How we study the microbes living in your gut Dan Knights
If I asked you to name a microbe
that’s living in your gut,
many of you would probably say E. coli.
A lot of people say this.
It’s the best-known of the gut microbes.
But it turns out that E. coli
is outnumbered in your gut
about a thousand to one
by other species, many of which
you probably haven’t heard of.
These are Bacteroides;
Prevotella is another example.
Those are the two that dominate
the modern human gut.
There are about a hundred trillion
microbes living inside you.
We call this your microbiome,
so it’s like a little world
living inside you –
actually more like a universe.
A hundred trillion means
if you took a blade of grass
and planted it for every microbe
living in your gut,
that could fill a million football fields.
So it’s incredibly complex.
But interestingly,
as our bodies have been adapting
to life in modern society,
we’re losing some of our normal microbes,
and at the same time,
there are quite a few diseases
related to the gut
that are skyrocketing
in developed nations all around the world.
And many of you probably know
someone who suffers from obesity,
diabetes, Crohn’s disease
or ulcerative colitis,
allergies and asthma.
Every one of these diseases
and many others related to metabolism
and autoimmunity
are linked to a loss
of healthy diversity in the gut.
My lab got our first indication of this
when actually we were studying
non-human primates.
We wanted to find out what happens
to a monkey’s microbiome
when they move from the jungle to a zoo.
Does their microbiome change?
Do they pick up new bugs?
Do they lose some?
Does it get better or worse?
We tracked two different
species in the jungle,
one in Vietnam, one in Costa Rica,
and then we sequenced
the DNA from their stool.
This is how we study the microbiome
in my research lab.
And what we found in the DNA
is that in the wild,
these two species had
totally different sets of microbes.
It was like a fingerprint for the species.
But in the zoo, they had lost
most of that diversity
and had acquired
some other set of microbes.
So this was very curious.
We’ve got these two different microbiomes.
In the wild, picture a lush
tropical rainforest
living the guts of these monkeys.
That’s the kind of diversity
that we’re talking about.
Then in the zoo, they’ve lost diversity.
Picture a rainforest
that’s been burned to the ground
and taken over by a few invasive species.
That’s more like the microbiome
in a captive primate.
Now, in the meantime,
many of the animals in the zoo
are not doing so well.
They have issues with obesity,
wasting,
gastroenteritis, diarrhea, bloating,
and some of them were barely
holding onto their lives.
Now, of course, we were
very interested to find out
what are these so-called invasive species
that are taking over in the zoo.
So we went back to the DNA,
and what the DNA told us
is that every monkey in the zoo
had become dominated
by Bacteroides and Prevotella,
the same microbes that we all have
in our guts as modern humans.
We wanted to find a way to visualize this,
and we used some tools
from multivariate ecology
to put all of the microbiomes
we were studying onto an axis.
And what you’re seeing here
is a distance plot
where every point
is a different animal’s microbiome.
So every point represents
a whole zoo of microbes.
And the microbiomes
that have a lot of microbes in common
are close to each other.
The ones that are very different
are farther apart.
So this is showing you
that the two groups of wild monkeys
are over on the left.
The top left are these
highly endangered monkeys
called the red-shanked douc in Vietnam.
And at the bottom left
are monkeys from Costa Rica.
So you can see that they have
totally different microbiomes in the wild.
And then the same two species
of monkey in the zoo are converging,
so their microbiomes change
and they become
much more similar to each other,
even though these are zoos
on different continents,
different geographical regions,
and they’re eating different diets.
Now, we did study
some other species of primate.
What species of primate
do you think is even more divergent
from the wild primates
than the captive primates?
Modern humans.
These are humans
living in developing nations.
So they were more different
from the wild primates
than those in the zoo.
And the final group that we studied,
all the way on the right,
is people living in the USA.
And when I saw this figure,
the hairs raised up
on the back of my neck,
because one way to think about it is,
“Oh, that’s interesting,
captive monkeys are sort of on their way
to becoming like Americans.”
(Laughter)
But the other way to think about it
is that Americans
are like super-captive monkeys.
And I was actually looking
at this figure on my computer screen
when I got the news
that four of the red-shanked doucs
had died in the zoo of gut-related issues.
So for some of these animals,
having the right microbes
living inside them
may be a matter of survival.
Now this brings us
to the human part of the story.
Obviously, the microbiomes in the USA
aren’t causing premature death
as frequently as in the zoo,
but we have major risk
of obesity, diabetes,
a number of these other diseases.
And this applies not just to people
who have been living in the USA
for many generations,
but also to immigrants and refugees,
who, for most immigrant
and refugee groups,
arrive in the USA metabolically healthy,
and then within a few years,
they become just as high-risk
for obesity and diabetes
as other Americans.
And we discussed
this issue with two groups
that have been coming to the USA
from Southeast Asia:
the Hmong, who started coming
in the mid-1970s
as refugees from the Vietnam War
and the US secret war in Laos;
and the Karen, who have been coming
more recently as refugees from Myanmar.
So we’ve been working for a few years
with these local
communities and clinicians
to study what happens
to the Hmong and Karen microbiomes
when people move from refugee camps
and villages in Thailand to the USA.
And what we found
is that when people
come to the USA from these groups,
they lose a large fraction
of their microbiome,
somewhere around 20 percent,
and those who come to the USA
and become obese
lose about a third of their microbes.
So we know that moving to the USA
is sufficient to cause
a dramatic change in your microbiome,
probably not for the better.
Are these microbes
actually causing the obesity,
or is the obesity causing
a change in the microbes?
This is something
that we’re following up on,
and the evidence we have now in my lab
combined with evidence
from a number of labs around the world
tells us that certain changes
in the microbiome
do lead to obesity,
and a number of other modern,
kind of Westernized diseases.
The good news is that
your microbiome can actually change.
Unlike your own genome,
it’s a living, breathing thing,
and there’s a broad front
of research happening right now
to better understand
how we can restore our microbiomes
when something goes wrong,
using diet,
using live microbes.
And in fact, one of the next steps for us
is collecting and preserving microbes
from healthy people around the world
so that they can be kept
as cultural assets for those groups
to potentially protect them
as they adapt to modern society,
and to protect future generations
who are currently growing up
to have increased risk of these diseases
with every generation.
I’m looking forward to a future
where we have the tools that we need
to restore and replenish our microbiomes,
and in that world, the monkeys
will live happier and healthier lives,
and so will we.
(Applause)