TEDMED 2017
Dan Knights: How we study the microbes living in your gut
丹奈 ． 特斯: 我們如何研究住在腸道內的微生物？
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大約有一百兆微生物住在你的腸道中——保護你不受感染、幫助消化和調節你的免疫系統。但當我們身體適應了現代化的生活，就開始失去了一些正常的微生物；同時，腸道缺乏多樣性所引起的相關疾病，在開發中國家正迅速地攀升。計算微生物學家丹奈．特斯分享了一些迷人的發現，比較在開發中國家和在美國的人們，他們體內的微生物群系有何不同，以及對我們的健康有什麼影響？讓我們一起進一步了解體內所住的微生物，和現在有什麼方式來協助恢復和補充這些微生物。
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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如果我請各位說出一種
住在你腸道中的微生物，
住在你腸道中的微生物，
00:18
many of you would probably say E. coli.
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許多人可能會說大腸桿菌。
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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很多人會這麼說。
它是最多人知道的腸道微生物。
它是最多人知道的腸道微生物。
00:25
But it turns out that E. coli
is outnumbered in your gut
is outnumbered in your gut
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但結果發現，在你的腸道中，
大腸桿菌的數量約只佔
腸道菌的千分之一，
腸道菌的千分之一，
00:30
about a thousand to one
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00:32
by other species, many of which
you probably haven't heard of.
you probably haven't heard of.
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而你可能沒有聽過其他這些
數量較多的菌種。
數量較多的菌種。
00:35
These are Bacteroides;
Prevotella is another example.
Prevotella is another example.
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像是擬桿菌或是普雷沃氏菌。
00:39
Those are the two that dominate
the modern human gut.
the modern human gut.
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這兩種菌種主宰了現代人的腸道。
00:43
There are about a hundred trillion
microbes living inside you.
microbes living inside you.
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大約有一百兆微生物住在你體內。
00:49
We call this your microbiome,
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我們稱之為你的微生物群系，
00:52
so it's like a little world
living inside you --
living inside you --
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它就像是個住在你體內的小世界——
00:54
actually more like a universe.
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其實更像是個宇宙。
00:56
A hundred trillion means
if you took a blade of grass
if you took a blade of grass
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一百兆的大小概念是
如果ㄧ片葉片代表住在你
腸道內的每一個微生物，
腸道內的每一個微生物，
01:00
and planted it for every microbe
living in your gut,
living in your gut,
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01:03
that could fill a million football fields.
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葉片可以填滿一百萬個足球場。
01:05
So it's incredibly complex.
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所以它非常複雜。
01:07
But interestingly,
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但有趣的是，
01:09
as our bodies have been adapting
to life in modern society,
to life in modern society,
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隨著我們的身體
適應現代社會的生活，
適應現代社會的生活，
01:13
we're losing some of our normal microbes,
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我們也失去了一些正常的微生物，
01:18
and at the same time,
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且同時，
在全世界的已開發國家中，
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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有相當多腸道相關的疾病迅速竄升。
01:29
And many of you probably know
someone who suffers from obesity,
someone who suffers from obesity,
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在座許多人可能認識
有下列狀況的人：肥胖、
有下列狀況的人：肥胖、
01:34
diabetes, Crohn's disease
or ulcerative colitis,
or ulcerative colitis,
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糖尿病、克隆氏症或潰瘍性結腸炎、
01:38
allergies and asthma.
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過敏及氣喘。
01:40
Every one of these diseases
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所有這些疾病
01:41
and many others related to metabolism
and autoimmunity
and autoimmunity
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以及許多其他和新陳代謝
及自體免疫相關的疾病
及自體免疫相關的疾病
01:46
are linked to a loss
of healthy diversity in the gut.
of healthy diversity in the gut.
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都和腸道中失去了
健康多樣性的細菌有關。
健康多樣性的細菌有關。
01:52
My lab got our first indication of this
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我的實驗室最初會發現這個現象，
01:54
when actually we were studying
non-human primates.
non-human primates.
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其實是因為我們正在
研究非人類的靈長類。
研究非人類的靈長類。
01:58
We wanted to find out what happens
to a monkey's microbiome
to a monkey's microbiome
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我們想要找出猴子
從叢林搬到動物園之後，
從叢林搬到動物園之後，
02:03
when they move from the jungle to a zoo.
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牠們的微生物群系會發生什麼事。
牠們的微生物群系會改變嗎？
牠們有得到新的菌種嗎？
牠們有得到新的菌種嗎？
02:08
Does their microbiome change?
Do they pick up new bugs?
Do they pick up new bugs?
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02:10
Do they lose some?
