Jonathan Eisen: Meet your microbes

Translator: Morton Bast Reviewer: Thu-Huong Ha

譯者: Alex M. Chang 審譯者: Yuguo Zhang

I'm going to start with a little story.

我要用一個小故事做開場。

So, I grew up in this neighborhood. When I was 15 years old,

我在這附近長大。15歲時，

I went from being what I think was a strapping young athlete,

我從一個自信身材魁梧的年輕運動員，

over four months, slowly wasting away until

四個多月，逐漸消瘦，

I was basically a famine victim

瘦到像是個饑荒的災民，

with an unquenchable thirst.

無時無刻覺得口渴

I had basically digested away my body.

我的身體基本上被消化掉了。

And this all came to a head when I was on a backpacking trip,

狀況嚴重到，當我自助旅行到西維吉尼亞州，

my first one ever actually, on Old Rag Mountain

到 Old Rag Mountain, 那是我頭一回自助旅行

in West Virginia, and was putting my face into puddles

我渴到像狗一樣趴到地上

of water and drinking like a dog.

從地上的水坑喝水

That night, I was taken into the emergency room

那天晚上，我被送進急診室，

and diagnosed as a type 1 diabetic in full-blown ketoacidosis.

確診為第一型糖尿病、導致酮酸中毒。

And I recovered, thanks to the miracles of modern medicine,

感謝現代醫學的奇蹟，胰島素和其他的東西，

insulin and other things, and gained all my weight back and more.

我恢復健康，體重也回復，而且又胖了一些。

And something festered inside me after this happened.

在那之後，一些念頭開始醞釀。

What I thought about was, what caused the diabetes?

我開始想，到底是什麼造成糖尿病？

You see, diabetes is an autoimmune disease

你們知道的，糖尿病是一種自體免疫疾病，

where your body fights itself, and at the time people thought

你的身體攻擊自身正常的細胞，當時的認知是，

that somehow maybe exposure to a pathogen

人體在某些狀況下接觸到的病原體

had triggered my immune system to fight the pathogen

引發了免疫系統來對抗病原體

and then kill the cells that make insulin.

結果殺死了製造胰島素的細胞。

And this is what I thought for a long period of time,

關於這個理論，我思考了很長一段時間，

and that's in fact what medicine and people have focused on quite a bit,

而醫界和大眾也大多專注在這個觀念上

the microbes that do bad things.

那就是： 微生物是有害的。

And that's where I need my assistant here now.

現在，我需要我的助理幫忙。

You may recognize her.

你們可能認得她。

So, I went yesterday, I apologize, I skipped a few of the talks,

其實，昨天，很抱歉的，我跳過了一些會談，

and I went over to the National Academy of Sciences building,

去了國家科學院的大樓一趟，

and they sell toys, giant microbes.

那邊有賣玩具，巨型微生物。

And here we go!

所以...接住!

So you have caught flesh-eating disease if you caught that one.

如果你接住那一個，你已經得到噬肉菌了

I gotta get back out my baseball ability here.

很明顯的我已經很久沒玩棒球了

(Laughter)

（笑聲）

So, unfortunately or not surprisingly, most of the microbes

因此，不幸的，但不意外的是，國家科學院大樓賣的微生物娃娃，

they sell at the National Academy building are pathogens.

大多數都是病菌，

Everybody focuses on the things that kill us,

大家都只看到有害致死的東西，

and that's what I was focusing on.

那也是我當時研究的重點。

And it turns out that we are covered in a cloud of microbes,

事實上，我們被厚厚一層微生物雲覆蓋，

and those microbes actually do us good much of the time,

而這些微生物大多時對我們有益，

rather than killing us.

並不會致我們於死地。

And so, we've known about this for some period of time.

而且我們了解這點已經有一段時間了。

People have used microscopes to look at the microbes that cover us,

人們用顯微鏡觀察研究覆蓋人體的微生物，

I know you're not paying attention to me, but ...

我知道你沒有在聽我講話，但...

(Laughter)

（笑聲）

The microbes that cover us.

這些覆蓋人體的微生物。

And if you look at them in the microscope,

如果你用顯微鏡觀察它們，

you can see that we actually have 10 times as many cells

你會發現，在人身上，

of microbes on us as we have human cells.

微生物細胞數量其實會有人體細胞的10倍。

There's more mass in the microbes than the mass of our brain.

