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更新時間:2019/5/3 9:09:56 來源:紐約時報中文網 作者:佚名

How your belly could heal your brain
美高梅官方网站的腸道對心理和精神美高梅官方网站也有好處

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.

尋找抑郁癥的根源時,患者的腸道可能不是最容易想到的地方。但早在20世紀初,醫生菲利普斯(George Porter Phillips)就直覺到人體腸道有名堂。

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.

在倫敦著名的貝特萊姆皇家醫院(Bethlem Royal Hospital)巡視病房時,菲利普斯注意到,他的抑郁癥患者往往有嚴重的便秘,以及其他顯示“新陳代謝過程總體不暢”的癥狀,比如指甲易脆、頭發沒有光澤、面色蠟黃等。

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?

這自然會令人假設,是抑郁癥導致了這些生理癥狀,但菲利普斯懷疑,因果關系是否相反,是否可以通過把目標對準腸道來緩解憂郁癥?

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.

為了找到答案,他讓病人在飲食上避開除魚肉之外的一切肉類。他還向他們提供了一種名為開菲爾(kefir)的發酵牛奶。這種乳飲含乳酸菌。當時,人們已經知道乳酸菌是一種可以幫助消化的“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.

令人驚奇的是,這種療法起效了。18名患者接受了菲利普斯博士的試驗,其中11人被徹底治愈,另外兩人的病情也有了顯著改善。這屬于最早的證據,說明腸道細菌可對我們的心理美高梅官方网站產生很深的影響。

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未來(BBC Future)的《微生物與我》(Microbes and Me)系列節目對各種有關腸道微生物群的傷害或治療能力的說法進行了研究,但認為腸道微生物是引起心理美高梅官方网站問題的元凶這個觀念,可能是最難理解的。這些以我們的食物殘渣為食的微型食腐動物,到底會以何種方式影響我們的大腦呢?

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.”

正如我們在本系列的其他文章中所看到的,其中一些發現被夸大了。但在菲利普斯最初那個試驗過去一個多世紀後的今天,大腦和腸道有關聯這個基本概念已非常牢固。“在我看來,毫無疑問,微生物會影響心理美高梅官方网站,”加拿大麥克馬斯特大學(McMaster University)的福斯特(Jane Allyson Foster)說。他領導的實驗室在這一領域的研究中處于領先地位。這意味著我們也許能夠通過飲食來治療心理疾病。他說︰“開發新療法和實行精準醫療都是有可能的。”

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.

福斯特強調,腸道不美高梅官方网站只是心理疾病眾多可能的病因之一,這意味著只有一部分病人會對新的"精神生物"治療反應良好。但對腸道細菌失調的患者來說,這種新療法可能會帶來他們急需的病情緩解。

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.

盡管有包括菲利普斯的發現在內的早期研究,但腸道可能會影響心理美高梅官方网站這個觀點在20世紀大部分時間里都不受歡迎。直到最近20年,這種神秘聯系的有力證據才再次出現。

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

日本九州大學(Kyushu University)在2004年進行的一場實驗,是最引人注目的現代實驗之一。

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,研究團隊證明“無菌”老鼠(在無菌環境下飼養的老鼠,因而其體內和體表均沒有微生物)的皮質酮和ACTH水平波動較大。我們都知道,這兩種激素都能反映壓力水平。這表明,美高梅官方网站老鼠的腸道細菌在某種程度上影響著它們的激素水平。

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.

然後,研究人員給一組無菌老鼠注射乳酸菌。這也是菲利普斯醫生給他的抑郁癥患者使用的“友好”微生物。盡管這些老鼠的應激反應仍高于從未接受過無菌飼養的老鼠,但其反應又不及完全沒有腸道微生物的老鼠那樣明顯。

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

甚至還有一些跡象表明,抑郁行為可通過腸道中的微生物跨物種傳播,從人傳給老鼠。

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.

在一項研究中,中國重慶的研究人員對重度抑郁癥患者的腸道菌群進行了取樣,並將其植入無菌老鼠體內。隨後,在一項“被迫”的游泳任務中,這些老鼠會較快停止游泳。這種行為通常被認為類似于抑郁癥中的疲倦乏力和絕望。把這些老鼠放進盒子里,它們探索中心區域的時間較少,而會待在更靠近邊緣的地方。因為靠近邊緣,這些老鼠感到較安全。

“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.”

與重慶研究者合作寫這篇論文的科學家、紐約州立大學上州醫科大學(New York Upstate Medical University)的利西尼奧(Julio Licinio)說︰“值得注意的是,接受‘抑郁’微生物群的動物也有抑郁行為,改變微生物群,就會改變抑郁行為。”

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.

當然我們只能從這些動物研究得出大量結論,不過這些結論已得到了以大量人類參與者為研究對象的流行病學研究(距今最近的發表于2019年2月4日)的支持。這些研究一致表明,腸道微生物區的差異都伴隨著不同的心理疾。 繅鐘糝 徒孤侵 。

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.

看來不是哪一種微生物造成了這些影響,似乎是不同種類的微生物間的比例組成起到重要作用。抑郁癥和焦慮人群的腸道微生物群的種類數量要低于心理美高梅官方网站的人群。

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.

令人驚訝的是,利西尼奧最近的一篇論文顯示,精神分裂癥也與腸道微生物群的缺乏有關。將患者的樣本植入無菌老鼠體內時,似乎會導致大腦活動的一些特征發生變化,而這些變化正是精神疾病的標志。

Multiple pathways

多途徑

These effects may arise through many pathways.

這些影響可能會通過多種途徑出現。

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.

