TEDMED 2017
Dan Knights: How we study the microbes living in your gut
丹·奈池: 我们是如何研究人体内的微生物的
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你的肠道内大约生存着一百万亿个微生物——它们有保护你免于感染、助消化和调节你的免疫系统的作用。然而，随着我们的身体适应现代生活，我们开始失去一些正常的微生物；与此同时，发达国家中，因为肠道内微生物失去多样性而引发的疾病正在飙升。计算微生物学家丹·奈池分享了他的关于发展中国家与美国人体内微生物群不同的一些有趣发现，以及它们如何影响我们的健康。了解更多生活在你体内的微生物世界吧——以及正在进行的创造关于恢复和补充微生物群工具的工作。
Dan Knights - Computational microbiologist
Dan Knights develops computational methods for doing precision medicine with gut bacterial communities, or microbiomes, and he applies those methods to study human disease. Full bio
Dan Knights develops computational methods for doing precision medicine with gut bacterial communities, or microbiomes, and he applies those methods to study human disease. Full bio
Double-click the English transcript below to play the video.
00:12
If I asked you to name a microbe
that's living in your gut,
that's living in your gut,
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如果请你举例说出一个
生活在你肠道里的微生物，
生活在你肠道里的微生物，
很多人可能会说大肠杆菌，
00:18
many of you would probably say E. coli.
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确实很多人都这么说。
大肠杆菌是最有名的肠道微生物，
大肠杆菌是最有名的肠道微生物，
00:21
A lot of people say this.
It's the best-known of the gut microbes.
It's the best-known of the gut microbes.
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但事实证明,
大肠杆菌只占你肠道中
大肠杆菌只占你肠道中
00:25
But it turns out that E. coli
is outnumbered in your gut
is outnumbered in your gut
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细菌数量的1‰，
00:30
about a thousand to one
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其它很多细菌你可能听都没听过，
00:32
by other species, many of which
you probably haven't heard of.
you probably haven't heard of.
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00:35
These are Bacteroides;
Prevotella is another example.
Prevotella is another example.
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像类杆菌属的细菌；
另一个例子是普氏菌。
另一个例子是普氏菌。
在现代人的肠道菌群中，
这两种细菌占主导地位。
这两种细菌占主导地位。
00:39
Those are the two that dominate
the modern human gut.
the modern human gut.
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00:43
There are about a hundred trillion
microbes living inside you.
microbes living inside you.
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人体内生活着约100万亿的微生物，
00:49
We call this your microbiome,
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我们称之为微生物群，
它们就像生活在
你体内的一个小世界——
你体内的一个小世界——
00:52
so it's like a little world
living inside you --
living inside you --
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实际更像一个宇宙。
00:54
actually more like a universe.
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00:56
A hundred trillion means
if you took a blade of grass
if you took a blade of grass
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100万亿的数量概念是这样的，
如果一根草
代表一个生活在你肠道内的微生物，
代表一个生活在你肠道内的微生物，
01:00
and planted it for every microbe
living in your gut,
living in your gut,
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那么就可以种满100万个足球场。
01:03
that could fill a million football fields.
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因此这是一个难以置信的复杂系统。
01:05
So it's incredibly complex.
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但有趣的是，
01:07
But interestingly,
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随着我们的身体逐渐适应现代生活，
01:09
as our bodies have been adapting
to life in modern society,
to life in modern society,
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我们正在失去一些正常的微生物，
01:13
we're losing some of our normal microbes,
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与此同时，
01:18
and at the same time,
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在世界发达国家，
01:21
there are quite a few diseases
related to the gut
related to the gut
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01:24
that are skyrocketing
in developed nations all around the world.
in developed nations all around the world.
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很多与肠道有关的疾病正在飙升。
01:29
And many of you probably know
someone who suffers from obesity,
someone who suffers from obesity,
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许多在座的各位
可能就认识一些饱受肥胖症、
可能就认识一些饱受肥胖症、
01:34
diabetes, Crohn's disease
or ulcerative colitis,
or ulcerative colitis,
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糖尿病、节段性回肠炎
或溃疡性结肠炎、
或溃疡性结肠炎、
过敏和哮喘疾病之苦的患者。
01:38
allergies and asthma.
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和许多
01:40
Every one of these diseases
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与新陈代谢及自身免疫相关
的病症一样，
的病症一样，
01:41
and many others related to metabolism
and autoimmunity
and autoimmunity
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这些疾病都与肠道（菌群）
缺少健康多样性有关。
缺少健康多样性有关。
01:46
are linked to a loss
of healthy diversity in the gut.
of healthy diversity in the gut.
