microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s that may be
commensal
Commensalism is a long-term biological interaction (symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism, in which both organisms benefit fro ...
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclu ...
s. Microbiota include
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
protist
A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the exc ...
s,
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
, and
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
es, and have been found to be crucial for immunologic, hormonal, and metabolic
homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
of their host.
The term ''
microbiome
A microbiome () 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 wel ...
'' describes either the collective
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
s of the microbes that reside in an
ecological niche
In ecology, a niche is the match of a species to a specific environmental condition.
Three variants of ecological niche are described by
It describes how an organism or population responds to the distribution of resources and competitors (for ...
or
within
Within may refer to:
* ''Within'' (William Joseph album) (2004), by pianist William Joseph
* ''Within'' (Embraced album) (2000), by Swedish melodic black metal band Embraced
* Within (company), a virtual reality content and technology company ba ...
the microbes themselves.
The microbiome and host emerged during
evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
epigenetics
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are ...
and genetic characteristics, sometimes collectively referred to as a
holobiont
A holobiont is an assemblage of a host and the many other species living in or around it, which together form a discrete ecological unit through symbiosis, though there is controversy over this discreteness. The components of a holobiont are i ...
. The presence of microbiota in human and other metazoan guts has been critical for understanding the co-evolution between metazoans and bacteria. Microbiota play key roles in the intestinal immune and metabolic responses via their fermentation product (
short-chain fatty acid Short-chain fatty acids (SCFAs) are fatty acids with fewer than six carbon atoms. Derived from intestinal microbial fermentation of indigestible foods, SCFAs are the main energy source of colonocytes, making them crucial to gastrointestinal healt ...
All plants and animals, from simple life forms to humans, live in close association with microbial organisms. Several advances have driven the perception of microbiomes, including:
* the ability to perform genomic and gene expression analyses of single cells and of entire microbial communities in the disciplines of
metagenomics
Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microb ...
and
metatranscriptomics Metatranscriptomics is the science that studies gene expression of microbes within natural environments, i.e., the metatranscriptome. It also allows to obtain whole gene expression profiling of complex microbial communities.
While metagenomics foc ...
* databases accessible to researchers across multiple disciplines
* methods of mathematical analysis suitable for complex data sets
Biologists have come to appreciate that microbes make up an important part of an organism's
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
, far beyond the occasional symbiotic case study.
Types of microbe-host relationships
Commensalism
Commensalism is a long-term biological interaction ( symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism, in which both organisms benefit fr ...
, a concept developed by Pierre-Joseph van Beneden (1809–1894), a Belgian professor at the University of Louvain during the nineteenth century is central to the microbiome, where microbiota colonize a host in a non-harmful coexistence. The relationship with their host is called mutualistic when organisms perform tasks that are known to be useful for the host,
parasitic
Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson ha ...
, when disadvantageous to the host. Other authors define a situation as mutualistic where both benefit, and commensal, where the unaffected host benefits the symbiont. A nutrient exchange may be bidirectional or unidirectional, may be context dependent and may occur in diverse ways. Microbiota that are expected to be present, and that under normal circumstances do not cause disease, are deemed ''normal flora'' or ''normal microbiota''; normal flora can not only be harmless, but can be protective of the host.
sponge
Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate throug ...
s is at birth, and may even occur through the germ cell line. In plants, the colonizing process can be initiated below ground in the root zone, around the germinating seed, the spermosphere, or originate from the above ground parts, the phyllosphere and the
flower
A flower, sometimes known as a bloom or blossom, is the reproductive structure found in flowering plants (plants of the division Angiospermae). The biological function of a flower is to facilitate reproduction, usually by providing a mechani ...
zone or anthosphere. The stability of the rhizosphere microbiota over generations depends upon the plant type but even more on the soil composition, i.e. living and non living environment. Clinically, new microbiota can be acquired through fecal microbiota transplant to treat infections such as chronic ''C. difficile'' infection.
Microbiota by host
Humans
The human microbiota includes
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
,
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
Micro-animal
Microfauna (Ancient Greek ''mikros'' "small" + New Latin ''fauna'' "animal") refers to microscopic animals and organisms that exhibit animal-like qualities. Microfauna are represented in the animal kingdom (e.g., nematodes, small arthropods) and t ...
s which live on the human body are excluded. The human microbiome refers to their collective
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
s.
