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代谢组:微生物组与人类健康的连接桥梁

放大字体  缩小字体 发布日期:2017-11-24
核心提示:人类微生物组是大型和复杂的。据认为,在你的身体中有许多土着微生物,因为有其他细胞,包括大约160种,存在于你的全身,包括你的口腔,你的皮肤,和你的肠道。样品从只有124个人metahit欧洲由欧洲联盟收集含有超过1000种不同的细菌物种基因330万独特的genes-150倍在人类基因互补。总之,科学家们对人类微生物组与自身的独特性,其自身的器官也是必要的,功能。
   研究人员需要看代谢组了解微生物与人体之间的动态关系
 
  编目人类微生物组有先进的生物医学研究通过揭示微生物对人体健康的重要性。
 
  在过去的15年中,科学家们开始描述他们认为是新发现的内分泌器官。到目前为止,他们发现它对于保护你免受感染和调节新陈代谢是至关重要的,而且它甚至可以影响你的行为。它可以被抗生素破坏,并且可以通过吞咽充满脱水粪便的胶囊来恢复。什么是这个不同寻常但功能多样的器官?它是人类微生物组。
 
  人类微生物组是大型和复杂的。据认为,在你的身体中有许多土着微生物,因为有其他细胞,包括大约160种,存在于你的全身,包括你的口腔,你的皮肤,和你的肠道。样品从只有124个人metahit欧洲由欧洲联盟收集含有超过1000种不同的细菌物种基因330万独特的genes-150倍在人类基因互补。总之,科学家们对人类微生物组与自身的独特性,其自身的器官也是必要的,功能。
 
  为了了解这种庞大多样的微生物细胞群,科学家们重新审视了他们20年前利用的方法来了解人类细胞的基因序列。事实上,微生物的基因组,宏基因组的研究,使得科学家能够描述和目录整个微生物获得它如何支持人类健康的一般认识。
 
  然而,基因组学并没有提供我们了解微生物与健康之间联系的所有信息。方法,如16S RNA(rRNA)测序和宏基因组学可以,在最好的情况下,揭示一个人的身份和给科学家微生物体内的微生物活性的估计。但基因组数据无法让科学家们直接窥视到人类微生物组动态和环境相互作用的。
 
  只有这样才能了解微生物的存在会影响身体在任何给定的时间是通过综合或全球代谢组收集代谢产物,微生物与宿主的相互作用产生的。代谢产物的微生物的语言。通过研究它们,除了他们来自微生物,科学家将揭示必然全面的微生物与人体之间不断变化的关系。代谢组学是最有效的,许多不同类的代谢物,包括外源性化学物质,细菌,和主机,需要同时测量。总之,试图不看代谢组解决微生物与人类健康的关系就像是试图预测一对夫妇的兼容性没有观察它们如何互相沟通。
 
  最近,研究代谢组学“喋喋不休”已导致发现在各个领域的疾病研究所不能描述的宏基因组本身的实现:
 
  ?而在哮喘和过敏的风险研究微生物和代谢组的婴儿,科学家发现这些条件不同的预测指标。研究人员最近比较微生物metabolomes和婴儿有不同程度的哮喘和过敏的易感性;其中最敏感的婴儿,他们发现在肠道细菌的天然缺陷。有趣的是,这一队列还显示了高浓度的促炎性T细胞和相对较低浓度的T细胞,可以抵抗哮喘和过敏。这些免疫的差异表明,在肠道微生物的同时,婴儿的代谢组学可以作为生物标志物来预测一个人的易过敏和哮喘。
 
  代谢产物也被发现链接微生物组精神疾病如自闭症。在一项研究中,一个自闭症小鼠模型表明在肠道中的两种菌的浓度升高和随后的代谢组学分析显示升高的几种代谢产物。令人震惊的是,把健康的小鼠与这些代谢产物引起自闭症样行为出现,证明因果关系的微生物和自闭症的症状。
 