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01:52
My lab got our first indication of this
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我的实验室在研究非人类
——灵长类动物时,
——灵长类动物时,
第一次发现了这个征兆。
01:54
when actually we were studying
non-human primates.
non-human primates.
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我们想了解
当猴子由丛林搬到动物园后，
当猴子由丛林搬到动物园后，
01:58
We wanted to find out what happens
to a monkey's microbiome
to a monkey's microbiome
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它们体内的微生物群
会发生什么变化。
会发生什么变化。
02:03
when they move from the jungle to a zoo.
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02:08
Does their microbiome change?
Do they pick up new bugs?
Do they pick up new bugs?
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它们体内的微生物群改变了吗？
是否增加了新微生物？
是否增加了新微生物？
失去一些微生物吗？
微生物群是在变好，还是变糟呢？
微生物群是在变好，还是变糟呢？
02:10
Do they lose some?
Does it get better or worse?
Does it get better or worse?
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我们分别对丛林中（生活的）
两个不同物种进行了追踪研究，
两个不同物种进行了追踪研究，
02:13
We tracked two different
species in the jungle,
species in the jungle,
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一个物种在越南，
一个在哥斯达黎加，
一个在哥斯达黎加，
02:17
one in Vietnam, one in Costa Rica,
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我们用它们的粪便
进行了DNA测序，
进行了DNA测序，
02:20
and then we sequenced
the DNA from their stool.
the DNA from their stool.
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这就是我们实验室
对微生物进行研究的方法。
对微生物进行研究的方法。
02:23
This is how we study the microbiome
in my research lab.
in my research lab.
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通过DNA比对，我们发现
野外的这两个物种体内，
野外的这两个物种体内，
02:27
And what we found in the DNA
is that in the wild,
is that in the wild,
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微生物群截然不同。
02:31
these two species had
totally different sets of microbes.
totally different sets of microbes.
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微生物群
就像物种的指纹一样。
就像物种的指纹一样。
02:35
It was like a fingerprint for the species.
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但在动物园里, 它们的微生物群
却失去了大部分的多样性，
却失去了大部分的多样性，
02:37
But in the zoo, they had lost
most of that diversity
most of that diversity
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并获得了一些其它的微生物，
02:43
and had acquired
some other set of microbes.
some other set of microbes.
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02:46
So this was very curious.
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这种现象非常奇怪。
我们有两个不同的微生物群：
02:49
We've got these two different microbiomes.
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野外动物体内的微生物群，
02:51
In the wild, picture a lush
tropical rainforest
tropical rainforest
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它就像郁郁葱葱的热带雨林
活在这些猴子的肠道内，
活在这些猴子的肠道内，
02:55
living the guts of these monkeys.
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02:58
That's the kind of diversity
that we're talking about.
that we're talking about.
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也就是我们说的多样性；
然而在动物园里, 它们
（微生物群）却失去了多样性，
（微生物群）却失去了多样性，
03:01
Then in the zoo, they've lost diversity.
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03:04
Picture a rainforest
that's been burned to the ground
that's been burned to the ground
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就好像一些入侵物种
接管了烧光的雨林，
03:07
and taken over by a few invasive species.
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03:11
That's more like the microbiome
in a captive primate.
in a captive primate.
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因此它们更像圈养灵长类
动物体内的微生物群。
动物体内的微生物群。
03:15
Now, in the meantime,
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与此同时，在动物园里，
03:17
many of the animals in the zoo
are not doing so well.
are not doing so well.
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许多动物身体状况都不太好，
它们有肥胖、
03:19
They have issues with obesity,
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消瘦、
03:22
wasting,
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肠胃炎、腹泻、腹胀等问题，
03:24
gastroenteritis, diarrhea, bloating,
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有些动物几乎活不下去了。
03:27
and some of them were barely
holding onto their lives.
holding onto their lives.
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03:31
Now, of course, we were
very interested to find out
very interested to find out
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因此，我们对找出这些
所谓的入侵物种很感兴趣，
所谓的入侵物种很感兴趣，
它们主宰着动物园里
动物体内的微生物群。
动物体内的微生物群。
03:34
what are these so-called invasive species
that are taking over in the zoo.
that are taking over in the zoo.