Humans are colonized by many microorganisms; the traditional estimate was that humans live with ten times more non-human cells than human cells; more recent estimates have lowered this to 3:1 and even to about 1:1.American Academy of Microbiolog FAQ: Human Microbiome January 2014Judah L. Rosner for Microbe Magazine, Feb 2014 Ten Times More Microbial Cells than Body Cells in Humans? /ref>Alison Abbott for Nature News. Jan 8 201 Scientists bust myth that our bodies have more bacteria than human cells /ref>
In fact, these are so small that there are around 100 trillion microbiota on the human body.
The
Human Microbiome Project
The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on ...
sequenced the genome of the human microbiota, focusing particularly on the microbiota that normally inhabit the skin, mouth, nose, digestive tract, and vagina. It reached a milestone in 2012 when it published initial results.
Non-human animals
* Amphibians have microbiota on their skin. Some species are able to carry a fungus named ''Batrachochytrium dendrobatidis'', which in others can cause a deadly infection
Chytridiomycosis
Chytridiomycosis ( ) is an infectious disease in amphibians, caused by the chytrid fungi '' Batrachochytrium dendrobatidis'' and '' Batrachochytrium salamandrivorans''. Chytridiomycosis has been linked to dramatic population declines or extinc ...
depending on their microbiome, resisting pathogen colonization or inhibiting their growth with antimicrobial skin peptides.
* In mammals, herbivores such as cattle depend on their
rumen
The rumen, also known as a paunch, is the largest stomach compartment in ruminants and the larger part of the reticulorumen, which is the first chamber in the alimentary canal of ruminant animals. The rumen's microbial favoring environment al ...
microbiome to convert cellulose into proteins, short chain fatty acids, and gases. Culture methods cannot provide information on all microorganisms present. Comparative metagenomic studies yielded the surprising result that individual cattle possess markedly different community structures, predicted phenotype, and metabolic potentials, even though they were fed identical diets, were housed together, and were apparently functionally identical in their utilization of plant cell wall resources.
* Mice have become the most studied mammalian regarding their microbiomes. The gut microbiota have been studied in relation to allergic airway disease, obesity, gastrointestinal diseases and diabetes. Perinatal shifting of microbiota through low dose antibiotics can have long-lasting effects on future susceptibility to allergic airway disease. The frequency of certain subsets of microbes has been linked to disease severity. The presence of specific microbes early in postnatal life, instruct future immune responses. In gnotobiotic mice certain gut bacteria were found to transmit a particular phenotype to recipient germ-free mice, that promoted accumulation of colonic regulatory T cells, and strains that modulated mouse adiposity and cecal metabolite concentrations. This combinatorial approach enables a systems-level understanding of microbial contributions to human biology. But also other mucoide tissues as lung and vagina have been studied in relation to diseases such as asthma, allergy and vaginosis.
* Insects have their own microbiomes. For example,
leaf-cutter ants
Leafcutter ants, a non-generic name, are any of 47 species of leaf-chewing ants belonging to the two genera '' Atta'' and ''Acromyrmex''.
These species of tropical, fungus-growing ants are all endemic to South and Central America, Mexico, and p ...
form huge underground colonies harvesting hundreds of kilograms of leaves each year and are unable to digest the cellulose in the leaves directly. They maintain fungus gardens as the colony's primary food source. While the fungus itself does not digest cellulose, a microbial community containing a diversity of bacteria is doing so. Analysis of the microbial population's genome revealed many genes with a role in cellulose digestion. This microbiome's predicted carbohydrate-degrading enzyme profile is similar to that of the bovine rumen, but the species composition is almost entirely different. Gut microbiota of the fruit fly can affect the way its gut looks, by impacting epithelial renewal rate, cellular spacing, and the composition of different cell types in the epithelium. When the moth
Spodoptera exigua
The beet armyworm or small mottled willow moth (''Spodoptera exigua'') is one of the best-known agriculture, agricultural pest insects. It is also known as the asparagus fern caterpillar. It is native to Asia, but has been introduced Cosmopolitan ...
is infected with
baculovirus
''Baculoviridae'' is a family of viruses. Arthropods, among the most studied being Lepidoptera, Hymenoptera and Diptera, serve as natural hosts. Currently, 85 species are placed in this family, assigned to four genera.
