Microbiota

{{short description|Community of microorganisms}} {{other uses}} {{lead too short|date=October 2018}} [[File:The plant microbiome.jpg|thumb|upright=2| Diverse microbial communities of characteristic microbiota are part of plant microbiomes, and are found on the outside surfaces and in the internal tissues of the host plant, as well as in the surrounding soil.<ref>?{{cite journal |last1=Dastogeer |first1=Khondoker M.G. |last2=Tumpa |first2=Farzana Haque |last3=Sultana |first3=Afruja |last4=Akter |first4=Mst Arjina |last5=Chakraborty |first5=Anindita |title=Plant microbiome–an account of the factors that shape community composition and diversity |journal=Current Plant Biology |date=2020 |volume=23 |article-number=100161 |doi=10.1016/j.cpb.2020.100161 |bibcode=2020CPBio..2300161D }}. 50px Material was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref>]]

'''Microbiota''' are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses,<ref>{{cite journal |last1=De Sordi|first1=Luisa |first2=Marta|last2=Lourenço |first3=Laurent|last3=Debarbieux |title=The battle within: interactions of bacteriophages and bacteria in the gastrointestinal tract |journal=Cell Host & Microbe |date=2019 |volume=25 |issue=2 |pages=210–218 |doi=10.1016/j.chom.2019.01.018 |pmid=30763535 |s2cid=73455329 |doi-access=free }}</ref><ref name="hmp">{{cite journal |publisher=NIH HMP Working Group |last1=Peterson|first1=J |last2=Garges|first2=S |display-authors=etal |year=2009 |title=The NIH Human Microbiome Project |journal=Genome Research |volume=19 |issue=12 |pages=2317–2323 |doi=10.1101/gr.096651.109 |pmc=2792171 |pmid=19819907}}</ref> and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

The term ''microbiome'' describes either the collective genomes of the microbes that reside in an ecological niche or else the microbes themselves.<ref>{{cite journal |last1=Backhed|first1=F. |last2=Ley|first2=R. E. |last3=Sonnenburg|first3=J. L. |last4=Peterson|first4=D. A. |last5=Gordon |first5=J. I. |year=2005 |title=Host-Bacterial Mutualism in the Human Intestine |journal=Science |volume=307 |issue=5717 |pages=1915–1920 |bibcode=2005Sci...307.1915B |doi=10.1126/science.1104816 |pmid=15790844 |s2cid=6332272|url=http://repositorioinstitucional.uea.edu.br//handle/riuea/2392 |url-access=subscription }}</ref><ref>{{cite journal |last1=Turnbaugh |first1=P. J. |last2=Ley |first2=R. E. |last3=Hamady |first3=M. |last4=Fraser-Liggett |first4=C. M. |last5=Knight |first5=R. |last6=Gordon |first6=J. I. |year=2007 |title=The Human Microbiome Project |journal=Nature |volume=449 |issue=7164 |pages=804–810 |bibcode=2007Natur.449..804T |doi=10.1038/nature06244 |pmc=3709439 |pmid=17943116}}</ref><ref>{{cite journal |last1=Ley |first1=R. E. |last2=Peterson |first2=D. A. |last3=Gordon |first3=J. I. |year=2006 |title=Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine |journal=Cell |volume=124 |issue=4 |pages=837–848 |doi=10.1016/j.cell.2006.02.017 |pmid=16497592 |s2cid=17203181|doi-access=free }}</ref>

The microbiome and host emerged during evolution as a synergistic unit from epigenetics and genetic characteristics, sometimes collectively referred to as a holobiont.<ref name=Salvucci2014>{{cite journal |doi=10.3109/1040841X.2014.962478 |title=Microbiome, holobiont and the net of life |journal=Critical Reviews in Microbiology |volume=42 |issue=3 |pages=485–494 |year=2016 |last1=Salvucci |first1=E. |pmid=25430522 |s2cid=30677140|hdl=11336/33456 |hdl-access=free }}</ref><ref>{{cite journal |pmid=24568029 |year=2013 |last1=Guerrero |first1=R. |title=Symbiogenesis: The holobiont as a unit of evolution |journal=International Microbiology |volume=16 |issue=3 |pages=133–143 |last2=Margulis |first2=Lynn |author2-link=Lynn Margulis |last3=Berlanga |first3=M. |doi=10.2436/20.1501.01.188}}</ref> The presence of microbiota in human and other metazoan guts has been critical for understanding the co-evolution between metazoans and bacteria.<ref>{{cite journal |last1=Davenport |first1=Emily R. |last2=Sanders |first2=Jon G. |last3=Song |first3=Se Jin |last4=Amato |first4=Katherine R. |last5=Clark |first5=Andrew G. |last6=Knight |first6=Rob |title=The human microbiome in evolution |journal=BMC Biology |date=2017 |volume=15 |issue=1 |article-number=127 |doi=10.1186/s12915-017-0454-7|doi-access=free |pmid=29282061 |pmc=5744394 |bibcode=2017BMCB...15..127D }}</ref><ref>{{cite journal |last1=Moeller |first1=Andrew H. |last2=Li |first2=Yingying |last3=Mpoudi Ngole |first3=Eitel |last4=Ahuka-Mundeke |first4=Steve |last5=Lonsdorf |first5=Elizabeth V. |last6=Pusey |first6=Anne E. |last7=Peeters |first7=Martine |last8=Hahn |first8=Beatrice H. |last9=Ochman |first9=Howard |title=Rapid changes in the gut microbiome during human evolution |journal=Proceedings of the National Academy of Sciences |date=2014 |volume=111 |issue=46 |pages=16431–16435 |doi=10.1073/pnas.1419136111 |doi-access=free |pmid=25368157 |pmc=4246287 |bibcode=2014PNAS..11116431M }}</ref> Microbiota play key roles in the intestinal immune and metabolic responses via their fermentation product (short-chain fatty acid), acetate.<ref>{{cite journal |last1=Jugder|first1=Bat-Erdene |last2=Kamareddine|first2=Layla |last3=Watnick|first3=Paula I. |year=2021 |title=Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex |url=|journal=Immunity |volume=54 |issue=8 |pages=1683–1697.e3 |doi=10.1016/j.immuni.2021.05.017 |pmid=34107298 |pmc=8363570 |issn=1074-7613 }}</ref>

== Introduction == [[File:Skin Microbiome20169-300.jpg|thumb|upright=2|The predominant species of bacteria on human skin]] All plants and animals, from simple life forms to humans, live in close association with microbial organisms.<ref name="Mendes2015">{{Cite journal | last1=Mendes | first1=R. | last2=Raaijmakers | first2=J.M. | doi=10.1038/ismej.2015.7 | title=Cross-kingdom similarities in microbiome functions | journal=The ISME Journal | volume=9 | issue=9 | pages=1905–1907 | year=2015 | pmid= 25647346| pmc=4542044| bibcode=2015ISMEJ...9.1905M }}</ref> Several advances have driven the perception of microbiomes, including: * the ability to perform genomic and gene expression analyses of single cells and of entire microbial communities in the disciplines of metagenomics and metatranscriptomics<ref name="BoMc2011"/> * databases accessible to researchers across multiple disciplines<ref name="BoMc2011"/> * methods of mathematical analysis suitable for complex data sets<ref name="BoMc2011"/>

Biologists discovered that microbes make up an important part of an organism's phenotype, far beyond the occasional symbiotic case study.<ref name="BoMc2011">{{Cite journal | last1=Bosch | first1=T. C. G. | last2=McFall-Ngai | first2=M. J. | doi=10.1016/j.zool.2011.04.001 | title=Metaorganisms as the new frontier | journal=Zoology | volume=114 | issue=4 | pages=185–190 | year=2011 | pmid= 21737250| pmc=3992624| bibcode=2011Zool..114..185B }}</ref>

