- So let's get on with what is a fantastic 24th
Mini Med School program.
It's frankly accidental that this time everybody
in the lineup is from the Department of Medicine.
This isn't about my department
or Dr. Rice's or Dr. Mentor's.
This is about really multidisciplinary care
but today we're going with the gut
and it's really my pleasure to introduce
one of my closest colleagues
here in the Department of Medicine.
The division head for Gastroenterology and Hepatology
which is one division of the Department of Medicine, Dr. Michael Lucey.
Dr. Lucey, his distinguished career is described
on the sheet, did I mention
there's a tear off at the bottom?
The sheet that describes the speakers
and he is a world-renowned international expert
on Hepatology and liver transplants, so please join me
in welcoming our emcee for tonight,
Dr. Michael Lucey.
(applause)
- Thank you very much Rick
and thank all of you for coming.
It's impossible to start without acknowledging
that it's a sad moment.
Partings are such sweet sorrow to see Rick leaving,
but it's extraordinary to see this meeting
because I was involved in one of the very early ones
when there were about 100 people
and I really did think 100 was a great attendance.
And coming over here today I was wondering
why has it grown such as it has?
It's clearly a testament to the leadership
from the Dean's office, from the Dean,
from the mini Deans, including Rick.
But I think there's another reason as well
because I think it has captured
one of the essential experiences of the medical student.
Now medical students have many and varied experiences
recorded in lots of books and movies
but perhaps one that is not recorded enough
or acknowledged enough is the sense of delight
that you get when you're at a lecture
or in a teaching experience and learn something new
and exciting, something that opens a vista
to you that you hadn't seen before
and it really does happen.
And it can change your life actually.
And so I think that that's the reason why
the hundred has grown to 200, and 400 and 600.
The early people have come back and everyone
has come back more and more
because you're getting one of those experiences
that has carried us as people who've been to medical school--
I went to medical school in 1970--
and has carried us forward because we have experienced
that delight and have kept looking for it ever since.
So I hope today that you're going to get
another opportunity for that experience.
We have four great speakers.
We're are going to start with Rich Halberg.
Rich is an associate professor of medicine
and he's a director
of the Biomedical Research Model Services.
He received his PhD in biochemistry
from Michigan State University
and he then did his postdoctoral work here
in the University of Wisconsin with Bill Dove,
and then set up a very successful laboratory of his own
in our division, the division
of gastroenterology and hepatology.
There's an arc to today's talks and it starts
with something that goes against one of the observations
of Alexander Pope, he said,
"The proper study of mankind is man."
But Rich is going to show you that it's equally proper
to study mice.
Why we can learn from our animal friends.
So with that introduction I'd like to give you Rich Halberg.
(applause)
- Thank you Dr. Lucey.
So, if I want you guys to think back to maybe first grade
when they came around and they said,
"What do you want to do when you grow up?"
When they asked me that question
I never one time said, I want to build a better mouse,
that was not an answer.
I think I said something about,
I wanted to detassel corn because my older brother
was detasseling corn and making lots of money,
so I thought that was really cool.
So why did I spend the last 20 years of my life
trying to build a better mouse?
The answer is on the next slide.
So colon cancer is the second leading cause of cancer death
in the United States
and in this year alone 150,000 people will be diagnosed
with colon cancer.
And those patients are all treated the same way.
They get surgery and then usually surgery's followed
by chemotherapy, and the chemotherapy
one of the drugs that we use is called,
5 Fluorouracil, it was a drug that was developed here
at the UW in the 1950s and it's still being used.
And for some of these patients they're very fortunate.
That drug works, and it works really well.
We cure them.
The big problem, we have two problems.
Half the people aren't cured
and the other problem is we don't know who will be cured
and who won't be cured,
and I think if I give you a simple analogy I can explain
why there is that different between those that'll be cured
and those that won't be cured.
So I want everybody to imagine their favorite car.
Do you got an image in your mind of your favorite car?
I bet you that car has tires, bumpers, doors, windshield
so on and so forth.
But when I think about my favorite car,
I think of about a 1965 Ford Mustang, red one.
'65 is the year I was born so that's why I picked that year.
If I talk to my mom, my mom talks about a Caddy.
She loves Cadillacs.
If I talk to my dad he thinks Model A's
with rumble seats are the best thing ever.
And when I talk to my wife she says,
"Rich, I want a yellow Volkswagen Beetle."
Guess what she owns?
Yes, a yellow Volkswagen Beetle.
(laughing)
So we know that there's cars,
there's many makes and models of cars.
That's absolutely true for cancers too.
We thought about cancer, colon cancer as being one thing,
but what we realize now is colon cancer isn't one thing.
Just like cars, there's many makes and models.
And if we just imagine in this particular example here,
we call 'em instead of makes and models,
we call 'em subtypes.
There's four different subtypes:
red, green, blue and yellow.
And it gets even more complex than that
because these subtypes can be mixed together,
and so you can get all kinds of mixes.
And so that's why probably some people respond to therapy
and some people don't.
Some of these mixtures will respond to these therapies
that we currently have, while other ones do not.
So Dr. Page, a couple months ago, came up to me
and he said, Rich can you summarize 20 years
worth of work,
over 50 publications, three book chapters,
in two slides?
I said, absolutely not.
I could do it in 200,
so we got a lot of slides to go through, just be still.
(laughing)
So, no we only have two slides to go through.
So in my lab what we try to do
is we try to model the complexity of these human tumors
as Dr. Lucey already indicated with the laboratory mouse.
And so what we've been able to do
is we've been able to do just that.
So our mice develop red tumors,
green tumors, and the tumors that are mixtures
of both red and green cells.
Now, for many, many, many years, over 100 years,
people have been saying that every cancer, each cancer
comes from a single rogue cell.
In fact a prominent scientist believed this so firmly
that he wrote a book called, The One Renegade Cell.
The fact that in our mice that we get these tumors
that are mixtures says this book is wrong, okay?
So that's the claim to fame for my laboratory,
that we've proven something we thought was true
for 100 years isn't accurate.
You might imagine though prominent scientists
don't like you throwing their books around though
and saying they're wrong.
So why do we care?
Why do we care whether or not a cell, a tumor's made
of a single cell or if it came from multiple cells,
why do we care?
I think we care, is shown here on this next slide.
So this is my only data slide
so just stay with me on this data slide.
It's pretty easy, pretty straightforward.
So I already told you and showed you on the previous slide
that our mice get red cancers, green cancers
and cancers that are mixtures of red and green cells.
So we use the colors, the red and the green--
they actually come from squids,
that's where those fluorescent proteins come from--
just to tell the difference between the tumors.
Are they made up of one color or the other
or are there mixtures, that's all we use those for.
But the more important thing is that the green cancers
are different at the molecular level than the red cancers.
That means that the green cancers have things
that we can target with experimental drugs.