Baculoviruses are known ...
immune-related genes are downregulated and the amount of its gut microbiota increases. In the dipteran intestine, enteroendocrine cells sense the gut microbiota-derived metabolites and coordinate antibacterial, mechanical, and metabolic branches of the host intestinal innate immune response to the commensal microbiota.
*Fish have their own microbiomes, including the short-lived species
Nothobranchius furzeri
''Nothobranchius furzeri'', the turquoise killifish, is a species of killifish from the family Nothobranchiidae native to Africa where it is only known from Zimbabwe and Mozambique. This annual killifish inhabits ephemeral pools in semi-arid area ...
(turquoise killifish). Transferring the gut microbiota from young killfish into middle-aged killifish significantly extends the lifespans of the middle-aged killfish.
Plants
The plant microbiome was recently discovered to originate from the seed. Microorganism which are transmitted via seed migrate into the developing seedling in a specific route in which certain community move to the leaves and others to the roots. In the diagram on the right, microbiota colonizing the
rhizosphere
The rhizosphere is the narrow region of soil or substrate that is directly influenced by root secretions and associated soil microorganisms known as the root microbiome. Soil pores in the rhizosphere can contain many bacteria and other microo ...
, entering the roots and colonizing the next tuber generation via the stolons, are visualized with a red color. Bacteria present in the mother
tuber
Tubers are a type of enlarged structure used as storage organs for nutrients in some plants. They are used for the plant's perennation (survival of the winter or dry months), to provide energy and nutrients for regrowth during the next growin ...
, passing through the stolons and migrating into the plant as well as into the next generation of tubers are shown in blue.
* The soil is the main reservoir for bacteria that colonize potato tubers
* Bacteria are recruited from the soil more or less independent of the potato variety
* Bacteria might colonize the tubers predominantly from the inside of plants via the stolon
* The bacterial microbiota of potato tubers consists of bacteria transmitted from one tuber generation to the next and bacteria recruited from the soil colonize potato plants via the root.
Plants are attractive hosts for microorganisms since they provide a variety of nutrients. Microorganisms on plants can be epiphytes (found on the plants) or
endophyte
An endophyte is an endosymbiont, often a bacterium or fungus, that lives within a plant for at least part of its life cycle without causing apparent disease. Endophytes are ubiquitous and have been found in all species of plants studied to date; h ...
s (found inside plant tissue).
Oomycetes
Oomycota forms a distinct phylogenetic lineage of fungus-like eukaryotic microorganisms, called oomycetes (). They are filamentous and heterotrophic, and can reproduce both sexually and asexually. Sexual reproduction of an oospore is the result ...
and
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
have, through convergent evolution, developed similar morphology and occupy similar ecological niches. They develop hyphae, threadlike structures that penetrate the host cell. In mutualistic situations the plant often exchanges hexose sugars for inorganic phosphate from the fungal symbiont. It is speculated that such very ancient associations have aided plants when they first colonized land.Plant-growth promoting bacteria (PGPB) provide the plant with essential services such as
nitrogen fixation
Nitrogen fixation is a chemical process by which molecular nitrogen (), with a strong triple covalent bond, in the air is converted into ammonia () or related nitrogenous compounds, typically in soil or aquatic systems but also in industry. Atmo ...
, solubilization of minerals such as phosphorus, synthesis of plant hormones, direct enhancement of mineral uptake, and protection from pathogens. PGPBs may protect plants from pathogens by competing with the pathogen for an ecological niche or a substrate, producing inhibitory allelochemicals, or inducing systemic resistance in host plants to the pathogen
Research
The symbiotic relationship between a host and its microbiota is under laboratory research for how it may shape the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
of mammals. In many animals, the immune system and microbiota may engage in "cross-talk" by exchanging chemical signals, which may enable the microbiota to influence immune reactivity and targeting. Bacteria can be transferred from mother to child through direct contact and after
birth
Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...
