Friends with Benefits: Microbes, Diet & Me – Eric Alm, PhD and Tim Spector, MD


Hi there. Hi, [LAUGH] good evening. Welcome to the Museum of Science. Welcome to our inaugural program for
our fall 2015 season. It’s exciting to be started back up and
it’s nice to see you all, great crowd. So please do the usual now. Take a moment to turn off
your cell phones and devices. If you need to leave before
the program is over, please exit through the door up the stairs
and out the rear of the theater. This helps to minimize interruptions. In honor of the museums
hall of human life, Lee and Nile Albright have established a way for us to spotlight notable scientists
researching human health and biology. We are honored to host
this annual symposium and look forward to many enlightening
evenings about cutting edge research, one of which we are revisiting tonight. The microbiom is now known to
be as significant to our health as are our genes. This population of trillions of
microbes cohabiting our bodies, may hold the key to maintaining good
health, both mentally and physically. We’re excited to welcome back to
the Museum two eminent scholars, both of whom have graced
this stage before. Dr. Tim Spector has blazed a trail with
his study of identical twins and diet. And he’ll give us the latest on what
he’s learned about how the foods we eat influence our health and our gut. Dr. Eric Alm, advanced the fields
knowledge of the microbiome by studying his own everyday for a year. Nicely done. [LAUGH]
Now he’s focused on how we can manipulate our gut bacteria for better health and
actually turn our bugs into drugs. Each gentlemen will present their work,
and then they’ll have a conversation together. Following that the audience will
have a chance to ask questions, and following that if you are interested Dr. Spector will be signing copies of
his new book behind the curtain. That’s not the title, but
it will take place behind the curtain. [LAUGH]
Now, we’re thrilled to bring together these luminaries who are discovering new
information about our gut microbiom. Before we dive in, Dr.
Albright would like to say a few words. Please join me in giving a warm
hand to Dr. Nile Albright.>>[APPLAUSE]
>>Welcome [COUGH] and what a great pleasure to be
leading this symposium again, which is an honor of
the Hall of Human Life. You all have an assignment and that is to go in this coming year at
least once through the Hall of Human Life and I know you’ll enjoyed because
of the interactive exhibits. And this museum is a pro
on interactive exhibits. They’re over 700 of them in addition to 200 other exhibits that
go on at the Museum of Science. And that’s why we say it truly
is a world class museum. This is a great privilege for us. Last night my wife Lee and I had
a delightful dinner with both Tim and Eric, and learned the inside scoops.>>[LAUGH]
>>You’re gonna hear about them tonight and it’s a first time that this symposium
has been, across the ocean on both sides. Tim Spector is in London,
at Guy’s, in St. Tommy’s Hospital. And is a genetic epidemiologist. Has put together what I think is so
remarkable, over 12,000 pairs of twins girls and boys that they study ongoing to learn what’s
different about one twin from the other. Why is one heavier,
why is one brighter or taller? or do, or does things differently. So those are important things to study. I’m pushing Tim to tell us why cancer
develops in some people and not others as I am the president of the Advanced
Federal Research Cancer Foundation so it’s of intense interest. But one other thing that I really and
very proud to honor tonight and that is my mentor and the founder
of this museum Bradford Washburn. And this really goes to the heart
of things because he came to our house to wish my sister Tenny Albright
off for the Olympic competition. And he noticed a little picture of me
when I was 15 climbing in the blue hills. He turned around, and as he left,
he invited me to join him. And soon, I was six weeks in the same
tent with him and Norman Reed. So we got to know each other well
at the foot of Mount McKinley and then onward to Mount McKinley,
now Mount Denali. So the Washburn family we’re extremely
grateful to, and that’s why I’d like to dedicate this symposium that we do
every year just to let others know how important the director, founder,
and inspiration of this museum was. We have two keynote speakers tonight, which is the first time we’ve
ever had more than one. Our first speaker spoke the first year,
some two years ago here. And talked about how
identically different we are, and that was one of his
books that he wrote. Identically Different, and
then if you ever pick it up, it says how we can change our genes,
what a relief. We think we’re born that way, or
born with cancer, but he has demonstrated elegantly through his work at
Kings College, Guys Hospital, St. Liz in managing 70 other
colleagues in London. So you’re gonna be treated to
something very special you won’t find any other place. Our second speaker is so prominent in
the Boston community that he’s actually, he is starting a new center for
the microbiome at MIT. He also deals, we learned last night,
with 500 other centers that are trying to learn in
the United States about our bacteria, bugs the good ones and the bad ones. So we expect great things for them. And I’ll just close by turning
this over to Tim Spector. Welcome him from London to here.>>[APPLAUSE]>>Well, good evening and it’s a great pleasure to be back here
again and talk about my favorite topics. And I’m the warm up act before Eric
gets on and gives you the detail and I’ll do my best to give a nice,
gentle overview of the problem.>>[LAUGH]
>>And this, as I see it, is the problem. This is, the fact that Nowadays
we are obsessed with what we eat, more than anything. More and
more diets are coming out every week and despite this obsession with food and our diets in the last 30 years,
rates of obesity have tripled. And the same time doctors like myself
have been my patients it’s simple. You just eat less, exercise more,
calories in equals calories out, you will lose weight. And this is found in every single country
that this line has been totted out. So clearly, this is one of the major
myths that we’re all facing and we are being mislead about the fact
that there is one diet that fits all. WE are mislead about the fact that it
is simple calorie counting would work. We are misled by the fact that
exercise makes you lose weight. And endless other myths. So let’s find out a bit more why this is
wrong and what else might be behind it. We’re told that these diets are crucial to
us and there is a new best selling diet all the time,
excluding something from our diet and this is the secret, just exclude that and
everything else will go our way. So let’s take away grains,
gluten is deadly. Let’s just take away fats, and
let’s take away carbohydrates. Let’s take away anything
that’s unrefined starches. Let’s take away dairy products, nasty
dairy products that give you allergies, things we’re never meant to have. Let’s just take away, there’s cheeses,
let’s take away meats. And all you’re left with, [LAUGH]
this may be e a glass of juice and lots of vitamin pills. Okay, perfect. You’re bound to lose weight,
if you just have those. And, this is the nub of the problem here,
we’re stuck with these extremely restrictive diets and this is affecting
us in ways we’ve never thought possible. Now, another big myth that actually
started predominantly in this country and spread across the world like a disease,
was the fact that fat is bad for you. High fat diets bad for you. They give you heart disease. Fat equals fat,
that was a very simple message. And everyone followed it. Every doctor followed it,
they still do today. And this study came out two years ago. And it follows epidemiological evidence that the people that eat the most
fat in Europe, live the longest. These are the people in
the southern Mediterranean. They eat two or three times as
much fat as the average American. And, they are the centenarians. They’re the ones laughing
in their retirement, at age 100 in a nice, in the sun.>>[LAUGH]
>>All that fat they’re eating. And, this study was the first randomized
trial that lasted five years, and has been the best study
ever done on nutrition. Seven-and-a-half thousand Spanish
people were randomized to two groups, and these were 60 year old Spaniards, who
are a bit on the fat side, but no disease. So, pretty average, and half of them were given the low fat diet
as prescribed by every American physician. And the other half were randomized
to a high-fat Mediterranean diet, supplemented with extra olive oil,
in case they didn’t have enough, and extra nuts in case they didn’t
have enough fat and calories. And what happened,
the study was actually stopped early, because of an excess of deaths. And that happened to be
in the low fat group. So, they had a third less heart disease,
stroke, diabetes. And even a third less, breast cancer. And this is the final nail in the coffin,
I think, for the low-fat hypothesis. But this is one of these extra myths that
would be misled for so long that what we’re eating is not just a simple
idea of fat, protein, carbohydrates. This reductionist idea,
there’s much more to it. It’s more complex, and
there’s an elephant in the room here and there’s also an elephant on the slide.>>[LAUGH]
>>And that is, we’ve been missing the most important organ in
our bodies, that is our microbiome. All of us have a hundred
thousand microbes in us that are ten times more than
we have cells in our body, so we are 90 percent microbe and
only ten percent human. And we’re only about one percent
genetically human because we actually have 100 times more genes. All of them pumping out chemicals and
vitamins and hormones that we all need and keep us
alive and until recently we thought they were just nasty things that we just had to
get rid of with sprays and antibiotics. They were deadly, because we
