Materiały źródłowe

• #1 Bacterial vaginosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Bacterial_vaginosis_pathophysiology

  Bacterial vaginosis results from the replacement of the normal, hydrogen peroxide-producing Lactobacillus spp. with high concentrations of anaerobic bacteria, Gardnerella vaginalis, Ureaplasma, and Mycoplasma in the vagina. […] While the exact pathogenesis of bacterial vaginosis is not fully understood, it is thought that BV is a result of an imbalance in the different types of bacteria in the vagina by following mechanisms: […] There is a loss of lactobacilli resulting in rising pH and massive overgrowth of vaginal anaerobes. […] Increase in pH may result in decreased hydrogen peroxide production, which also facilitates adherence of Gardnerella vaginalis to the exfoliating epithelial cells. […] Decrease in hydrogen-peroxide production results in overgrowth of the anaerobes. […] Anaerobes produce large amounts of proteolytic carboxylase enzymes.

• #2 Bacterial Vaginosis (BV) – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis-cervicitis-and-pelvic-inflammatory-disease/bacterial-vaginosis-bv

  Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. […] The pathogenesis is unclear but involves the overgrowth of multiple bacterial pathogens and a decrease in the usual lactobacillus-predominant vaginal flora. […] Anaerobic pathogens that overgrow include Prevotella species, Peptostreptococcus species, Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis, which increase in concentration by 10- to 100-fold and replace the lactobacilli that usually maintain a normal vaginal environment. […] Bacterial vaginosis appears to increase the risk of pelvic inflammatory disease, postabortion and postpartum endometritis, and posthysterectomy vaginal cuff infection. […] BV increases the risk of pelvic inflammatory disease, postpartum endometritis, and some pregnancy complications, including prelabor rupture of membranes and preterm birth.

• #3 Bacterial Vaginosis (BV) – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis-cervicitis-and-pelvic-inflammatory-disease/bacterial-vaginosis-bv

  Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. […] The pathogenesis is unclear but involves the overgrowth of multiple bacterial pathogens and a decrease in the usual lactobacillus-predominant vaginal flora. […] Anaerobic pathogens that overgrow include Prevotella species, Peptostreptococcus species, Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis, which increase in concentration by 10- to 100-fold and replace the lactobacilli that usually maintain a normal vaginal environment. […] Bacterial vaginosis appears to increase the risk of pelvic inflammatory disease, postabortion and postpartum endometritis, and posthysterectomy vaginal cuff infection. […] BV increases the risk of pelvic inflammatory disease, postpartum endometritis, and some pregnancy complications, including prelabor rupture of membranes and preterm birth.

• #4 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4957507/

  In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. […] Despite its public health importance, however, the pathogenesis of BV remains unclear, so much so that some refer to this condition not as an infection but rather as a dysbiosis, a microbial imbalance in the vaginal flora that can precipitate changes in the normal activities of the vagina. […] There is agreement that the shift away from an optimal vaginal flora consisting of lactobacilli is the biological risk factor for associated adverse outcomes of BV. […] Determining the trigger for the development of BV is crucial to improving the treatment, management, and prevention of this important condition.

• #5 Bacterial Vaginosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459216/

  Bacterial vaginosis is caused by an imbalance of the naturally occurring vaginal flora, characterized by both a change in the most common type of bacteria present as well as an increase in the total number of bacteria present. The Lactobacillus species dominates normal vaginal microbiota. Bacterial vaginosis is associated with a decline in the overall number of lactobacilli. Although still uncertain, it is thought that most bacterial vaginosis infections start with Gardnerella vaginosis, which creates a biofilm that subsequently provides a conducive environment for the proliferation of other opportunistic bacteria. Gardnerella vaginalis also produces vaginolysin, a pore-forming toxin affecting human cells. Vaginolysin is a cholesterol-dependent cytolysin that initiates complex signaling cascades that trigger target cell lysis and enhance Gardnerella virulence.

• #6 Vaginitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/257141-overview

  A complex and intricate balance of microorganisms maintains the normal vaginal flora. Important organisms include lactobacilli, corynebacteria, and yeast. […] Disturbance of the normal vaginal pH can alter the vaginal flora, leading to overgrowth of pathogens. […] Loss of vaginal lactobacilli appears to be the primary factor in the changes leading to bacterial vaginosis. Recurrences of vaginitis are associated with a failure to establish a healthy vaginal microflora dominated by lactobacilli. […] Bacterial vaginosis is caused by an overgrowth of organisms such as Gardnerella vaginalis (a gram-variable coccobacillus), Mobiluncus species, Mycoplasma hominis, and Peptostreptococcus species. […] Bacterial vaginosis accounts for 40-50% of vaginitis cases; vaginal candidiasis, 20-25%; and trichomoniasis, 15-20%.