. As the infant microbiome is established, commensal bacteria quickly populate the gut, prompting a range of immune responses and "programming" the immune system with long-lasting effects. The bacteria are able to stimulate lymphoid tissue associated with the gut mucosa, which enables the tissue to produce antibodies for pathogens that may enter the gut.
The human microbiome may play a role in the activation of
toll-like receptors
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize s ...
in the intestines, a type of pattern recognition receptor host cells use to recognize dangers and repair damage. Pathogens can influence this coexistence leading to immune dysregulation including and susceptibility to diseases, mechanisms of
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
,
immune tolerance
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that would otherwise have the capacity to elicit an immune response in a given organism. It is induced by ...
Organisms evolve within ecosystems so that the change of one organism affects the change of others. The
hologenome theory of evolution
The hologenome theory of evolution recasts the individual animal or plant (and other multicellular organisms) as a community or a "holobiont" – the host plus all of its symbiotic microbes. Consequently, the collective genomes of the holobiont for ...
proposes that an object of natural selection is not the individual organism, but the organism together with its associated organisms, including its microbial communities.
Coral reefs. The hologenome theory originated in studies on coral reefs. Coral reefs are the largest structures created by living organisms, and contain abundant and highly complex microbial communities. Over the past several decades, major declines in coral populations have occurred.
Climate change
In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to ...
, water pollution and over-fishing are three stress factors that have been described as leading to disease susceptibility. Over twenty different coral diseases have been described, but of these, only a handful have had their causative agents isolated and characterized.
Coral bleaching
Coral bleaching is the process when corals become white due to various stressors, such as changes in temperature, light, or nutrients. Bleaching occurs when coral polyps expel the zooxanthellae ( dinoflagellates that are commonly referred to as a ...
is the most serious of these diseases. In the Mediterranean Sea, the bleaching of ''
Oculina
''Oculina'' is a genus of colonial stony coral in the family Oculinidae. These corals are mostly found in the Caribbean Sea, the Gulf of Mexico and BermudaVibrio shiloi. From 1994 to 2002, bacterial bleaching of ''O. patagonica'' occurred every summer in the eastern Mediterranean. Surprisingly, however, after 2003, ''O. patagonica'' in the eastern Mediterranean has been resistant to ''V. shiloi'' infection, although other diseases still cause bleaching. The surprise stems from the knowledge that corals are long lived, with lifespans on the order of decades, and do not have
adaptive immune system
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
s. Their innate immune systems do not produce antibodies, and they should seemingly not be able to respond to new challenges except over evolutionary time scales.
The puzzle of how corals managed to acquire resistance to a specific pathogen led to a 2007 proposal, that a dynamic relationship exists between corals and their symbiotic microbial communities. It is thought that by altering its composition, the
holobiont
A holobiont is an assemblage of a host and the many other species living in or around it, which together form a discrete ecological unit through symbiosis, though there is controversy over this discreteness. The components of a holobiont are i ...
can adapt to changing environmental conditions far more rapidly than by genetic mutation and selection alone. Extrapolating this hypothesis to other organisms, including higher plants and animals, led to the proposal of the hologenome theory of evolution.
the hologenome theory was still being debated.
A major criticism has been the claim that ''V. shiloi'' was misidentified as the causative agent of coral bleaching, and that its presence in bleached ''O. patagonica'' was simply that of opportunistic colonization. If this is true, the basic observation leading to the theory would be invalid. The theory has gained significant popularity as a way of explaining rapid changes in adaptation that cannot otherwise be explained by traditional mechanisms of natural selection. Within the hologenome theory, the holobiont has not only become the principal unit of natural selection but also the result of other step of integration that it is also observed at the cell (
symbiogenesis
Symbiogenesis (endosymbiotic theory, or serial endosymbiotic theory,) is the leading evolutionary theory of the origin of eukaryotic cells from prokaryotic organisms. The theory holds that mitochondria, plastids such as chloroplasts, and pos ...
,
endosymbiosis
An ''endosymbiont'' or ''endobiont'' is any organism that lives within the body or cells of another organism most often, though not always, in a mutualistic relationship.
(The term endosymbiosis is from the Greek: ἔνδον ''endon'' "within ...
) and genomic levels.
