Autism-spectrum disorder

自闭症谱系障碍

More evidence that autism is linked to gut bacteria

更多的证据表明自闭症与肠道细菌有关

词汇

Gut/内脏；肠子

Understanding that link may be crucial to treatment

理解这种联系对治疗可能是至关重要的

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.

范式转换是一个被过度使用的术语。正确地说，它指的是对一个话题的观点的根本性转变，比如从牛顿物理学转向爱因斯坦物理学，或者把板块构造学引入地质学。这样的事情很少见。然而，一些历史上可能被视为真正范式转变的事情，似乎正在医学领域发生。这是一种认识，即人体上和体内的大量非致病菌对人们的健康实际上非常重要。它们甚至可能有助于解释一些神秘情况的形成。

词汇

PARADIGM SHIFT /典范转移；思考模式的转移

Radical/激进的；根本的；彻底的

Tectonic/构造的；建筑的

Zillion/ 庞大的数字；无法计算的大数字；

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.

其中一种情况就是自闭症——现在通常被称为自闭症谱系障碍(ASD)。ASD的特征是重复、刻板和受限的行为，比如点头，以及患有ASD的人在阅读他人情绪和与他人沟通方面存在的困难。这些症状在两岁以上的儿童中很明显。目前，在美国，大约每59个孩子中就有一个被诊断出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世纪中叶汉斯·阿斯伯格(Hans Asperger)和里奥·坎纳(Leo Kanner)首次描述ASD以来，ASD的病因一直困扰着精神病学家和神经学家。但证据指向肠道细菌。最近发表的两项研究——一项关于人类，另一项关于实验室啮齿类动物——进一步证实了这一观点。

词汇

Syndrome/综合症状；并发症状

Rodent/  啮齿目动物

Restoring the balance

恢复平衡

 

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.

亚利桑那州立大学的Rosa krajmalick - brown和她的同事们正在进行这项人体研究，其最新结果几周前发表在《科学报告》上。这项研究是由krajmalick - brown博士和他在亚利桑那州立大学的同事James Adams对20名自闭症儿童肠道细菌的DNA进行测序后得出的，目的是发现存在哪些种类的细菌。他们发现，在他们的样本中，儿童缺失了数百种细菌，而这些细菌寄生在人体与神经相连肠道上，它们有上千种。一个值得注意的细菌缺陷是普氏菌属的缺少。这种细菌通过发酵膳食纤维中原本难以消化的碳水化合物聚合物为生，在非洲等地的农民和狩猎采集者的消化道中大量存在，在西欧和美国很少见，在患有自闭症的儿童中几乎不存在。

词汇

Autistic/孤独症的；孤僻的

Colonise/居住；开拓殖民地

Intestine/（脊椎动物的）肠；

Ferment/发酵；动乱；

Dietary/饮食的，饭食的；规定食物的

Fibre/纤维；纤维制品

Alimentary/滋养的；食物的

Canal/运河； 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.

他们的发现使krajmalick - brown博士和Adams博士认为，修复缺失的细菌可能会减轻自闭症的症状。两年前，他们对18名年龄在7岁至16岁之间的自闭症儿童进行了一项名为“微生物群转移疗法”(MTT)的测试。根据儿童自闭症评定量表，15名参与者被认为患有“严重”自闭症。

词汇

Alleviate/减轻，缓和

Microbiota/小型生物群，微生物区

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是一种已经用于治疗难辨梭状芽孢杆菌感染的过程的延长版，这种细菌会导致危及生命的腹泻。它包括将精心准备的粪便细菌从健康个体移植到病人体内。研究人员首先给这些孩子服用口服抗生素、排便剂和口服抗酸剂(以确保口腔中的微生物能在通过胃的过程中存活下来)。随后，他们用口服或直肠剂量的肠道细菌进行跟踪，然后，在七到八周的时间里，每天服用口服剂量的抗酸剂。

词汇

Faecal/排泄物的

Rectal/直肠的

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.