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03:39
So we went back to the DNA,
and what the DNA told us
and what the DNA told us
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所以我们分析了它们的DNA，
发现动物园里的
每只猴子的肠道内
每只猴子的肠道内
03:42
is that every monkey in the zoo
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都被类杆菌和普氏菌所主宰，
03:47
had become dominated
by Bacteroides and Prevotella,
by Bacteroides and Prevotella,
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这些猴子和现代人肠内
拥有相同的微生物群。
拥有相同的微生物群。
03:52
the same microbes that we all have
in our guts as modern humans.
in our guts as modern humans.
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03:59
We wanted to find a way to visualize this,
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为找到让这一发现结果
可视化的方法，
可视化的方法，
我们使用了一些多元生态学工具,
04:01
and we used some tools
from multivariate ecology
from multivariate ecology
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把我们研究的微生物群
放在（坐标图的）轴线上。
放在（坐标图的）轴线上。
04:05
to put all of the microbiomes
we were studying onto an axis.
we were studying onto an axis.
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这里你看到的是一个距离图，
04:10
And what you're seeing here
is a distance plot
is a distance plot
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每个点代表着
不同动物的微生物群，
不同动物的微生物群，
04:14
where every point
is a different animal's microbiome.
is a different animal's microbiome.
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所以，每一点也代表了
整个动物园的微生物。
整个动物园的微生物。
04:19
So every point represents
a whole zoo of microbes.
a whole zoo of microbes.
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04:23
And the microbiomes
that have a lot of microbes in common
that have a lot of microbes in common
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如果不同微生物群中
彼此的微生物相似的话，
彼此的微生物相似的话，
它们在图中的距离就很近；
04:27
are close to each other.
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差异很大的微生物群，
在图中则离彼此很远。
在图中则离彼此很远。
04:28
The ones that are very different
are farther apart.
are farther apart.
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这里展示的是：
04:30
So this is showing you
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最左边的点
代表两组野外的猴子，
代表两组野外的猴子，
04:32
that the two groups of wild monkeys
are over on the left.
are over on the left.
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左上方的点是
高度濒危的越南猴，
高度濒危的越南猴，
04:38
The top left are these
highly endangered monkeys
highly endangered monkeys
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叫做白臀叶猴，
04:42
called the red-shanked douc in Vietnam.
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左下角的点则是
来自哥斯达黎加的猴子。
来自哥斯达黎加的猴子。
04:45
And at the bottom left
are monkeys from Costa Rica.
are monkeys from Costa Rica.
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04:49
So you can see that they have
totally different microbiomes in the wild.
totally different microbiomes in the wild.
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从图中看出，野外生活的猴子
有着完全不同的微生物群。
有着完全不同的微生物群。
而在动物园里，这两种猴子
（的微生物群）正在汇合，
（的微生物群）正在汇合，
04:52
And then the same two species
of monkey in the zoo are converging,
of monkey in the zoo are converging,
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它们的微生物群改变了，
04:58
so their microbiomes change
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变得更加相似，
05:00
and they become
much more similar to each other,
much more similar to each other,
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尽管它们（猴子）来自
不同大洲的动物园、
不同大洲的动物园、
05:03
even though these are zoos
on different continents,
on different continents,
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不同的地理区域和不同的饮食。
05:06
different geographical regions,
and they're eating different diets.
and they're eating different diets.
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我们也研究过
其他种类的灵长类动物，
其他种类的灵长类动物，
05:09
Now, we did study
some other species of primate.
some other species of primate.
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你觉得哪种灵长类动物
05:12
What species of primate
do you think is even more divergent
do you think is even more divergent
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比圈养的灵长类
更加与野生灵长类不同？
更加与野生灵长类不同？
05:18
from the wild primates
than the captive primates?
than the captive primates?
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05:24
Modern humans.
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是现代人类！
05:27
These are humans
living in developing nations.
living in developing nations.
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图中这些点代表
生活在发展中国家的人，
生活在发展中国家的人，
和物园里的灵长类比起来，
05:30
So they were more different
from the wild primates
from the wild primates
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他们与野生灵长类更加不同。
05:33
than those in the zoo.
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我们研究的最后一组
在图中最右边，
在图中最右边，
05:35
And the final group that we studied,
all the way on the right,
all the way on the right,
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05:41
is people living in the USA.
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他们是生活在美国的人们。
05:44
And when I saw this figure,
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当我看到这个图时，
脖子后面的汗毛都竖起来了！
05:46
the hairs raised up
on the back of my neck,
on the back of my neck,
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因为一种解释是,
"我的妈呀，太有趣了，
"我的妈呀，太有趣了，
05:50
because one way to think about it is,
"Oh, that's interesting,
"Oh, that's interesting,
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圈养的猴子
快变成美国人了！“
快变成美国人了！“
05:53
captive monkeys are sort of on their way
to becoming like Americans."
to becoming like Americans."
