Human microbiome

{{short description|Microorganisms in or on human skin and biofluids}} {{Distinguish|Microbiome}} {{Use dmy dates|date=November 2018}} [[File:Skin_Microbiome20169-300.jpg|upright=1.25|thumb|Graphic depicting the human skin microbiota, with relative prevalences of various classes of bacteria]] [[File:Microbiome.jpg|upright=1.25|thumb|Diagram of human gastrointestinal tract microbiota depicted in various regions]]

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,<ref name="pmid26229597" /><ref>{{cite journal |last1=Mousa |first1=Walaa K. |last2=Chehadeh |first2=Fadia |last3=Husband |first3=Shannon |title=Recent Advances in Understanding the Structure and Function of the Human Microbiome |journal=Frontiers in Microbiology |date=2022 |volume=13 |article-number=825338 |doi=10.3389/fmicb.2022.825338 |pmid=35185849 |doi-access=free |pmc=8851206}}</ref> including the gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, ocular surface, and the biliary 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 genomes of resident microorganisms;<ref name="Prescotts">{{Cite book | vauthors = Sherwood L, Willey J, Woolverton C |url={{google books|plainurl=y|id=sBCSRAAACAAJ}} |title=Prescott's Microbiology |publisher=McGraw Hill |year=2013 |isbn=978-0-07-340240-6 |edition=9th |location=New York |pages=713–721 |oclc=886600661 |name-list-style=vanc}}</ref> however, the term ''human metagenome'' has the same meaning.<ref name="pmid26229597">{{cite journal | vauthors = Marchesi JR, Ravel J | title = The vocabulary of microbiome research: a proposal | journal = Microbiome | volume = 3 | article-number = 31 | date = 2015 | issue = 1 | pmid = 26229597 | pmc = 4520061 | doi = 10.1186/s40168-015-0094-5 | quote = Microbiome This term refers to the entire habitat, including the microorganisms (bacteria, archaea, lower and higher eurkaryotes, and viruses), their genomes (i.e., genes), and the surrounding environmental conditions. This definition is based on that of "biome," the biotic and abiotic factors of given environments. Others in the field limit the definition of microbiome to the collection of genes and genomes of members of a microbiota. It is argued that this is the definition of metagenome, which combined with the environment constitutes the microbiome. | doi-access = free | bibcode = 2015Micb....3...31M }}</ref>

The human body hosts many microorganisms, with approximately the same order of magnitude of non-human cells as human cells.<ref name="Sender">{{Cite journal |vauthors=Sender R, Fuchs S, Milo R |date=January 2016 |title=Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans |journal=Cell |volume=164 |issue=3 |pages=337–40 |doi=10.1016/j.cell.2016.01.013 |pmid=26824647 |doi-access=free |bibcode=2016Cell..164..337S }}</ref> Some microorganisms that humans host are commensal, meaning they co-exist without harming humans; others have a mutualistic relationship with their human hosts.<ref name="Prescotts" />{{rp|700}}<ref name="Quigley2013rev">{{Cite journal |vauthors=Quigley EM |date=September 2013 |title=Gut bacteria in health and disease |journal=Gastroenterology & Hepatology |volume=9 |issue=9 |pages=560–9 |pmc=3983973 |pmid=24729765}}</ref> 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.<ref name="TMA">{{Cite journal |vauthors=Falony G, Vieira-Silva S, Raes J |date=2015 |title=Microbiology Meets Big Data: The Case of Gut Microbiota-Derived Trimethylamine |journal=Annual Review of Microbiology |volume=69 |pages=305–21 |doi=10.1146/annurev-micro-091014-104422 |pmid=26274026 |quote=we review literature on trimethylamine (TMA), a microbiota-generated metabolite linked to atherosclerosis development.|doi-access=free }}</ref><ref name="TMA diseases">{{Cite journal |vauthors=Gaci N, Borrel G, Tottey W, O'Toole PW, Brugère JF |date=November 2014 |title=Archaea and the human gut: new beginning of an old story |journal=World Journal of Gastroenterology |volume=20 |issue=43 |pages=16062–78 |doi=10.3748/wjg.v20.i43.16062 |pmc=4239492 |pmid=25473158 |quote=Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. |doi-access=free }}</ref> 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''.<ref name="Prescotts" />

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.<ref name="Prescotts" /> It reached a milestone in 2012 when it published its initial results.<ref name="hmpdata">{{Cite web |url=http://www.nih.gov/news/health/jun2012/nhgri-13.htm |archive-url=https://web.archive.org/web/20120617171944/http://www.nih.gov/news/health/jun2012/nhgri-13.htm |archive-date=17 June 2012 |title=NIH Human Microbiome Project defines normal bacterial makeup of the body |date=13 June 2012 |publisher=NIH News}}</ref> {{toclimit|3}}

==Terminology== {{Life timeline}} 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.<ref name=Quigley2013rev/>

==Relative numbers== The number of bacterial cells in the human body is estimated to be around 38 trillion, while the estimate for human cells is around 30 to 40 trillion.<ref>{{Cite journal |last1=Sender |first1=Ron |last2=Fuchs |first2=Shai |last3=Milo |first3=Ron |date=2016-08-19 |title=Revised Estimates for the Number of Human and Bacteria Cells in the Body |journal=PLOS Biology |language=en |volume=14 |issue=8 |article-number=e1002533 |doi=10.1371/journal.pbio.1002533 |issn=1545-7885 |pmc=4991899 |pmid=27541692 |doi-access=free }}</ref><ref>{{Cite journal |last1=Lacy |first1=Brian E. |last2=Spiegel |first2=Brennan |date=July 2019 |title=Introduction to the Gut Microbiome Special Issue |url=https://journals.lww.com/ajg/fulltext/2019/07000/introduction_to_the_gut_microbiome_special_issue.1.aspx |journal= American Journal of Gastroenterology|language=en-US |volume=114 |issue=7 |page=1013 |doi=10.14309/ajg.0000000000000303 |pmid=31205134 |issn=0002-9270|url-access=subscription }}</ref><ref>{{Cite journal |last1=Sung |first1=Jaeyun |last2=Rajendraprasad |first2=Sanu S. |last3=Philbrick |first3=Kemuel L. |last4=Bauer |first4=Brent A. |last5=Gajic |first5=Ognjen |last6=Shah |first6=Aditya |last7=Laudanski |first7=Krzysztof |last8=Bakken |first8=Johan S. |last9=Skalski |first9=Joseph |last10=Karnatovskaia |first10=Lioudmila V. |date=February 2024 |title=The human gut microbiome in critical illness: disruptions, consequences, and therapeutic frontiers |journal=Journal of Critical Care |volume=79 |article-number=154436 |doi=10.1016/j.jcrc.2023.154436 |issn=1557-8615 |pmid=37769422|doi-access=free |pmc=11034825 }}</ref><ref name="NN2016">{{Cite journal |last=Abbott |first=Alison |date=2016-01-08 |title=Scientists bust myth that our bodies have more bacteria than human cells |url=https://www.nature.com/articles/nature.2016.19136 |journal=Nature |language=en |doi=10.1038/nature.2016.19136 |issn=1476-4687 |s2cid=190879263 |doi-access=free}}</ref> The number of bacterial genes is estimated to be 2 million, 100 times the number of approximately 20,000 human genes.<ref>{{Cite journal |last1=Gilbert |first1=Jack A. |last2=Blaser |first2=Martin J. |last3=Caporaso |first3=J. Gregory |last4=Jansson |first4=Janet K. |last5=Lynch |first5=Susan V. |last6=Knight |first6=Rob |date=2018-04-10 |title=Current understanding of the human microbiome |journal=Nature Medicine |volume=24 |issue=4 |pages=392–400 |doi=10.1038/nm.4517 |issn=1546-170X |pmc=7043356 |pmid=29634682}}</ref><ref>{{Cite journal |last1=Wischmeyer |first1=Paul E. |last2=McDonald |first2=Daniel |last3=Knight |first3=Rob |date=August 2016 |title=Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness |journal=Current Opinion in Critical Care |volume=22 |issue=4 |pages=347–353 |doi=10.1097/MCC.0000000000000321 |issn=1531-7072 |pmc=5065053 |pmid=27327243}}</ref><ref>{{Cite journal |last1=Qin |first1=Junjie |last2=Li |first2=Ruiqiang |last3=Raes |first3=Jeroen |last4=Arumugam |first4=Manimozhiyan |last5=Burgdorf |first5=Kristoffer Solvsten |last6=Manichanh |first6=Chaysavanh |last7=Nielsen |first7=Trine |last8=Pons |first8=Nicolas |last9=Levenez |first9=Florence |last10=Yamada |first10=Takuji |last11=Mende |first11=Daniel R. |last12=Li |first12=Junhua |last13=Xu |first13=Junming |last14=Li |first14=Shaochuan |last15=Li |first15=Dongfang |date=2010-03-04 |title=A human gut microbial gene catalogue established by metagenomic sequencing |journal=Nature |volume=464 |issue=7285 |pages=59–65 |doi=10.1038/nature08821 |issn=1476-4687 |pmc=3779803 |pmid=20203603|bibcode=2010Natur.464...59. }}</ref>

==Evaluation== {{main|Human Microbiome Project}} thumb|upright=1.25|right|Flowchart illustrating how the human microbiome is studied on the DNA level. {{microbiomes|human}}

The problem of elucidating the human microbiome is essentially identifying the numerous members of a diverse microbial community, which includes bacteria, eukaryotes, and viruses.<ref name="hmp">{{Cite journal |display-authors=6 |vauthors=Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, Bonazzi V, McEwen JE, Wetterstrand KA, Deal C, Baker CC, Di Francesco V, Howcroft TK, Karp RW, Lunsford RD, Wellington CR, Belachew T, Wright M, Giblin C, David H, Mills M, Salomon R, Mullins C, Akolkar B, Begg L, Davis C, Grandison L, Humble M, Khalsa J, Little AR, Peavy H, Pontzer C, Portnoy M, Sayre MH, Starke-Reed P, Zakhari S, Read J, Watson B, Guyer M |date=December 2009 |title=The NIH Human Microbiome Project |journal=Genome Research |volume=19 |issue=12 |pages=2317–23 |doi=10.1101/gr.096651.109 |pmc=2792171 |pmid=19819907}}</ref> This is done primarily using deoxyribonucleic acid (DNA)-based studies, though ribonucleic acid (RNA), protein and metabolite based studies are also performed.<ref name=hmp/><ref name="Kucz2012">{{Cite journal |vauthors=Kuczynski J, Lauber CL, Walters WA, Parfrey LW, Clemente JC, Gevers D, Knight R |date=December 2011 |title=Experimental and analytical tools for studying the human microbiome |journal=Nature Reviews. Genetics |volume=13 |issue=1 |pages=47–58 |doi=10.1038/nrg3129 |pmc=5119550 |pmid=22179717}}</ref> 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.<ref name=hmp/> 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.<ref name="Vest2008">{{Cite journal |vauthors=Vestheim H, Jarman SN |date=July 2008 |title=Blocking primers to enhance PCR amplification of rare sequences in mixed samples - a case study on prey DNA in Antarctic krill stomachs |journal=Frontiers in Zoology |volume=5 |page=12 |doi=10.1186/1742-9994-5-12 |pmc=2517594 |pmid=18638418 |doi-access=free }}</ref>

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.<ref>{{Cite journal |display-authors=6 |vauthors=Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP, Ugarte E, Muñoz-Tamayo R, Paslier DL, Nalin R, Dore J, Leclerc M |date=October 2009 |title=Towards the human intestinal microbiota phylogenetic core |journal=Environmental Microbiology |volume=11 |issue=10 |pages=2574–84 |doi=10.1111/j.1462-2920.2009.01982.x |pmid=19601958|bibcode=2009EnvMi..11.2574T |doi-access=free }}</ref><ref name="HK2009">{{Cite journal |vauthors=Hamady M, Knight R |date=July 2009 |title=Microbial community profiling for human microbiome projects: Tools, techniques, and challenges |journal=Genome Research |volume=19 |issue=7 |pages=1141–52 |doi=10.1101/gr.085464.108 |pmc=3776646 |pmid=19383763}}</ref> 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 also observed in mice.<ref name=Quigley2013rev/>

On 13 June 2012, a major milestone of the HMP was announced by the National Institutes of Health (NIH) director Francis Collins.<ref name=hmpdata/> The announcement was accompanied with a series of coordinated articles published in Nature<ref>{{Cite journal |vauthors=Methé BA, Nelson KE, Pop M, Creasy HH, Giglio MG, Huttenhower C, etal |date=June 2012 |title=A framework for human microbiome research |journal=Nature |volume=486 |issue=7402 |pages=215–21 |bibcode=2012Natur.486..215T |doi=10.1038/nature11209 |pmc=3377744 |pmid=22699610 |collaboration=Human Microbiome Project Consortium}}</ref><ref>{{Cite journal |last=The Human Microbiome Project Consortium |date=June 2012 |title=Structure, function and diversity of the healthy human microbiome |journal=Nature |volume=486 |issue=7402 |pages=207–14 |bibcode=2012Natur.486..207T |doi=10.1038/nature11234 |pmc=3564958 |pmid=22699609 |doi-access=free}}</ref> 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 15 body sites in men and 18 sites in women, including 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. The researchers calculated that more than 10,000 microbial species occupy the human ecosystem, and they have identified 81–99% of the genera.<ref>{{Cite web |date=2015-08-31 |title=NIH Human Microbiome Project defines normal bacterial makeup of the body |url=https://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body |archive-url=https://web.archive.org/web/20151105153226/http://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body |archive-date=5 November 2015 |access-date=2023-07-07 |website=National Institutes of Health (NIH) |language=EN}}</ref>