And so there was a new experimental drug
that was developed that was for these green cancers
and we treated our mice with these drugs.
And what we found when we treated 'em,
no effect on red, no surprise right?
What do you think happened with the green ones?
Did we get more or less?
Who thinks more?
Who thinks less?
Hey, you win! (laughing)
Yeah, we saw significantly less.
It went from 50 to 20%.
What do you think happened when we looked at the mixed ones?
The ones that had some cells that this drug's going to work on
and some cells it shouldn't work on.
Do you think they responded to therapy or not?
Who says no?
Who says yes?
The no's have it.
They did not respond to therapy.
So that's why these studies in the animal models
are so important because they inform us
on personalized medicine.
That you have to target all the cells
that are within a tumor and so just knowing
what alterations may be in a tumor isn't enough.
You actually have to know what the structure of the tumor is.
And for any drug, any experimental drug
to move from the bench to the bedside
it has to go through these studies
in which we show pre-clinically with our animal models
that the drug actually is effective.
So in this case if a patient had a tumor
that looked like these green cancers
then they would likely benefit from this drug.
If they have something that's mixed they would not.
Now scientists are great at trying to reduce things
down to just one thing at a time.
We're reductionist by nature
and that's essentially what I've done here.
I've talked about the complexity of the tumor
and how that potentially affects response to therapy.
What we know though is it's a lot more complex than that,
and the complexity comes in that
you're different than I am,
and you eat different foods than I do.
So not only do we have to think about the complexity
of the tumors, but we got to think about
who are the patients that we're treating,
what types of food do they eat,
what pathogens have they been exposed to.
And so Dr. Saftar's going to talk a little bit about
the bacteria that live normally in our gut
and how that affects our overall wellbeing.
And Dr. Caldera is going to talk about
how when we're vaccinated against some of these pathogens
how our immune system, whether it's functioning
really well or not, affects how well
that vaccine's going to protect us from those pathogens.
So in my two-slide summary of my 20 years of work
(laughing)
I'm hoping that you got this.
That colon cancer is a leading cause of cancer death.
That colon cancer isn't just one thing,
but there's actually a collection of cancers.
And that those collections can actually be mixtures
because they can be derived from multiple rogue cells
rather than just a single rogue cell.
And because of this complexity
they're going to be difficult to treat.
So one cure isn't going to treat everyone.
So when we think about personalized medicine
we have to think about treating all the cells
within the tumor and not just a single population of cells.
And that whether or not these drugs
are going to be effective or not could be affected
by who we are, our own genetics,
as well as what we eat.
And moving forward what we do is we continue to use
these animal models to test these experimental drugs.
So I think my laboratory this year alone
has tested three different experimental drugs for colon cancer.
And what we need is we need animal models
that are very accurate
because it cost millions of dollars
and it takes years and years to move a drug
from the bench into the clinic.
And so if our animal models are accurate
and they show that a drug's going to work
and it actually works in a clinic, that's a win.
And our animal models, our innovative animal models
are much better models than what has been out there.
The UW is a fabulous place to work.
I feel extremely fortunate to be part
of the Department of Medicine, as well as the cancer center.
I've had the great fortune to work with many, many people
some of which are listed on this slide,
not everybody, there's just not enough room.
Used to be when I started my lab I could do it,
but I can't do it any longer.
And the work in my laboratory's mostly been funded
by the National Cancer Institute,
The American Cancer Society,
The American Association of Cancer Researchers.
And I just got a grant from NASA about two years ago
so believe it or not they want me to study
cancers in astronauts using my mouse model, okay.
But I've also been very fortunate that Dr. Lucey
decided to take a chance on a farmer from Illinois,
so I appreciate that Dr. Lucey.
And there's these guys that every year in June
I go up and visit
and they ride motorcycles through the woods
at a very incredibly fast speed
and their handlebars barely fit between these trees.
I don't know how they do it,
but they raise money for my laboratory.
I really appreciate that.
This is the Wisconsin Dual Sports Riders
and I also am pretty lucky that I have
friends and family that have donated
to my laboratory believing in the work that we do.
So thank you, and I guess we'll answer questions
at the end.
- Thank you very much Rich.
That was great and we're going to move along
as you've got a little foreshadowing there
of what the next talk is.
It's going to be given to us by Nasia Safdar
Nasia is an associate professor of medicine
and she's also got some other important titles.
She's the vice chair for research
in the Department of Medicine and the ACOS for research
at the William Middleton Memorial Veterans Affairs Hospital.
And she is an infectious diseases expert
and she's going to speak to us about
the interaction between the world of microorganisms
the gut and our health.
So thank you very much Nasia.
(applause)
- Good evening everyone.
It's lovely to be here talking to you today
about the gut microbiome.
I want to thank Dr. Lucey, Page, Rice, Minter
and Dean Golden for inviting me to speak
to you today.
The objectives of my session will be
to review the role of the gut bacteria
both in health as well as we'll take a case example
of an intestinal infection, C. difficile
to examine the impact of what happens
when there are changes in the gut microbiome
or gut bacteria and to illustrate how that imbalance
can profoundly affect our health
in ways that we couldn't even fathom a decade ago.
We are more bacterial than we are human.
I think that's worth chewing on for a little bit, don't you think?
It's a very humbling realization.
Just to get the terminology out of the way,
when you read the literature on gut bacteria,
as you might be prompted to do so after today's session,
if you've have nothing else to do
and you're really at a loose end,
microbiome just refers to the collection of genes
that are present in the genomes of bacteria.
And microbiota refers to the actual bacteria themselves.
In essence a human body is really
a multi species consortium of human cells,
bacterial cells, human genes, and bacterial genes.
Why is this important?
Well surely all these bacteria that are present in our system
and even though today we're focusing on the gut
we have bacteria literally everywhere that you can imagine.
The skin, the nose, any other orifice you care to name,
there's bacteria there.
So there's a state of symbiosis that exists
between us and the gut bacteria
and if there's any imbalance in the normal
harmonious relationship that exists
that's what causes us to feel ill.
The gut bacteria really has just one role
and that is to defend us from the insults
that we get exposed to.
It's role sometimes may be to defend us from ourselves.
So say the donut you had this morning.
Some of your good bacteria probably groaned
when they saw it coming their way.
Some of the bad bacteria probably felt really good
about the sugars that they could get from it.
So the multitudes within us
guide how we live our lives
and even though we're going to focus mostly
on the bacteria, there are of course viruses, fungi
and other types of organisms in the intestine.
I think it's instructive to point out
that most of the bacteria that are in our intestine
are actually in the colon.
So that's where if we were to intervene in any way
to manipulate the gut bacteria that's really
where we would need to intervene.
But the entire intestinal tract is host
to a whole bunch of organisms.
The majority of these are anaerobic.
This is important only because they're very difficult to culture.