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（笑声）
05:57
(Laughter)
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但另一种解读则是，
05:58
But the other way to think about it
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美国人就像超级圈养的猴子。
06:00
is that Americans
are like super-captive monkeys.
are like super-captive monkeys.
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06:04
And I was actually looking
at this figure on my computer screen
at this figure on my computer screen
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当我听到四只动物园白臀叶猴
因为肠道疾病而死的消息时，
06:09
when I got the news
that four of the red-shanked doucs
that four of the red-shanked doucs
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我正看着电脑屏幕上的这个图。
06:14
had died in the zoo of gut-related issues.
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因此，对这些动物来说,
06:17
So for some of these animals,
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它们体内
是否生存着正常的微生物，
是否生存着正常的微生物，
06:19
having the right microbes
living inside them
living inside them
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可能是个生死攸关的问题。
06:22
may be a matter of survival.
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我们自然就要谈到人的问题，
06:24
Now this brings us
to the human part of the story.
to the human part of the story.
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显然，美国人体内
微生物群的失衡，
微生物群的失衡，
06:27
Obviously, the microbiomes in the USA
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并没有造成
像动物园那么多夭折，
像动物园那么多夭折，
06:30
aren't causing premature death
as frequently as in the zoo,
as frequently as in the zoo,
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但我们有肥胖、糖尿病、
06:36
but we have major risk
of obesity, diabetes,
of obesity, diabetes,
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和其他类似疾病的高发病率。
06:40
a number of these other diseases.
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不仅是在美国生活了好几代的人
06:43
And this applies not just to people
who have been living in the USA
who have been living in the USA
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存在这样的问题，
06:47
for many generations,
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而且新移民和难民也一样，
06:49
but also to immigrants and refugees,
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多数移民
和难民群体抵达美国时，
和难民群体抵达美国时，
06:52
who, for most immigrant
and refugee groups,
and refugee groups,
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他们在新陈代谢方面很健康，
06:55
arrive in the USA metabolically healthy,
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然后，在几年之内,
06:58
and then within a few years,
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他们患上肥胖和糖尿病的风险
07:00
they become just as high-risk
for obesity and diabetes
for obesity and diabetes
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与美国人一样高。
07:03
as other Americans.
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我们与两个
从东南亚迁来美国的团体
从东南亚迁来美国的团体
07:05
And we discussed
this issue with two groups
this issue with two groups
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07:09
that have been coming to the USA
from Southeast Asia:
from Southeast Asia:
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讨论过这个问题：
一个是洪族人，因越南战争
和老挝美国秘密战争，
和老挝美国秘密战争，
07:12
the Hmong, who started coming
in the mid-1970s
in the mid-1970s
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从 20 世纪 70 年代中叶开始，
他们以难民身份来到美国；
他们以难民身份来到美国；
07:16
as refugees from the Vietnam War
and the US secret war in Laos;
and the US secret war in Laos;
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另一个是凯伦人，
最近才从缅甸来的难民。
最近才从缅甸来的难民。
07:21
and the Karen, who have been coming
more recently as refugees from Myanmar.
more recently as refugees from Myanmar.
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我们已经与这些当地社区
07:26
So we've been working for a few years
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和临床医生一起工作了几年，
07:28
with these local
communities and clinicians
communities and clinicians
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研究洪族人和凯伦人
从泰国难民营和村庄来到美国后，
从泰国难民营和村庄来到美国后，
07:31
to study what happens
to the Hmong and Karen microbiomes
to the Hmong and Karen microbiomes
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他们体内的微生物群
会发生怎样的变化。
会发生怎样的变化。
07:36
when people move from refugee camps
and villages in Thailand to the USA.
and villages in Thailand to the USA.
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07:44
And what we found
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我们发现，
当这些人来到美国后，
07:45
is that when people
come to the USA from these groups,
come to the USA from these groups,
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他们体内的微生物群
失去了很大一部分，
失去了很大一部分，
07:51
they lose a large fraction
of their microbiome,
of their microbiome,
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07:56
somewhere around 20 percent,
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约 20%；
07:58
and those who come to the USA
and become obese
and become obese
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而那些来美国后
患肥胖症的人，
患肥胖症的人，
则失去了(原来)
微生物群的三分之一。
微生物群的三分之一。
08:02
lose about a third of their microbes.