=== Post-processing analysis === Statistical analysis is essential to validate the obtained results (ANOVA can be used to size the differences between the groups); when paired with graphical tools, the outcome is easily visualized and understood.<ref name=":0">{{cite journal | vauthors = Quince C, Walker AW, Simpson JT, Loman NJ, Segata N | title = Shotgun metagenomics, from sampling to analysis | journal = Nature Biotechnology | volume = 35 | issue = 9 | pages = 833–844 | date = September 2017 | pmid = 28898207 | doi = 10.1038/nbt.3935 | url = http://aura.abdn.ac.uk/bitstream/2164/10167/1/NBT_R37313C_line_edit_SJ_1493899923_1_final_for_self_archiving.pdf | hdl = 2164/10167 | s2cid = 19041044 | hdl-access = free }}</ref>

Once a metagenome is assembled, it is possible to infer the functional potential of the microbiome. The computational challenges for this type of analysis are greater than for single genomes, because metagenome assemblers typically have poorer quality, and many recovered genes are incomplete or fragmented. After the gene identification step, the data can be used to carry out a functional annotation by means of multiple alignment of the target genes against orthologs databases.<ref>{{cite journal | vauthors = Claesson MJ, Clooney AG, O'Toole PW | title = A clinician's guide to microbiome analysis | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 14 | issue = 10 | pages = 585–595 | date = October 2017 | pmid = 28790452 | doi = 10.1038/nrgastro.2017.97 | s2cid = 24644894 }}</ref>

=== Marker gene analysis === Marker gene analysis is a technique that exploits primers to target a specific genetic region and enables the determination of the microbial phylogenies. The genetic region is characterized by a highly variable region, which can confer detailed identification; it is delimited by conserved regions, which function as binding sites for primers used in PCR. The main gene used to characterize bacteria and archaea is 16S rRNA gene, while fungi identification is based on Internal Transcribed Spacer (ITS). The technique is fast and relatively inexpensive and enables a low-resolution classification of a microbial sample. It is optimal for samples that may be contaminated by host DNA. Primer affinity varies among all DNA sequences, which may result in biases during the amplification reaction. Low-abundance samples are susceptible to overamplification errors, since the other contaminating microorganisms are over-represented with increasing PCR cycles. Optimization of primer selection can help to decrease such errors, although it requires complete knowledge of the microorganisms present in the sample and their relative abundances.<ref name=":1">{{cite journal | vauthors = Knight R, Vrbanac A, Taylor BC, Aksenov A, Callewaert C, Debelius J, Gonzalez A, Kosciolek T, McCall LI, McDonald D, Melnik AV, Morton JT, Navas J, Quinn RA, Sanders JG, Swafford AD, Thompson LR, Tripathi A, Xu ZZ, Zaneveld JR, Zhu Q, Caporaso JG, Dorrestein PC | display-authors = 6 | title = Best practices for analysing microbiomes | journal = Nature Reviews. Microbiology | volume = 16 | issue = 7 | pages = 410–422 | date = July 2018 | pmid = 29795328 | doi = 10.1038/s41579-018-0029-9 | s2cid = 43936002 | url = https://biblio.ugent.be/publication/8678762 | url-access = subscription }}</ref>

Marker gene analysis can be influenced by the primer choice; in this kind of analysis, it is desirable to use a well-validated protocol (such as the one used in the Earth Microbiome Project). The first step in marker gene amplicon analysis is to remove sequencing errors. Many sequencing platforms are reliable, but most of the apparent sequence diversity is still due to errors during the sequencing process. To reduce this phenomenon, the first approach is to cluster sequences into Operational taxonomic unit (OTUs): this process consolidates similar sequences (a 97% similarity threshold is usually adopted) into a single feature that can be used in further analysis steps. However, this method would discard SNPs because they would get clustered into a single OTU. Another approach is Oligotyping, which includes position-specific information from 16s rRNA sequencing to detect small nucleotide variations and to discriminate between closely related, distinct taxa. These methods give as an output a table of DNA sequences and counts of the different sequences per sample rather than OTU.<ref name=":1" />

Another important step in the analysis is to assign a taxonomic name to microbial sequences in the data. This can be done using machine learning approaches that can reach an accuracy at genus-level of about 80%. Other popular analysis packages provide support for taxonomic classification using exact matches to reference databases and should provide greater specificity, but poor sensitivity. Unclassified microorganism should be further checked for organelle sequences.<ref name=":1" />

=== Phylogenetic analysis === Many methods that exploit phylogenetic inference use the 16SRNA gene for Archaea and Bacteria and the 18SRNA gene for Eukaryotes. Phylogenetic comparative methods (PCMs) are based on the comparison of multiple traits among microorganisms, where a higher number of shared traits correlates with closer relationships. Usually, PCMs are coupled with phylogenetic generalized least squares (PGLS) or other statistical analyses to get more significant results. Ancestral state reconstruction is used in microbiome studies to impute trait values for taxa whose traits are unknown. This is commonly performed with PICRUSt, which relies on available databases. Phylogenetic variables are chosen by researchers according to the type of study: through the selection of some variables with significant biological information, it is possible to reduce the dimension of the data to be analysed.<ref name=":2" />

Phylogeny-aware distance is usually performed with UniFrac or similar tools, such as Sørensen's index or Rao's D, to quantify the differences between the different communities. All of these methods are negatively affected by horizontal gene transmission (HGT), since they can generate errors and lead to the correlation of distant species. There are different ways to reduce the negative impact of HGT, including the use of multiple genes or computational tools to assess the probability of putative HGT events.<ref name=":2">{{cite journal | vauthors = Washburne AD, Morton JT, Sanders J, McDonald D, Zhu Q, Oliverio AM, Knight R | title = Methods for phylogenetic analysis of microbiome data | journal = Nature Microbiology | volume = 3 | issue = 6 | pages = 652–661 | date = June 2018 | pmid = 29795540 | doi = 10.1038/s41564-018-0156-0 | s2cid = 43962376 }}</ref>

=== Ecological Network analysis === Microbial communities develop in a very complex dynamic that can be viewed and analyzed as an ecosystem. The ecological interactions between microbes govern its change, equilibrium and stability, and can be represented by a population dynamic model.<ref>{{cite journal |doi=10.1186/s40168-020-00875-0 |title=Microbiome definition re-visited: Old concepts and new challenges |year=2020 |last1=Berg |first1=Gabriele |last2=Rybakova |first2=Daria |last3=Fischer |first3=Doreen |last4=Cernava |first4=Tomislav |last5=Vergès |first5=Marie-Christine Champomier |last6=Charles |first6=Trevor |last7=Chen |first7=Xiaoyulong |last8=Cocolin |first8=Luca |last9=Eversole |first9=Kellye |last10=Corral |first10=Gema Herrero |last11=Kazou |first11=Maria |last12=Kinkel |first12=Linda |last13=Lange |first13=Lene |last14=Lima |first14=Nelson |last15=Loy |first15=Alexander |last16=MacKlin |first16=James A. |last17=Maguin |first17=Emmanuelle |last18=Mauchline |first18=Tim |last19=McClure |first19=Ryan |last20=Mitter |first20=Birgit |last21=Ryan |first21=Matthew |last22=Sarand |first22=Inga |last23=Smidt |first23=Hauke |last24=Schelkle |first24=Bettina |last25=Roume |first25=Hugo |last26=Kiran |first26=G. Seghal |last27=Selvin |first27=Joseph |last28=Souza |first28=Rafael Soares Correa de |last29=Van Overbeek |first29=Leo |last30=Singh |first30=Brajesh K. |journal=Microbiome |volume=8 |issue=1 |page=103 |pmid=32605663 |pmc=7329523 |display-authors=1 |doi-access=free }}</ref> The ongoing study of ecological features of the microbiome is growing rapidly and allows us to understand the fundamental properties of the microbiome. Understanding the underlying rules of microbial communities could help with treating diseases related to unstable microbial communities. A very basic question is whether different humans, who share different microbial communities, have the same underlying microbial dynamics.<ref>{{cite journal |doi=10.1038/534182a |title=Rules of the game for microbiota |year=2016 |last1=Faust |first1=Karoline |last2=Raes |first2=Jeroen |journal=Nature |volume=534 |issue=7606 |pages=182–183 |pmid=27279206 |s2cid=205089271 |doi-access=free }}</ref> Increasing evidence supports microbial dynamics as universal.<ref>{{cite journal |doi=10.1038/nature18301 |title=Universality of human microbial dynamics |year=2016 |last1=Bashan |first1=Amir |last2=Gibson |first2=Travis E. |last3=Friedman |first3=Jonathan |last4=Carey |first4=Vincent J. |last5=Weiss |first5=Scott T. |last6=Hohmann |first6=Elizabeth L. |last7=Liu |first7=Yang-Yu |journal=Nature |volume=534 |issue=7606 |pages=259–262 |pmid=27279224 |pmc=4902290 |bibcode=2016Natur.534..259B }}</ref> This question is a basic step that will allow scientists to develop treatment strategies, based on the complex dynamics of human microbial communities. There are many important properties on which considerations should be taken into account for developing intervention strategies for controlling the human microbial dynamics, with the goal of decreasing microbially-influenced disease states.<ref>{{cite journal |last1=Liu |first1=Yang-Yu |title=Controlling the human microbiome |url=https://www.cell.com/cell-systems/pdf/S2405-4712(22)00498-7.pdf |journal=Cell Systems |pages=135–159 |language=English |doi=10.1016/j.cels.2022.12.010 |date=15 February 2023|volume=14 |issue=2 |pmid=36796332 |pmc=9942095 }}</ref>

== Types ==

=== Bacteria === thumb|upright=1.25|Commensals vs pathogens mechanism, underlying the inflammation in COPD. Airway epithelium has a complex structure, consisting of at least seven diverse cell types interacting with each other by means of tight junctions. Epithelial cells can deliver some signals into the underlying tissues, taking part in the mechanisms of innate and adaptive immune defence, but the key transmitters of these signals are dendritic cells. Once a pathogenic bacterium (e.g., ''S. pneumoniae'', ''P. aeruginosa'') has activated particular pattern recognition receptors on/in epithelial cells, the proinflammatory signaling pathways are activated. This results mainly in IL-1, IL-6 and IL-8 production. These cytokines induce chemotaxis to the site of infection in their target cells (e.g., neutrophils, dendritic cells, and macrophages). On the other hand, representatives of standard microbiota cause only weak signaling, which does not induce inflammation. The mechanism of distinguishing between harmless and harmful bacteria on the molecular as well as on physiological levels is not completely understood.

Populations of microbes (such as bacteria and yeasts) inhabit the skin and mucosal surfaces in various parts of the body. Their role forms part of normal, healthy human physiology, however if microbe numbers grow beyond their typical ranges (often due to a compromised immune system) or if microbes populate (such as through poor hygiene or injury) areas of the body normally not colonized or sterile (such as the blood, or the lower respiratory tract, or the abdominal cavity), disease can result (causing, respectively, bacteremia/sepsis, pneumonia, and peritonitis).<ref>{{Cite journal |last1=Kennedy |first1=Katherine M. |last2=de Goffau |first2=Marcus C. |last3=Perez-Muñoz |first3=Maria Elisa |last4=Arrieta |first4=Marie-Claire |last5=Bäckhed |first5=Fredrik |last6=Bork |first6=Peer |last7=Braun |first7=Thorsten |last8=Bushman |first8=Frederic D. |last9=Dore |first9=Joel |last10=de Vos |first10=Willem M. |last11=Earl |first11=Ashlee M. |last12=Eisen |first12=Jonathan A. |last13=Elovitz |first13=Michal A. |last14=Ganal-Vonarburg |first14=Stephanie C. |last15=Gänzle |first15=Michael G. |date=January 2023 |title=Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies |journal=Nature |language=en |volume=613 |issue=7945 |pages=639–649 |doi=10.1038/s41586-022-05546-8 |pmid=36697862 |pmc=11333990 |bibcode=2023Natur.613..639K |s2cid=256268291 |issn=1476-4687|hdl=2164/21298 |hdl-access=free }}</ref>

The Human Microbiome Project found that individuals host thousands of bacterial types, with different body sites having their own distinctive communities. Skin and vaginal sites showed smaller diversity than the mouth and gut, these showing the greatest richness. The bacterial makeup for a given site on a body varies from person to person, not only in type, but also in abundance. Bacteria of the same species found throughout the mouth are of multiple subtypes, preferring to inhabit distinctly different locations in the mouth. Even the enterotypes in the human gut, previously thought to be well understood, are from a broad spectrum of communities with blurred taxon boundaries.<ref>[http://www.plos.org/media/press/2012/PLoS_%20HMP_Collection_Manuscript_Summaries.pdf PLoS Human Microbiome Project Collection Manuscript Summaries] {{Webarchive|url=https://web.archive.org/web/20140304161937/http://www.plos.org/media/press/2012/PLoS_%20HMP_Collection_Manuscript_Summaries.pdf |date=4 March 2014 }} 13 June 2012</ref><ref>{{cite web|url = http://www.ucsf.edu/news/2012/06/12149/consortium-scientists-map-human-bodys-bacterial-ecosystem|title = Consortium of Scientists Map the Human Body's Bacterial Ecosystem|work = ucsf.edu| date=13 June 2012 }}</ref>

It is estimated that 500 to 1,000 species of bacteria live in the human gut, but belong to just a few phyla: Bacillota and Bacteroidota dominate but there are also Pseudomonadota, Verrucomicrobiota, Actinobacteriota, Fusobacteriota, and Cyanobacteria.<ref name=Sommer2013rev>{{cite journal | vauthors = Sommer F, Bäckhed F | title = The gut microbiota--masters of host development and physiology | journal = Nature Reviews. Microbiology | volume = 11 | issue = 4 | pages = 227–38 | date = April 2013 | pmid = 23435359 | doi = 10.1038/nrmicro2974 | s2cid = 22798964 }}</ref>