So for many decades using conventional
microbiology techniques people weren't able to figure out
exactly how many organisms were there in the intestine.
It's only been in the last couple of decades
that we have PCR techniques
and other molecular methods to be able to determine
what actually exists
and now that we know what exists we can figure out
what it does.
The number of bacterial cells in your body
are 10 times greater than the number of human cells.
I can't say this enough it seems.
So how do we figure out what the role is
of these gut bacteria?
Well, there's three distinct lines of inquiry.
The most fundamental is to determine what's there
and that's where the field started
with these culture independent methods
and using PCR and other sophisticated approaches
we're now able to get a pretty good handle
on what the structure is of organisms
in the intestinal tract.
The next step is to figure out what's the function.
If they're there, what kind of role are they playing,
and how important is that role for health and disease?
And that's the new areas of transcriptomics
and proteomics and metabolomics
that is determining the function of these organisms.
The holy grail of everything will of course
be to determine what does manipulation
of this gut bacteria look like
and how can we change the course of disease
by doing something as seemingly fundamental
as changing the composition and the function
of the bacteria that exist within us?
We are a ways away from that
but the field is moving at an astonishing speed.
This list of conditions associated with imbalance
in the gut bacteria has probably gotten longer
in the five minutes that I started talking.
Literally it seems every day that there's a new condition
that is associated with it
and this is by no means an exhaustive list
but obesity, diabetes, metabolic syndrome,
cancer, something as disperate as allergies
and bowel diseases such as inflammatory bowel disease
that Dr. Caldera will talk about in a little bit
and Metabolic Syndrome that Dr. Rice will talk about in a little bit.
It all boils down to this imbalance.
So there are some bacteria, just to go with this analogy here,
that are good in this instance and some that aren't
and the relative abundance of one versus the other
will determine whether you are healthy
or whether you're ill.
The gut bacteria is also very flexible
throughout our lifespan.
We start out as a child with a lot of modification
that happens from the time that one is born
to a baby and a toddler.
And just to orient people to this slide,
if you look at the colors most of the gut bacteria
are really go into these two groups.
They're called firmicutes and bacteroidetes.
The light blue and the pink is what
most of the gut bacteria should look like.
And you can see that in the healthy adult population here
that's what most of it is.
There's a little smattering of other colors
but those are the two predominant ones.
However, that's not the case in individuals
of obese, and that's not the case in people
who are malnourished.
This red here is very alarming
because it suggests that there's new populations
of bacteria that are not beneficial
to the host that have now taken over
some of the beneficial bacteria that should be there instead.
This is also the case with advancing age,
although for the most part,
it's only after the age of 100 that these changes
really occur dramatically.
But any condition that you can think of
will affect this balance that exists
and that's what we think accounts for
the symptomatology of that condition in part.
Now everything is multifactorial and very complex
but the gut bacteria certainly shouldn't be discounted.
They seem to play a key role.
So as an example, we're going to take the case
of clostridium difficile infection
commonly called C. diff.
It's almost always in the press
as it has grown to be a very common healthcare
associative infection.
What does it look like?
It's an anaerobic bacteria.
It forms a spore which is in part
why it's so difficult to contain.
The reason that it got its name, Difficile,
is that it was very difficult to culture.
It needs special microbiologic media
and so most places find it difficult to culture.
And this spore is the reason that it's difficult
to eradicate from health care institutions
because the spore is resistant
to virtually any disinfectant that you can think of.
The only thing that works for it is a high concentration
of bleach and even that it can find ways to get around.
So there's one pathogen we really want to try and prevent
in healthcare institutions, it's clostridium difficile.
Having said that the current state of affairs
is that there are still about 500,000 cases a year.
About 30,000 deaths.
There's a 30% recurrence rate, which is very problematic,
because you can get away,
you can be treated for the first episode of C. diff
but if 30% recurrence rate means that you're going
down into this vicious cycle of second episode,
third episode and so on.
It's a severe diarrheal illness
that has a major impact on quality of life and suffering.
Some of my patients in clinic tell me
that they have had to completely change their lifestyle
ever since they got C. diff.
They no longer go to see their grandkids.
They no longer go to eat out.
They're always trying to make sure
that there's a rest room close by.
These things are not trivial especially when you think
about the fact that the incidence is highest
in those over the age of 65 years.
Those individuals are getting somewhat frail
and might find it difficult to
now handle their lives with C. diff.
So what role does the gut bacteria play
in the manifestations of C. diff?
This slide shows us, let me just orient you here to this.
So this is a study where they took some control patients
who were healthy.
Some patients who had had an initial episode
of C. difficile such as the one episode
and then others that had had multiple episodes.
So if you look at the colors here
the green and the red are what's normal.
So in the control populations
asides from this minor smattering here
the vast majority of bacteria are either in the green
or in the red group.
This remains the case with the first episode of C. diff.
So even though you've had C. diff this hasn't altered
the bacteria to a great extent.
But look what happens to the group with recurrent disease.
In this individual for example,
the entire green has been replaced with this purple group
which again is not something you want to see
and it's not advantageous to the host at all.
Same thing with this patient here
where most of the beneficial bacteria
have been replaced by this abnormal imbalance.
And it is that imbalance that must be cured
if we are to treat the symptoms of C. difficile effectively.
Well, this gives us an idea
for therapeutic manipulation, doesn't it?
How can we get back to a healthy gut bacteria?
Well fecal microbiota transplantation
or taking healthy stool from a donor
and putting it into the intestine of somebody
with C. difficile is now a therapy
that has really taken the whole field by storm
because nothing else seems to really work very well
and this does seem to work well.
I don't necessarily recommend that people try it at home.
(laughing)
But you'd be surprised how many people have.
You know, desperate times call for desperate measures.
But this is basically what it looks like.
And if you do the at home equivalent,
this is all you need. (laughing)
All of these items are readily available.
Don't forget the Lysol, it's really kind of critical
to the whole approach.
And who are the donors?
There's a wide variety of them.
We also have an oral form
of fecal microbiotic transplantation that comes like this.
Unlike any other medication where you have to take one pill
or two, if you're undergoing this procedure
you have to take 30 capsules of this.
But the most important question I think is
does it work and how well does it work?
This is an example of how well
fecal microbiota transplantation work.
If you look at the control treatment here
which is what's considered usual care.
So for most people with C. diff
they'll get oral Vancomycin, which is an antibiotic.
Oral Vancomycin works about 30% of the time
which is a very dismal cure rate
for recurrent C. difficile infection.
However, when you do infusion of donor feces,
and in this case they did it via a nasogastric tube in a form of a slurry.
But no matter which route you take
it works about 81 to 94% of the time.
Those are astounding cure rates
and there's no other antibiotic that comes even close.
So I think that's part of the reason why patients are willing
to go the route of fecal microbiota transplantation
because it relieves the symptoms associated with C. diff.
