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健康的肠道对心理和精神健康也有好处

更新时间:2019/5/3 9:09:56 来源:纽约时报中文网 作者:佚名

How your belly could heal your brain
健康的肠道对心理和精神健康也有好处

A patient’s gut may not be the most obvious place to look for the origins of depression. But that was the hunch of George Porter Phillips in the early 20th Century.

寻找抑郁症的根源时,患者的肠道可能不是最容易想到的地方。但早在20世纪初,医生菲利普斯(George Porter Phillips)就直觉到人体肠道有名堂。

As he walked the wards of London’s notorious Bethlem Royal Hospital, Phillips had observed that his patients with melancholia often suffered from severe constipation, along with other signs of a “general clogging of the metabolic processes” – including brittle nails, lustreless hair and a sallow complexion.

在伦敦著名的贝特莱姆皇家医院(Bethlem Royal Hospital)巡视病房时,菲利普斯注意到,他的抑郁症患者往往有严重的便秘,以及其他显示“新陈代谢过程总体不畅”的症状,比如指甲易脆、头发没有光泽、面色蜡黄等。

The natural assumption might have been that the depression had led to those physiological problems, but Phillips wondered if the arrow of causation instead pointed in the other direction. By targeting the gut, could you ease the melancholia?

这自然会令人假设,是抑郁症导致了这些生理症状,但菲利普斯怀疑,因果关系是否相反,是否可以通过把目标对准肠道来缓解忧郁症?

To find out, he fed the patients a reduced diet devoid of all meats, except fish. He also offered them a fermented milk drink known as kefir, which contains the lactobacillus bacteria, a “friendly” microbe that was already known to ease digestion.

为了找到答案,他让病人在饮食上避开除鱼肉之外的一切肉类。他还向他们提供了一种名为开菲尔(kefir)的发酵牛奶。这种乳饮含乳酸菌。当时,人们已经知道乳酸菌是一种可以帮助消化的“友好”微生物。

Amazingly, it worked. Of the 18 patients Phillips tested, 11 were cured completely, with two others showing significant improvement – offering some of the first evidence that our gut bacteria can have a profound influence over our mental wellbeing.

令人惊奇的是,这种疗法起效了。18名患者接受了菲利普斯博士的试验,其中11人被彻底治愈,另外两人的病情也有了显著改善。这属于最早的证据,说明肠道细菌可对我们的心理健康产生很深的影响。

BBC Future’s Microbes and Me series has now examined various claims about the power of our gut microbiota to harm or heal – but the notion that they could be responsible for our mental health is perhaps the most difficult to behold. How could these microscopic scavengers, feeding on the debris of our digestion, possibly affect the brain?

BBC未来(BBC Future)的《微生物与我》(Microbes and Me)系列节目对各种有关肠道微生物群的伤害或治疗能力的说法进行了研究,但认为肠道微生物是引起心理健康问题的元凶这个观念,可能是最难理解的。这些以我们的食物残渣为食的微型食腐动物,到底会以何种方式影响我们的大脑呢?

As we have seen with the other articles in this series, some of these findings have been overhyped. But more than a century after Phillips’ initial experiment, the fundamental idea of a gut-brain axis is now remarkably solid. “There is no debate, in my mind, that microbes influence mental health,” says Jane Allyson Foster, whose lab at McMaster University in Canada is leading research in this area. And that means we may be able to heal the brain through the belly. “There is the potential both for the development of novel therapeutics and for precision medicine.”

正如我们在本系列的其他文章中所看到的,其中一些发现被夸大了。但在菲利普斯最初那个试验过去一个多世纪后的今天,大脑和肠道有关联这个基本概念已非常牢固。“在我看来,毫无疑问,微生物会影响心理健康,”加拿大麦克马斯特大学(McMaster University)的福斯特(Jane Allyson Foster)说。他领导的实验室在这一领域的研究中处于领先地位。这意味着我们也许能够通过饮食来治疗心理疾病。他说:“开发新疗法和实行精准医疗都是有可能的。”

Foster emphasises that an unhealthy gut is just one of many possible causes of mental illness, meaning that only a subset of patients will respond well to the new “psychobiotic” treatments. But for those patients who are suffering from an imbalance in their gut bacteria, the new therapies might bring much-needed relief.

