microbiome microbiome a microbiome (from ancient greek μικρός (mikrós) 'small', and βίος (bíos) 'life') is the community of microorganisms that can usually be found living together in any given habitat. it was defined more precisely in 1988 by whipps et al. as "a characteristic microbial community occupying a reasonably well-defined habitat which has distinct physio-chemical properties. the term thus not only refers to the microorganisms involved but also encompasses their theatre of activity". in 2020, an international panel of experts published the outcome of their discussions on the definition of the microbiome. they proposed a definition of the microbiome based on a revival of the "compact, clear, and comprehensive description of the term" as originally provided by whipps et al., but supplemented with two explanatory paragraphs. the first explanatory paragraph pronounces the dynamic character of the microbiome, and the second explanatory paragraph clearly separates the term microbiota from the term microbiome. part of a series onmicrobiomes plant microbiomes endosphere phyllosphere rhizosphere laimosphere root microbiome soil microbiome spermosphere marine microbiomes seagrass coral cetacean marine microbial symbiosis human microbiomes human milk fecal transplant gut–brain axis placental salivary uterine necrobiome other microbiomes mycobiome phycosphere built environment drosophila gut microbiota plant endophyte epiphyte rhizobacteria human gut lung oral skin vaginal marine microbial community initial acquisition accessible carbohydrates flora (microbiology) holobionts plant holobiont marine holobiont coral crab seagrass sponge rhodolith hologenomics hologenome evolution viromes bat human mangrove viriome virosphere related biomass partitioning dysbiosis gnotobiosis phytobiome quorum sensing biological dark matter microbial population biology microbial cooperation metagenomics viral metatranscriptomics metabolomics pan-genome superorganism symbiogenesis projects human microbiome project earth microbiome project category the microbiota consists of all living members forming the microbiome. most microbiome researchers agree bacteria, archaea, fungi, algae, and small protists should be considered as members of the microbiome. the integration of phages, viruses, plasmids, and mobile genetic elements is more controversial. whipps's "theatre of activity" includes the essential role secondary metabolites play in mediating complex interspecies interactions and ensuring survival in competitive environments. quorum sensing induced by small molecules allows bacteria to control cooperative activities and adapts their phenotypes to the biotic environment, resulting, e.g., in cell-cell adhesion or biofilm formation. all animals and plants form associations with microorganisms, including protists, bacteria, archaea, fungi, and viruses. in the ocean, animal–microbial relationships were historically explored in single host–symbiont systems. however, new explorations into the diversity of microorganisms associating with diverse marine animal hosts is moving the field into studies that address interactions between the animal host and the multi-member microbiome. the potential for microbiomes to influence the health, physiology, behaviour, and ecology of marine animals could alter current understandings of how marine animals adapt to change. this applies to especially the growing climate-related and anthropogenic-induced changes already impacting the ocean. the plant microbiome plays key roles in plant health and food production and has received significant attention in recent years. plants live in association with diverse microbial consortia, referred to as the plant microbiota, living both inside (the endosphere) and outside (the episphere) of plant tissues. they play important roles in the ecology and physiology of plants. the core plant microbiome is thought to contain keystone microbial taxa essential for plant health and for the fitness of the plant holobiont. likewise, the mammalian gut microbiome has emerged as a key regulator of host physiology, and coevolution between host and microbial lineages has played a key role in the adaptation of mammals to their diverse lifestyles. microbiome research originated in microbiology back in the seventeenth century. the development of new techniques and equipment boosted microbiological research and caused paradigm shifts in understanding health and disease. the development of the first microscopes allowed the discovery of a new, unknown world and led to the identification of microorganisms. infectious diseases became the earliest focus of interest and research. however, only a small proportion of microorganisms are associated with disease or pathogenicity. the overwhelming majority of microbes are essential for healthy ecosystem functioning and known for beneficial interactions with other microbes and organisms. the concept that microorganisms exist as single cells began to change