而這些微生物的總重量比我們的大腦還重。

We are literally a teeming ecosystem of microorganisms.

我們的身體是其實的微生物豐富的生態系統。

And unfortunately, if you want to learn about the microorganisms,

可惜的是，如果你想了解這些微生物，

just looking at them in a microscope is not sufficient.

只是用顯微鏡觀察是不夠的

And so we just heard about the DNA sequencing.

我們剛才聽到的DNA定序，

It turns out that one of the best ways to look at microbes

後來發現是研究微生物的最佳方法之一，

and to understand them is to look at their DNA.

藉由研究它們的DNA，我們得到更多資訊。

And that's what I've been doing for 20 years,

而這是我這20年來的一直在做的，

using DNA sequencing, collecting samples from various places,

我用DNA定序分析不同來源收集的樣本，

including the human body, reading the DNA sequence

包括人體樣本。藉由DNA定序技術，

and then using that DNA sequencing to tell us about

我們可以從收集到DNA序列來了解

the microbes that are in a particular place.

特定地方的微生物。

And what's amazing, when you use this technology,

神奇的是，當你使用這個技術

for example, looking at humans, we're not just covered

研究，例如，人體，覆蓋我們的微生物

in a sea of microbes.

不只是數量眾多，

There are thousands upon thousands of different kinds of microbes on us.

這些微生物有數千種不同的種類。

We have millions of genes of microbes in our human

我們身上的「人體微生物群系」包含了

microbiome covering us.

數百萬的基因，

And so this microbial diversity differs between people,

而且每個人身上的微生物體系的組成都不相同，

and what people have been thinking about in the last 10,

在過去10或15年，人們一直在思考，

maybe 15 years is, maybe these microbes,

也許是人體裡外的微生物，

this microbial cloud in and on us,

每個人身上的微生物雲

and the variation between us, may be responsible

組成的差異，可能決定了

for some of the health and illness differences between us.

一些的健康和疾病上的個體差異。

And that comes back to the diabetes story I was telling you.

而這回到剛剛的我的糖尿病故事，

It turns out that people now think that one of the triggers

現在人們認為，引發一型糖尿病的原因

for type 1 diabetes is not fighting a pathogen,

不是因為人體不去對抗病原體，

but is in fact trying to -- miscommunicating with the microbes

而是人體跟居住於其內外的微生物群

that live in and on you.

溝通不良。

And somehow maybe the microbial community that's

而也許是在我身上的微生物群突然不知怎的

in and on me got off, and then this triggered some sort

消失了，然後引發某種免疫反應，

of immune response and led to me killing the cells

導致我體內製造胰島素的細胞

that make insulin in my body.

被攻擊破壞。

And so what I want to tell you about for a few minutes is,

所以，接下來這幾分鐘，我想分享的是，

what people have learned using DNA sequencing techniques

經由DNA定序技術，我們學到了些什麼，

in particular, to study the microbial cloud

尤其是在研究人體內外的

that lives in and on us.

存在的微生物雲。

And I want to tell you a story about a personal project.

我現在要告訴你們另一個故事，是關於我的個人計畫。

My first personal experience with studying the microbes

我第一次開始研究人體微生物的個人經驗，

on the human body actually came from a talk that I gave,

其實是緣起一個我發表的講座。

right around the corner from here at Georgetown.

那講座是在喬治城，就在附近而已。

I gave a talk, and a family friend who happened to be

我是主講人，喬治城醫學院院長

the Dean of Georgetown Medical School was at the talk,

也是我們家族的朋友，出席了那個講座。

and came up to me afterwards saying, they were doing

講座結束後，院長上前來告訴我

a study of ileal transplants in people.

他們正在做人體迴腸移植的研究。

And they wanted to look at the microbes after the transplants.

他們想研究移植後的微生物分布情況。

And so I started a collaboration with this person,

所以我開始跟 Michael Zasloff 及 Thomas Fishbein合作，

Michael Zasloff and Thomas Fishbein, to look at the microbes

我們觀察迴腸移植後，

that colonized these ilea after they were transplanted into a recipient.

微生物在迴腸內繁殖的情形。

And I can tell you all the details about the microbial study

我可以告訴你這個微生物研究的所有細節

that we did there, but the reason I want to tell you this story

還有我們做了什麼。但我想告訴你這個故事的原因

is something really striking that they did at the beginning

是因為在研究計畫的初期階段，他們做了一個

of this project.

