How we study the microbes living in your gut | Dan Knights

72,659 views ・ 2018-08-08

TED


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00:12
If I asked you to name a microbe that's living in your gut,
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many of you would probably say E. coli.
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A lot of people say this. It's the best-known of the gut microbes.
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But it turns out that E. coli is outnumbered in your gut
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about a thousand to one
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by other species, many of which you probably haven't heard of.
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These are Bacteroides; Prevotella is another example.
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Those are the two that dominate the modern human gut.
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There are about a hundred trillion microbes living inside you.
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We call this your microbiome,
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so it's like a little world living inside you --
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actually more like a universe.
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A hundred trillion means if you took a blade of grass
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and planted it for every microbe living in your gut,
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that could fill a million football fields.
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So it's incredibly complex.
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But interestingly,
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as our bodies have been adapting to life in modern society,
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we're losing some of our normal microbes,
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and at the same time,
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there are quite a few diseases related to the gut
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that are skyrocketing in developed nations all around the world.
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And many of you probably know someone who suffers from obesity,
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diabetes, Crohn's disease or ulcerative colitis,
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allergies and asthma.
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Every one of these diseases
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and many others related to metabolism and autoimmunity
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are linked to a loss of healthy diversity in the gut.
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My lab got our first indication of this
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when actually we were studying non-human primates.
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We wanted to find out what happens to a monkey's microbiome
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when they move from the jungle to a zoo.
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Does their microbiome change? Do they pick up new bugs?
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Do they lose some? Does it get better or worse?
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We tracked two different species in the jungle,
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one in Vietnam, one in Costa Rica,
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and then we sequenced the DNA from their stool.
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This is how we study the microbiome in my research lab.
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And what we found in the DNA is that in the wild,
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these two species had totally different sets of microbes.
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It was like a fingerprint for the species.
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But in the zoo, they had lost most of that diversity
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and had acquired some other set of microbes.
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So this was very curious.
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We've got these two different microbiomes.
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In the wild, picture a lush tropical rainforest
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living the guts of these monkeys.
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That's the kind of diversity that we're talking about.
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Then in the zoo, they've lost diversity.
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Picture a rainforest that's been burned to the ground
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and taken over by a few invasive species.
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That's more like the microbiome in a captive primate.
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Now, in the meantime,
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many of the animals in the zoo are not doing so well.
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They have issues with obesity,
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wasting,
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gastroenteritis, diarrhea, bloating,
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and some of them were barely holding onto their lives.
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Now, of course, we were very interested to find out
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what are these so-called invasive species that are taking over in the zoo.
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So we went back to the DNA, and what the DNA told us
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is that every monkey in the zoo
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had become dominated by Bacteroides and Prevotella,
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the same microbes that we all have in our guts as modern humans.
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We wanted to find a way to visualize this,
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and we used some tools from multivariate ecology
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to put all of the microbiomes we were studying onto an axis.
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And what you're seeing here is a distance plot
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where every point is a different animal's microbiome.
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So every point represents a whole zoo of microbes.
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And the microbiomes that have a lot of microbes in common
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are close to each other.
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The ones that are very different are farther apart.
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So this is showing you
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that the two groups of wild monkeys are over on the left.
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The top left are these highly endangered monkeys
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called the red-shanked douc in Vietnam.
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And at the bottom left are monkeys from Costa Rica.
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So you can see that they have totally different microbiomes in the wild.
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And then the same two species of monkey in the zoo are converging,
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so their microbiomes change
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and they become much more similar to each other,
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even though these are zoos on different continents,
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different geographical regions, and they're eating different diets.
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Now, we did study some other species of primate.
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What species of primate do you think is even more divergent
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from the wild primates than the captive primates?
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Modern humans.
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These are humans living in developing nations.
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So they were more different from the wild primates
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than those in the zoo.
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And the final group that we studied, all the way on the right,
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is people living in the USA.
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And when I saw this figure,
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the hairs raised up on the back of my neck,
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because one way to think about it is, "Oh, that's interesting,
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captive monkeys are sort of on their way to becoming like Americans."
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(Laughter)
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But the other way to think about it
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is that Americans are like super-captive monkeys.
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And I was actually looking at this figure on my computer screen
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when I got the news that four of the red-shanked doucs
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had died in the zoo of gut-related issues.
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So for some of these animals,
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having the right microbes living inside them
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may be a matter of survival.
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Now this brings us to the human part of the story.
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Obviously, the microbiomes in the USA
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aren't causing premature death as frequently as in the zoo,
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but we have major risk of obesity, diabetes,
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a number of these other diseases.
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And this applies not just to people who have been living in the USA
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for many generations,
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but also to immigrants and refugees,
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who, for most immigrant and refugee groups,
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arrive in the USA metabolically healthy,
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and then within a few years,
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they become just as high-risk for obesity and diabetes
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as other Americans.
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And we discussed this issue with two groups
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that have been coming to the USA from Southeast Asia:
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the Hmong, who started coming in the mid-1970s
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as refugees from the Vietnam War and the US secret war in Laos;
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and the Karen, who have been coming more recently as refugees from Myanmar.
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So we've been working for a few years
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with these local communities and clinicians
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to study what happens to the Hmong and Karen microbiomes
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when people move from refugee camps and villages in Thailand to the USA.
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And what we found
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is that when people come to the USA from these groups,
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they lose a large fraction of their microbiome,
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somewhere around 20 percent,
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and those who come to the USA and become obese
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lose about a third of their microbes.
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So we know that moving to the USA
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is sufficient to cause a dramatic change in your microbiome,
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probably not for the better.
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Are these microbes actually causing the obesity,
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or is the obesity causing a change in the microbes?
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This is something that we're following up on,
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and the evidence we have now in my lab
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combined with evidence from a number of labs around the world
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tells us that certain changes in the microbiome
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do lead to obesity,
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and a number of other modern, kind of Westernized diseases.
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The good news is that your microbiome can actually change.
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Unlike your own genome,
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it's a living, breathing thing,
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and there's a broad front of research happening right now
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to better understand how we can restore our microbiomes
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when something goes wrong,
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using diet,
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using live microbes.
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And in fact, one of the next steps for us
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is collecting and preserving microbes from healthy people around the world
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so that they can be kept as cultural assets for those groups
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to potentially protect them as they adapt to modern society,
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and to protect future generations
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who are currently growing up to have increased risk of these diseases
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with every generation.
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I'm looking forward to a future
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where we have the tools that we need to restore and replenish our microbiomes,
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and in that world, the monkeys will live happier and healthier lives,
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and so will we.
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(Applause)
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