vaginal flora

The primary colonizing bacteria of a healthy individual are of the genus Lactobacillus (90–95%), the most common being L. crispatus, L. iners, L. jensenii, and L. gasseri.{{cite journal | last1=Tidbury | first1=Fiona Damaris | last2=Langhart | first2=Anita | last3=Weidlinger | first3=Susanna | last4=Stute | first4=Petra | title=Non-antibiotic treatment of bacterial vaginosis—a systematic review | journal=Archives of Gynecology and Obstetrics | publisher=Springer Science and Business Media LLC | volume=303 | issue=1 | date=2020-10-06 | issn=0932-0067 | pmid=33025086 | doi=10.1007/s00404-020-05821-x | pages=37–45| s2cid=222149236 }} Since the first description of lactobacilli by Döderlein, lactobacilli have been generally considered the gatekeepers of the vaginal ecosystem. Lactobacilli have been shown to inhibit in vitro growth of pathogenic microorganisms, e.g. Bacteroides fragilis, Escherichia coli, Gardnerella vaginalis, Mobiluncus spp., Neisseria gonorrhoeae, Peptostreptococcus anaerobius, Prevotella bivia and Staphylococcus aureus. It is generally accepted that this is achieved mainly through the action of lactic acid.{{cite journal | vauthors = Graver MA, Wade JJ | title = The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth | journal = Annals of Clinical Microbiology and Antimicrobials | volume = 10 | pages = 8 | date = February 2011 | pmid = 21329492 | pmc = 3045876 | doi = 10.1186/1476-0711-10-8 | doi-access = free }}{{cite journal | vauthors = Matu MN, Orinda GO, Njagi EN, Cohen CR, Bukusi EA | title = In vitro inhibitory activity of human vaginal lactobacilli against pathogenic bacteria associated with bacterial vaginosis in Kenyan women | journal = Anaerobe | volume = 16 | issue = 3 | pages = 210–5 | date = June 2010 | pmid = 19925874 | doi = 10.1016/j.anaerobe.2009.11.002 | url = http://ir-library.ku.ac.ke/handle/123456789/5929 }}{{cite journal | vauthors = Skarin A, Sylwan J | title = Vaginal lactobacilli inhibiting growth of Gardnerella vaginalis, Mobiluncus and other bacterial species cultured from vaginal content of women with bacterial vaginosis | journal = Acta Pathologica et Microbiologica Scandinavica, Section B| volume = 94 | issue = 6 | pages = 399–403 | date = December 1986 | pmid = 3494379 | doi = 10.1111/j.1699-0463.1986.tb03074.x }}{{cite journal | last1 = Strus | first1 = M. | first2 = M. | last2 = Malinowska | first3 = P.B. | last3 = Heczko | date = 2002 | title = In vitro antagonistic effect of Lactobacillus on organisms associated with bacterial vaginosis | journal = J. Reprod. Med. | volume = 47 | issue = 1 | pages = 41–46 | pmid = 11838310}} Moreover, lactobacilli normally help to prevent long-term colonization of the vagina by adhering to vaginal epithelial cells. This usually reduces pathogens from infecting to the vaginal epithelium.{{cite journal | vauthors = Boris S, Barbés C | title = Role played by lactobacilli in controlling the population of vaginal pathogens | journal = Microbes and Infection | volume = 2 | issue = 5 | pages = 543–6 | date = April 2000 | pmid = 10865199 | doi = 10.1016/s1286-4579(00)00313-0 }}

Next to lactic acid production and competition for adherence, other antagonistic mechanisms include hydrogen peroxide (a broad-spectrum antimicrobial) and bacteriocins (target-specific antimicrobials) production.{{cite journal | vauthors = Martín R, Suárez JE | title = Biosynthesis and degradation of H2O2 by vaginal lactobacilli | journal = Applied and Environmental Microbiology | volume = 76 | issue = 2 | pages = 400–5 | date = January 2010 | pmid = 19948869 | pmc = 2805228 | doi = 10.1128/AEM.01631-09 | bibcode = 2010ApEnM..76..400M }}{{cite journal | vauthors = O'Hanlon DE, Moench TR, Cone RA | title = In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide | journal = BMC Infectious Diseases | volume = 11 | pages = 200 | date = July 2011 | pmid = 21771337 | pmc = 3161885 | doi = 10.1186/1471-2334-11-200 | doi-access = free }}

