人体内的微生物是影响健康的关键吗？

What are microbiomes?

什么是微生物群？

Both inside and out, our bodies harbour a huge array of micro-organisms. While bacteria are the biggest players, we also host single-celled organisms known as archaea, as well as fungi, viruses and other microbes – including viruses that attack bacteria. Together these are dubbed the human microbiota. Your body’s microbiome is all the genes your microbiota contains, however colloquially the two terms are often used interchangeably.

无论是体内还是体外，都有着大量的微生物栖息在我们的身体上。虽然细菌是其中最主要的群体，但我们同时也拥有被称为古生菌的单细胞生物，以及真菌、病毒和其他微生物。它们被统称为人类微生物群。

Hang on, aren’t microbes supposed to be dangerous?

等会儿，微生物不应该是危险、有害的吗？

It’s a bit of a spectrum: some are pathogens, but others only become harmful if they get in the wrong place or boom in number, and some are very useful to the body – such as by helping to break down the array of sugars found in human breast milk. “These sugars are not broken down by the infant,” said Prof John Cryan, a neuropharmacologist and microbiome expert from University College Cork. Instead, microbes in the baby’s gut do the job.

事实并非总是如此：不可否认有些的确是病原体；但有些只有在错误的地方出现或数量暴增时才会变得有害；还有一些对身体非常有益。例如母乳类含有大量婴儿无法直接分解的糖，但肠道内的微生物能帮助婴儿完成这项工作。

Other key roles of our microbes include programming the immune system, providing nutrients for our cells and preventing colonisation by harmful bacteria and viruses.

人体内的微生物还扮演着许多其他的重要角色，其中包括设置了我们的免疫系统，为人体的细胞提供营养，并防止有害细菌和病毒的定植。

Where do my gut microbes come from? Do I just pick them up from my surroundings?

那么，肠道微生物来自哪儿？是我们从周围环境中接触到的吗？

Partly. But it is more complicated than that. “It is still a little bit controversial but for the most part it is thought that we are sterile when we are in utero, and as we are being born, as we emerge through the birth canal from our mums, we get this handover bacteria,” said Cryan. “It is like a gulp at birth. Those bacteria are really important for starting the whole process.”

这只是部分原因，它其实比这要更加复杂。爱尔兰科克大学的神经药理学家 John Cryan 教授解释说：“虽然仍存有一点争议，但大多时候我们认为当我们还在子宫内时，我们是无菌的；在通过母体产道出生时，我们才接触到了细菌。”

Cryan notes that during pregnancy a mother’s microbiome shifts, apparently to an optimum mix for offspring. “If you are not born by vaginal delivery, but are born by [caesarean] section, things start off being different,” he said. Indeed, studies have suggested that these differences could be one of the reasons why babies born by caesarean section have a higher risk of conditions including asthma and type 1 diabetes. That said, doctors have cautioned parents against attempting to seed babies born by caesarean section with vaginal bacteria.

Cryan指出，在怀孕期间，母亲的微生物群体会调整成一个对后代最好的组合。也正因如此，如果生产时不是通过阴道分娩，而是剖宫产出生，情况就会有些不同。据研究表明，这种差异可能是导致剖宫产出生的婴儿患哮喘和1型糖尿病的风险更高的原因之一。但是，医生们告诫家长，不要试图给剖宫产出生的婴儿接种阴道细菌。

Our gut microbiome changes quickly over our first year or two, shaped by microbes in breast milk, the environment and other factors, and stabilises by the time we are about three years old. But our environment, our long-term diet, stress and the drugs we take, such as antibiotics, continue to play a role as we age, meaning our microbiome can change throughout our life.

在母乳中的微生物、环境和其他因素的作用下，肠道微生物群会在我们生命的头一两年快速地变化着，大约到三岁时基本稳定下来。但是，随着年龄的增长，环境、长期饮食、压力以及抗生素等药物的服用将继续发挥作用，这意味着微生物群可以在我们的整个生命进程中不断改变。

It seems like microbes are everywhere – how many are we talking about?

看似无处不在的微生物，到底有多少量呢？

The figure that has been bandied out since the 1970s is that microbes outnumber our own cells by about 10 to one. But a study from 2016 suggests that in fact microbial cells and human cells coexist in somewhere around a 1.3 to one ratio – suggesting they only slightly outnumber our own cells, although that doesn’t count viruses and viral particles.

自1970年代以来，被众人传述的数字是微生物的数量远超人类细胞，比例大约为10 : 1。但2016年开始的一项研究表明，微生物细胞和人类细胞共存的比例约为1.3 : 1，这表明微生物细胞只比人体细胞略多一点，尽管这不包括病毒和病毒颗粒。

Does this mean I am not human?