Does it get better or worse?
Does it get better or worse?
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還是牠們失去一些？
這樣是好或不好？
這樣是好或不好？
02:13
We tracked two different
species in the jungle,
species in the jungle,
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我們在叢林中追蹤兩種不同的物種，
02:17
one in Vietnam, one in Costa Rica,
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一種在越南，另一種在哥斯大黎加，
02:20
and then we sequenced
the DNA from their stool.
the DNA from their stool.
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我們從牠們的糞便
取得 DNA 來做定序。
取得 DNA 來做定序。
02:23
This is how we study the microbiome
in my research lab.
in my research lab.
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在我的研究實驗室中，
就是這樣研究微生物群系的。
就是這樣研究微生物群系的。
02:27
And what we found in the DNA
is that in the wild,
is that in the wild,
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我們從 DNA 發現，
野外這兩個物種體內的
微生物群組完全不同。
微生物群組完全不同。
02:31
these two species had
totally different sets of microbes.
totally different sets of microbes.
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02:35
It was like a fingerprint for the species.
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它就像是那些物種的指紋。
02:37
But in the zoo, they had lost
most of that diversity
most of that diversity
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但在動物園中，
牠們的多樣性卻少了大半，
牠們的多樣性卻少了大半，
02:43
and had acquired
some other set of microbes.
some other set of microbes.
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還取得了其他的微生物群組。
02:46
So this was very curious.
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這非常讓人好奇。
02:49
We've got these two different microbiomes.
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我們有這兩種不同的微生物群系。
02:51
In the wild, picture a lush
tropical rainforest
tropical rainforest
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想像一個蒼翠繁茂的熱帶雨林，
02:55
living the guts of these monkeys.
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就居住在這些野外猴子的腸道中。
02:58
That's the kind of diversity
that we're talking about.
that we're talking about.
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我們在談的多樣性就類似這樣。
03:01
Then in the zoo, they've lost diversity.
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而在動物園，
牠們就失去了多樣性。
牠們就失去了多樣性。
03:04
Picture a rainforest
that's been burned to the ground
that's been burned to the ground
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想像一個被燒毀的雨林，
03:07
and taken over by a few invasive species.
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只被幾種入侵的物種佔據。
03:11
That's more like the microbiome
in a captive primate.
in a captive primate.
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那就像是被關起來的
靈長類的微生物群系。
靈長類的微生物群系。
03:15
Now, in the meantime,
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同時，
03:17
many of the animals in the zoo
are not doing so well.
are not doing so well.
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動物園中有許多動物的
狀況沒有很好。
狀況沒有很好。
03:19
They have issues with obesity,
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牠們遇到的問題包括肥胖、
03:22
wasting,
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消瘦、
03:24
gastroenteritis, diarrhea, bloating,
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胃腸炎、腹瀉、脹氣，
03:27
and some of them were barely
holding onto their lives.
holding onto their lives.
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有些動物幾乎無法活下去。
03:31
Now, of course, we were
very interested to find out
very interested to find out
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當然，我們非常想要找出
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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在動物園中這些所謂的
入侵菌種到底是什麼。
入侵菌種到底是什麼。
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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所以我們又回到 DNA，
而 DNA 告訴我們
而 DNA 告訴我們
03:42
is that every monkey in the zoo
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動物園中的每一隻猴子
03:47
had become dominated
by Bacteroides and Prevotella,
by Bacteroides and Prevotella,
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都被擬桿菌與普雷沃氏菌所主宰，
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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我們現代人的腸道中
也都有同樣的這些微生物。
也都有同樣的這些微生物。
03:59
We wanted to find a way to visualize this,
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我們想以圖像呈現出這個結果，
04:01
and we used some tools
from multivariate ecology
from multivariate ecology
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所以我們用了一些
多變量生態學的工具，
多變量生態學的工具，
04:05
to put all of the microbiomes
we were studying onto an axis.
we were studying onto an axis.
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把所有我們在研究的
微生物群系放到一個軸上。
微生物群系放到一個軸上。
04:10
And what you're seeing here
is a distance plot
is a distance plot
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各位現在看見的是一張距離圖，
04:14
where every point
is a different animal's microbiome.
is a different animal's microbiome.
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圖上的每一點代表著
不同動物的微生物群系。
不同動物的微生物群系。
04:19
So every point represents
a whole zoo of microbes.
a whole zoo of microbes.
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所以每一個點都代表
整個動物園的微生物。
整個動物園的微生物。
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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微生物越相似的微生物群系，
它們在圖上的距離就會越接近彼此。
04:27
are close to each other.