In your spare time you might want to consider
being a donor for fecal microbiota transplantation.
What else are you going to be doing in the evenings?
You might as well proceed with that.
The criteria to be donor though
for a fecal microbiota transplantation
are very, very strict.
Only about 2% of people that apply to be a donor
actually get selected to be a donor,
because you have to be free not only of all chronic
and infectious conditions,
but a whole host of other things that one is tested for.
This is our way, the field's way of making sure
that even if we have to do this procedure for patients
that it in the safest possible way
and we're not inadvertently transmitting something
that we shouldn't be transmitting.
In the future we hope that there will be
precision fecal microbiota transplantation
where you can get the benefits without the mess,
so to speak.
There's also a bunch of other reasons
why fecal microbiota transplantation
should be employed for treatment of C. difficile.
There's no production shortage. (laughing)
And there's no addiction potential. (laughing)
Thank you very much for your time
and we'll be taking questions at the end.
(applause)
- Thank you very much Nasia.
We're going to continue our move
to another clinical indication
of the interaction between
the gut microbial world and human health.
We're now going to look at inflammatory bowel disease.
Our speaker is Freddy Caldera.
Freddy received his medical degree
from Des Moines University
and then his medical residency and G.I. fellowship
at the University of Kentucky
and since then has been here
as an assistant professor in our division
with a special interest in Inflammatory Bowel Disease
and he's going to talk to us today about
Inflammatory Bowel Disease, building better therapies.
(applause)
- So I want to thank the organizers for allowing me
to talk today on a topic that's very dear to my heart
which is treatment of patients with Inflammatory Bowel Disease.
I'm actually a little jealous of Dr. Halberg.
I didn't know we could bring props.
I would've brought a scope from the DHC,
but I think Dr. Lucey might have had a talk with me
afterwards for taking it.
(laughter)
So over the next eight to 10 minutes
I'll be talking about
what is Inflammatory Bowel Disease,
how we treat it
and how we can keep patients safe with treatment.
And some of you in this room or the additional two rooms
or maybe at four o'clock in the morning
might actually have Inflammatory Bowel Disease
or have a loved one, whether it be a child,
a grandchild or a friend that's afflicted
with Inflammatory Bowel Disease
because at times having Inflammatory Bowel Disease
can be like, untreated, can be like having C. diff
all the time, where it can control your life.
But Inflammatory Bowel Disease
it's a group of intestinal disorders.
So even going back to Dr. Halberg's talk
you know there's more than one but for the most part
it's a condition where our own immune system
causes inflammation in the intestine.
The two main types that many of you
and what we'll definitely talk about today
is ulcerative colitis and Crohn's Disease.
It's a chronic condition that can cause inflammation
that's incurable.
It's autoimmune just like other autoimmune conditions
like rheumatoid arthritis,
but nowadays it's a very treatable condition.
You might be asking yourself,
well I've never heard of inflammatory bowel disease,
is this really common?
So it affects about three to four million Americans
with 70,000 new cases each year.
So that means one in 200 people.
You might actually be surprised.
You might actually know someone who has
inflammatory bowel disease
but probably has never said anything
because you know, talking about diarrhea,
about bleeding or having an accident
are not really socially acceptable conversations.
But even if you don't know someone
you might actually know someone in the future
because we're actually seeing more cases
of inflammatory bowel disease now
in all the industrialized nations
and what's really interesting is we're actually seeing it
in parts of the world where we never saw it before.
So where it's being seen more in the Middle East,
in Asian countries, and in Latin America.
We didn't see that in the past.
You might be saying, well what is really inflammation?
So, our immune system, so the part of our body
that keeps us healthy, you know,
has a very basic way to deal with an insult.
So we all have had a splinter.
And at times that splinter gets really irritated,
and gets red, and it's not infected.
It's just your own body responding to that insult.
And what it does, it causes inflammation.
So these are white blood cells that go to this area,
make it warm, they can cause pain.
So just like if you have an infection in your hand
you could see that this is very inflamed
compared to that.
And the same thing can happen with someone
with inflammatory bowel disease.
Where their intestine gets inflamed.
And after learning that we're actually
more bacteria walking around in human bodies
you might be saying,
well why doesn't everybody get inflammatory bowel disease?
And so basic research actually asks that question.
Why doesn't everybody?
And we know that there's 163 genes
associated with inflammatory bowel disease
but we know that most people with those genes
don't get it.
So it's a disturbance in the microbiome, you know.
Is it we live in a very clean environment?
Is it changes in our diet?
Is it changes in the environment or pollution?
We actually don't know.
But we know once this immune response happens
you have the state of inflammation.
And once that happens you can't go back.
So we have two types.
We have ulcerative colitis.
So as you can see in red
this is the large intestine or colon
so if any of you here had a colonoscopy
that's the part of the intestine we look at
and depending on the amount of inflammation
in the colon, it can lead to bleeding,
diarrhea, to the point where some of my patients,
they're like, looking bathroom, after bathroom, after bathroom.
And they can have periods of abdominal pain,
they can have incontinence.
And as you can see in this picture,
you don't need to go to medical school
to say one looks better than the other.
This is the picture of someone with ulcerative colitis.
This is one of my patients where they were newly diagnosed,
they're in their 20s, they just got into college.
And at first they didn't want to go seek care
because they were worried why they were bleeding
and they had lost about 20 pounds.
And we got his colon to look like this
which is a normal colon.
So you can definitely see how this can afflict someone.
And some of the complications that these people can suffer
is they can develop anemia,
they have an increased risk for colon cancer.
This is a picture right here of colon cancer
in a patient with ulcerative colitis.
And they can even develop a perforation or ruptured bowel.
While Crohn's disease is a condition
that can affect anywhere in the intestine.
So it can go from the mouth, all the way to the anus
and depending on where you have inflammation
it can cause either abdominal pain,
diarrhea, it can make it feel like someone
has an ulcer if it's only in the stomach.
And it can also lead to complications.
It can lead to a blockage
where someone might also need emergent surgery.
It could lead to colon cancer
in patients who have inflammation of their colon.
It could lead to an abscess so a pocket of infection
or narrowing.
You might be thinking, wow this is really depressing.
This sounds like a horrible disease.
And while it can be a very bad disease
and in the 1960s or the 80s
there wasn't much to treat it, you know.
So this would've been a way shorter Mini Medical School one.
But most people would have surgery,
might need Prednisone,
but nowadays most patients are actually treated
with immuno-suppressants.
And these medicines that decrease
the activity of the immune system have actually
transformed the field.
And actually not only are the medicines we have now,
but medicines that are in the pipeline,
have really transformed it to the point where
you saw that colon where it went from
inflamed to not inflamed.
Where we're actually changing
how the disease is behaving.