那么这是否意味着人非人？我非我？

Some say we should be seen as a holobiont, a term that reflects the intimate, co-dependent relationship humans have with microbes. “I tell this joke that the next time someone goes to the bathroom and they get rid of some of their microbes they are becoming more human,” said Cryan.

有人说我们应该被看作是一个共生功能体（holobiont），这是一个反映了人类与微生物间亲密且相互依赖的关系的术语。Cryan 很爱说一个笑话：“当我们每去一次卫生间，就能摆脱掉一部分微生物，变得更像人一点。”

But Ellen Clarke, a philosopher of biology at the University of Leeds, is not convinced. “It all depends on what you mean by ‘human’ in the first place,” she said. “If you think that a human is a collection of cells that all share copies of the same chromosomes, then it is shocking to be told that our bodies contain cells with bacterial DNA.”

但利兹大学的生物学哲学家 Ellen Clarke 并不相信这种说法。她认为这一切都取决于我们最初如何定义“人”，她说：“如果把人当作是一群有着相同染色体的细胞结合体，那么如何解释我们的细胞中含有细菌DNA一事。”

But as Clarke points out, human cells don’t just contain chromosomes, but also carry DNA within our cellular powerhouses, mitochondria, which are evolutionary descendants of bacteria. Our genome also contains stretches of genetic material called transposons that, at least in some cases, are thought to have been introduced long ago by viruses. “I prefer to define a human in evolutionary terms, and if we do this then mitochondria are parts of a human, and so are transposons, but gut microbes are not, and neither are prosthetic limbs nor unborn foetuses,” said Clarke, pointing out that microbes can escape the body and live without us.

但正如 Clarke 所指出的那样，人类细胞不仅含有染色体，而且在细胞的动力室线粒体中携带DNA，而内共生学说认为线粒体来源于某种细菌。我们的基因组还包含一系列被称为转座子（transposons）的遗传物质，有人认为至少在某些情况下，它们是源自于病毒。Clarke 说：“我更喜欢从进化的角度来定义人类，这样的话，那么线粒体就是人类的一部分，转座子也是如此，但肠道微生物就不是，假肢和胎儿也都不是。”也就是说，她认为微生物可以离开我们的身体，没有我们也照样生存。

Are microbes the same in my gut as on my skin?

肠道里的微生物和皮肤上的一样吗？

No, different parts of the body – the skin, vagina, gut – all have very different, distinct communities of microbes. While gut microbes have gained a lot of attention, microbes elsewhere are also important: in recent studies, scientists have found that bacteria commonly found on the skin might help to protect against skin cancer.

不，不同的身体部位有着截然不同的微生物群落。虽然肠道微生物受到了很多研究的关注，但其他地方的微生物也很重要：在最近一些研究中，科学家发现皮肤上常见的细菌或许有助于防止皮肤癌。

Microbiomes also differ from person to person. “When you look at the overall active microbiomes between two healthy people, even if they are living in the same city, you see a tremendous amount of disagreement in their microbiome,” said Rob Knight, professor of paediatrics, computer science and engineering at the University of California San Diego and an expert on the human microbiome.Variability in the gut microbiome, Knight notes, helps to explain why people respond differently to the same foods. “Whether tomatoes are good or bad for you, whether rice is good for you or worse for you than ice cream and so on is explained by your microbiome,” he said.

并且，微生物群也因人而异。加州大学圣地亚哥分校的人类微生物群专家 Rob Knight 指出，即便是两个同样健康的人在同样的环境下生活，它们的整体活性微生物群也存在巨大的差异。肠道微生物组的不同之处解释了为什么人们对同样的食物有着不同的反应。他说：“西红柿对你有益还是有害，米饭比冰淇淋更好还是更糟，都需要通过你的微生物群才能解释。”

Why has the microbiome become such a hot topic for research?

为什么微生物组会成为热门的研究课题？

Over recent years the gut microbiome in particular has been linked to a plethora of diseases and conditions, from diabetes to autism and anxiety to obesity. The gut microbiome has also been linked to how individuals respond to certain drugs, including how cancer patients respond to chemotherapy, and it has even, tentatively, been suggested that it could be linked with how well we sleep.

近年来，肠道微生物群被认为与糖尿病、自闭症、焦虑症、肥胖症等多种病症相关。肠道微生物也被认为与不同个体对相同药物的不同反应有联系，甚至有人还将它与我们的睡眠质量联系在一起。

Meanwhile, a range of studies have raised the importance of other aspects of our microbiome, including that the vaginal microbiome is important in whether an HIV-prevention drug applied to the vagina is effective.

同时，一系列研究表明了微生物组在其他方面的重要性，例如阴道微生物组对于应用于阴道的HIV预防药物是否有效十分关键。

Why do we think the microbiome is linked to all these conditions?