File:Glycogen structure.svg that is metabolized into lactic acid]]

Low pH is generally accepted to be the main mechanism controlling the composition of the vaginal microflora. Although the lactic acid produced by lactobacilli contributes to the vaginal acidity, it is still not proven to be the primary source of low vaginal pH, but the fact remains that most lactobacilli thrive best at a pH < 3.5 .{{cite journal | vauthors = Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, Gurguis A, Faro S | display-authors = 6 | title = Defense factors of vaginal lactobacilli | journal = American Journal of Obstetrics and Gynecology | volume = 185 | issue = 2 | pages = 375–9 | date = August 2001 | pmid = 11518895 | doi = 10.1067/mob.2001.115867 }}{{cite journal | vauthors = Linhares IM, Summers PR, Larsen B, Giraldo PC, Witkin SS | title = Contemporary perspectives on vaginal pH and lactobacilli | journal = American Journal of Obstetrics and Gynecology | volume = 204 | issue = 2 | pages = 120.e1–5 | date = February 2011 | pmid = 20832044 | doi = 10.1016/j.ajog.2010.07.010 }}{{cite journal | vauthors = Redondo-Lopez V, Cook RL, Sobel JD | title = Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora | journal = Reviews of Infectious Diseases | volume = 12 | issue = 5 | pages = 856–72 | year = 1990 | pmid = 2237129 | doi = 10.1093/clinids/12.5.856 }}

Normal vaginal pH is considered to be under 4.5 with a range of 3.8 to 4.4.

Production of hydrogen peroxide (H₂O₂) is a proposed mechanism for bacterial antagonism in vitro,{{cite journal | vauthors = Dahiya RS, Speck ML | title = Hydrogen peroxide formation by lactobacilli and its effect on Staphylococcus aureus | journal = Journal of Dairy Science | volume = 51 | issue = 10 | pages = 1568–72 | date = October 1968 | pmid = 5682478 | doi = 10.3168/jds.s0022-0302(68)87232-7 | doi-access = free }}{{cite journal | vauthors = Thompson R, Johnson A | title = The inhibitory action of saliva on the diphtheria bacillus: hydrogen peroxide, the inhibitory agent produced by salivary streptococci | journal = The Journal of Infectious Diseases | volume = 88 | issue = 1 | pages = 81–5 | year = 1951 | pmid = 14803753 | doi = 10.1093/infdis/88.1.81 }}{{cite journal | vauthors = Wheater DM, Hirsch A, Mattick AT | title = Possible identity of lactobacillin with hydrogen peroxide produced by lactobacilli | journal = Nature | volume = 170 | issue = 4328 | pages = 623–4 | date = October 1952 | pmid = 13002389 | doi = 10.1038/170623a0 | s2cid = 4169333 | bibcode = 1952Natur.170..623W }} inhibiting growth of microorganisms via direct interaction or via human myeloperoxidase.{{cite journal | vauthors = Eschenbach DA, Davick PR, Williams BL, Klebanoff SJ, Young-Smith K, Critchlow CM, Holmes KK | title = Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis | journal = Journal of Clinical Microbiology | volume = 27 | issue = 2 | pages = 251–6 | date = February 1989 | pmid = 2915019 | pmc = 267286 | doi = 10.1128/JCM.27.2.251-256.1989 }}{{cite journal | vauthors = Hillier SL, Krohn MA, Klebanoff SJ, Eschenbach DA | title = The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women | journal = Obstetrics and Gynecology | volume = 79 | issue = 3 | pages = 369–73 | date = March 1992 | pmid = 1738516 | doi = 10.1097/00006250-199203000-00008 }}{{cite journal | vauthors = Klebanoff SJ, Smith DC | title = Peroxidase-mediated antimicrobial activity of rat uterine fluid | journal = Gynecologic Investigation | volume = 1 | issue = 1 | pages = 21–30 | year = 1970 | pmid = 4320447 | doi = 10.1159/000301903 }} However, in vivo, the role of peroxide is uncertain. Under optimal anaerobic growth conditions, physiological concentrations of lactic acid inactivated the BV-associated pathogens without affecting the vaginal lactobacilli. Although the hydrogen peroxide production of lactobacilli has been considered as an important antimicrobial component, contributing to the colonization resistance provided by lactobacilli,{{cite journal | vauthors = Vallor AC, Antonio MA, Hawes SE, Hillier SL | title = Factors associated with acquisition of, or persistent colonization by, vaginal lactobacilli: role of hydrogen peroxide production | journal = The Journal of Infectious Diseases | volume = 184 | issue = 11 | pages = 1431–6 | date = December 2001 | pmid = 11709785 | doi = 10.1086/324445 | doi-access = free }} and although there seems to be a link between H₂O₂-producing lactobacilli and normal vaginal microflora, recent data do not support this role for H₂O₂.