Many species of bacteria, primarily ''Streptococcus mutans'' and other anaerobes live in the mouth, where they are part of a sticky substance called plaque. If this is not removed by brushing, it hardens into calculus (also called tartar). The same bacteria also secrete acids that dissolve tooth enamel, causing tooth decay.<ref name = "ten_Cate_2006">{{cite journal | vauthors = ten Cate JM | title = Biofilms, a new approach to the microbiology of dental plaque | journal = Odontology | volume = 94 | issue = 1 | pages = 1–9 | date = September 2006 | pmid = 16998612 | doi = 10.1007/s10266-006-0063-3 | s2cid = 24330907 }}</ref>

The vaginal microflora consist mostly of various lactobacillus species. It was long thought that the most common of these species was ''Lactobacillus acidophilus'', but it has later been shown that ''L. iners'' is in fact most common, followed by ''L. crispatus''. Other lactobacilli found in the vagina are ''L. jensenii, L. delbrueckii'' and ''L. gasseri''. Disturbance of the vaginal flora can lead to infections such as bacterial vaginosis and candidiasis.<ref>{{Cite journal |last1=Gajer |first1=Pawel |last2=Brotman |first2=Rebecca M. |last3=Bai |first3=Guoyun |last4=Sakamoto |first4=Joyce |last5=Schütte |first5=Ursel M. E. |last6=Zhong |first6=Xue |last7=Koenig |first7=Sara S. K. |last8=Fu |first8=Li |last9=Ma |first9=Zhanshan (Sam) |last10=Zhou |first10=Xia |last11=Abdo |first11=Zaid |last12=Forney |first12=Larry J. |last13=Ravel |first13=Jacques |date=2012-05-02 |title=Temporal Dynamics of the Human Vaginal Microbiota |journal=Science Translational Medicine |language=en |volume=4 |issue=132 |pages=132ra52 |doi=10.1126/scitranslmed.3003605 |issn=1946-6234 |pmc=3722878 |pmid=22553250}}</ref>

=== Archaea === Archaea are present in the human gut, but, in contrast to the enormous variety of bacteria in this organ, the numbers of archaeal species are much more limited.<ref>{{cite journal | vauthors = Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA | display-authors = 6 | title = Diversity of the human intestinal microbial flora | journal = Science | volume = 308 | issue = 5728 | pages = 1635–8 | date = June 2005 | pmid = 15831718 | pmc = 1395357 | doi = 10.1126/science.1110591 | bibcode = 2005Sci...308.1635E }}</ref> The dominant group are the methanogens, particularly ''Methanobrevibacter smithii'' and ''Methanosphaera stadtmanae''.<ref>{{cite journal | vauthors = Duncan SH, Louis P, Flint HJ | title = Cultivable bacterial diversity from the human colon | journal = Letters in Applied Microbiology | volume = 44 | issue = 4 | pages = 343–50 | date = April 2007 | pmid = 17397470 | doi = 10.1111/j.1472-765X.2007.02129.x | s2cid = 43706882 | doi-access = | bibcode = 2007LAppM..44..343D }}</ref> However, colonization by methanogens is variable, and only about 50% of humans have easily detectable populations of these organisms.<ref>{{cite journal | vauthors = Florin TH, Zhu G, Kirk KM, Martin NG | title = Shared and unique environmental factors determine the ecology of methanogens in humans and rats | journal = The American Journal of Gastroenterology | volume = 95 | issue = 10 | pages = 2872–9 | date = October 2000 | doi = 10.1111/j.1572-0241.2000.02319.x | pmid = 11051362 | citeseerx = 10.1.1.606.4187 | s2cid = 1087298 }}</ref>

As of 2007, no clear examples of archaeal pathogens were known,<ref>{{cite journal | vauthors = Eckburg PB, Lepp PW, Relman DA | title = Archaea and their potential role in human disease | journal = Infection and Immunity | volume = 71 | issue = 2 | pages = 591–6 | date = February 2003 | pmid = 12540534 | pmc = 145348 | doi = 10.1128/IAI.71.2.591-596.2003 }}</ref><ref>{{cite journal | vauthors = Cavicchioli R, Curmi PM, Saunders N, Thomas T | title = Pathogenic archaea: do they exist? | journal = BioEssays | volume = 25 | issue = 11 | pages = 1119–28 | date = November 2003 | pmid = 14579252 | doi = 10.1002/bies.10354 | doi-access = free | hdl = 1959.4/39571 | hdl-access = free }}</ref> although a relationship has been proposed between the presence of some methanogens and human periodontal disease.<ref>{{cite journal | vauthors = Lepp PW, Brinig MM, Ouverney CC, Palm K, Armitage GC, Relman DA | title = Methanogenic Archaea and human periodontal disease | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 16 | pages = 6176–81 | date = April 2004 | pmid = 15067114 | pmc = 395942 | doi = 10.1073/pnas.0308766101 | bibcode = 2004PNAS..101.6176L | doi-access = free }}</ref> Methane-dominant small intestinal bacterial overgrowth (SIBO) is also predominantly caused by methanogens, and ''Methanobrevibacter smithii'' in particular.<ref name=":02">{{Cite journal |last1=Takakura |first1=Will |last2=Pimentel |first2=Mark |date=2020-07-10 |title=Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome – An Update |journal=Frontiers in Psychiatry |volume=11 |article-number=664 |doi=10.3389/fpsyt.2020.00664 |issn=1664-0640 |pmc=7366247 |pmid=32754068 |doi-access=free}}</ref>

=== Fungi === {{See also|Mycobiota}} Fungi, in particular yeasts, are present in the human gut.<ref name="mycobiome">{{cite journal | vauthors = Cui L, Morris A, Ghedin E | title = The human mycobiome in health and disease | journal = Genome Medicine | volume = 5 | issue = 7 | page = 63 | date = July 2013 | pmid = 23899327 | pmc = 3978422 | doi = 10.1186/gm467 | doi-access = free }} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978422/figure/F2/ Figure 2: Distribution of fungal genera in different body sites]</ref><ref name=Martins2014Candidiasis>{{cite journal | vauthors = Martins N, Ferreira IC, Barros L, Silva S, Henriques M | title = Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment | journal = Mycopathologia | volume = 177 | issue = 5–6 | pages = 223–40 | date = June 2014 | pmid = 24789109 | doi = 10.1007/s11046-014-9749-1 | url = http://repositorium.sdum.uminho.pt/bitstream/1822/31482/1/document_17753_1.pdf | quote = ''Candida'' species and other microorganisms are involved in this complicated fungal infection, but ''Candida albicans'' continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. | hdl = 10198/10147 | s2cid = 795450 | hdl-access = free }}</ref><ref name=Wang2014rev>{{cite journal | vauthors = Wang ZK, Yang YS, Stefka AT, Sun G, Peng LH | title = Review article: fungal microbiota and digestive diseases | journal = Alimentary Pharmacology & Therapeutics | volume = 39 | issue = 8 | pages = 751–66 | date = April 2014 | pmid = 24612332 | doi = 10.1111/apt.12665 | s2cid = 22101484 | quote = In addition, GI fungal infection is reported even among those patients with normal immune status. Digestive system-related fungal infections may be induced by both commensal opportunistic fungi and exogenous pathogenic fungi. ... ''Candida'' sp. is also the most frequently identified species among patients with gastric IFI. ... It was once believed that gastric acid could kill microbes entering the stomach and that the unique ecological environment of the stomach was not suitable for microbial colonisation or infection. However, several studies using culture-independent methods confirmed that large numbers of acid-resistant bacteria belonging to eight phyla and up to 120 species exist in the stomach, such as ''Streptococcus'' sp., ''Neisseria'' sp. and ''Lactobacillus'' sp. etc.26, 27 Furthermore, ''Candida albicans'' can grow well in highly acidic environments,28 and some genotypes may increase the severity of gastric mucosal lesions.29 | doi-access = free }}</ref><ref name="SIFO">{{cite journal | vauthors = Erdogan A, Rao SS | title = Small intestinal fungal overgrowth | journal = Current Gastroenterology Reports | volume = 17 | issue = 4 | article-number = 16 | date = April 2015 | pmid = 25786900 | doi = 10.1007/s11894-015-0436-2 | s2cid = 3098136 | quote = Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. ... Fungal-bacterial interaction may act in different ways and may either be synergistic or antagonistic or symbiotic [29]. Some bacteria such as ''Lactobacillus'' species can interact and inhibit both the virulence and growth of ''Candida'' species in the gut by producing hydrogen peroxide [30]. Any damage to the mucosal barrier or disruption of GI microbiota with chemotherapy or antibiotic use, inflammatory processes, activation of immune molecules and disruption of epithelial repair may all cause fungal overgrowth [27]. }}</ref> The best-studied of these are ''Candida'' species due to their ability to become pathogenic in immunocompromised and even in healthy hosts.<ref name=Martins2014Candidiasis/><ref name=Wang2014rev/><ref name="SIFO" /> Yeasts are also present on the skin,<ref name="mycobiome" /> such as ''Malassezia'' species, where they consume oils secreted from the sebaceous glands.<ref>{{cite journal | vauthors = Marcon MJ, Powell DA | title = Human infections due to Malassezia spp | journal = Clinical Microbiology Reviews | volume = 5 | issue = 2 | pages = 101–19 | date = April 1992 | pmid = 1576583 | pmc = 358230 | doi = 10.1128/CMR.5.2.101 }}</ref><ref>{{cite journal | vauthors = Roth RR, James WD | title = Microbial ecology of the skin | journal = Annual Review of Microbiology | volume = 42 | issue = 1 | pages = 441–64 | year = 1988 | pmid = 3144238 | doi = 10.1146/annurev.mi.42.100188.002301 }}</ref>

=== Viruses === {{See also|Human virome}}Viruses, especially bacterial viruses (bacteriophages), colonize various body sites. These colonized sites include the skin,<ref>{{cite journal | vauthors = Hannigan GD, Meisel JS, Tyldsley AS, Zheng Q, Hodkinson BP, SanMiguel AJ, Minot S, Bushman FD, Grice EA | display-authors = 6 | title = The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome | journal = mBio | volume = 6 | issue = 5 | article-number = e01578-15 | date = October 2015 | pmid = 26489866 | pmc = 4620475 | doi = 10.1128/mBio.01578-15 | doi-access = free}}</ref> gut,<ref>{{cite journal | vauthors = Minot S, Sinha R, Chen J, Li H, Keilbaugh SA, Wu GD, Lewis JD, Bushman FD | display-authors = 6 | title = The human gut virome: inter-individual variation and dynamic response to diet | journal = Genome Research | volume = 21 | issue = 10 | pages = 1616–25 | date = October 2011 | pmid = 21880779 | pmc = 3202279 | doi = 10.1101/gr.122705.111 }}</ref> lungs,<ref>{{cite journal | vauthors = Young JC, Chehoud C, Bittinger K, Bailey A, Diamond JM, Cantu E, Haas AR, Abbas A, Frye L, Christie JD, Bushman FD, Collman RG | display-authors = 6 | title = Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients | journal = American Journal of Transplantation | volume = 15 | issue = 1 | pages = 200–9 | date = January 2015 | pmid = 25403800 | pmc = 4276431 | doi = 10.1111/ajt.13031 }}</ref> and oral cavity.<ref>{{cite journal | vauthors = Abeles SR, Robles-Sikisaka R, Ly M, Lum AG, Salzman J, Boehm TK, Pride DT | title = Human oral viruses are personal, persistent and gender-consistent | journal = The ISME Journal | volume = 8 | issue = 9 | pages = 1753–67 | date = September 2014 | pmid = 24646696 | pmc = 4139723 | doi = 10.1038/ismej.2014.31 | bibcode = 2014ISMEJ...8.1753A }}</ref> Virus communities have been associated with some diseases, and do not simply reflect the bacterial communities.<ref>{{cite journal | vauthors = Ly M, Abeles SR, Boehm TK, Robles-Sikisaka R, Naidu M, Santiago-Rodriguez T, Pride DT | title = Altered oral viral ecology in association with periodontal disease | journal = mBio | volume = 5 | issue = 3 | article-number = e01133-14 | date = May 2014 | pmid = 24846382 | pmc = 4030452 | doi = 10.1128/mBio.01133-14 | doi-access = free| bibcode = 2014mBio....533.14L }}</ref><ref>{{cite journal | vauthors = Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, Lankowski A, Baldridge MT, Wilen CB, Flagg M, Norman JM, Keller BC, Luévano JM, Wang D, Boum Y, Martin JN, Hunt PW, Bangsberg DR, Siedner MJ, Kwon DS, Virgin HW | display-authors = 6 | title = Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome | journal = Cell Host & Microbe | volume = 19 | issue = 3 | pages = 311–22 | date = March 2016 | pmid = 26962942 | pmc = 4821831 | doi = 10.1016/j.chom.2016.02.011 }}</ref><ref>{{cite journal | vauthors = Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY, Keller BC, Kambal A, Monaco CL, Zhao G, Fleshner P, Stappenbeck TS, McGovern DP, Keshavarzian A, Mutlu EA, Sauk J, Gevers D, Xavier RJ, Wang D, Parkes M, Virgin HW | display-authors = 6 | title = Disease-specific alterations in the enteric virome in inflammatory bowel disease | journal = Cell | volume = 160 | issue = 3 | pages = 447–60 | date = January 2015 | pmid = 25619688 | pmc = 4312520 | doi = 10.1016/j.cell.2015.01.002 | bibcode = 2015Cell..160..447N }}</ref>

