2014年7月21日 星期一

We Are Our Bacteria「我們更多的是微生物」體內微生物平衡對健康至關重要



體內微生物平衡對健康至關重要

個人健康2014年07月14日
Ken Orvidas
我們或許認為自己只是一個人,但我們實際上是寄存在人體軀殼內的大量微生物。每個活着的人體內都有大約100萬億個微生物細胞。微生物細胞的數量是人體細胞的10倍,在人體的獨特基因中佔99.9%。
《自然評論》(Nature Review)的高級編輯卡特里娜·雷(Katrina Ray)最近表示,可以把內臟中的大量微生物當作一個「人類微生物『器官』」,並問道,「我們更多的是微生物,還是人?」
我們的微生物菌群,也就是微生物組,相當於人體中的環境生態系統。雖然細菌的總重量只有三磅,它們的構成在很大程度上決定着人體的運轉,哎,以及機能失常。
就像全世界的生態系統一樣,人類微生物菌群正在失去它們的多樣性,以至於可能會損害它們所寄居的主體的健康。
紐約大學醫學院(New York University School of Medicine)傳染病專家、 人類微生物組計劃(Human Microbiome Program)負責人馬丁·J·布拉澤(Martin J. Blaser)博士在過去30多年間,一直研究細菌在疾病中發揮的作用。除傳染病外,他的研究範圍還囊括了自體免疫疾病,以及其他在世界範圍內急劇增加的疾病。
布拉澤在他的新書《消失的微生物》(Missing Microbes)中表示,微生物組多樣性的減少導致我們更容易感染嚴重且通常都是慢性的疾病——從過敏、乳糜瀉到一型糖尿病和肥胖症。布拉澤及其他人認為,這主要是由抗生素造成的。
布拉澤表示,抗生素很早就開始對微生物多樣性產生破壞。普通的美國兒童在出生的頭兩年要接受大約三個療程的抗生素,在接下來的八年里,要再進行八個療程。很短療程的抗生素就能致使人體的微生物環境發生長期轉變,比如被廣泛使用的Z-pack(阿奇黴素,服用五天)。
但抗生素並不是破壞平衡的唯一因素。布拉澤接受採訪時表示,近幾十年,選擇剖腹產的人激增,剖腹產促使嬰兒內臟中的微生物來自母親的皮膚,而不是產道。
微生物組的變化能夠改變嬰兒的新陳代謝和免疫系統。最近,相關人員查閱了15項共涉及16萬3796個分娩案例的研究,結果發現,與順產的嬰兒相比,剖腹產嬰兒成人後超重的幾率要高26%,肥胖的風險要高22%。
胎盤有自己的微生物,研究人員發現,這個微生物組可能也有助於嬰兒的內臟健康,減少由剖腹產引發的微生物損耗。
其他研究發現了正常體重者與肥胖者腸道中微生物的主要差異。雖然這些研究不能說明最先出現的是哪個問題——體重問題或微生物組的變化,但研究說明,肥胖的老鼠體內存在能夠更好地從食物中吸取熱量的腸道菌群。
與肥胖相關的進一步證據來自農場里的動物。在美國出售的抗生素中,大約有四分之三都用在牲畜身上。這些抗生素改變了動物的微生物菌群,加快了它們的生長速度。
布拉澤說,當我們把用於牲畜的抗生素用在老鼠身上時,它們的新陳代謝就會發生改變,並促使它們的體脂增加。
更嚴重的是,如今有越來越多嚴重的功能失調都與人類內髒的微生物平衡被破壞有關。其中有幾種在發達國家中變得越來越常見:克隆氏症、潰瘍性結腸炎和乳糜瀉等胃腸疾病;心血管疾病;非酒精性脂肪肝;慢性反流症等消化失調問題;多發性硬化和風濕性關節炎等自體免疫疾病,以及哮喘和過敏。
有些研究人員甚至推斷,內臟微生物菌群失調是造成乳糜瀉的原因,所以甚至連沒得這種病的人對無麩質食物的需求也會激增。布拉澤說,以患1型糖尿病的老鼠為例,對這些動物使用抗生素,只會加速疾病的發展。
他和其他研究人員,其中包括來自瑞士和德國的一組研究人員也認為哮喘患病率的大幅上升與「幽門螺桿菌從西方社會快速消失有關,幽門螺桿菌是一種長期寄存在人類胃裡的細菌性病原體」。曾幾何時,幾乎每個人體內都有這種細菌,歐洲研究者已經證明它能防止老鼠出現過敏性哮喘的癥狀。
在生命的早期階段,幽門螺桿菌的存在能促使血液中產生T細胞。布拉澤表示,壓制過敏反應就需要這種細胞。他的研究表明,雖然有些類型的幽門螺桿菌與消化性潰瘍和胃癌有關,但其他類型則具有保護作用。
布拉澤和同事的研究進一步表明,胃部的幽門螺桿菌能夠防止胃食管返流疾病、巴雷特氏食管和食道癌。
然而,研究者不是總能說明腸道菌群紊亂會在人們生病之前還是之後出現。不過,對實驗室動物的研究往往表明,菌群紊亂會發生在生病之前。
布拉澤等人提醒人們注意不要濫用抗生素,尤其是現在普遍使用的用途廣泛的藥物。他突出強調了減少在兒童身上使用抗生素的重要性。
「在瑞典,任何年齡段中,抗生素的使用都只是我們的40%,但是他們的得病率沒有增加,」他說。「我們要告訴醫生和家長,抗生素是有代價的。我們需要改進診斷。導致感染的究竟是病毒還是細菌,如果是細菌,那麼是哪一種?」
「然後我們需要運用窄譜抗菌素來消滅病原菌,同時又不對那些有益健康的菌群造成影響,」布拉澤說。「這就能讓人們在治療嚴重感染的同時,產生更小的副作用。」
翻譯:許欣、陳柳

