How gene-edited microbiomes could improve our health

基因编辑微生物组如何改善我们的健康

Scientists are engineering microbes to make healthier compounds. They hope they’ll help treat disease and save the planet.科学家们正在改造微生物以制造更健康的化合物。他们希望他们能帮助治疗疾病并拯救地球。

Microbes have been on my mind this week. These tiny organisms are everywhere, and the ones that reside in our bodies appear to be incredibly important for our health.本周，微生物一直在我的脑海中。这些微小的生物无处不在，而存在于我们体内的生物似乎对我们的健康非常重要。

Microbes are ancient—they were evolving on the planet for millions of years before humans came along. So it’s no surprise that they’ve developed intricate relationships with other living systems. They feed on chemicals in their environments to produce other chemicals—some of which are more beneficial to nearby organisms than others.微生物是古老的——在人类出现之前，它们已经在地球上进化了数百万年。因此，他们与其他生命系统发展出错综复杂的关系也就不足为奇了。它们以环境中的化学物质为食，以生产其他化学物质——其中一些对附近的生物体比其他化学物质更有益。

The question is: can we tweak the genomes of these microbes to control exactly which chemicals they break down or produce? Imagine the possibilities. What if we could get microbes to help us reduce pollution? What if we could create microbes that make medicines, or that churn out gut-friendly products in our intestines?问题是：我们能否调整这些微生物的基因组，以准确控制它们分解或产生哪些化学物质？想象一下各种可能性。如果我们能得到微生物来帮助我们减少污染呢？如果我们能创造出制造药物的微生物，或者在肠道中生产出对肠道有益的产品，那会怎样？

Modified microbes seem to help treat cancer in mice, and human trials are on the way, as I reported earlier this year. (For a more general update on gene editing, you can read about how the editing tool CRISPR is already changing people’s lives, and how some believe we’ll eventually be using the technology to treat the majority of people.)修饰的微生物似乎有助于治疗小鼠的癌症，正如我今年早些时候报道的那样，人体试验正在进行中。（有关基因编辑的更一般更新，您可以阅读有关编辑工具CRISPR如何改变人们生活的信息，以及有些人如何相信我们最终将使用该技术来治疗大多数人。

Getting microbes to work for us has been a tantalizing prospect to scientists for decades. New technologies are bringing us ever closer to making it a reality. So for this week’s newsletter, let’s focus on a couple of particularly exciting ways people are engineering microbes to benefit our health and environment.几十年来，让微生物为我们工作一直是科学家们的一个诱人的前景。新技术使我们越来越接近使之成为现实。因此，在本周的时事通讯中，让我们关注人们改造微生物以造福我们的健康和环境的几种特别令人兴奋的方式。

The air-cleaning qualities of plants get a genetically modified boost植物的空气净化质量得到转基因提升

Indoor plants aren’t as good for air quality as you might think. Neoplants, a startup, aims to fix that.室内植物对空气质量的影响并不像您想象的那么好。初创公司Neoplants旨在解决这个问题。

Take the work being done by Brad Ringeisen, executive director of the Innovative Genomics Institute in Berkeley, California, and his colleagues. The team recently received a huge amount of funding to explore new ways to engineer microbes for the well-being of people and the planet—particularly people living in low- and middle-income countries.以加州伯克利创新基因组学研究所执行主任布拉德·林盖森（Brad Ringeisen）及其同事所做的工作为例。该团队最近获得了巨额资金，用于探索设计微生物的新方法，以促进人类和地球的福祉 - 特别是生活在低收入和中等收入国家的人们。

“We got $70 million to develop precision microbiome-editing tools,” says Ringeisen. The team is focusing on using CRISPR to change the behavior of microbes—not just bacteria, but also their lesser-studied co-habitants, such as fungi and archaea. The idea is that feeding such treatments to people or animals could get their gut microbiomes to a healthier state.“我们获得了7000万美元来开发精确的微生物组编辑工具，”Ringeisen说。该团队专注于使用CRISPR来改变微生物的行为 - 不仅仅是细菌，还有它们较少研究的共同居住者，如真菌和古细菌。这个想法是，将这种治疗喂给人或动物可以使他们的肠道微生物组进入更健康的状态。

