他她話題:現代醫學 微生物造就人類(上)

POLITICAL revolutionaries turn the world upside down. Scientific ones more often turn it inside out. And that, almost literally, is happening to the idea of what, biologically speaking, a human being is.

世界在政治革命家手中上下顛倒，在科技革命者手中卻常常裏外顛倒。在字面上來看，這句話恰巧從生物學角度解釋了：人類到底是什麼。

The traditional view is that a human body is a collection of 10 trillion cells which are themselves the products of 23,000 genes. If the revolutionaries are correct, these numbers radically underestimate the truth. For in the nooks and crannies of every human being, and especially in his or her guts, dwells the microbiome: 100 trillion bacteria of several hundred species bearing 3m non-human genes. The biological Robespierres believe these should count, too; that humans are not single organisms, but superorganisms made up of lots of smaller organisms working together.

傳統觀點認爲，人體是十萬億個細胞的集合體，這些細胞又是23000個基因表達後的生成物。如果生物革命者的觀點正確，那這些數字就遠遠的低估了實際情況。因爲在人體的各個部位，尤其是內臟寄居着微生物羣落：來自幾百個類型的上百萬億個細胞攜帶着300萬個非人類基因。生物學家羅伯斯比爾認爲：這些數字是有價值的，因爲人體不是單一的有機個體，而是由成千上萬個微小的有機體共同作用構成的超級個體。

It might sound perverse to claim bacterial cells and genes as part of the body, but the revolutionary case is a good one. For the bugs are neither parasites nor passengers. They are, rather, fully paid-up members of a community of which the human "host" is but a single (if dominating) member. This view is increasingly popular: the world's leading scientific journals, Nature and Science, have both reviewed it extensively in recent months. It is also important: it will help the science and practice of medicine.

要說細菌、細胞和基因是人體的一部分，可能令人無法接受，但這一革命性的結論確是有益的。這些小東西既非寄生生物，也非人體系統的過客，而是人體獨立這個宿主環境內的忠實成員。這個觀點越來越普及，全球先進的科學報刊《自然》和《科學》，用大篇幅對該觀點進行評論，它的重要性在於能夠幫助醫學理論和實踐的發展。

All in this together

齊聚一堂

The microbiome does many jobs in exchange for the raw materials and shelter its host provides. One is to feed people more than 10% of their daily calories. These are derived from plant carbohydrates that human enzymes are unable to break down. And not just plant carbohydrates. Mother's milk contains carbohydrates called glycans which human enzymes cannot digest, but bacterial ones can.

微生物羣落通過許多工作向人體換取生存原材料和環境。有一種微生物向人體提供每月所需熱量的10%，這些熱量產生自一種人體酶無法分解的植物碳水化合物，其實不僅是植物糖類，人類母乳中包含的多糖也無法被人體自身的酶消化，細菌酶卻可以。

This alone shows how closely host and microbiome have co-evolved over the years. But digestion is not the only nutritional service provided. The microbiome also makes vitamins, notably B2, B12 and folic acid. It is, moreover, capable of adjusting its output to its host's needs and diet. The microbiomes of babies make more folic acid than do those of adults. And microbiomes in vitamin-hungry places like Malawi and rural Venezuela turn out more of these chemicals than do those in the guts of North Americans.

這個例子只能說明人體和微生物羣落是如何在幾十年內協同作用產生進化的。但消化只是微生物爲人體提供的多種營養服務之一，它們還能產生維生素，特別是B2、B12和葉酸（維生素B），此外它還能根據人體需要和膳食情況調節產量。嬰兒體內的微生物可以產生比成人多的維B，維生素缺乏地區，如馬拉維和委內瑞拉的農村，這些地方的人們內臟產生的維生素就要多於北美地區。

The microbiome also maintains the host's health by keeping hostile interlopers at bay. An alien bug that causes diarrhoea, for instance, is as much an enemy of the microbiome as of the host. Both have an interest in zapping it. And both contribute to the task. Host and microbiome, then, are allies. But there is more to it than that. For the latest research shows their physiologies are linked in ways which make the idea of a human superorganism more than just a rhetorical flourish.