• #7 Bacterial Vaginosis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/11965

  With the depletion of Lactobacillus spp., the vaginal pH fails to be maintained at the normal range (i.e., 3.8–4.5), which successively creates a cascade of undesirable events in the host, including persistent infection, potentially caused by a mixture of difficult-to-treat pathogens, especially when some of them possess the ability to form biofilms. […] The first step of invasion is adherence to the host cell. […] The virulence of G. vaginalis can be attributed to several features: (a) the production of a cytolysin known as vaginolysin, which targets human cell specifically and activates the cell death pathways via binding to the complement regulatory molecule CD59, (b) strong adherence to host cells which avoid clearance by the host, and (c) ability to form biofilms. […] On top of its capability in producing hydrolytic enzyme-like sialidase, which damages vaginal mucosal surfaces and thus increases the level of pro-inflammatory cytokines, G. vaginalis has the propensity to form dense biofilms, allowing it to persist in the environment and serve as a scaffold that supports the growth of other opportunistic pathogens.

• #8 Bacterial Vaginosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/254342-overview

  Bacterial vaginosis (BV), formerly known as nonspecific vaginitis, was named because bacteria are the etiologic agent in this infection and an associated inflammatory response is lacking. […] Many studies have demonstrated the relationship of Gardnerella vaginalis with other bacteria in causing BV. BV is known to be a synergistic polymicrobic infection. Some of the associated bacteria include Lactobacillus species, Prevotella, and anaerobes, including Mobiluncus, Bacteroides, Peptostreptococcus, Fusobacterium, Veillonella, and Eubacterium species. […] In BV, the vaginal flora becomes altered through known and unknown mechanisms, causing an increase in the local pH. This may result from a reduction in the hydrogen peroxide-producing lactobacilli. […] G vaginalis forms a biofilm in the vagina. Some studies show that this biofilm may be resistant to some forms of medical treatment.

• #9 Bacterial Vaginosis – STI Treatment Guidelines

  https://www.cdc.gov/std/treatment-guidelines/bv.htm

  BV is a vaginal dysbiosis resulting from replacement of normal hydrogen peroxide and lactic-acidproducing Lactobacillus species in the vagina with high concentrations of anaerobic bacteria, including G. vaginalis, Prevotella species, Mobiluncus species, A. vaginae, and other BV-associated bacteria. […] The cause of the microbial alteration that precipitates BV is not fully understood, and whether BV results from acquisition of a single sexually transmitted pathogen is unknown. […] BV also increases HIV infection acquisition because specific BV-associated bacteria can increase susceptibility to HIV and the risk for HIV transmission to male sex partners. […] Although BV-associated bacteria can be identified on male genitalia, treatment of male sex partners has not been beneficial in preventing the recurrence of BV.

• #10 Bacterial Vaginosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459216/

  Bacterial vaginosis is caused by an imbalance of the naturally occurring vaginal flora, characterized by both a change in the most common type of bacteria present as well as an increase in the total number of bacteria present. The Lactobacillus species dominates normal vaginal microbiota. Bacterial vaginosis is associated with a decline in the overall number of lactobacilli. Although still uncertain, it is thought that most bacterial vaginosis infections start with Gardnerella vaginosis, which creates a biofilm that subsequently provides a conducive environment for the proliferation of other opportunistic bacteria. Gardnerella vaginalis also produces vaginolysin, a pore-forming toxin affecting human cells. Vaginolysin is a cholesterol-dependent cytolysin that initiates complex signaling cascades that trigger target cell lysis and enhance Gardnerella virulence.

• #11 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4957507/

  The majority of epidemiologic data support the hypothesis that BV is a STI. […] Assuming that sexual transmission plays a key role in the pathogenesis of BV, the next question concerns the transmitted pathogen(s). […] More recently it was shown that previously unrecognized, unculturable bacteria are also part of the BV flora. […] Although it is highly likely that anaerobes contribute to the symptoms of BV, there has been renewed interest in the hypothesis that G. vaginalis is the inciting pathogen, with studies confirming its virulence factors (ability to adhere to host receptor sites on vaginal epithelial cells, production of cytotoxic substances specific for host cells, and biofilm formation) as well as its concordance in sexual partners. […] In 2014, Schwebke et al presented a conceptual model for the pathogenesis of BV with G. vaginalis as the founder or keystone pathogen.

• #12

  https://journals.lww.com/co-infectiousdiseases/fulltext/2020/02000/host_vaginal_microbiota_interactions_in_the.9.aspx

  The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. […] We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. […] Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. […] These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. […] Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes. […] Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.

