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The human microbiome is the aggregate of all
microbiota Microbiota are "ecological communities of commensal, symbiotic and pathogenic microorganisms A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usu ...
that reside on or within human tissues and
biofluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible fluid In physics, a fluid is a substance that continually Deformation (mechanics), deforms (flows) under an applied shear stress, or external force. ...
s along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva,
oral mucosa The oral mucosa is the mucous membrane A mucous membrane or mucosa is a biological membrane, membrane that lines various cavities in the body and covers the surface of internal organs. It consists of one or more layers of Epithelium, epithelial c ...

oral mucosa
,
conjunctiva The conjunctiva is a tissue (biology), tissue that lines the inside of the eyelids and covers the sclera (the white of the human eye, eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar ...
,
biliary tract The biliary tract, (biliary tree or biliary system) refers to the liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal ...
, and
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system The human digestive system consists of the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, d ...
. Types of
human microbiota'' spp. anaerobically cultured in blood agar medium '' colonies growing on XLD agar plate An agar plate is a Petri dish that contains a growth medium solidified with agar, used to Microbiological culture, culture microorganisms. Sometimes selecti ...
include
bacteria Bacteria (; common noun 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. Typ ...
,
archaea Archaea ( ; singular archaeon ) constitute a domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a pa ...

archaea
,
fungi A fungus (plural The plural (sometimes abbreviated An abbreviation (from Latin ''brevis'', meaning ''short'') is a shortened form of a word or phrase, by any method. It may consist of a group of letters, or words taken from the full ...

fungi
,
protist A protist () is any eukaryotic Eukaryotes () are organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are c ...
s and
viruses A virus is a wikt:submicroscopic, submicroscopic infectious agent that Viral replication, replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, incl ...
. Though
micro-animal 210px, A microscopic arachnid ''Lorryia formosa''">Lorryia_formosa.html" ;"title="arachnid ''Lorryia formosa">arachnid ''Lorryia formosa'' Micro-animals are animals so small that they can be visually observed only under a microscope. Unlike most ...
s can also live on the human body, they are typically excluded from this definition. In the context of
genomics Genomics is an interdisciplinary field of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interact ...
, the term ''human microbiome'' is sometimes used to refer to the collective
genome In the fields of molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...

genome
s of resident microorganisms; however, the term '' human metagenome'' has the same meaning. Humans are colonized by many microorganisms, with approximately the same order of magnitude of non-human cells as human cells. Some microorganisms that colonize humans are
commensal Commensalism is a long-term biological interaction In ecology Ecology (from el, οἶκος, "house" and el, -λογία, label=none, "study of") is the study of the relationships between living organisms, including humans, and their phy ...

commensal
, meaning they co-exist without harming humans; others have a mutualistic relationship with their human hosts. Conversely, some non-
pathogenic In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, ...
microorganisms can harm human hosts via the
metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabo ...

metabolites
they produce, like
trimethylamine Trimethylamine (TMA) is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, propertie ...

trimethylamine
, which the human body converts to
trimethylamine N-oxide Trimethylamine ''N''-oxide (TMAO) is an organic compound , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen chemical bond, bonds. Due to carbon's abi ...
via
FMO3 Flavin-containing monooxygenase 3 (FMO3), also known as dimethylaniline ''N'',''N''-Dimethylaniline (DMA) is an organic chemical compound, a substituted derivative of aniline Aniline is an organic compound with the formula C6Hydrogen, H5Ni ...
-mediated oxidation. Certain microorganisms perform tasks that are known to be useful to the human host, but the role of most of them is not well understood. Those that are expected to be present, and that under normal circumstances do not cause disease, are sometimes deemed ''normal flora'' or ''normal microbiota''. The
Human Microbiome Project The Human Microbiome Project (HMP) was a United States National Institutes of Health The National Institutes of Health (NIH) () is the primary agency of the United States government responsible for biomedical and public health research. It was ...
(HMP) took on the project of sequencing 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 its initial results.