福斯特强调,肠道不健康只是心理疾病众多可能的病因之一,这意味着只有一部分病人会对新的"精神生物"治疗反应良好。但对肠道细菌失调的患者来说,这种新疗法可能会带来他们急需的病情缓解。

Despite early studies, including Phillips’, the idea that the gut might influence our mental health fell out of favour for much of the 20th Century, and strong evidence for this mysterious link has only emerged again over the last two decades.

尽管有包括菲利普斯的发现在内的早期研究,但肠道可能会影响心理健康这个观点在20世纪大部分时间里都不受欢迎。直到最近20年,这种神秘联系的有力证据才再次出现。

One of the most striking modern experiments came from Kyushu University in Japan in 2004.

日本九州大学(Kyushu University)在2004年进行的一场实验,是最引人注目的现代实验之一。

The team first demonstrated that “germfree” mice – raised in sterilised conditions so they have no microbes on or in their bodies – showed greater fluctuations in the hormones corticosterone and ACTH, both of which are known to reflect stress levels. This suggested that the gut bacteria of healthy mice were somehow shaping their hormonal profile.

首先,研究团队证明“无菌”老鼠(在无菌环境下饲养的老鼠,因而其体内和体表均没有微生物)的皮质酮和ACTH水平波动较大。我们都知道,这两种激素都能反映压力水平。这表明,健康老鼠的肠道细菌在某种程度上影响着它们的激素水平。

The researchers then dosed a group of germfree mice with lactobacillus bacteria – the class of ‘friendly’ bacteria that Phillips had also used on his melancholic patients. Although these mice still showed a higher stress response than the mice that had never been raised germ-free, their stress responses were less pronounced than the mice without any gut microbes.

然后,研究人员给一组无菌老鼠注射乳酸菌。这也是菲利普斯医生给他的抑郁症患者使用的“友好”微生物。尽管这些老鼠的应激反应仍高于从未接受过无菌饲养的老鼠,但其反应又不及完全没有肠道微生物的老鼠那样明显。

There are even some signs that depressive behaviours can be transmitted across species – from human to mouse – through the microbes in the gut.

甚至还有一些迹象表明,抑郁行为可通过肠道中的微生物跨物种传播,从人传给老鼠。

In one study, Chinese researchers in Chongqing took a sample of the gut microbiota from patients with Major Depressive Disorder and planted them in germfree mice. These mice subsequently were quicker to quit, on a "forced" swimming task – a behaviour that is often considered to be analogous to the lethargy and hopelessness found in depression. And when the mice were placed in a box, they spent less time exploring the central areas and instead stayed closer to the edge, where they felt more secure.

在一项研究中,中国重庆的研究人员对重度抑郁症患者的肠道菌群进行了取样,并将其植入无菌老鼠体内。随后,在一项“被迫”的游泳任务中,这些老鼠会较快停止游泳。这种行为通常被认为类似于抑郁症中的疲倦乏力和绝望。把这些老鼠放进盒子里,它们探索中心区域的时间较少,而会待在更靠近边缘的地方。因为靠近边缘,这些老鼠感到较安全。

“What was remarkable was that the animals that receive the ‘depressed’ microbiome, behave depressed,” says Julio Licinio at New York Upstate Medical University, who was a co-author on the paper. “If you change the microbiome, you change the behaviour.”

与重庆研究者合作写这篇论文的科学家、纽约州立大学上州医科大学(New York Upstate Medical University)的利西尼奥(Julio Licinio)说:“值得注意的是,接受‘抑郁’微生物群的动物也有抑郁行为,改变微生物群,就会改变抑郁行为。”

We can only draw so many conclusions from these animal studies, of course – but their conclusions are supported by epidemiological studies examining vast numbers of human participants (the most recent was published on 4 February 2019.) These studies have consistently shown that differences in the gut microbiota coincide with various mental illnesses, include depression and anxiety.