• #13 Bacterial Vaginosis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/11965

  The formation of a “new community” within the biofilm subsequently competes with Lactobacillus spp. as those living within the biofilms of G. vaginalis have a higher tolerance against lactic acid and hydrogen peroxide produced by Lactobacillus spp.; this increases their survival chances and failure to purge these opportunistic pathogens from the environment will eventually tilt the balance of the entire vaginal ecosystem. […] The role of A. vaginae in BV has always been the centre of the argument until lately, whereby researchers unveiled that the bacterium is indeed an important focal component in the abnormal microflora of BV. […] As demonstrated through in vitro experiments, A. vaginae triggered the host’s innate immune response via vaginal epithelial cells, which later increased the localized production of IL-6 and IL-8 and an antimicrobial β-defensin peptide, mediated through the toll-like receptor 2.

• #14 Molecular Testing for the Diagnosis of Bacterial Vaginosis

  https://www.mdpi.com/1422-0067/25/1/449

  Bacterial vaginosis (BV) is characterized by a high recurrence rate due to so-called biofilm formation. Currently, biofilm-associated and non-biofilm-associated forms of BV are distinguished. Fannyhessea vaginae (Atopobium vaginae) and Prevotella bivia are known to exert synergistic interactions with Gardnerella spp., resulting in BV. […] G. vaginalis, being a microaerophilic and facultative anaerobic microorganism, tolerates high redox potential created by microbiota predominated by vaginal lactobacilli, allowing them to coexist. After intercourse, virulent strains of Gardnerella spp. displace vaginal Lactobacillus spp. and form a biofilm on the surface of the vaginal epithelium. Later, P. bivia joins the biofilm formed by Gardnerella spp. and microorganisms exert synergistic relationships with each other. Gardnerella-induced proteolysis results in the production of amino acids enhancing the growth of P. bivia; ammonia produced by P. bivia, in turn, promotes Gardnerella spp. growth. In addition, both bacteria produce an enzyme, sialidase, which destroys the layer of mucin on the vaginal epithelium. Because of the alteration of the protective mucous layer, the adhesion of other BV-associated bacteria, including F. vaginae, to the biofilm increases. Currently, the role of other bacteria in the pathogenesis of BV remains unknown and requires further investigation. Thus, polymicrobial biofilms are detected in 90% of BV-affected women.

• #15 Bacterial Vaginosis (BV) – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis-cervicitis-and-pelvic-inflammatory-disease/bacterial-vaginosis-bv

  Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. […] The pathogenesis is unclear but involves the overgrowth of multiple bacterial pathogens and a decrease in the usual lactobacillus-predominant vaginal flora. […] Anaerobic pathogens that overgrow include Prevotella species, Peptostreptococcus species, Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis, which increase in concentration by 10- to 100-fold and replace the lactobacilli that usually maintain a normal vaginal environment. […] Bacterial vaginosis appears to increase the risk of pelvic inflammatory disease, postabortion and postpartum endometritis, and posthysterectomy vaginal cuff infection. […] BV increases the risk of pelvic inflammatory disease, postpartum endometritis, and some pregnancy complications, including prelabor rupture of membranes and preterm birth.

• #16 Vaginitis, TSS, and other Genitourinary Tract Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/stdd.htm

  Bacterial vaginosis is caused by an overgrowth of bacteria rather than yeast. […] These organisms include various anaerobic bacteria, Gardnerella vaginalis, Atopobium vaginae, and Mycoplasma hominis. […] All of these organisms are kept to low numbers in the healthy vaginal microflora by Lactobacilli sp. […] In women with BV, the vaginal balance is disrupted so that these bacteria overgrow at the expense of the protective bacteria; Lactobacillus. […] Lactobacilli produce hydrogen peroxide to maintain a healthy and normal balance of microorganisms in the vaginal mucosa. […] Women who have been diagnosed with BV have up to 1,000 times more anaerobic bacteria than women without the disease. […] Instead of the normal predominance of Lactobacillus bacteria, increased numbers of organisms such as Gardnerella vaginalis, Atopobium vaginae, various anaerobes and Mycoplasma hominis are found in the vagina in women with BV.

• #17 Bacterial Vaginosis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/254342-overview

  Bacterial vaginosis (BV), formerly known as nonspecific vaginitis, was named because bacteria are the etiologic agent in this infection and an associated inflammatory response is lacking. […] Many studies have demonstrated the relationship of Gardnerella vaginalis with other bacteria in causing BV. BV is known to be a synergistic polymicrobic infection. Some of the associated bacteria include Lactobacillus species, Prevotella, and anaerobes, including Mobiluncus, Bacteroides, Peptostreptococcus, Fusobacterium, Veillonella, and Eubacterium species. […] In BV, the vaginal flora becomes altered through known and unknown mechanisms, causing an increase in the local pH. This may result from a reduction in the hydrogen peroxide-producing lactobacilli. […] G vaginalis forms a biofilm in the vagina. Some studies show that this biofilm may be resistant to some forms of medical treatment.

