微生物组相关词汇定义

The vocabulary of microbiome research: a proposal

Microbiome, [9.133], 30 July 2015

https://doi.org/10.1186/s40168-015-0094-5

译者：秦媛

责编：刘永鑫

作者

Julian R. Marchesi

Cardiff School of Biosciences, Division of Microbiology, Cardiff University

Jacques Ravel

University of Maryland School of Medicine
http://ravel-lab.org/people/

摘要

DNA/RNA、蛋白质以及代谢物分析技术平台的发展和计算技术的提高已经改变了微生物群落分析研究领域。最直接的证据就是，近期对人体肠道菌群组成与结构，以及功能相关研究报道呈指数生长。与此同时，描述这些菌群及其环境的专业词汇，例如微生物组、微生物群、代谢组学、宏基因组以及宏基因组学等，很容易混淆和误解。先前一些综述性文章对这些词汇进行了定义，但是主要放在侧边栏，没有明确的定义。因此在这篇社论中，我们旨在对这些术语进行定义。

The advancement of DNA/RNA, proteins, and metabolite analytical platforms, combined with increased computing technologies, has transformed the field of microbial community analysis. This transformation is evident by the exponential increase in the number of publications describing the composition and structure, and sometimes function, of the microbial communities inhabiting the human body. This rapid evolution of the field has been accompanied by confusion in the vocabulary used to describe different aspects of these communities and their environments. The misuse of terms such as microbiome, microbiota, metabolomic, and metagenome and metagenomics among others has contributed to misunderstanding of many study results by the scientific community and the general public alike. A few review articles have previously defined those terms, but mainly as sidebars, and no clear definitions or use cases have been published. In this editorial, we aim to propose clear definitions of each of these terms, which we would implore scientists in the field to adopt and perfect.

Microbiota 微生物群

特定环境中存在的微生物的集合。
首先由Lederberg和McCray于2001年定义[1]，强调的是人体健康和疾病相关的微生物的重要性。
研究微生物组成主要通过分子方法，基于16S、18S rRNA或其它marker基因或基因组区域进行分析，对生物样品扩增，测序，最后根据序列划分为不同门类。

The assemblage of microorganisms present in a defined environment. The term microbiota was first defined by Lederberg and McCray [1] who emphasized the importance of microorganisms inhabiting the human body in health and disease. This microbial census is established using molecular methods relying predominantly on the analysis of 16S rRNA genes, 18S rRNA genes, or other marker genes and genomic regions, amplified and sequenced from given biological samples. Taxonomic assignments are performed using a variety of tools that assign each sequence to a microbial taxon (bacteria, archaea, or lower eukaryotes) at different taxonomic levels from phylum to species.

(注：Microbiota也可翻译为微生物组，在维基百科中Microbiota与Microbiome为同一词条，参阅《Microbiota, metagenome, microbiome傻傻分不清》)

Metataxonomics 宏分类组

通过高通量测序过程描述整个微生物群体并建立系统发育树，称为宏分类树，可以用来表示所有获得的序列之间的关系。
虽然病毒也是微生物群体的一部分，但是没有通用的病毒标记基因可以用来进行分类。(注：在研究中更多称为扩增子-Amplicon)

Metataxonomics is a term we propose and define as the high-throughput process used to characterize the entire microbiota and create a metataxonomic tree, which shows the relationships between all sequences obtained. While viruses are an integral part of the microbiota, no universal viral marker genes are available to perform such taxonomic assignments.

Metagenome 宏基因组

宏基因组指的是及微生物群体成员的基因组和基因。
通过对样品DNA进行鸟枪法测序收集所得，与参考数据库比对进行注释。宏分类组分析是依赖于分类标记基因测序和扩增，并不基于宏基因组。
宏基因组学(Metagenomics)，指的是描述宏基因组的过程，从中我们可以获得与微生物群体潜在功能相关的信息。

The collection of genomes and genes from the members of a microbiota. This collection is obtained through shotgun sequencing of DNA extracted from a sample (metagenomics) followed by assembly or mapping to a reference database followed by annotation. Metataxonomic analysis, because it relies on the amplification and sequencing of taxonomic marker genes, is not metagenomics. Metagenomics is the process used to characterize the metagenome, from which information on the potential function of the microbiota can be gained.

Handelsman等人于1998年首先使用了宏基因组学[2]；然而，这是在作者称之为功能性宏基因组学的背景下，一种将环境DNA的随机片段克隆到合适的载体中，用于在替代宿主中进行功能筛选，以寻求在替代宿主中获得功能的方法。

Metagenomics was first used by Handelsman et al. [2]; however, it was in the context of what the authors called functional metagenomics, an approach where random fragments of environmental DNA are cloned into a suitable vector for maintenance in a surrogate host for functional screening, looking for gain of function in the surrogate host.