当然我们只能从这些动物研究得出大量结论,不过这些结论已得到了以大量人类参与者为研究对象的流行病学研究(距今最近的发表于2019年2月4日)的支持。这些研究一致表明,肠道微生物区的差异都伴随着不同的心理疾病,如抑郁症和焦虑症等。

No single species appears to be responsible for these effects; instead, it appears to be the overall ratio of the different families of the microbes that matters, with the gut microbiomes of depressed and anxious people showing less overall diversity than individuals without mental health problems.

看来不是哪一种微生物造成了这些影响,似乎是不同种类的微生物间的比例组成起到重要作用。抑郁症和焦虑人群的肠道微生物群的种类数量要低于心理健康的人群。

Astonishingly, one of Licinio’s recent papers has revealed that schizophrenia is associated with an impoverished gut microbiota, and when samples from patients were implanted in germ-free mice, it seemed to lead to some of the characteristic shifts in brain activity that are the signatures of the disorder.

令人惊讶的是,利西尼奥最近的一篇论文显示,精神分裂症也与肠道微生物群的缺乏有关。将患者的样本植入无菌老鼠体内时,似乎会导致大脑活动的一些特征发生变化,而这些变化正是精神疾病的标志。

Multiple pathways

多途径

These effects may arise through many pathways.

这些影响可能会通过多种途径出现。

Certain species of gut microbes can protect the gut wall – helping to maintain its mucous membrane that stops the contents spilling into the blood stream. Without that barrier, you may suffer from a “leaky gut”, which triggers, among other things, the release of pro-inflammatory cytokines, proteins that increase the blood flow around sites of infection and regulate the body’s immune response.

某些种类的肠道微生物可以保护肠道壁,帮助维持肠道黏膜。肠道黏膜可阻止肠道内的物質渗入血流。如果没有这道屏障,你可能会患上“肠漏”,肠漏会触发促炎细胞因子的释放。促炎细胞因子是一种蛋白质,会增加感染部位周围的血液流动,并调节身体的免疫反应。

While this reaction is crucial to fight infection, these cytokines can also lead to a low mood and lethargy. It’s the reason we often feel tired when we’re ill – and over the short term, that response helps us to preserve energy to find the infection. But over the long term, it may lead to depression.

虽然这种反应对抵抗感染至关重要,但这些细胞因子也会导致情绪低落和精神萎靡。正是因为这个原因,我们生病时往往会感到疲倦。从短期来看,这种反应有助于我们保持精力,以便发现感染。但从长远来看,可能会导致抑郁。

Gut microbes also influence how we digest and metabolise the precursors of important neurotransmitters like serotonin and dopamine. Our gut flora even has a direct line of communication to the brain, through the vagus nerve, which has receptors near the gut lining that allow it to keep a check on our digestion. Microbes in the intestine can therefore release chemical messengers that alter the signalling of the vagus nerve – and, as a consequence, the brain’s activity. (To find out more about the vagus nerve, read Gaia Vince’s explainer over at Mosaic.) “Locally in the gut, there’s a lot of opportunity for the bacteria to communicate with the host systems – including the nervous system,” says Foster. “It’s a very dynamic, interactive, rich space.”

肠道微生物还会影响我们消化和代谢重要神经递质,如血清素和多巴胺前体的方式。我们的肠道菌群甚至能通过迷走神经与大脑直接沟通,迷走神经在肠道内壁附近有感受器,使其得以检查我们的消化情况。因此,肠道内的微生物可以释放化学物,改变迷走神经的信号,从而改变大脑的活动。福斯特说:“在肠道内,细菌有很多机会与宿主系统,包括神经系统交流。这是一个非常动态,相互影响的丰富空间。”

These pathways are not one-way streets however, so brain activity can also influence the gut flora composition. Stress can itself increase inflammation, for instance, which can then affect the microbes in our gut. The result could be a kind of feedback loop.