  代谢组学可能是预防致死性艰难梭菌感染的关键。具有讽刺意味的是,艰难梭菌感染的最大危险因素之一是抗生素治疗。抗生素消灭了各种各样的本土细菌,创造了一种更适合艰难梭菌生长的环境。然而,由于抗生素的非特异性性质,很难确定一种土着细菌的灭绝是促进艰难梭菌生长的原因。
 
  但一个代谢组学分析发现,虽然抗生素杀死许多细菌物种,他们只会在一些代谢物浓度的变化,潜在的简化路径的治疗方法,不提倡艰难梭菌的生长发育。这些数据表明,除了编目如何改变肠道微生物的抗生素,确定它们是如何影响代谢组学是认识健康与疾病之间的关系的关键。
 
  代谢组学研究甚至可以理解肠道内血清素的合成,其中90%的人体血清素产生。肠道血清素与多种疾病有关,包括心血管疾病、肠易激综合征和骨质疏松症。直到最近,人们还不理解肠道内血清素的产生是如何调节的。代谢组学的研究表明,它是由土着的孢子形成的细菌释放代谢产物的调节,进一步确定了肠道微生物对人体健康的重要性。
 
  代谢组学已阐明微生物和许多其他条件从牙周病与肥胖的关系,其相关性是必然为我们了解更多关于我们的土着微生物在疾病中的作用增加。
 
  现在,我们要分析我们的与我们一起充满微生物代谢组的能力,我们相信这是集中不仅对微生物的遗传组成,而且它们产生的代谢物的生物医学研究社区的时间。由于代谢组学方法允许科学家检查体内所有的小分子,包括激素、氨基酸、共同因子、神经传递素和其他化合物,它使我们能够从基因到表型了解疾病病因的每一个步骤。
 
  编目人类微生物组有先进的生物医学研究通过揭示微生物对人体健康的重要性。现在,我们必须采取下一个步骤,利用代谢组学把我们剩下的路。因为它占人体所有的小分子,代谢组学是最全面的方法来研究微生物可用于检测和治疗疾病。由于其通用性和影响,我们不能忽视代谢组了。(Mike Milburn和Kirk Beebe)

       原文如下:

  Researchers Need to Look at the metabolome to Understand the Dynamic Relationship between the Microbiome and the Human Body
 
  Cataloguing the human microbiome has advanced biomedical research by revealing the importance of the microbiome in human health.
 
  · In the past 15 years, scientists have begun to characterize what they consider to be a newly discovered endocrine organ. So far, they have found that it is critical for protecting you against infection and regulating your metabolism, and that it can even affect your behavior. It can be damaged by antibiotics, and it can be restored by swallowing capsules filled with dehydrated fecal matter. What is this unusual yet versatile organ? It is the human microbiome.
 
  The human microbiome is large and complex. It is thought that there are as many indigenous microbes in your body as there are other cells, comprising about 160 species and present throughout your body—including in your mouth, on your skin, and in your intestines. Samples from only 124 European individuals collected by the European metaHIT consortium contained more than 1,000 different bacterial species with 3.3 million unique genes—150 times more genes than in the human gene complement. Altogether, scientists treat the human microbiome as its own organ with its own unique, but necessary, functions.
 
  To make sense of this vast and diverse population of microbial cells, scientists have revisited an approach that they exploited 20 years ago to understand human cells—genetic sequencing. In fact, the study of the microbiome’s genome, the metagenome, has allowed scientists to characterize and catalog the entire microbiome and gain a general understanding of how it supports human health.
 
  Genomics, however, does not give us all the information we need to understand the link between microbes and health. Approaches like 16S RNA (rRNA) sequencing and metagenomics can, at best, reveal the identity of an individual’s microbiota and give scientists an estimation of microbial activity in the body. But genomic data alone is unable to give scientists a direct peek into how the human microbiome dynamically interacts with its surroundings.
 