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08:06
So we know that moving to the USA
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因此，我们得出结论，
移居到美国生活后，会造成
体内微生物群发生巨大改变，
体内微生物群发生巨大改变，
08:08
is sufficient to cause
a dramatic change in your microbiome,
a dramatic change in your microbiome,
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很可能不是在变好。
08:12
probably not for the better.
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08:15
Are these microbes
actually causing the obesity,
actually causing the obesity,
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这些微生物群
真的会导致肥胖，
真的会导致肥胖，
还是肥胖造成了
微生物群的改变？
微生物群的改变？
08:20
or is the obesity causing
a change in the microbes?
a change in the microbes?
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这是我们正在跟进的事情，
08:23
This is something
that we're following up on,
that we're following up on,
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我们实验室发现的证据，
08:26
and the evidence we have now in my lab
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以及来自世界各地一些实验室的
证据都告诉我们，
证据都告诉我们，
08:29
combined with evidence
from a number of labs around the world
from a number of labs around the world
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微生物群的某些变化
08:32
tells us that certain changes
in the microbiome
in the microbiome
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会导致肥胖、
08:36
do lead to obesity,
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以及其它一些现代病，
或者说西方病。
或者说西方病。
08:38
and a number of other modern,
kind of Westernized diseases.
kind of Westernized diseases.
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08:43
The good news is that
your microbiome can actually change.
your microbiome can actually change.
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好消息是，你体内的
微生物群是可以改变的。
微生物群是可以改变的。
和你的基因组不同的是，
08:48
Unlike your own genome,
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它（微生物群）是活生生、
会呼吸的东西。
会呼吸的东西。
08:51
it's a living, breathing thing,
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（科学家们）正在进行
一项广泛的前沿研究，
一项广泛的前沿研究，
08:53
and there's a broad front
of research happening right now
of research happening right now
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以便更好地了解
当微生物群出现问题时，
当微生物群出现问题时，
08:57
to better understand
how we can restore our microbiomes
how we can restore our microbiomes
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09:00
when something goes wrong,
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如何通过饮食、
09:02
using diet,
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使用活的微生物，
09:04
using live microbes.
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去恢复体内的微生物群。
09:06
And in fact, one of the next steps for us
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事实上, 我们下一步要做的是，
为那些（患病）的人群收集和保存
来自世界各地健康人士的微生物，
来自世界各地健康人士的微生物，
09:09
is collecting and preserving microbes
from healthy people around the world
from healthy people around the world
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以便作为文化资产进行保存，
09:14
so that they can be kept
as cultural assets for those groups
as cultural assets for those groups
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在他们适应现代社会时，
对之进行潜在保护；
对之进行潜在保护；
09:19
to potentially protect them
as they adapt to modern society,
as they adapt to modern society,
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保护正在成长、
09:24
and to protect future generations
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后代有较高风险
09:27
who are currently growing up
to have increased risk of these diseases
to have increased risk of these diseases
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患西方病的这一代人，
09:31
with every generation.
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09:33
I'm looking forward to a future
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未来，我期待，
会有我们需要的工具，以修复
和补充我们体内的微生物群，
和补充我们体内的微生物群，
09:36
where we have the tools that we need
to restore and replenish our microbiomes,
to restore and replenish our microbiomes,
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09:43
and in that world, the monkeys
will live happier and healthier lives,
will live happier and healthier lives,
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在未来世界里，不但猴子们
会过上更快乐、更健康的生活，
会过上更快乐、更健康的生活，
我们也会！
09:48
and so will we.
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09:51
(Applause)
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（掌声）
ABOUT THE SPEAKER
Dan Knights - Computational microbiologistDan Knights develops computational methods for doing precision medicine with gut bacterial communities, or microbiomes, and he applies those methods to study human disease.
Why you should listen
Trillions of bacteria live in our guts, protecting us from infection and aiding our digestion, yet these communities are so complex that we need advanced computational methods to study them. In his multidisciplinary research lab, Dan Knights combines expertise in data mining and biology to learn about how modern lifestyles and medical practices are affecting our microbiomes and leading to increases in modern diseases.
Knights received his PhD in computer science from the University of Colorado, followed by a post-doctoral fellowship at Harvard Medical School. He has co-authored more than 70 highly cited articles in top multidisciplinary journals. In 2015 he was named a McKnight Land-Grant Professor by the University of Minnesota. His lab is building a next-generation informatics pipeline for microbiome-targeted drug discovery, linking nutrition and microbial activity to clinical outcomes.
Dan Knights | Speaker | TED.com