• #18 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4957507/

  In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. […] Despite its public health importance, however, the pathogenesis of BV remains unclear, so much so that some refer to this condition not as an infection but rather as a dysbiosis, a microbial imbalance in the vaginal flora that can precipitate changes in the normal activities of the vagina. […] There is agreement that the shift away from an optimal vaginal flora consisting of lactobacilli is the biological risk factor for associated adverse outcomes of BV. […] Determining the trigger for the development of BV is crucial to improving the treatment, management, and prevention of this important condition.

• #19 Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02077-3

  Bacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners. […] Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.

• #20 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4957507/

  The majority of epidemiologic data support the hypothesis that BV is a STI. […] Assuming that sexual transmission plays a key role in the pathogenesis of BV, the next question concerns the transmitted pathogen(s). […] More recently it was shown that previously unrecognized, unculturable bacteria are also part of the BV flora. […] Although it is highly likely that anaerobes contribute to the symptoms of BV, there has been renewed interest in the hypothesis that G. vaginalis is the inciting pathogen, with studies confirming its virulence factors (ability to adhere to host receptor sites on vaginal epithelial cells, production of cytotoxic substances specific for host cells, and biofilm formation) as well as its concordance in sexual partners. […] In 2014, Schwebke et al presented a conceptual model for the pathogenesis of BV with G. vaginalis as the founder or keystone pathogen.

• #21

  https://www-.grantome.com/grant/NIH/K23-AI106957-02

  Bacterial vaginosis (BV) is the most common vaginal infection in the United States, with an estimated prevalence of 30%. It is associated with adverse outcomes including preterm birth, pelvic inflammatory disease, and increased risk for sexually transmitted infections (STIs), including HIV. BV represents a shift in the vaginal microbiota from Lactobacillus-predominate species to facultative (Gardnerella vaginalis; GV) and strict anaerobic bacteria. […] However, the pathogenesis of BV remains unclear. It remains controversial as to whether BV results from acquisition of GV as the founder organism which subsequently leads to the complex changes in the vaginal microbiota associated with BV, whether BV is transmitted as a polymicrobial consortium, […] GV, as a facultative anaerobe, may be able to tolerate the high oxidation-reduction (redox) potential of a healthy vaginal microbiome, unlike strict anaerobes (i.e. other BV-associated bacteria: BVAB).

• #22 Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors | The ISME Journal

  https://www.nature.com/articles/s41396-018-0337-0

  Bacterial vaginosis (BV) is characterized by a highly structured polymicrobial biofilm, which is strongly adhered to the vaginal epithelium and primarily consists of the bacterium Gardnerella vaginalis. However, despite the presence of other BV-associated bacteria, little is known regarding the impact of other species on BV development. […] The role of G. vaginalis in BV is not without controversy, however. First proposed as the sole etiological agent by Gardner and Dukes and later studied by cultivation-independent approaches, its presence in healthy women cast doubt on its virulence potential. Nevertheless, in the past decade, it has been demonstrated that G. vaginalis had a significantly higher virulence potential than many other BV-associated species, as defined by higher initial adhesion and cytotoxic effect, as well as a greater propensity to form a biofilm.

• #23 Bacterial Vaginosis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/11965

  With the depletion of Lactobacillus spp., the vaginal pH fails to be maintained at the normal range (i.e., 3.8–4.5), which successively creates a cascade of undesirable events in the host, including persistent infection, potentially caused by a mixture of difficult-to-treat pathogens, especially when some of them possess the ability to form biofilms. […] The first step of invasion is adherence to the host cell. […] The virulence of G. vaginalis can be attributed to several features: (a) the production of a cytolysin known as vaginolysin, which targets human cell specifically and activates the cell death pathways via binding to the complement regulatory molecule CD59, (b) strong adherence to host cells which avoid clearance by the host, and (c) ability to form biofilms. […] On top of its capability in producing hydrolytic enzyme-like sialidase, which damages vaginal mucosal surfaces and thus increases the level of pro-inflammatory cytokines, G. vaginalis has the propensity to form dense biofilms, allowing it to persist in the environment and serve as a scaffold that supports the growth of other opportunistic pathogens.