We Are Our Bacteria

July 14, 2014

We may think of ourselves as just human, but we’re really a mass of microorganisms housed in a human shell. Every person alive is host to about 100 trillion bacterial cells. They outnumber human cells 10 to one and account for 99.9 percent of the unique genes in the body.
Katrina Ray, a senior editor of Nature Reviews, recently suggested that the vast number of microbes in the gut could be considered a “human microbial ‘organ’” and asked, “Are we more microbe than man?”
Our collection of microbiota, known as the microbiome, is the human equivalent of an environmental ecosystem. Although the bacteria together weigh a mere three pounds, their composition determines much about how the body functions and, alas, sometimes malfunctions.
Like ecosystems the world over, the human microbiome is losing its diversity, to the potential detriment of the health of those it inhabits.
Dr. Martin J. Blaser, a specialist in infectious diseases at the New York University School of Medicine and the director of the Human Microbiome Program, has studied the role of bacteria in disease for more than three decades. His research extends well beyond infectious diseases to  autoimmune conditions and other ailments that have been increasing sharply worldwide.
In his new book, “Missing Microbes,” Dr. Blaser links the declining variety within the microbiome to our increased susceptibility to serious, often chronic conditions,  from allergies and celiac disease to Type 1 diabetes and obesity. He and others primarily blame antibiotics for the connection.
The damaging effect of antibiotics on microbial diversity starts early, Dr. Blaser said. The average American child is given nearly three courses of antibiotics in the first two years of life, and eight more  during the next eight years. Even a short course of antibiotics like the widely prescribed  Z-pack (azithromycin, taken for five days), can result in long-term shifts in the body’s microbial environment.
But antibiotics are not the only way the balance within us can be disrupted. Cesarean deliveries, which  have soared  in recent decades, encourage the growth of microbes from the mother’s skin, instead of from the birth canal, in the baby’s gut, Dr. Blaser said in an interview.
This change in microbiota can reshape an infant’s metabolism and immune system. A recent review of 15 studies involving 163,796 births found that, compared with  babies delivered vaginally, those born by cesarean section were 26 percent more likely to be overweight and 22 percent more likely to be obese as adults.
The placenta has a microbiome of its own, researchers have discovered, which may also contribute to the infant’s gut health and help mitigate the microbial losses caused by cesarean sections.
Other studies have found major differences in the microorganisms living in the guts of normal-weight and obese individuals. Although such studies cannot tell which came first — the weight problem or the changed microbiota — studies indicate obese mice have gut bacteria that are better able to extract calories from food.
Further evidence of a link to obesity comes from farm animals. About three-fourths of the antibiotics sold in the United States are used  in  livestock. These  antibiotics change the animals’ microbiota, hastening their growth.
When mice are given the same  antibiotics used on livestock, the metabolism of their liver changes, stimulating an increase in body fat, Dr. Blaser said.
Even more serious is  the increasing number of serious disorders now linked to a distortion in the microbial balance in the human gut. They include several that are becoming more common in developed countries: gastrointestinal ailments like Crohn’s disease, ulcerative colitis and celiac disease; cardiovascular disease; nonalcoholic fatty liver disease; digestive disorders like chronic reflux; autoimmune diseases like multiple sclerosis and rheumatoid arthritis; and asthma and allergies.
Some researchers have even speculated that  disruptions of gut microbiota play a role in celiac disease and the resulting explosion in demand for gluten-free foods even among people without this disease.  In a mouse model of Type 1 diabetes, treating the animals with antibiotics accelerates the development of the disease, Dr. Blaser said.
He and other researchers, including a team from Switzerland and Germany, have also linked  the serious rise in asthma rates to the “rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies.” Once, virtually everyone harbored this microbe, which European researchers have shown protected mice from developing hallmarks of allergic asthma.
H. pylori colonization in early life encourages  production of regulatory T-cells in the blood, which Dr. Blaser said are needed to tamp down allergic responses. Although certain strains of H. pylori are linked to the development of peptic ulcer and stomach cancer, other strains are protective, his studies indicate.
Research by Dr. Blaser and his colleagues further suggests that H. pylori in the stomachprotects against gastroesophageal reflux diseaseBarrett’s esophagus and esophageal cancer.
Still, it is not always possible for researchers to tell whether disruptions in gut microbiota occur before or after people become ill. However, studies in laboratory animals often suggest the bacterial disturbances come first.
Dr. Blaser, among many others, cautions against the overuse of antibiotics, especially the broad-spectrum drugs now commonly prescribed. He emphasized in particular the importance of using fewer antibiotics in  children.
“In Sweden, antibiotic use is 40 percent of ours at any age, with no increase in disease,” he said. “We need to educate physicians and parents that antibiotics have costs. We need improved diagnostics. Is the infection caused by a virus or bacteria, and if bacteria, which one?
“Then we need narrow-spectrum antibiotics designed to knock out the pathogenic bacteria without disrupting the health-promoting ones,” Dr. Blaser added. “This will make it possible to treat serious infections with less collateral effect.”

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