很特別的嘗試。

They take the donor ileum, which is filled with microbes from a donor

他們取得捐贈者的迴腸，充滿捐贈者身上的微生物，

and they have a recipient who might have a problem

同時，受贈的病人體內微生物群也許已經失常了，

with their microbial community, say Crohn's disease,

舉例來說，克隆氏症的患者，

and they sterilized the donor ileum.

然後他們消毒捐贈者的迴腸，

Cleaned out all the microbes, and then put it in the recipient.

清除所有的微生物，然後移植到受贈患者的體內。

They did this because this was common practice

他們這樣做，是因為醫學上這是通常的手續，

in medicine, even though it was obvious

即使很明顯的，

that this was not a good idea.

並不是個好主意。

And fortunately, in the course of this project,

還好，在這個研究的過程中

the transplant surgeons and the other people

移植外科醫生和所有其他成員，

decided, forget common practice. We have to switch.

決定：「別用慣用的手續了，我們必須更新做法。」

So they actually switched to leaving some of the microbial

因此，他們留下部分原有的微生物群

community in the ileum. They leave the microbes with the donor,

在迴腸裡。這些從捐贈者來源留下來

and theoretically that might help the people who are

的微生物，理論上，可能會

receiving this ileal transplant.

對接受移植的人有幫助。

And so, people -- this is a study that I did now.

所以了，大家，這就是我過去幾年中所做的研究。

In the last few years there's been a great expansion

用DNA技術來檢視人體微生物的研究

in using DNA technology to study the microbes in and on people.

在過去幾年來有很大的擴展。

There's something called the Human Microbiome Project

人類微生物群系研究計畫

that's going on in the United States,

正在美國進行中，

and MetaHIT going on in Europe, and a lot of other projects.

而在歐洲，人類腸道菌叢誌基因辨異研究計畫(MetaHIT)，和很多其他的研究也在進行。

And when people have done a variety of studies,

當人們做了各種研究，

they have learned things such as, when a baby is

他們發現，如，當一個嬰兒

born, during vaginal delivery you get colonized by the

經由產道出生時，會得到

microbes from your mother.

母體的微生物群。

There are risk factors associated with cesarean sections,

剖腹產是帶有風險的，

some of those risk factors may be due to mis-colonization

部分的風險因素可能起因為，

when you carve a baby out of its mother

嬰兒直接經由剖腹被取出母體時

rather than being delivered through the birth canal.

無法經由產道取得母體的菌群。

And a variety of other studies have shown that the

許多不同的研究已經發現，

microbial community that lives in and on us

在於我們體內及表面的微生物群落，

helps in development of the immune system,

有益於我們免疫系統的發展，

helps in fighting off pathogens, helps in our metabolism,

幫助我們擊退病原體，促進新陳代謝，

and determining our metabolic rate, probably

並調節我們的代謝速度，可能

determines our odor, and may even shape our behavior

還形成了我們的體味，甚至在很多的方面都，

in a variety of ways.

影響我們的行為.

And so, these studies have documented or suggested

而且這些研究已經證明或是推斷

out of a variety of important functions for the microbial community,

各種重要機能經由這些微生物群、

this cloud, the non-pathogens that live in and on us.

這層雲、非-病原體，在我們體內及體表的運作。

And one area that I think is very interesting,

有個領域我覺得相當有意思的是，

which many of you may have now that we've thrown

剛剛既然我們丟了一堆菌給你們，你們之中有許多人也許有這個

microbes into the crowd, is something that I would call "germophobia."

我會稱之為「 恐菌症」。

So people are really into cleanliness, right?

人們真的很重視清潔，你說是嗎？

We have antibiotics in our kitchen counters,

我們廚房流理台上有抗菌產品，

people are washing every part of them all of the time,

人們無時無刻在清洗身上的每個部分，

we pump antibiotics into our food, into our communities,

抗生素被注入我們的食物、我們的居住環境，

we take antibiotics excessively.

我們無結制地濫用抗生素。

And killing pathogens is a good thing if you're sick,

如果你生病，殺光病原體是好事，

but we should understand that when we pump chemicals

但是我們必須了解，當我們使用化學製品

and antibiotics into our world, that we're also killing

跟抗生素在我們的環境裡，我們同時也在抹滅

the cloud of microbes that live in and on us.