Experimentally, hydrogen peroxide-producing lactobacilli have been shown to inactivate HIV-1, herpes simplex virus type 2 (HSV-2), Trichomonas vaginalis, G. vaginalis, P. bivia and E. coli. O'Hanlon and Baeten{{cite journal | vauthors = Baeten JM, Hassan WM, Chohan V, Richardson BA, Mandaliya K, Ndinya-Achola JO, Jaoko W, McClelland RS | display-authors = 6 | title = Prospective study of correlates of vaginal Lactobacillus colonisation among high-risk HIV-1 seronegative women | journal = Sexually Transmitted Infections | volume = 85 | issue = 5 | pages = 348–53 | date = September 2009 | pmid = 19329442 | pmc = 2837477 | doi = 10.1136/sti.2008.035451 }} found that 96% of Lactobacillus species from a healthy vaginal ecosystem produced H₂O₂ (L. jensenii and L. vaginalis produce the highest levels of H₂O₂),{{cite journal | vauthors = Wilks M, Wiggins R, Whiley A, Hennessy E, Warwick S, Porter H, Corfield A, Millar M | display-authors = 6 | title = Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome | journal = Journal of Clinical Microbiology | volume = 42 | issue = 2 | pages = 713–7 | date = February 2004 | pmid = 14766841 | pmc = 344438 | doi = 10.1128/jcm.42.2.713-717.2004 }} whereas only 6% of the lactobacilli recovered from women with BV produced H₂O₂. In agreement with this, L. iners, most frequently associated with disturbed vaginal microflora,{{cite journal | vauthors = Verhelst R, Verstraelen H, Claeys G, Verschraegen G, Van Simaey L, De Ganck C, De Backer E, Temmerman M, Vaneechoutte M | display-authors = 6 | title = Comparison between Gram stain and culture for the characterization of vaginal microflora: definition of a distinct grade that resembles grade I microflora and revised categorization of grade I microflora | journal = BMC Microbiology | volume = 5 | pages = 61 | date = October 2005 | pmid = 16225680 | pmc = 1266370 | doi = 10.1186/1471-2180-5-61 | doi-access = free }}{{cite journal | vauthors = De Backer E, Verhelst R, Verstraelen H, Alqumber MA, Burton JP, Tagg JR, Temmerman M, Vaneechoutte M | display-authors = 6 | title = Quantitative determination by real-time PCR of four vaginal Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse relationship between L. gasseri and L. iners | journal = BMC Microbiology | volume = 7 | pages = 115 | date = December 2007 | pmid = 18093311 | pmc = 2233628 | doi = 10.1186/1471-2180-7-115 | doi-access = free }} is a poor producer of H₂O₂.{{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 }}{{cite journal | vauthors = Antonio MA, Rabe LK, Hillier SL | title = Colonization of the rectum by Lactobacillus species and decreased risk of bacterial vaginosis | journal = The Journal of Infectious Diseases | volume = 192 | issue = 3 | pages = 394–8 | date = August 2005 | pmid = 15995952 | doi = 10.1086/430926 | doi-access = free }} Vaginal colonization by H₂O₂-producing lactobacilli has been associated with a decrease in the occurrence of bacterial vaginosis (BV).{{cite journal | vauthors = Hawes SE, Hillier SL, Benedetti J, Stevens CE, Koutsky LA, Wolner-Hanssen P, Holmes KK | title = Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections | journal = The Journal of Infectious Diseases | volume = 174 | issue = 5 | pages = 1058–63 | date = November 1996 | pmid = 8896509 | doi = 10.1093/infdis/174.5.1058 | doi-access = free }} However, more recently O'Hanlon et al.{{cite journal | vauthors = O'Hanlon DE, Lanier BR, Moench TR, Cone RA | title = Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli | journal = BMC Infectious Diseases | volume = 10 | pages = 120 | date = May 2010 | pmid = 20482854 | pmc = 2887447 | doi = 10.1186/1471-2334-10-120 | doi-access = free }} demonstrated that cervicovaginal fluid and semen have a significant H₂O₂-blocking activity and they later demonstrated that physiological concentrations of H₂O₂ below 100 μM fail to inactivate any of the 17 tested BV-associated bacteria, e.g. A. vaginae, G. vaginalis, Mobiluncus spp., P. bivia, P. corporis, Mycoplasma hominis, even in the presence of human myeloperoxidase, known to increase the microbicidal activity of H₂O₂. Only supraphysiologic concentrations of exogenous H₂O₂ (0.34% w/v, 100 mM) were sufficient to inactivate BV-associated bacteria at which concentration it more potently inactivated vaginal lactobacilli (L. crispatus, L. gasseri, L. iners and L. jensenii). A concentration of 100 mM H₂O₂ is approximately 50-fold higher than lactobacilli are capable of producing even under optimal aerobic, low-antioxidant conditions, and approximately 5,000-fold higher than the estimated H₂O₂ concentration in vivo. Even more remarkable, the addition of only 1% vaginal fluid blocked the microbicidal activity of 1 M H₂O₂. Possible explanations may be that cervicovaginal fluid and semen contain proteins, glycoproteins, polysaccharides, lipids, and other molecules with the potential to react with and inactivate H₂O₂. In addition, the vagina is hypoxic most of the time, whereas lactobacilli require oxygen to produce hydrogen peroxide. It is also remarkable that catalase, which provides bacteria protection against toxic H₂O₂, is absent in lactobacilli,{{cite journal | vauthors = Klebanoff SJ, Hillier SL, Eschenbach DA, Waltersdorph AM | title = Control of the microbial flora of the vagina by H2O2-generating lactobacilli | journal = The Journal of Infectious Diseases | volume = 164 | issue = 1 | pages = 94–100 | date = July 1991 | pmid = 1647428 | doi = 10.1093/infdis/164.1.94 }} and as such they would be unprotected against their own H₂O₂ production. Consequently, hydrogen peroxide production may not be the major mechanism of defense.