could just culture a few of them. It turns out that with genetic technology
we can now measure hundreds and thousands of the different
species very precisely and we know that 99% of them are good for us. They’re our friends and we’ve been
trying to kill them for decades. And it also turns out this new technology
that when you study people and we’ve studied thousands of
people now in the population. Everybody is quite unique. We share only a small percentage of our
microbes with the rest of the population. Even the person sitting next to you,
even in our families. We have a unique finger print
that goes of us all our lives. And this also explaining why perhaps one
diet, one idea doesn’t fit everybody. Because we’re much more
different than we thought. Now I’ve been studying twins as
you’ve heard for over 21 years. And we have thousands of them. And we’ve started looking
at their microbes as well. As you know,
when identical twins are born, they are genetic clones, exactly the same. But like any other babies when they’re
born, they’re born predominantly sterile, no microbes at all, and at birth,
those microbes get into the system and develop this community
that lasts all our lives. And those first few days,
months are really crucial to forming these microbes that play such
an important role in our lives. And it turns out that there
are the major factors that alter this, that if natural birth
which by evolution for millions of years has meant that
the babies face goes through the birth canal and get’s exposed to all the mucky
bits that come out is deliberate. And it all gets in through the mouth and those microbes act as fertilizers for
all the other things that happen, and allow the baby to then
digest breast milk, etcetera. And also build the immune system. Without it, babies would die very quickly
and have no decent immune system or brain. Now we now know that in the modern world, where everything is safety first,
Caesarean sections rule. And in the U.S. over a third of babies are now brought
into life by Caesarean section. And in places like New York and
certain bits of Boston, it’s over 65%. And this totally changes the microbes,
and when we looked at twins. The fact that they can differ
depends on who picked them up first in the delivery room. I was delivered by Caesarean section, so I am desperately trying to find out
who that nurse was so I can blame her. So these things are very important and
twins generally have similar microbes. As they grow up, as all other things but
then they can separate and be quite different and so although we found on average there was
a genetic component to having no microbes. There were individuals, twin pairs look
quite different like this pair here who differed by about 30 pounds in weight and
had very different microbial compositions. So it looks like, the microbes
inside them are playing a role, in some of these metabolic differences. And, we went on to look at over a thousand
of these, looking at the role but putting which microbes might
be important in obesity. And we did this with our
colleagues at Cornell University who did all the genotyping and
the hard work. And what it showed was yes, there were
certain microbes that if you had them, either made you more likely to get fat or
less likely. And the one that the tabloid
newspapers in the UK called the fat busting microbe is this one which most
people can’t spell, christensenella. I can’t even say it. But, it was a very unknown microbe that
all of us have in tiny amounts, but a few people have a lot of it. And those people invariably were skinny. And it turns out that when you
take the poo from somebody with this bug and you put it into mice,
who have made sterile, you will be able to keep that mouse skinny
even if you feed it endless junk food. So people are now
scouring the internet for this microbe to put on their
breakfast cereal in the mornings.>>[LAUGH]
>>But some of you will have it and others won’t. And this is just an example, the tip
of the iceberg, of what we can find by digging deeper into our own microbes
and the whole world that’s inside us. Now, what I’ve said for obesity needs to be thought in a way of
many other disease, as a garden. Basically if you’re healthy,
and skinny, and you don’t have any diseases, your microbes
will be like a rich country garden. This is how all our gardens
in England are like this.>>[LAUGH]
>>Cuz it’s always raining and its always sunny. But If you have a disease, if you’re
obese, if you’re diabetic, if you have any number of gut infections, colitis,
autoimmune disease, allergies, irritable bowel syndrome, autism, you name
it, you will have a disordered garden. You will have a barren garden that
has less diversity of species, and in that barrenness,
you get these nasty bugs taking over. And Eric is gonna talk a bit more
about some of those bugs taking over that whole system. Which wouldn’t be allowed to in your nice
garden that’s full of all these species which are protecting each other. Very important to bear this in mind. Now cheese, I went on a three day intensive
unpasteurized french smelly cheese diet.>>[LAUGH].>>I wouldn’t advise it.>>[LAUGH].>>Great for day one. Fantastic cause I was allowed two
glasses of red wine with it and I was enjoying my smelly French
cheese a lot, but by day three, really I’d had enough and I think,
my microbes as well, also have had enough. You can have too much of a good thing,
but all doctors tell us, don’t have fatty cheeses,
very bad for you. Particularly people with heart disease or
on statins and things. It’s a taboo area, and yet
people that eat regular cheese, all the epidemiology studies show, they
have less heart disease, less diabetes. And the French,
our great rivals across the channel, annoyingly, live much
longer than the Britains.>>[LAUGH]
>>And they eat three times as much cheese
as we do, it’s just not fair.>>[LAUGH]
>>So what are we doing about it? And what’s,
what is it about cheese that’s fair? Well, if you take just a crumb of cheese, you’re going to find billions
of microbes in it, billions. And these microbes, as you can see,
are mainly bacteria. But on top of that, they’re also
five times as many viruses and they’re fungi as well. If you take the Roquefort in
those blue veins of the cheeses, they’re all funguses that
you’re eating quite merrily. So, we’re eating this whole living
organism when we eat cheese, and it’s likely that these have
effects directly or indirectly on our other microbes and keep us
healthy in ways we don’t yet understand. And, for
those who like to eat cheeses like this, with crusts on it, that are aged
in the old, traditional ways, you should know there are other little
things on there called cheese mites, which bury into the cheese and
give it its flavor. And, these cheese mites
upset a few vegetarians for some reason because they get eaten
every time you have your cheese.>>[LAUGH]
>>They’re chubby little things, and they all taste just of cheese
cuz that’s all they’re made of.>>[LAUGH]
>>But it’s something to bear in
mind when you do tuck in.>>[LAUGH]
>>But you may have to go out of your way to get it because the FDA, in its wisdom,
has banned unpasteurized cheese. Now after cheese, I want to then go and
do a junk food diet and decided I wanted to do a ten days
intensive McDonald’s diet to really see if I could really improve my microbes
through all that healthy eating. After my cheese diet,
I wasn’t feeling quite up to it and I thought I really need an expert to do
this, someone who was really trained and dedicated and he happened to also
be a student, which was good. He was hard up for money and
he also happened to be my son.>>[LAUGH]
>>So it all fitted. His friends are very jealous,
I gave him the cash, sent him off to have all his
meals at McDonald’s for ten days. He was delighted, by day three,
the novelty was beginning to wear off.>>[LAUGH]
>>And some of that zest he had for life was going. And he said, Dad, do I really have
to carry on for another week? And I said, I’m afraid you do.>>[LAUGH]
>>But, and by day ten, really his opinion had changed
and he didn’t feel so good at all.>>[LAUGH].>>But what was really serious
about this was after day four or five we’d start to see a dramatic
massacre of his microbes. He’d lost 40% of his
diversity in his species. And this is getting rid
of over twelve hundred, of these species type that we’d seen. And the conventional idea was, well
that’s just high fats, and high sugar, a bit of salt, these things must
be upsetting his metabolism. But actually that probably isn’t the case, because that doesn’t really
affect the microbes. The explanations are that he was
getting very little fiber for the microbes to feed off,
except that little bit of gherkin you get, that little tiny sliver, which might be
the only bit of fiber you get in a burger. But it could also be the other
products you get in processed foods. The emulsifiers, which we now know affect
our microbes and can distort them. All these things in the mayonnaises and
the tomato ketchups, plus also preservatives and sweeteners. All of these things are bad and
affected him. Now, what else can you do
to help your own guts? Well, obviously eat more greens,
that’s the standard treatment. But knowing why is important and We now know that there are certain
greens that are better than others. Lettuce doesn’t really help you very much,
but if you take these root vegetables. Things like chicory roots,
or artichokes, or leeks, onions, garlic, those
are the basis of the Mediterranean diet. They are packed with things called
inulins, which microbes absolutely love, and they produce lots of helpful chemicals
that help our immune system based on them. Then you’ve got other things
that also are rather strange, we’ve been told are bad for us. Like peanuts and assorted nuts and seeds and even coffee and dark chocolate. Full of sugars and things. Red wine and olive oil. What unites them and why are they good for our microbes, is