===Types of microbe-host relationships=== Commensalism, a concept developed by Pierre-Joseph van Beneden (1809–1894), a Belgian professor at the University of Louvain during the nineteenth century<ref>Poreau B., ''[http://www.theses.fr/2014LYO10114 Biologie et complexité : histoire et modèles du commensalisme]''. PhD Dissertation, University of Lyon, France, 2014.</ref> is central to the microbiome, where microbiota colonize a host in a non-harmful coexistence. The relationship with their host is called mutualistic when organisms perform tasks that are known to be useful for the host,<ref name="Prescotts"/>{{rp|700}}<ref name=Quigley2013rev>{{cite journal | last1=Quigley | first1=E. M. | date=Sep 2013 | title=Gut bacteria in health and disease | journal=Gastroenterol Hepatol (N Y) | volume=9 | issue=9| pages=560–569 | pmid=24729765 | pmc=3983973}}</ref> parasitic, when disadvantageous to the host. Other authors define a situation as mutualistic where both benefit, and commensal, where the unaffected host benefits the symbiont.<ref name=pnas/> A nutrient exchange may be bidirectional or unidirectional, may be context dependent and may occur in diverse ways.<ref name=pnas/> Microbiota that are expected to be present, and that under normal circumstances do not cause disease, are deemed ''normal flora'' or ''normal microbiota'';<ref name="Prescotts"/> normal flora can not only be harmless, but can be protective of the host.<ref>{{Cite journal|last=Copeland|first=CS|date=Sep–Oct 2017|title=The World Within Us|url=https://www.biomebliss.com/learning-center/gi-microbiome-and-the-immune-system/|journal=Healthcare Journal of New Orleans|access-date=2019-12-07|archive-date=2019-12-07|archive-url=https://web.archive.org/web/20191207230327/https://www.biomebliss.com/learning-center/gi-microbiome-and-the-immune-system/}}</ref>

===Acquisition and change=== The initial acquisition of microbiota in animals from mammalians to marine sponges is at birth, and may even occur through the germ cell line. In plants, the colonizing process can be initiated below ground in the root zone, around the germinating seed, the spermosphere, or originate from the above ground parts, the phyllosphere and the flower zone or anthosphere.<ref name= pgpg/> The stability of the rhizosphere microbiota over generations depends upon the plant type but even more on the soil composition, i.e. living and non living environment.<ref>{{cite journal | last1=Tkacz | first1=Andrzej | last2=Cheema | first2=Jitender | last3=Chandra | first3=Govind | last4=Grant | first4=Alastair | last5=Poole | first5=Philip S. | date=Nov 2015 | title=Stability and succession of the rhizosphere microbiota depends upon plant type and soil composition | journal=ISME J. | volume=9 | issue=11 | pages=2349–2359 | doi=10.1038/ismej.2015.41 | pmc=4611498 | pmid=25909975| bibcode=2015ISMEJ...9.2349T }}</ref> Clinically, new microbiota can be acquired through fecal microbiota transplant to treat infections such as chronic ''C. difficile'' infection.<ref>{{Cite web|url=https://www.vitalacy.com/post/clostridium-difficile-and-hand-hygiene|title=What is Clostridium difficile?|last=Copeland|first=CS|date=19 April 2019|website=Vitalacy}}</ref>

== Microbiota by host == [[File:Commensals vs pathogens mechanism.png|thumb|Pathogenic microbiota causing inflammation in the lung]]

=== Humans === {{main|Human microbiota}}  The human microbiota includes bacteria, fungi, archaea and viruses. Micro-animals which live on the human body are excluded. The human microbiome refers to their collective genomes.<ref name="Prescotts">{{cite book|last2 = Willey|first2 = Joanne|last1 = Sherwood|first1 = Linda|last3 = Woolverton|first3 = Christopher|title = Prescott's Microbiology|url = {{google books |plainurl=y |id=sBCSRAAACAAJ}}|year = 2013|isbn = 978-0-07-340240-6|publisher = McGraw Hill|location = New York|edition = 9th|pages = 713–721|oclc = 886600661}}</ref>

Humans are colonized by many microorganisms; the traditional estimate was that humans live with ten times more non-human cells than human cells; more recent estimates have lowered this to 3:1 and even to about 1:1 by number (1:350 by mass).<ref name=AAM2014>American Academy of Microbiology [http://academy.asm.org/index.php/faq-series/5122-humanmicrobiome FAQ: Human Microbiome] {{Webarchive|url=https://web.archive.org/web/20161231092333/http://academy.asm.org/index.php/faq-series/5122-humanmicrobiome |date=2016-12-31 }} January 2014</ref><ref name=Rosner>{{cite journal | last1=Rosner | first1=Judah L. | title=Ten Times More Microbial Cells than Body Cells in Humans? | journal=Microbe Magazine | date=2014 | volume=9 | issue=2 | page=47 | doi=10.1128/microbe.9.47.2 }}</ref><ref name=NN2016>{{cite journal | last1=Abbott | first1=Alison | title=Scientists bust myth that our bodies have more bacteria than human cells | journal=Nature | date=2016 | doi=10.1038/nature.2016.19136 }}</ref><ref name=Sender>{{cite journal | last1 = Sender | first1 = R | last2 = Fuchs | first2 = S | last3 = Milo | first3 = R | date = Jan 2016 | title = Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans | journal = Cell | volume = 164 | issue = 3| pages = 337–340 | doi = 10.1016/j.cell.2016.01.013 | pmid = 26824647 | s2cid = 1790146 | doi-access = free | bibcode = 2016Cell..164..337S }}</ref><ref name="PLOS">{{Cite journal |date=2016-08-19 |title=Revised Estimates for the Number of Human and Bacteria Cells in the Body |journal=PLOS Biology |language=en |doi=10.1371/journal.pbio.1002533 |doi-access=free |pmc=4991899 |last1=Sender |first1=Ron |last2=Fuchs |first2=Shai |last3=Milo |first3=Ron |volume=14 |issue=8 |article-number=e1002533 |pmid=27541692 }}</ref>

In fact, these are so small that there are around 100 trillion microbiota on the human body,<ref>"On and in You." Micropia, https://www.micropia.nl/en/discover/stories/on-and-in-you/#:~:text=They're%20on%20you%2C%20in,re%20known%20as%20human%20microbiota.</ref> around 39 trillion by revised estimates, with only 0.2 kg of total mass in a "reference" 70 kg human body.<ref name="PLOS"/>

The Human Microbiome Project sequenced 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 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=June 17, 2012 |title=NIH Human Microbiome Project defines normal bacterial makeup of the body |publisher=NIH News |date=13 June 2012}}</ref>