So the majority of patients I see in clinic
can lead a normal life, you know,
whether they're a physician, whether they're a CEO
whether they're a nurse or a policeman.
For the most part they lead a normal life.
Where I usually have 'em come in
when they're healthy also and then they're like
well, do I still have to see you?
I feel fine, why do I have to come in? But that's the goal.
The goal is we want to keep that patient safe
and we want to keep him in remission and feeling well.
But being well and staying well comes with a price.
That price is there's a risk for infection.
So one of the most common complications
of all the treatments we have,
because they're altering the immune system,
is there's a risk for infection.
But many of these infections are actually preventable.
So for anyone in the room,
so there are not many vaccines we give to adults.
Obviously everyone if they've watched the news
in the past nine months has heard that
the flu was very bad this year.
So that's why everybody should get a flu shot.
You know, everyone in this room should also get
a booster shot for pertussis or whooping cough.
A vaccine for pneumonia.
There's actually a new shingles vaccine
that now the age actually went down to 50.
And this really doesn't change for patients
with inflammatory bowel disease
and it's actually of extreme importance,
because we said, infection is the most common
complication they can have.
And actually that's what our work at UW
has focused on is trying to prevent
these infections so we're not trading
one complication for another.
So some of our research has shown,
which has been aided by philanthropy,
that patients with inflammatory bowel disease
don't respond to the regular flu vaccine.
So we did a study where we gave them
a high dose influenza vaccine
which is the influenza vaccine for anyone
above age 65 and we showed we had better protection.
We did a study where we checked their titers to pertussis
and we found that they have lower protection
to healthy people.
So because of that we're recommending
they should get pertussis vaccine every 10 years.
And we just finished a study where we did
in people 35 to 49 and we found
that someone with inflammatory bowel disease
whether they're on medicines that suppress their immune system or not
actually had the same risks for shingles
as someone in their 50s.
So that's going to follow a study
where we're going to try and vaccinate people under 50
with the new shingles vaccine.
So some of these common complications
you know we can prevent.
That's where we want to improve the quality of care
we give these people.
But in summary if you've not heard anything at all
if you meet someone or you heard someone
that is dealing with inflammatory bowel disease,
at least let them know that there are treatment options
because it has severely changed
and we can give someone back their normal life.
So there are two conditions called Crohn's
and ulcerative colitis that can have bad complications
but nowadays we can treat it to the point
where they almost don't know they have it.
So, thank you.
(applause)
- Thank you very much Freddy.
If you're reliving the medical school experience,
another very common and repeated experience was,
are we nearly at the end yet?
But you are nearly at the end.
Even when it's been a great set of lectures
the end is something that's welcome
when it's in sight and so we have a closing talk.
It's from Dr. John Rice.
John received his medical degree
from the University of Nebraska
and he did his medical residency and G.I. fellowship
at Northwestern University in Chicago.
He then came here
and is our assistant professor
in the Department of Medicine.
He's also the section chief of the section of hepatology
in the division of gastroenterology and hepatology
and he is going to talk to us about,
what is the big deal about fatty liver.
(applause)
- Thank you Michael.
Thank you to our mini Deans here
and thank you for the opportunity to speak.
I'm going to spend some time tonight talking about fatty liver disease.
Some of you may be familiar with it, some of you may not.
But we're going to kind of give you the lowdown here
about fatty liver and why we care about it.
Why I care about it from a liver perspective.
So the objectives are relatively simple here.
We're going to talk about what is fatty liver disease
and something called the metabolic syndrome.
Why do we care? So if somebody has fatty liver why do we care about that?
And then the most important thing of course is how do we treat it?
So what do we mean by fatty liver?
Okay, so what fatty liver is
is the accumulation of triglycerides or fat droplets
in the hepatocytes or the cells of the liver.
So your body is made up of cells.
The liver cells are called hepatocytes
and in fatty liver the hepatocytes get fat deposits in them.
If you look at the picture associated with this slide here
the top picture is a normal liver.
The bottom picture is a liver that has
fat droplets and you can see the clear areas there
as fat deposition of the liver.
So when we see somebody with fatty liver
there are two principle causes of fatty liver.
The first one is alcohol, okay?
So people who drink alcohol particularly to excess,
it causes fat accumulation in the liver.
And then there's not alcohol.
A cleverly named non-alcoholic fatty liver disease
also called, NAFLD as the term we'll use for it.
Okay, and NAFLD is closely related to something
called the metabolic syndrome.
That's the fatty liver I'm going to be talking about tonight
is the non-alcoholic version.
So what is the metabolic syndrome?
The metabolic syndrome is a condition that's associated
most commonly with obesity.
Obesity's defined as a body mass index
which is a ratio of your height to your weight
of greater than 30.
And when that sort of condition happens
when obesity happens it puts you at risk
for other things happening.
That includes the elevation of blood pressure
or hypertension, cholesterol problems,
so an elevation of bad cholesterol
and a lowering of good cholesterol.
And then something called, insulin resistance.
Insulin is a key hormone in your body
that's involved in blood sugar regulation.
When somebody becomes obese their body can become resistant to the effects of insulin
which leads to elevated blood sugars which is diabetes.
But also along with those core pieces
of the metabolic syndrome we see people get fatty liver,
we see people develop heart disease,
kidney disease and then sleep apnea.
So it's a systemic problem.
It goes along with the prevalence of obesity
and as you can see the rising rate of obesity
is concerning because we're seeing more and more people
with the metabolic syndrome.
Many people have probably seen this map.
This is the map of obesity prevalence in the United States
through the years.
And as you can see here back in,
I think it was 1985 when this started,
you see that there was a lot of whites and blues.
That's a very low, or light blues.
That's a very low prevalence of obesity.
As we move up into the 2000s it just gets worse
and worse, and worse, and worse, and worse.
Colorado held out for a long time,
but even they are getting more and more obese.
So obesity is a major public health crisis.
And obesity is a major cause of fatty liver.
But why do we care? Why do I care about fatty liver when I see it?
Well, fat deposition of liver can lead to inflammation.
Freddy talked a little bit about inflammation
is basically a wound healing
or an inflammatory response to an insult.
When that happens as a response to fatty liver
scarring of the liver can develop
and over the course of time, often times many, many years
that process of inflammation and scarring
and inflammation and scarring, and inflammation and scarring
leads to cirrhosis of the liver.
So the first thing I always hear when I tell somebody
they have cirrhosis is, but I don't drink.
Yeah, I believe you.
It's that most of these people who have fatty liver
related to obesity.
And then cirrhosis sets in
and all sorts of complications can develop.
The scary thing is that whole process of developing
cirrhosis is oftentimes asymptomatic.
We've talked a lot about the microbiome tonight
and this also plays a role in obesity and fatty liver.
Dr. Saftar mentioned the role of the microbiome
in the development of obesity.
We also see importances in the microbiome
in the development of fatty liver and fatty liver
and inflammation, okay, so it's a vicious cycle.