they contain polyphenols in huge amounts. They are superbly rich in these
polyphenols and again this is food for the microbes. Microbes feed off all the different
types and just in red wine alone, there are nearly a hundred
different polyphenols, and about 60 in extra virgin olive oil,
not the cheap stuff. You gotta get the expensive good stuff. Cold extracted extra virgin olive oil,
we get the maximum polyphenols. And if you do that,
you’re giving them a huge treat. Then we got yogurts and
fermented products. Obviously they’re good,
cuz they contain microbes. But are probiotics good for everybody? Well, they are if you’re a rat. All the mouse studies,
all the rodent studies, show absolutely that virtually every
single test, they’re fantastic. They can prevent anything. The data in humans, unfortunately,
isn’t quite as good. You’ve got to be very sick,
or very old, or very young to really benefit,
or be on nasty antibiotics. And Eric’s gonna talk
a bit more about those. So yes it works, but
if you’re really healthy, they don’t seem to have
a great effect at the moment. Antibiotics, we’ve gotta
talk about them and there’s a great book on this
subject by Martin Blaser. Some people believe that the epidemic
of obesity in this country is due to overuse of antibiotics, and in the U.S. they’re overused more than pretty
much any other country in the world. Average 18 year old is about
18 courses of antibiotics. Average three year old has had three. Three quarters of the time,
totally unnecessarily. And each time, it’s like a nuclear bomb
going off in your gut, and you have enough of them, you wipe out all the good guys,
and this is where you get problems. So avoiding those is really important for
our future health. But also in the food we eat cuz much
the food we have is contaminated with antibiotics anyway,
as is our water supply. What do you do if all this fails? You’ve tried everything, and you’ve still got rotten microbes
that you can’t get rid of. Well, a microbial makeover
is the ultimate solution. And these could be
the tablets that help you. We call these technically Poo capsules.>>[LAUGH]
>>And they are frozen poo. And basically take 10 or 30 of these, and you will be cured of serious infections. And people are now looking at
this much more seriously, and there’s now 500 centers in the US
offering these transplants for serious diseases, of which,
14,000 people a year die in the US. So, this is now a mainstream treatment. And, Eric is at the forefront of helping
this system on get around the world. And as part of this new
interest in the microbes, people are testing their own microbes. And the British Gut project is
an off-shoot of the American Gut project, which my colleague Rob Knight
started a couple of years ago. And it’s a citizen science project
where anybody can go online, look up American Gut, make a small
donation, in both senses of the word,>>[LAUGH]>>and get the results back. And also, contribute to a huge database
telling about not only the American Gut, or the British Gut, but, hopefully,
the global gut about what’s normal and what’s not normal. And we see this amazing variety. So, do go there, and you can get your own. You can compare yourself with other
people, which is what people want to do. So, to summarize, we should all treat your own bodies
like you would this precious garden. And that means looking after it carefully, understanding that everybody’s soil
is different in all your gardens. And treat it with good fertilizers. You sprinkle on nice products
every now and again. Add new seeds to it. You change the soill. You add variety. You eat seasonally. You give it, above all,
care so that you avoid toxins, those nasty antibiotics and other things
that we’re being, processed foods. And above all, the key is diversity. Eat as much diverse foods as you can. You will have a diverse garden,
and you’ll stay healthy. And the other thing to remember
is that if you do that, you’ve gotta realize that with diversity,
never again will you eat alone because you’ll have 100
trillion friends in there who’s with you.>>[LAUGH]
>>[LAUGH]>>Thank you very much.>>[APPLAUSE]
>>So, I’m gonna hand over now to my colleague,
Eric Alm from MIT, who’s going to take the baton on, and
take us, get us into the next level. Thank you, Eric. Well, thanks, Dr. Albright, and thanks to The Museum
of Science for inviting me back. I’m really honored and really humbled
to kinda share this stage with Tim. I wanna talk to you about basically taking the microbiomine and
thinking about, I’m at MIT, we’re engineers, we always
think about here’s some new science. How do we engineer it to improve
the human condition and so, one of the things that I always ask
people when I give this talk is, why are we talking about
the human microbiome in 2015? Was there some new technology
that was invented on the microbiology side of things? Did we learn how to culture
more of these organisms? Was there a new microscope that
was invented that allowed us to recognize the importance
of the microbiome? Does anybody have a guess?>>[INAUDIBLE] So, yeah, so. So there’s some clinical information
that says it’s important, but I would argue that the field of microbiology
started with infectious disease roots. And so we’ve had that on the forefront
of our knowledge for over 100 years. So what is it about 2015, and
really the, maybe the last five years, that’s sparked this interest
in the microbiome, and most of the microbiome being
these healthy bacteria. The ones that aren’t really germs?>>[INAUDIBLE]
>>DNA sequencing. So a few years ago,
we decided that if we could only sequence the human genome,
we would reveal all of the drug targets. At that time,
we didn’t know if there were 5,000 or 100,000 genes in the human genome, but
once we had those precious drug targets, they would each be the target of a new
drug that would impact human health. And so as soon as we figured out
how to sequence the human genome, it was a $3 billion dollar project,
we got the first human genome. We waited for those drugs. And we put a lot of work in to
developing the technology and making it very high through put. And during the process,
we go really, really, really good at sequencing DNA, okay. So it’s hard to see here but
this is an logarithmic graph. So if I follow this line, that’s gonna
be similar to Moore’s Law for computing. And it says that every couple of years,
the computing power doubles for the same price, the same amount of
electricity and things like that. This logarithmic graph, so, you can see,
this is growing faster than exponential. Very few processes obey laws like this. Very few things grow faster
than exponential and I don’t think it’s slowing down,
which is amazing. So, not only have we been able to
exponentially increase our sequencing power, we are doing it
faster than exponential. We are so good at sequencing. We should have all the drugs we will ever
need within the next few years, right? This is the number of
billion dollars of research required to produce one
new FDA approved drug. And the time axis here is the same. And this goes up to 2010, I’m sorry. The inverse of that. So the number of new drugs
that we’re getting for each billion dollars of research that we put
in, the graph is going in the wrong way. [LAUGH] We got really good at sequencing
that DNA, and the drugs haven’t come. To some extent, maybe we were over
optimistic about our ability to take that complex genetic knowledge and
turn it into new drugs. And I for one am very confident that soon,
as we start to sequence more humans, and figure out, like, what the action
of each of those drug targets are, that we are gonna be able to see
that explosion in new drugs. But it’s gonna be a few years out. And what I’m going to argue to you
today is that the microbiome offers a really unique opportunity. And that opportunity is that we can
leverage the fact that we’re really, really good at DNA sequencing,
and use that expertise to develop new drugs that are based on microbial
species that are in our guts. So it’s the idea of bugs to drugs. Okay, and I’m gonna explain essentially
how I think this is gonna work. This is an oversimplification. But essentially,
we’re looking at healthy humans and we wanna culture all of the bugs that
live in and on those human beings. This is a culture plate, each one of those
little dots is one bacterial isolate. We wanna take those isolates, put them
in the freezer, make master stock so we can always so back and we can find
that organism, we can grow it up. We can study it in the lab, or
maybe we can put it in a pill and feed it to a patient. At the same time,
we’re taking that same material and we’re getting the DNA sequenced. We using that to identify the bacteria. And then we compare the microbiome, the bacterial content of healthy groups
of people and sick groups of people. And if we find that the sick people have
a very similar microbiome to the healthy people, except they’re
missing one particular drug, now we have a hypothesis that
we can test in the clinic. We can take that species
that they’re missing, we can take it out of our freezer,
we can put it in a pill, and we can feed it to those sick people,
and we can see if they get better, right. And so, this is a very short circuit from,
DNA sequencing to a clinical trail, okay, That’s very naive, we probably
wouldn’t do it just based on that, we do a little bit of background
work before we enter it into a human clinical trail, but that’s the basic idea. It looks like the mic is out but
I’ll try to speak a little louder so you guys can hear. So this is the idea, this is the sort
of new paradigm that we imagine in drug development that could result from
the emergent science of the microbody. So what are the diseases that
microbiome is associated with? This is a very,
very non-comprehensive list of a number of different diseases that have been
associated with the microbiome. Do you wanna change the battery? All right.
