow on a Mediterranean diet.
Never use anything pre-done,cook from scratch.
Now he's five.
His favorite food is, I believe, pizza escarole that he eats

(39:04):
very methodically.
Capers first, then olives, thenthe escarole, then the dough.
He doesn't know what a Frenchfries is.
He has no desire of a Frenchfries.
Junk food.
Never done.
A taste.
What I'm coming from with this.
Oh, by the way, and I need torush it up, you know, because

(39:25):
you know Wednesday is dedicatedto these folks, because he's my
sous chef, we cook togetherevery Wednesday.
Yes, to rush it up, you know,because you know Wednesday is
dedicated to these folks,because he's my sous chef, we
cook together every Wednesday.

Yes.

What I'm trying to achieve with this,
that transformational change todo not smoke anymore, if the
next generation knows that tocook healthy would not take that
much, because you know he spentonly an hour with us.
Would not take that muchbecause he spent only an hour
with us, including.
He needs to eat what we cook.
It takes 20 minutes, maybe halfan hour.

(39:54):
You've got to be prepared withfood shopping.
But again, think about thisno-transcript.
I take a tray out and put it inmy microwave because it's
prepared by somebody else.
I don't know what junk is inthere.
Why do we want to do this toour body?
So my hope is that this guy,when he will become a father,

(40:17):
will change the attitude andwill break that vicious loop and
say you know what?
Cooking is not a big deal andthis is the way that we need to
eat, and this is the way that weneed to eat.
And finally, we will reversethis trend of childhood obesity
and chronic inflammatorydiseases due to inappropriate
nutrition.

And people will feel the effects of that right.
You feel better when you havethose foods and, to your point,
exactly last night my kids hadsoccer.
It was late, it was 7.30 atnight.
I looked in the refrigerator.
I'm like I could do a frozenpizza, but that will not make me
feel good.
I don't feel good when I eatthat.
So I threw asparagus in theoven with some peppers and I had

(40:59):
some white rice that hadalready been cooked for dinner
for the kids.
So while I was doing bath time,the oven was on and I did eat
it late.
I ate it later at night, but Ididn't go to bed feeling bad
about the food choice that I hadmade and I felt full and good
and I didn't have anyconsequences the next day.
So it's not that hard.

(41:20):
I'm a working mom with threekids.
It just takes to your pointplanning and getting outside of
some of the habits that we'veidentified that just probably
aren't going to be sustainablefor us long-term.

And then also sharing with the others the
duty of cooking and cleaning.
It's one thing.
The families that make the kidsappreciate, you know, the value
of food.
You don't trust that yourecycle for you know, as you did
, you know, with the rice thatwas left over from the previous
day.
Modern nature will not be ableto sustain the way that we're

(41:53):
doing this stuff.
30% of our, you know food istrashed every day.

Yeah, we can't afford that.
No, it's good meal planning.
I feel like when I meal planI'm really excited to cook what
I am going to have for dinner,because I have the fresh basil,
I have whatever fresh vegetablesto put everything together and
it just it's easier.
I don't have to get creativelooking like what can I put

(42:18):
together tonight?

So if you think about again back to
evolution, when we were gutterhunters 10,000 years ago, what
were we eating?
Because that's the other waythat I answer to my people.
So, okay, you say goodnutrition, what do I have to eat
to stay healthy?
I said you know what?
We've been built for twomillion years to eat a lot of
fruits, a lot of vegetables,tubers, nuts, olive oil, that

(42:40):
kind of stuff.
Meat, absolutely.
Once in a while you have to be agood hunter and eat lean meat,
because these animals wereescaping predators, including
human predators, so they werelean, not fatty stuff, and if
the proportions are right, thenyou are pretty much in the right
track to do the best thing youcan.

(43:02):
What I described pretty much isthe Mediterranean diet bottom
line.
That has been proved to be goodfor you.
But why?
Back to the microbiome and gutlicking here.
The microbiome is like a farmwith different animals.
They are chicken, they are cows, they are pigs, they are
rabbits, and so they eatdifferent stuff.

(43:22):
And, evolution speaking, wedecided that we need 100 chicken
and two cows.
Okay, now we feed only the cowsand we don't give the food to
chicken.
What's going to happen to myfarm?
I'm not going to have eggsanymore, I don't have chicken
anymore, and we were wonderingwhy we're in trouble.
So all this to say?

(43:44):
If you don't have enough fibersin your diet, if you don't have
good stuff, anti-inflammatorystuff that protects your gut
barrier in your food, likepolyphenols and so on and so
forth, you pay consequences, andthat's the reason why it's not
just the sterility to be fat.
Obesity is an inflammatoryprocess, now we know.