• #24 Bacterial Vaginosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459216/

  Bacterial vaginosis is caused by an imbalance of the naturally occurring vaginal flora, characterized by both a change in the most common type of bacteria present as well as an increase in the total number of bacteria present. The Lactobacillus species dominates normal vaginal microbiota. Bacterial vaginosis is associated with a decline in the overall number of lactobacilli. Although still uncertain, it is thought that most bacterial vaginosis infections start with Gardnerella vaginosis, which creates a biofilm that subsequently provides a conducive environment for the proliferation of other opportunistic bacteria. Gardnerella vaginalis also produces vaginolysin, a pore-forming toxin affecting human cells. Vaginolysin is a cholesterol-dependent cytolysin that initiates complex signaling cascades that trigger target cell lysis and enhance Gardnerella virulence.

• #25 The presence of the putative Gardnerella vaginalis sialidase A gene in vaginal specimens is associated with bacterial vaginosis biofilm | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172522

  Bacterial vaginosis (BV) is a difficult-to-treat recurrent condition in which health-associated lactobacilli are outnumbered by other anaerobic bacteria, such as Gardnerella vaginalis. Certain genotypes of G. vaginalis can produce sialidase, while others cannot. Sialidase is known to facilitate the destruction of the protective mucus layer on the vaginal epithelium by hydrolysis of sialic acid on the glycans of mucous membranes. This process possibly facilitates adhesion of bacterial cells on the epithelium since it has been linked with the development of biofilm in other pathogenic conditions. […] It has been suggested that G. vaginalis initiates the colonisation of the vaginal mucosa and acts as a scaffold to which other species subsequently can attach. […] Certain G. vaginalis genotypes can produce sialidase, also known as neuraminidase. Sialidase is an enzyme that cleaves sialic acid from terminal glycans of glycoproteins, which are also present in the cervicovaginal fluid. Sialidases have been studied in many contexts of bacterial pathogenesis, and these studies provide several examples of possible mechanisms by which these enzymes could also act in the pathogenesis of BV.

• #26

  https://www-.grantome.com/grant/NIH/K23-AI106957-02

  Similar to facultative anaerobes involved in the initiation of oral disease, it is possible that GV creates a lower redox potential in the vaginal microbiome which causes a marked decrease in lactobacilli and an increase in other BVAB (which may normally be present in very low concentrations), leading to the BV syndrome. […] I hypothesize that sexual exposure to GV among AAWSW is the inciting event leading to the complex vaginal flora associated with BV. […] Aim1: Use cultivation-independent molecular methods to determine the sequence of microbiological events culminating in BV among sexually active AAWSW. I hypothesize that the appearance of GV and its relative abundance will increase in women with incident BV prior to increases in the abundance of other BVAB. […] Aim 2: Determine if specific GV oligotypes are associated with the development of BV among sexually active AAWSW. I hypothesize that GV oligotypes differ in their pathogenic potential with regards to the development of BV given the conflicting observation that GV can be present in both normal women and women with BV.

• #27 Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors | The ISME Journal

  https://www.nature.com/articles/s41396-018-0337-0

  Due to its strong adherence to vaginal cells and biofilm-forming capacities, it has been suggested that BVGv initiates the colonization of the vaginal epithelium and serves as a scaffold to which other species subsequently can attach. […] The study of these microbial interactions is extremely important for obtaining knowledge of the pathogenicity of microbes in the host and for the development of effective treatments without relapses, a common problem in BV. […] We hypothesize that molecular interactions between G. vaginalis and multiple BV-associated bacteria could be very specific, highlighting possible key roles in BV development by some secondary anaerobes. […] Our results indicated that in dual-species biofilms, the expression levels of vly were greatly up-regulated when G. vaginalis was associated with A. neuii or E. faecalis.

• #28

  https://www.scirp.org/journal/paperinformation?paperid=93586

  Bacterial vaginosis (BV) is defined as a condition characterized by the replacement of the normal vaginal flora with a high numbers of anaerobic, aerobic, and microaerophilic microorganisms. […] The disease mechanism relates to the formation of bacterial biofilms, which are colonies of microorganisms that attach the vaginal epithelium and cover it completely or partially. Such biofilms are often resistant to antibiotic therapy, they raise the pH, and displace endogenous flora. […] However, it is well known that the pathogenesis of the disease is associated with the presence of several microorganisms, such as high number of anaerobic Gram-negative, aerobic and microaerophilic microorganisms, together with a dramatically depletion in Lactobacillus count. […] The new product tested in our study contains Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020 and Bifidobacterium animalis spp. lactis BL050, all constituents that have important effects on the main mechanism involved in the pathogenesis of BV.