>>[LAUGH]>>You can take that. So, this very short list, and one in
particular I’ll talk a lot about today and that’s Clostridium difficile infection,
but I’ll get to that in a moment. But, just fair to say that
there’s a whole host of diseases that we know are associated
with the microbiome, but sometimes an association
doesn’t mean causation, right? Two variables can be very
correlated with each other. It doesn’t necessarily mean
one is causing the other. Okay, so we’ll try this speaker. So, if it turns out that
most of these associations are just correlations and not causation,
that’s fine, especially if a few are, then maybe we’ll get drugs for a few of
these diseases, which would be fantastic. But when we can’t establish causation, in many cases all is not lost because
what we have is a diagnostic. We have a molecular diagnostic and a lot of these diseases that
are associated with microbiome don’t currently have a good molecular
diagnostic that we can use in the clinic. Perfect. All right, that’s great. Because Tim told us we
should get exercise.>>[LAUGH]
>>So I don’t want to stand behind the podium all night here. So how would this work? Here’s one case that’s really close to
kind of the research that we’re doing. This is a fictitious student,
she’s a 20 year old student at MIT, comes into my office says,
Eric, my grades are suffering. I tell her to go see the doctor
because she’s having nausea, weight loss, depression, slipping grades. So she goes to the clinic,
tells him about her symptoms and the doctor is now thinking IBS. So IBS and IBD are very different
diseases but very similar symptoms, okay, but
very different treatment regimens. So, the doctor’s thinking IBS because
she doesn’t have any of the external, extra intestinal manifestations
that we usually expect for IBD. Then finds out that her
father had Crohn’s disease. Crohn’s disease is one of
the different variants of IBD, so now the clinician is thinking, maybe it’s
Crohn’s, looks at all the information, and really doesn’t know one way or
the other, so she needs a colonoscopy. Well turns out that her dad was one
of the rare cases of folks who come into the clinic, get a colonoscopy,
end up with a punctured colon. And, so that was a huge ordeal. She absolutely doesn’t want that. Okay?
So, she refuses to get the colonoscopy, but her grades are suffering and our MIT students really care
a lot about their grades. Okay, so this is a big deal. Maybe bigger than the other symptoms. And she wants a diagnosis and
she wants a treatment plan. And this is not like
a completely hypothetical case. This is something that could be fairly
typical that we might see in the clinic. And currently, we don’t have a lot of
really great non-invasive diagnostics. That can really compete
with colonoscopy and get Ashley sort of the diagnosis and
the treatment plan she needs. What do we mention in the future? Well we mentioned sequencing her gut
microbiome and trying to figure out, is this the microbiome that’s
telling us maybe Ashley has IBS. Or does it look like the microbiome with
someone with IBD if this is a microbially associated disease. And so we imagine bringing out
these diagnostic tests and then taking that very big data that
a clinician’s not gonna sit there and plot and analyze and
putting it into electronic medical records system that doesn’t just
track all of the symptoms. And what the result of the lab test is,
but a medical record that
actually makes predictions. It makes predictions,
makes a diagnosis, and then gives a probability of remission if
we tweak with this drug or that drug. And makes recommendations based on all
the genomic data that we’re putting in. So that’s kind of the future
that we envision. Microbiome really contributing toward. How close is this feature? I would argue it’s not very far off. So, I’ll tell you a little story
about a project that we started and this is a project that rally drew
me into the field of Microbiome. So, Athos over at children’s hospital came
to me and said, Eric, we’ve got a problem. At this time, Athos ran the Pediatric
Inflammatory Bowel Disease Clinic over at Children’s Hospital. And he said we’ve got a problem because
on average there’s a three year lag time before the onset of disease, onset of
IBD in children, and after a diagnosis. And what that means is that there’s three
years go by before symptoms show up, and patients get
the treatment they need and often times that can
lead to poor outcomes. So, often times, the first intervention
has to be surgical, okay, and these kids have to have part
of their colon removed. Whereas, if we had gotten them earlier,
and managed the disease,
maybe we could establish a better outcome. So he said, maybe there’s some
way that we could sequence get us noninvasive stool sample, sequence
it and determine if the patient had inflammatory valve disease or
maybe just IBS, something like that. So the other option of course,
the gold standard, is colonoscopy. But, the downside here is, is every eight
year old child that comes into the clinic, you don’t wanna send them out for
a colonoscopy, right?>>[LAUGH]
>>Colonoscopy is not very pleasant. And so, so
there’s this fundamental tradeoff, and Athos said, maybe we can do
better with microbiome science. So what Athos did is he went out,
and he took a good sample of, folks that came to his clinic,
that he later diagnosed as not having inflammatory bowel disease, so
he did a colonoscopy, he ruled IBD out. And then he recruited some patients that
had inflammatory disease and two different versions, Crohn’s disease and ulcerative
colitis, the two main forms of IBD. And that’s what you’re seeing here, so there’s a lot of data but
I’ll kind of walk you through it. So, every column in this
graph is a patient, it’s a sick kid and
these are the control kids. They’re still sick. They’re showing up like Ashley did, right? They maybe have weight loss,
depression, their grades are slipping. And, they’re showing up to the clinic. But after it was later determined
that they did not have IBD. These are the children
that had Crohn’s Disease, and these are the children
that had ulcerative colitis. And on the rows, here, what you see are all the different
bacteria that we sequenced in their guts. So I want you to look at this and tell me if you see any bacterium that
is really indicative of disease. If they have this bacterium they’re sick. That’s the germ,
that’s the one we need to get rid of.>>[INAUDIBLE]>>The clostridia? I actually see more in the controls
than I do in the sick kids. So I think these kids lack clostridia. But I still see it in the sick kids. So the only bug that’s more
abundant in the sick kids than the ones without IBD is E.coli. Okay, so all of the kids that had a lot
of E.coli had inflammatory disease. But, if you’re gonna use lots of
E.coli as your biomarker for disease, you’d only detect disease in about ten or
15% of the kids. So on its own it’s not good enough. So there’s not a key hallmark
change in microbiome that tells you whether a child
has inflammatory disease or not. But what we were able to do is we were
able to take all these weak signals. All of these things that look like
maybe if they have a little bit less clostridia than you would imagine,
maybe they have disease. And take all of those weak signals, combine them together with
machine learning, and we actually built a very good predictor
that we later found was better than the current gold standard in non-invasive
tests, which is fecal calprotectin. So I would argue that this future’s not
very far off, and one of the things that we found in the study was that
when we re-analyze the data, and as we put more and
more patients into the model. The predictive ability of the model,
the accuracy of the model got better. So it’s a diagnostic that the more times
you use it, the more accurate it gets. And that’s one of the really exciting
things about microbiome based diagnostics. So we don’t just want doctors
to have access to this data. We wanna get this data, this non-invasive
data that we might be eventually collecting daily with smart toilets, or
we’re thinking about systems with smart wipes that patients could use that will
give the information back to clinicians. We wanna get it back to patients. And so if we diagnose Ashley
with inflammatory bowel disease, we want Ashley’s cell phone to buzz two
weeks before she has a flare up and say, Ashley, there’s something going on. You need to maybe see your doctor
now because you’re not sick yet, but based on your microbiome,
we think you might be getting sick. And that’s sort of the direction
that we’re heading. I would argue that this
feature is not very far off. So I’ll tell you a little story about
a self experimentation study that I think Tim alluded to. So my student,
Lawrence Davin and I in 2009, decided that we would track our microbiome