(44:07):
So you really instigate yourimmune system to fight, and
obesity comes with comorbidity.
That is all inflammatory based,and all this is due to the fact
that there is dysbiosis andincreased antigen trafficking
and therefore leaky gut.
That leads to all this.

Get your vegetables.
Get your vegetables.

You know fruits and pizza, it's okay, but
once in a while that's right.
That's right.
I mean for the dish-freesituation.
Absolutely Choose wisely,though.

Choose wisely, to the best of your ability.

We do make pizza ourselves and in general
we make enough that we freezethem.
So you have your own frozenpizza or any kind of dish that
takes a little bit extra time.
I don't know.
You do a lasagna or whatever.
Freeze down, that's your stuff.

I'll send you my address so that the Fasano
family can ship their frozenlasagna and pizza to my house.
That's the pizza.

I want.
No, we can do it better.
We do cook classes so youbecome independent.
You're going to need me to dothis.

Sign me up.
Sign me up.
I think so many people don'treally know how to cook,
especially in my generationagain, because so much was out
of a box.
I always loved cooking, so I'mone of nine kids so my mother
couldn't feed us out of a boxall the time we had to eat.
You know she cooked a lot offresh fruit but, yeah, a lot of

(45:34):
people don't know how to cookand I'm constantly giving tips
on just simple how to roastvegetables.
You know they've never done itbefore.
It's like oh, it's reallysimple.

There are many hobbies that we're engaged
in.
Yeah, cooking, I believe, issomething that we should look
very seriously into because,again, you need to do that
anyhow.
Make this something funsustainable, bonding the family
around, preparing meals and notjust putting on the shoulder a
single individual.

(46:05):
It's a lot of fun.

I have to agree with you, so I just
want to like peek back into thetopic a little bit more.
I know our listeners are goingto be curious.
Are there any supplements thatyou would recommend?
I know there was a study onglutamine and post-infectious
IBS as being potentiallybeneficial as far as their
intestinal permeability markersthey used and as well as IBS

(46:30):
symptoms.
But, like colostrum, there'sbeen other things that have been
put out there, so I'm justcurious do you ever dabble in
that?
Is there any evidence-basedsupplements that you would
consider in certain patients?

So glutamine is the fuel for the gut.
You know, no matter how old arewe, our cells are one week old.
So we change the entire layerof cells every week and the
reason why we do that is becausethey need to stay up to speed
to be extremely efficient.
One of the major jobs they haveto do is to maintain that
barrier function.
That it takes a lot of energyand glutamine is the fuel that

(47:05):
they use to do that.
So glutamine is bona fide, agood supplement to consider.
The same.
Colostrum is very much in reachto favor a subgroup of
microorganisms.
There are probiotics thatproduce postbiotic, like
butyrate or acetate, that havebeen demonstrated to fortify the
barrier.
I mentioned polyphenols.

(47:26):
They've been also demonstratedto be anti-inflammatory because
they fortify the barrier.
Anything that again helps thatcomponent of the microbiome that
is there to help to maintainthe barrier function, because
that's something that themicrobiome contributed to, it's
important.

But if I have to pick one: fibers. (47:43):
undefined

Fibers.

Fibers is the staple for any kind of
microorganism that you canimagine that is in our ecosystem
.
That's what they eat.
You know they don't eatanything else.
If they eat anything else, likesugars, they're stealing.
You know 99% of our microbesare in the colon.
There's no nutrients there.
The only thing that will reachthere is stuff that we cannot

(48:07):
digest ie fibers.
There's no nutrients there.
The only thing that we reachthere is stuff that we cannot
digest ie fibers.
And we as a societyparticularly US we eat, you know
, one-tenth, one-fifth of whatis recommended doses of fibers,
I know so.
That's the reason why fruitsand vegetables that,
unfortunately, I don't want tointroduce.
Also, another variable here whenI grew up in Italy, I didn't

(48:33):
know that I was raised the rightway by eating the Mediterranean
diet that was called the dietof the poor.
I come from an humble family.
We can't afford to buy meatmore than once every two weeks.
If so, our protein sources werefrom legumes, for example,
lentils, beans, peas, that kindof stuff.
Yeah, meat, but you know, onceevery week or two weeks, but
that's what we were, and fruitsand vegetables were extremely

(48:56):
cheap.
Now this is a diet of thewealthy.
Who's going to kind of affordthat?
If I'm a single mother with twokids with $10 a day, am I going
to buy fruit and vegetablesthat will fill their belly?
I will buy fat, you know, junkfood.
That's another source ofdiscrimination, but for people
that can afford it and be savvy.