In January 2024, biologists reported the discovery of "obelisks", a new class of viroid-like elements, and "oblins", their related group of proteins, in the human microbiome.<ref name="SA-20240129">{{cite journal |last=Koumoundouros |first=Tessa |title='Obelisks': Entirely New Class of Life Has Been Found in The Human Digestive System |url=https://www.sciencealert.com/obelisks-entirely-new-class-of-life-has-been-found-in-the-human-digestive-system |date=29 January 2024 |journal=ScienceAlert |url-status=live |archive-url=https://archive.today/20240129133614/https://www.sciencealert.com/obelisks-entirely-new-class-of-life-has-been-found-in-the-human-digestive-system |archive-date=29 January 2024 |access-date=29 January 2024 }}</ref><ref name="BRX-20240121">{{cite journal |author=Zheludev, Ivan N. |display-authors=et al. |title=Viroid-like colonists of human microbiomes |journal=Cell |date=2024 |volume=187 |issue=23 |pages=6521–6536.e18 |doi=10.1016/j.cell.2024.09.033 |pmid=39481381 |biorxiv=10.1101/2024.01.20.576352 }}</ref>

=== Amoebas === A number of species of non-pathogenic amoebas are known to live in the human gastrointestinal tract as commensals, including ''Endolimax nana'', several species of the genus ''Entamoeba'' (particularly ''Entamoeba coli'', ''E. hartmanni'' and ''E. polecki''), and the species ''Iodamoeba buetschlii''.<ref>{{Cite web |date=2019-10-29 |title=CDC - DPDx - Intestinal (Non-Pathogenic) Amebae |url=https://www.cdc.gov/dpdx/intestinalamebae/index.html |access-date=2025-08-26 |website=www.cdc.gov |language=en-us}}</ref>

== Anatomical areas == {{Main|List of human microbiota}}

=== Skin === {{Main|Skin flora}} A study of 20 skin sites on each of ten healthy humans found 205 identified genera in 19 bacterial phyla, with most sequences assigned to four phyla: Actinomycetota (51.8%), Bacillota (24.4%), Pseudomonadota (16.5%), and Bacteroidota (6.3%).<ref>{{cite journal | vauthors = Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC, Bouffard GG, Blakesley RW, Murray PR, Green ED, Turner ML, Segre JA | display-authors = 6 | title = Topographical and temporal diversity of the human skin microbiome | journal = Science | volume = 324 | issue = 5931 | pages = 1190–2 | date = May 2009 | pmid = 19478181 | pmc = 2805064 | doi = 10.1126/science.1171700 | bibcode = 2009Sci...324.1190G | collaboration = NISC Comparative Sequencing Program }}</ref> A large number of fungal genera are present on healthy human skin, with some variability by region of the body; however, during pathological conditions, certain genera tend to dominate in the affected region.<ref name="mycobiome" /> For example, ''Malassezia'' is dominant in atopic dermatitis and ''Acremonium'' is dominant on dandruff-affected scalps.<ref name="mycobiome" />

The skin acts as a barrier to deter the invasion of pathogenic microbes. The human skin contains microbes that reside either in or on the skin and can be residential or transient. Resident microorganism types vary in relation to skin type on the human body. A majority of microbes reside on superficial cells on the skin or prefer to associate with glands. These glands, such as oil or sweat glands, provide the microbes with water, amino acids, and fatty acids. In addition, resident bacteria associated with oil glands are often Gram-positive and can be pathogenic.<ref name="Prescotts" />

=== Conjunctiva === A small number of bacteria and fungi are normally present in the conjunctiva.<ref name="mycobiome" /><ref name=Textbook/> Classes of bacteria include Gram-positive cocci (e.g., ''Staphylococcus'' and ''Streptococcus'') and Gram-negative rods and cocci (e.g., ''Haemophilus'' and ''Neisseria'') are present.<ref name=Textbook>{{cite web|url = http://www.textbookofbacteriology.net/normalflora_3.html|title = The Normal Bacterial Flora of Humans|work = textbookofbacteriology.net|access-date = 26 September 2010|archive-date = 18 December 2017|archive-url = https://web.archive.org/web/20171218153049/http://www.textbookofbacteriology.net/normalflora_3.html}}</ref> Fungal genera include ''Candida'', ''Aspergillus'', and ''Penicillium''.<ref name="mycobiome" /> The lachrymal glands continuously secrete, keeping the conjunctiva moist, while intermittent blinking lubricates the conjunctiva and washes away foreign material. Tears contain bactericides such as lysozyme, so that microorganisms have difficulty in surviving the lysozyme and settling on the epithelial surfaces.

=== Gastrointestinal tract === {{Tryptophan metabolism by human microbiota|align=right}} {{Main|Gut microbiota}} {{see also|Gut–brain axis}}  In humans, the composition of the infant gastrointestinal microbiome is established during birth, maturing to the adult microbiome within the first few years.<ref>{{cite journal | vauthors = Yang I, Corwin EJ, Brennan PA, Jordan S, Murphy JR, Dunlop A | title = The Infant Microbiome: Implications for Infant Health and Neurocognitive Development | journal = Nursing Research | volume = 65 | issue = 1 | pages = 76–88 | date = 2016 | pmid = 26657483 | pmc = 4681407 | doi = 10.1097/NNR.0000000000000133 }}</ref> Birth by Cesarean section or vaginal delivery also influences the gut's microbial composition. Babies born through the vaginal canal have non-pathogenic, beneficial gut microbiota similar to those found in the mother.<ref>{{cite journal | vauthors = Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG | title = The infant microbiome development: mom matters | journal = Trends in Molecular Medicine | volume = 21 | issue = 2 | pages = 109–17 | date = February 2015 | pmid = 25578246 | pmc = 4464665 | doi = 10.1016/j.molmed.2014.12.002 }}</ref> However, the gut microbiota of babies delivered by C-section harbor more pathogenic bacteria such as ''Escherichia coli'' and ''Staphylococcus'' and require more time to develop non-pathogenic, beneficial gut microbiota.<ref>{{cite journal | vauthors = Wall R, Ross RP, Ryan CA, Hussey S, Murphy B, Fitzgerald GF, Stanton C | title = Role of gut microbiota in early infant development | journal = Clinical Medicine. Pediatrics | volume = 3 | pages = 45–54 | date = 4 March 2009 | article-number = CMPed.S2008 | pmid = 23818794 | pmc = 3676293 | doi = 10.4137/cmped.s2008 }}</ref>

The relationship between some gut microbiota and humans is not merely commensal (a non-harmful coexistence), but rather a mutualistic relationship.<ref name="Prescotts" /> Some human gut microorganisms benefit the host by fermenting dietary fiber into short-chain fatty acids (SCFAs), such as acetic acid and butyric acid, which are then absorbed by the host.<ref name=Quigley2013rev/><ref name=Clarke2014rev/> Intestinal bacteria also play a role in synthesizing B vitamins and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics.<ref name="Prescotts" /><ref name=Clarke2014rev>{{cite journal | vauthors = Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG | title = Minireview: Gut microbiota: the neglected endocrine organ | journal = Molecular Endocrinology | volume = 28 | issue = 8 | pages = 1221–38 | date = August 2014 | pmid = 24892638 | pmc = 5414803 | doi = 10.1210/me.2014-1108 }}</ref> The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ,<ref name=Clarke2014rev/> and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.<ref name=Quigley2013rev/><ref name=Shen2016rev>{{cite journal | vauthors = Shen S, Wong CH | title = Bugging inflammation: role of the gut microbiota | journal = Clinical & Translational Immunology | volume = 5 | issue = 4 | article-number = e72 | date = April 2016 | pmid = 27195115 | pmc = 4855262 | doi = 10.1038/cti.2016.12 }}</ref>

The composition of human gut microbiota changes over time, when the diet changes, and as overall health changes.<ref name=Quigley2013rev/><ref name=Shen2016rev/> A systematic review of 15 human randomized controlled trials from July 2016 found that certain commercially available strains of probiotic bacteria from the ''Bifidobacterium'' and ''Lactobacillus'' genera (''B. longum'', ''B. breve'', ''B. infantis'', ''L. helveticus'', ''L. rhamnosus'', ''L. plantarum'', and ''L. casei''), when taken by mouth in daily doses of 109–1010 colony forming units (CFU) for 1–2 months, possess treatment efficacy (i.e., improves behavioral outcomes) in certain central nervous system disorders – including anxiety, depression, autism spectrum disorder, and obsessive–compulsive disorder – and improves certain aspects of memory.<ref name="CNS SystRev 2016">{{cite journal | vauthors = Wang H, Lee IS, Braun C, Enck P | title = Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review | journal = Journal of Neurogastroenterology and Motility | volume = 22 | issue = 4 | pages = 589–605 | date = October 2016 | pmid = 27413138 | pmc = 5056568 | doi = 10.5056/jnm16018 | quote = These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. ... According to the qualitative analyses of current studies, we can provisionally draw the conclusion that B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei were most effective in improving CNS function, including psychiatric disease-associated functions (anxiety, depression, mood, stress response) and memory abilities }}</ref>

==== Esophagus ==== While the esophagus was previously considered to lack a microbiome, since the 1980s it has been known to contain a diverse microbiome. However, it is poorly studied with little known about its role in disease pathogenesis and esophageal health. This is partially due to the difficulty in sampling the microbes in the esophagus. Many bacteria can be found here such as Firmicutes (''Streptococcus'', ''Veillonella'', ''Megasphaera'', ''Granulicatella'', ''Gemella'', ''Clostridium'', and ''Bulleidia''), Bacteroidetes (''Prevotella'' and ''Bacteroides''), Fusobacteria, Actinobacteria (''Rothia'' and ''Actinomyces''), and Saccharibacteria. The most abundant species found was ''Streptococcus mitis''.<ref>Bonazzi, Erica & Lorenzon, Greta & Maniero, Daria & de Barba, Caterina & Bertin, Luisa & Barberio, Brigida & Salvador, Renato & Valmasoni, Michele & Zingone, Fabiana & Ghisa, Matteo & Savarino, Edoardo. (2024). The Esophageal Microbiota in Esophageal Health and Disease. Gastroenterology Insights. 15. 998-1013. 10.3390/gastroent15040069. </ref> In a healthy esophagus, it is dominated by gram-positive bacteria such as ''Streptococcus''.<ref>{{Cite journal |last=May |first=Michael |last2=Abrams |first2=Julian A. |date=March 2018 |title=Emerging Insights into the Esophageal Microbiome |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5843540/ |journal=Current Treatment Options in Gastroenterology |volume=16 |issue=1 |pages=72–85 |doi=10.1007/s11938-018-0171-5 |issn=1092-8472 |pmc=5843540 |pmid=29350339}}</ref>

=== Urethra and bladder === The genitourinary system appears to have a microbiota,<ref name="nu">{{cite journal | vauthors = Drake MJ, Morris N, Apostolidis A, Rahnama'i MS, Marchesi JR | title = The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015 | journal = Neurourology and Urodynamics | volume = 36 | issue = 4 | pages = 850–853 | date = April 2017 | pmid = 28444712 | doi = 10.1002/nau.23006 | url = https://research-information.bris.ac.uk/en/publications/the-urinary-microbiome-and-its-contribution-to-lower-urinary-tract-symptoms-icirs-2015(3b024f95-9f86-406a-9be3-ce35984b8de1).html | hdl = 1983/3b024f95-9f86-406a-9be3-ce35984b8de1 | s2cid = 27636043 | hdl-access = free }}</ref><ref name="euf">{{cite journal | vauthors = Aragón IM, Herrera-Imbroda B, Queipo-Ortuño MI, Castillo E, Del Moral JS, Gómez-Millán J, Yucel G, Lara MF | display-authors = 6 | title = The Urinary Tract Microbiome in Health and Disease | journal = European Urology Focus | volume = 4 | issue = 1 | pages = 128–138 | date = January 2018 | pmid = 28753805 | doi = 10.1016/j.euf.2016.11.001 }}</ref> which is an unexpected finding in light of the long-standing use of standard clinical microbiological culture methods to detect bacteria in urine when people show signs of a urinary tract infection; it is common for these tests to show no bacteria present.<ref name="dai">{{cite journal | vauthors = Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E | title = The diagnosis of urinary tract infection: a systematic review | journal = Deutsches Ärzteblatt International | volume = 107 | issue = 21 | pages = 361–7 | date = May 2010 | pmid = 20539810 | pmc = 2883276 | doi = 10.3238/arztebl.2010.0361 }}</ref> It appears that common culture methods do not detect many kinds of bacteria and other microorganisms that are normally present.<ref name=dai/> As of 2017, sequencing methods were used to identify these microorganisms to determine if there are differences in microbiota between people with urinary tract problems and those who are healthy.<ref name=nu/><ref name=euf/><ref>{{Cite journal|last1=Al|first1=Kait F.|last2=Denstedt|first2=John D.|last3=Daisley|first3=Brendan A.|last4=Bjazevic|first4=Jennifer|last5=Welk|first5=Blayne K.|last6=Pautler|first6=Stephen E.|last7=Gloor|first7=Gregory B.|last8=Reid|first8=Gregor|last9=Razvi|first9=Hassan|last10=Burton|first10=Jeremy P.|date=September 2020|title=Ureteral Stent Microbiota Is Associated with Patient Comorbidities but Not Antibiotic Exposure|journal=Cell Reports Medicine|language=en|volume=1|issue=6|article-number=100094|doi=10.1016/j.xcrm.2020.100094|pmc=7659606|pmid=33205072}}</ref> To properly assess the microbiome of the bladder as opposed to the genitourinary system, the urine specimen should be collected directly from the bladder, which is often done with a catheter.<ref>{{cite journal | vauthors = Wolfe AJ, Brubaker L | title = Urobiome updates: advances in urinary microbiome research | journal = Nature Reviews. Urology | volume = 16 | issue = 2 | pages = 73–74 | date = February 2019 | pmid = 30510275 | pmc = 6628711 | doi = 10.1038/s41585-018-0127-5 }}</ref>