=== Non-human animals === * Amphibians have microbiota on their skin.<ref>{{cite journal | last1 = Bataille | first1 = A | last2 = Lee-Cruz | first2 = L | last3 = Tripathi | first3 = B | last4 = Kim | first4 = H | last5 = Waldman | first5 = B | date = Jan 2016 | title = Microbiome Variation Across Amphibian Skin Regions: Implications for Chytridiomycosis Mitigation Efforts | journal = Microb. Ecol. | volume = 71 | issue = 1| pages = 221–232 | pmid = 26271741 | doi=10.1007/s00248-015-0653-0| bibcode = 2016MicEc..71..221B | s2cid = 12951957 }}</ref> Some species are able to carry a fungus named ''Batrachochytrium dendrobatidis'', which in others can cause a deadly infection Chytridiomycosis depending on their microbiome, resisting pathogen colonization or inhibiting their growth with antimicrobial skin peptides.<ref>{{cite journal |vauthors=Woodhams DC, Rollins-Smith LA, Alford RA, Simon MA, Harris RN |title=Innate immune defenses of amphibian skin: antimicrobial peptides and more |journal=Animal Conservation|year=2007|volume=10|issue=4|pages=425–428 |doi=10.1111/j.1469-1795.2007.00150.x|s2cid=84293044 |doi-access=free|bibcode=2007AnCon..10..425W }}</ref> *Newborn marsupials are born with histologically immature immune tissues and unable to mount their own specific immune defence. They are therefore heavily reliant on their mother's immune system<ref>{{cite journal |vauthors=Old JM, Deane EM |title=Development of the immune system and immunological protection in marsupial pouch young |journal=Developmental and Comparative Immunology|year=2000|volume=24|issue=5|pages=445–454 |doi=10.1016/S0145-305X(00)00008-2|pmid=10785270 }}</ref> and the milk<ref>{{cite journal |vauthors=Stannard HJ, Miller RD, Old JM |title=Marsupial and monotreme milk – a review of its nutrients and immune properties |journal=PeerJ|year=2020|volume=8|article-number=e9335 |doi=10.7717/peerj.9335|pmid=32612884 |pmc=7319036 |doi-access=free }}</ref> for their protection. Most marsupials have pouches, and their own microbiota changes throughout the reproductive stages: oestrus, birth/oestrus, and post-oestrus.<ref>{{cite journal |vauthors=Old JM, Deane EM |title=The effect of oestrus and the presence of pouch young on aerobic bacteria isolated from the pouch of the tammar wallaby, ''Macropus eugenii'' |journal=Comparative Immunology Microbiology and Infectious Diseases|year=1998|volume=21|issue=4|pages=237–245 |doi=10.1016/s0147-9571(98)00022-8|pmid=9775355 }}</ref> Some pouch and skin secretions have had antimicrobial peptides identified, that presumably support the young at this vulnerable time. * In mammals, herbivores such as cattle depend on their rumen microbiome to convert cellulose into proteins, short chain fatty acids, and gases. Culture methods cannot provide information on all microorganisms present. Comparative metagenomic studies yielded the surprising result that individual cattle possess markedly different community structures, predicted phenotype, and metabolic potentials,<ref>{{cite journal |author1=Brulc JM |author2=Antonopoulos DA |author3=Miller MEB |display-authors=et al |title=Gene-centric metagenomics of the fiber-adherent bovine rumen microbiome reveals forage specific glycoside hydrolases |journal=Proc. Natl. Acad. Sci. USA|year=2009|volume=106|issue=6|pages=1948–1953|pmid=19181843|pmc=2633212|doi=10.1073/pnas.0806191105|bibcode = 2009PNAS..106.1948B |doi-access=free }}</ref> even though they were fed identical diets, were housed together, and were apparently functionally identical in their utilization of plant cell wall resources. * Mice have become the most studied mammalian regarding their microbiomes. The gut microbiota have been studied in relation to allergic airway disease, obesity, gastrointestinal diseases and diabetes. Perinatal shifting of microbiota through low dose antibiotics can have long-lasting effects on future susceptibility to allergic airway disease. The frequency of certain subsets of microbes has been linked to disease severity. The presence of specific microbes early in postnatal life, instruct future immune responses.<ref name="pmid = 22422004">{{cite journal | author = Russell SL, Gold MJ| title = Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma | journal = EMBO Rep. | volume = 13 | issue = 5 |date=May 2012 | pmid = 22422004 | pmc = 3343350 | pages = 440–447 | doi=10.1038/embor.2012.32|display-authors=etal}}</ref><ref name="pmid = 25145536">{{cite journal |vauthors=Russell SL, Gold MJ, etal | title = Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases | journal = J Allergy Clin Immunol |date=Aug 2014 | pmid = 25145536 | doi=10.1016/j.jaci.2014.06.027 | volume=135 | issue = 1 | pages=100–109}}</ref> In gnotobiotic mice certain gut bacteria were found to transmit a particular phenotype to recipient germ-free mice, that promoted accumulation of colonic regulatory T cells, and strains that modulated mouse adiposity and cecal metabolite concentrations.<ref name="pmid = 17183312">{{cite journal |vauthors=Turnbaugh PJ, etal | title = An obesity-associated gut microbiome with increased capacity for energy harvest | journal = Nature | volume = 444 | issue = 7122 |date=Dec 2006 | pmid = 17183312 | pages = 1027–1031 | doi=10.1038/nature05414| bibcode = 2006Natur.444.1027T | s2cid = 4400297 }}</ref> This combinatorial approach enables a systems-level understanding of microbial contributions to human biology.<ref name="pmid = 24452263">{{cite journal |vauthors=Faith JJ, Ahern PP, Ridaura VK, etal | title = Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. | journal = Sci. Transl. Med. | volume = 6 | issue = 220 |date=Jan 2014 | pmid = 24452263 | page = 220 | doi=10.1126/scitranslmed.3008051 | pmc=3973144}}</ref> But also other mucoide tissues as lung and vagina have been studied in relation to diseases such as asthma, allergy and vaginosis.<ref>{{cite journal | last1 = Barfod | first1 = KK | last2 = Roggenbuck | first2 = M | last3 = Hansen | first3 = LH | last4 = Schjørring | first4 = S | last5 = Larsen | first5 = ST | last6 = Sørensen | first6 = SJ | last7 = Krogfelt | first7 = KA | year = 2013 | title = The murine lung microbiome in relation to the intestinal and vaginal bacterial communities | journal = BMC Microbiol | volume = 13 | page = 303 | doi = 10.1186/1471-2180-13-303 | pmid = 24373613 | pmc = 3878784 | doi-access = free }}</ref> * Insects have their own microbiomes. For example, leaf-cutter ants form huge underground colonies harvesting hundreds of kilograms of leaves each year and are unable to digest the cellulose in the leaves directly. They maintain fungus gardens as the colony's primary food source. While the fungus itself does not digest cellulose, a microbial community containing a diversity of bacteria is doing so. Analysis of the microbial population's genome revealed many genes with a role in cellulose digestion. This microbiome's predicted carbohydrate-degrading enzyme profile is similar to that of the bovine rumen, but the species composition is almost entirely different.<ref>{{cite journal |author1=Suen |author2=Scott JJ |author3=Aylward FO |display-authors=et al |title=An Insect Herbivore Microbiome with High Plant Biomass-Degrading Capacity |journal=PLOS Genet|year=2010|volume=6|issue=9|article-number=e1001129 |editor1-last=Sonnenburg |editor1-first=Justin |pmid=20885794|pmc=2944797|doi=10.1371/journal.pgen.1001129 |doi-access=free }}</ref> Gut microbiota of the fruit fly can affect the way its gut looks, by impacting epithelial renewal rate, cellular spacing, and the composition of different cell types in the epithelium.<ref>{{cite journal | last1 = Broderick | first1 = Nichole A. | last2 = Buchon | first2 = Nicolas | last3 = Lemaitre | first3 = Bruno | year = 2014 | title = Microbiota-Induced Changes in Drosophila melanogaster Host Gene Expression and Gut Morphology | journal = mBio | volume = 5 | issue = 3| pages = e01117–14 | pmc=4045073 | pmid=24865556 | doi=10.1128/mBio.01117-14 | doi-access=free | bibcode = 2014mBio....517.14B }}</ref> When the moth Spodoptera exigua is infected with baculovirus immune-related genes are downregulated and the amount of its gut microbiota increases.<ref name=baculo>{{cite journal | last1 = Jakubowska | first1 = Agata K. | last2 = Vogel | first2 = Heiko | last3 = Herrero | first3 = Salvador | date = May 2013 | title = Increase in Gut Microbiota after Immune Suppression in Baculovirus-infected Larvae | journal = PLOS Pathog | volume = 9 | issue = 5| article-number = e1003379 | doi = 10.1371/journal.ppat.1003379 | pmc=3662647 | pmid=23717206 | doi-access = free }}</ref> In the dipteran intestine, enteroendocrine cells sense the gut microbiota-derived metabolites and coordinate antibacterial, mechanical, and metabolic branches of the host intestinal innate immune response to the commensal microbiota.<ref>{{Cite journal|last1=Watnick|first1=Paula I.|last2=Jugder|first2=Bat-Erdene|date=2020-02-01|title=Microbial Control of Intestinal Homeostasis via Enteroendocrine Cell Innate Immune Signaling|url= |journal=Trends in Microbiology|language=en|volume=28|issue=2|pages=141–149|doi=10.1016/j.tim.2019.09.005|issn=0966-842X|pmc=6980660|pmid=31699645}}</ref> *Fish have their own microbiomes, including the short-lived species Nothobranchius furzeri (turquoise killifish). Transferring the gut microbiota from young killfish into middle-aged killifish significantly extends the lifespans of the middle-aged killfish.<ref name="pmid31403049">{{cite journal | vauthors=Tibbs TN, Lopez LR, Arthur JC | title=The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging | journal=Microbial Cell | volume=6 | issue=8 | pages=324–334 | year=2019 | doi = 10.15698/mic2019.08.685 | pmc=6685047 | pmid=31403049 }}</ref>