为什么认为微生物组与这些病症有关？

While some links have come from comparing the microbiomes of different groups of people, such as those with a particular disease compared with healthy individuals, a big player in microbiome research is the germ-free mouse.

虽然有些关联来自于对不同人群之间微生物群体的比较，比如将具有某种疾病的人群与健康个体相比，但微生物群体研究的一个重要参与者就是——无菌小鼠。

This organism is raised in a sterile environment and can then be exposed to particular microbes, or groups of microbes, to explore their impact. Such studies have been key in raising possible links between the gut microbiome and numerous aspects of our health, including mood and obesity.

这种生物体培养于无菌的环境中，可将其暴露于特定的微生物或微生物群体之下，以探索它们的影响。这类研究一直是提高肠道微生物群与人体健康的诸多方面（包括情绪和肥胖）之间的潜在联系的关键。

Is it that particular microbes are important, or is it about the microbial community as a whole?

是否只有某些特定的微生物是重要的，还是整个微生物群体都重要？

This is the knotty issue. In some experiments, particular strains of bacteria have been linked to particular effects or conditions, while others have shown that the diversity of the microbiome, or relative abundances of species, is important.

这是一个棘手的问题。在一些实验中，特定的细菌菌株被认为与特定的反应或疾病有关，而另一些实验则表明微生物组的多样性或物种的相对丰度非常重要。

“It is a bit like a rainforest: you might have a very nice fern that is very happy but if that is the only thing in your rainforest and you don’t have a diversity it is not going to be good [for the] soil,” said Tim Spector, professor of genetic epidemiology at King’s College London and author of The Diet Myth. When it comes to the microbiome, “it’s having the right community of bacteria that are working together and together producing the right chemicals for your body.”

伦敦国王学院的遗传流行病学教授 Tim Spector 解释说：“这有点像热带雨林：雨林中可能有一棵很生长良好的蕨类植物，但如果这是雨林中唯一的植物，那么就缺乏多样性，对土壤不好。说回到微生物群时，当它拥有合适的细菌群体，才能共同为人体产生正确的化学物质。”

So might microbes be affecting our weight, or even our brains? That sounds a bit sci-fi.

微生物是否会影响我们的体重、甚至大脑呢？

When it comes to obesity, there are several ways gut microbes might influence matters, including through appetite, production of gases, efficiency of using food, and impact on the immune system and inflammation.

当谈到肥胖时，肠道微生物可能会通过几种方式产生影响，其中包括食欲、产生气体、消化吸收食物的效率、以及对免疫系统和炎症的影响。

When it comes to affecting mood, there are also several mechanisms. One is via the vagus nerve, a two-way highway that runs from our brain to various organs in the body, including the gut.

对于情绪影响也有几种机制，一个是通过迷走神经，这是一条从我们的大脑流向包括肠道在内的身体各器官的双向大道。

With the microbiome linked to so many conditions, does tinkering with it promise a whole range of new treatments?

微生物菌群与这么多病症有关，对其进行修改是否能提供新的治疗方法？

It is worth being cautious: many studies show associations rather than cause and effect, and some are based only on studies in germ-free mice and have not been explored in humans. Even in mice things aren’t straightforward – effects are not always the same for both sexes and can differ for different strains of mice.

值得谨慎的是：许多研究显示出的是联系而非因果关系，而且有些结果仅来自于对无菌小鼠的研究，并未在人类身上进行过探索。即使在小鼠身上，事情也并非显而易见，有些影响对会因性别而出现差异，还可能因老鼠种类而表现不同。

And there are other factors to consider: “For obesity what it looks like is in different human populations, different kinds of microbes are involved in the differences between lean and obese humans,” said Knight.

还有其他需要考虑的因素，如 Knight 所说：“对于肥胖症来说，似乎在不同的人群中，不同种类的微生物与纤瘦和肥胖人群间的差异有关。”

Spector said: “I think everyone is right to be sceptical, and a lot of the links may just be that [microbes] are not necessarily the cause of [a disease], but they might be a secondary effect of it.”

Spector 说：“我认为每个人都有权持怀疑态度，许多关联可能未必代表微生物是病症的原因，它们或许只是一种次级效应。”

Others say it isn’t surprising that our microbiome might be closely linked to our health. “All of human development and all the systems in the body have all evolved, or co-evolved, with our microbes,” said Cryan. “As humans we are very much human-focused and we feel that human cells and genes have primacy, but the microbes were there first.”

也有人表示，微生物组可能与我们的健康息息相关。这并不奇怪，因为人体发育和体内所有系统都与微生物一起演化或共同发展。Cryan说：“作为人类，我们非常以人类为中心，认为人类细胞和基因占有首要地位，但其实微生物才是更先存在的。”

Does any of this actually affect patients?