=== Vagina === {{Main|Vaginal flora}}

{{see also|List of microbiota species of the lower reproductive tract of women|List of bacterial vaginosis microbiota|Vaginal microbiota in pregnancy}} Vaginal microbiota refers to those species and genera that colonize the vagina. These organisms play an important role in protecting against infections and maintaining vaginal health.<ref name="PetrovaLievens2015" /> The most abundant vaginal microorganisms found in premenopausal women are from the genus ''Lactobacillus'', which suppress pathogens by producing hydrogen peroxide and lactic acid.<ref name=Wang2014rev /><ref name="PetrovaLievens2015">{{cite journal | vauthors = Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S | title = Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health | journal = Frontiers in Physiology | volume = 6 | page = 81 | year = 2015 | pmid = 25859220 | pmc = 4373506 | doi = 10.3389/fphys.2015.00081 | doi-access = free }}</ref><ref name="witkin2012" /> Bacterial species composition and ratios vary depending on the stage of the menstrual cycle.<ref name="Todar">{{cite book| vauthors = Todar K |year = 2012|title = Todar's Online Textbook of Bacteriology|publisher = Kenneth Todar|location = Madison, WI|chapter = The Normal Bacterial Flora of Humans|chapter-url = http://textbookofbacteriology.net/normalflora_3.html|url = http://textbookofbacteriology.net/|access-date = 6 April 2012}}</ref><ref>{{cite journal | vauthors = Onderdonk AB, Zamarchi GR, Walsh JA, Mellor RD, Muñoz A, Kass EH | title = Methods for quantitative and qualitative evaluation of vaginal microflora during menstruation | journal = Applied and Environmental Microbiology | volume = 51 | issue = 2 | pages = 333–9 | date = February 1986 | pmid = 3954346 | pmc = 238869 | doi = 10.1128/AEM.51.2.333-339.1986 | bibcode = 1986ApEnM..51..333O }}</ref>{{update inline|date=June 2016}} Ethnicity also influences vaginal flora. The occurrence of hydrogen peroxide-producing lactobacilli is lower in African American women and vaginal pH is higher.<ref name="antonio1999">{{cite journal | vauthors = Antonio MA, Hawes SE, Hillier SL | title = The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species | journal = The Journal of Infectious Diseases | volume = 180 | issue = 6 | pages = 1950–6 | date = December 1999 | pmid = 10558952 | doi = 10.1086/315109 | doi-access = free | bibcode = 1999JInfD.180.1950A }}</ref> Other influential factors such as sexual intercourse and antibiotics have been linked to the loss of lactobacilli.<ref name="witkin2012">{{cite journal | vauthors = Witkin SS, Linhares IM, Giraldo P | title = Bacterial flora of the female genital tract: function and immune regulation | journal = Best Practice & Research. Clinical Obstetrics & Gynaecology | volume = 21 | issue = 3 | pages = 347–54 | date = June 2007 | pmid = 17215167 | doi = 10.1016/j.bpobgyn.2006.12.004 }}</ref> Moreover, studies have found that sexual intercourse with a condom does appear to change lactobacilli levels, and does increase the level of ''Escherichia coli'' within the vaginal flora.<ref name="witkin2012" /> Changes in the normal, healthy vaginal microbiota is an indication of infections,<ref>{{cite journal | vauthors = Usyk M, Zolnik CP, Castle PE, Porras C, Herrero R, Gradissimo A, Gonzalez P, Safaeian M, Schiffman M, Burk RD | display-authors = 6 | title = Cervicovaginal microbiome and natural history of HPV in a longitudinal study | journal = PLOS Pathogens | volume = 16 | issue = 3 | article-number = e1008376 | date = March 2020 | pmid = 32214382 | pmc = 7098574 | doi = 10.1371/journal.ppat.1008376 | doi-access = free }}</ref> such as candidiasis or bacterial vaginosis.<ref name="witkin2012" /> ''Candida albicans'' inhibits the growth of ''Lactobacillus'' species, while ''Lactobacillus'' species which produce hydrogen peroxide inhibit the growth and virulence of ''Candida albicans'' in both the vagina and the gut.<ref name="mycobiome" /><ref name=Wang2014rev /><ref name="SIFO" />

Fungal genera that have been detected in the vagina include ''Candida'', ''Pichia'', ''Eurotium'', ''Alternaria'', ''Rhodotorula'', and ''Cladosporium'', among others.<ref name="mycobiome" />

===Placenta=== {{Main|Placental microbiome}}

Until recently the placenta was considered to be a sterile organ but commensal, nonpathogenic bacterial species and genera have been identified that reside in the placental tissue.<ref name="FoxEichelberger2015">{{cite journal | vauthors = Fox C, Eichelberger K | title = Maternal microbiome and pregnancy outcomes | journal = Fertility and Sterility | volume = 104 | issue = 6 | pages = 1358–63 | date = December 2015 | pmid = 26493119 | doi = 10.1016/j.fertnstert.2015.09.037 | doi-access = free }}</ref><ref name="WassenaarPanigrahi2014">{{cite journal | vauthors = Wassenaar TM, Panigrahi P | title = Is a foetus developing in a sterile environment? | journal = Letters in Applied Microbiology | volume = 59 | issue = 6 | pages = 572–9 | date = December 2014 | pmid = 25273890 | doi = 10.1111/lam.12334 | s2cid = 206169539 | doi-access =}}</ref><ref>{{cite book | last = Schwiertz | first = Andreas | name-list-style = vanc | title = Microbiota of the human body: implications in health and disease | publisher = Springer | location = Switzerland | year = 2016 | page= 1 |isbn = 978-3-319-31248-4 }}</ref> However, the existence of a microbiome in the placenta is controversial as criticized in several researches. The so-called "placental microbiome" is likely derived from contamination of reagents because low-biomass samples are easily contaminated.<ref>{{cite journal | vauthors = Tamburini S, Shen N, Wu HC, Clemente JC | title = The microbiome in early life: implications for health outcomes | journal = Nature Medicine | volume = 22 | issue = 7 | pages = 713–22 | date = July 2016 | pmid = 27387886 | doi = 10.1038/nm.4142 | s2cid = 2462790 | doi-access = free | bibcode = 2016NatMe..22..713T }}</ref><ref>{{cite journal | vauthors = de Goffau MC, Lager S, Sovio U, Gaccioli F, Cook E, Peacock SJ, Parkhill J, Charnock-Jones DS, Smith GC | display-authors = 6 | title = Human placenta has no microbiome but can contain potential pathogens | journal = Nature | volume = 572 | issue = 7769 | pages = 329–334 | date = August 2019 | pmid = 31367035 | pmc = 6697540 | doi = 10.1038/s41586-019-1451-5 | bibcode = 2019Natur.572..329D }}</ref><ref>{{cite journal | vauthors = Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS | title = Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations | journal = Trends in Microbiology | volume = 27 | issue = 2 | pages = 105–117 | date = February 2019 | pmid = 30497919 | doi = 10.1016/j.tim.2018.11.003 | hdl = 2440/122027 | s2cid = 54166123 | hdl-access = free }}</ref>

===Uterus=== {{Main|Uterine microbiome}}

Until recently, the upper reproductive tract of women was considered to be a sterile environment. A variety of microorganisms inhabit the uterus of healthy, asymptomatic women of reproductive age. The microbiome of the uterus differs significantly from that of the vagina and gastrointestinal tract.<ref name="FranasiakScott2015">{{cite journal | vauthors = Franasiak JM, Scott RT | title = Reproductive tract microbiome in assisted reproductive technologies | journal = Fertility and Sterility | volume = 104 | issue = 6 | pages = 1364–71 | date = December 2015 | pmid = 26597628 | doi = 10.1016/j.fertnstert.2015.10.012 | doi-access = free }}</ref>

=== Oral cavity ===  {{Main|Oral microbiology}}

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.<ref name="Prescotts" /> 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.<ref name="Prescotts" /><ref name=Wang2014rev/>

Anaerobic bacteria in the oral cavity include: ''Actinomyces'', ''Arachnia'', ''Bacteroides'', ''Bifidobacterium'', ''Eubacterium'', ''Fusobacterium'', ''Lactobacillus'', ''Leptotrichia'', ''Peptococcus'', ''Peptostreptococcus'', ''Propionibacterium'', ''Selenomonas'', ''Treponema'', and ''Veillonella''.<ref name="sutter">{{cite journal|vauthors=Sutter VL|title=Anaerobes as normal oral flora|journal=Reviews of Infectious Diseases|volume=6|issue=Suppl 1|pages=S62-566|year=1984|pmid= 6372039|doi= 10.1093/clinids/6.Supplement_1.S62}}</ref>{{update inline|date=June 2016}} Genera of fungi that are frequently found in the mouth include ''Candida'', ''Cladosporium'', ''Aspergillus'', ''Fusarium'', ''Glomus'', ''Alternaria'', ''Penicillium'', and ''Cryptococcus'', among others.<ref name="mycobiome" />

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.<ref name="systemic disease 4">{{cite journal | vauthors = Kumar PS | title = Oral microbiota and systemic disease | journal = Anaerobe | volume = 24 | pages = 90–3 | date = December 2013 | pmid = 24128801 | doi = 10.1016/j.anaerobe.2013.09.010 | s2cid = 40735283 }}</ref> Saliva plays a key biofilm homeostatic role allowing recolonization of bacteria for formation and controlling growth by detaching biofilm buildup.<ref name="ArweilerNetuschil2016">{{cite book | vauthors = Arweiler NB, Netuschil L |title=Microbiota of the Human Body |series=Advances in Experimental Medicine and Biology |chapter=The Oral Microbiota | veditors = Schwiertz A |volume=902 |date=May 2016 |publisher=Springer, Cham |isbn=978-3-319-31248-4 |pages=45–60 |doi=10.1007/978-3-319-31248-4_4 |pmid=27161350 }}</ref> It also provides a means of nutrients and temperature regulation. The location of the biofilm determines the type of exposed nutrients it receives.<ref name="AvilaOjcius2009">{{cite journal | vauthors = Avila M, Ojcius DM, Yilmaz O | title = The oral microbiota: living with a permanent guest | journal = DNA and Cell Biology | volume = 28 | issue = 8 | pages = 405–11 | date = August 2009 | pmid = 19485767 | pmc = 2768665 | doi = 10.1089/dna.2009.0874 }}</ref>

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 bacterial colonization to prevent bacterial invasion of local tissues. A dynamic equilibrium exists between dental plaque bacteria and the innate host defense system.<ref name="AnthonyHRogers"/>

This dynamic between host oral cavity and oral microbes plays a key role in health and disease, as it provides entry into the body.<ref name="ZarcoVess2012">{{cite journal | vauthors = Zarco MF, Vess TJ, Ginsburg GS | s2cid = 24411104 | title = The oral microbiome in health and disease and the potential impact on personalized dental medicine | journal = Oral Diseases | volume = 18 | issue = 2 | pages = 109��20 | date = March 2012 | pmid = 21902769 | doi = 10.1111/j.1601-0825.2011.01851.x | doi-access = free }}</ref> 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.<ref name="ZarcoVess2012" /><ref name="systemic disease 4" /> 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.<ref name="systemic disease 4" /> Systemic diseases such as diabetes and cardiovascular diseases has been correlated to poor oral health.<ref name="ZarcoVess2012" /> Of particular interest is the role of oral microorganisms in the two major dental diseases: dental caries and periodontal disease.<ref name=AnthonyHRogers>{{cite book | veditors = Rogers AH | title = Molecular Oral Microbiology | url = https://archive.org/details/molecularoralmic0000unse | url-access = registration | publisher = Caister Academic Press | year = 2008 | isbn = 978-1-904455-24-0 }}</ref> Pathogen colonization at the periodontium cause an excessive immune response resulting in a periodontal pocket- a deepened space between the tooth and gingiva.<ref name="systemic disease 4" /> This acts as a protected blood-rich reservoir with nutrients for anaerobic pathogens.<ref name="systemic disease 4" /> Systemic disease at various sites of the body can result from oral microbes entering the blood by passing through diseased tissue at periodontal pockets and oral membranes.<ref name="ZarcoVess2012" />

Persistent proper oral hygiene is the primary method for preventing oral and systemic disease.<ref name="ZarcoVess2012" /> It reduces the density of biofilm and overgrowth of potential pathogenic bacteria that cause disease.<ref name="AvilaOjcius2009" /> 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.<ref name="AvilaOjcius2009" /> Use of antibiotics could treat already spreading infection, but is ineffective against bacteria within biofilms.<ref name="AvilaOjcius2009" />

=== Nasal cavity ===  ''Staphylococcus aureus'' is a major pathogenic species in the nasal cavity.{{Citation needed|date=January 2026}}

=== Lung === {{Main|Lung microbiota}}

Much like the oral cavity, the upper and lower respiratory system possess mechanical deterrents to remove microbes. Goblet cells produce mucus which traps microbes and moves them out of the respiratory system via continuously moving ciliated epithelial cells.<ref name="Prescotts" /> In addition, a bactericidal effect is generated by nasal mucus which contains the enzyme lysozyme.<ref name="Prescotts" /> The upper and lower respiratory tract appears to have its own set of microbiota.<ref name="Man2017">{{Cite journal |author-link3=Debby Bogaert |author1=Wing Ho Man |author2=Wouter A A de Steenhuijsen Piters |author3=Debby Bogaert |doi=10.1038/NRMICRO.2017.14 |issn=1740-1534 | volume = 15 |issue=5 |journal=Nature Reviews Microbiology |language=en |pages=259–270 |pmc=7097736 |pmid=28316330 |publication-date=20 March 2017 |title=The microbiota of the respiratory tract: gatekeeper to respiratory health |year=2017 | hdl = 20.500.11820/f1137874-9c51-401b-bca4-e2a5da3e219b}}Wikidata: Q34553608</ref> 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''.{{citation needed|date=October 2016}} Fungal genera that compose the pulmonary mycobiome include ''Candida'', ''Malassezia'', ''Neosartorya'', ''Saccharomyces'', and ''Aspergillus'', among others.<ref name="mycobiome" />

