Human microbiome

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva,

oral mucosa

, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria,

archaea

,

fungi

, protists and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term ''human microbiome'' is sometimes used to refer to the collective

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

, meaning they co-exist without harming humans; others have a mutualistic relationship with their human hosts. Conversely, some non-pathogenic microorganisms can harm human hosts via the

metabolites

they produce, like

trimethylamine

, which the human body converts to trimethylamine N-oxide via FMO3-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 (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 in technical terms, since the word root ''

flora

'' pertains to plants, and '' biota'' refers to the total collection of organisms in a particular ecosystem. Recently, the more appropriate term ''microbiota'' 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 published a

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 (DNA)-based studies, though ribonucleic acid (RNA), protein and metabolite based studies are also performed. DNA-based microbiome studies typically can be categorized as either targeted

amplicon

studies or, more recently, shotgun

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 (NIH) director

Francis Collins

. The announcement was accompanied with a series of coordinated articles published in Nature 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

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