Vaginal lactobacilli produce antimicrobial peptides, i.e. bacteriocins such as lactocin 160 and crispasin. with inhibitory activity ranging from narrow (closely related Lactobacillus species) to broad (diverse groups of bacteria, including G. vaginalis and P. bivia), and bacteriocin-like substances, with a broader spectrum of activity than bacteriocins (e.g. a heat-resistant peptide produced by Ligilactobacillus salivarius subsp. salivarius CRL 1328). Several studies have indicated that the activity of bacteriocins is favored by low pH.

The inhibitory substances produced by vaginal Lactobacillus is a primary factor in protecting the vaginal microbiota, with organic acids, bacteriocins, and hydrogen peroxide. These act synergistically against infection by pathogens. Not all Lactobacillus spp. and not all strains within one Lactobacillus species exhibit all 3 mechanisms. Lactobacillus species differ in premenopausal women, i.e. L. crispatus, L. jensenii, L. iners, L. gasseri (and possibly Limosilactobacillus vaginalis), as assessed through cultivation-dependent and cultivation-independent techniques.{{cite journal | vauthors = Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ | display-authors = 6 | title = Vaginal microbiome of reproductive-age women | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 Suppl 1 | issue = Supplement 1 | pages = 4680–7 | date = March 2011 | pmid = 20534435 | pmc = 3063603 | doi = 10.1073/pnas.1002611107 | bibcode = 2011PNAS..108.4680R | doi-access = free }} Vaginal lactobacilli have been shown to display a pronounced vaginotropism, and their pili act as ligands for attachment to receptors of vaginal epithelial cells. The limited number of Lactobacillus spp. found in the human vagina is remarkable, which leads to the possibility that there are host factors that select for specific organisms, that these species

have unusual characteristics that allow them to successfully colonize the vagina, or both