Unusual distributions of bacterial and fungal genera in the respiratory tract is observed in people with cystic fibrosis.<ref name="mycobiome" /><ref name="beringer2000">{{cite journal | vauthors = Beringer PM, Appleman MD | title = Unusual respiratory bacterial flora in cystic fibrosis: microbiologic and clinical features | journal = Current Opinion in Pulmonary Medicine | volume = 6 | issue = 6 | pages = 545–50 | date = November 2000 | pmid = 11100967 | doi = 10.1097/00063198-200011000-00015 | s2cid = 845977 | url = http://www.usc.edu/hsc/pharmacy/pd_labs/COPM11-00.pdf | archive-url = https://web.archive.org/web/20131016102359/http://www.usc.edu/hsc/pharmacy/pd_labs/COPM11-00.pdf | archive-date = 16 October 2013 }}</ref> Their bacterial flora often contains antibiotic-resistant and slow-growing bacteria, and the frequency of these pathogens changes in relation to age.<ref name="beringer2000" />

=== Biliary tract === Traditionally, the biliary tract had 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 that protects the biliary tract from colonization by exogenous microorganisms.<ref name=Verdier2015>{{cite journal | vauthors = Verdier J, Luedde T, Sellge G | title = Biliary Mucosal Barrier and Microbiome | journal = Viszeralmedizin | volume = 31 | issue = 3 | pages = 156–61 | date = June 2015 | pmid = 26468308 | pmc = 4569210 | doi = 10.1159/000431071 }}</ref>

=== Blood === The presence of viable bacteria in the bloodstream can provoke strong immune activation, resulting in clinical syndromes ranging from relatively mild forms of bacteremia to the potentially life-threatening condition known as sepsis. Bacteremia may occur spontaneously or as a complication of medical procedures, including liver transplantation.<ref name="Mammadov2023"> {{cite journal |last1=Mammadov |first1=RA |last2=Selten |first2=JW |last3=Roest |first3=HP |last4=Verhoeven |first4=CJ |last5=Maroni |first5=L |last6=Bril |first6=SI |last7=Tolenaars |first7=D |last8=Gadjradj |first8=PS |last9=van de Graaf |first9=SFJ |last10=Oude Elferink |first10=RPJ |last11=Kwekkeboom |first11=J |last12=Metselaar |first12=HJ |last13=Peppelenbosch |first13=MP |last14=Beuers |first14=U |last15=IJzermans |first15=JNM |last16=van der Laan |first16=LJW |title=Intestinal bacteremia after liver transplantation is a risk factor for recurrence of primary sclerosing cholangitis |journal=Transplantation |year=2023 |volume=107 |issue=8 |pages=1764–1775 |doi=10.1097/TP.0000000000004563 |pmid=36978227 |url=https://research.rug.nl/en/publications/b04b57f7-c04c-4615-b6e8-e69b4e60fab0 }}</ref>

Even in the absence of live microorganisms, bacterial breakdown products, particularly fragments of microbial DNA, can enter the circulation and persist transiently until cleared by renal filtration or enzymatic degradation. This observation has led to the concept of a ''blood microbiome,'' which primarily reflects circulating microbial DNA rather than intact, viable bacteria.{{cn|date=January 2026}}

The precise mechanisms by which microbial DNA enters the bloodstream remain incompletely understood, though translocation from the gastrointestinal tract is considered a major source, particularly in the setting of impaired intestinal barrier function, a feature observed in several chronic inflammatory diseases.<ref name="Potgieter2015"> {{cite journal |last1=Potgieter |first1=M |last2=Bester |first2=J |last3=Kell |first3=DB |last4=Pretorius |first4=E |title=The dormant blood microbiome in chronic, inflammatory diseases |journal=FEMS Microbiology Reviews |year=2015 |volume=39 |issue=4 |pages=567–591 |doi=10.1093/femsre/fuv013 |pmid=26084648 }}</ref>

Blood-derived microbial DNA signatures have been explored as potential non-invasive biomarkers for a variety of conditions, including diabetes, cardiovascular disease, and cancer. Some studies suggest that such signatures may even differentiate between cancer types.<ref name="Velmurugan2020"> {{cite journal |last1=Velmurugan |first1=G |last2=Dinakaran |first2=V |last3=Rajendhran |first3=J |last4=Swaminathan |first4=K |title=Blood microbiota and circulating microbial metabolites in diabetes and cardiovascular disease |journal=Trends in Endocrinology & Metabolism |year=2020 |volume=31 |issue=11 |pages=835–847 |doi=10.1016/j.tem.2020.09.003 |pmid=33082024 }}</ref> <ref name="Battaglia2024"> {{cite journal |last1=Battaglia |first1=TW |last2=Mimpen |first2=IL |last3=Traets |first3=JJH |last4=van Hoeck |first4=A |last5=Zeverijn |first5=LJ |last6=Geurts |first6=BS |last7=de Wit |first7=GF |last8=Noë |first8=M |last9=Hofland |first9=I |last10=Vos |first10=JL |last11=Cornelissen |first11=S |last12=Alkemade |first12=M |last13=Broeks |first13=A |last14=Zuur |first14=CL |last15=Cuppen |first15=E |last16=Wessels |first16=L |last17=van de Haar |first17=J |last18=Voest |first18=E |title=A pan-cancer analysis of the microbiome in metastatic cancer |journal=Cell |year=2024 |volume=187 |issue=9 |pages=2324–2335.e19 |doi=10.1016/j.cell.2024.03.021 |pmid=38599211 }}</ref>

Despite growing interest, the existence and biological relevance of a distinct blood microbiome remain debated. Major concerns include technical limitations in sequencing and bioinformatic analysis, as well as the high risk of contamination and analytical artifacts.<ref name="Tan2023"> {{cite journal |last1=Tan |first1=CS |last2=Ko |first2=KKK |last3=Chen |first3=H |last4=Liu |first4=J |last5=Loh |first5=M |last6=Nagarajan |first6=N |title=No evidence for a common blood microbiome based on a population study of 9,770 healthy humans |journal=Nature Microbiology |year=2023 |volume=8 |issue=5 |pages=973–985 |doi=10.1038/s41564-023-01350-w |pmid=36997797 |pmc=10159858 }}</ref> <ref name="Gihawi2023"> {{cite journal |last1=Gihawi |first1=A |last2=Ge |first2=Y |last3=Lu |first3=J |last4=Puiu |first4=D |last5=Xu |first5=A |last6=Cooper |first6=CS |last7=Brewer |first7=DS |last8=Pertea |first8=M |last9=Salzberg |first9=SL |title=Major data analysis errors invalidate cancer microbiome findings |journal=mBio |year=2023 |volume=14 |issue=5 |pages=e01607-23 |doi=10.1128/mbio.01607-23 |pmid=37610390 |pmc=10418938 |doi-access=free }}</ref>

To address these uncertainties, rigorously controlled, prospective, and multinational proof-of-concept studies have been proposed to determine how representative circulating microbial DNA is of the overall human microbiome.<ref name="Su2025"> {{cite journal |last1=Su |first1=J |last2=Hansen |first2=BE |last3=Wang |first3=Z |last4=Sharmenov |first4=A |last5=Xia |first5=X |last6=Broekhuizen |first6=M |last7=Ma |first7=Z |last8=Peppelenbosch |first8=MP |title=Yogurt reintroduction and the circulating microbiome in healthy volunteers: protocol for a prospective, longitudinal, species-controlled crossover clinical trial (MAMI) |journal=Contemporary Clinical Trials Communications |year=2025 |volume=48 |article-number=101579 |doi=10.1016/j.conctc.2025.101579 |doi-access=free |pmid=41399631 }}</ref>

== Disease and death == Human bodies rely on the innumerable bacterial genes as the source of essential nutrients.<ref>{{cite journal | vauthors = Yu B, Yu B, Yu L | title = Commentary: Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome | journal = Indian Journal of Microbiology | volume = 60 | issue = 2 | pages = 259–261 | date = June 2020 | pmid = 32255860 | pmc = 7105528 | doi = 10.1007/s12088-020-00863-w }}</ref> 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.<ref>Copeland CS. [http://claudiacopeland.com/uploads/3/5/5/6/35560346/_hjno_the_world_within_us.pdf The World Within Us: Health and the Human Microbiome.] ''Healthcare Journal of New Orleans, Sept-Oct 2017.''</ref> A symbiotic relationship between the gut microbiota and different bacteria may influence an individual's immune response.<ref>{{cite journal | vauthors = Honda K, Littman DR | title = The microbiota in adaptive immune homeostasis and disease | journal = Nature | volume = 535 | issue = 7610 | pages = 75–84 | date = July 2016 | pmid = 27383982 | doi = 10.1038/nature18848 | s2cid = 4461492 | bibcode = 2016Natur.535...75H }}</ref> Metabolites generated by gut microbes appear to be causative factors in type 2 diabetes.<ref>{{Cite web |title=Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes |url=https://www.metabolon.com/resources/publications/diabetes-serum-metabolites-gut-microbiome/ |access-date=2022-11-03 |website=Metabolon |language=en-US}}</ref> Although in its infancy, microbiome-based treatment is also showing promise, most notably for treating drug-resistant ''C. difficile'' infection<ref>{{cite journal | vauthors = Liubakka A, Vaughn BP | title = Clostridium difficile Infection and Fecal Microbiota Transplant | journal = AACN Advanced Critical Care | volume = 27 | issue = 3 | pages = 324–337 | date = July 2016 | pmid = 27959316 | pmc = 5666691 | doi = 10.4037/aacnacc2016703 }}</ref> and in diabetes treatment.<ref>{{cite journal | vauthors = Burton JH, Johnson M, Johnson J, Hsia DS, Greenway FL, Heiman ML | title = Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels | journal = Journal of Diabetes Science and Technology | volume = 9 | issue = 4 | pages = 808–14 | date = July 2015 | pmid = 25802471 | pmc = 4525649 | doi = 10.1177/1932296815577425 }}</ref>

=== ''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.<ref name="Bakken">{{cite journal | vauthors = Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC, Franzos MA, Kelly C, Khoruts A, Louie T, Martinelli LP, Moore TA, Russell G, Surawicz C | display-authors = 6 | title = Treating Clostridium difficile infection with fecal microbiota transplantation | journal = Clinical Gastroenterology and Hepatology | volume = 9 | issue = 12 | pages = 1044–9 | date = December 2011 | pmid = 21871249 | pmc = 3223289 | doi = 10.1016/j.cgh.2011.08.014 }}</ref> Traditional treatment for ''C. difficile'' infections includes an additional regime of antibiotics, however, efficacy rates average between 20 and 30%.<ref name=":4">{{cite journal | vauthors = Gough E, Shaikh H, Manges AR | title = Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection | journal = Clinical Infectious Diseases | volume = 53 | issue = 10 | pages = 994–1002 | date = November 2011 | pmid = 22002980 | doi = 10.1093/cid/cir632 | doi-access = free }}</ref> Recognizing the importance of healthy gut bacteria, researchers turned to a procedure known as fecal microbiota transplant (FMT), where patients experiencing gastrointestinal diseases, such as ''C. difficile'' infection (CDI), receive fecal content from a healthy individual in hopes of restoring a normal functioning intestinal microbiota.<ref>{{cite journal | vauthors = Brown WR | title = Fecal microbiota transplantation in treating Clostridium difficile infection | journal = Journal of Digestive Diseases | volume = 15 | issue = 8 | pages = 405–8 | date = August 2014 | pmid = 24825534 | doi = 10.1111/1751-2980.12160 | s2cid = 44651256 }}</ref> 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.<ref name=Burke2013>{{cite journal | vauthors = Burke KE, Lamont JT | title = Fecal transplantation for recurrent Clostridium difficile infection in older adults: a review | journal = Journal of the American Geriatrics Society | volume = 61 | issue = 8 | pages = 1394–8 | date = August 2013 | pmid = 23869970 | doi = 10.1111/jgs.12378 | s2cid = 34998497 | doi-access = free }}</ref><ref name="Drekonja_2015">{{cite journal | vauthors = Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ | display-authors = 6 | title = Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review | journal = Annals of Internal Medicine | volume = 162 | issue = 9 | pages = 630–8 | date = May 2015 | pmid = 25938992 | doi = 10.7326/m14-2693 | s2cid = 1307726 }}</ref> Most people with CDI recover with one FMT treatment.<ref name="Brandt">{{cite journal | vauthors = Brandt LJ, Borody TJ, Campbell J | title = Endoscopic fecal microbiota transplantation: "first-line" treatment for severe clostridium difficile infection? | journal = Journal of Clinical Gastroenterology | volume = 45 | issue = 8 | pages = 655–7 | date = September 2011 | pmid = 21716124 | doi = 10.1097/MCG.0b013e3182257d4f | s2cid = 2508836 | doi-access = free }}</ref><ref name="Bakken"/><ref>{{cite journal | vauthors = Kelly CR, de Leon L, Jasutkar N | title = Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results | journal = Journal of Clinical Gastroenterology | volume = 46 | issue = 2 | pages = 145–9 | date = February 2012 | pmid = 22157239 | doi = 10.1097/MCG.0b013e318234570b | s2cid = 30849491 }}</ref>

=== Cancer === Although cancer is generally a disease of host genetics and environmental factors, microorganisms are implicated in some 20% of human cancers.<ref name=Garrett2015Cancer>{{cite journal | vauthors = Garrett WS | title = Cancer and the microbiota | journal = Science | volume = 348 | issue = 6230 | pages = 80–6 | date = April 2015 | pmid = 25838377 | pmc = 5535753 | doi = 10.1126/science.aaa4972 | bibcode = 2015Sci...348...80G }}</ref> 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 rectal cancers.<ref name="wjg">{{cite journal | vauthors = Gagnière J, Raisch J, Veziant J, Barnich N, Bonnet R, Buc E, Bringer MA, Pezet D, Bonnet M | display-authors = 6 | title = Gut microbiota imbalance and colorectal cancer | journal = World Journal of Gastroenterology | volume = 22 | issue = 2 | pages = 501–18 | date = January 2016 | pmid = 26811603 | pmc = 4716055 | doi = 10.3748/wjg.v22.i2.501 | doi-access = free }}</ref> Microbial density may be used as a prognostic tool in assessment of colorectal cancers.<ref name=wjg/>

