Autism-spectrum disorder

自閉癥譜系障礙

More evidence that autism is linked to gut bacteria

更多的證據(jù)表明自閉癥與腸道細(xì)菌有關(guān)

詞匯

Gut/內(nèi)臟；腸子

Understanding that link may be crucial to treatment

理解這種聯(lián)系對(duì)治療可能是至關(guān)重要的

May 30th 2019 | PHOENIX, ARIZONA

PARADIGM SHIFT is an overused term. Properly, it refers to a radical change of perspective on a topic, such as the move from the physics of Newton to the physics of Einstein, or the introduction of plate tectonics into geology. Such things are rare. Something which history may come to regard as a true paradigm shift does, however, seem to be going on at the moment in medicine. This is a recognition that the zillions of apparently non-pathogenic bacteria on and in human bodies, hitherto largely ignored, are actually important for people’s health. They may even help to explain the development of some mysterious conditions.

范式轉(zhuǎn)換是一個(gè)被過度使用的術(shù)語。正確地說，它指的是對(duì)一個(gè)話題的觀點(diǎn)的根本性轉(zhuǎn)變，比如從牛頓物理學(xué)轉(zhuǎn)向愛因斯坦物理學(xué)，或者把板塊構(gòu)造學(xué)引入地質(zhì)學(xué)。這樣的事情很少見。然而，一些歷史上可能被視為真正范式轉(zhuǎn)變的事情，似乎正在醫(yī)學(xué)領(lǐng)域發(fā)生。這是一種認(rèn)識(shí)，即人體上和體內(nèi)的大量非致病菌對(duì)人們的健康實(shí)際上非常重要。它們甚至可能有助于解釋一些神秘情況的形成。

詞匯

PARADIGM SHIFT /典范轉(zhuǎn)移；思考模式的轉(zhuǎn)移

Radical/激進(jìn)的；根本的；徹底的

Tectonic/構(gòu)造的；建筑的

Zillion/?龐大的數(shù)字；無法計(jì)算的大數(shù)字；

non-pathogenic/非致病性

?

One such condition is autism—these days often called autism-spectrum disorder (ASD). ASD is characterised by repetitive, stereotypical and often restricted behaviour such as head-nodding, and by the difficulties those with it have in reading the emotions of, and communicating with, other people. These symptoms are noticeable in children from the age of two onwards. Currently, in America, about one child in 59 is diagnosed with ASD.

其中一種情況就是自閉癥——現(xiàn)在通常被稱為自閉癥譜系障礙(ASD)。ASD的特征是重復(fù)、刻板和受限的行為，比如點(diǎn)頭，以及患有ASD的人在閱讀他人情緒和與他人溝通方面存在的困難。這些癥狀在兩歲以上的兒童中很明顯。目前，在美國(guó)，大約每59個(gè)孩子中就有一個(gè)被診斷出ASD。

?

What causes ASD has baffled psychiatrists and neurologists since the syndrome was first described, in the mid-20th century, by Hans Asperger and Leo Kanner. But the evidence is pointing towards the bacteria of the gut. That suggestion has been reinforced by two recently published studies—one on human beings and one on laboratory rodents.

自20世紀(jì)中葉漢斯·阿斯伯格(Hans Asperger)和里奧·坎納(Leo Kanner)首次描述ASD以來，ASD的病因一直困擾著精神病學(xué)家和神經(jīng)學(xué)家。但證據(jù)指向腸道細(xì)菌。最近發(fā)表的兩項(xiàng)研究——一項(xiàng)關(guān)于人類，另一項(xiàng)關(guān)于實(shí)驗(yàn)室嚙齒類動(dòng)物——進(jìn)一步證實(shí)了這一觀點(diǎn)。

詞匯

Syndrome/綜合癥狀；并發(fā)癥狀

Rodent/ ?嚙齒目動(dòng)物

Restoring the balance

恢復(fù)平衡

?

The human study, the latest results of which came out a few weeks ago in Scientific Reports, is being conducted by Rosa Krajmalnik-Brown of Arizona State University and her associates. It was prompted by earlier work in which Dr Krajmalnik-Brown and James Adams, a colleague at Arizona State, sequenced the DNA of gut bacteria from 20 autistic children to discover which species were present. They found that the children in their sample were missing hundreds of the thousand-plus bacterial species that colonise a “neurotypical” person’s intestine. One notable absence was Prevotella. This bug, which makes its living by fermenting otherwise-indigestible carbohydrate polymers in dietary fibre, is abundant in the alimentary canals of farmers and hunter-gatherers in places like Africa, rare in western Europeans and Americans, and nearly nonexistent in children with ASD.