.{{cite journal | vauthors = Zhou X, Bent SJ, Schneider MG, Davis CC, Islam MR, Forney LJ | title = Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods | journal = Microbiology | volume = 150 | issue = Pt 8 | pages = 2565–2573 | date = August 2004 | pmid = 15289553 | doi = 10.1099/mic.0.26905-0 | url = https://zenodo.org/record/898195 | doi-access = free }} However, the vaginotropism, does not only apply to this selected group of lactobacilli

that stand for a healthy vagina, but also for the bacterial species associated with BV.{{cite journal | vauthors = Danielsson D, Teigen PK, Moi H | title = The genital econiche: focus on microbiota and bacterial vaginosis | journal = Annals of the New York Academy of Sciences | volume = 1230 | issue = 1 | pages = 48–58 | date = August 2011 | pmid = 21824165 | doi = 10.1111/j.1749-6632.2011.06041.x | s2cid = 205936163 | bibcode = 2011NYASA1230...48D }} The microbiota detected in the human genital and gut econiche do not appear to grow outside their

host and probably are likely to rely on the close contact between parents and their children for transmission, e.g. mother to neonate transmission of genital microflora, most probably also with gut microflora homogenously distributed over the baby's body including skin, the oral cavity, nasopharynx, and feces.{{cite journal | vauthors = Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R | title = Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 26 | pages = 11971–5 | date = June 2010 | pmid = 20566857 | pmc = 2900693 | doi = 10.1073/pnas.1002601107 | bibcode = 2010PNAS..10711971D | doi-access = free }}

{{main|Bacterial vaginosis}}

Bacterial vaginosis (BV) is associated with the presence of Gardnerella vaginalis and Peptostreptococcus anaerobius{{cite web |title= Bacterial Vaginosis (BV): Condition Information |url= http://www.nichd.nih.gov/health/topics/bacterialvag/conditioninfo/Pages/default.aspx |website=National Institute of Child Health and Human Development|access-date=3 March 2015|date=2013-05-21}} and a decrease in the number of Lactobacillus species that comprise the healthy vaginal microbiota.{{cite journal | vauthors = Nardis C, Mosca L, Mastromarino P | title = Vaginal microbiota and viral sexually transmitted diseases | journal = Annali di Igiene | volume = 25 | issue = 5 | pages = 443–56 | date = September 2013 | pmid = 24048183 | doi = 10.7416/ai.2013.1946 }}{{cite web |title= What are the symptoms of bacterial vaginosis?|url= http://www.nichd.nih.gov/health/topics/bacterialvag/conditioninfo/Pages/symptoms.aspx |website=National Institute of Child Health and Human Development|access-date=22 May 2016|date=2013-05-21}}{{cite journal | vauthors = Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ | display-authors = 6 | title = Vaginal microbiome of reproductive-age women | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = Suppl. 1 | pages = 4680–7 | date = March 2011 | pmid = 20534435 | pmc = 3063603 | doi = 10.1073/pnas.1002611107 | bibcode = 2011PNAS..108.4680R | doi-access = free }} BV is characterized by overgrowth of opportunistic bacteria and a decrease in Lactobacillus species. BV can present itself as symptomatic or asymptomatic. Symptoms include vaginal malodor, increased vaginal pH, and vaginal itching. {{cite journal |vauthors=Schwebke JR, Desmond R |title=Natural history of asymptomatic bacterial vaginosis in a high-risk group of women |journal=Sexually Transmitted Diseases |volume=34 |issue=11 |pages=876–7 |date=November 2007 |pmid=17522586 |doi=10.1097/OLQ.0b013e318073bd82 |url=}} There is no one known cause as to why BV occurs but it is typically associated with abnormal vaginal discharge (Coudray & Madhivanan, 2020).  To diagnose BV in a clinical setting, an Amsel's criteria is used. This means that a patient must have an increased homogeneous thin vaginal discharge, pH secretion higher than 4.5, amine odor when secretions are exposed to hydroxide 10% solution, or clue cells visible on a wet mount. Another way to diagnose BV that is less often used in a clinical setting is a Nugent score. To obtain a Nugent score, gram stain techniques are carried out and it characterizes the bacterial morphology on a scale. A score greater than 7 is associated with BV, 4-6 is an intermediate abnormality, and 0-3 is normal.{{cite journal |vauthors=Coudray MS, Madhivanan P |title=Bacterial vaginosis-A brief synopsis of the literature |journal=European Journal of Obstetrics, Gynecology, and Reproductive Biology |volume=245 |issue= |pages=143–148 |date=February 2020 |pmid=31901667 |pmc=6989391 |doi=10.1016/j.ejogrb.2019.12.035 |url=}} Typically, only women with symptoms receive treatment. Treatment include antibiotics, specifically metronidazole and clindamycin (Hay, 2010).