as it became increasingly obvious that microbes occur within complex assemblages in which species interactions and communication are critical. discovery of dna, the development of sequencing technologies, pcr, and cloning techniques enabled the investigation of microbial communities using cultivation-independent approaches. further paradigm shifts occurred at the beginning of this century and still continue, as new sequencing technologies and accumulated sequence data have highlighted both the ubiquity of microbial communities in association within higher organisms and the critical roles of microbes in human, animal, and plant health. these have revolutionised microbial ecology. the analysis of genomes and metagenomes in a high-throughput manner now provide highly effective methods for researching the functioning of both individual microorganisms as well as whole microbial communities in natural habitats. background history microbiome research originated in microbiology and started back in the seventeenth century. the development of new techniques and equipment has boosted microbiological research and caused paradigm shifts in understanding health and disease. since infectious diseases have affected human populations throughout most of history, medical microbiology was the earliest focus of research and public interest. additionally, food microbiology is an old field of empirical applications. the development of the first microscopes allowed the discovery of a new, unknown world and led to the identification of microorganisms. paradigm shift shift of paradigm from microbes as unsocial organisms causing diseases to a holistic view of microorganisms as the centre of the one health concept interconnecting all areas of human lives. access to the previously invisible world opened the eyes and the minds of the researchers of the seventeenth century. antonie van leeuwenhoek investigated diverse bacteria of various shapes, fungi, and protozoa, which he called animalcules, mainly from water, mud, and dental plaque samples, and discovered biofilms as a first indication of microorganisms interacting within complex communities. robert koch's explanation of the origin of human and animal diseases as a consequence of microbial infection and development of the concept of pathogenicity was an important milestone in microbiology. these findings shifted the focus of the research community and the public on the role of microorganisms as disease-forming agents that needed to be eliminated. however, comprehensive research over the past century has shown only a small proportion of microorganisms are associated with disease or pathogenicity. the overwhelming majority of microbes are essential for ecosystem functioning and known for beneficial interactions with other microbes as well as macroorganisms. in fact, maintaining a healthy microbiome is essential for human health and may be a target for new therapeutics. at the end of the nineteenth century, microbial ecology started with the pioneering work by martinus w. beijerinck and sergei winogradsky. the newly established science of environmental microbiology resulted in another paradigm shift: microorganisms are everywhere in natural environments, often associated with hosts and, for the first time, beneficial effects on their hosts were reported. subsequently, the concept that microorganisms exist as single cells began to change as it became increasingly obvious that microbes occur within complex assemblages in which species interactions and communication are critical to population dynamics and functional activities. discovery of dna, the development of sequencing technologies, pcr, and cloning techniques enabled the investigation of microbial communities using cultivation-independent, dna and rna-based approaches. a further important step was the introduction of phylogenetic markers such as the 16s rrna gene for microbial community analysis by carl woese and george e. fox in 1977. nowadays biologists can barcode bacteria, archaea, fungi, algae, and protists in their natural habitats, e.g., by targeting their 16s and 18s rrna genes, internal transcribed spacer (its), or, alternatively, specific functional regions of genes coding for specific enzymes. another major paradigm shift was initiated at the beginning of this century and continues through today, as new sequencing technologies and accumulated sequence data have highlighted both the ubiquity of microbial communities in association within higher organisms and the critical roles of microbes in human, animal, and plant health. these new possibilities have revolutionized microbial ecology, because the analysis of genomes and metagenomes in a high-throughput manner provides efficient methods for addressing the functional potential of individual microorganisms as well as of whole communities in their natural habitats. multiomics technologies including metatranscriptome, metaproteome and metabolome approaches now provide detailed