但这些交流并非单向的,因此大脑活动也可影响肠道菌群的组成。比如,压力本身会加剧发炎,进而影响肠道内的微生物。结果会形成一种反馈循环。

New avenues

新途径

Foster says research in this field is now rapidly accelerating, conducted both by university scientists and commercial companies; academic meetings, discussing the findings, are now “dime-a-dozen every week”.

福斯特说,这个领域的研究发展很快,研究者有大学的科学家,也有商业公司,学术会议和讨论研究发现的活动现在也“比比皆是”。

Ultimately, these researchers hope that their findings will offer a new treatment target for illnesses such as depression.

最终,这些研究人员希望他们的发现能为抑郁症等精神疾病提供新的治疗目标。

Existing antidepressants aim to alter the balance of chemicals such as serotonin in the brain, but they are not effective for all patients: only two out of every 10 patients taking antidepressant drugs show signs of improvement, over and above the placebo effect. And although they help many patients, talking therapies such as cognitive behavioural therapy are similarly hit and miss. As a result, many patients are left without and struggle to find an appropriate treatment, and the gut-brain axis would seem to offer one of the most promising lines of enquiry.

现有的抗抑郁药物旨在改变大脑中血清素等化学物质的平衡,但这并不是对所有患者都有效:服用抗抑郁药物的患者中,只有十分之二的人有病情缓解的迹象,其效果只超过安慰剂。谈话治疗之类,如认知行为疗法,尽管会帮助很多患者,但也同样具有随机性。这导致的结果就是,很多患者得不到或难以找到合适的治疗方法,而大脑的健康与肠道相关这一现象似乎提供了最有希望的研究方向之一。

Some attempts – like Phillips’ study in 1910 – have fed patients fermented drinks such as kefir that might seed the gut with bacteria and proteins that are known to be beneficial to digestion, or soluble fibres known as “prebiotics” that are also thought to encourage our gut flora to flourish. Unfortunately, many of these studies have tended to be small, with only a handful of participants, and their results have been mixed: in some studies, the interventions successfully reduced symptoms; in other trials, they proved to be no better than a placebo treatment.

一些治疗尝试,比如菲利普斯在1910年进行的研究,让患者服用开菲尔等发酵饮品,可能会让肠道内产生已知有利于消化的细菌和蛋白质,或是让患者摄入被称作“益生元”的可溶性纤维,这也被认为有助于我们的肠道菌群发展。遗憾的是,很多此类研究往往规模小,参与者少,结果也是喜忧参半:在一些研究中,干预措施成功减轻了症状;在另一些试验中,结果证明并不比安慰剂治疗强。

One explanation, Foster says, is that the failed studies have not targeted the patients who would benefit most from this kind of treatment. There are many causes of depression, after all, and while disruptions to the gut flora may be the underlying cause of some people’s depression or anxiety, in others the trigger could be quite different. For them, a probiotic drink is unlikely to make a big difference to their symptoms.

福斯特说,一种解释是,那些失败的研究没有把目标对准最能从这种治疗中获益的患者。毕竟,抑郁症的病因有很多,肠道菌群紊乱可能只是部分人抑郁或焦虑的潜在原因,而在另一些人身上,引发抑郁的原因可能完全不同。对这些人来说,益生菌饮料不太可能让他们的症状发生大的改变。

To further complicate matters, each person’s microbiome is unique – so any treatment that targets the gut flora should take account of those differences. Overall, the exact composition between any two individuals only overlaps by around 10%.

更复杂的是,每个人的微生物菌群都是独一无二的,因此任何针对肠道菌群的治疗都应该考虑到这些差异。总的来说,任何两个人体之间的微生物菌群精确构成只会重叠大约10%。

For this reason, she thinks we need to find more sophisticated ways of matching the treatment to the patient. “This is where the gut-brain axis is going to help us, in precision medicine.” The hope, Foster says, is “to map out ‘bio-types’ or clusters of individuals who share the biology that might be driving their symptoms”. You might, for instance, first test whether a patient has high or low inflammation before deciding on the treatment.