and we would also track 300 different parameters that corresponded to
our daily life and behavior. So we wrote down every morsel of food
we ate, we wrote how much sleep we got, our sickness and any medicine we took,
all of our travel. Basically, everything we could think of,
recorded it for about a full year. Laurence said if I write an iPhone
app to track that information, can I charge an iPhone to the branch? I said sure. So now there’s an app for
that for anyone that’s interested. And so this is what we found. In 2009 this is my microbiome in 2009. This is Lawrence’s microbiome in 2009 and the thing I want you guys to
notice is they’re very distinct. Okay, so
there’s a lot of variation day to day. But I could pick any day from my time
series and show it to you and you wouldn’t need any fancy computer algorithms
to figure out if it was my sample or Lawrence’s sample. So our microbiomes are very,
very distinct. They are very distinct ecosystems. And they change day to day but
they maintain their, sort of, unique quality that’s
different from each other. Okay, so,
what are the things that affected it? Certainly, diet played a big role. But, one particular life
event really affected mine. So about three quarters of the way
into the study, actually I would say, almost six years ago to the day, [LAUGH] I took a colleague up
on an offer to go out to brunch. I made the mistake of ordering the chef’s
special french toast and 48 hours later, I was deep in the throws of
a horrible salmonella infection and you can see the salmonella down here. So this is my microbiome again. And here I’ve blown it up so every
single row is a different bacterium, and the red colors mean there’s more of that
bacteria on that day than other days, and the blue colors mean there’s
less than on other days. And you can see, as soon as the salmonella
appeared all of these bacteria basically disappeared in
about a week after infection. Some of those bacteria came back, but
the majority went permanently extinct and were sort of extinguished
from my microbiome, but they were replaced with all
of these bacteria in here. And so we saw complete
restructuring of the microbiome as the result of this life event. And what I think is fascinating is, even
after that total restructuring you can still tell it looks like me if we go
back to the other picture, right? So here is the event. It still looks like me,
it doesn’t look like Lawrence. So my microbiome was able to
completely reboot itself but reboot sort of a different
operating system than Lawrence had. And that’s still, I think, one of the mysteries from that study
that we still don’t fully understand. So we know we can start
to monitor these things. The technology’s getting cheap enough
that we can really roll it out and we’re thinking of doing that next year for
inflammatory bowel disease patients. Microbiome is only the beginning
of the things we want to measure. So we want to use wearable devices and a lot of technologies that are making all
of this whole process quite a bit easier. We want to look at the immune system and see how the body is responding to those
microbes, not just look at the microbes. And so
that’s what we see as kind of the future. I wanna talk about one more thing,
so we talked about diagnosis but I didn’t tell you,
I said wanna make drugs from bugs. How do we do that? And the best model for doing that we have right now is looking
at Clostridium difficile infection. And so we wanna move from diagnosing
to engineering the microbiome, but let me tell you a little bit about
the course of the disease first. So what we have, we generally
have a person with a healthy gut. So all these germs and
stuff, that’s good, okay? You guys should know that by
this point in the presentation. So this is a healthy microbiome. We hit it with antibiotics. And we sort of clear cut that beautiful
forest or that beautiful English garden. And so now we have all this empty
niche space that invasive species can come in and get a foothold in. Okay, so, if we deliver antibiotics, and the patient is exposed to C difficile,
that C diff can basically take over. And, once C diff takes over,
what do we do? We give the patient antibiotics again,
of course, cuz now they have a terrible infection. In many cases, the antibiotics
will return us to this state. In which case, the patient will
become reinfected with C difficile. Then it becomes even more likely that the
next time we treat him, and what do we do, of course, we give him antibiotics again. It becomes more likely that
they’re gonna recur with C diff. And after three or four or five cycles
of antibiotics, it starts to become very unlikely that the patient is ever going to
respond to another course of antibiotics. So they’re sort of locked, sort of
alternating between living on vancomycin, which is not fun, and
having C diff, which is less fun. Okay, and so two very terrible choices. But it turns out that there’s a cure,
and the cure is to treat the patient with antibiotics and
then instead of waiting for the patient to be exposed to C diff and
recur, we give him a fecal transplant. So we take bacteria from a healthy
donor and we infuse that into their gut ecosystem, let those healthy bugs take
over, and they sort of crowd out the, we replace the clear cut forest with
the beautiful lush English garden and then C diff can’t get a foothold. And it is effective in
85 to 90% of the cases. So we got involved in
a study at Mass General. This is a study where there were four
healthy donors that treated about 20 patients and
about 18 of those patients were recovered. Especially one of those donors
treated 12 patients, okay? And this was a study that was
carried out by Libby Hohmann, Ilan Youngster,
Jenny Sauk over at Mass General, and Dirk Gevers and
Bruce Birren at the Broad Institute. And we used that, so we went in and
we looked at the clinical study and we say, we wanna get some genomics. We wanna see what’s really
going on with those microbes. And so we did that, and so a really great
graduate student in my lab, Chris Smiley, he’s a computer scientist, he made this
graphic of what a patient looks like, what their microbes look like,
just coming off of vancomycin. So this is a patient with
Clostridium difficile, okay? And so each one of these blue bands is
a different bacteria in our patient, in our sick patient. Down here you see these are all different
bacteria that where in the healthy person that gave bacteria to the patient and
you can see they’re very different. And now I want you to try to squint and
see if I combine, if I add these bacteria to this patient,
what’s gonna happen. And this is what happens. So this is our patient after the patient
gets a fecal transplant from this donor. And we squinted at that for a long time, it doesn’t look like just
adding the two profiles together. It doesn’t look like an AND gate or an OR gate or any of the different
things that we could think of. The human eye is pretty good
at pattern recognition, but we didn’t see any patterns here. But Chris went back. He built a machine learning algorithm
to try to solve the problem of given the patient and the donor, what are they
gonna look like post fecal transplant? Whoops. And this is what he found. So he found, his algorithm was about
86% accurate in actually predicting what the patient would look like
after the fecal transplant. And the thing that’s very exciting
to us is that now it says, if we know what the patient
is supposed to look like, and we know what they look like now,
and we have a lot of different possible donors to combine them with,
then we can sequence our patient. We can sequence all
the different donors and we can ask our computer algorithm,
which of the possible donors that we could use to give a fecal
transplant to this patient will transform this patient into what we think
the ideal healthy gut would look like. So the only other step that we
need to do that is we need a bank of hundreds of different healthy donors
that we can just call up and say, yeah, give us donor number 51.>>[LAUGH]
>>So it turns out, a few years ago, a student in my lab had a family friend. And this was a young guy. Most of our C diff patients are,
they’re geriatric patients, and so they’re a little bit older. This was a young guy who’s a Princeton
grad, had his whole life ahead of him, got a terrible round of C difficile
infection, got multiple recurrences, couldn’t hold down a job,
was really ruining his life. He was an insider in
the health care industry so he knew about fecal transplants. And he knew if he could just get a fecal
transparent maybe he would get that 90% likelihood to be cured. He called around, he heard that
some people were doing this as part of a research study, nobody really was
doing it, nobody had availability. Eventually he resorted to giving
himself a fecal transplant, and eventually was cured. But the whole ordeal took much