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04:28
The ones that are very different
are farther apart.
are farther apart.
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反之，則會離越遠。
04:30
So this is showing you
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這張圖是要讓各位看看
04:32
that the two groups of wild monkeys
are over on the left.
are over on the left.
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兩群野生猴子的點都落在圖的左側。
04:38
The top left are these
highly endangered monkeys
highly endangered monkeys
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左上角是嚴重瀕臨絕種的猴子，
04:42
called the red-shanked douc in Vietnam.
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是越南的白臀葉猴。
04:45
And at the bottom left
are monkeys from Costa Rica.
are monkeys from Costa Rica.
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左下角則是在哥斯大黎加的猴子。
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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各位可以看見，野外的猴子
有著迥然不同的微生物群系。
有著迥然不同的微生物群系。
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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而同樣是這兩種猴子，
在放入動物園後卻變得很相似，
在放入動物園後卻變得很相似，
04:58
so their microbiomes change
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所以牠們的微生物群系會變，
05:00
and they become
much more similar to each other,
much more similar to each other,
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彼此變得更相似，
05:03
even though these are zoos
on different continents,
on different continents,
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即使牠們所屬的動物園
位在不同的大陸，
位在不同的大陸，
05:06
different geographical regions,
and they're eating different diets.
and they're eating different diets.
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不同的地理區，
牠們還吃不同的食物。
牠們還吃不同的食物。
05:09
Now, we did study
some other species of primate.
some other species of primate.
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我們的確也研究了其他靈長類物種。
05:12
What species of primate
do you think is even more divergent
do you think is even more divergent
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你們認為哪種靈長類的差異性
比起動物園和野生靈長類的
差異性更大？
差異性更大？
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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現代人類。
05:27
These are humans
living in developing nations.
living in developing nations.
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這些是住在開發中國家的人。
05:30
So they were more different
from the wild primates
from the wild primates
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和在動物園中的靈長類相比，
他們和野生靈長類的差異更大。
05:33
than those in the zoo.
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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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我們研究的最後一個族群，
在圖的最右邊，
在圖的最右邊，
05:41
is people living in the USA.
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就是住在美國的人。
05:44
And when I saw this figure,
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當我看到這張圖，
05:46
the hairs raised up
on the back of my neck,
on the back of my neck,
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讓我寒毛直豎，
05:50
because one way to think about it is,
"Oh, that's interesting,
"Oh, that's interesting,
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因為對這現象的一種思考方式是：
「喔，好有趣，
「喔，好有趣，
05:53
captive monkeys are sort of on their way
to becoming like Americans."
to becoming like Americans."
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被關起來的猴子漸漸
變得和美國人一樣了。」
變得和美國人一樣了。」
05:57
(Laughter)
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（笑聲）
05:58
But the other way to think about it
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但另一種思考方式是
06:00
is that Americans
are like super-captive monkeys.
are like super-captive monkeys.
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美國人就像是被關過頭的猴子。
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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當我在我的電腦螢幕上
看著這張圖時，
看著這張圖時，
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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我聽到一個消息，
動物園中有四隻白臀葉猴
動物園中有四隻白臀葉猴
06:14
had died in the zoo of gut-related issues.
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死於腸道相關疾病。
06:17
So for some of these animals,
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所以對這些動物園的動物而言，
06:19
having the right microbes
living inside them
living inside them
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體內是否有對的微生物，
06:22
may be a matter of survival.
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可能是生死攸關的事。
06:24
Now this brings us
to the human part of the story.
to the human part of the story.
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所以接下來就要談到
關於人類的部分了。
關於人類的部分了。
06:27
Obviously, the microbiomes in the USA
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很顯然，在美國的微生物群系
06:30
aren't causing premature death
as frequently as in the zoo,
as frequently as in the zoo,
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所造成的過早死亡，
並沒有動物園中那麼頻繁，
並沒有動物園中那麼頻繁，
06:36
but we have major risk
of obesity, diabetes,
of obesity, diabetes,
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但我們有很大的風險，
可能會產生肥胖、糖尿病，
可能會產生肥胖、糖尿病，
06:40
a number of these other diseases.
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以及許多其他這類疾病。
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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這不僅適用於已經在美國
住了數個世代的人，
06:47
for many generations,
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06:49
but also to immigrants and refugees,
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也適用於移民和難民，
06:52
who, for most immigrant
and refugee groups,
and refugee groups,
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大部分的移民和難民族群
06:55
arrive in the USA metabolically healthy,
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在抵達美國時，
新陳代謝是很健康的，
新陳代謝是很健康的，
06:58
and then within a few years,
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然而短短幾年後，
07:00
they become just as high-risk
for obesity and diabetes
for obesity and diabetes
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他們卻變成和美國人一樣，
有很高的肥胖和糖尿病風險。
07:03
as other Americans.