这是否能影响患者？

Up to a point. The field has already led to advances in the treatment of C difficile – an infection that causes serious diarrhoea and can prove deadly. Patients can now receive faecal transplants from a donor with a healthy microbiome to “reset” their inner community – a procedure that has been shown to rapidly cure the condition.

在一定程度上，是的。该领域已经使研究人员在艰难梭菌（C difficile）治疗方面取得了进展，这是一种能导致严重腹泻的致命感染。现在，患者可以接受来自捐赠者提供的健康微生物组进行粪便移植，来“重设”他们体内的内部系统。这一过程已被证明可以快速治愈这种疾病。

Some researchers, including Cryan, believe microbiome research could lead to the development of new mental health therapies. “We have coined the term ‘psychobiotic’ [by which we mean] a targeted intervention of the microbiome for brain health,” he said.

许多研究人员认为，微生物组研究或许能发展出新的心理健康疗法。Cryan 也是这种说法的支持者之一，他表示：“我们已经创造了‘精神病菌’这个词，用精神病菌来对与大脑健康有关的微生物组进行有针对性的干预。”

While that may be some way off, Cryan believes it will become routine for doctors to keep an eye on the makeup of patients’ microbiomes. “I think personally that bacteria- or microbiome-derived medicine is the future of precision medicine,” he said.

虽然这或许还有一段路要走，但 Cryan 认为，医生对患者微生物群构成的密切关注将成为例行检查。他说：“我个人认为细菌或微生物源药物是精准医学的未来。”

Let’s cut to the chase: what can I do to keep my microbiome in good shape?

让我们切入正题：做什么才能保持微生物群体的良好状态呢？

This is where prebiotics and probiotics come in: the former are substances, such as the fibre inulin, on which useful microbes can thrive, while the latter are microbes themselves that are thought to be beneficial for health, such as the Lactobacillus and Bifidobacterium species.

这就是益生元和益生菌切入的地方了：前者是让有益微生物可以繁殖的物质，如菊粉纤维；而后者是被认为有益于健康的微生物本身，例如乳酸菌和双歧杆菌。

While both prebiotics and probiotics can be taken as supplements, whether you should shell out for them is another matter: there is little advice on which prebiotics or probiotics people should consume for a particular situation, and when it comes to probiotics it isn’t a dead cert that the microbes will colonise your gut when they get there, or if they will offer benefits to already healthy people, such as preventing diseases. That said, if you are taking antibiotics or have IBS, there is some evidence probiotics might be a good idea.

虽然益生元和益生菌都可以被作为补充剂摄入，但是你是否应该为它们买单又是另一回事：关于人们在某种特定情况下应该摄入哪种益生元或益生菌方面的建议其实很少；而对于益生菌，我们并不能斩钉截铁的确定它们能在肠道里定植，又或者说它们能为已处于健康状态的人提供更多益处，例如预防疾病。也就是说，如果你正在服用抗生素或有肠易激综合征（IBS），有证据表明益生菌或许是不错的选择。

“It is not clear yet whether you’re better off just having lots of yoghurt and other fermented foods or actually taking these formulations,” said Spector, adding that in general he recommends opting for tweaking your diet to get a dose of probiotics, since it isn’t clear which strains individuals should take. The same goes for prebiotics: “there is more variety in food in terms of the fibre, therefore more variety in the microbes,” he said. “Ideally you combine a prebiotic and a probiotic: something like sauerkraut or kimchi.”

Spector 说：“目前尚不清楚你是否应该多吃酸奶和其他发酵食品，或者该直接服用这些制剂。” 总体上的建议是选择调整饮食以获取一定剂量的益生菌，因为目前还不清楚不同个体应服用哪类菌株。益生元也是如此，Spector 补充说：“纤维类食物的种类更多，因此该种类的微生物种也更多。理想情况下，你可以将益生元和益生菌结合起来，如酸菜或泡菜。”

What next?

下一步？

The spotlight is on unpicking the mechanisms by which microbes are linked to human health. Among the conundrums is how and why the different strains of bacteria have different effects, while researchers are also developing studies to explore how the microbiome influences our response to food, and how different diets can tweak the microbiome. There is also a need to take more of the exciting findings from mouse studies and probe them in humans, preferably through randomised control trials.

焦点在于如何揭开微生物与人体健康相关的机制。难题之一是为什么不同细菌菌株有不同的作用，研究人员正试图探讨微生物会如何影响我们对食物的反应，以及不同的饮食会如何调整微生物群。同时，我们也还需要从小鼠研究中获得更多令人激动的发现，最好能通过随机对照试验，应用于人体探究中。