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.<ref name=Garrett2015Cancer /> 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.<ref name=Garrett2015Cancer /><ref name=wjg/> Of the around 1030 microbes on earth, ten are designated by the International Agency for Research on Cancer as human carcinogens.<ref name=Garrett2015Cancer /> Microbes may secrete proteins or other factors directly drive cell proliferation in the host, or may up- or down-regulate the host immune system including driving acute or chronic inflammation in ways that contribute to carcinogenesis.<ref name=Garrett2015Cancer />

Concerning the relationship of immune function and development of inflammation, 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.<ref name=Garrett2015Cancer/> For example, cancer-associated microbes appear to activate NF-κΒ signaling within the tumor microenvironment. Other pattern recognition receptors, such as nucleotide-binding oligomerization domain–like receptor (NLR) family members ''NOD-2'', ''NLRP3'', ''NLRP6'' and ''NLRP12'', may play a role in mediating colorectal cancer.<ref name=Garrett2015Cancer/> Likewise ''Helicobacter pylori'' appears to increase the risk of gastric cancer, due to its driving a chronic inflammatory response in the stomach.<ref name=Garrett2015Cancer /><ref name=wjg/>

=== 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,<ref name=Sartor2012IBD>{{Cite journal| vauthors = Sartor RB, Mazmanian SK |date=July 2012|title=Intestinal Microbes in Inflammatory Bowel Diseases|journal=The American Journal of Gastroenterology Supplements|volume=1|issue=1|pages=15–21|doi=10.1038/ajgsup.2012.4}}</ref><ref>{{cite journal | vauthors = Hold GL, Smith M, Grange C, Watt ER, El-Omar EM, Mukhopadhya I | title = Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? | journal = World Journal of Gastroenterology | volume = 20 | issue = 5 | pages = 1192–210 | date = February 2014 | pmid = 24574795 | pmc = 3921503 | doi = 10.3748/wjg.v20.i5.1192 | doi-access = free }}</ref> and is correlated to defects in host genes that changes the innate immune response in individuals.<ref name=Sartor2012IBD/>

=== Disorders of the gut-brain interaction ===

In patients with Irritable bowel syndrome and other functional gastrointestinal disorders like abdominal bloating, studies have noted alterations in the abundance of specific bacterial groups. In particular, decreased levels of beneficial bacteria like ''Bifidobacterium'' and ''Lactobacillus''; increased levels of potentially harmful bacteria like ''Bacteroides'' and Proteobacteria. These microbial alterations can contribute to: increased intestinal permeability ("leaky gut"), visceral hypersensitivity (increased sensitivity of the gut to stimuli), altered gut motility, immune system activation.<ref>Collins, Stephen M. "A role for the gut microbiota in IBS." Nature reviews Gastroenterology & hepatology 11.8 (2014): 497-505.</ref> <ref>Pittayanon, R., Lau, J. T., Yuan, Y., Leontiadis, G. I., Tse, F., Surette, M., & Moayyedi, P. (2019). Gut microbiota in patients with irritable bowel syndrome—a systematic review. Gastroenterology, 157(1), 97-108.</ref><ref>Crucillà S, Caldart F, Michelon M, Marasco G, Costantino A. Functional Abdominal Bloating and Gut Microbiota: An Update. Microorganisms. 2024; 12(8):1669. https://doi.org/10.3390/microorganisms12081669</ref> <ref>Öhman, Lena, and Magnus Simrén. "Intestinal microbiota and its role in irritable bowel syndrome (IBS)." Current gastroenterology reports 15 (2013): 1-7.</ref>

=== Disorders of the gut–skin interaction === A relationship between microorganisms residing in the gastrointestinal tract and skin health has long been proposed. As early as the early 20th century, the oral consumption of baker's yeast (''Saccharomyces cerevisiae'') was commercially promoted as a treatment for acne.<ref name="ScienceHistoryYeast"> {{cite web |title=The healing power of compressed yeast |website=Science History Institute |url=https://www.sciencehistory.org/stories/magazine/the-healing-power-of-compressed-yeast/ |access-date=20 January 2026 }}</ref>

Subsequent scientific studies have provided evidence supporting a gut microbiome–skin connection. In patients with psoriasis, depletion of ''Saccharomyces cerevisiae'' has been observed and shown to be reversible following treatment with dimethyl fumarate, suggesting a role for gut-associated fungi in disease modulation.<ref name="Eppinga2017"> {{cite journal |last1=Eppinga |first1=H |last2=Thio |first2=HB |last3=Schreurs |first3=MWJ |last4=Blakaj |first4=B |last5=Tahitu |first5=RI |last6=Konstantinov |first6=SR |last7=Peppelenbosch |first7=MP |last8=Fuhler |first8=GM |title=Depletion of ''Saccharomyces cerevisiae'' in psoriasis patients, restored by dimethyl fumarate therapy |journal=PLOS ONE |year=2017 |volume=12 |issue=5 |article-number=e0176955 |doi=10.1371/journal.pone.0176955 |pmid=28489890 |pmc=5424058 |doi-access=free |bibcode=2017PLoSO..1276955E }}</ref>

Alterations in the gut microbiome have also been reported in other inflammatory skin diseases. For example, changes in gut microbial composition correlate with disease activity in hidradenitis suppurativa, supporting the concept of a microbiome-mediated gut–skin axis.<ref name="Lam2021"> {{cite journal |last1=Lam |first1=SY |last2=Radjabzadeh |first2=D |last3=Eppinga |first3=H |last4=Nossent |first4=YRA |last5=van der Zee |first5=HH |last6=Kraaij |first6=R |last7=Konstantinov |first7=SR |last8=Fuhler |first8=GM |last9=Prens |first9=EP |last10=Thio |first10=HB |last11=Peppelenbosch |first11=MP |title=A microbiome study to explore the gut–skin axis in hidradenitis suppurativa |journal=Journal of Dermatological Science |year=2021 |volume=101 |issue=3 |pages=218–220 |doi=10.1016/j.jdermsci.2020.12.008 |pmid=33419665 |url=https://pure.eur.nl/en/publications/4cd90f98-29e6-48d3-ad90-b16eeb81184f }}</ref>

The gut–skin relationship is further illustrated by extra-intestinal manifestations of chronic inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In these conditions, gut microbiome alterations and particularly depletion of the anti-inflammatory bacterium ''Faecalibacterium prausnitzii'' have been shown to parallel inflammatory skin disorders, including psoriasis.<ref name="Eppinga2016"> {{cite journal |last1=Eppinga |first1=H |last2=Sperna Weiland |first2=CJ |last3=Thio |first3=HB |last4=van der Woude |first4=CJ |last5=Nijsten |first5=TE |last6=Peppelenbosch |first6=MP |last7=Konstantinov |first7=SR |title=Similar depletion of protective ''Faecalibacterium prausnitzii'' in psoriasis and inflammatory bowel disease, but not in hidradenitis suppurativa |journal=Journal of Crohn's and Colitis |year=2016 |volume=10 |issue=9 |pages=1067–1075 |doi=10.1093/ecco-jcc/jjw070 |pmid=27067916 }}</ref>

Together, these observations support the concept of a bidirectional, microbiota-driven gut–skin axis. This framework challenges the traditional view of the gut and skin as independent organ systems and suggests new opportunities for understanding disease mechanisms and developing therapeutic strategies that target microbial ecosystems to improve both gastrointestinal and cutaneous health.<ref name="JimenezSanchez2025"> {{cite journal |last1=Jiménez-Sánchez |first1=M |last2=Celiberto |first2=LS |last3=Yang |first3=H |last4=Sham |first4=HP |last5=Vallance |first5=BA |title=The gut–skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential |journal=Gut Microbes |year=2025 |volume=17 |issue=1 |article-number=2473524 |doi=10.1080/19490976.2025.2473524 |pmid=40050613 |pmc=11901370 |doi-access=free }}</ref>

===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-ART HIV-positive populations.{{citation needed|date=July 2017}} 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.<ref name=Zilberman2016HIV>{{cite journal | vauthors = Zilberman-Schapira G, Zmora N, Itav S, Bashiardes S, Elinav H, Elinav E |author6-link=Eran Elinav | title = The gut microbiome in human immunodeficiency virus infection | journal = BMC Medicine | volume = 14 | issue = 1 | page = 83 | date = June 2016 | pmid = 27256449 | pmc = 4891875 | doi = 10.1186/s12916-016-0625-3 |doi-access=free }}</ref>

Vaginal microbiota plays a role in the infectivity of HIV, with an increased risk of infection and transmission when the woman has bacterial vaginosis, a condition characterized by an abnormal balance of vaginal bacteria.<ref>{{cite journal | vauthors = Petrova MI, van den Broek M, Balzarini J, Vanderleyden J, Lebeer S | title = Vaginal microbiota and its role in HIV transmission and infection | journal = FEMS Microbiology Reviews | volume = 37 | issue = 5 | pages = 762–92 | date = September 2013 | pmid = 23789590 | doi = 10.1111/1574-6976.12029 | s2cid = 32045698 | doi-access =}}</ref> The enhanced infectivity is seen with the increase in pro-inflammatory cytokines and 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.<ref name=Zilberman2016HIV/>

===Gut microbiome of centenarians===

Humans who are 100 years old or older, called centenarians, have a distinct gut microbiome. This microbiome is characteristically enriched in microorganisms that are able to synthesize novel secondary bile acids.<ref name="Sato2021">{{cite journal | last1=Sato | first1=Yuko | last2=Atarashi | first2=Koji | last3=Plichta | first3=Damian R. | last4=Arai | first4=Yasumichi | last5=Sasajima | first5=Satoshi | last6=Kearney | first6=Sean M. | last7=Suda | first7=Wataru | last8=Takeshita | first8=Kozue | last9=Sasaki | first9=Takahiro | last10=Okamoto | first10=Shoki | last11=Skelly | first11=Ashwin N. | last12=Okamura | first12=Yuki | last13=Vlamakis | first13=Hera | last14=Li | first14=Youxian | last15=Tanoue | first15=Takeshi | last16=Takei | first16=Hajime | last17=Nittono | first17=Hiroshi | last18=Narushima | first18=Seiko | last19=Irie | first19=Junichiro | last20=Itoh | first20=Hiroshi | last21=Moriya | first21=Kyoji | last22=Sugiura | first22=Yuki | last23=Suematsu | first23=Makoto | last24=Moritoki | first24=Nobuko | last25=Shibata | first25=Shinsuke | last26=Littman | first26=Dan R. | last27=Fischbach | first27=Michael A. | last28=Uwamino | first28=Yoshifumi | last29=Inoue | first29=Takashi | last30=Honda | first30=Akira | display-authors=1 | title=Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians | journal=Nature | date=2021 | volume=599 | issue=7885 | pages=458–464 | doi=10.1038/s41586-021-03832-5 | pmid=34325466 | bibcode=2021Natur.599..458S }}</ref> These secondary bile acids include various isoforms of lithocholic acid that may contribute to healthy aging.<ref name = Sato2021/>

=== Death === {{main|Necrobiome}}

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.<ref name=sa16>{{cite magazine |url=https://www.scientificamerican.com/podcast/episode/necrobiome-reveals-a-corpses-time-of-death/ | vauthors = Intagliata C |title="Necrobiome" Reveals a Corpse's Time of Death |magazine=Scientific American |date=22 December 2016 |access-date=26 March 2018}}</ref><ref name=atl15>{{cite magazine |url= https://www.theatlantic.com/science/archive/2015/12/meet-the-necrobiome-the-predictable-microbes-that-will-eat-your-dying-corpse/419676/ | vauthors = Young E |title= Meet the Necrobiome: The Waves of Microbes That Will Eat Your Corpse |magazine=The Atlantic| date=10 December 2015| access-date=26 March 2018}}</ref>

== 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.<ref>{{cite magazine |url = http://www.scientificamerican.com/article.cfm?id=human-microbiome-change|title = Bugs Inside: What Happens When the Microbes That Keep Us Healthy Disappear? | vauthors = Harmon K |magazine = Scientific American|date = 16 December 2009|access-date = 27 December 2008}}</ref>