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07:05
And we discussed
this issue with two groups
this issue with two groups
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我們和兩個族群討論了這個議題，
07:09
that have been coming to the USA
from Southeast Asia:
from Southeast Asia:
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他們是從東南亞來到美國的：
07:12
the Hmong, who started coming
in the mid-1970s
in the mid-1970s
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赫蒙族，他們從七○年代中期
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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就以越戰與美寮秘密戰爭的
難民身分來到美國；
難民身分來到美國；
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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還有克倫族，他們是比較近期
才以緬甸難民的身份到美國。
才以緬甸難民的身份到美國。
07:26
So we've been working for a few years
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我們花了幾年的時間，
07:28
with these local
communities and clinicians
communities and clinicians
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和當地的社區和臨床醫生合作，
07:31
to study what happens
to the Hmong and Karen microbiomes
to the Hmong and Karen microbiomes
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研究赫蒙族和克倫族從難民營
和泰國的村落搬到美國之後，
和泰國的村落搬到美國之後，
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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他們的微生物群系產生了什麼變化。
07:44
And what we found
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我們發現
07:45
is that when people
come to the USA from these groups,
come to the USA from these groups,
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當這些族群的人來到美國，
07:51
they lose a large fraction
of their microbiome,
of their microbiome,
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他們失去了很多的微生物群系，
07:56
somewhere around 20 percent,
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大約 20% 上下，
07:58
and those who come to the USA
and become obese
and become obese
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而到了美國且變肥胖的人，
08:02
lose about a third of their microbes.
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少了大約三分之一的微生物。
08:06
So we know that moving to the USA
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所以，我們知道搬到美國
08:08
is sufficient to cause
a dramatic change in your microbiome,
a dramatic change in your microbiome,
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就足以造成微生物群系的巨大改變，
08:12
probably not for the better.
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且可能不是變好。
08:15
Are these microbes
actually causing the obesity,
actually causing the obesity,
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真的是這些微生物造成了肥胖？
08:20
or is the obesity causing
a change in the microbes?
a change in the microbes?
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還是肥胖造成了微生物的改變？
08:23
This is something
that we're following up on,
that we're following up on,
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我們後續還在追蹤探究，
08:26
and the evidence we have now in my lab
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而將我實驗室中得到的證據
和來自世界各地的實驗室
所發現的證據彙整後，
所發現的證據彙整後，
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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08:32
tells us that certain changes
in the microbiome
in the microbiome
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顯示了微生物群系的某些改變
08:36
do lead to obesity,
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的確會導致肥胖
以及其他數種現代西化的疾病。
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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好消息是你的微生物群系
可以被改變。
可以被改變。
08:48
Unlike your own genome,
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不像你自己的基因組，
08:51
it's a living, breathing thing,
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它是活的、會呼吸的生物，
08:53
and there's a broad front
of research happening right now
of research happening right now
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且現有廣泛大量的研究正在進行，
讓我們更明瞭當我們的
微生物群系發生問題時，
微生物群系發生問題時，
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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我們要如何
09:02
using diet,
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透過飲食、
09:04
using live microbes.
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透過活的微生物來恢復。
09:06
And in fact, one of the next steps for us
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事實上，我們接下來的其中一步，
09:09
is collecting and preserving microbes
from healthy people around the world
from healthy people around the world
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就是要收集和保存來自
全世界健康人類的微生物，
全世界健康人類的微生物，
09:14
so that they can be kept
as cultural assets for those groups
as cultural assets for those groups
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將其作為這些族群的文化資產
而予保存下來，
而予保存下來，
09:19
to potentially protect them
as they adapt to modern society,
as they adapt to modern society,
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在族群適應現代社會的過程中
提供所需的保護，
提供所需的保護，
09:24
and to protect future generations
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也可以保護未來的世代，
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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這些世代目前成長的過程中，
得到這些疾病的風險越來越高，
得到這些疾病的風險越來越高，
09:31
with every generation.
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一代比一代高。
09:33
I'm looking forward to a future
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我很期待看到在未來
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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我們會有所需的工具
來恢復和補充我們的微生物群系，
來恢復和補充我們的微生物群系，
09:43
and in that world, the monkeys
will live happier and healthier lives,
will live happier and healthier lives,
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在那個世界中，猴子能過著
比較快樂、健康的生活，
比較快樂、健康的生活，
09:48
and so will we.
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我們也一樣。
09:51
(Applause)
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（掌聲）
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