亞利桑那州立大學(xué)的Rosa krajmalick - brown和她的同事們正在進(jìn)行這項(xiàng)人體研究，其最新結(jié)果幾周前發(fā)表在《科學(xué)報(bào)告》上。這項(xiàng)研究是由krajmalick - brown博士和他在亞利桑那州立大學(xué)的同事James Adams對(duì)20名自閉癥兒童腸道細(xì)菌的DNA進(jìn)行測(cè)序后得出的，目的是發(fā)現(xiàn)存在哪些種類的細(xì)菌。他們發(fā)現(xiàn)，在他們的樣本中，兒童缺失了數(shù)百種細(xì)菌，而這些細(xì)菌寄生在人體與神經(jīng)相連腸道上，它們有上千種。一個(gè)值得注意的細(xì)菌缺陷是普氏菌屬的缺少。這種細(xì)菌通過發(fā)酵膳食纖維中原本難以消化的碳水化合物聚合物為生，在非洲等地的農(nóng)民和狩獵采集者的消化道中大量存在，在西歐和美國(guó)很少見，在患有自閉癥的兒童中幾乎不存在。

詞匯

Autistic/孤獨(dú)癥的；孤僻的

Colonise/居??；開拓殖民地

Intestine/（脊椎動(dòng)物的）腸；

Ferment/發(fā)酵；動(dòng)亂；

Dietary/飲食的，飯食的；規(guī)定食物的

Fibre/纖維；纖維制品

Alimentary/滋養(yǎng)的；食物的

Canal/運(yùn)河； 水道

Their discovery led Dr Krajmalnik-Brown and Dr Adams to the idea that restoring the missing bacteria might alleviate autism’s symptoms. Two years ago they tested a process called microbiota transfer therapy (MTT) on 18 autistic children aged between seven and 16. Of their participants 15 were regarded, according to the Childhood Autism Rating Scale, as having “severe” autism.

他們的發(fā)現(xiàn)使krajmalick - brown博士和Adams博士認(rèn)為，修復(fù)缺失的細(xì)菌可能會(huì)減輕自閉癥的癥狀。兩年前，他們對(duì)18名年齡在7歲至16歲之間的自閉癥兒童進(jìn)行了一項(xiàng)名為“微生物群轉(zhuǎn)移療法”(MTT)的測(cè)試。根據(jù)兒童自閉癥評(píng)定量表，15名參與者被認(rèn)為患有“嚴(yán)重”自閉癥。

詞匯

Alleviate/減輕，緩和

Microbiota/小型生物群，微生物區(qū)

MTT is a prolonged version of a process already used to treat infection by a bug called Clostridium difficile, which causes life-threatening diarrhoea. It involves transplanting carefully prepared doses of faecal bacteria from a healthy individual to a patient. The researchers gave the children, first, an oral antibiotic, a bowel cleanse and an oral antacid (to ensure that microbes administered by mouth would survive their passage through the stomach). They followed this up with either an oral or a rectal dose of gut bacteria, and then, for seven to eight weeks, a daily antacid-assisted oral dose.

MTT是一種已經(jīng)用于治療難辨梭狀芽孢桿菌感染的過程的延長(zhǎng)版，這種細(xì)菌會(huì)導(dǎo)致危及生命的腹瀉。它包括將精心準(zhǔn)備的糞便細(xì)菌從健康個(gè)體移植到病人體內(nèi)。研究人員首先給這些孩子服用口服抗生素、排便劑和口服抗酸劑(以確?？谇恢械奈⑸锬茉谕ㄟ^胃的過程中存活下來)。隨后，他們用口服或直腸劑量的腸道細(xì)菌進(jìn)行跟蹤，然后，在七到八周的時(shí)間里，每天服用口服劑量的抗酸劑。

詞匯

Faecal/排泄物的

Rectal/直腸的

Ten weeks after treatment started the children’s Prevotella levels had multiplied 712-fold. In addition, those of another species, Bifidobacterium, had quadrupled. Bifidobacterium is what is known as a “probiotic” organism—something that acts as a keystone species in the alimentary ecosystem, keeping the mixture of gut bacteria healthy. Now, two years later, although levels of Prevotella have fallen back somewhat, they are still 84 times higher than they were before the experiment started. Levels of Bifidobacterium, meanwhile, have gone up still further—being five times higher than they had been at the beginning of the study. This, says Dr Krajmalnik-Brown, suggests the children’s guts have become healthy environments that can recruit beneficial microbes by themselves.