Studies have shown a correlation between vaginal microbiota and BV development through 16S RNA sequencing. Community state types (CSTs) are used to identify variation between a healthy vaginal microbiota and vaginal microbiota of someone with BV. Most CSTs in a healthy vaginal microbiome consist of different species of Lactobacillus. Studies found that L.iners is the dominant species in BV and L.crispatus is the dominant species in healthy vaginal microbiomes.{{cite journal |vauthors=Parolin C, Marangoni A, Laghi L, Foschi C, Ñahui Palomino RA, Calonghi N, Cevenini R, Vitali B |title=Isolation of Vaginal Lactobacilli and Characterization of Anti-Candida Activity |journal=PLOS ONE |volume=10 |issue=6 |pages=e0131220 |date=2015 |pmid=26098675 |pmc=4476673 |doi=10.1371/journal.pone.0131220 |doi-access=free |bibcode=2015PLoSO..1031220P |url=}}

File:Lactobacilli (Gram stain).jpg

Healthy, normal vaginal microbiota that is dominated by lactobacilli may differ among some ethnic groups. Non-pathogenic vaginal species are part of the normal microbiota of some women.{{cite journal | vauthors = Santiago GL, Cools P, Verstraelen H, Trog M, Missine G, El Aila N, Verhelst R, Tency I, Claeys G, Temmerman M, Vaneechoutte M | display-authors = 6 | title = Longitudinal study of the dynamics of vaginal microflora during two consecutive menstrual cycles | journal = PLOS ONE | volume = 6 | issue = 11 | pages = e28180 | year = 2011 | pmid = 22140538 | pmc = 3227645 | doi = 10.1371/journal.pone.0028180 | bibcode = 2011PLoSO...628180L | doi-access = free }} Several studies have demonstrated that a significant proportion (7–33%) of healthy asymptomatic women (especially black and Hispanic women){{cite journal | vauthors = Zhou X, Brown CJ, Abdo Z, Davis CC, Hansmann MA, Joyce P, Foster JA, Forney LJ | display-authors = 6 | title = Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women | journal = The ISME Journal | volume = 1 | issue = 2 | pages = 121–33 | date = June 2007 | pmid = 18043622 | doi = 10.1038/ismej.2007.12 | s2cid = 8143221 | doi-access = free | bibcode = 2007ISMEJ...1..121Z }} lack appreciable numbers of Lactobacillus species in the vagina, and instead have a vaginal microbiota that consist of other lactic acid-producing bacteria, i.e. species from the genera Atopobium, Leptotrichia, Leuconostoc, Megasphaera, Pediococcus, Streptococcus and Weissella, All ethnic populations have vaginal microflora communities containing lactic acid producing bacteria. This implies that not all communities may be equally resilient, so that if the resilience of a vaginal community is low then transitory changes in the structure of these communities may occur more readily in response to disturbances of various kinds, including menses, sexual intercourse, douching and contraceptive practices. These differences in the structure and composition of microbial communities may underlie well-known differences in the susceptibility of women in these racial groups to BV and various vaginal infections.{{cite journal | vauthors = Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews TJ, Kirmeyer S, Osterman MJ | title = Births: final data for 2007 | journal = National Vital Statistics Reports | volume = 58 | issue = 24 | pages = 1–85 | date = August 2010 | pmid = 21254725 }}{{cite journal | vauthors = Ness RB, Hillier S, Richter HE, Soper DE, Stamm C, Bass DC, Sweet RL, Rice P | display-authors = 6 | title = Can known risk factors explain racial differences in the occurrence of bacterial vaginosis? | journal = Journal of the National Medical Association | volume = 95 | issue = 3 | pages = 201–12 | date = March 2003 | pmid = 12749680 | pmc = 2594421 }} Though vaginal microflora may be disturbed, and lactic acid is produced by other species,{{cite journal | vauthors = Mirmonsef P, Gilbert D, Veazey RS, Wang J, Kendrick SR, Spear GT | title = A comparison of lower genital tract glycogen and lactic acid levels in women and macaques: implications for HIV and SIV susceptibility | journal = AIDS Research and Human Retroviruses | volume = 28 | issue = 1 | pages = 76–81 | date = January 2012 | pmid = 21595610 | pmc = 3251838 | doi = 10.1089/aid.2011.0071 }} vaginal pH and acid production establish normal vaginal microbiota. The pH further decreases during pregnancy.{{cite journal | vauthors = Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, Cotch MF, Edelman R, Pastorek JG, Rao AV | display-authors = 6 | title = Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group | journal = The New England Journal of Medicine | volume = 333 | issue = 26 | pages = 1737–42 | date = December 1995 | pmid = 7491137 | doi = 10.1056/nejm199512283332604 | doi-access = free }}