Terminology

Though widely known as ''flora or'' ''microflora'', this is a
misnomer A misnomer is a name that is incorrectly or unsuitably applied. Misnomers often arise because something was named long before its correct nature was known, or because an earlier form of something has been replaced by a later form to which the na ...
in technical terms, since the word root ''
flora Flora is all the plant Plants are predominantly photosynthetic Photosynthesis is a process used by plants and other organisms to Energy transformation, convert light energy into chemical energy that, through cellular respiration, ca ...

flora
'' pertains to plants, and '' biota'' refers to the total collection of organisms in a particular ecosystem. Recently, the more appropriate term ''
microbiota Microbiota are "ecological communities of commensal, symbiotic and pathogenic microorganisms A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usu ...
'' is applied, though its use has not eclipsed the entrenched use and recognition of ''flora'' with regard to bacteria and other microorganisms. Both terms are being used in different literature.


Relative numbers

As of 2014, it was reported in popular media and in the scientific literature that there are about 10 times as many microbial cells in the human body as there are human cells; this figure was based on estimates that the human microbiome includes around 100 trillion bacterial cells and that an adult human typically has around 10 trillion human cells.American Academy of Microbiolog
FAQ: Human Microbiome
January 2014
In 2014, the
American Academy of Microbiology The American Society for Microbiology (ASM), originally the Society of American Bacteriologists, is a professional organization for scientists who study virus A virus is a submicroscopic infectious agent that Viral replication, replicates ...
published a
FAQ A frequently asked questions (FAQ) list is often used in articles, websites, email lists, and online forums where common questions tend to recur, for example through posts or queries by new users related to common knowledge gaps. The purpose ...

FAQ
that emphasized that the number of microbial cells and the number of human cells are both estimates, and noted that recent research had arrived at a new estimate of the number of human cellsapproximately 37.2 trillion, meaning that the ratio of microbial-to-human cells, if the original estimate of 100 trillion bacterial cells is correct, is closer to 3:1.Judah L. Rosner for Microbe Magazine, February 2014
Ten Times More Microbial Cells than Body Cells in Humans?
/ref> In 2016, another group published a new estimate of the ratio being roughly 1:1 (1.3:1, with "an uncertainty of 25% and a variation of 53% over the population of standard 70-kg [] males").Alison Abbott for Nature News. 8 January 201
Scientists bust myth that our bodies have more bacteria than human cells
/ref> A more recent estimate is a ratio of 1.3:1 bacterial cells for every human cell, whereas the number of phages and viruses outnumber bacterial cells by at least a order of magnitude more. The number of bacterial genes (assuming 1000 bacterial species in the gut with 2000 genes per species) is estimated to be 2,000,000 genes, 100 times the number of approximately 20,000 human genes.


Study

The problem of elucidating the human microbiome is essentially identifying the members of a microbial community, which includes bacteria, eukaryotes, and viruses. This is done primarily using
deoxyribonucleic acid Deoxyribonucleic acid (; DNA) is a molecule composed of two polynucleotide chains that coil around each other to form a Nucleic acid double helix, double helix carrying genetics, genetic instructions for the development, functioning, growth ...
(DNA)-based studies, though
ribonucleic acid Ribonucleic acid (RNA) is a polymer A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance or material consisting of very large molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of ...
(RNA), protein and metabolite based studies are also performed. DNA-based microbiome studies typically can be categorized as either targeted
amplicon In molecular biology Molecular biology is the branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, molecular synthesis, modification, mechan ...

amplicon
studies or, more recently,
shotgun A shotgun (also known as a scattergun, or historically as a fowling piece) is a long gun, long-barreled firearm designed to shoot a straight-walled cartridge (firearms), cartridge known as a shotshell, which usually discharges numerous small ...
metagenomic Metagenomics is the study of genetic material recovered directly from environmental A biophysical environment is a life, biotic and Abiotic component, abiotic surrounding of an organism or population, and consequently includes the factors th ...

metagenomic
studies. The former focuses on specific known marker genes and is primarily informative taxonomically, while the latter is an entire metagenomic approach which can also be used to study the functional potential of the community. One of the challenges that is present in human microbiome studies, but not in other metagenomic studies, is to avoid including the host DNA in the study. Aside from simply elucidating the composition of the human microbiome, one of the major questions involving the human microbiome is whether there is a "core", that is, whether there is a subset of the community that is shared among most humans. If there is a core, then it would be possible to associate certain community compositions with disease states, which is one of the goals of the HMP. It is known that the human microbiome (such as the gut microbiota) is highly variable both within a single subject and among different individuals, a phenomenon which is also observed in mice. On 13 June 2012, a major milestone of the HMP was announced by the
National Institutes of Health The National Institutes of Health (NIH ) is the primary agency of the United States government The federal government of the United States (U.S. federal government or U.S. government) is the national government of the United States ...
(NIH) director
Francis Collins Francis Sellers Collins (born April 14, 1950) is an American Medical genetics, physician-geneticist who discovered the genes associated with a number of diseases and led the Human Genome Project. He is the former director of the National Instit ...

