The Human Microbiome and the Future Practice of Medicine.
The Human Microbiome and the Future Practice of Medicine.
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人类微生物组和未来的医学实践。
DOI：
10.1001/jama.2015.10700
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
D. Relman
中科院分区：
文献类型：
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作者：
D. Relman
所有动物都与微生物以亲密、依赖的关系共存。人类也不例外。与宿主相关的微生物，就像地球上几乎所有的其他微生物一样，形成群落，其中的整体组成，结构和功能由生态过程和环境因素解释。相互适应和互利的证据是宿主与其微生物群落或微生物群之间共生的关键特征。1人类微生物群是人类的基本组成部分。最近的研究表明，人类从微生物中获得的益处可能对健康产生深远的影响。这些益处包括宿主粘膜的分化、食物消化和营养、代谢的调节、环境化学物质的加工和解毒、免疫系统的发育和持续调节以及预防病原体的入侵和生长。相反，人类微生物群及其集体基因和基因组（即微生物组）的干扰和改变与多种人类疾病相关，如慢性牙周炎，炎症性肠病和腹泻相关性腹泻。第一次直接观察和测量人类微生物群是在300多年前，随着显微镜和牙齿刮屑的出现。从那时起，研究人类微生物群的工具在范围、复杂性和可用性方面都有所扩展。目前对这一主题的兴趣激增，部分反映了DNA测序技术的最新进展及其在直接从环境样品中表征微生物世界中的应用，以及对生态学原理的重新认识，包括生物体之间相互作用的重要性;微生物群落的形成，活动和稳定性;以及群落与环境之间的关系。对人类微生物群的研究具有改善人类健康和疾病管理的巨大潜力。身体部位是人类微生物群组成多样性变化的最强决定因素之一。2例如，健康个体暴露的牙齿表面上的微生物群落通常与另一健康个体牙齿上的微生物群落的分类组成比同一个体舌头上的微生物群落的分类组成更相似。相比之下，当来自同一身体部位的样本在一组不同的健康个体中进行比较时，个体特异性微生物群特征是明显的。微生物群分类和基因组组成的生物地理模式反映了在不同身体部位发现的不同选择压力，以及对群落演替、扩散速率和当地微生物多样化的优先影响。微生物群落之间微妙的区别特征可能会告诉我们正常和异常人体生理学和细胞生物学中重要的潜在变化。例如，不同类型的上皮细胞、温度和其他环境条件与鼻前鼻孔、中鼻道和筛窦隐窝之间不同的细菌群落相关，并与感兴趣的群落成员（如金黄色葡萄球菌）之间不同的竞争相互作用相关。3从高多样性的口腔栖息地到低多样性的阴道栖息地，微生物地理学表明，人类景观中存在不同的生态区（图）。在皮肤上，有3种类型的微生物群落，每种都具有干燥、潮湿或皮脂腺环境的特征。4痤疮丙酸杆菌、葡萄球菌、棒状杆菌属和丙酸杆菌噬菌体解释了这些群落类型之间的最大变化;真菌和其他真核微生物相对罕见。痤疮丙酸杆菌菌株倾向于对个体具有特异性，而表皮葡萄球菌菌株倾向于对身体部位具有特异性。DNA病毒，特别是细菌病毒（噬菌体），在皮肤和人体粘膜的其他地方的个体之间的数量和类型差异很大，并且在鼻子和阴道中相对丰富。因为它们可以杀死细菌或通过携带新基因来修改它们，所以它们有助于塑造人类微生物群的结构和功能。微生物群结构和功能的位点特异性特征可以作为未来局部疾病的早期标志。慢性牙周炎、龋齿、特应性皮炎和克罗恩病等局灶性过程对于识别此类特征来说是有吸引力的环境。小分子介导微生物群落成员之间的各种相互作用，从而促进群落稳定;对于人类微生物群，小分子也介导和促进宿主适应。随着用于基于其“元基因组”来识别复杂混合群落的推定产物的计算工具的出现，在人类微生物群中发现了大量新分子。其中一些已经证明具有显著的医学潜力的药物样活性。5最近对直接从5个身体部位的人类微生物群样本中获得的宏基因组序列数据的检查鉴定出超过3000个生物合成基因簇，每个预测产生小molVIEWPOINT。
All animals coexist in intimate, dependent relationships with microbes. Humans are no exception. Hostassociated microbes, like nearly all others on this planet, form communities in which the overall composition, structure, and function are explained by ecological processes and environmental factors. Evidence of coadaptation and mutual benefit are key features of these symbioses between hosts and their microbial communities, or microbiotas.1 The human microbiota is a fundamental component of what it means to be human. Recent work suggests that the benefits derived by humans from their microbiotas may have profound consequences for health. These benefits include differentiation of host mucosa, food digestion and nutrition, regulation of metabolism, processing and detoxification of environmental chemicals, development and ongoing regulation of the immune system, and prevention of invasion and growth of pathogens. Conversely, disturbance and alterations of the human microbiota and its collective genes and genomes, ie, the microbiome, are associated with a wide variety of human diseases, such as chronic periodontitis, inflammatory bowel disease, and antibiotic-associated diarrhea. The first direct observations and measurements of the human microbiota were made more than 300 years ago with the advent of the microscope and scrapings from teeth. Since then, the tools for studying the human microbiota have expanded in scope, sophistication, and availability. The current surge of interest in this topic reflects in part recent advances in DNA sequencing technology and its use in characterizing the microbial world directly from environmental samples, as well as a renewed appreciation for ecological principles, including the importance of interactions among organisms; the formation, activities, and stability of