=== Plants === [[File:Colonization of potato tubers by bacteria.png|thumb|upright=1.7| {{center|Routes of colonization of potato tubers by bacteria{{hs}}<ref name=Buchholz2019>Buchholz, F., Antonielli, L., Kostić, T., Sessitsch, A. and Mitter, B. (2019) "The bacterial community in potato is recruited from soil and partly inherited across generations". ''PLOS One'', '''14'''(11): e0223691. {{doi|10.1371/journal.pone.0223691|doi-access=free}}. 50px Material was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref>}}]] {{see also|Plant microbiome}}

The plant microbiome was recently discovered to originate from the seed.<ref name=":2">{{Cite journal|last1=Abdelfattah|first1=Ahmed|last2=Wisniewski|first2=Michael|last3=Schena|first3=Leonardo|last4=Tack|first4=Ayco J. M.|title=Experimental evidence of microbial inheritance in plants and transmission routes from seed to phyllosphere and root|journal=Environmental Microbiology|year=2021|volume=23|issue=4|pages=2199–2214|language=en|doi=10.1111/1462-2920.15392|pmid=33427409|s2cid=231576517|issn=1462-2920|doi-access=free|bibcode=2021EnvMi..23.2199A }}</ref> Microorganism which are transmitted via seed migrate into the developing seedling in a specific route in which certain community move to the leaves and others to the roots.<ref name=":2" /> In the diagram on the right, microbiota colonizing the rhizosphere, entering the roots and colonizing the next tuber generation via the stolons, are visualized with a red color. Bacteria present in the mother tuber, passing through the stolons and migrating into the plant as well as into the next generation of tubers are shown in blue.<ref name=Buchholz2019 /> * The soil is the main reservoir for bacteria that colonize potato tubers * Bacteria are recruited from the soil more or less independent of the potato variety * Bacteria might colonize the tubers predominantly from the inside of plants via the stolon * The bacterial microbiota of potato tubers consists of bacteria transmitted from one tuber generation to the next and bacteria recruited from the soil colonize potato plants via the root.<ref name=Buchholz2019 />

thumb|200px|left| Light micrograph of a cross section of a coralloid root of a cycad, showing the layer that hosts symbiotic cyanobacteria

Plants are attractive hosts for microorganisms since they provide a variety of nutrients. Microorganisms on plants can be epiphytes (found on the plants) or endophytes (found inside plant tissue).<ref>{{Cite journal|last=Berlec|first=Aleš|date=2012-09-01|title=Novel techniques and findings in the study of plant microbiota: Search for plant probiotics|journal=Plant Science|volume=193–194|pages=96–102|doi=10.1016/j.plantsci.2012.05.010|pmid=22794922|bibcode=2012PlnSc.193...96B }}</ref><ref>{{Cite journal| last1=Whipps| first1=J.m.| last2=Hand| first2=P.|last3=Pink|first3=D.|last4=Bending|first4=G.d.|date=2008-12-01|title=Phyllosphere microbiology with special reference to diversity and plant genotype|journal=Journal of Applied Microbiology| language=en| volume=105| issue=6| pages=1744–1755|doi=10.1111/j.1365-2672.2008.03906.x| pmid=19120625| s2cid=35055151|issn=1365-2672| url=http://wrap.warwick.ac.uk/449/1/WRAP_Bending_JAM_review_revised_4_April_2008.pdf}}</ref> Oomycetes and fungi have, through convergent evolution, developed similar morphology and occupy similar ecological niches. They develop hyphae, threadlike structures that penetrate the host cell. In mutualistic situations the plant often exchanges hexose sugars for inorganic phosphate from the fungal symbiont. It is speculated that such very ancient associations have aided plants when they first colonized land.<ref name=pnas>{{cite journal | vauthors=Remy W, Taylor TN, Hass H, Kerp H | title=Four hundred-million-year-old vesicular arbuscular mycorrhizae | journal=Proc. Natl. Acad. Sci. USA|year=1994|volume=91|issue=25|pages=11841–11843 | bibcode=1994PNAS...9111841R | doi=10.1073/pnas.91.25.11841 | pmid=11607500 | pmc=45331 | doi-access=free }}</ref><ref>{{cite journal |vauthors=Chibucos MC, Tyler BM | title=Common themes in nutrient acquisition by plant symbiotic microbes, described by the Gene Ontology | journal=BMC Microbiology|year=2009|volume=9(Suppl 1)| issue=Suppl 1 |pages=S6 | doi=10.1186/1471-2180-9-S1-S6 | pmid=19278554 | pmc=2654666 | doi-access=free }}</ref> Plant-growth promoting bacteria (PGPB) provide the plant with essential services such as nitrogen fixation, solubilization of minerals such as phosphorus, synthesis of plant hormones, direct enhancement of mineral uptake, and protection from pathogens.<ref>{{cite book | title=Soil microbial ecology: applications in agricultural and environmental management | chapter=Plant growth-promoting rhizobacteria as biological control agents | last=Kloepper | first=J. W | editor=Metting, F. B. Jr | year=1993 | publisher=Marcel Dekker Inc | location=New York | isbn=978-0-8247-8737-0 |pages=255–274}}</ref><ref name=BloembergLugt2001>{{Cite journal | last1 = Bloemberg | first1 = G. V. | last2 = Lugtenberg | first2 = B. J. J. | doi = 10.1016/S1369-5266(00)00183-7 | title = Molecular basis of plant growth promotion and biocontrol by rhizobacteria | journal = Current Opinion in Plant Biology | volume = 4 | issue = 4 | pages = 343–350 | year = 2001 | pmid = 11418345| bibcode = 2001COPB....4..343B }}</ref> PGPBs may protect plants from pathogens by competing with the pathogen for an ecological niche or a substrate, producing inhibitory allelochemicals, or inducing systemic resistance in host plants to the pathogen<ref name= pgpg>{{cite journal |vauthors=Compant S, Duffy B, Nowak J, Clément C, Barka EA | title=Use of Plant Growth-Promoting Bacteria for Biocontrol of Plant Diseases: Principles, Mechanisms of Action, and Future Prospects | journal=Appl Environ Microbiol|year=2005|volume=71|issue=9|pages=4951–4959 | doi=10.1128/AEM.71.9.4951-4959.2005 | pmc=1214602|pmid=16151072 | bibcode=2005ApEnM..71.4951C }}</ref> {{clear left}}