跟我們共生的微生物雲。

And excessive use of antibiotics, in particular in children,

抗生素的過度使用，尤其是在兒童身上，

has been shown to be associated with, again, risk factors

研究發現，跟造成肥胖、自體免疫疾病

for obesity, for autoimmune diseases, for a variety

還有其他各種健康問題的風險因素息息相關，

of problems that are probably due to disruption

因為人體的微生物群落，

of the microbial community.

被抗生素干擾破壞。

So the microbial community can go wrong

所以微生物群落可能會失常，

whether we want it to or not,

不管我們喜不喜歡,

or we can kill it with antibiotics,

或者可以用抗生素殺光這些微生物，

but what can we do to restore it?

但我們怎樣可以重建微生物群落？

I'm sure many people here have heard about probiotics.

我相信這裡有很多人聽說過關於益生菌。

Probiotics are one thing that you can try and do to restore

益生菌可以用來嘗試

the microbial community that is in and on you.

重建體內及體表的微生物群落，

And they definitely have been shown to be effective in some cases.

而且已經有些成功的案例。

There's a project going on at UC Davis where people are using

在加州大學戴維斯分校正在進行一個計畫，

probiotics to try and treat, prevent,

他們嘗試用益生菌來治療和預防

necrotizing enterocolitis in premature infants.

早產兒的壞死性腸炎。

Premature infants have real problems with their microbial community.

早產兒的身上的微生物群落問題多多，

And it may be that probiotics can help prevent

而也許益生菌可以幫助預防

the development of this horrible necrotizing enterocolitis

早產兒罹患

in these premature infants.

這可怕的壞死性腸炎。

But probiotics are sort of a very, very simple solution.

但是，益生菌是一個非常，非常簡易的解決方式。

Most of the pills that you can take or the yogurts that you can eat

大多數的益生菌錠或是優酪乳

have one or two species in them, maybe five species in them,

含有一或兩種菌種，或是五種菌種，

and the human community is thousands upon thousands of species.

而人體的微生物群系有數千種的菌種。

So what can we do to restore our microbial community

所以，什麼方法可以重建我們的微生物群系

when we have thousands and thousands of species on us?

當我們的微生物群系是由數千種菌種組成的?

Well, one thing that animals seem to do is,

嗯，動物所做的一件事是，

they eat poo -- coprophagia.

他們吃便便 - 所謂的嗜糞癖。

And it turns out that many veterinarians,

原來，許多獸醫，

old school veterinarians in particular,

尤其是老經驗的獸醫，

have been doing something called "poo tea,"

一直在用一種叫「便便茶」，

not booty, but poo tea, to treat colic and other

不是屁屁，而是便便茶，來治療馬和牛

ailments in horses and cows and things like that,

腹絞痛及其他之類的毛病。

where you make tea from the poo from a healthy

作法是用健康的動物的糞便做成茶，

individual animal and you feed it to a sick animal.

然後餵食給生病的動物。

Although, unless you have a fistulated cow with a big hole in its side,

但是，除非你有隻牛，肚子一側開了一個大洞，

and you can put your hand into its rumen,

你可以把你的手，伸入牠的瘤胃之外，

it's hard to imagine that the delivery of microbes

很難想像，從嘴巴經過整個上消化道

directly into the mouth and through the entire

將微生物送入

top of the digestive tract is the best delivery system,

會是最好的運輸方式。

so you may have heard in people they are now doing

所以，你可能已經聽說有人在做

fecal transplants, where rather than delivering

糞便移植，與其將少數益生菌種

a couple of probiotic microbes through the mouth,

經由口部送入，

they are delivering a community of probiotics,

他們是將整個益生菌的群系，

a community of microbes from a healthy donor,

從健康的捐贈者取得的群系，

through the other end.

從消化道的另一端送入。

And this has turned out to be very effective in fighting

結果發現這樣做對於

certain intransigent infectious diseases

對抗某些頑固的傳染病非常有效。

like Clostridium difficile infections that can stay

例如可以存留人體多年的

with people for years and years and years.

困難腸梭菌。

Transplants of the feces, of the microbes from the feces,

經由糞便移植，

from a healthy donor has actually been shown to cure

取得健康捐贈者的糞便中的微生物，

systemic C. dif infections in some people.