• #29 Bacterial vaginosis and biofilms: Therapeutic challenges and innovations – A narrative review – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/bacterial-vaginosis-and-biofilms-therapeutic-challenges-and-innovations-a-narrative-review/

  BV biofilms are complex structures formed by bacterial species like Gardnerella vaginalis, Atopobium vaginae, and others on the vaginal epithelium. These biofilms consist of bacteria encased in an extracellular matrix, providing a protective environment that shields them from host immune defenses and antibiotic treatments. […] Studies have shown that BV biofilms contribute to the recurrence of BV episodes. Even after successful antibiotic treatment, biofilms can persist in the vaginal environment. […] Biofilm-embedded bacteria exhibit increased resistance to antibiotics compared to planktonic bacteria. The extracellular matrix of biofilms acts as a physical barrier, preventing antibiotics from effectively reaching bacterial cells. […] BV biofilms alter the local vaginal microenvironment, creating conditions favourable for dysbiosis. The disruption of the acidic environment maintained by beneficial Lactobacillus species promotes the growth of anaerobic bacteria, further perpetuating BV.

• #30 Vaginitis, TSS, and other Genitourinary Tract Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/stdd.htm

  The bacterial cells in the biofilm are packed inside a network of polysaccharide fibrils. […] This dense bacterial biofilm coats at least half the epithelial surface, in 90% of biopsies from women with BV. […] Healthy women have a lot less biofilm coating the epithelial cells. […] Only 10% of biopsies in healthy women have evidence of biofilm coating the epithelial cells. […] There are several bacteria in the biofilm besides Gardnerella vaginalis. […] One of increasing interest is a gram positive facultative anaerobic rod called Atopobium vaginae. […] In symptomatic BV it has been detected together with Gardnerella vaginalis. […] The bacterial composition and organization of the biofilm was examined. […] Gardnerella vaginalis made up 60-95% of the film mass. […] Atopobium vaginae accounted for 1-40% of the film mass and Lactobacillus made up only 5% of the mass of the biofilm.

• #31 Vaginitis, TSS, and other Genitourinary Tract Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/stdd.htm

  The bacterial cells in the biofilm are packed inside a network of polysaccharide fibrils. […] This dense bacterial biofilm coats at least half the epithelial surface, in 90% of biopsies from women with BV. […] Healthy women have a lot less biofilm coating the epithelial cells. […] Only 10% of biopsies in healthy women have evidence of biofilm coating the epithelial cells. […] There are several bacteria in the biofilm besides Gardnerella vaginalis. […] One of increasing interest is a gram positive facultative anaerobic rod called Atopobium vaginae. […] In symptomatic BV it has been detected together with Gardnerella vaginalis. […] The bacterial composition and organization of the biofilm was examined. […] Gardnerella vaginalis made up 60-95% of the film mass. […] Atopobium vaginae accounted for 1-40% of the film mass and Lactobacillus made up only 5% of the mass of the biofilm.

• #32 Bacterial vaginosis and biofilms: Therapeutic challenges and innovations – A narrative review – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/bacterial-vaginosis-and-biofilms-therapeutic-challenges-and-innovations-a-narrative-review/

  BV biofilms are complex structures formed by bacterial species like Gardnerella vaginalis, Atopobium vaginae, and others on the vaginal epithelium. These biofilms consist of bacteria encased in an extracellular matrix, providing a protective environment that shields them from host immune defenses and antibiotic treatments. […] Studies have shown that BV biofilms contribute to the recurrence of BV episodes. Even after successful antibiotic treatment, biofilms can persist in the vaginal environment. […] Biofilm-embedded bacteria exhibit increased resistance to antibiotics compared to planktonic bacteria. The extracellular matrix of biofilms acts as a physical barrier, preventing antibiotics from effectively reaching bacterial cells. […] BV biofilms alter the local vaginal microenvironment, creating conditions favourable for dysbiosis. The disruption of the acidic environment maintained by beneficial Lactobacillus species promotes the growth of anaerobic bacteria, further perpetuating BV.

• #33 Bacterial Vaginosis: A Review

  https://www.uspharmacist.com/article/bacterial-vaginosis-a-review

  Patients with BV have a dense biofilm consisting of a matrix of polysaccharides, proteins, extracellular DNA, and embedded bacteria that is tightly attached to the vaginal epithelial surface.11,12 The biofilm is polymicrobial and consists mainly of G vaginalis, with 80% of G vaginalis containing biofilms also containing A vaginae.11 Bacteria residing within a biofilm enjoy relative protection from antimicrobial agents and the host immune system, as well as high resistance to lactobacilli-produced defense factors (such as lactic acid, hydrogen peroxide, and bacteriocins), which may be due in part to differences in gene expression.10,13-15 Therefore, infections involving biofilm, such as BV, are difficult to clear and often have high rates of recurrence.13,16 […] It is unknown whether one pathogen transmitted through sexual exposure causes BV, and the mechanism that causes the disruption of lactobacilli that leads to BV is not completely understood.4 Sexual exposure (particularly having multiple or new sex partners) increases the risk of BV, and this condition rarely occurs in women who have never had sex. Additionally, regular douching and the absence of vaginal lactobacilli or protection during sex are related to the development of BV.4