Research methods
Targeted amplicon sequencing
Targeted
amplicon
In molecular biology, an amplicon is a piece of DNA or RNA that is the source and/or product of amplification or replication events. It can be formed artificially, using various methods including polymerase chain reactions (PCR) or ligase chai ...
sequencing relies on having some expectations about the composition of the community that is being studied. In target amplicon sequencing a phylogenetically informative marker is targeted for sequencing. Such a marker should be present in ideally all the expected organisms. It should also evolve in such a way that it is conserved enough that primers can target genes from a wide range of organisms while evolving quickly enough to allow for finer resolution at the taxonomic level. A common marker for human microbiome studies is the gene for bacterial
16S rRNA 16S rRNA may refer to:
* 16S ribosomal RNA
16 S ribosomal RNA (or 16 S rRNA) is the RNA component of the 30S subunit of a prokaryotic ribosome ( SSU rRNA). It binds to the Shine-Dalgarno sequence and provides most of the SSU structure.
The g ...
(''i.e.'' "16S rDNA", the sequence of DNA which encodes the ribosomal RNA molecule). Since ribosomes are present in all living organisms, using 16S rDNA allows for DNA to be amplified from many more organisms than if another marker were used. The 16S rRNA gene contains both slowly evolving regions and 9 fast evolving regions, also known as
hypervariable region
A hypervariable region (HVR) is a location within nuclear DNA or the D-loop of mitochondrial DNA in which base pairs of nucleotides repeat (in the case of nuclear DNA) or have substitutions (in the case of mitochondrial DNA). Changes or repeat ...
s (HVRs); the former can be used to design broad primers while the latter allow for finer taxonomic distinction. However, species-level resolution is not typically possible using the 16S rDNA. Primer selection is an important step, as anything that cannot be targeted by the primer will not be amplified and thus will not be detected, moreover different sets of primers can be selected to amplify different HVRs in the gene, or pairs of them. The appropriate choice of which HVRs to amplify has to be made according to the taxonomic groups of interest, as different target regions has been shown to influence taxonomical classification.
Targeted studies of eukaryotic and viral communities are limited and subject to the challenge of excluding host DNA from amplification and the reduced eukaryotic and viral biomass in the human microbiome.
After the amplicons are sequenced, molecular phylogenetic methods are used to infer the composition of the microbial community. This can be done through clustering methodologies, by clustering the amplicons into
operational taxonomic unit
An Operational Taxonomic Unit (OTU) is an operational definition used to classify groups of closely related individuals. The term was originally introduced in 1963 by Robert R. Sokal and Peter H. A. Sneath in the context of numerical taxonomy, w ...
s (OTUs); or alternatively with denoising methodologies, identifying
amplicon sequence variant An amplicon sequence variant (ASV) is any one of the inferred single DNA sequences recovered from a high-throughput analysis of marker genes. Because these analyses, also called "amplicon reads," are created following the removal of erroneous seque ...
s (ASVs).
Phylogenetic relationships are then inferred between the sequences. Due to the complexity of the data, distance measures such as UniFrac distances are usually defined between microbiome samples, and downstream multivariate methods are carried out on the distance matrices. An important point is that the scale of data is extensive, and further approaches must be taken to identify patterns from the available information. Tools used to analyze the data include VAMPS,
QIIME QIIME (an abbreviation for ''Quantitative Insights Into Microbial Ecology'') is a bioinformatic pipeline designated for the task of analysing microbial communities that were sampled through marker gene (e.g. 16S or 18S rRNA genes) amplicon sequenc ...
Metagenomics
Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microb ...
is also used extensively for studying microbial communities. In metagenomic sequencing, DNA is recovered directly from environmental samples in an untargeted manner with the goal of obtaining an unbiased sample from all genes of all members of the community. Recent studies use shotgun
Sanger sequencing
Sanger sequencing is a method of DNA sequencing that involves electrophoresis and is based on the random incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication. After first being developed by Fred ...
or
pyrosequencing
Pyrosequencing is a method of DNA sequencing (determining the order of nucleotides in DNA) based on the "sequencing by synthesis" principle, in which the sequencing is performed by detecting the nucleotide incorporated by a DNA polymerase. Pyroseq ...
to recover the sequences of the reads. The reads can then be assembled into
contig
A contig (from ''contiguous'') is a set of overlapping DNA segments that together represent a consensus region of DNA.Gregory, S. ''Contig Assembly''. Encyclopedia of Life Sciences, 2005.