longer than it should have. And he had to practice a potentially
very dangerous medical technique not under medical supervision. So, a really fantastic graduate
student in my lab, Mark Smith, said, this is unacceptable. We know how to make this stuff in the lab. And so, for about a year we shut
down all other activity in the lab. So we could manufacture pharmaceuticals
in the corner of the lab. We didn’t tell MIT,
they would have shut us down. But now they’re happy [LAUGH]
because the result, the result was really amazing
due to all their hard work. And so, eventually spun off into
a non-profit organization that today has about 36 full time employees that ship
fecal transplants around the countries. So, Tim mentioned there’s about
500 facilities treating folks. 430 of them are within our network and
receiving product from Open Biome. And that means that about 94% of US
population is within about a three hour drive of one of our clinical partners. So we’re really trying to provide
safe access to this product. [COUGH] Serving about 49 different states, about 7,000 patients have been cured so
far. And one statistic that’s not on here
that I think is really phenomenal is, based on our internal estimates. We’ve saved the healthcare industry
about $100 million in the first year or two of operation. And so I think I’ll sort of end there and I want to note that there’s a couple
folks from Open Biome in the audience. I’m sure they might come up afterwards
if people have questions and tell you more about their
non-profit operation. So I wanna thank some of the folks that
contributed, and this will be a good time, I have a few questions for Tim. So maybe if you’d come back up here
we could start the conversation part of the evening.>>[APPLAUSE]>>So Tim, I was really pleased to see the self experimentation,
something that I’m also a big fan of. And so I thought we could start
out with sort of a fun question.>>No one should share
a refrigerator with us guys.>>[LAUGH]
>>Absolutely not. What’s the most exciting experiment
that you’ve personally participated in related to either diet or
microbium or anything, really? I have an exciting, I had to abandon one, which was I wanted to really do
the intensive olive oil diet. I’d heard that fishermen in Crete used to
drink a glass of olive oil for breakfast.>>[LAUGH]
>>And it gave, they lived to be 100 and it was all fantastic. So I said, I’d never actually met anyone
who’d done this or actually seen it. So I said, well is it possible? So I got the best grade Spanish extra
virgin olive oil, and I sort of built myself and I said well in a week,
I’ve gotta have half a liter of olive oil. And I just wasn’t getting
through it with the salads. So I said should start
drinking it in a glass. So I made the mistake of having
a glass on an empty stomach and then I went off to get my haircut and
then fainted.>>[LAUGH]
>>So I decided some things were just
a bit too dodgy for me to do. But yeah, and I had a colonoscopy and saw what happened to my
microbes before and after. And not much happened, actually. I was very disappointed. But, it was an experience.>>[LAUGH]
>>And then the cheese you know about. And other ones, but yeah, it was fun. But you traveled, you went around
the world with your one, didn’t you?>>So Lawrence went to Bangkok. He went to Bangkok and
his experience was a lot different. So his microbes changed almost
as soon as he got off the plane. He picked up a cocktail of about
three different enteric pathogens. I had to Wikipedia one of them. I had never even heard of it before. But his microbiome completely shifted. But what was really interesting is, as soon as he got back to the US,
it came right back. So that was really different than
what happened to me with salmonella. Where it was more of a permanent change.>>But I’ve heard it said that it’s a
cheaper way of getting a fecal transplant, is to just go to India for
a couple of weeks.>>[LAUGH]
>>Get a reboot. So would you recommend that?>>The thing about fecal transplants is
you probably don’t want the cheapest one.>>[LAUGH]
>>[LAUGH] I guess so, but if you went 20 times,
eventually you might strike lucky.>>That’s right.>>So where do you see fecal transplants
going if we were talking 5 years from now? What do you envision? Because at the moment,
clostridium difficile, it’s accepted because it’s killing
people and it’s a life saving procedure. And yet many people on the internet
are discussing doing it themselves, but for more minor conditions. And yet,
the data isn’t that great at the moment. But where do you think,
what will we be treating it for, do you think, in five years,
what would you guess?>>Yeah, so
I think five years is such a crucial time. So it’s like right now, we’ve got
the technology to look at microbiome. We also now have the infrastructure
to do fecal transplants and for example,
Open Biome is releasing pills soon. So it’s becoming very easy
to conduct these trials. And I think in the next five years,
what we’re going to do is we’re gonna look at all of the different diseases that
have an association with a microbiome. And we’re gonna find of those dozens,
maybe even hundreds of diseases. Which are the five or six,
where microbiome is actually gonna cure, where it’s gonna work like a charm,
just like c diff. So I think in the next five years,
we’re gonna try fecal transplants, and try these very crude interventions for
lots of diseases. And we’re gonna narrow down on, what
are the diseases where it has a chance. And then, I think that the five years
after that are gonna be spent saying, we know fecal transplants kind of work. They probably won’t be as
effective as they are for clostridium difficile, I think that’s
gonna ultimately prove to be an outlier. But when they worked a little bit,
then we’re gonna think about okay, can we make a synthetic cocktail of drugs? Then some of those organisms in those
drugs might be engineered to have even stronger phenotypes and
treat disease even better. And so after five years, we’ll maybe narrow the list of
diseases that we care about. But right now is really exciting because
we don’t know what diseases can respond. And so at least at our microbiome center, we’re trying to have
a really diverse portfolio. We have a focus on IBD, but we want to have our hands involved
in many different diseases.>>When you have a bone marrow transplant,
generally you get genotyped and you get H and you’re matched for
your HLA system with the donor. And until recently we thought that that
wasn’t important in the microbiome but. Twin studies that we did
with Ruth Lane Cornell shown quite conclusively that
genes do play a part and our new data suggesting it’s even
stronger than with the 16-S data. So, in a way your best
donor is gonna be yourself, because you have the same
genetic background. So do you think we should be setting
aside our poop when we’re nice and healthy and young,
stick it in the freezer, and then get it back again later in life,
maybe to keep us forever young or healthy? What about that as a future? Do you see that as a-
>>So yeah, self stool baiting.>>[LAUGH]
>>Well, people are doing it for stem cells in their babies. They’re paying their money at birth. So maybe when we think we’re at
our healthiest, wherever that is, that’s what we should be doing.>>So, one of the things in it, it brings
up an interesting question because there’s a very confusing set of regulations
around fecal transplants right now, and basically any sort of
microbial-based therapeutic right now. By those regulations you can
bank your stool today but you can’t get it out of the bank. You can’t get it out of the bank unless
you have recurrent clostridium difficile. And so it might be good idea to bank your stool
before you take a round of antibiotics, then if you get an infection, you’ll get
the antibiotics to get rid of the germ. And then you go back to the freezers and repopulate with your own bacteria, or
maybe for me it would be after salmonella I go back and repopulate-
>>What you’re saying is you currently wouldn’t be allowed to?>>I can put it in a bank-
>>You can’t put your own stuff back.>>The FDA won’t allow the bank
to give me my own poop back.>>[LAUGH]
>>Unless I get a recurrence c diff infection, but that’s not worth it.>>So, and the analogy was if you
spit in to a tube, freeze it. The FDA wouldn’t allow you to have
your saliva back in your body, be treated as a drug, is that right?>>You’d have to ask the FDA that. I don’t put words in the FDA’s mouth,
but, [LAUGH].>>Okay, sounds kinda crazy.>>I can definitely tell you that at
a stool bank you wouldn’t be allowed to get that material back.>>So the whole thing is thrown up, this
whole problem, about what is our microbe? Is it ours? We say we’re only 10% human. We carry it around with us. If it is ours, does it not belong to us?>>Right.