==Research== The symbiotic relationship between a host and its microbiota is under laboratory research for how it may shape the immune system of mammals.<ref name="Palm">{{cite journal | last1=Palm | first1=Noah W. | last2=de Zoete | first2=Marcel R. | last3=Flavell | first3=Richard A. | title=Immune–microbiota interactions in health and disease | journal=Clinical Immunology| volume=159 | issue=2 | date=30 June 2015 | issn=1521-6616 | pmid=26141651 | pmc=4943041 | doi=10.1016/j.clim.2015.05.014 | pages=122–127}}</ref><ref name="Round">{{cite journal | last1=Round | first1=June L. | last2=O'Connell | first2=Ryan M. |last3=Mazmanian |first3=Sarkis K. | title=Coordination of tolerogenic immune responses by the commensal microbiota | journal=Journal of Autoimmunity | volume=34 | issue=3 | year=2010 | pages=J220–J225 | pmid=19963349| doi=10.1016/j.jaut.2009.11.007 | pmc=3155383}}</ref> In many animals, the immune system and microbiota may engage in "cross-talk" by exchanging chemical signals, which may enable the microbiota to influence immune reactivity and targeting.<ref name="Cahenzli">{{cite journal | last1=Cahenzli | first1=Julia | last2=Balmer | first2=Maria L. | last3=McCoy | first3=Kathy D. | title=Microbial-immune cross-talk and regulation of the immune system | journal=Immunology | volume=138 | issue=1 | year=2012 | pages=12–22 | pmid= 22804726 |doi=10.1111/j.1365-2567.2012.03624.x | pmc=3533697}}</ref> Bacteria can be transferred from mother to child through direct contact and after birth.<ref name="Rosenberg">{{Cite journal |last1=Rosenberg |first1=Eugene |last2=Zilber-Rosenberg |first2=Ilana |year=2016 |title=Microbes drive evolution of animals and plants: the hologenome concept |journal=mBio |volume=7 |issue=2 |pages=e01395–15 |doi=10.1128/mbio.01395-15 |doi-access=free|pmc=4817260 |pmid=27034283}}</ref> As the infant microbiome is established, commensal bacteria quickly populate the gut, prompting a range of immune responses and "programming" the immune system with long-lasting effects.<ref name="Cahenzli"/> The bacteria are able to stimulate lymphoid tissue associated with the gut mucosa, which enables the tissue to produce antibodies for pathogens that may enter the gut.<ref name="Cahenzli"/>

The human microbiome may play a role in the activation of toll-like receptors in the intestines, a type of pattern recognition receptor host cells use to recognize dangers and repair damage. Pathogens can influence this coexistence leading to immune dysregulation including and susceptibility to diseases, mechanisms of inflammation, immune tolerance, and autoimmune diseases.<ref name="Blander">{{cite journal | last1=Blander | first1=J Magarian | last2=Longman | first2=Randy S | last3=Iliev | first3=Iliyan D | last4=Sonnenberg | first4=Gregory F | last5=Artis | first5=David | title=Regulation of inflammation by microbiota interactions with the host | journal=Nature Immunology | volume=18 | issue=8 | date=19 July 2017 | issn=1529-2908 | pmid=28722709 | pmc=5800875 | doi=10.1038/ni.3780 | pages=851–860}}</ref><ref>{{cite journal | last1 = Nikoopour | first1 = E | last2 = Singh | first2 = B | year = 2014 | title = Reciprocity in microbiome and immune system interactions and its implications in disease and health | url = https://ir.lib.uwo.ca/cgi/viewcontent.cgi?article=1038&context=mnipub| journal = Inflamm Allergy Drug Targets | volume = 13 | issue = 2| pages = 94–104 | pmid = 24678760 | doi=10.2174/1871528113666140330201056| url-access = subscription }}</ref>

== Co-evolution of microbiota == {{Main|Hologenome theory of evolution}} [[File:Keppelbleaching.jpg|thumb|200px|Bleached branching coral (foreground) and normal branching coral (background). Keppel Islands, Great Barrier Reef.]]

Organisms evolve within ecosystems so that the change of one organism affects the change of others. The hologenome theory of evolution proposes that an object of natural selection is not the individual organism, but the organism together with its associated organisms, including its microbial communities.

'''Coral reefs'''. The hologenome theory originated in studies on coral reefs.<ref name=":0" /> Coral reefs are the largest structures created by living organisms, and contain abundant and highly complex microbial communities. Over the past several decades, major declines in coral populations have occurred. Climate change, water pollution and over-fishing are three stress factors that have been described as leading to disease susceptibility. Over twenty different coral diseases have been described, but of these, only a handful have had their causative agents isolated and characterized. Coral bleaching is the most serious of these diseases. In the Mediterranean Sea, the bleaching of ''Oculina patagonica'' was first described in 1994 and shortly determined to be due to infection by Vibrio shiloi. From 1994 to 2002, bacterial bleaching of ''O. patagonica'' occurred every summer in the eastern Mediterranean. Surprisingly, however, after 2003, ''O. patagonica'' in the eastern Mediterranean has been resistant to ''V. shiloi'' infection, although other diseases still cause bleaching. The surprise stems from the knowledge that corals are long lived, with lifespans on the order of decades,<ref name="BBRT2009">{{cite journal |vauthors=Baird AH, Bhagooli R, Ralph PJ, Takahashi S |title=Coral bleaching: the role of the host |journal=Trends in Ecology and Evolution|year=2009|volume=24|issue=1|pages=16–20 |url=http://www.reefresilience.org/pdf/Baird_etal_2009.pdf |pmid=19022522|doi=10.1016/j.tree.2008.09.005|bibcode=2009TEcoE..24...16B }}</ref> and do not have adaptive immune systems.{{citation needed|date=February 2017}} Their innate immune systems do not produce antibodies, and they should seemingly not be able to respond to new challenges except over evolutionary time scales.{{citation needed|date=February 2017}}

The puzzle of how corals managed to acquire resistance to a specific pathogen led to a 2007 proposal, that a dynamic relationship exists between corals and their symbiotic microbial communities. It is thought that by altering its composition, the holobiont can adapt to changing environmental conditions far more rapidly than by genetic mutation and selection alone. Extrapolating this hypothesis to other organisms, including higher plants and animals, led to the proposal of the hologenome theory of evolution.<ref name=":0">{{cite journal|vauthors=Rosenberg E, Koren O, Reshef L, Efrony R, Zilber-Rosenberg I|title=The role of microorganisms in coral health, disease and evolution|journal=Nature Reviews Microbiology|year=2007|volume=5|issue=5|pages=355–362|pmid=17384666|doi=10.1038/nrmicro1635|s2cid=2967190}}</ref>

{{as of |2007}} the hologenome theory was still being debated.<ref>{{cite journal |vauthors=Leggat W, Ainsworth T, Bythell J, Dove S, Gates R, Hoegh-Guldberg O, Iglesias-Prieto R, Yellowlees D | title=The hologenome theory disregards the coral holobiont | journal=Nature Reviews Microbiology|year=2007|volume=5|pages=Online Correspondence | doi=10.1038/nrmicro1635-c1 | issue=10| s2cid=9031305 | doi-access=free}}</ref> A major criticism has been the claim that ''V. shiloi'' was misidentified as the causative agent of coral bleaching, and that its presence in bleached ''O. patagonica'' was simply that of opportunistic colonization.<ref>{{cite journal |vauthors=Ainsworth TD, Fine M, Roff G, Hoegh-Guldberg O | title=Bacteria are not the primary cause of bleaching in the Mediterranean coral ''Oculina patagonica'' | journal=The ISME Journal|year=2008|volume=2|pages=67–73 | doi=10.1038/ismej.2007.88 | pmid=18059488 | issue=1 | s2cid=1032896 | doi-access=free | bibcode=2008ISMEJ...2...67A }}</ref> If this is true, the basic observation leading to the theory would be invalid. The theory has gained significant popularity as a way of explaining rapid changes in adaptation that cannot otherwise be explained by traditional mechanisms of natural selection. Within the hologenome theory, the holobiont has not only become the principal unit of natural selection but also the result of other step of integration that it is also observed at the cell (symbiogenesis, endosymbiosis) and genomic levels.<ref name="Salvucci2014" />