治療開始10周后，兒童的普氏菌屬量增加了712倍。此外，另一種雙歧桿菌的數(shù)量翻了兩番。雙歧桿菌是一種被稱為“益生菌”的生物，它是消化道生態(tài)系統(tǒng)中的關(guān)鍵物種，保持腸道細(xì)菌混合物的健康。兩年后的今天，盡管普氏菌屬量有所回落，但仍比實(shí)驗(yàn)開始前高出84倍。與此同時(shí)，雙歧桿菌的水平還在進(jìn)一步上升——比研究開始時(shí)高出5倍。krajmalick - brown博士說，這表明兒童的腸道已經(jīng)成為健康的環(huán)境，可以自己吸收有益的微生物。

詞匯

Prevotella/普氏菌屬

Probiotic/刺激微生物生長(zhǎng)的，益菌的

Microbe/?細(xì)菌，微生物

Crucially, these changes in gut bacteria have translated into behavioural changes. Even 18 weeks after treatment started the children had begun showing reduced symptoms of autism. After two years, only three of them still rated as severe, while eight fell below the diagnostic cut-off point for ASD altogether. These eight thus now count as neurotypical.

至關(guān)重要的是，腸道細(xì)菌的這些變化已經(jīng)轉(zhuǎn)化為行為變化。即使在治療開始18周后，孩子們的自閉癥癥狀也開始減輕。兩年后，其中只有3例仍然被評(píng)為嚴(yán)重，8例完全低于ASD的診斷分界點(diǎn)。因此，這八個(gè)現(xiàn)在被認(rèn)為是神經(jīng)系統(tǒng)正常的人。

Exactly how gut bacteria might contribute to autism is a puzzle. But light has been shed on the matter by the second study, published this week in Cell by a team led by Sarkis Mazmanian of the California Institute of Technology. Dr Mazmanian and a group of colleagues that also included Dr Krajmalnik-Brown performed a type of MTT on mice. They collected bacteria from the faeces of both neurotypical and autistic people (who ranged in their symptoms from mild to severe) and transplanted these into hundreds of mice. They then interbred the recipient mice and studied the offspring of these crosses—animals that had picked up the transplanted bacteria from their mothers at birth.

腸道細(xì)菌究竟是如何導(dǎo)致自閉癥的仍是個(gè)謎。但是，加州理工學(xué)院的Sarkis Mazmanian領(lǐng)導(dǎo)的研究小組本周在《細(xì)胞》雜志上發(fā)表的第二項(xiàng)研究為這個(gè)問題提供了線索。Mazmanian博士和一組包括krajmalick - brown博士在內(nèi)的同事對(duì)老鼠進(jìn)行了一種MTT試驗(yàn)。他們從神經(jīng)正常的人和自閉癥患者(癥狀從輕微到嚴(yán)重不等)的糞便中收集細(xì)菌，并將其移植到數(shù)百只老鼠身上。然后，他們將受體小鼠進(jìn)行雜交，并研究這些雜交小鼠的后代——這些動(dòng)物在出生時(shí)就從它們的母親那里獲得了被移植的細(xì)菌。

詞匯

Interbred/（使）異種交配

?

Signal results

信號(hào)的結(jié)果

?

They were looking for the rodent equivalent of ASD. And they found it. Most of the young mice harbouring gut bacteria from autistic human donors showed features of autism themselves. These included repetitive behaviours, reduced social and vocal communication with other mice, and restricted movement. In contrast, none of the mice colonised with bacteria from neurotypical people ended up autistic. Dr Mazmanian and his team discovered, moreover, that the intensity of a human donor’s autism was transferred to the recipient mice. If an individual’s symptoms were severe then so, too, were those of mice that hosted his gut bacteria.

他們正在尋找與ASD相當(dāng)?shù)膰X動(dòng)物。他們找到了。大多數(shù)攜帶自閉人類捐贈(zèng)者腸道細(xì)菌的幼鼠都表現(xiàn)出自閉的特征。這些包括重復(fù)行為，減少與其他老鼠的社交和聲音交流，以及限制運(yùn)動(dòng)。與此相反，沒有一只老鼠在帶有神經(jīng)正常的人細(xì)菌的環(huán)境下患上自閉癥。此外，Mazmanian博士和他的團(tuán)隊(duì)還發(fā)現(xiàn)，人類捐菌者的自閉癥強(qiáng)度會(huì)轉(zhuǎn)移到受體小鼠身上。如果一個(gè)人的癥狀很嚴(yán)重，那么那些攜帶腸道細(xì)菌的老鼠的癥狀也很嚴(yán)重。