It's a situation where dietary changes
can lead to alterations in the microbiome
which can then promote fatty liver
and fatty liver and inflammation and eventually cirrhosis.
But it's important to point out
that it's not just liver disease.
People with NASH, which is fatty liver and inflammation,
are three to four times more likely to die
than people without NASH.
But the most common reason they die is heart disease.
Okay, so it's a systemic illness.
It's not just liver disease,
but you can't forget about the liver disease.
This is a graph that shows the number of liver transplant
wait list editions on one side,
and the number of obese Americans on another.
And they're linearly correlated.
Meaning that as more and more Americans become obese
the number of people who need liver transplants
for fatty liver disease goes up.
And unfortunately there's a cancer risk with this as well.
Liver cancer or cancer that originates in the liver
almost occurs exclusively in cirrhosis, okay?
NASH is the most common reason that people are developing
liver cancer nowadays.
So we're seeing more and more of this liver cancer
and cirrhosis related to fatty liver.
It's interesting because the world of liver disease
has changed quite a bit in just my short career.
Many of you are familiar with Hepatitis C.
For those of you not familiar with Hepatitis C,
you may see cryptic ads on the TV that suggest
you might have Hepatitis C, okay?
Well the reason that happens is that Hepatitis C
is very prevalent among baby boomers.
They are the most prevalent population
in the United States, okay?
There's a lot of reasons that that happened
most of it was a lack of public health awareness
to be perfectly honest with you.
For years, and years, and years, and years
the most common reason we transplanted people
in the United States was Hepatitis C.
About five years ago the first direct acting
antiviral medications for Hepatis C were introduced
and in this short amount of time
multiple drugs have come out in the market
and almost everybody who has Hepatitis C
can be cured at this point with drugs.
12 weeks, all pills, pretty easy to take
and 99% of people will get rid of their Hepatitis C, okay?
So those of you born between 1945 and 1965
the recommendation of the CDC is to be tested,
one time, for Hepatitis C because again,
it's usually an asymptomatic infection
until something bad happens to you.
But as these drugs have come on the market
the number of people who need a liver transplant
from Hepatitis C is plummeting, okay?
And last year, or 2015 I should say,
Hepatitis C no longer became
the leading indication for transplant.
But as you can see here in the dashed line,
the big dashes, fatty liver disease is now passing it.
So we're seeing the sunset in some ways of one disease
and in some ways the dawn of another.
Okay, so that's fatty liver.
We know it's getting more common, it's more prevalent,
it rises with obesity, how do we treat it?
What would you do if told you that I had a great treatment for you?
Here's what it does. It lowers weight, it builds muscle mass,
it improves bone strength, it improves mood,
it lowers blood pressure, it lowers cholesterol.
This sounds pretty good right?
It treats fatty liver, what is it?
- [Audience] Exercise. - Hey!
(laughing) Diet and exercise, okay?
That is really the cornerstone treatment
for fatty liver disease.
Weight loss via dietary restriction and regular exercise
can lead to improvement of liver blood tests.
So one of the ways we measure if the liver looks
like it's inflamed or injured is to just simple blood work.
The liver will release things into the blood that we can measure.
We know that if people who have fatty liver lose weight,
their liver tests can normalize.
People who have biopsies,
so they have biopsies before they lose weight
and then biopsies after they lose weight,
tough to sign people up for those kind of studies
but you can see improvement
in the liver inflammation and resolution of the fat.
In addition you can see improvements in everything else.
Lower blood pressure, better cholesterol,
better sensitivity to insulin.
There's a lot of dietary fads out there.
You know, intermittent fasting, keto, all that sort of stuff.
To be honest with fatty liver there's been no
optimal diet that's been studied.
What's clear though is if they lose weight
and get some regular exercise you can improve fatty liver.
The real challenge I have to say about that though
is that because fatty liver is usually
an asymptomatic process until cirrhosis
or liver cancer develops.
It can be a challenge to get people
to really buy into what you're telling them,
because what I'm telling them is
even though you feel fine now for the most part
this process is going on in your body
and might actually kill you at some point.
Medications,
there are no FDA approved medication for fatty liver.
There's stuff in trials, there's stuff they're investigating.
I don't know if they'll be effective or not
but it's also when you think about the sheer number
of people, I think at one point they said
there were four million Americans with Hepatitis C.
Think about fatty liver, 30% of the population, way more than that.
So, right now there are no FDA approved medications.
What about weight loss surgery?
So you guys are probably familiar with the term, gastric bypass.
So weight loss surgery has been studied
in people with fatty liver and obesity
and the results have been mixed.
It's clear that people who undergo
gastric bypass or their weight loss surgery or procedure
lose weight, most of them will lose weight
as long as they stick to the diet.
And it's definite that some people with fatty liver
will see the fat resolve in the liver.
They'll see the inflammation decrease.
Interesting though some people have seen
a worsening of the scarring in that process.
So we're not quite sure why that happens, okay.
So the role of weight loss surgery
in the treatment of fatty liver is still being explored
but it's definitely an option for people
who really aren't losing weight by any other means.
Liver transplantation.
So this is sort of the final pathway.
If you develop cirrhosis
and you start getting complications from that.
For many patients with liver cancer
this is the only option that's life saving, okay?
So as I mentioned before we're seeing more and more people
who need liver transplants because of fatty liver disease.
One of the things that really attracted me
to the study of liver disease and the practice of liver disease
is it really is a team sport.
We have an enormous team at UW
who participate in liver transplants
and these are just some of the members of it.
It really is a sport where everybody gets together
and works in a collaborative fashion
to try to help people manage their end stage liver disease
or their liver cancer
and then manage themselves after transplant.
It's really one of the most attractive parts of the process.
We have a very robust transplant program at UW.
So the comprehensive UW transplant program
which was established in 1966,
one of the first programs in the country,
is the sixth largest program in the country.
So in terms of solid organ transplants,
kidney, liver, heart, lung,
it is the sixth largest program in the country.
We've served patients from every state
and 10 different countries.
We started doing liver transplants here in 1984
and have completed over 2500 liver transplants at UW.
Last year was the most number of transplants
from a liver standpoint we've ever done.
We did 125 liver transplants.
We're a multidisciplinary team as mentioned before.
We have five surgeons, seven hepatologists,
or liver specialists.
14 nurse coordinators and many social workers,
addiction counselors, administrative staff,
who all help keep the liver transplant team up and running.
We offer different donors.
So most are deceased donors so people
who've been generous enough to donate their organs
as part of their last wishes.
We also do live donors,
occasionally we do pediatric transplants
and then multi organ options such as liver, kidneys.
We've done our first heart and liver transplant
simultaneously this year.
So a different number of options there.
And part of maintaining a solid and state of the art
transplant program is through groundbreaking research.