Francis Collins
. The announcement was accompanied with a series of coordinated articles published in
Nature Nature, in the broadest sense, is the natural, physical, material world or universe The universe ( la, universus) is all of space and time and their contents, including planets, stars, galaxy, galaxies, and all other forms of matter an ...
and several journals in the Public Library of Science (PLoS) on the same day. By mapping the normal microbial make-up of healthy humans using genome sequencing techniques, the researchers of the HMP have created a reference database and the boundaries of normal microbial variation in humans. From 242 healthy U.S. volunteers, more than 5,000 samples were collected from tissues from 15 (men) to 18 (women) body sites such as mouth, nose, skin, lower intestine (stool), and vagina. All the DNA, human and microbial, were analyzed with DNA sequencing machines. The microbial genome data were extracted by identifying the bacterial specific ribosomal RNA,
16S rRNA 16S rRNA may refer to: * 16S ribosomal RNA, the prokaryotic ribosomal subunit * Mitochondrially encoded 16S RNA, the eukaryotic ribosomal subunit {{Short pages monitor The environment present in the human mouth allows the growth of characteristic microorganisms found there. It provides a source of water and nutrients, as well as a moderate temperature. Resident microbes of the mouth adhere to the teeth and gums to resist mechanical flushing from the mouth to stomach where acid-sensitive microbes are destroyed by hydrochloric acid. Anaerobic bacteria in the oral cavity include: ''
Actinomyces ''Actinomyces'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, including the principles that underlie such classification. The term may also refer ...
'', ''Arachnia (bacterium), Arachnia'', ''Bacteroides'', ''Bifidobacterium'', ''Eubacterium'', ''Fusobacterium'', ''Lactobacillus'', ''Leptotrichia'', ''Peptococcus'', ''Peptostreptococcus'', ''Propionibacterium'', ''Selenomonas'', ''Treponema'', and ''Veillonella''. Genera of fungi that are frequently found in the mouth include ''Candida (fungus), Candida'', ''Cladosporium'', ''Aspergillus'', ''Fusarium'', ''Glomus (fungus), Glomus'', ''Alternaria'', ''Penicillium'', and ''Cryptococcus'', among others. Bacteria accumulate on both the hard and soft oral tissues in biofilm allowing them to adhere and strive in the oral environment while protected from the environmental factors and antimicrobial agents. Saliva plays a key biofilm homeostatic role allowing recolonization of bacteria for formation and controlling growth by detaching biofilm buildup. It also provides a means of nutrients and temperature regulation. The location of the biofilm determines the type of exposed nutrients it receives. Oral bacteria have evolved mechanisms to sense their environment and evade or modify the host. However, a highly efficient innate host defense system constantly monitors the bacterial colonization and prevents bacterial invasion of local tissues. A dynamic equilibrium exists between dental plaque bacteria and the innate host defense system. This dynamic between host oral cavity and oral microbes plays a key role in health and disease as it provides entry into the body. A healthy equilibrium presents a symbiotic relationship where oral microbes limit growth and adherence of pathogens while the host provides an environment for them to flourish. Ecological changes such as change of immune status, shift of resident microbes and nutrient availability shift from a mutual to parasitic relationship resulting in the host being prone to oral and systemic disease. Systemic diseases such as diabetes and cardiovascular diseases has been correlated to poor oral health. Of particular interest is the role of oral microorganisms in the two major dental diseases: dental caries and
periodontal disease Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis Gingivitis is a non-destructive disease that causes inflammation Inflam ...
. Pathogen colonization at the periodontium cause an excessive immune response resulting in a periodontal pocket- a deepened space between the tooth and gingiva. This acts as a protected blood-rich reservoir with nutrients for anaerobic pathogens. Systemic disease at various sites of the body can result from oral microbes entering the blood bypassing periodontal pockets and oral membranes. Persistent proper oral hygiene is the primary method for preventing oral and systemic disease. It reduces the density of biofilm and overgrowth of potential pathogenic bacteria resulting in disease. However, proper oral hygiene may not be enough as the oral microbiome, genetics, and changes to immune response play a factor in developing chronic infections. Use of antibiotics could treat already spreading infection but ineffective against bacteria within biofilms.