詞匯

Harbour/隱匿；包庇攜帶

vocal/歌唱的；聲音的，有聲的；直言不諱的

Dr Mazmanian’s study also dealt with the question of mechanism. One long-held suspicion is that a molecule called gamma-aminobutyric acid (GABA) is involved. GABA is a neurotransmitter, meaning that it carries signals between nerve cells. In particular, it counters the action of another neurotransmitter, glutamate, that excites nervous activity in the brain. Studies have shown that levels of GABA are lower than normal in the brains of autistic children (though, inexplicably, not in autistic adults). Some researchers suspect that this deficiency takes the brakes off glutamate’s excitatory activity, thus stimulating things like repetitive behaviour.

Mazmanian博士的研究也涉及到機(jī)制的問題。一種長(zhǎng)期存在的懷疑是一種叫做伽馬氨基丁酸(GABA)的分子參與其中。GABA是一種神經(jīng)遞質(zhì)，意思是它在神經(jīng)細(xì)胞之間傳遞信號(hào)。特別是，它能對(duì)抗另一種神經(jīng)遞質(zhì)谷氨酸的作用，谷氨酸能刺激大腦中的神經(jīng)活動(dòng)。研究表明，自閉癥兒童大腦中的GABA水平低于正常水平(但令人費(fèi)解的是，這種情況不存在于成年的自閉癥患者種)。一些研究人員懷疑，這種缺乏會(huì)抑制谷氨酸的興奮性活動(dòng)，從而刺激重復(fù)性行為等。

詞匯

Molecule/分子；微小顆粒，微粒

Neurotransmitter/ 神經(jīng)遞質(zhì)

Glutamate/谷氨酸鹽

Dr Mazmanian and his colleagues produced evidence supporting this idea. They collected faeces, blood and brain tissue from the rodents in the experiment. When they analysed these they found that the “autistic” animals were deficient in taurine and 5-aminovaleric acid, two substances that stimulate GABA’s activity.

Mazmanian博士和他的同事提出了支持這一觀點(diǎn)的證據(jù)。他們從實(shí)驗(yàn)中的嚙齒動(dòng)物身上收集糞便、血液和腦組織。當(dāng)他們分析這些時(shí)，他們發(fā)現(xiàn)“自閉癥”動(dòng)物缺乏?；撬岷?-氨基戊酸，這兩種物質(zhì)刺激GABA的活動(dòng)。

詞匯

Taurine/ ?牛磺酸；氨基乙磺酸

?

They, too, drew potentially therapeutic conclusions from their results, and tested those conclusions by giving the missing substances to female mice carrying autism-inducing bacteria in the weeks before those females become pregnant. The resulting offspring, though still showing some symptoms of autism, scored 30% better on the rating scale than did the offspring of untreated females.

他們也從研究結(jié)果中得出了可能具有治療作用的結(jié)論，并通過在患有自閉癥的雌性小鼠懷孕前幾周給它們服用缺失的物質(zhì)來測(cè)試這些結(jié)論。由此產(chǎn)生的后代，雖然仍然表現(xiàn)出一些自閉癥的癥狀，但在評(píng)分量表上比未治療的女性的后代得分高30%。

詞匯

Therapeutic/治療的；治療學(xué)的

?

Meanwhile, the success of the study in Arizona has prompted America’s Food and Drug Administration (FDA) to look into the matter. A firm called Finch Therapeutics Group, based in Massachusetts, hopes to commercialise the use of MTT as a treatment for autism and the FDA has now granted this effort “fast track” status, which should speed up the review process. Dr Krajmalnik-Brown and Dr Adams are now recruiting volunteers for a large-scale trial of MTT for adults with autism, to see if they, too, can benefit. The paradigm, it seems, really is shifting.

與此同時(shí)，亞利桑那州研究的成功促使美國(guó)食品和藥物管理局(FDA)調(diào)查此事。馬薩諸塞州一家名為Finch Therapeutics Group的公司希望將MTT作為自閉癥治療手段的應(yīng)用商業(yè)化，美國(guó)食品藥品監(jiān)督管理局(FDA)現(xiàn)在已經(jīng)批準(zhǔn)了這一努力的“快車道”地位，這將加快審查進(jìn)程。krajmalick - brown博士和Adams博士正在招募志愿者，為成人自閉癥患者進(jìn)行大規(guī)模的MTT試驗(yàn)，看看他們是否也能從中受益。這種（治療）模式似乎正在發(fā)生轉(zhuǎn)變。

詞匯

paradigm/ 范式；范例