How we study the microbes living in your gutThere are about a hundred trillion microbes living inside your gut -- protecting you from infection, aiding digestion and regulating your immune system. As our bodies have adapted to life in modern society, we've started to lose some of our normal microbes; at the same time, diseases linked to a loss of diversity in microbiome are skyrocketing in developed nations. Computational microbiologist Dan Knights shares some intriguing discoveries about the differences in the microbiomes of people in developing countries compared to the US, and how they might affect our health. Learn more about the world of microbes living inside you -- and the work being done to create tools to restore and replenish them.
1,521,018 views Nov.2017~~July 2022 | Dan Knights • TED MED Dan Knights
Computational microbiologist 计算微生物学家
Dan Knights develops computational methods for doing precision medicine with gut bacterial communities, or microbiomes, and he applies those methods to study human disease.
If I asked you to name a microbe that's living in your gut, many of you would probably say E. coli. A lot of people say this. It's the best-known of the gut microbes. 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. Those are the two that dominate the modern human gut.
00:31
There are about a hundred trillion microbes living inside you. We call this your microbiome, so it's like a little world living inside you -- actually more like a universe. 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. 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. And many of you probably know someone who suffers from obesity, diabetes, Crohn's disease or ulcerative colitis, allergies and asthma. Every one of these diseases and many others related to metabolism and autoimmunity are linked to a loss of healthy diversity in the gut.
01:40
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. Does their microbiome change? Do they pick up new bugs? Do they lose some? Does it get better or worse? 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. 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.
02:34
So this was very curious. We've got these two different microbiomes. 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. 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. 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.
03:19
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.
03:47
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. 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. 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. 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. 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.
04:57
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? Modern humans. These are humans living in developing nations. So they were more different from the wild primates than those in the zoo.
05:23
And the final group that we studied, all the way on the right, is people living in the USA. 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."
05:45
(Laughter)
05:46
But the other way to think about it is that Americans are like super-captive monkeys. 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. So for some of these animals, having the right microbes living inside them may be a matter of survival.
06:12
Now this brings us to the human part of the story. 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. 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. 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. 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.
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.