Microbiome 微生物组

微生物组指的是包括微生物（细菌、古细菌、低等或高等真核生物和病毒）的基因组（基因），以及其周围环境在内的全部。这个定义是基于’biome(生物群落)'而形成的，包括环境中的所有生物和微生物因素。
本领域的一些人将这个概念仅限制为微生物群体成员及其基因的集合。
有人认为这是宏基因组(包括 microbiome + environment)的定义。
微生物组(Microbiome)的特点是结合了宏基因组学、代谢组学、宏转录组学、以及宏蛋白组学等和临床/环境数据的集合。

This term refers to the entire habitat, including the microorganisms (bacteria, archaea, lower and higher eurkaryotes, and viruses), their genomes (i.e., genes), and the surrounding environmental conditions. This definition is based on that of “biome,” the biotic and abiotic factors of given environments. Others in the field limit the definition of microbiome to the collection of genes and genomes of members of a microbiota. It is argued that this is the definition of metagenome, which combined with the environment constitutes the microbiome. The microbiome is characterized by the application of one or combinations of metagenomics, metabonomics, metatranscriptomics, and metaproteomics combined with clinical or environmental metadata.

Metabolomics 代谢组学

该术语指的是，用来确定给定菌株或单个组织代谢物特征的分析方法。给定菌株和单个组织内存在的所有代谢物统称为代谢组（metabolome）。大多数用来描述代谢组的平台包括核磁共振（NMR）、质谱(MS)与液相色谱(liquid chromatography)联合分离系统。

This term describes the analytical approaches used to determine the metabolite profile(s) in any given strain or single tissue. The resulting census of all metabolites present in any given strain or single tissue is called the metabolome. Most commonly used platforms to characterize the metabolome include nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) linked to a liquid chromatography separation system.

Metabonomics 宏代谢组学

这是代谢组学(Metabolomics)方法的变体，它描述的是用于从复杂的系统中产生代谢谱的方法。复杂的系统指的是不只一种菌株或组织，如粪便、尿液、血浆等。
为避免混淆，Jeremy Nicholson于2006年将其首次定义为：meta-metabolomics[3]。

The term is a variant of the metabolomic approach; however, it describes the approach used to generate a metabolite profile(s) from complex systems, e.g., mammals in which more than one strain or tissue has contributed to the total metabolite pool, for example, fecal water, urine, or plasma. This term avoids the clumsy use of meta-metabolomics and was first defined by Jeremy Nicholson [3].

Metatranscriptomics 宏转录组学

这个概念指的是，通过对微生物群落中的表达的RNAs (meta-RNAs)，采用进行高通量测序分析相应的meta-cDNA。这种方法可提供微生物组的调控和表达层面的整体信息。

This term refers to the analysis of the suite of expressed RNAs (meta-RNAs) by high-throughput sequencing of the corresponding meta-cDNAs. This approach provides information on the regulation and expression profiles of complex microbiomes.

Metaproteomics 宏蛋白质组

宏蛋白质组的概念首先由Rodriguez-Valera于2004提出[4]，同Wilmes和Bond在2006年重新定义[5]，指的是在特定时间、特定环境/临床样品中的整个蛋白质组的大规模描述。
这种方法并不区分蛋白质是从微生物群体而来，还是从宿主或环境（metagenome）中而来。
通过计算分析确定这些蛋白质的来源。常用手段为基于液相色谱分离和质谱联用进行多肽鉴定。

First coined by Rodriguez-Valera [4] and refined by Wilmes and Bond [5], this term refers to the large-scale characterization of the entire protein complement of environmental or clinical samples at a given point in time. The method indiscriminately identifies proteins from the microbiota and the host/environments (metagenome). Computational analyses afford assignments of these proteins to their biological origins. It is often performed using liquid-chromatography-based separation coupled to mass spectrometry for peptide identification.

用词不当和正确使用术语

Misnomers and correct usage of the terms

在讨论基于16S rRNA基因测序和分析的宏分类组分析的研究中，经常发现用词不当。在文献中，我们可以见到如“16S survey”、“16S sequencing”或“16S analysis”的用法。没有所谓的“16S.”，16S中的“S”是沉淀率的non-SI单位，代表Svedberg单位。Svedberg单位提供了一种基于其在高重(g)力作用下的管内移动速率的颗粒尺寸测量方法。细菌核糖体和古细菌核糖体的小亚单位为30S，包含一个结合21个蛋白质的结构16S核糖体RNA（rRNA，约1540个核苷酸）。因此，我们认为恰当的术语应该是“16S rRNA genes(16S rRNA基因)”或“16S rRNA gene sequencing/analysis(16S rRNA基因测序/分析)”。

Misnomers are often found in studies discussing metataxonomic analyses relying on sequencing and analysis of 16S rRNA genes. In the literature, one can find the use of “16S survey,” “16S sequencing,” or “16S analysis,” for example. There is no such thing as “16S.” The “S” in 16S is a non-SI unit for sedimentation rate and stands for the Svedberg unit. The Svedberg unit offers a measure of particle size based on its rate of travel in a tube subjected to high g force. The small subunits of the bacterial and archaeal ribosomes are 30S and comprise one structural 16S ribosomal RNA (rRNA, ~1540 nucleotides) bound to 21 proteins. Thus, we would like to argue that the proper terms should be “16S rRNA genes” or “16S rRNA gene sequencing/analysis.”