Studying transplant, making it better,
improving quality and that's through generous donations
from donors we're able to do that.
So, to sum up did we talk about in my short little time here?
Fatty liver disease or also called NAFLD
is most often a consequence of obesity.
And as a result of the obesity epidemic in the United States
fatty liver is becoming much more common
in the United States.
Fatty liver is a leading cause of liver cirrhosis
and liver cancer.
The treatment is still weight loss through diet and exercise
and it can lead to improvement or resolution of fatty liver.
And fatty liver is a leading indication
for liver transplantation.
Thank you.
(applause)
- Thank you very much John, thank you to all four speakers.
Thank you to all of you for paying such good attention.
We've heard four great talks
and listening to them
two things occurred to me.
One was the span from bench to bedside
starting with Rich Halberg showing that changes
that really can affect the wellbeing of patients
start at basic science research.
And then through Nasia's talk, through Freddy
and from what you've heard even from John,
the range of changes that are related
to this important aspect of health,
the microbiome and the gut.
And the final thing I would say
is I think all of the talks emphasize the value of research,
all of them have looked forward as well as look back,
and we will not improve the health of patients
in the future without continuing that commitment
to improving health by working
from the bench to the bedside.
So with that brief summary I'm going to hand over
to one of our mini Deans, or maybe both our mini Deans.
- Dr. Halberg I'm aware
that you are at a whole different level
of expertise and you do colonoscopy on mice.
Can you give us a little bit of insight on how that happens?
- So you actually want to come see me if you need
your colonoscopy, my scope's only this long.
(laughing)
And it's only that big around.
So unfortunately I can't tell you too much though.
So yeah, we do colonoscopy on the mice.
I showed you the red and green fluorescent proteins.
We can actually see the tumors in living breathing mice
and see how they respond to therapies.
So in some cases, not an example I showed tonight,
we can actually see the green cells
melt away from a tumor while the red cells persist.
So it's a very powerful tool.
The beauty of it is that because we can do colonoscopy
on the mice and we can see the response in real time,
the number of mice that we need to use goes way, way down.
And so we're very contentious of the animals that we use for our research.
- [Dr. Page] Thank you Dr. Halberg.
- [Dr. Rice] I have several questions here about probiotics
in the human biome so, Nasia?
- So probiotics seem very attractive
because if we know there's an imbalance
in the gut bacteria can replacing it
with one or two different species of bacteria
restore the balance that we seek?
The problem is I think two-fold,
one is that we don't know enough about which probiotic
to use, is it sufficient for example overdose on yogurt
once in a while, will that get us what we need?
Probably not.
And the other is that given the millions of bacteria
that exist in our intestine
I think it's a little simplistic to think
that taking a few million probiotics
will restore imbalance that there is.
They probably don't hurt the vast majority of the time
but whether they help or not
I think remains to be determined.
- You know, I have quite a few on probiotics as well,
but here's one that's not exactly
and perhaps this would be for Dr. Caldera.
Are there fecal treatments for inflammatory bowel disease?
- So not yet, I've actually had more than a couple patients
who whether their inflammatory bowel disease
was pretty severe that they tried fecal transplant at home.
But to date there's no definitive
either fecal transplant or probiotics
have been shown to work for a lot of people.
- [Dr. Rice] Okay, I understand that drugs
to treat Crohn's disease are expensive
and often not covered by insurance.
Is the hope that the cost of the treatment
will be decreasing in the near future?
- So not all drugs are expensive.
The ones you see on TV are expensive.
But honestly, very rarely does cost become an issue
in limiting me in treating someone in my clinic.
Actually the majority of the time regardless
of the insurance it might take maybe an hour phone call
with me doing a peer review,
but we usually get the medicine that's needed.
- Thank you.
I have two questions actually.
One is Dr. Page, will you ask my niece
in Burlington to call, email, text more often?
(laughing) We'll talk later.
I like that.
Dr. Rice, this is really serious.
Should we opt out or opt in for organ transplantation?
- Well we always say you can't take 'em with you
so you might as well leave 'em here.
But you know obviously in the United States
it is a completely voluntary donor pool,
meaning that people have to opt in.
In some countries actually it's an opt out,
meaning that you have to say I do not
want to be an organ donor.
I would encourage anybody to be an organ donor.
There are way more people on the wait list
for all organ types, then there are organs available
and it truly is a life-changing event
for somebody to get an organ transplant.
You're talking about people who are suffering mightily
from end stage disease and it really does restore quantity,
and quality of life, so I'd encourage anybody to be an organ donor.
- Okay, this is for Dr. Halberg.
What percentage of drugs that are effective in mice
transition to be helpful in humans?
- That's a challenging question.
There's been in the animal models
that we've used in the past there's been
over 300 drugs that have been tested.
I'd say about 10% of them have made it on
to being shown to be effective in the clinic.
But those models aren't as effective as our new models,
so I think we'll get better as time goes on.
- Maybe I'll have Dr. Lucey comment on this
because you all may not know this
but the University of Wisconsin was a pioneer
in offering both the endoscopic colonoscopy
and virtual colonoscopy.
And the question is-- first of all Michael
you might comment on virtual colonoscopy--
and also the question was,
how does the prep for that or perhaps
routine colonoscopy affect the microbiome?
- Well, I can answer the second question first
because I don't know.
(laughing)
It clearly can't like it because
it's cleaning out the colon
but one of the aspects of this
which I think was eluded to by Nasia
is that the microbiome is a dynamic thing.
It's not a fixed thing.
So at all times there are pressures on it
to increase in one direction or another
according to the composition of it.
In a healthy person one presumes,
but I've no data on this,
that after having colon prep for a colonoscopy
you restore the microbiome that you had before,
that would be what one would anticipate.
The prep for virtual colonoscopy is virtually the same
as the prep for standard colonoscopy.
- [Dr. Page] Thank you. - Okay, here we go.
How quickly should a meal pass through your gut or your body?
What causes bowel movements almost immediately
after every meal?
- Well I can answer the second part.
That's a reflex, so any of you who have
seen a baby being fed at the breast
and you hear a squirting sound coming out the other end,
that's not the milk coming in at the top
coming out at the other end.
That's a gastrocolic reflex.
So the gut is contracting in response to feeding.
I forget the first part was how long does it take.
Anywhere from a few hours to a few weeks.
It depends on who you are.
(laughing)
- Thank you.
This might actually go to any of you.
Just asking about prevention for the problems
we've discussed today.
Any further advice and specifically
does organic food play any role in digestive health?
- So I will tell you what I tell most of my patients
even with inflammatory bowel disease,
because you could Google all kinds of things
of treatment of inflammatory bowel disease.
I definitely think a healthy diet, a diverse diet,
where there's actually a study in the microbiome
showing that you want to diverse microbiome
is probably more worthwhile than getting
supplements where we don't know what's really needed.