communities of microbes; and the relationships between communities and their environment. The study of the human microbiota has substantial potential for improving the management of human health and disease. Body site is one of the strongest determinants of variation in human microbiota compositional diversity.2 For example, microbial communities on the exposed tooth surfaces of a healthy individual generally have more similar taxonomic compositions to those on the teeth of another healthy individual than they do to those on the tongue of the same individual. In contrast, when specimens from the same body site are compared among a group of different healthy individuals, individualspecific microbiota features are apparent. Biogeographic patterns in microbiota taxonomic and genomic composition reflect differing selective pressures found at distinct body sites, as well as priority effects on community succession, rates of dispersal, and local microbial diversification. The subtle distinguishing features between microbial communities may teach us about important, underlying variation in both normal and abnormal human physiology and cell biology. For example, distinct types of epithelium, temperatures, and other environmental conditions are associated with differing bacterial communities between the anterior naris of the nose and the middle meatus and sinoethmoidal recess and associated with distinct competitive interactions among community members of interest, like Staphylococcus aureus.3 From high-diversity oral habitats to low-diversity vaginal habitats, microbial biogeography suggests distinct ecological zones across the human landscape (Figure). On the skin, there are 3 types of microbial communities, each characteristic of either dry, moist, or sebaceous environments.4 Propionibacterium acnes, commensal staphylococci, Corynebacterium species, and Propionibacterium phage explain the greatest amount of variation between these community types; fungi and other eukaryotic microbes are relatively rare. P acnes strains tend to be specific to an individual, whereas Staphylococcus epidermidis strains tend to be specific to body site. DNA viruses, especially bacterial viruses (phage), vary considerably in number and type between individuals on the skin and elsewhere across human body mucosa and are relatively abundant in the nose and vagina. Because they can kill bacteria or modify them by carrying in new genes, phages help shape the structure and function of the human microbiota. Site-specific features of microbiota structure and function may serve as early markers of future local disease. Focal processes such as chronic periodontitis, dental caries, atopic dermatitis, and Crohn disease are attractive settings for the identification of such features. Smallmoleculesmediateawidevarietyof interactions among members of microbial communities, and in so doing, promote community stability; with regard to the human microbiota, small molecules also mediate and facilitate host adaptation. With the advent of computational tools for identifying the putative products of complex mixed communities based on their “meta-genomes,” a wealth of new molecules have been discovered within the human microbiota. A number of them have demonstrated drug-like activities with significant medical potential.5 A recent examination of metagenomic sequence data obtained directly from human microbiota samples at 5 body sites identified more than 3000 biosynthetic gene clusters, each predicted to produce a small molVIEWPOINT
影响因子：
30.3
作者：
Yan M;Pamp SJ;Fukuyama J;Hwang PH;Cho DY;Holmes S;Relman DA
通讯作者：
Relman DA