此外，在科学和医学文献中，“microflora(微生物区系/微生物群落)”这个词已经使用了很长时间。然而，它的定义并不能证明它用于描述与人类相关的微生物群落（即微生物群）是合理的。它的定义随着时间的推移而演变，但仍然是“微型栖息地的微型植物，或植物或植物群”。该定义的起源可以追溯到20世纪初。

Additionally, the word microflora has been used for a long time in the scientific and medical literature. However, its definition does not justify its use to describe microbial communities associated with human (i.e., microbiota). Its definition has evolved over time, but remains “microscopic plants, or the plants or flora of a microhabitat.” The origin of the definition dates back to the early 1900s.

此外，“植物群(flora)”一词的定义进一步突出了微生物组科学文献中“微生物群落(microflora)”一词的不恰当：“一个特定地区或时期的植物，按物种列出并被认为是一个整体的”或“系统地描述植物”或“植物群(flora)区别于动物群(fauna)”。“植物群flora”的定义可以追溯到1600年代中期，其起源于拉丁名“Flora”，罗马花神和拉丁词“flor”，意思是花。

Furthermore, the definition of the word “flora” further highlights the inappropriateness of the word microflora in the microbiome scientific literature: “the plants of a particular region or period, listed by species and considered as a whole” or “a work systematically describing plants” or “plants, as distinguished from fauna.” The definition of flora dates back to mid 1600s and has its origin in the Latin name “Flora,” the Roman goddess of flowers and the Latin word “flor,” meaning flower.

这些定义及其起源使得“microflora”明显指的是植物而不是微生物。虽然一些词典现在包括了microflora的第三个定义：“通常发生在人类和其他动物身上或体内的细菌、真菌和其他微生物的集合：肠道菌群(intestinal flora)”，但这些新增加的定义是由于一个多世纪以来人们对这个词的误用而导致的，这是由于人们对这个词的理解有限。与人类有关的微生物。我们对微生物群落的认识是这样的，科学界不应该继续在科学文献中使用这个词。现在是时候改变了，我们建议用“微生物群microbiota”来描述生活在微环境中的微生物的组合。有趣的是，微生物群几乎只在涉及人类或动物相关微生物群落的文献中使用，但很少在与环境相关的文献中使用。我们认为，微生物群在流行文学或面向大众的酸奶/益生菌广告中仍然占有一席之地，但在科学和医学文献中却没有。

These definitions and their origins make it obvious that “microflora” refers to plants and not microbes. While some dictionaries are now including a third definition for microflora, “the aggregate of bacteria, fungi, and other microorganisms normally occurring on or in the bodies of humans and other animals: intestinal flora,” these newly added definitions are the results of over one century of misuse of the word, driven by a limited understanding of the microbes associated with humans. Our knowledge of microbial communities is such that the scientific community should not continue to use the word in the scientific literature. It is time to change, and we suggest that to describe the assemblage of microbes living in a microhabitat we use “microbiota.” Interestingly, microflora is almost exclusively used in the literature referring to microbial community associated with human or animal, but rarely in those associated with the environment. We believe that microflora has still its place in the popular literature or in a yogurt/probiotic advertisement destined to the general public, but it does not in the scientific and medical literature.

详者注：早期的微生物组叫microflora的确实比较多，如之前发布的纪录片 《NHK一片看懂肠道菌群在人体中的作用》

公众、科学大众媒体、医学博士和其他科学家需要科学界采用共同语言。“microbiota”这个词足以描述微生物群落的组成和丰富程度，无论它们居住在人体还是环境中。

The public, the scientific popular press, medical doctors, and other scientists need to be educated, but this will come if the scientific community adopts a common language. The word microbiota is adequate and appropriate to describe the composition and abundance of microbial communities whether they inhabit the human body or the environment.

这篇社论是从我们与同事的论文和其他交流中总结的。我们希望在不远的将来，能够以协商一致的方式使用这些术语。这篇社论旨在激发讨论，规范微生物研究的词汇。微生物组将继续努力使这个不断扩大的研究领域中使用的词汇标准化。

This editorial was informed from papers and other communications we have had with colleagues. We hope that a consensus use of these terms could be adopted in the near future. This editorial aims at stimulating a discussion and standardizing the vocabulary of microbiome research. Microbiome will continue to strive toward a standardization of the vocabulary used in this ever-expanding field of research.

Reference

1. Lederberg J, McCray AT. ‘Ome sweet ‘omics - a genealogical treasury of words. Scientist. 2001;15(7):8–8.
2. Handelsman J, Rondon MR, Brady SF, Clardy J, Goodman RM. Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chem Biol. 1998;5(10):R245–9.
3. Nicholson JK. Global systems biology, personalized medicine and molecular epidemiology. Mol Syst Biol. 2006;2:52.
4. Rodriguez-Valera F. Environmental genomics, the big picture? FEMS Microbiol Lett. 2004;231(2):153–8.
5. Wilmes P, Bond PL. Metaproteomics: studying functional gene expression in microbial ecosystems. Trends Microbiol. 2006;14(2):92–7.
6. Marchesi, J. R. and J. Ravel (2015). “The vocabulary of microbiome research: a proposal.” Microbiome 3: 31. https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-015-0094-5

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