So getting your fair share of fruits and vegetables,
fruits, fish, all the things that kind of Dr. Rice said,
that's what I would suggest.
As far as organic, I don't know.
Depends how much you want to pay. (laughing)
- The non-MD can add one thing.
So there was an eloquent mouse study
that was recently done showing there is no perfect diet
for any particular mouse model.
So what they did is the tried four different diets
and they had four different strains of mice
and they showed none worked perfectly
for all four strains of mice.
So as we talked about in my talk the differences
between each one of us and what we eat.
What may be best for me, may not be best for you.
- So how can there be such a thing as live liver donor?
You take a piece of the liver out and put it in
and then it regenerates in the donor?
- That's a good question.
The liver is made up of two lobes, the left and the right
and it has tremendous regenerative capacity.
That doesn't mean that the blood vessels
and the bile ducts and none of the plumbing
of the liver regenerates but the liver will grow
to whatever size a person needs.
So the way a live donor liver transplant works
is if somebody has compatible anatomy
and can give enough liver to the recipient
and keep enough liver of their own,
you can remove half the liver and transplant it
into somebody else.
Six, eight weeks later they'll both have enough liver
for what they need.
It'll be way bigger than when they planted it in.
A healthy liver has the ability to hypertrophy
or grow to accommodate the needs of the person.
- Thank you.
Dr. Caldera, we saw the fact that the risk of shingles
goes up and the recommendations for shingle vaccination
apply to at least a few of us in the room.
But what if someone's had shingles before.
Do they need a shingles vaccine?
- You definitely should.
Shingles, remember it's chicken pox
that everyone probably in this room had.
Nowadays most people when Dean Golden was talking about
they probably got the chicken pox vaccine.
So chicken pox virus kind of stays around,
and once you get shingles,
it can still come back and visit you
and anyone whose had shingles knows
they don't want it to come back.
So you should definitely get it.
- Exactly, okay this is for Nasia.
Is it true that a potential side effect
of fecal transplant is negative psychological conditions
can be brought out such as depression,
bipolar disease, and anxiety?
- You know that's interesting.
I think you get sort of the bad with the good.
So depending upon your donor,
it's possible that you could be subject
to some of the same experiences that the donor was feeling,
which is why this criteria for picking a donor
is so strict and medical students are popularly believed
to be a really good choice for a donor for this very reason.
This is before the first year of med school.
After that they probably get too stressed
to really serve as good donors. (laughing)
So there is at least one case report in the literature
where somebody who was lean
before they got the stool transplant
became obese after it and blamed it on the donor
who gave them the stool, so anything's possible.
- I guess this might be Freddy.
What is the role of heredity in developing Crohn's disease?
- So it's not completely,
so we said it's one in 200 people in the U.S.
will get inflammatory bowel disease.
So if you have a first-degree relative,
or the question I get always is,
will my child have inflammatory bowel disease.
So that only increases to 10 to 15 in 200.
So genetic plays a role, but it's not the only thing
where most of my patients don't have a family member
with inflammatory bowel disease.
- [Dr. Rice] How does sugar affect gut health?
- [Dr. Page] Dr. Safdar?
- So what you eat really depends on what the bacteria
like to see for growth and development.
So as an example some bacteria
that are present in our gut will produce enzymes
that will influence our ability to digest certain things
and sugar plays a role because those bacteria
I'll call them the bad bacteria in this instance
use those sugars to go through their own
metabolic pathways and multiply to the extent
that it is no longer beneficial to the human.
That's a very sort of simplistic way of displaying it
but that's the reason why a high sugar diet
for example people that take that have a very
completely different composition of gut bacteria
than those that eat a very diverse vegetable, fruit,
Mediterranean kind of diet.
This has been the subject of intense interest
to try and prevent C. Difficile using natural methods
such as diet manipulation and broccoli
is one thing that seems to work really well
for C. diff prevention, surprisingly.
- Thank you, perhaps for Dr. Rice.
How do you know if you have
non-alcoholic fatty liver disease if it's asymptomatic
and a further question specifically says,
is there a specialized blood test
to tell one if they have fatty liver disease?
- So the answer to those actually both is
really it's no. You don't really know.
So up to 30% of the population has fatty liver disease
and to be honest if you have type 2 diabetes,
the odds are better than average that you probably do
have fatty liver disease.
There is no specific blood test that's used
to diagnose fatty liver disease.
Often times the blood test will show mild elevations
in liver tests, so this is the substances
released into the blood, but not 100% of the time.
An ultrasound of the liver will usually show
fat deposition of the liver.
That's usually fairly obvious on an ultrasound.
So it's usually a clinical diagnosis based on risk factors.
So again, type 2 diabetes, obesity,
cholesterol problems, maybe blood tests
that show some mildly elevated liver tests
and then an ultrasound usually will show
fat deposition of the liver.
- So if colon cancer is the second leading cause
of cancer death
why is the time between colonoscopies being lengthened?
- Well it's not being lengthened for everybody.
It gets back to one of the other themes of today
which is individualized medicine.
So not everybody has the same set of risks.
So if you have one colonoscopy
which is done with a good preparation
and by a competent individual and it shows no polyps,
your risk, and if you have no family members
who have colon cancer, then your risk
drops down compared to the person
who is found to have polyps
or has a first-degree relative with colon cancer.
It's an individualized approach to the practice
of medicine because determining the risk
based on individual characteristics.
- I can just add to that.
So my lab just got funding.
What we did is using our mouse models,
we actually followed the tumors in the mice.
They start out as a benign state
and then they become dangerous, malignant.
And we're able to identify a signature
that predicted whether or not that tumor
was going to progress or not.
We're now going back and looking at human polyps
to see if we can use that signature to predict
was that person at higher risk to develop a cancer or not.
And then that will dictate how we do our screening.
Those polyps that are removed by Dr. Lucey
and colleagues, can we tell who is at higher risk
and who needs to have screening more often?
Who's at lower risk and needs screening less often so.
- Great, thank you and we have time
for just one more question
and this might apply to any or all of you.
How would stress affect the digestive system
and the diseases that we've discussed this evening?
We'll start with Dr. Lucey.
- So stress does affect the digestive system
and this has been studied
and it's a difficult thing to study
because it's difficult to mimic what is a real stress.
But I'll just tell you one study
that looked at bowel motility,
so just to show that stress and the gut function
are affected and it was using a simple pressure gauge
that you swallowed and then gave a read out.
And the stress that was most affective
in changing the natural sequence of bowel motility
was driving in traffic.
(laughing)
And that was a good stress because it wasn't
outside the range of normal behavior.
So stress does make a difference.
The brain and the gut are closely linked.
The gut has more nervous tissue
than the spinal cord, so it's no surprise
that your gut does respond to stress.
- Let's have a final round of applause for our speakers.
Thank you.
(applause)