事實上已經有成功治癒困難腸梭菌感染的案例。

Now what these transplants, these fecal transplants, or

因為這些新的移植手術手法、糞便移植

the poo tea suggest to me, and many other people

或是便便茶的應用，讓我還有許多人

have come up with this same idea, is that

有了同一個想法，就是

the microbial community in and on us, it's an organ.

這存在於我們體內及表面的微生物群系，其實是個器官。

We should view it as a functioning organ, part of ourselves.

我們應該把這當做是一個正常運作的器官，自己的一部分看待。

We should treat it carefully and with respect,

我們應該認真對待和尊重，

and we do not want to mess with it, say by C-sections

不應該擾亂其平衡，像是沒有必要的狀況下，

or by antibiotics or excessive cleanliness,

進行剖腹產、使用抗生素、

without some real good justification.

或是過度清潔。

And what the DNA sequencing technologies are allowing people to do now

而因為DNA定序技術，今天人們可以

is do detailed studies of, say, 100 patients who have Crohn's disease

做詳細的研究，比方說，比較100個克隆氏症患者

and 100 people who don't have Crohn's disease.

跟100個沒有克隆氏症的人。

Or 100 people who took antibiotics when they were little,

或是比較100個小時候服用過生素的人，

and 100 people who did not take antibiotics.

跟100個沒有服用抗生素的人。

And we can now start to compare the community of microbes

我們現在可以開始比較群系裡的微生物，

and their genes and see if there are differences.

和他們的基因，看看是否有差異。

And eventually we may be able to understand if they're not

最終我們可能能夠明白，是否他們不

just correlative differences, but causative.

只是有相關的差異，還有因果上的差異性。

Studies in model systems like mouse and other animals

使用老鼠或是其他動物的實驗模型系統所做的研究，

are also helping do this, but people are now using

也同時幫助我們了解更多，但人們使用DNA

these technologies because they've gotten very cheap,

技術是因為其成本已經變得非常低廉，

to study the microbes in and on a variety of people.

可研究不同人身上的微生物。

So, in wrapping up, what I want to tell you about is,

作為總結，我現在想告訴你們的是，

I didn't tell you a part of the story of coming down with diabetes.

我剛剛沒告訴你們我得到糖尿病的過程。

It turns out that my father was an M.D.,

其實，我父親是醫生，

actually studied hormones. I told him many times

而且他的專科是研究內分泌激素。 很多次我告訴他，

that I was tired, thirsty, not feeling very good.

我很累，很渴，人很不舒服。

And he shrugged it off, I think he either thought

他聳聳肩，我認為，他要麼想，

I was just complaining a lot, or it was the typical

我只是愛抱怨，或是

M.D. "nothing can be wrong with my children."

醫生常有的「我的小孩怎麼可能會有毛病」心態

We even went to the International Society of Endocrinology

甚至 我們全家一起去魁北克

meeting as family in Quebec.

參加國際內分泌學會會議時，

And I was getting up every five minutes to pee,

我每五分鐘就要起床尿尿，

and drinking everybody's water at the table,

吃飯時我渴到得喝光每個人的水

and I think they all thought I was a druggie.

我想，他們大概都認為我嗑藥了。

(Laughter)

（笑聲）

But the reason I'm telling you this is that

但我告訴你這個的原因是，

the medical community, my father as an example,

醫學界，以我父親作為一個例子，

sometimes doesn't see what's right in front of their eyes.

有時反而看不見眼前發生的事。

The microbial cloud, it is right in front of us.

這層微生物雲，就在我們眼前，

We can't see it most of the time. It's invisible.

即使大部分時間我們看不見它，它是隱形的。

They're microbes. They're tiny.

微生物是極渺小的，

But we can see them through their DNA,

但是我們可以看見他們，經由他們的DNA。

we can see them through the effects that they have on people.

但是我們可以看見他們，經由他們對人們的影響。

And what we need now

而我們現在需要的是，

is to start thinking about this microbial community in the context

開始思考微生物群落

of everything in human medicine.

在人類醫學的每一個層面。

It doesn't mean that it affects every part of us,

這不表示微生物影響我們的每一部分，

but it might.

但不排除這樣的可能性。

What we need is a full field guide to the microbes

我們需要的是對人體的微生物

that live in and on people, so that we can understand

有一個整體的了解，才能了解

what they're doing to our lives.

他們對我們生活的影響。

We are them. They are us.

微生物跟人類，共生共存。

Thank you.

謝謝

(Applause)

（掌聲）