某些種類的腸道微生物可以保護腸道壁,幫助維持腸道黏膜。腸道黏膜可阻止腸道內的物滲入血流。如果沒有這道屏障,你可能會患上“腸漏”,腸漏會觸發促炎細胞因子的釋放。促炎細胞因子是一種蛋白質,會增加感染部位周圍的血液流動,並調節身體的免疫反應。

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.

雖然這種反應對抵抗感染至關重要,但這些細胞因子也會導致情緒低落和精神萎靡。正是因為這個原因,我們生病時往往會感到疲倦。從短期來看,這種反應有助于我們保持精力,以便發現感染。但從長遠來看,可能會導致抑郁。

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.”

腸道微生物還會影響我們消化和代謝重要神經遞質,如血清素和多巴胺前體的方式。我們的腸道菌群甚至能通過迷走神經與大腦直接溝通,迷走神經在腸道內壁附近有感受器,使其得以檢查我們的消化情況。因此,腸道內的微生物可以釋放化學物,改變迷走神經的信號,從而改變大腦的活動。福斯特說︰“在腸道內,細菌有很多機會與宿主系統,包括神經系統交流。這是一個非常動態,相互影響的豐富空間。”

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.

但這些交流並非單向的,因此大腦活動也可影響腸道菌群的組成。比如,壓力本身會加劇發炎,進而影響腸道內的微生物。結果會形成一種反饋循環。

New avenues

新途徑

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”.

福斯特說,這個領域的研究發展很快,研究者有大學的科學家,也有商業公司,學術會議和討論研究發現的活動現在也“比比皆是”。

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

最終,這些研究人員希望他們的發現能為抑郁癥等精神疾病提供新的治療目標。

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.

現有的抗抑郁藥物旨在改變大腦中血清素等化學物質的平衡,但這並不是對所有患者都有效︰服用抗抑郁藥物的患者中,只有十分之二的人有病情緩解的跡象,其效果只超過安慰劑。談話治療之類,如認知行為療法,盡管會幫助很多患者,但也同樣具有隨機性。這導致的結果就是,很多患者得不到或難以找到合適的治療方法,而大腦的美高梅官方网站與腸道相關這一現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.

一些治療嘗試,比如菲利普斯在1910年進行的研究,讓患者服用開菲爾等發酵飲品,可能會讓腸道內產生已知有利于消化的細菌和蛋白質,或是讓患者攝入被稱作“益生元”的可溶性縴維,這也被認為有助于我們的腸道菌群發展。遺憾的是,很多此類研究往往規模。 斡胝呱,結果也是喜憂參半︰在一些研究中,干預措施成功減輕了癥狀;在另一些試驗中,結果證明並不比安慰劑治療強。

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.

福斯特說,一種解釋是,那些失敗的研究沒有把目標對準最能從這種治療中獲益的患者。畢竟,抑郁癥的病因有很多,腸道菌群紊亂可能只是部分人抑郁或焦慮的潛在原因,而在另一些人身上,引發抑郁的原因可能完全不同。對這些人來說,益生菌飲料不太可能讓他們的癥狀發生大的改變。

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%.

更復雜的是,每個人的微生物菌群都是獨一無二的,因此任何針對腸道菌群的治療都應該考慮到這些差異。總的來說,任何兩個人體之間的微生物菌群精確構成只會重疊大約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.

正因為如此,她認為我們必須找到更精準的方法來配合患者和療法。福斯特說︰“在精準醫療中,這正是大腦和腸道的相關性能幫到我們的地方。”其希望是“找出‘生物類型’或引發病癥的生理習性相同的人群”。比如,在決定治療方法之前,可以先檢查患者炎癥程度的高低。

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.”

對于未來的研究會找出針對大腦腸道相關性的療法,利西尼奧持謹慎樂觀的態度。他說,抗抑郁藥物副作用顯著,限制了新型藥物治療的發展,但針對大腦腸道相關性的療法可以避免這些問題。他說︰“你不是在干預大腦,所以我認為任何副作用都不會太嚴重。”

Eat like an Italian

仿照意大利人的飲食習慣

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.

目前對大腦腸道相關性的了解至少又增加了一項證據,說明美高梅官方网站均衡的飲食可能是一項重要的預防措施,可降低患抑郁癥等疾病的風險。此類證據越來越多。

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.

這些研究中很多都研究了“地中海飲食”。“地中海飲食”是一個籠統的說法,指的是富含蔬菜、水果、堅果、海鮮、不飽和脂肪和植物油,同時少精制糖、紅肉和加工肉制品的飲食。(當然,這是一個非常粗略的概括,因為在整個南歐,人們吃的具體食物仍有很大差別。)在一項來自西班牙的研究中,在四年時間里,堅持傳統地中海飲食的人被診斷患抑郁癥的可能性大約是其他飲食習慣者的一半。

“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.

“有關營養對心理和大腦美高梅官方网站的重要性的數據現在很多,並且高度一致,”澳大利亞迪肯大學(Deakin University)的營養精神病學家、《良好的心理美高梅官方网站飲食改變大腦》(Brain Changer: The Good Mental Health Diet)的作者杰卡(Felice Jacka)說。盡管還有很多潛在的生理機制因素,但地中海飲食已經被證明可增加腸道細菌的多樣性,並減輕其他生理變化,如慢性發炎。慢性炎癥似乎也是抑郁癥的伴隨癥狀。

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.

菲利普斯在貝特萊姆皇家醫院進行的實驗已經過去了一個多世紀,但我們依然難以找到治療抑郁癥的靈丹妙藥,不過至少對部分人來說,讓腸道更美高梅官方网站可能是邁向心理更美高梅官方网站、更快樂重要的第一步。

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