正因为如此,她认为我们必须找到更精准的方法来配合患者和疗法。福斯特说:“在精准医疗中,这正是大脑和肠道的相关性能帮到我们的地方。”其希望是“找出‘生物类型’或引发病症的生理习性相同的人群”。比如,在决定治疗方法之前,可以先检查患者炎症程度的高低。

Licinio is also cautiously optimistic that future research will identify therapies that target the gut-brain axis. He says that the significant side-effects of antidepressant drugs have limited the development of new pharmaceutical treatments – but this approach could avoid those issues. “You are not tampering with the brain,” he says, “so I think that any side effects you have will be less problematic.”

对于未来的研究会找出针对大脑肠道相关性的疗法,利西尼奥持谨慎乐观的态度。他说,抗抑郁药物副作用显著,限制了新型药物治疗的发展,但针对大脑肠道相关性的疗法可以避免这些问题。他说:“你不是在干预大脑,所以我认为任何副作用都不会太严重。”

Eat like an Italian

仿照意大利人的饮食习惯

The current understanding of the gut-brain axis does at least add to the growing evidence that a healthy, balanced diet could be an important preventative measure to reduce the risk of developing an illness like depression in the first place.

目前对大脑肠道相关性的了解至少又增加了一项证据,说明健康均衡的饮食可能是一项重要的预防措施,可降低患抑郁症等疾病的风险。此类证据越来越多。

Many of these studies have examined the “Mediterranean diet” – a catch-all term to describe diets rich in vegetables, fruit, nuts, sea food, and unsaturated fats and vegetable oils, and low in refined sugar and red and processed meat. (This is a very rough generalisation, of course, since there is still a great variation in the particular foods eaten across southern Europe.) In one study from Spain, people eating the traditional Mediterranean diet were roughly half as likely to be diagnosed with depression over a four-year period.

这些研究中很多都研究了“地中海饮食”。“地中海饮食”是一个笼统的说法,指的是富含蔬菜、水果、坚果、海鲜、不饱和脂肪和植物油,同时少精制糖、红肉和加工肉制品的饮食。(当然,这是一个非常粗略的概括,因为在整个南欧,人们吃的具体食物仍有很大差别。)在一项来自西班牙的研究中,在四年时间里,坚持传统地中海饮食的人被诊断患抑郁症的可能性大约是其他饮食习惯者的一半。

“The data regarding the importance of nutrition for mental and brain health is now extensive and highly consistent,” says Felice Jacka, a nutritional psychiatrist at Deakin University in Australia and author of Brain Changer: The Good Mental Health Diet. Although there are many potential mechanisms, the Mediterranean diet has been shown to increase the diversity of gut bacteria, and reduces the other physiological changes such as chronic inflammation that also seems to accompany depression.

“有关营养对心理和大脑健康的重要性的数据现在很多,并且高度一致,”澳大利亚迪肯大学(Deakin University)的营养精神病学家、《良好的心理健康饮食改变大脑》(Brain Changer: The Good Mental Health Diet)的作者杰卡(Felice Jacka)说。尽管还有很多潜在的生理机制因素,但地中海饮食已经被证明可增加肠道细菌的多样性,并减轻其他生理变化,如慢性发炎。慢性炎症似乎也是抑郁症的伴随症状。

More than a century after Phillips’ experiment in Bethlem Royal Hospital, a panacea for depression remains elusive – but for some people at least, a healthier gut may be an important first step to a healthier and happier mind.

菲利普斯在贝特莱姆皇家医院进行的实验已经过去了一个多世纪,但我们依然难以找到治疗抑郁症的灵丹妙药,不过至少对部分人来说,让肠道更健康可能是迈向心理更健康、更快乐重要的第一步。

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