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We Might Absorb Billions of Viruses Every Day

我们可能每天都在吸收数十亿的病毒

And that’s a good thing.

而且这是一件好事。



The viruses, Jeremy Barr realized, were in the wrong place.

Jeremy Barr意识到,这些病毒出现在了错误的地方。

Barr and his colleagues at San Diego State University had grown a layer of gut cells in a dish, much like those that line the surface of our own twisting intestines. The cells formed such tight connections with each other that bacteria couldn’t sneak past them. Even a dye couldn’t get through. The layer was meant to be impermeable, until the team infused the water on one side of it with viruses called phages.

Barr和他在圣地亚哥州立大学的同事们在一个培养皿中培育了一层肠道细胞,就像我们自己的肠子一样。这些细胞之间形成了非常紧密的联系,以至于细菌都无法通过它们,甚至连染料也无法通过。这一层的细胞是不可渗透的,直到研究小组将含有一种叫做噬菌体的病毒的水注入到这一层细胞的一侧。

After a few hours, they found a few of these phages on the other side. The cells had absorbed them at one end, and shoved them out the other. “It took us a while to realize what we were seeing, but when we did, it was really exciting,” Barr says.

几个小时后,他们在另一侧发现了一些噬菌体。细胞在一端吸收了它们,然后把它们推到另一端。Barr说:“我们花了一段时间才意识到我们观察到的是怎么一回事,但当我们意识到的时候,真的非常令人兴奋。”

Barr believes that the same process happens in our bodies, frequently and relentlessly. If he’s right, it means that our guts are absorbing billions of viruses every day, sending a steady stream of them into our bloodstream and the rest of our organs.

Barr认为,同样的过程也在我们的身体里持续而频繁地发生着。如果他是对的,那就意味着我们的内脏每天都吸收了数十亿的病毒,把它们源源不断地输送到我们的血液和其他器官中去。

That’s not something to worry about. Phages don’t infect human cells and they don’t cause disease. Their full name, bacteriophages, means “eaters of bacteria,” and as that suggests, they infect and destroy bacteria. In doing so, Barr says, they could act as part of our immune system. They anchor themselves in the layer of mucus that lines our gut. By infecting the bacteria that also thrive there, they keep these microbial populations in check, and could determine which species get to live in our bodies.

这不是什么值得担心的事情。噬菌体不会感染人类细胞,也不会引发疾病。它们名称的意思是“食用细菌的东西”,也就是说,它们会感染并消灭细菌。Barr说,在这样做的时候,它们可以被当作我们的免疫系统的一部分。它们将自己固定在我们肠道的粘液层中。通过对在那里繁殖的细菌进行感染,它们可以控制这些微生物群落,并确定哪些物种可以生活在我们的身体里。

This relationship is likely an ancient one. Mucus is universal to animals from corals to fish to humans, and phages are universal to mucus. Perhaps this was how the very first animals defended themselves against infections. They developed mucus to concentrate phages that were plentiful in their environment, and the viruses in turn helped their hosts to control the microbial multitudes around them. It was a mutually beneficial relationship between animal and virus, and one that continues today.

这种关系很可能是一种古老的关系。粘液对动物来说是普遍存在的,从珊瑚到鱼类,再到人类,噬菌体都是普遍存在的粘液。也许这就是第一批动物如何保护自己不受感染的方式。它们开发出粘液来集中位于它们体内的大量噬菌体,而这些病毒反过来帮助他们的宿主控制周围的微生物群。这是动物和病毒之间的一种互利关系,而这种关系至今仍继续存在着。

But the latest experiments from Barr’s team, many of which were done by his colleague Sophie Nguyen, suggest that this relationship between animals and phages is even more intimate. The phages aren’t just sitting atop human gut cells, acting as bouncers. They are actually being trafficked through the cells themselves. The team even used powerful microscopes to confirm the presence of phages within the cells. “A cell is enormous compared to a phage,” says Barr. “It’s like finding a cup of coffee by sectioning a skyscraper.”

但是,Barr团队的最新实验——其中许多实验是由他的同事Sophie Nguyen所完成的——表明动物和噬菌体之间的关系更加亲密。噬菌体并不仅仅附着在人类的肠道细胞上,充当着保镖的角色。它们实际上会穿过细胞自行移动。研究小组甚至使用了威力强大的显微镜来证实噬菌体在细胞内部的存在。Barr说:“与噬菌体相比,一个细胞是非常庞大的。这就像在一幢摩天大楼里找一杯咖啡。”

In the experiment, just 0.1 percent of the total phages made it through. But based on their rate of travel, and the staggering number of them in the average human gut, the team estimated that our gut cells absorb around 31 billion phages every day. “The percentage feels like it can’t be that important but when you turn that percentage into absolute numbers, it feels biologically relevant,” says Corinne Maurice from McGill University, who also studies phages and was not involved in this study.

在实验中,只有0.1%的噬菌体通过了细胞。但根据它们的通过率,以及它们在人类肠道中的惊人数量,研究小组估计,我们的肠道细胞每天吸收了大约310亿个噬菌体。麦吉尔大学的Corinne Maurice——他同样从事噬菌体的研究,但是没有参与这项研究——指出:“这个百分比感觉没什么,但是当你把这个百分比转化为绝对数字时,它就有着生物学上的相关性。” 

The team only did experiments using lab-grown cells, but Barr says there’s good reason to think that the same viral journeys take place in living bodies. For over 70 years, scientists have been “finding phages in parts of the body where they shouldn’t be,” he says, including supposedly sterile organs like the lungs. Microbiologist René Dubos found hints of this in 1943, by injecting phages into the guts of mice and finding those same viruses in the rodents’ brains.