== Research methods == === Targeted amplicon sequencing === {{microbiomes|microbiota}}

Targeted amplicon sequencing relies on having some expectations about the composition of the community that is being studied. In target amplicon sequencing a phylogenetically informative marker is targeted for sequencing. Such a marker should be present in ideally all the expected organisms. It should also evolve in such a way that it is conserved enough that primers can target genes from a wide range of organisms while evolving quickly enough to allow for finer resolution at the taxonomic level. A common marker for human microbiome studies is the gene for bacterial 16S rRNA (''i.e.'' "16S rDNA", the sequence of DNA which encodes the ribosomal RNA molecule).<ref name="Kucz2012">{{Cite journal | last1 = Kuczynski | first1 = J. | last2 = Lauber | first2 = C. L. | last3 = Walters | first3 = W. A. | last4 = Parfrey | first4 = L. W. | last5 = Clemente | first5 = J. C. | last6 = Gevers | first6 = D. | last7 = Knight | first7 = R. | doi = 10.1038/nrg3129 | title = Experimental and analytical tools for studying the human microbiome | journal=Nature Reviews Genetics | volume = 13 | issue = 1 | pages = 47–58 | year = 2011 | pmid = 22179717 | pmc =5119550}}</ref> Since ribosomes are present in all living organisms, using 16S rDNA allows for DNA to be amplified from many more organisms than if another marker were used. The 16S rRNA gene contains both slowly evolving regions and 9 fast evolving regions, also known as hypervariable regions (HVRs);<ref>{{Cite journal |last1=Chakravorty |first1=Soumitesh |last2=Helb |first2=Danica |last3=Burday |first3=Michele |last4=Connell |first4=Nancy |last5=Alland |first5=David |date=May 2007 |title=A detailed analysis of 16S ribosomal RNA gene segments for the diagnosis of pathogenic bacteria |journal=Journal of Microbiological Methods |language=en |volume=69 |issue=2 |pages=330–339 |doi=10.1016/j.mimet.2007.02.005 |pmc=2562909 |pmid=17391789}}</ref> the former can be used to design broad primers while the latter allow for finer taxonomic distinction. However, species-level resolution is not typically possible using the 16S rDNA. Primer selection is an important step, as anything that cannot be targeted by the primer will not be amplified and thus will not be detected, moreover different sets of primers can be selected to amplify different HVRs in the gene, or pairs of them. The appropriate choice of which HVRs to amplify has to be made according to the taxonomic groups of interest, as different target regions has been shown to influence taxonomical classification.<ref>{{Cite journal |last1=Soriano-Lerma |first1=Ana |last2=Pérez-Carrasco |first2=Virginia |last3=Sánchez-Marañón |first3=Manuel |last4=Ortiz-González |first4=Matilde |last5=Sánchez-Martín |first5=Victoria |last6=Gijón |first6=Juan |last7=Navarro-Mari |first7=José María |last8=García-Salcedo |first8=José Antonio |last9=Soriano |first9=Miguel |date=December 2020 |title=Influence of 16S rRNA target region on the outcome of microbiome studies in soil and saliva samples |journal=Scientific Reports |language=en |volume=10 |issue=1 |page=13637 |doi=10.1038/s41598-020-70141-8 |issn=2045-2322 |pmc=7423937 |pmid=32788589|bibcode=2020NatSR..1013637S }}</ref>

Targeted studies of eukaryotic and viral communities are limited<ref name="Marchesi2010">{{Cite book | last1 = Marchesi | first1 = J. R. | chapter = Prokaryotic and Eukaryotic Diversity of the Human Gut | doi = 10.1016/S0065-2164(10)72002-5 | title = Advances in Applied Microbiology Volume 72 | volume = 72 | pages = 43–62 | year = 2010 | isbn = 978-0-12-380989-6 | pmid = 20602987 }}</ref> and subject to the challenge of excluding host DNA from amplification and the reduced eukaryotic and viral biomass in the human microbiome.<ref name="Vest2008">{{Cite journal | last1 = Vestheim | first1 = H. | last2 = Jarman | first2 = S. N. | doi = 10.1186/1742-9994-5-12 | 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 | year = 2008 | pmid = 18638418 | pmc =2517594 | doi-access = free }}</ref>

After the amplicons are sequenced, molecular phylogenetic methods are used to infer the composition of the microbial community. This can be done through clustering methodologies, by clustering the amplicons into operational taxonomic units (OTUs); or alternatively with denoising methodologies, identifying amplicon sequence variants (ASVs).

Phylogenetic relationships are then inferred between the sequences. Due to the complexity of the data, distance measures such as UniFrac distances are usually defined between microbiome samples, and downstream multivariate methods are carried out on the distance matrices. An important point is that the scale of data is extensive, and further approaches must be taken to identify patterns from the available information. Tools used to analyze the data include VAMPS,<ref>{{cite web|title=VAMPS: The Visualization and Analysis of Microbial Population Structures|url=http://vamps.mbl.edu/|publisher=Bay Paul Center, MBL, Woods Hole|access-date=11 March 2012}}</ref> QIIME,<ref name="CapoKucz2010">{{Cite journal | last1 = Caporaso | first1 = J. G. | last2 = Kuczynski | first2 = J. | last3 = Stombaugh | first3 = J. | last4 = Bittinger | first4 = K. | last5 = Bushman | first5 = F. D. | last6 = Costello | first6 = E. K. | last7 = Fierer | first7 = N. | last8 = Peña | first8 = A. G. | last9 = Goodrich | first9 = J. K. | doi = 10.1038/nmeth.f.303 | last10 = Gordon | first10 = J. I. | last11 = Huttley | first11 = G. A. | last12 = Kelley | first12 = S. T. | last13 = Knights | first13 = D. | last14 = Koenig | first14 = J. E. | last15 = Ley | first15 = R. E. | last16 = Lozupone | first16 = C. A. | last17 = McDonald | first17 = D. | last18 = Muegge | first18 = B. D. | last19 = Pirrung | first19 = M. | last20 = Reeder | first20 = J. | last21 = Sevinsky | first21 = J. R. | last22 = Turnbaugh | first22 = P. J. | last23 = Walters | first23 = W. A. | last24 = Widmann | first24 = J. | last25 = Yatsunenko | first25 = T. | last26 = Zaneveld | first26 = J. | last27 = Knight | first27 = R. | title = QIIME allows analysis of high-throughput community sequencing data | journal = Nature Methods | volume = 7 | issue = 5 | pages = 335–336 | year = 2010 | pmid = 20383131 | pmc =3156573 | bibcode = 2010NatCB...7..335C }}</ref> mothur<ref name="SchlossWest2009">{{Cite journal | last1 = Schloss | first1 = P. D. | last2 = Westcott | first2 = S. L. | last3 = Ryabin | first3 = T. | last4 = Hall | first4 = J. R. | last5 = Hartmann | first5 = M. | last6 = Hollister | first6 = E. B. | last7 = Lesniewski | first7 = R. A. | last8 = Oakley | first8 = B. B. | last9 = Parks | first9 = D. H. | doi = 10.1128/AEM.01541-09 | last10 = Robinson | first10 = C. J. | last11 = Sahl | first11 = J. W. | last12 = Stres | first12 = B. | last13 = Thallinger | first13 = G. G. | last14 = Van Horn | first14 = D. J. | last15 = Weber | first15 = C. F. | title = Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities | journal = Applied and Environmental Microbiology | volume = 75 | issue = 23 | pages = 7537–7541 | year = 2009 | pmid = 19801464 | pmc =2786419 | bibcode = 2009ApEnM..75.7537S }}</ref> and DADA2<ref>{{Cite journal |last1=Callahan |first1=Benjamin J. |last2=McMurdie |first2=Paul J. |last3=Rosen |first3=Michael J. |last4=Han |first4=Andrew W. |last5=Johnson |first5=Amy Jo A. |last6=Holmes |first6=Susan P. |date=July 2016 |title=DADA2: High-resolution sample inference from Illumina amplicon data |journal=Nature Methods |language=en |volume=13 |issue=7 |pages=581–583 |doi=10.1038/nmeth.3869 |issn=1548-7105 |pmc=4927377 |pmid=27214047 |bibcode=2016NatCB..13..581C }}</ref> or UNOISE3<ref>{{cite bioRxiv |last=Edgar |first=Robert C. |date=2016-10-15 |title=UNOISE2: improved error-correction for Illumina 16S and ITS amplicon sequencing |language=en |biorxiv=10.1101/081257}}</ref> for denoising.