{{Further|List of bacterial vaginosis microbiota}}

File:Neisseria gonorrhoeae and pus cells in a vaginal swab (Gram stain).jpg

Other bacterial species are frequently found in the vagina, such as the Gram positive cocci: Atopobium vaginae, Peptostreptococcus spp., Staphylococcus spp., Streptococcus spp., and Bacteroides spp., Fusobacterium spp., Gardnerella vaginalis, Mobiluncus, Prevotella spp., and Gram-negative enteric organisms, such as Escherichia coli. Mycoplasma and Ureaplasma are frequently found in the vagina. Some of the obligate and facultative anaerobic bacteria are associated with BV.{{cite journal | vauthors = Hummelen R, Fernandes AD, Macklaim JM, Dickson RJ, Changalucha J, Gloor GB, Reid G | title = Deep sequencing of the vaginal microbiota of women with HIV | journal = PLOS ONE | volume = 5 | issue = 8 | pages = e12078 | date = August 2010 | pmid = 20711427 | pmc = 2920804 | doi = 10.1371/journal.pone.0012078 | bibcode = 2010PLoSO...512078H | doi-access = free }} Neisseria gonorrhoeae is found in the vagina and is considered a pathogen that is sexually transmitted.{{cite journal |vauthors=Aaron KJ, Griner S, Footman A, Boutwell A, Van Der Pol B |title=Vaginal Swab vs Urine for Detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis: A Meta-Analysis |journal=Annals of Family Medicine |volume=21 |issue=2 |pages=172–179 |date=2023 |pmid=36973065 |pmc=10042575 |doi=10.1370/afm.2942}}

{{Main|Vaginal microbiota in pregnancy}}

The effect of tampon use on vaginal flora is debated, but application of tampons appears not to significantly modify the balance of bacterial presence.{{cite journal | vauthors = Briancesco R, Paduano S, Semproni M, Bonadonna L | title = A study on the microbial quality of sealed products for feminine hygiene | journal = Journal of Preventive Medicine and Hygiene | volume = 59 | issue = 3 | pages = E226–E229 | date = September 2018 | pmid = 30397679 | pmc = 6196378 | doi = 10.15167/2421-4248/JPMH2018.59.3.920 }} Pregnancy alters the microbiota with a reduction in species/genus diversity.{{cite journal | vauthors = Sharma H, Tal R, Clark NA, Segars JH | title = Microbiota and pelvic inflammatory disease | journal = Seminars in Reproductive Medicine | volume = 32 | issue = 1 | pages = 43–9 | date = January 2014 | pmid = 24390920 | pmc = 4148456 | doi = 10.1055/s-0033-1361822 }}

File:Normal vaginal flora versus bacterial vaginosis on Pap stain.jpg on Pap stain. Normal vaginal flora (left) is predominantly rod-shaped Lactobacilli, whereas in bacterial vaginosis (right) there is an overgrowth of bacteria, which can be of various species.]]