  The only way to understand how the microbiome’s presence affects the body at any given time is through studying the comprehensive or global metabolome—the collection of metabolites that the microbiome and host produces and interacts with. metabolites are the microbiome’s language. By studying them, in addition to the microbes they come from, scientists will reveal an invariably fuller picture of the ever-changing relationship between the microbiome and the human body. For metabolomics to be most effective, many different classes of metabolites, including xenobiotics, bacterial, and host, need to be measured simultaneously. In short, trying to resolve the link between the microbiome and human health without looking at the metabolome is like trying to predict a married couple’s compatibility without observing how they communicate with each other.
 
  Recently, studying this metabolomic “chatter” has led to discoveries in all areas of disease research that could not be achieved by characterizing the metagenome itself:
 
  While studying the microbiome and metabolome of infants at risk for asthma and allergy, scientists discovered distinct predictive biomarkers for these conditions. Researchers recently compared the microbiomes and metabolomes of infants with varying levels of susceptibility to asthma and allergy; and among the most susceptible infants, they found deficiencies of several native bacterial species in the gut. Interestingly, this cohort also displayed high concentrations of pro-inflammatory T-cells and relatively low concentrations of T cells that protect against asthma and allergy. These immunological differences suggest that, in conjunction with the gut microbiome, an infant’s metabolome can be used as a biomarker to predict one’s susceptibility to allergy and asthma.
 
  metabolites have also been found to link the microbiome to psychiatric disorders such as autism. In one study, a mouse model for autism showed an elevation in the concentration of two bacterial species in the gut, and a subsequent metabolomic analysis revealed elevated levels of several metabolites. Shockingly, injecting healthy mice with one of these metabolites caused autistic-like behaviors to arise, proving the causal link between the microbiome and autistic symptomatology.
 
  metabolomics may also be the key to preventing lethal C. difficile infections. Ironically, one of the largest risk factors for C. difficile infection is antibiotic treatment. Antibiotics wipe out a wide variety of indigenous bacteria, creating an environment that is more suitable for C. difficile growth. Due to the nonspecific nature of antibiotics, however, it is difficult to determine which extinction of an indigenous bacterial species was responsible for promoting C. difficile growth.
 
  But a metabolomic analysis found that while antibiotics kill many bacterial species, they only cause a change in the concentrations of a few metabolites, potentially simplifying the path to the development of treatments that do not promote C. difficile growth. These data show that, in addition to cataloguing how antibiotics alter the gut microbiome, identifying how they affect the metabolome is critical for understanding the relationship between health and disease.
 
  metabolomics research can even yield an understanding of serotonin synthesis in the gut, where 90% of the body’s serotonin is produced. Gut serotonin has been implicated in several disorders, including cardiovascular disease, irritable bowel syndrome, and osteoporosis. Until recently, it was not understood how serotonin production in the gut is regulated. A metabolomics study revealed that it is regulated by metabolites released by indigenous spore-forming bacteria, further confirming the importance of the gut microbiome to human health.
 
  metabolomics has elucidated the link between the microbiome and many other conditions ranging from periodontal disease to obesity, and its relevance is only bound to increase as we learn more about the role of our indigenous microbes in disease.
 
  Now that we have the ability to profile our full metabolome in conjunction with our microbiome, we believe it is time for the biomedical research community to concentrate not only on the genetic makeup of the microbiome but also the metabolites they produce. Since a metabolomics approach allows scientists to examine all the small molecules in our body, including hormones, amino acids, co-factors, neurotransmitters, and other compounds, it gives us a shot at understanding every step of disease etiology, from gene to phenotype.
 
  Cataloguing the human microbiome has advanced biomedical research by revealing the importance of the microbiome in human health. Now, we must take the next step and use the metabolome to bring us the rest of the way. Since it accounts for all the small molecules in the body, metabolomics is the most comprehensive approach to studying how the microbiome can be used to detect and treat disease. Given its versatility and impact, we cannot afford to overlook the metabolome anymore. (by Mike Milburn and Kirk Beebe)

 
 
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