=== Metagenomic sequencing === {{Main|Metagenomics}} Metagenomics is also used extensively for studying microbial communities.<ref name="TurnHamady2009">{{Cite journal | last1 = Turnbaugh | first1 = P. J. | last2 = Hamady | first2 = M. | last3 = Yatsunenko | first3 = T. | last4 = Cantarel | first4 = B. L. | last5 = Duncan | first5 = A. | last6 = Ley | first6 = R. E. | last7 = Sogin | first7 = M. L. | last8 = Jones | first8 = W. J. | last9 = Roe | first9 = B. A. | doi = 10.1038/nature07540 | last10 = Affourtit | first10 = J. P. | last11 = Egholm | first11 = M. | last12 = Henrissat | first12 = B. | last13 = Heath | first13 = A. C. | last14 = Knight | first14 = R. | last15 = Gordon | first15 = J. 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G. | last2 = Von Mering | first2 = C. | last3 = Kobayashi | first3 = A. | last4 = Salamov | first4 = A. A. | last5 = Chen | first5 = K. | last6 = Chang | first6 = H. W. | last7 = Podar | first7 = M. | last8 = Short | first8 = J. M. | last9 = Mathur | first9 = E. J. | last10 = Detter | first10 = J. C. | last11 = Bork | first11 = P. | last12 = Hugenholtz | first12 = P. | last13 = Rubin | first13 = E. M. | title = Comparative Metagenomics of Microbial Communities | doi = 10.1126/science.1107851 | journal = Science | volume = 308 | issue = 5721 | pages = 554–557 | year = 2005 | pmid = 15845853| bibcode = 2005Sci...308..554T | citeseerx = 10.1.1.377.2288 | s2cid = 161283 }}</ref> In metagenomic sequencing, DNA is recovered directly from environmental samples in an untargeted manner with the goal of obtaining an unbiased sample from all genes of all members of the community. Recent studies use shotgun Sanger sequencing or pyrosequencing to recover the sequences of the reads.<ref name="Wooley2010">{{Cite journal | last1 = Wooley | first1 = J. C. | last2 = Godzik | first2 = A. | last3 = Friedberg | first3 = I. | editor1-last = Bourne | editor1-first = Philip E. | title = A Primer on Metagenomics | doi = 10.1371/journal.pcbi.1000667 | journal = PLOS Computational Biology | volume = 6 | issue = 2 | article-number = e1000667 | year = 2010 | pmid = 20195499| pmc =2829047 | bibcode = 2010PLSCB...6E0667W | doi-access = free }}</ref> The reads can then be assembled into contigs. To determine the phylogenetic identity of a sequence, it is compared to available full genome sequences using methods such as BLAST. One drawback of this approach is that many members of microbial communities do not have a representative sequenced genome, but this applies to 16S rRNA amplicon sequencing as well and is a fundamental problem.<ref name=Kucz2012/> With shotgun sequencing, it can be resolved by having a high coverage (50–100x) of the unknown genome, effectively doing a de novo genome assembly. As soon as there is a complete genome of an unknown organism available it can be compared phylogenetically and the organism put into its place in the tree of life, by creating new taxa. An emerging approach is to combine shotgun sequencing with proximity-ligation data (Hi-C) to assemble complete microbial genomes without culturing.<ref>{{Cite journal|last1=Watson|first1=Mick|last2=Roehe|first2=Rainer|last3=Walker|first3=Alan W.|last4=Dewhurst|first4=Richard J.|last5=Snelling|first5=Timothy J.|last6=Ivan Liachko|last7=Langford|first7=Kyle W.|last8=Press|first8=Maximilian O.|last9=Wiser|first9=Andrew H.|date=2018-02-28|title=Assembly of 913 microbial genomes from metagenomic sequencing of the cow rumen|journal=Nature Communications|language=en|volume=9|issue=1|page=870|doi=10.1038/s41467-018-03317-6|pmid=29491419|pmc=5830445|issn=2041-1723|bibcode=2018NatCo...9..870S}}</ref>

Despite the fact that metagenomics is limited by the availability of reference sequences, one significant advantage of metagenomics over targeted amplicon sequencing is that metagenomics data can elucidate the functional potential of the community DNA.<ref name="MullerSzkl2010">{{Cite journal | last1 = Muller | first1 = J. | last2 = Szklarczyk | first2 = D. | last3 = Julien | first3 = P. | last4 = Letunic | first4 = I. | last5 = Roth | first5 = A. | last6 = Kuhn | first6 = M. | last7 = Powell | first7 = S. | last8 = Von Mering | first8 = C. | last9 = Doerks | first9 = T. | last10 = Jensen | doi = 10.1093/nar/gkp951 | first10 = L. J. | last11 = Bork | first11 = P. | title = EggNOG v2.0: Extending the evolutionary genealogy of genes with enhanced non-supervised orthologous groups, species and functional annotations | journal = Nucleic Acids Research | volume = 38 | issue = Database issue | pages = D190–D195 | year = 2009 | pmid = 19900971 | pmc =2808932 }}</ref><ref name="KanehisaGoto2010">{{Cite journal | last1 = Kanehisa | first1 = M. | last2 = Goto | first2 = S. | last3 = Furumichi | first3 = M. | last4 = Tanabe | first4 = M. | last5 = Hirakawa | first5 = M. | title = KEGG for representation and analysis of molecular networks involving diseases and drugs | doi = 10.1093/nar/gkp896 | journal = Nucleic Acids Research | volume = 38 | issue = Database issue | pages = D355–D360 | year = 2009 | pmid = 19880382 | pmc =2808910 }}</ref> Targeted gene surveys cannot do this as they only reveal the phylogenetic relationship between the same gene from different organisms. Functional analysis is done by comparing the recovered sequences to databases of metagenomic annotations such as KEGG. The metabolic pathways that these genes are involved in can then be predicted with tools such as MG-RAST,<ref name="MeyerPaar2008">{{Cite journal | last1 = Meyer | first1 = F. | last2 = Paarmann | first2 = D. | last3 = d'Souza | first3 = M. | last4 = Olson | first4 = R. | last5 = Glass | first5 = E. M. | last6 = Kubal | first6 = M. | last7 = Paczian | first7 = T. | last8 = Rodriguez | first8 = A. | last9 = Stevens | first9 = R. | last10 = Wilke | first10 = A. | last11 = Wilkening | first11 = J. | last12 = Edwards | first12 = R. A. | title = The metagenomics RAST server – a public resource for the automatic phylogenetic and functional analysis of metagenomes | doi = 10.1186/1471-2105-9-386 | journal = BMC Bioinformatics | volume = 9 | article-number = 386 | year = 2008 | pmid = 18803844 | pmc =2563014 | doi-access = free }}</ref> CAMERA<ref name="SunChen2011">{{Cite journal | last1 = Sun | first1 = S. | last2 = Chen | first2 = J. | last3 = Li | first3 = W. | last4 = Altintas | first4 = I. | last5 = Lin | first5 = A. | last6 = Peltier | first6 = S. | last7 = Stocks | first7 = K. | last8 = Allen | first8 = E. E. | last9 = Ellisman | first9 = M. | last10 = Grethe | doi = 10.1093/nar/gkq1102 | first10 = J. | last11 = Wooley | first11 = J. | title = Community cyberinfrastructure for Advanced Microbial Ecology Research and Analysis: The CAMERA resource | journal = Nucleic Acids Research | volume = 39 | issue = Database issue | pages = D546–D551 | year = 2010 | pmid = 21045053 | pmc =3013694 }}</ref> and IMG/M.<ref name="MarkowitzIvan2008">{{Cite journal | last1 = Markowitz | first1 = V. M. | last2 = Ivanova | first2 = N. N. | last3 = Szeto | first3 = E. | last4 = Palaniappan | first4 = K. | last5 = Chu | first5 = K. | last6 = Dalevi | first6 = D. | last7 = Chen | first7 = I. M. A. | last8 = Grechkin | first8 = Y. | last9 = Dubchak | first9 = I. | last10 = Anderson | doi = 10.1093/nar/gkm869 | first10 = I. | last11 = Lykidis | first11 = A. | last12 = Mavromatis | first12 = K. | last13 = Hugenholtz | first13 = P. | last14 = Kyrpides | first14 = N. C. | title = IMG/M: A data management and analysis system for metagenomes | journal = Nucleic Acids Research | volume = 36 | issue = Database issue | pages = D534–D538 | year = 2007 | pmid = 17932063 | pmc =2238950 }}</ref>