The likely first recipients of such treatments will be cows. The way we farm these animals has a tremendous impact on the environment, for several reasons. (Read more from Tech Review about what it would take to clean up farming here and here.) But one significant element is the methane they emit, since methane is a powerful greenhouse gas that contributes to climate change.这种治疗的可能第一批接受者将是奶牛。我们养殖这些动物的方式对环境产生了巨大的影响，原因有几个。（阅读更多来自技术评论，了解在这里和这里清理农业需要什么。但一个重要的因素是它们排放的甲烷，因为甲烷是一种强大的温室气体，会导致气候变化。

Technically, the methane isn’t made by the cows themselves. It’s produced by the bacteria in their guts. Ringeisen and his colleagues are looking at ways to alter microbes that reside in the rumen—the first and largest stomach compartment—so that they produce much less of the gas, if any.从技术上讲，甲烷不是由奶牛自己制造的。它是由肠道中的细菌产生的。Ringeisen和他的同事们正在寻找改变存在于瘤胃中的微生物的方法 - 第一个也是最大的胃隔室 - 以便它们产生的气体更少，如果有的话。

Ringeisen thinks that modifying existing microbes should be less disruptive than introducing entirely new ones. He likens the approach to that of a conductor fine-tuning the sound of an orchestra. “[It would be like] bringing up the violin and lowering the bass drum, but to tune the microbiome,” he says.Ringeisen认为，修改现有的微生物应该比引入全新的微生物更具破坏性。他将这种方法比作指挥家微调管弦乐队的声音。“[这就像]拉起小提琴并降低低音鼓，但要调整微生物组，”他说。

The team is also looking at how a CRISPR microbiome treatment might benefit human infants. A baby’s first microbiome—thought to be picked up at birth—is especially malleable during the first two years of life. So microbiologists believe it’s important to get an infant’s microbiome as healthy as possible early on.该团队还在研究CRISPR微生物组治疗如何使人类婴儿受益。婴儿的第一个微生物组 - 被认为是在出生时被拾取的 - 在生命的头两年特别具有可塑性。因此，微生物学家认为，尽早让婴儿的微生物组尽可能健康是很重要的。

We still don’t know exactly what that means, or what a healthy microbiome should look like. But ideally, we want to avoid having bugs that make chemicals that cause harmful inflammation or damage the gut lining, for example. And we might want to encourage the growth of microbes that make chemicals that aid gut health—like butyrate, which is made when some microbes ferment fiber and seems to strengthen the intestine’s natural barrier.我们仍然不知道这到底意味着什么，或者健康的微生物组应该是什么样子。但理想情况下，我们希望避免产生化学物质的虫子，例如引起有害炎症或损害肠道内壁的细菌。我们可能希望鼓励微生物的生长，这些微生物会产生有助于肠道健康的化学物质 - 例如丁酸盐，当一些微生物发酵纤维时产生的，似乎可以增强肠道的天然屏障。

The work being done here is still in its early stages. But the researchers envision an oral treatment that would be fed to babies to manipulate their microbiomes. They don’t have a specific age in mind, but it could be quite soon after birth.这里正在开展的工作仍处于初期阶段。但研究人员设想了一种口服治疗，可以喂给婴儿以操纵他们的微生物组。他们没有具体的年龄，但可能是出生后不久。

As long as the modified microbes aren’t making anything harmful, it should be relatively straightforward to approve these treatments, says Ringeisen. “Those are experiments that are going to be relatively easy to do,” he says.只要改良的微生物没有产生任何有害的东西，批准这些治疗应该相对简单，Ringeisen说。“这些实验将相对容易做到，”他说。

