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如何研究生活在肠道中的微生物?

How to study microbes living in the gut?
如何研究生活在肠道中的微生物?
1393字
2019-11-08 19:21
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火星译客

If I asked you to name a microbe that's living in your gut, many of you would probably say E. coli.

如果我请各位说出一种住在你肠道中的微生物,许多人可能会说大肠杆菌。

A lot of people say this. It's the best-known of the gut microbes.

很多人会这么说。它是最多人知道的肠道微生物。

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.

但结果发现,在你的肠道中,大肠杆菌的数量约只占肠道菌的千分之一,而你可能没有听过其他这些数量较多的菌种,比如拟杆菌或是普雷沃氏菌。

Those are the two that dominate the modern human gut. There are about a hundred trillion microbes living inside you.

这两种菌种主宰了现代人的肠道。大约有一百兆微生物住在你体内。

We call this your microbiome, so it's like a little world living inside you -- actually more like a universe.

我们称之为你的微生物群系,它就像是个住在你体内的小世界--其实更像是个宇宙。

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.

一百兆大小表示如果一片叶片代表住在你肠道内的每一个微生物,那么可以填满一百万个足球场。所以它非常复杂。

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.

但有趣的是,随着我们的身体适应现代社会的生活,我们也失去了一些正常的微生物,而与此同时,在全世界的发达国家中,有相当多肠道相关的疾病迅速窜升。

And many of you probably know someone who suffers from obesity, diabetes, Crohn's disease or ulcerative colitis, allergies and asthma.

在座许多人可能认识有下列状况的人:肥胖、糖尿病、克隆氏症或溃疡性结肠炎、过敏及气喘。

Every one of these diseases and many others related to metabolism and autoimmunity are linked to a loss of healthy diversity in the gut.

所有这些疾病以及许多其他和新陈代谢及自体免疫相关的疾病,都和肠道中失去了健康多样性的细菌有关。

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.

我的实验室最初会发现这个现象,其实是因为我们正在研究非人类的灵长类动物。我们想要找出猴子从丛林搬到动物园之后,它们的微生物群系会发生什么变化。

Does their microbiome change? Do they pick up new bugs? Do they lose some? Does it get better or worse?

它们的微生物群系会改变吗?它们有得到新的菌种吗?还是它们失去一些?这样是好或不好?

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.

我们在丛林中追踪两种不同的物种,一种在越南,另一种在哥斯达黎加,我们从它们的粪便取得DNA来做定序。在我的研究实验室中,就是这样研究微生物群系的。我们从DNA发现,野外这两个物种体内的微生物群组完全不同。

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.

它就像是那些物种的指纹。但在动物园中,它们的多样性却少了大半,还取得了其他的微生物群组。这非常让人好奇。最后竟有这两种不同的微生物群系。

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.

想象一个苍翠繁茂的热带雨林,就居住在这些野外猴子的肠道中。我们所谈论的多样性就类似这样。而在动物园,它们就失去了多样性。

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.

想象一个被烧毁的雨林,那里只被几种入侵的物种占据。那就像是被关起来的灵长类的微生物群系。

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.

同时,动物园中有许多动物的状况没有很好。它们遇到的问题包括肥胖、消瘦、胃肠炎、腹泻、胀气,有些动物几乎无法活下去。

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.

当然,我们非常想要找出在动物园中这些所谓的入侵菌种到底是什么。所以我们又回到DNA,而DNA告诉我们,动物园中的每一只猴子都被拟杆菌与普雷沃氏菌所主宰,我们现代人的肠道中也都有同样的这些微生物。

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.

我们想以图像呈现出这个结果,所以我们用了一些多变量生态学的工具,把所有我们在研究的微生物群系放到一个轴上。各位现在看见的是一张距离图,图上的每一点代表着不同动物的微生物群系。

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.

所以每一个点都代表整个动物园的微生物。微生物越相似的微生物群系,它们在图上的距离就会越接近彼此。

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.