=== RNA and protein-based approaches === Metatranscriptomics studies have been performed to study the gene expression of microbial communities through methods such as the pyrosequencing of extracted RNA.<ref name="ShiTyson2009">{{Cite journal| last1 = Shi | first1 = Y.| last2 = Tyson | first2 = G. W. | last3 = Delong | first3 = E. F.| doi = 10.1038/nature08055| title = Metatranscriptomics reveals unique microbial small RNAs in the ocean's water column| journal = Nature| volume = 459| issue = 7244| pages = 266–269| year = 2009| pmid = 19444216 | bibcode = 2009Natur.459..266S| s2cid = 4340144}}</ref> Structure based studies have also identified non-coding RNAs (ncRNAs) such as ribozymes from microbiota.<ref name="JimenezDel2011">{{Cite journal| last1 = Jimenez | first1 = R. M.| last2 = Delwart | first2 = E. | last3 = Luptak | first3 = A | doi = 10.1074/jbc.C110.209288| title = Structure-based Search Reveals Hammerhead Ribozymes in the Human Microbiome| journal = Journal of Biological Chemistry| volume = 286| issue = 10| pages = 7737–7743| year = 2011| pmid = 21257745| pmc =3048661| doi-access = free}}</ref> Metaproteomics is an approach that studies the proteins expressed by microbiota, giving insight into its functional potential.<ref name="MaronRan2007">{{Cite journal| last1 = Maron | first1 = PA | last2 = Ranjard | first2 = L. | last3 = Mougel | first3 = C. | last4 = Lemanceau | first4 = P. | title = Metaproteomics: A New Approach for Studying Functional Microbial Ecology | doi = 10.1007/s00248-006-9196-8 | journal = Microbial Ecology | volume = 53 | issue = 3 | pages = 486–493 | year = 2007 | pmid = 17431707 | bibcode = 2007MicEc..53..486M | s2cid = 26953155 }}</ref>

== Projects == The Human Microbiome Project launched in 2008 was a United States National Institutes of Health initiative to identify and characterize microorganisms found in both healthy and diseased humans.<ref name="nih">{{cite web | url=http://hmpdacc.org/overview/about.php | title=NIH Human Microbiome Project | publisher=US National Institutes of Health, Department of Health and Human Services, US Government | date=2016 | access-date=14 June 2016 | archive-url=https://web.archive.org/web/20160611035755/http://hmpdacc.org/overview/about.php | archive-date=11 June 2016 }}</ref> The five-year project, best characterized as a feasibility study with a budget of $115 million, tested how changes in the human microbiome are associated with human health or disease.<ref name=nih/>

The Earth Microbiome Project (EMP) is an initiative to collect natural samples and analyze the microbial community around the globe. Microbes are highly abundant, diverse and have an important role in the ecological system. Yet {{As of|2010|lc=on}}, it was estimated that the total global environmental DNA sequencing effort had produced less than 1 percent of the total DNA found in a liter of seawater or a gram of soil,<ref>{{Cite journal | last1 = Gilbert | first1 = J. A. | last2 = Meyer | first2 = F. | last3 = Antonopoulos | first3 = D. | display-authors = et al| title = Meeting Report: The Terabase Metagenomics Workshop and the Vision of an Earth Microbiome Project | journal = Standards in Genomic Sciences | volume = 3 | issue = 3 | pages = 243–248 | year = 2010 | pmid = 21304727| pmc =3035311 | doi=10.4056/sigs.1433550| bibcode = 2010SGenS...3..243G }}</ref> and the specific interactions between microbes are largely unknown. The EMP aims to process as many as 200,000 samples in different biomes, generating a complete database of microbes on earth to characterize environments and ecosystems by microbial composition and interaction. Using these data, new ecological and evolutionary theories can be proposed and tested.<ref name=GilbertDor2011>{{Cite journal | last1 = Gilbert | first1 = J. A. | last2 = O'Dor | first2 = R. | last3 = King | first3 = N. | last4 = Vogel | first4 = T. M. | title = The importance of metagenomic surveys to microbial ecology: Or why Darwin would have been a metagenomic scientist | doi = 10.1186/2042-5783-1-5 | journal = Microbial Informatics and Experimentation | volume = 1 | issue = 1 | page = 5 | year = 2011 | pmid = 22587826| pmc = 3348666 | doi-access = free }}</ref>

== Privacy issues == Microbial DNA inhabiting a person's human body can uniquely identify the person. A person's privacy may be compromised if the person anonymously donated microbe DNA data. Their medical condition and identity could be revealed.<ref>{{Cite web|title = Microbial DNA in Human Body Can Be Used to Identify Individuals|url = http://www.scientificamerican.com/article/microbial-dna-in-human-body-can-be-used-to-identify-individuals|access-date = 2015-05-17|first = Ewen|last = magazine| website=Scientific American }}</ref><ref>{{Cite journal|title = Microbiomes raise privacy concerns|journal = Nature|volume = 521|issue = 7551|page = 136|doi = 10.1038/521136a|pmid = 25971486|year = 2015|last1 = Callaway|first1 = Ewen|bibcode = 2015Natur.521..136C|s2cid = 4393347|doi-access = free}}</ref><ref>{{cite journal|journal=National Geographic|title = Can The Microbes You Leave Behind Be Used to Identify You?|url = http://phenomena.nationalgeographic.com/2015/05/11/can-the-microbes-you-leave-behind-be-used-to-identify-you/|archive-url = https://web.archive.org/web/20150530081450/http://phenomena.nationalgeographic.com/2015/05/11/can-the-microbes-you-leave-behind-be-used-to-identify-you/|archive-date = May 30, 2015|access-date = 2015-05-17|first = Ed|last = Yong|date = 2015-05-11}}</ref>

== References == {{Reflist}}

Category:Microbiology Category:Bacteriology Category:Bacteria Category:Microbiomes