information on microbial activities in the environment. based on the rich foundation of data, the cultivation of microbes, which was often ignored or underestimated over the last thirty years, has gained new importance, and high throughput culturomics is now an important part of the toolbox to study microbiomes. the high potential and power of combining multiple "omics" techniques to analyze host-microbe interactions are highlighted in several reviews. timeline of microbiome research from the seventeenth century to the present technological advances year scientific discoveries scientists sources microscopy 1670 discovery of microorganisms antonie van leeuwenhoekfather of microbiology 1729 classification of plants and fungi pier antonio micheli 1796 first vaccination edward jenner 1837 yeast in alcoholic fermentation charles de la tourfriedrich kützingtheodor schwann cultivation based approaches 1855-1857 pasteurisation, fermentation,vaccine against rabies louis pasteur 1875 foundation for bacteriological taxonomy ferdinand cohn 1884 koch's postulates robert koch 1888 start of microbial ecologynitrification, nitrogen-fixation, soil microbiology, life cycle sergei winogradsky 1892 tobacco mosaic virus extraction from leaves dmitri ivanovskymartinus beijerinck 1904 concept of the rhizosphere lorenz hiltner fluorescence microscopy 1911 mass spectrometry 1919 francis aston 1922 chemolithotrophy sergei winogradsky 1928 transformation of genetic informationto offspring frederick griffith 1928 discovery of antibiotics alexander fleming scanning electron microscopy 1931-1938 1944 dna as carrier of genetic information oswald averycolin macleodmaclyn mccarty 1946 "sexual reproduction" of bacteria joshua lederbergedward tatum 1953 3d-double-helix structure james watsonfrancis crick in situ hybridisation isis 1969 hplc 1970s central dogma of molecular biology francis crick dna array/colony hybridisation 1975 sanger sequencing 1977 frederick sanger 1977 discovery of archaea carl woesegeorge e. fox 1977 first full genome sequence of a virus 1982 discovery of prions stanley b. prusiner pcr technique 1983 fluorescence in situ hybridisation 1988 1991 theory of the holobiont eugene rosenbergilana zilber-rosenberg quantitative real-time pcr 1993 1993 the complex structure of biofilms hans-curt flemming full cycle rrna approach 1995 1995 first full genome sequencingof haemophilus influenzae craig venterand colleagues next-generation sequencing 2005 2005 hmp: human microbiome project third-generation sequencing 2008 2008 terragenome:reference soil metagenome project 2010 earth microbiome project etymology the word microbiome (from the greek micro meaning "small" and bíos meaning "life") was first used by j.l. mohr in 1952 in the scientific monthly to mean the microorganisms found in a specific environment. definitions microbial communities have commonly been defined as the collection of microorganisms living together. more specifically, microbial communities are defined as multi-species assemblages, in which (micro) organisms interact with each other in a contiguous environment. in 1988, whipps and colleagues working on the ecology of rhizosphere microorganisms provided the first definition of the term microbiome. they described the microbiome as a combination of the words micro and biome, naming a "characteristic microbial community" in a "reasonably well-defined habitat which has distinct physio-chemical properties" as their "theatre of activity". this definition represents a substantial advancement of the definition of a microbial community, as it defines a microbial community with distinct properties and functions and its interactions with its environment, resulting in the formation of specific ecological niches. however, many other microbiome definitions have been published in recent decades. by 2020 the most cited definition was by lederberg, and described microbiomes within an ecological context as a community of commensal, symbiotic, and pathogenic microorganisms within a body space or other environment. marchesi and ravel focused in their definition on the genomes and microbial (and viral) gene expression patterns and proteomes in a given environment and its prevailing biotic and abiotic conditions. all these definitions imply that general concepts of macro-ecology could be easily applied to microbe-microbe as well as to microbe-host interactions. however, the extent to which these concepts, developed for macro-eukaryotes, can be applied to prokaryotes with their different lifestyles regarding dormancy, variation of phenotype, and horizontal gene transfer as well as to micro-eukaryotes that is not quite clear. this raises the challenge of considering an entirely novel body of conceptual ecology models and theory for microbiome ecology, particularly in relation to the diverse hierarchies of interactions of microbes with one another and with the host biotic and abiotic environments. many current definitions fail to capture this