(49:17):
I will say that's the way to doit.
Every Saturday, every FridaySaturday is a produce market in
Boston here, and when I was alittle bit younger, as a joke,
my family gave me one.
You know the carts, the oldladies they used to go shopping.

Yeah, yeah.

I take that.
I don't use car, by the way,because, you know, I want to be
contributing to my health andalso to the health of the planet
, so I use public transportation, I go on the metro, get to the
market and I spend a couplehours there.
I'm a busy man, by the way.
That's very valuable because Italk with the people, I got in a

(49:56):
relationship with them and theysay, oh, you know, no, no
eggplants this week.
They are not good.
And you know, that is mypreparation for the week and
that's the reason why the restof the week, my wife and I, we
can do this in 20 minutes.
So, all this to say, and again,if you go to the markets, they

(50:16):
are more affordable than WholeFoods or any other big retail
stores, and so on and so forth.
So it's doable, but you have totake the effort to do that.

And if you do have a limited budget, you know
frozen fruits and vegetables.

Those are still wonderful ways to Sea
reach of vitamins, minerals,fibers, absolutely.

Yep, I like having the frozen fruits
and vegetables, but when you'renot planned, or like this
afternoon for lunch, I wanted asmoothie and it's just so nice
to have that handy, all frozen,ready to whip up, so you can get
them for a little less moneytoo.
Less food waste as well.

That's right.
So, Dr.
Fasano, what is the emergingresearch or therapies, as we
kind of wrap up here, what holdsthe most promise in addressing
our intestinal permeability?
And you've talked about thisrevolution.
Anything else to share on that?

There are a couple approaches that people
are taking.
They've been now for a while.
This inhibitor, zonulin, that'sbeen done in clinical trials
for celiac disease has been usedalso for long COVID and
remdesivir.
So this is to block thatmechanism if you produce too
much zonulin.
Similarly, the same kind ofgoal has been tackled by using

(51:37):
probiotics that eventuallyfortify your barrier function
and possibly decrease zonulinlevels.
That's also a very active, youknow, line of research.
And third, postbiotics.
A lot of research on usingpostbiotics fortified plus or
minus with glutamine to see ifthat can fortify your barrier.

Can you just tell our listeners a little
bit about what a postbiotic is,because that's kind of a newer
kid on the block.

That's right .
So prebiotics are stuff thatfeed the good bacteria.
In general they're sugars,human monogamy, saccharides,
breast milk, classical example.
The probiotics are, you know,the good bacteria.
The postbiotics are the productof this bacteria, in general
the good bacteria thatcommunicate with the host for
good gut health, in this caseincluding fortified the barrier.

(52:25):
And, you know, short-chainfatty acids like propionate,
acetate, are the classicalexample of postbiotics.

I like the postbiotics too, because
they're not live and viable, sothat's probably good for the
little ones too, or someonethat's at risk for that's right.

They're a little bit more costly to make
than probiotics, but there's alot of efforts and technologies
coming along to make that moreaffordable than that can be used
.
But you're right, I mean, youknow, if we know the mechanism,
why not use it directly?

The actual.
Thing.

That's right .

Yeah, is therea particular postbiotic
product that you are looking at?

No, because again, there is a lot of
research on the matter.
You know which postbiotic youuse.
But you know because, again,there is a lot of research on
the matter of which postbioticyou use.
But in general, thiscombination of postbiotics would
be ideal.

Okay, awesome, all right Well you've shared
some definitely inspiring waysin which you live your lifestyle
.
You're taking publictransportation, you're at the
farmer's markets, you're cookingwith the family.
Is there anything else that youdo that you prioritize for your
own health and well-being?

I drink good wine, good red wine, good
Italian red wine.
Of course, a little glass a daywill do it.

You know what We've said moderation is key.
And when you're doing all theother things that you're doing,
you know, I'm sure, that littleglass of Italian wine really
boosts your endorphins.

With meals, by the way.
There you go.
Yes, that's good gut health.
Yeah, not on an empty stomach.

Nope.

That's good.
Well, that wraps up our episodetoday.
Thank you so much, dr Fasano,for sharing your expertise in
such a unique and complex way,because it's a complex science,
and dispelling some myths aroundleaky gut syndrome, which I
think need to be dispelledbecause a lot of people get

(54:24):
caught up in the snake salesmanout there on the internet.
So, thanks again for coming onand listeners, thanks for
listening, subscribe and shareThe Gut Health Podcast.
Thanks, friends.

Thank you for joining us as we grow this gut
health community.
We hope you enjoyed thisepisode and don't forget to
subscribe, rate and leave us acomment.
You can also follow us onsocial media at The Gut Health
Podcast, where we'd love for youto share your thoughts,
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