In bottom-up sequencing projects, a contig refers to ov ...
s. To determine the phylogenetic identity of a sequence, it is compared to available full genome sequences using methods such as
BLAST
Blast or The Blast may refer to:
*Explosion, a rapid increase in volume and release of energy in an extreme manner
*Detonation, an exothermic front accelerating through a medium that eventually drives a shock front
Film
* ''Blast'' (1997 film), ...
. One drawback of this approach is that many members of microbial communities do not have a representative sequenced genome, but this applies to 16S rRNA amplicon sequencing as well and is a fundamental problem. With shotgun sequencing, it can be resolved by having a high coverage (50-100x) of the unknown genome, effectively doing a de novo
genome assembly
In bioinformatics, sequence assembly refers to aligning and merging fragments from a longer DNA sequence in order to reconstruct the original sequence. This is needed as DNA sequencing technology might not be able to 'read' whole genomes in one ...
. As soon as there is a complete genome of an unknown organism available it can be compared phylogenetically and the organism put into its place in the
tree of life
The tree of life is a fundamental archetype in many of the world's mythological, religious, and philosophical traditions. It is closely related to the concept of the sacred tree.Giovino, Mariana (2007). ''The Assyrian Sacred Tree: A Hist ...
, by creating new
taxa
In biology, a taxon (back-formation from ''taxonomy''; plural taxa) is a group of one or more populations of an organism or organisms seen by taxonomists to form a unit. Although neither is required, a taxon is usually known by a particular nam ...
. An emerging approach is to combine shotgun sequencing with proximity-ligation data (
Hi-C
Hi-C is a fruit juice–flavored drink made by the Minute Maid division of The Coca-Cola Company. It was created by Niles Foster in 1946 and released in 1947. The sole original flavor was orange.
History
Niles Foster, a former bakery and ...
) to assemble complete microbial genomes without culturing.
Despite the fact that metagenomics is limited by the availability of reference sequences, one significant advantage of metagenomics over targeted amplicon sequencing is that metagenomics data can elucidate the functional potential of the community DNA. Targeted gene surveys cannot do this as they only reveal the phylogenetic relationship between the same gene from different organisms. Functional analysis is done by comparing the recovered sequences to databases of metagenomic annotations such as
KEGG
KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances. KEGG is utilized for bioinformatics research and education, including data analysis i ...
. The metabolic pathways that these genes are involved in can then be predicted with tools such as MG-RAST, CAMERA and IMG/M.
RNA and protein-based approaches
Metatranscriptomics studies have been performed to study the gene expression of microbial communities through methods such as the pyrosequencing of extracted RNA. Structure based studies have also identified
non-coding RNAs
A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non- ...
(ncRNAs) such as ribozymes from microbiota.Metaproteomics is an approach that studies the proteins expressed by microbiota, giving insight into its functional potential.
Projects
The
Human Microbiome Project
The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on ...
launched in 2008 was a United States
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
initiative to identify and characterize microorganisms found in both healthy and diseased humans. The five-year project, best characterized as a feasibility study with a budget of $115 million, tested how changes in the human microbiome are associated with human health or disease.
The
Earth Microbiome Project
The 'Earth Microbiome Project'' (EMP) is an initiative founded by Janet Jansson, Jack Gilbert and Rob Knight in 2010 to collect natural samples and to analyze the microbial community around the globe.
Microbes are highly abundant, diverse, and h ...
(EMP) is an initiative to collect natural samples and analyze the microbial community around the globe. Microbes are highly abundant, diverse and have an important role in the ecological system. Yet , it was estimated that the total global environmental DNA sequencing effort had produced less than 1 percent of the total DNA found in a liter of seawater or a gram of soil, and the specific interactions between microbes are largely unknown. The EMP aims to process as many as 200,000 samples in different biomes, generating a complete database of microbes on earth to characterize environments and ecosystems by microbial composition and interaction. Using these data, new ecological and evolutionary theories can be proposed and tested.