>>It belongs to the institution that decides whether we can have it back again. So is it a device? Is it a tissue? Is it a drug?>>Right, and so
I’ve argued that it’s a tissue product. It should be treated as a tissue product. And if you run a stool bank, you should follow regulations that
are similar to running a blood bank. But the FDA has said very
clearly that it’s a drug. Poop is a drug.>>[LAUGH]
>>So it’s very weird stance to take. And it’s leading to these sorta
very weird situations where yes, if you give me your poop and
I put it in my freezer, I can’t give it back to you until
you get infected with c diff, right? And so I think we definitely need to
rethink the regulations around stool, if we’re gonna use it
as a medical product?>>Hopefully, in five years,
things will have moved on and people will have come to grips
with this and treat it properly. And you think in five years, we’ll be
having a much more personalized service, tailor-made, working out what the exact
bugs are, going to these databases. Pulling off the one that
fits both the disease and the person, and have a much
more rational approach to this. That’s you’re hope.>>That’s the dream. Yeah, exactly.>>I’m gonna have special yogurts
that are also made perfectly for us to live forever.>>[LAUGH]
>>Definitely a big fan of yogurt.>>A big fan of yogurt. Okay, on an optimistic note, I think perhaps we could open up for
some questions.>>I think so.
>>From the audience. I’m sure we’ve wetted someone’s appetite.>>[LAUGH]
>>Here’s a question right here.>>Thank you very much, very enlightening. My question is about the use of bacteria
for cancer treatment such as the BCG.>>So, I think, what are the use
of microbes for cancer treatments?>>Yeah, just looking into the future.>>Okay, well there’s a paper
coming out soon that I’ve been told about that does show that chemotherapy
can be altered by your gut microbes. So that it’s likely that some of these
transplants or special antibiotics will be used in conjunction with chemotherapy
to improve the response to the drugs. So, this is very hot, exciting news. So, it looks like again, for another life
threatening illness by manipulating our gut microbes which produces these
vitamins, these hormones, these immune suppressant chemicals which are really
crucial in fighting cancer, that these could be another use and potentially
another use of these fecal transplants. And why perhaps banking your own healthy
stool for when you might get cancer, or you might get infections,
could be the big thing of the future. Good?>>Yeah, I think we certainly know that the immune system plays
a very big role in cancer. And we’re seeing therapies that are based
on modulating the immune system come out. So the fact that the immune
system really is primed and programmed by the microbes,
lends a lot of plausibility, I think, to the idea that you could modulate
things like chemotherapy and cancer therapy by changing the microbes. But I don’t know about the study that you
mentioned, so I don’t know of any work yet, on that topic, but
it certainly seems very plausible.>>Yeah. Okay.>>[INAUDIBLE]
>>Who’s got the microphone? Okay.>>Hi, thanks very much for the talk. Very interesting. So I had a question regarding Crohn’s
disease in pediatric populations. I understand that there’s been a lot of
work with taking look at their microbia and so forth. And one of the things you mentioned
is about altering your diet and how that changes
the microbial environment. Has there been any correlation
with changing diet and success with treating Crohn’s disease?>>Yes, diet can be very effective. So there’s enteric feeding,
there’s recently a trial that showed that it’s basically
as effective as some of strongest-
>>This is feeding with the tube, where you liquidize everything and
so you know exactly whats going in, in someone who’s rather sick and
can’t eat normally.>>Right.
>>So you can get extra fiber and extra fertilizers for
the microbes in this way.>>Yeah and so it’s very,
very efficacious. So we know diet can have an effect. But enteric feeding, it’s pretty extreme. So you couldn’t do it every day. Right?
And so I don’t know that there’s a lot that’s been shown, in terms of diets that
you could seek to like Mediterranean diet and things like that,
in their role in suppressing IBD. But then again,
I think there’s less work on that topic then there are on more
sort of molecular approaches. So it’s also very, very,
very difficult to track diet. So you can do a diet study
where you do an intervention. But, by logistical constraints, that’s gonna be a relatively short
term intervention, in most cases. And then if you try to track diet via
questionnaires and things like that, they’re notoriously inaccurate, so you need to have extremely large
cohorts to kinda get the signal out. So it’s difficult to study, but
I suspect diet is pretty important.>>Do we have our next question over here?>>Emanuel. I understand that when you’re sick you
have very little choice on what you take. Have you done any study in anal
administration of the transplant?>>So
giving the transplant through the rectum.>>Yes.>>Yes so it’s either given through
a nasal tube down into through the stomach or it’s given through an enema or
through a colonoscopy. So it can go either way. So increasingly it’s been
used through the bottom and that seems to be the route
that’s gaining more approval. So you’re right, when people are very
ill that seems to be a route, but either seem to work,
as well as these capsules.>>Next question right here.>>I was just wondering whether in
consideration of the significant rise of food allergies that we see now in kids
that we didn’t see in the population years ago, whether you’ve seen any
connection between this and changes in the gut micro biomes and
specifically, even within the same families through which birth canal
several children have been born. Have you looked at that at all?>>So I haven’t looked at that personally,
but studies are starting to come out. Especially in mice, showing that
you can transfer some of these food allergy phenotypes
through microbiome. So, those are pretty early studies. And we need to see them confirmed
in humans, and repeated, and things like that. But there’s certainly some
promising leads on that front.>>Epidemiologically,
lack of diversity in the diet, has tracked the increase
in food allergies. So and also the lack of reducing fiber
in the diet has tracked food allergies. So the more people are worried
about food allergies, the more restrictive their diets are. Like saying all those peanut,
I heard of someone with peanut allergies, I’m gonna avoid peanuts
particularly in pregnancy. That actually increases the risk of
the kids getting peanut allergy and other things. So the more restrictive people are going,
listening to all these wacky diets, cutting out grains, worrying about gluten,
all this, they are causing problems. And these animal studies are confirming
that because you can reverse the allergy in the kids, they’ve done it
more with [INAUDIBLE] with food allergies, it’s very hard to do food allergy properly
in animals, but by giving extra fiber to the pregnant mums, they can actually
eliminate the allergies in the kids. So, I think we need to be realizing
that it is a general trend, nothing else really explains this massive increase
in food allergies in the last 20 years. Remember, the first case
report ever was in the 1970s. And you could tour the world
on that one case report as a celebrity if you had a food allergy. We forget quite how common it’s now being,
and I think we have to re-address and realize that the more microbial
exposure we have to our kids, antibiotics, having pets,
dirt everywhere, these are good things. As well as a huge diversity
of high fiber foods, then we can start to reverse this trend.>>Next question over here.>>Hi.
