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Vaginal flora, vaginal microbiota or vaginal microbiome are the
microorganisms A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...
that colonize the
vagina In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...
. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora. The amount and type of bacteria present have significant implications for an individual's overall health. The primary colonizing bacteria of a healthy individual are of the genus ''
Lactobacillus ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'', such as '' L. crispatus'', and the
lactic acid Lactic acid is an organic acid. It has the molecular formula C3H6O3. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as wel ...
they produce is thought to protect against infection by pathogenic species.


Lactobacilli

The primary colonizing bacteria of a healthy individual are of the genus ''
Lactobacillus ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'' (90–95%), the most common being '' L. crispatus'', '' L. iners'', '' L. jensenii'', and '' L. gasseri''. 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 ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'', '' Gardnerella vaginalis'', ''Mobiluncus'' spp., ''
Neisseria gonorrhoeae ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular) or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria first isolated by Albert Ludwig Sigesmund Neisser, Albert Neisser in 1879. An obligate human pathog ...
'', '' Peptostreptococcus anaerobius'', '' Prevotella bivia'' and ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
''. It is generally accepted that this is achieved mainly through the action of lactic acid. 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 The vaginal epithelium is the inner lining of the vagina consisting of multiple layers of (Epithelium, squamous) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie u ...
. Next to lactic acid production and competition for adherence, other antagonistic mechanisms include
hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...
(a broad-spectrum antimicrobial) and
bacteriocin Bacteriocins are proteinaceous or peptide, peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally ...
s (target-specific antimicrobials) production.


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


Hydrogen peroxide

Production of hydrogen peroxide (H2O2) is a proposed mechanism for bacterial antagonism in vitro, inhibiting growth of microorganisms via direct interaction or via human myeloperoxidase. 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, 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 The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics. HIV-1 e ...
, herpes simplex virus type 2 (HSV-2), ''
Trichomonas vaginalis ''Trichomonas vaginalis'' is an Anaerobic organism, anaerobic, flagellated protozoan parasite and the causative agent of a Sexually transmitted infection, sexually transmitted disease called trichomoniasis. It is the most common pathogenic protoz ...
'', '' G. vaginalis'', '' P. bivia'' and '' E. coli''. O'Hanlon and Baeten found that 96% of ''
Lactobacillus ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'' species from a healthy vaginal ecosystem produced H2O2 ('' L. jensenii'' and '' L. vaginalis'' produce the highest levels of H2O2), 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, is a poor producer of H2O2. Vaginal colonization by H2O2-producing lactobacilli has been associated with a decrease in the occurrence of
bacterial vaginosis Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urina ...
(BV). However, more recently O'Hanlon et al. 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, and as such they would be unprotected against their own H2O2 production. Consequently, hydrogen peroxide production may not be the major mechanism of defense.


Bacteriocins

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 ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'' 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. 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 . 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. 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.


Bacterial vaginosis

Bacterial vaginosis Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urina ...
(BV) is associated with the presence of '' Gardnerella vaginalis'' and '' Peptostreptococcus anaerobius'' and a decrease in the number of ''
Lactobacillus ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'' species that comprise the healthy vaginal microbiota. 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. 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. 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.


Other microbiota

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. Several studies have demonstrated that a significant proportion (7–33%) of healthy asymptomatic women (especially black and Hispanic women) 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 ''Streptococcus'' is a genus of gram-positive spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs along a sing ...
'' 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 Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
, 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. Though vaginal microflora may be disturbed, and lactic acid is produced by other species, vaginal pH and acid production establish normal vaginal microbiota. The pH further decreases during pregnancy.


Other vaginal bacterial species

Other bacterial species are frequently found in the vagina, such as the Gram positive cocci: ''
Atopobium vaginae ''Fannyhessea vaginae'' is a species of bacteria in the family ''Atopobiaceae''. It is a facultative anaerobic organism, anaerobic, Gram-positive rod-shaped or elliptical coccobacillus found as single elements or in pairs or short chains. It is ...
'', ''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 ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
''. ''
Mycoplasma ''Mycoplasma'' is a genus of bacteria that, like the other members of the class ''Mollicutes'', lack a cell wall, and its peptidoglycan, around their cell membrane. The absence of peptidoglycan makes them naturally resistant to antibiotics ...
'' and '' Ureaplasma'' are frequently found in the vagina. Some of the obligate and facultative anaerobic bacteria are associated with BV. ''
Neisseria gonorrhoeae ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular) or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria first isolated by Albert Ludwig Sigesmund Neisser, Albert Neisser in 1879. An obligate human pathog ...
'' is found in the vagina and is considered a
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
that is sexually transmitted.


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. Pregnancy alters the microbiota with a reduction in species/genus diversity.


Disease prevention

A healthy vaginal microbiome aids in the prevention of bacterial vaginosis,
yeast infections Candidiasis is a fungal infection due to any species of the genus '' Candida'' (a yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the ...
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 In ecology, a niche is the match of a species to a specific environmental condition. Three variants of ecological niche are described by It describes how an organism or population responds to the distribution of Resource (biology), resources an ...
that would otherwise be available for exploitation by pathogenic organisms. However, harmful bacteria or an imbalance in bacteria can lead to infection. 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. Smoking and alcohol consumption can also increase likelihood of BV development because it indirectly impacts the metabolite production profile. 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.


Research

Investigations have found that the presence of lactobacilli in the vagina is associated with a lower incidence of sexually transmitted infections.


See also

* Human Microbiome Project *
Lactic acid bacteria Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped (bacilli) or spherical ( cocci) bacteria that share common metabolic and physiological characteristics. These bact ...
* List of microbiota species of the lower reproductive tract of women *
Skin flora Skin flora, also called skin microbiota, refers to microbiota (community (ecology), communities of microorganisms) that reside on the skin, typically human skin. Many of them are bacterium, bacteria of which there are around 1,000 species upon hu ...
* Vaginal microbiota in pregnancy


References


External links

*
Döderlein's bacteria
{{Authority control Bacteriology Microbiology Feminine hygiene Vagina Microbiomes