这个团队只使用了实验室培养的细胞进行实验,但Barr指出:有充分的理由相信,同样的病毒旅行在活体中进行着。他说,在过去的70多年里,科学家们一直“在身体的某些部位中寻找噬菌体,”其中包括像肺这样的无菌器官。微生物学家René Dubos在1943年发现了这一点,他将噬菌体注入老鼠的肠道,并在这种啮齿类动物的大脑中发现同种的病毒。

“Phages can be detected outside the gastrointestinal tract, but there hasn’t been any real proof of how they get there,” says Lori Holtz from Washington University School of Medicine in St Louis. Many scientists believed that they were just leaking through gaps between the cells, but Nguyen’s work suggests that they are actually going through the cells themselves. In her experiments, the phages could traverse cells that line the kidneys, lungs, liver, and even the brain. “That’s absolutely astonishing in my view,” says Barr. The brain is separated from other organs by the blood-brain barrier—one of the most tightly controlled borders in the body. It’s incredibly hard for scientists to get small molecules through it. And yet, phages seem to do so.

圣路易斯华盛顿大学医学院的Lori Holtz说:“噬菌体可以在胃肠道外被检测到,但没有任何真正的证据表明它们是如何到达那里的。”许多科学家认为,它们只是通过细胞间的缝隙渗漏过去,但Nguyen的工作表明它们实际上是自行通过了细胞。在她的实验中,噬菌体可以穿过肾脏、肺、肝脏甚至大脑的细胞。Barr说:“在我看来,这绝对是令人震惊的。”大脑是通过血脑屏障与其他器官隔离开的,这是人体中受到最严格控制的边界之一。科学家很难小分子通过血脑屏障。然而,噬菌体似乎可以做到这一点。

This isn’t an infection in any meaningful way. The phages aren’t hijacking human cells to make more copies of themselves, as viruses like influenza, Zika, or Ebola might. Instead, Barr thinks that the cells are in control. They’re actively engulfing phages, and shuttling them from one end to the other. Why?

这不是任何一种意义上的感染。噬菌体并没有劫持人体细胞,借以进行更多的自我复制,就像流感病毒、寨卡病毒或埃博拉病毒一样。相反,Barr认为,这些细胞掌控着局势。它们正积极地吞噬着噬菌体,并将它们从一端移动到另一端。为什么会这样呢?

For a start, this would suffuse our bodies with a sparse but continuous stream of phages, which might then protect our organs against wayward, opportunistic bacteria. But Barr speculates there are more unexpected purposes at work. By sensing and studying the phages they absorb, cells could fine-tune the production of the mucus that houses these viruses, or the chemicals that feed the microbes that the phages then infect. If the cells break down some of the absorbed phages, they could access and use the viruses’ genetic material. All of this is possible, and none of it is certain. Scientists are only starting to eavesdrop on the three-way conversations between bacteria, phages, and our own cells. “It’s a big unknown,” says Barr.

首先,这将使我们的身体充满稀疏但持续不断存在的噬菌体,这可能可以保护我们的器官免受任性不羁的、机会主义的细菌的攻击。但Barr推测存在更多意想不到的运作目的。通过对它们吸收的噬菌体进行感知和研究,细胞可以对产生这些病毒的粘液的产生进行微调,或者是为噬菌体传播的微生物提供化学物质。如果这些细胞分解了一些被吸收的噬菌体,它们就可以进入并使用这些病毒的遗传物质。所有这些情况都是可能的,而且没有一个是确定的。科学家们才刚刚开始窃听细菌、噬菌体和我们自己的细胞之间的三方对话。Barr说:“这是一个很大的未知领域。”

Maurice also notes that phages aren’t just a homogenous group. They are incredibly diverse in their own right, and they exist in large communities. “Do they compete with each other?” she wonders. “Could some of them facilitate the entrance of others into human cells? I have no idea.”

Maurice还指出,噬菌体不仅仅是一个同质化的群体。它们本身便有着难以置信的多样性,它们存在于一个非常庞大的群落中。“它们会互相竞争吗?”她对此感到好奇,“它们中的一些能促进其他噬菌体进入人类细胞吗?我不知道。”

These discoveries could have potential medical implications. For a century, scientists have looked to phages as a way of curing bacterial diseases, without having to resort to antibiotics. Although phage therapy fell out of favor in Western countries, research continued to blossom in Eastern Europe and Russia. And in recent years, there have been some spectacular successes, in which patients were pulled back from death’s door by infusions of these viruses

这些发现可能会对医学产生潜在的影响。一个世纪以来,科学家们一直把噬菌体作为一种治疗细菌疾病的方法,而不用求助于抗生素。尽管在西方国家,噬菌体疗法不再受欢迎,但在东欧和俄罗斯,这一研究仍在继续。近年来,它已经取得了一些惊人的成功,通过注入这些病毒,病人被从死神那里拉了回来。

Martha Clokie from the University of Leicester notes that several infectious bacteria, including those that cause tuberculosis and Lyme disease, can enter and infect human cells. “If we want to treat these diseases, having phages that can cross into human cells would be very useful,” she says. “This is a neglected research field.”

来自莱斯特大学的Martha Clokie指出:一些有传染性的细菌——包括那些导致肺结核和莱姆病的细菌,可以进入并感染人类细胞。她说:“如果我们想要治疗这些疾病,就可以使用那些可以进入人体细胞的噬菌体,这是非常有用的。这是一个被忽视的研究领域。”