== Changes, modulation and transmission == thumb|Microbiome-based interventions to modulate gut ecology and the immune system<ref name="10.1038/s41385-022-00564-1"/> Hygiene,<ref>{{Cite journal |last1=Yu |first1=Boxuan |last2=Yu |first2=Bowei |last3=Yu |first3=Ligen |date=June 2020 |title=Commentary: Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome |journal=Indian Journal of Microbiology |volume=60 |issue=2 |pages=259–261 |doi=10.1007/s12088-020-00863-w |issn=0046-8991 |pmc=7105528 |pmid=32255860}}</ref> probiotics,<ref name="10.1038/s41385-022-00564-1">{{cite journal |last1=Hitch |first1=Thomas C. A. |last2=Hall |first2=Lindsay J. |last3=Walsh |first3=Sarah Kate |last4=Leventhal |first4=Gabriel E. |last5=Slack |first5=Emma |last6=de Wouters |first6=Tomas |last7=Walter |first7=Jens |last8=Clavel |first8=Thomas |title=Microbiome-based interventions to modulate gut ecology and the immune system |journal=Mucosal Immunology |date=June 2022 |volume=15 |issue=6 |pages=1095–1113 |doi=10.1038/s41385-022-00564-1 |pmid=36180583 |pmc=9705255 |language=en |issn=1935-3456|doi-access=free}}</ref> prebiotics,<ref>{{Cite journal |last1=Roberfroid |first1=Marcel |last2=Gibson |first2=Glenn R. |last3=Hoyles |first3=Lesley |last4=McCartney |first4=Anne L. |last5=Rastall |first5=Robert |last6=Rowland |first6=Ian |last7=Wolvers |first7=Danielle |last8=Watzl |first8=Bernhard |last9=Szajewska |first9=Hania |last10=Stahl |first10=Bernd |last11=Guarner |first11=Francisco |last12=Respondek |first12=Frederique |last13=Whelan |first13=Kevin |last14=Coxam |first14=Veronique |last15=Davicco |first15=Marie-Jeanne |date=August 2010 |title=Prebiotic effects: metabolic and health benefits |journal=The British Journal of Nutrition |volume=104 |issue=Suppl 2 |pages=S1–63 |doi=10.1017/S0007114510003363 |issn=1475-2662 |pmid=20920376}}</ref> synbiotics,<ref>{{Cite journal |last1=Alli |first1=Sauliha R. |last2=Gorbovskaya |first2=Ilona |last3=Liu |first3=Jonathan C. W. |last4=Kolla |first4=Nathan J. |last5=Brown |first5=Lisa |last6=Müller |first6=Daniel J. |date=2022-04-19 |title=The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies |journal=International Journal of Molecular Sciences |volume=23 |issue=9 |page=4494 |doi=10.3390/ijms23094494 |doi-access=free |issn=1422-0067 |pmc=9101152 |pmid=35562885 |bibcode=2022IJMSc..23.4494A }}</ref> light therapy,<ref>{{Cite journal |last1=Ellis |first1=Jeremy R. |last2=Powell |first2=Eron J. |last3=Tomasovic |first3=Luke M. |last4=Marcheskie |first4=Rachel L. |last5=Girish |first5=Vishruth |last6=Warman |first6=Anmol |last7=Sivaloganathan |first7=Darshan |date=June 2024 |title=Changes in the Skin Microbiome Following Dermatological Procedures: A Scoping Review |journal=Applied Microbiology|language=en |volume=4 |issue=2 |pages=972–985 |doi=10.3390/applmicrobiol4020066 |doi-access=free |issn=2673-8007}}</ref> microbiota transplants (fecal<ref>{{Cite journal |last1=Zhou |first1=Siyu |last2=Cui |first2=Ying |last3=Zhang |first3=Yun |last4=Zhao |first4=Tianyu |last5=Cong |first5=Jing |date=2023-03-08 |title=Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis |journal=International Journal of Colorectal Disease |volume=38 |issue=1 |page=62 |doi=10.1007/s00384-023-04354-4 |issn=1432-1262 |pmid=36882658}}</ref> or skin<ref>{{cite journal |last1=Callewaert |first1=Chris |last2=Knödlseder |first2=Nastassia |last3=Karoglan |first3=Ante |last4=Güell |first4=Marc |last5=Paetzold |first5=Bernhard |title=Skin microbiome transplantation and manipulation: Current state of the art |journal=Computational and Structural Biotechnology Journal |date=1 January 2021 |volume=19 |pages=624–631 |doi=10.1016/j.csbj.2021.01.001 |pmid=33510866 |pmc=7806958 |language=en |issn=2001-0370}}</ref>), antibiotics,<ref>{{Cite journal |last1=McDonnell |first1=Lucy |last2=Gilkes |first2=Alexander |last3=Ashworth |first3=Mark |last4=Rowland |first4=Victoria |last5=Harries |first5=Timothy Hugh |last6=Armstrong |first6=David |last7=White |first7=Patrick |date=2021 |title=Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis |journal=Gut Microbes |volume=13 |issue=1 |pages=1–18 |article-number=1870402 |doi=10.1080/19490976.2020.1870402 |issn=1949-0984 |pmc=7928022 |pmid=33651651}}</ref> exercise,<ref>{{cite journal |last1=Monda |first1=Vincenzo |last2=Villano |first2=Ines |last3=Messina |first3=Antonietta |last4=Valenzano |first4=Anna |last5=Esposito |first5=Teresa |last6=Moscatelli |first6=Fiorenzo |last7=Viggiano |first7=Andrea |last8=Cibelli |first8=Giuseppe |last9=Chieffi |first9=Sergio |last10=Monda |first10=Marcellino |last11=Messina |first11=Giovanni |title=Exercise Modifies the Gut Microbiota with Positive Health Effects |journal=Oxidative Medicine and Cellular Longevity |date=5 March 2017 |volume=2017 |article-number=e3831972 |doi=10.1155/2017/3831972 |pmid=28357027 |pmc=5357536 |language=en |issn=1942-0900 |doi-access=free }}</ref><ref>{{cite journal |last1=Mailing |first1=Lucy J. |last2=Allen |first2=Jacob M. |last3=Buford |first3=Thomas W. |last4=Fields |first4=Christopher J. |last5=Woods |first5=Jeffrey A. |title=Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health |journal=Exercise and Sport Sciences Reviews |date=April 2019 |volume=47 |issue=2 |pages=75–85 |doi=10.1249/JES.0000000000000183 |pmid=30883471 |s2cid=83461620 |issn=0091-6331|doi-access=free }}</ref> diet,<ref>{{Cite journal |last1=So |first1=Daniel |last2=Whelan |first2=Kevin |last3=Rossi |first3=Megan |last4=Morrison |first4=Mark |last5=Holtmann |first5=Gerald |last6=Kelly |first6=Jaimon T. |last7=Shanahan |first7=Erin R. |last8=Staudacher |first8=Heidi M. |last9=Campbell |first9=Katrina L. |date=2018-06-01 |title=Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis |journal=The American Journal of Clinical Nutrition |volume=107 |issue=6 |pages=965–983 |doi=10.1093/ajcn/nqy041 |issn=1938-3207 |pmid=29757343|hdl=10536/DRO/DU:30117355 |hdl-access=free }}</ref> breastfeeding,<ref>{{Cite journal |last1=Ho |first1=Nhan T. |last2=Li |first2=Fan |last3=Lee-Sarwar |first3=Kathleen A. |last4=Tun |first4=Hein M. |last5=Brown |first5=Bryan P. |last6=Pannaraj |first6=Pia S. |last7=Bender |first7=Jeffrey M. |last8=Azad |first8=Meghan B. |last9=Thompson |first9=Amanda L. |last10=Weiss |first10=Scott T. |last11=Azcarate-Peril |first11=M. Andrea |last12=Litonjua |first12=Augusto A. |last13=Kozyrskyj |first13=Anita L. |last14=Jaspan |first14=Heather B. |last15=Aldrovandi |first15=Grace M. |date=2018-10-09 |title=Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations |journal=Nature Communications |volume=9 |issue=1 |page=4169 |doi=10.1038/s41467-018-06473-x |issn=2041-1723 |pmc=6177445 |pmid=30301893|bibcode=2018NatCo...9.4169H }}</ref> aging<ref>{{Cite journal |last1=Lozupone |first1=Catherine A. |last2=Stombaugh |first2=Jesse |last3=Gonzalez |first3=Antonio |last4=Ackermann |first4=Gail |last5=Wendel |first5=Doug |last6=Vázquez-Baeza |first6=Yoshiki |last7=Jansson |first7=Janet K. |last8=Gordon |first8=Jeffrey I. |last9=Knight |first9=Rob |date=October 2013 |title=Meta-analyses of studies of the human microbiota |journal=Genome Research |volume=23 |issue=10 |pages=1704–1714 |doi=10.1101/gr.151803.112 |issn=1549-5469 |pmc=3787266 |pmid=23861384}}</ref> can change the human microbiome across various anatomical systems or regions such as skin and gut.

=== Person-to-person transmission === The human microbiome is transmitted between a mother and her children, as well as between people living in the same household.<ref>{{cite news |title=Comprehensive profiling of human-to-human oral and intestinal microbial transmission |url=https://www.news-medical.net/news/20230120/Comprehensive-profiling-of-human-to-human-oral-and-intestinal-microbial-transmission.aspx |access-date=16 February 2023 |work=News-Medical.net |date=20 January 2023 |language=en |archive-date=16 February 2023 |archive-url=https://web.archive.org/web/20230216215257/https://www.news-medical.net/news/20230120/Comprehensive-profiling-of-human-to-human-oral-and-intestinal-microbial-transmission.aspx |url-status=live }}</ref><ref>{{cite journal |last1=Valles-Colomer |first1=Mireia |last2=Blanco-Míguez |first2=Aitor |last3=Manghi |first3=Paolo |display-authors=et al.|doi-access=free |title=The person-to-person transmission landscape of the gut and oral microbiomes |journal=Nature |date=February 2023 |volume=614 |issue=7946 |pages=125–135 |doi=10.1038/s41586-022-05620-1 |pmid=36653448 |pmc=9892008 |bibcode=2023Natur.614..125V |language=en |issn=1476-4687}}</ref>

== Research ==

=== Migration === Primary research indicates that immediate changes in the microbiota may occur when a person migrates from one country to another, such as when Thai immigrants settled in the United States<ref name="vangay">{{cite journal |display-authors=6 |vauthors=Vangay P, Johnson AJ, Ward TL, Al-Ghalith GA, Shields-Cutler RR, Hillmann BM, Lucas SK, Beura LK, Thompson EA, Till LM, Batres R, Paw B, Pergament SL, Saenyakul P, Xiong M, Kim AD, Kim G, Masopust D, Martens EC, Angkurawaranon C, McGready R, Kashyap PC, Culhane-Pera KA, Knights D |date=November 2018 |title=US Immigration Westernizes the Human Gut Microbiome |journal=Cell |volume=175 |issue=4 |pages=962–972.e10 |doi=10.1016/j.cell.2018.10.029 |pmc=6498444 |pmid=30388453}}</ref> or when Latin Americans immigrated into the United States.<ref name=":3">{{cite journal |display-authors=6 |vauthors=Kaplan RC, Wang Z, Usyk M, Sotres-Alvarez D, Daviglus ML, Schneiderman N, Talavera GA, Gellman MD, Thyagarajan B, Moon JY, Vázquez-Baeza Y, McDonald D, Williams-Nguyen JS, Wu MC, North KE, Shaffer J, Sollecito CC, Qi Q, Isasi CR, Wang T, Knight R, Burk RD |date=November 2019 |title=Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity |journal=Genome Biology |volume=20 |issue=1 |article-number=219 |doi=10.1186/s13059-019-1831-z |pmc=6824043 |pmid=31672155 |doi-access=free}}</ref> Losses of microbiota diversity were greater in obese individuals and children of immigrants.<ref name="vangay" /><ref name=":3" />

=== Cellulose digestion === A 2024 study suggests that gut microbiota capable of digesting cellulose can be found in the human microbiome, and they are less abundant in people living in industrialized societies.<ref>{{Cite journal |last1=Moraïs |first1=Sarah |last2=Winkler |first2=Sarah |last3=Zorea |first3=Alvah |last4=Levin |first4=Liron |last5=Nagies |first5=Falk S. P. |last6=Kapust |first6=Nils |last7=Lamed |first7=Eva |last8=Artan-Furman |first8=Avital |last9=Bolam |first9=David N. |last10=Yadav |first10=Madhav P. |last11=Bayer |first11=Edward A. |last12=Martin |first12=William F. |last13=Mizrahi |first13=Itzhak |date=2024-03-15 |title=Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans |journal=Science |language=en |volume=383 |issue=6688 |article-number=eadj9223 |doi=10.1126/science.adj9223 |pmid=38484069 |issn=0036-8075|pmc=7615765 |bibcode=2024Sci...383j9223M }}</ref><ref>{{cite web |last=Stewart |date=2024-03-14 |first=Linda |title=Cellulose-degrading gut bacteria found in the human gut, although at lower levels in industrialized countries |url=https://www.the-microbiologist.com/news/cellulose-degrading-gut-bacteria-found-in-the-human-gut-although-at-lower-levels-in-industrialized-countries/2731.article |access-date=2024-03-24 |website=The Microbiologist }}</ref>

===Sexome=== The sexome refers to microbes left on genitalia after penetrative sex. In the context of forensic science, the sexome can potentially aid in sexual assault casework for perpetrator identification when human male DNA is absent.<ref>{{cite journal | doi=10.1016/j.isci.2025.111861 | title=Bacterial transfer during sexual intercourse as a tool for forensic detection | date=2025 | last1=Dixon | first1=Ruby | last2=Egan | first2=Siobhon | last3=Payne | first3=Matthew | last4=Mullally | first4=Christopher | last5=Chapman | first5=Brendan | journal=iScience | volume=28 | issue=2 | article-number=111861 | doi-access=free | pmid=40061054 | pmc=11889491 | bibcode=2025iSci...28k1861D }}</ref>

== See also == {{div col|colwidth=27em}} * Human Microbiome Project * Human milk microbiome * Human virome * Hygiene hypothesis * Initial acquisition of microbiota * Microbiome * Microbiome Immunity Project * Microorganism {{div col end}}

==Bibliography== * Ed Yong. ''I Contain Multitudes: The Microbes Within Us and a Grander View of Life.'' 368 pages, Published 9 August 2016 by Ecco, {{ISBN|0062368591}}.

== References == {{Reflist|30em}}

== External links == * [http://www.amnh.org/calendar/the-secret-world-inside-you The Secret World Inside You] Exhibit 2015–2016, American Museum of Natural History * [https://web.archive.org/web/20161231092333/http://academy.asm.org/index.php/faq-series/5122-humanmicrobiome FAQ: Human Microbiome, January 2014] American Society For Microbiology

{{DEFAULTSORT:Human Flora}} Category:Bacteriology Category:Bacteria and humans Category:Microbiology Category:Microbiomes Category:Environmental microbiology Category:Gut flora Category:Human genome projects