微生物還通過抵禦外界有毒物質入侵，幫助人體的健康。例如引起腹瀉的細菌，是人體和體內微生物共同的敵人，兩者都希望消滅它，這就需要"宿主"與微生物羣聯合才能完成任務。除此以外，近期研究還表明，人體與微生物在生理機能上也存在一定的聯繫，這讓人體是超級個體的說法脫離了繁冗修辭的嫌疑。

These links are most visible when they go wrong. A disrupted microbiome has been associated with a lengthening list of problems: obesity and its opposite, malnutrition; diabetes (both type-1 and type-2); atherosclerosis and heart disease; multiple sclerosis; asthma and eczema; liver disease; numerous diseases of the intestines, including bowel cancer; and autism. The details are often obscure, but in some cases it looks as if bugs are making molecules that help regulate the activities of human cells. If these signals go wrong, disease is the consequence. This matters because it suggests doctors have been looking in the wrong place for explanations of these diseases. It also suggests a whole new avenue for treatment. If an upset microbiome causes illness, settling it down might effect a cure.

生理機能上的聯繫在它出現問題時體現得更加突出，微生物功能將產生許多問題：過度肥胖或消瘦；營養不良；1型和2型糖尿病；動脈硬化和心臟病；多發性硬化症；哮喘和溼疹；肝病；腸道內的多種疾病，包括腸道癌；孤獨症。這些問題的細節不甚明瞭，但在一些病例中反應出，似乎微生物製造的分子可以幫助調節人體細胞功能。這一點很重要，因爲它反映出醫生在分析這些疾病時錯誤的切入點。同時也提出了出全新的治療方法，如果是微生物功能紊亂引起疾病，那隻需要解決這個問題就可能治癒。

Yogurt companies and health-food fanatics have been banging this drum for years. And in the case of at least one malady, irritable-bowel syndrome, they are right. So-called probiotics, a mixture of about half a dozen bacterial species found in yogurt, do act to calm this condition. But there is little evidence that consuming probiotics has the tonic effect on healthy people that certain adverts suggest.

酸奶製造商和營養品熱衷者多年前就鼓吹這種說法。但至少在過敏性腸道綜合症這個病症上，他們說對了，所謂的益生菌，主要存在於酸奶中，混合了大約六個菌種，可以緩解這一病症。但有些廣告說益生菌對人體有滋補作用，目前暫無證據可以證實。

A handful of doctors are taking a more fundamental approach to another microbiome-related disease, infection with Clostridium difficile. This bacterium, which causes life-threatening distension of the gut in some people who have been treated with antibiotics and thus had their microbiomes disrupted, is a bane of hospitals. It kills 14,000 people a year in America alone. But recent experiments have shown it can be eliminated by introducing, as an enema, the faeces of a healthy individual. "Stool transplants" are a pretty crude approach, to be sure, but the crucial point is that microbes are much easier to manipulate than human cells. For all the talk of superorganisms (and despite the yuck factor of what is being moved from one body to another), transplanting a microbiome is far easier than transplanting a heart or a kidney.

一小部分醫生採取更爲基本的方式治療另外一與微生物有關的疾病：梭狀芽胞桿菌感染。一些病患曾接受抗生素治療。導致體內微生物羣落紊亂。梭狀芽胞桿菌可以引起致命的腸道擴張，這種病向來是讓醫院極其苦惱的，僅在美國，每年死於該疾病的就有14000人。但近期有實驗結果表明，可將一個健康人體的糞便，用灌腸劑的方法引入體內消除這類芽胞桿菌。糞便移植的確是種殘忍的手段，不可否認，但關鍵在於處理微生物要比人體細胞簡便得多。儘管關於超級有機體衆說紛紜，儘管在人體間轉移的東西很噁心，移植微生物的簡易性遠不是心臟或腎臟移植可比。