反之,则会离越远。这张图是要让各位看看两群野生猴子的点都落在图的左侧。

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.

左上角是严重濒临绝种的猴子,是越南的白臀叶猴。左下角则是在哥斯达黎加的猴子。各位可以看到,野外的猴子有着迥然不同的微生物群系。

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.

而同样是这两种猴子,在放入动物园后却变得很相似,所以它们的微生物群系会变,彼此变得更相似,即使它们所属的动物园位于不同的大陆,不同的地理区,而且还吃不同的食物。

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?

我们的确也研究了其他灵长类物种。你们认为哪种灵长类的差异性比起动物园和野生灵长类的差异性更大?

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.

现代人类。这些是住在发展中国家的人。和在动物园中的灵长类相比,他们和野生灵长类的差异更大。我们研究的最后一个族群,在图的最右边,就是住在美国的人。

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."

当我看到这张图,让我寒毛直竖,因为对这现象的一种思考方式是:“喔,好有趣,被关起来的猴子渐渐变得和美国人一样了。”

But the other way to think about it is that Americans are like super-captive monkeys.

但另一种思考方式是美国人就像是被关过头的猴子。

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.

当我在我的计算机屏幕上看着这张图时,我得到一个消息,动物园中有四只白臀叶猴死于肠道相关疾病。

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.

所以对这些动物园的动物而言,体内是否有对的微生物,可能是生死攸关的事。因此接下来就要谈到关于人类的部分了。

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.

很显然,在美国,由微生物群系所造成的过早死亡,并没有动物园中那么频繁,但我们有很大的风险,可能会产生肥胖、糖尿病以及许多其他这类疾病。

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.

这不仅适用于已经在美国住了数个世代的人,也适用于移民和难民,大部分的移民和难民族群在抵达美国时,新陈代谢是很健康的,然而短短几年后,他们却变成和美国人一样,有很高的肥胖和糖尿病风险。

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.

我们和两个族群讨论了这个议题,他们是从东南亚来到美国的:赫蒙族,他们从70年代中期就以越战与美国在老挝的秘密战争的难民身份来到美国;还有克伦族,他们是近期才以缅甸难民的身份到美国。

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.

我们花了几年的时间,和当地的小区和临床医生合作,研究赫蒙族和克伦族从难民营和泰国的村落搬到美国之后,他们的微生物群系产生了什么变化。

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.

我们发现,当这些族群的人来到美国,他们失去了很多的微生物群系,大约20%上下,而到了美国且变肥胖的人,少了大约三分之一的微生物。

So we know that moving to the USA is sufficient to cause a dramatic change in your microbiome, probably not for the better.

所以,我们知道搬到美国就足以造成微生物群系的巨大改变,并且可能不是变好。

Are these microbes actually causing the obesity, or is the obesity causing a change in the microbes?

真的是这些微生物造成了肥胖?还是肥胖造成了微生物的改变?

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.

我们后续还在追踪探究,而将我实验室中得到的证据和来自世界各地的实验室所发现的证据汇整后,显示了微生物群系的某些改变的确会导致肥胖以及其他数种现代西化的疾病。

The good news is that your microbiome can actually change.

好消息是你的微生物群系可以被改变。

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.

不像你自己的基因组,它是活的、会呼吸的生物,并且现有广泛大量的研究正在进行,让我们更明了当我们的微生物群系发生问题时,我们要如何透过饮食、透过活的微生物来恢复。

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.

事实上,我们接下来的其中一步,就是要收集和保存来自全世界健康人类的微生物,将其作为这些族群的文化资产而予保存下来。在族群适应现代社会的过程中提供所需的保护,也可以保护未来的世代,这些世代目前成长的过程中,得到这些疾病的风险越来越高,一代比一代高。

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.

我很期待看到在未来我们会有所需的工具来恢复和补充我们的微生物群系。在那个世界中,猴子能过着比较快乐、健康的生活,我们也一样。

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