Nasal cavity

The healthy nasal microbiome is dominated by Corynebacterium, and Staphylococcus. The mucosal microbiome plays a critical role in modulating viral infection.


Lung

Much like the oral cavity, the upper and lower respiratory system possess mechanical deterrents to remove microbes. Goblet cells produce mucous which traps microbes and moves them out of the respiratory system via continuously moving Cilium, ciliated epithelial cells. In addition, a bactericidal effect is generated by nasal mucus which contains the enzyme lysozyme. The upper and lower respiratory tract appears to have its own set of microbiota. Pulmonary bacterial microbiota belong to 9 major bacterial genera: ''Prevotella'', ''Sphingomonas'', ''Pseudomonas'', ''Acinetobacter'', ''Fusobacterium'', ''Megasphaera'', ''Veillonella'', ''Staphylococcus'', and ''Streptococcus''. Some of the bacteria considered "normal biota" in the respiratory tract can cause serious disease especially in immunocompromised individuals; these include ''Streptococcus pyogenes'', ''Haemophilus influenzae'', ''Streptococcus pneumoniae'', ''Neisseria meningitidis'', and ''Staphylococcus aureus''. Fungal genera that compose the pulmonary mycobiome include ''Candida'', ''Malassezia'', ''Neosartorya'', ''Saccharomyces'', and ''Aspergillus'', among others. Unusual distributions of bacterial and fungal genera in the respiratory tract is observed in people with cystic fibrosis. Their bacterial flora often contains antibiotic-resistant and slow-growing bacteria, and the frequency of these pathogens changes in relation to age.


Biliary tract

Traditionally the biliary tract has been considered to be normally sterile, and the presence of microorganisms in bile is a marker of pathological process. This assumption was confirmed by failure in allocation of bacterial strains from the normal bile duct. Papers began emerging in 2013 showing that the normal biliary microbiota is a separate functional layer which protects a biliary tract from colonization by exogenous microorganisms.


Disease and death

Human bodies rely on the innumerable bacterial genes as the source of essential nutrients. Both metagenomic and epidemiological studies indicate vital roles for the human microbiome in preventing a wide range of diseases, from type 2 diabetes and obesity to inflammatory bowel disease, Parkinson's disease, and even mental health conditions like depression. A symbiotic relationship between the gut microbiota and different bacteria may influence an individual's immune response. Although in its infancy, microbiome-based treatment is also showing promise, most notably for treating drug-resistan
''C. difficile''
infection and in diabetes treatment.


''Clostridioides difficile'' infection

An overwhelming presence of the bacteria, ''C. difficile,'' leads to an infection of the gastrointestinal tract, normally associated to dysbiosis with the microbiota believed to have been caused by the administration of antibiotics. Use of antibiotics eradicates the beneficial gut flora within the gastrointestinal tract, which normally prevents pathogenic bacteria from establishing dominance. Traditional treatment for ''C. difficile'' infections includes an additional regime of antibiotics, however, efficacy rates average between 20-30%. Recognizing the importance of healthy gut bacteria, researchers turned to a procedure known as fecal microbiota transplant, where patients experiencing gastrointestinal diseases, such as ''C. difficile'' infection, receive fecal content from a healthy individual in hopes of restoring a normal functioning intestinal microbiota. Fecal microbiota transplant is approximately 85–90% effective in people with CDI for whom antibiotics have not worked or in whom the disease recurs following antibiotics. Most people with CDI recover with one FMT treatment.