That was actually a good segue because I was going to ask, to what degree do you
think your micro biome is affected by external things versus things
that you actually ingest?>>One for you Eric.>>So let’s see. You mean how’s it changed or
how’s it inoculated from the->>Well so, how is it determined? So are you just as likely to have your
micro biome be changed because you touched something versus because you got
food poisoning at a restaurant one day?>>Right, right, right. So, the kind of changes that we see in
the data that I showed you on myself, what you saw is that I got food poisoning
and then everything radically changed. And they’re totally new species in there,
right. The same type of species, but totally
new ones that I’ve never seen before. That’s actually quite rare, so
the normal day to day variation, is generally a change in the abundance
of the species that you have. And there’s studies showing that apart
from these events like food poisoning, that actually change what species those
are, the species that you have can stably colonize for decades, or
potentially even your entire adult life. So what we see is, the external events, the behavior and the diet, are really
changing the abundances of the microbes that you have and it’s these more
rare events where something actually is ingested and
kind a blooms within the gut. So, I would say it sort of
can happen either way and it normally just effects how
much of each bug there is. And the biggest factor is diet. And within diet the biggest factor
that we were able to track was fiber.>>I have another question over here.>>You said that you’ve ruined
your son’s Micro biome. How did you get it back?>>[LAUGH]
>>I often get asked this.>>[LAUGH].>>He hasn’t keene to be in more
of my experiments since then. Well, I did offer him some salad and
some things afterwards. But seriously,
three weeks later we did test him and he was still way below his
initial starting point. So, they hadn’t recovered
three weeks after. We’ve sent off some other
samples which would be a year after to see if he’s recovered,
but I haven’t got those back yet. But I suspect that, if the insult is
enough, so ten days of zero fiber and all these preservatives and emulsifiers,
you will lose some species permanently. And I think that’s sort of a test. Or they’re below that
level of detection and you can’t be encouraged to
come out of the cracks again. So it is a worry, but it sounds like you can have the odd
burger every now and again. That probably won’t affect you too much. But if you really have nothing else along
it, as well as it, then you’re in trouble. And this is this idea that you
can have some bad things to eat, as long as, there are some
experiments in animals now showing that if you have some very
high fat junk food diets, but at the same time, you have lots of fiber
with them, you’re much better off. So I think we can, in a way, safeguard ourselves against some of these
problems by increasing a variety of fiber, not just one type of fiber, but
a whole range of normal natural fibers.>>We have another question over here.>>This is probably way to
complicated to answer tonight, but my daughter has an auto-immune disease
it shows in alopecia areata and for a while she saw a huge effect of
changing her diet, but then it kind of just Stopped being effective, the change
in diet even though she continues it. What is the correlation
between the microbiome, is that how you say it,
and autoimmune diseases?>>Yes, so there’s a very deep association between many
autoimmune diseases and microbiome. I’ve even heard case reports
connecting microbiome to alopecia. It’s certainly in the sort of
sphere of things that can be influenced by the microbiome. And we think that really
the connection is that the microbiome in the gut is sort of infinitely
interacting with the immune system, and then that immune system has
effects that are more systemic. So there’s interactions that
are happening in the gut that aren’t necessarily related
to gastrointestinal disease. They might be related to conditions in the
hair and in the skin and things like that, other areas where the immune system
is definitely playing a role. So yeah, so
autoimmune is one of the sorta key target areas that a lot of folks
are interested in testing fecal transplants and
trying to find therapeutics in.>>[INAUDIBLE]
>>[LAUGH]>>I don’t know of any current trials, but yeah, we’re almost [CROSSTALK]-
>>Cuz I guess, the point is, sometimes if you have a severe illness and you have
a severe disruption of the microbes, the feeling is that just by eating
a bit more fiber isn’t enough. That there isn’t enough there to
actually regenerate, so it maybe worked better in mild cases, but when it’s
a very severe autoimmune disease, or something else severe, just changes
in diet alone may not be enough. You need a kickstart as well.>>Next question right here.>>You mentioned the sphere of influence
of the microbiome, I’m curious about the different kinds of impacts that
the microbiome has in the human body. What’s being studied now? Does it effect our mood,
does it effect our brain development? Where are scientists really going in terms of how microbiome affects us?>>Yeah, no it’s interesting
that you bring up mood. There have been a lot of papers
establishing sort of a gut brain access. And we know that there are microbes
that are releasing chemicals that are neurotransmitters. And we know that these neurotransmitters
can have an effect on mood and we know the enteric nervous
system is one of the highest concentrations of neurons in the body. And so
there’s a lot of mechanistic evidence and there’s also some compelling animal
experiments sort of showing the power of this gut brain access, but
it’s also one of the kind of big unknowns. So there’s maybe fewer
people studying that, but in terms of clinical impact,
it’s really huge.>>There’s also worry,
isn’t there, that these animals studies are showing that if you make some
mice anxious, and you take their poop and you transplant it to another mouse,
you can make that mouse anxious as well. Which, it sounds a bit fun, but then you
start thinking about fecal transplants in humans, what happens if the donor
was a bit stressed out, and you cure your disease, but
you end up with this long term, these neurochemicals that are being
produced that you weren’t ready for.>>So in turn, you make the FDA anxious.>>[LAUGH].>>And then that makes all
of us researchers anxious.>>[LAUGH]
>>And the cycle->>We transmit it all.>>Positive feedback.>>[LAUGH]
>>But I think the payoff is huge. And it’s one of the things I’d like
to see a lot more people work on, because psychiatric disease in general is
one of those areas where we don’t have the same array of really good
molecular diagnostics and really good small molecule therapeutics. So I think it’s understudied, very
exciting and potentially a big impact.>>Next question here.>>Yes, I’m Mike. When a person has a complete cleanout
prior to an operation, how does the microbiome regenerate on its own,
and will it resemble what it was before?>>I looked at that. I asked some of these gastroenterologists
doing these colonoscopies, and I also tested my own gut before and
after. And generally it does return
fairly quickly to where it was, and we think that’s because
they know where to hide. Our guts are very long and there’s lots
of crevices, little cracks, to hide in. And they’re very skillful and
they know, there’s a big tempest comes, they all batten down the hatches.>>[LAUGH]
>>And they wait for the storm to pass, and you’ve been to the toilet 20 times and
then they come out again. And they say hey, it’s all sunny now and
food starts to come again and they grow. And that happens in most cases. But most gastroenterologists report
that about one in six people who have a colonoscopy end up with
some change in symptoms. And can be improved just by that process,
so we respond differently. So it could be that in some people,
just that process of being washed out can get rid of some of these more toxic
bacteria, but in most people, it doesn’t. It’s again, one of these real mysteries
of why we react differently and why some people take a long time to
recover, some people instantly recovery. It would be like after antibiotics,
huge variation between people and how our microbes respond.>>This will be our last question.>>I wanted to thank the speakers and
I wanted to continue sort of the dialogue and the great interest
that has been shown here and ask Eric, you’re setting up a brand new
microbiome center at MIT. How do we follow the progress of that and learn what interest we
have initiated here? How do we follow you?>>Absolutely, so you can follow us
on Facebook and Twitter, of course. And you can also go to microbiome.mit.edu, where you can get all the news and events. And we have a blog where we regularly
find microbiome science that we think is gonna have a short term clinical
impact and really affect patient care. And then we write a blog entry on that and sort of convey that science
to the general public there. So the best way is to go
to microbiome.mit.edu and find out all about our different
events and activities.>>Excellent.
We wanna thank both speakers for their attention and what they brought to
us here and we’re saving some time so Tim can do some book signing of
his new book, The Diet Myth. Which is really new,
isn’t it out just in the last month, Tim?>>Yes, that’s right.>>So thank you very much.>>[APPLAUSE]>>All right, well thank you very much for joining us tonight for a fascinating
examination of microbes and diet, and the thought of stool as medicine. As an insurance policy,
remember to feed your body fiber and polyphenols and
don’t be afraid of dark chocolate, red wine and olive oil,
the good stuff, the fresh stuff. And the good news is you’ll
never dine alone, and you will have your own
little English garden. So thank you very much for joining us, we hope to see you back next week when
we have a screening of Mass Extinction. Thank you, have a great night.

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