A healthy vaginal microbiome aids in the prevention of bacterial vaginosis, yeast infections and other possible problems by maintaining an acidic pH (< 4.5) that is unfavourable for the growth of common pathogens, such as Gardnerella vaginalis. The lactobacilli present in a healthy vaginal microbiome also occupy the ecological niche that would otherwise be available for exploitation by pathogenic organisms. However, harmful bacteria or an imbalance in bacteria can lead to infection.{{Cite journal |last1=Lewis |first1=Felicia M. T. |last2=Bernstein |first2=Kyle T. |last3=Aral |first3=Sevgi O. |date=April 2017 |title=Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases |journal=Obstetrics and Gynecology |volume=129 |issue=4 |pages=643–654 |doi=10.1097/AOG.0000000000001932 |issn=1873-233X |pmc=6743080 |pmid=28277350}}

There are many factors that contribute to the composition of vaginal microbiota including stress, age, lifestyle, diet, gut microbiota, antibiotics, probiotics, and vaginal infections.

Lifestyle can impact microbiota by means of personal hygiene. Research suggests that vaginal douching is associated with increased risk of BV. It also shows that sexual practices that include multiple sexual partners can increase BV or throw off stable microbiota composition.{{cite journal |vauthors=Lehtoranta L, Ala-Jaakkola R, Laitila A, Maukonen J |title=Healthy Vaginal Microbiota and Influence of Probiotics Across the Female Life Span |journal=Frontiers in Microbiology |volume=13 |issue= |pages=819958 |date=2022 |pmid=35464937 |pmc=9024219 |doi=10.3389/fmicb.2022.819958 |doi-access=free |url=}} Smoking and alcohol consumption can also increase likelihood of BV development because it indirectly impacts the metabolite production profile.{{cite journal |vauthors=Nelson TM, Borgogna JC, Michalek RD, Roberts DW, Rath JM, Glover ED, Ravel J, Shardell MD, Yeoman CJ, Brotman RM |title=Cigarette smoking is associated with an altered vaginal tract metabolomic profile |journal=Scientific Reports |volume=8 |issue=1 |pages=852 |date=January 2018 |pmid=29339821 |pmc=5770521 |doi=10.1038/s41598-017-14943-3 |bibcode=2018NatSR...8..852N |url=}} There is also research supporting the idea that increased stress levels can have an impact on the balance of vaginal lactobacilli by elevating cortisol levels, reducing vaginal glycogen, lowering lactobacilli, elevating vaginal pH, and increasing proinflammatory response.

It is becoming more commonly known how our diets can impact our gut microbiota, but it can have the same impact on vaginal microbiota. Research shows that diets rich in nutrients with low glycemic index and lower fat intake may be associated with a decreased chance of getting BV.

Investigations have found that the presence of lactobacilli in the vagina is associated with a lower incidence of sexually transmitted infections.{{cite journal | vauthors = Nunn KL, Wang YY, Harit D, Humphrys MS, Ma B, Cone R, Ravel J, Lai SK | display-authors = 6 | title = Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota | journal = mBio | volume = 6 | issue = 5 | pages = e01084-15 | date = October 2015 | pmid = 26443453 | pmc = 4611035 | doi = 10.1128/mBio.01084-15 }}{{cite journal | vauthors = Anderson DJ, Marathe J, Pudney J | title = The structure of the human vaginal stratum corneum and its role in immune defense | journal = American Journal of Reproductive Immunology | volume = 71 | issue = 6 | pages = 618–23 | date = June 2014 | pmid = 24661416 | pmc = 4024347 | doi = 10.1111/aji.12230 }}

• Human Microbiome Project
• Lactic acid bacteria
• List of microbiota species of the lower reproductive tract of women
• Skin flora
• Vaginal microbiota in pregnancy

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• [http://www.risingwomen.com/arcberry1.htm Döderlein's bacteria]

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Category:Bacteriology

Category:Microbiology

Category:Feminine hygiene

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Category:Microbiomes