Cancer

Although cancer is generally a disease of host genetics and environmental factors, microorganisms are implicated in some 20% of human cancers. Particularly for potential factors in colon cancer, bacterial density is one million times higher than in the small intestine, and approximately 12-fold more cancers occur in the colon compared to the small intestine, possibly establishing a pathogenic role for microbiota in colon and rectum, rectal cancers. Microbial density may be used as a prognosis, prognostic tool in assessment of colorectal cancers. The microbiota may affect carcinogenesis in three broad ways: (i) altering the balance of tumor cell proliferation and death, (ii) regulating immune system function, and (iii) influencing metabolism of host-produced factors, foods and pharmaceuticals. Tumors arising at boundary surfaces, such as the skin, oropharynx and respiratory, digestive and urogenital tracts, harbor a microbiota. Substantial microbe presence at a tumor site does not establish association or causal links. Instead, microbes may find tumor oxygen tension or nutrient profile supportive. Decreased populations of specific microbes or induced oxidative stress may also increase risks. Of the around 1030 microbes on earth, ten are designated by the International Agency for Research on Cancer as human carcinogens. Microbes may secrete proteins or other factors directly drive cell proliferation in the host, or may upregulation, up- or downregulation, down-regulate the host immune system including driving acute or chronic inflammation in ways that contribute to carcinogenesis. Concerning the relationship of immune function and development of inflammation, Mucous membrane, mucosal surface barriers are subject to environmental risks and must rapidly repair to maintain homeostasis. Compromised host or microbiota resiliency also reduce resistance to malignancy, possibly inducing inflammation and cancer. Once barriers are breached, microbes can elicit proinflammatory or immunosuppressive programs through various pathways. For example, cancer-associated microbes appear to activate NF-κΒ signaling within the tumor microenviroment. Other pattern recognition receptors, such as NOD-like receptor, nucleotide-binding oligomerization domain–like receptor (NLR) family members NOD2, ''NOD-2'', ''NLRP3'', ''NLRP6'' and ''NLRP12'', may play a role in mediating colorectal cancer. Likewise ''Helicobacter pylori'' appears to increase the risk of gastric cancer, due to its driving a chronic inflammatory response in the stomach.


Inflammatory bowel disease

Inflammatory bowel disease consists of two different diseases: ulcerative colitis and Crohn's disease and both of these diseases present with disruptions in the gut microbiota (also known as dysbiosis). This dysbiosis presents itself in the form of decreased microbial diversity in the gut, and is correlated to defects in host genes that changes the innate immune response in individuals.


Human immunodeficiency virus

The HIV disease progression influences the composition and function of the gut microbiota, with notable differences between HIV-negative, HIV-positive, and post-Anti-retroviral, ART HIV-positive populations. HIV decreases the integrity of the gut epithelial barrier function by affecting tight junctions. This breakdown allows for translocation across the gut epithelium, which is thought to contribute to increases in inflammation seen in people with HIV. Vaginal microbiota plays a role in the infectivity of HIV, with an increased risk of infection and transmission when the woman has
bacterial vaginosis Bacterial vaginosis (BV) is a of the caused by excessive growth of . Common symptoms include increased that often smells like fish. The discharge is usually white or gray in color. may occur. Itching is uncommon. Occasionally, there may be n ...
, a condition characterized by an abnormal balance of vaginal bacteria. The enhanced infectivity is seen with the increase in Proinflammatory cytokine, pro-inflammatory cytokines and CCR5, CCR5 + CD4+ cells in the vagina. However, a decrease in infectivity is seen with increased levels of vaginal ''Lactobacillus,'' which promotes an anti-inflammatory condition.


Death

With death, the microbiome of the living body collapses and a different composition of microorganisms named ''necrobiome'' establishes itself as an important active constituent of the complex physical decomposition process. Its predictable changes over time are thought to be useful to help determine the time of death.


Environmental health

Studies in 2009 questioned whether the decline in biota (including microfauna) as a result of human intervention might impede human health, hospital safety procedures, food product design, and treatments of disease.


Migration

Preliminary research indicates that immediate changes in the microbiota may occur when a person International migration, migrates from one country to another, such as when Thailand, Thai immigrants settled in the United States or when Latin Americans immigrated into the United States. Losses of microbiota diversity were greater in obese individuals and children of immigrants.


See also

* Carbon monoxide-releasing molecules * Drug resistance *
Human Microbiome Project The Human Microbiome Project (HMP) was a United States National Institutes of Health The National Institutes of Health (NIH) () is the primary agency of the United States government responsible for biomedical and public health research. It was ...
* Human milk microbiome * Human virome * Initial acquisition of microbiota * List of bacterial vaginosis microbiota * Microbiome * World Community Grid#Active projects, Microbiome Immunity Project * Microorganism * uBiome


Bibliography

*Ed Yong. ''I Contain Multitudes: The Microbes Within Us and a Grander View of Life.'' 368 pages, Published 9 August 2016 by Ecco, .


References


External links


The Secret World Inside You
Exhibit 2015–2016, American Museum of Natural History
FAQ: Human Microbiome, January 2014
American Society For Microbiology {{DEFAULTSORT:Human Flora Bacteriology Bacteria and humans Microbiology Microbiomes Environmental microbiology Gut flora, Human genome projects