Gut microbiota and type 2 diabetes
The gut microbiota are very important for the host health because they play role in degradation of non-digestible polysaccharides (fermentation of resistant starch, oligosaccharides, inulin) strengthening gut integrity or shaping the intestinal epithelium, harvesting energy, protecting against pathogens, and regulating host immunity.
Several studies showed that the gut bacterial composition in diabetic patients became altered with increased levels of ''Lactobacillus gasseri'', ''Streptococcus mutans'' and Clostridiales members, with decrease in butyrate-producing bacteria such as ''Roseburia intestinalis'' and ''Faecalibacterium prausnitzii.'' This alteration is due to many factors such as antibiotic abuse, diet, and age''.''
The decrease in butyrate production is associated with defects in intestinal permeability, which could lead to
endotoxemia
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
, which is the increased level of circulating Lipopolysaccharides from gram negative bacterial cells wall. It is found that endotoxemia has association with development of insulin resistance.
In addition that butyrate production affects serotonin level. Elevated serotonin level has contribution in obesity, which is known to be a risk factor for development of diabetes.
Microbiota can be transplanted in the human body for medical purposes.
Gut microbiota development and antibiotics
The colonization of the human gut microbiota may start already before birth. There are multiple factors in the environment that affects the development of the microbiota with birthmode being one of the most impactful.
Another factor that has been observed to cause huge changes in the gut microbiota, particularly in children, is the use of antibiotics, associating with health issues such as higher BMI, and further an increased risk towards metabolic diseases such as obesity. In infants it was observed that amoxicillin and macrolides cause significant shifts in the gut microbiota characterized by a change in the bacterial classes Bifidobacteria, Enterobacteria and Clostridia. A single course of antibiotics in adults causes changes in both the bacterial and fungal microbiota, with even more persistent changes in the fungal communities.Seelbinder, B., Chen, J., Brunke, S., Vazquez-Uribe, R., Santhaman, R., Meyer, A. C., ... & Panagiotou, G. (2020). Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome, 8(1), 1-20 The bacteria and fungi live together in the gut and there is most likely a competition for nutrient sources present. Seelbinder ''et al''. found that commensal bacteria in the gut regulate the growth and pathogenicity of ''Candida albicans'' by their metabolites, particularly by propionate, acetic acid and 5-dodecenoate. ''Candida'' has previously been associated with IBD and further it has been observed to be increased in non-responders to a biological drug, infliximab, given to IBD patients with severe IBD. Propionate and acetic acid are both short-chain fatty acids (SCFAs) that have been observed to be beneficial to gut microbiota health. When antibiotics affect the growth of bacteria in the gut, there might be an overgrowth of certain fungi, which might be pathogenic when not regulated.
Privacy issues
Microbial DNA inhabiting a person's human body can uniquely identify the person. A person's privacy may be compromised if the person anonymously donated microbe DNA data. Their medical condition and identity could be revealed.
See also
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Anagenesis
Anagenesis is the gradual evolution of a species that continues to exist as an interbreeding population. This contrasts with cladogenesis, which occurs when there is branching or splitting, leading to two or more lineages and resulting in separate ...
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Biome
A biome () is a biogeographical unit consisting of a biological community that has formed in response to the physical environment in which they are found and a shared regional climate. Biomes may span more than one continent. Biome is a broader ...
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Human virome
The human virome is the total collection of viruses in and on the human body. Viruses in the human body may infect both human cells and other microbes such as bacteria (as with bacteriophages). Some viruses cause disease, while others may be asy ...
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List of bacterial vaginosis microbiota
Bacterial vaginosis is caused by an imbalance of the naturally occurring bacteria in the vagina. The normally predominant species of ''Lactobacilli'' are markedly reduced. This is the list of organisms that are found in the vagina that are assoc ...
Probiotic
Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria- host ...
Vaginal flora
Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms that colonize the vagina. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora.
The amount and type of ...
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Vaginal microbiota in pregnancy
The vaginal flora in pregnancy, or vaginal microbiota in pregnancy, is different from the vaginal flora (the population of microorganisms that resides in the vagina) before sexual maturity, during reproductive years, and after menopause. A descrip ...