治疗开始10周后，儿童的普氏菌属量增加了712倍。此外，另一种双歧杆菌的数量翻了两番。双歧杆菌是一种被称为“益生菌”的生物，它是消化道生态系统中的关键物种，保持肠道细菌混合物的健康。两年后的今天，尽管普氏菌属量有所回落，但仍比实验开始前高出84倍。与此同时，双歧杆菌的水平还在进一步上升——比研究开始时高出5倍。krajmalick - brown博士说，这表明儿童的肠道已经成为健康的环境，可以自己吸收有益的微生物。

词汇

Prevotella/普氏菌属

Probiotic/刺激微生物生长的，益菌的

Microbe/ 细菌，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.

至关重要的是，肠道细菌的这些变化已经转化为行为变化。即使在治疗开始18周后，孩子们的自闭症症状也开始减轻。两年后，其中只有3例仍然被评为严重，8例完全低于ASD的诊断分界点。因此，这八个现在被认为是神经系统正常的人。

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.

肠道细菌究竟是如何导致自闭症的仍是个谜。但是，加州理工学院的Sarkis Mazmanian领导的研究小组本周在《细胞》杂志上发表的第二项研究为这个问题提供了线索。Mazmanian博士和一组包括krajmalick - brown博士在内的同事对老鼠进行了一种MTT试验。他们从神经正常的人和自闭症患者(症状从轻微到严重不等)的粪便中收集细菌，并将其移植到数百只老鼠身上。然后，他们将受体小鼠进行杂交，并研究这些杂交小鼠的后代——这些动物在出生时就从它们的母亲那里获得了被移植的细菌。

词汇

Interbred/（使）异种交配

 

Signal results

信号的结果

 

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.

他们正在寻找与ASD相当的啮齿动物。他们找到了。大多数携带自闭人类捐赠者肠道细菌的幼鼠都表现出自闭的特征。这些包括重复行为，减少与其他老鼠的社交和声音交流，以及限制运动。与此相反，没有一只老鼠在带有神经正常的人细菌的环境下患上自闭症。此外，Mazmanian博士和他的团队还发现，人类捐菌者的自闭症强度会转移到受体小鼠身上。如果一个人的症状很严重，那么那些携带肠道细菌的老鼠的症状也很严重。

词汇

Harbour/隐匿；包庇携带

vocal/歌唱的；声音的，有声的；直言不讳的

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机制的问题。一种长期存在的怀疑是一种叫做伽马氨基丁酸(GABA)的分子参与其中。GABA是一种神经递质，意思是它在神经细胞之间传递信号。特别是，它能对抗另一种神经递质谷氨酸的作用，谷氨酸能刺激大脑中的神经活动。研究表明，自闭症儿童大脑中的GABA水平低于正常水平(但令人费解的是，这种情况不存在于成年的自闭症患者种)。一些研究人员怀疑，这种缺乏会抑制谷氨酸的兴奋性活动，从而刺激重复性行为等。

词汇

Molecule/分子；微小颗粒，微粒

Neurotransmitter/ 神经递质

Glutamate/谷氨酸盐

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这一观点的证据。他们从实验中的啮齿动物身上收集粪便、血液和脑组织。当他们分析这些时，他们发现“自闭症”动物缺乏牛磺酸和5-氨基戊酸，这两种物质刺激GABA的活动。

词汇

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.

他们也从研究结果中得出了可能具有治疗作用的结论，并通过在患有自闭症的雌性小鼠怀孕前几周给它们服用缺失的物质来测试这些结论。由此产生的后代，虽然仍然表现出一些自闭症的症状，但在评分量表上比未治疗的女性的后代得分高30%。

词汇

Therapeutic/治疗的；治疗学的

 

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.

与此同时，亚利桑那州研究的成功促使美国食品和药物管理局(FDA)调查此事。马萨诸塞州一家名为Finch Therapeutics Group的公司希望将MTT作为自闭症治疗手段的应用商业化，美国食品药品监督管理局(FDA)现在已经批准了这一努力的“快车道”地位，这将加快审查进程。krajmalick - brown博士和Adams博士正在招募志愿者，为成人自闭症患者进行大规模的MTT试验，看看他们是否也能从中受益。这种（治疗）模式似乎正在发生转变。

词汇

paradigm/ 范式；范例