• #34 Molecular Testing for the Diagnosis of Bacterial Vaginosis

  https://www.mdpi.com/1422-0067/25/1/449

  Bacterial vaginosis (BV) is characterized by a high recurrence rate due to so-called biofilm formation. Currently, biofilm-associated and non-biofilm-associated forms of BV are distinguished. Fannyhessea vaginae (Atopobium vaginae) and Prevotella bivia are known to exert synergistic interactions with Gardnerella spp., resulting in BV. […] G. vaginalis, being a microaerophilic and facultative anaerobic microorganism, tolerates high redox potential created by microbiota predominated by vaginal lactobacilli, allowing them to coexist. After intercourse, virulent strains of Gardnerella spp. displace vaginal Lactobacillus spp. and form a biofilm on the surface of the vaginal epithelium. Later, P. bivia joins the biofilm formed by Gardnerella spp. and microorganisms exert synergistic relationships with each other. Gardnerella-induced proteolysis results in the production of amino acids enhancing the growth of P. bivia; ammonia produced by P. bivia, in turn, promotes Gardnerella spp. growth. In addition, both bacteria produce an enzyme, sialidase, which destroys the layer of mucin on the vaginal epithelium. Because of the alteration of the protective mucous layer, the adhesion of other BV-associated bacteria, including F. vaginae, to the biofilm increases. Currently, the role of other bacteria in the pathogenesis of BV remains unknown and requires further investigation. Thus, polymicrobial biofilms are detected in 90% of BV-affected women.

• #35 Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors | The ISME Journal

  https://www.nature.com/articles/s41396-018-0337-0

  Due to its strong adherence to vaginal cells and biofilm-forming capacities, it has been suggested that BVGv initiates the colonization of the vaginal epithelium and serves as a scaffold to which other species subsequently can attach. […] The study of these microbial interactions is extremely important for obtaining knowledge of the pathogenicity of microbes in the host and for the development of effective treatments without relapses, a common problem in BV. […] We hypothesize that molecular interactions between G. vaginalis and multiple BV-associated bacteria could be very specific, highlighting possible key roles in BV development by some secondary anaerobes. […] Our results indicated that in dual-species biofilms, the expression levels of vly were greatly up-regulated when G. vaginalis was associated with A. neuii or E. faecalis.

• #36 Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors | The ISME Journal

  https://www.nature.com/articles/s41396-018-0337-0

  Importantly, it was found that HMPREF0424_1196 transcript levels were greatly elevated when E. faecalis or S. warneii was co-cultured with the BVGv pre-established biofilm. […] Overall, the evidence from this study points towards the idea that social networking between co-infecting bacteria can profoundly affect the progress of BV and its clinical outcome.

• #37 Bacterial vaginosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Bacterial_vaginosis_pathophysiology

  Bacterial vaginosis results from the replacement of the normal, hydrogen peroxide-producing Lactobacillus spp. with high concentrations of anaerobic bacteria, Gardnerella vaginalis, Ureaplasma, and Mycoplasma in the vagina. […] While the exact pathogenesis of bacterial vaginosis is not fully understood, it is thought that BV is a result of an imbalance in the different types of bacteria in the vagina by following mechanisms: […] There is a loss of lactobacilli resulting in rising pH and massive overgrowth of vaginal anaerobes. […] Increase in pH may result in decreased hydrogen peroxide production, which also facilitates adherence of Gardnerella vaginalis to the exfoliating epithelial cells. […] Decrease in hydrogen-peroxide production results in overgrowth of the anaerobes. […] Anaerobes produce large amounts of proteolytic carboxylase enzymes.

• #38 Bacterial vaginosis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Bacterial_vaginosis_pathophysiology

  Proteolytic carboxylase enzymes break down vaginal peptides into a variety of amines that are volatile, malodorous, and associated with increased vaginal transudation. […] It is also thought that Gardnerella vaginalis is the pathogen responsible for the initiation of bacterial vaginosis, with other pathogens acting as secondary intruders.