Justin Sonnenburg, a professor of microbiology and immunology at Stanford University in California, is also looking at ways to reengineer the microbes in our guts to improve our health. One important target is inflammation—a process that has been linked to all sorts of diseases, ranging from arthritis to cardiovascular disease.加州斯坦福大学微生物学和免疫学教授贾斯汀·索嫩伯格（Justin Sonnenburg）也在寻找重新设计肠道微生物以改善我们健康的方法。一个重要的目标是炎症 - 这一过程与各种疾病有关，从关节炎到心血管疾病。

Microbes that live in our guts can sense inflammation, says Sonnenburg. If we could “rewire the genetic circuit” of these microbes, we could potentially enable them to secrete anti-inflammatory compounds that treat inflammation if and when it arises. “All this [would be] happening behind the scenes without the person harboring the microbes even knowing about it,” he says.生活在我们肠道中的微生物可以感知炎症，Sonnenburg说。如果我们能够“重新连接这些微生物的遗传回路”，我们就有可能使它们分泌抗炎化合物，在炎症发生时治疗炎症。“所有这一切都发生在幕后，而携带微生物的人甚至不知道，”他说。

One of the challenges will be to develop a treatment that works the same way in different people, who will have different microbiomes. But there may be some ways around this. In a study a few years ago, Sonnenburg and his colleagues delivered a modified microbe into the guts of mice. This microbe glowed under a microscope, so the scientists could tell how well it had settled in the mice’s intestines. It was quite variable—some of the mice had more of the microbes than others.挑战之一是开发一种治疗方法，在不同人群中以相同的方式工作，他们将拥有不同的微生物组。但可能有一些方法可以解决这个问题。在几年前的一项研究中，Sonnenburg和他的同事将一种改良的微生物输送到小鼠的肠道中。这种微生物在显微镜下发光，因此科学家们可以判断它在小鼠肠道中的定居情况。这是相当可变的 - 一些小鼠比其他小鼠具有更多的微生物。

This particular microbe also fed on a carbohydrate found in seaweed, called porphyran. And when the scientists fed the mice seaweed, they found they could influence levels of the microbe in the gut. A diet rich in seaweed brought up the levels in all the mice, for example. “Now we have the ability to control engraftment and the level of the microbe independent of the background microbiota,” says Sonnenburg.这种特殊的微生物也以海藻中发现的一种碳水化合物为食，称为卟啉。当科学家给小鼠喂食海藻时，他们发现它们会影响肠道中微生物的水平。例如，富含海藻的饮食提高了所有小鼠的水平。“现在我们有能力控制植入和独立于背景微生物群的微生物水平，”Sonnenburg说。

Some of the scientists who worked with Sonnenburg on this study have since formed a company, called Novome, which has shown that it can achieve similar results in people. The company is working on a proprietary microbial strain that has been engineered to break down oxalate, a compound that contributes to the formation of kidney stones. The company is also working on engineered microbes for irritable bowel syndrome and inflammatory bowel disease.一些与Sonnenburg合作进行这项研究的科学家已经成立了一家名为Novome的公司，该公司已经证明它可以在人类身上取得类似的结果。该公司正在研究一种专有的微生物菌株，该菌株已被设计用于分解草酸盐，草酸盐是一种有助于肾结石形成的化合物。该公司还在研究用于肠易激综合征和炎症性肠病的工程微生物。

Scientists have been working on “designer microbes” for decades. But the progress made in recent years has brought such treatments closer to reality. Ringeisen reckons we’re four to six years away from a human treatment, and he thinks cow treatments are even closer than that. It’s an exciting time. Let’s wait and see.几十年来，科学家们一直在研究“设计师微生物”。但近年来取得的进展使这种治疗更接近现实。林盖森认为，我们距离人类治疗还有四到六年的时间，他认为奶牛的治疗甚至比这更接近。这是一个激动人心的时刻。让我们拭目以待。