07:54
So we know that moving to the USA is sufficient to cause a dramatic change in your microbiome, probably not for the better. Are these microbes actually causing the obesity, or is the obesity causing a change in the microbes? 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.
08:31
The good news is that your microbiome can actually change. 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. 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.
09:21
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.
09:39
(Applause)
Carol Wang, Translator
Tianji Li, Reviewer
00:00
如果请你举例说出一个 生活在你肠道里的微生物， 很多人可能会说大肠杆菌， 确实很多人都这么说。 大肠杆菌是最有名的肠道微生物， 但事实证明, 大肠杆菌只占你肠道中 细菌数量的1‰， 其它很多细菌你可能听都没听过， 像类杆菌属的细菌； 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。
00:31
人体内生活着约100万亿的微生物， 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—— 实际更像一个宇宙。 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， 那么就可以种满100万个足球场。 因此这是一个难以置信的复杂系统。 但有趣的是， 随着我们的身体逐渐适应现代生活， 我们正在失去一些正常的微生物， 与此同时， 在世界发达国家， 很多与肠道有关的疾病正在飙升。 许多在座的各位 可能就认识一些饱受肥胖症、 糖尿病、节段性回肠炎 或溃疡性结肠炎、 过敏和哮喘疾病之苦的患者。 和许多 与新陈代谢及自身免疫相关 的病症一样， 这些疾病都与肠道（菌群） 缺少健康多样性有关。
01:40
我的实验室在研究非人类 ——灵长类动物时, 第一次发现了这个征兆。 我们想了解 当猴子由丛林搬到动物园后， 它们体内的微生物群 会发生什么变化。 它们体内的微生物群改变了吗？ 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？ 我们分别对丛林中（生活的） 两个不同物种进行了追踪研究， 一个物种在越南， 一个在哥斯达黎加， 我们用它们的粪便 进行了DNA测序， 这就是我们实验室 对微生物进行研究的方法。 通过DNA比对，我们发现 野外的这两个物种体内， 微生物群截然不同。 微生物群 就像物种的指纹一样。 但在动物园里, 它们的微生物群 却失去了大部分的多样性， 并获得了一些其它的微生物，
02:34
这种现象非常奇怪。 我们有两个不同的微生物群： 野外动物体内的微生物群， 它就像郁郁葱葱的热带雨林 活在这些猴子的肠道内， 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， 就好像一些入侵物种 接管了烧光的雨林， 因此它们更像圈养灵长类 动物体内的微生物群。 与此同时，在动物园里， 许多动物身体状况都不太好， 它们有肥胖、 消瘦、 肠胃炎、腹泻、腹胀等问题， 有些动物几乎活不下去了。
03:19
因此，我们对找出这些 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。 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 都被类杆菌和普氏菌所主宰， 这些猴子和现代人肠内 拥有相同的微生物群。
03:47
为找到让这一发现结果 可视化的方法， 我们使用了一些多元生态学工具, 把我们研究的微生物群 放在（坐标图的）轴线上。 这里你看到的是一个距离图， 每个点代表着 不同动物的微生物群， 所以，每一点也代表了 整个动物园的微生物。 如果不同微生物群中 彼此的微生物相似的话， 它们在图中的距离就很近； 差异很大的微生物群， 在图中则离彼此很远。 这里展示的是： 最左边的点 代表两组野外的猴子， 左上方的点是 高度濒危的越南猴， 叫做白臀叶猴， 左下角的点则是 来自哥斯达黎加的猴子。 从图中看出，野外生活的猴子 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， 它们的微生物群改变了， 变得更加相似， 尽管它们（猴子）来自 不同大洲的动物园、 不同的地理区域和不同的饮食。
04:57
我们也研究过 其他种类的灵长类动物， 你觉得哪种灵长类动物 比圈养的灵长类 更加与野生灵长类不同？ 是现代人类！ 图中这些点代表 生活在发展中国家的人， 和物园里的灵长类比起来， 他们与野生灵长类更加不同。
05:23
我们研究的最后一组 在图中最右边， 他们是生活在美国的人们。 当我看到这个图时， 脖子后面的汗毛都竖起来了！ 因为一种解释是, "我的妈呀，太有趣了， 圈养的猴子 快变成美国人了！“
05:45
（笑声）
05:46
但另一种解读则是， 美国人就像超级圈养的猴子。 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， 我正看着电脑屏幕上的这个图。 因此，对这些动物来说, 它们体内 是否生存着正常的微生物， 可能是个生死攸关的问题。
06:12
我们自然就要谈到人的问题， 显然，美国人体内 微生物群的失衡， 并没有造成 像动物园那么多夭折， 但我们有肥胖、糖尿病、 和其他类似疾病的高发病率。 不仅是在美国生活了好几代的人 存在这样的问题， 而且新移民和难民也一样， 多数移民 和难民群体抵达美国时， 他们在新陈代谢方面很健康， 然后，在几年之内, 他们患上肥胖和糖尿病的风险 与美国人一样高。 我们与两个 从东南亚迁来美国的团体 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， 从 20 世纪 70 年代中叶开始， 他们以难民身份来到美国； 另一个是凯伦人， 最近才从缅甸来的难民。 我们已经与这些当地社区 和临床医生一起工作了几年， 研究洪族人和凯伦人 从泰国难民营和村庄来到美国后， 他们体内的微生物群 会发生怎样的变化。
我们发现， 当这些人来到美国后， 他们体内的微生物群 失去了很大一部分， 约 20%； 而那些来美国后 患肥胖症的人， 则失去了(原来) 微生物群的三分之一。07:54
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， 很可能不是在变好。 这些微生物群 真的会导致肥胖， 还是肥胖造成了 微生物群的改变？ 这是我们正在跟进的事情， 我们实验室发现的证据， 以及来自世界各地一些实验室的 证据都告诉我们， 微生物群的某些变化 会导致肥胖、 以及其它一些现代病， 或者说西方病。
08:31
好消息是，你体内的 微生物群是可以改变的。 和你的基因组不同的是， 它（微生物群）是活生生、 会呼吸的东西。 （科学家们）正在进行 一项广泛的前沿研究， 以便更好地了解 当微生物群出现问题时， 如何通过饮食、 使用活的微生物， 去恢复体内的微生物群。 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， 以便作为文化资产进行保存， 在他们适应现代社会时， 对之进行潜在保护； 保护正在成长、 后代有较高风险 患西方病的这一代人，
09:21
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， 在未来世界里，不但猴子们 会过上更快乐、更健康的生活， 我们也会！
09:39
（掌声）
https://www.ted.com/talks/dan_knights_how_we_study_the_microbes_living_in_your_gut/transcript