• #39 Clinical Features of Bacterial Vaginosis in a Murine Model of Vaginal Infection with Gardnerella vaginalis | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059539

  Bacterial vaginosis (BV) is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and Gram-negative bacilli. […] Gardnerella vaginalis was the first bacterium implicated in the pathogenesis of BV and continues to be associated with the disease. […] However, there has been much debate in the literature concerning the contribution of G. vaginalis to the development and pathogenesis of BV. […] The results from this murine model suggest that G. vaginalis alone is sufficient to yield BV phenotypes and provide further justification for considering G. vaginalis as a contributor to the causes and complications associated with BV. […] A hallmark feature of bacterial vaginosis is the presence of high levels of sialidase activity in vaginal fluid compared to specimens from women with normal flora.

• #40 The presence of the putative Gardnerella vaginalis sialidase A gene in vaginal specimens is associated with bacterial vaginosis biofilm | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172522

  Bacterial vaginosis (BV) is a difficult-to-treat recurrent condition in which health-associated lactobacilli are outnumbered by other anaerobic bacteria, such as Gardnerella vaginalis. Certain genotypes of G. vaginalis can produce sialidase, while others cannot. Sialidase is known to facilitate the destruction of the protective mucus layer on the vaginal epithelium by hydrolysis of sialic acid on the glycans of mucous membranes. This process possibly facilitates adhesion of bacterial cells on the epithelium since it has been linked with the development of biofilm in other pathogenic conditions. […] It has been suggested that G. vaginalis initiates the colonisation of the vaginal mucosa and acts as a scaffold to which other species subsequently can attach. […] Certain G. vaginalis genotypes can produce sialidase, also known as neuraminidase. Sialidase is an enzyme that cleaves sialic acid from terminal glycans of glycoproteins, which are also present in the cervicovaginal fluid. Sialidases have been studied in many contexts of bacterial pathogenesis, and these studies provide several examples of possible mechanisms by which these enzymes could also act in the pathogenesis of BV.

• #41 Pathogenesis – GPnotebook

  https://gpnotebook.com/pages/gynaecology/bacterial-vaginosis-(bv)/pathogenesis?nextLocale=en

  Male partners may be colonised with Gardnerella vaginalis, and some organisms causing vaginosis have also been found in the rectum suggesting that this may provide a reservoir for vaginal infection. […] The initial change in the pathogenesis is probably an increase in vaginal pH from pH 4.0 to pH 5.5. This is probably due to the production of amines by Gardnerella and and Prevotella. […] It is unclear why only some women are susceptible.

• #42 Bacterial vaginosis – Wikipedia

  https://en.wikipedia.org/wiki/Bacterial_vaginosis

  Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. […] BV is caused by an imbalance of the naturally occurring bacteria in the vagina. There is a change in the most common type of bacteria and a hundred to thousandfold increase in total numbers of bacteria present. […] Healthy vaginal microbiota consists of species that neither cause symptoms or infections, nor negatively affect pregnancy. It is dominated mainly by Lactobacillus species. BV is defined by the disequilibrium in the vaginal microbiota, with decline in the number of lactobacilli. While the infection involves a number of bacteria, it is believed that most infections start with Gardnerella vaginalis creating a biofilm, which allows other opportunistic bacteria, such as Prevotella and Bacteroides, to thrive. […] The cause of the fishy smell of BV is mainly due to reduction of trimethylamine oxide (TMAO) to trimethylamine (TMA) by bacteria in vaginal secretion. TMA is the same compound that is predominantly responsible for the smell of decomposing fish.

• #43 Diagnosis of Vaginitis | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0901/p1095.html

  In bacterial vaginosis, it is believed that some inciting event decreases the number of hydrogen peroxide-producing Lactobacillus acidophilus organisms. The resultant change in pH allows proliferation of organisms that are normally suppressed, such as Gardnerella vaginalis, Mycoplasma hominis and Mobiluncus species. These organisms produce metabolic byproducts, such as amines, that further increase the vaginal pH and cause exfoliation of vaginal epithelial cells. The amines are also responsible for the characteristic malodorous discharge in bacterial vaginosis. […] Similarly, changes in the vaginal environment, such as an increase in glycogen production in pregnancy or altered estrogen and progesterone levels from the use of oral contraceptives, enhance the adherence of Candida albicans to vaginal epithelial cells and facilitate the germination of yeast. These changes may transform asymptomatic colonization into symptomatic infection. In patients with trichomoniasis, changes in estrogen and progesterone levels, as well as elevations of vaginal pH and glycogen levels, may enhance the growth and virulence of Trichomonas vaginalis.

• #44 Bacterial Vaginosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459216/

  Gardnerella has the necessary virulence factors that facilitate its adherence to host epithelial cells, enabling it to compete with Lactobacillus for dominance within the vaginal environment effectively. The symptoms of bacterial vaginosis are believed to arise from the proliferation of usually dormant vaginal anaerobes that establish symbiotic relationships with Gardnerella. […] The association between bacterial vaginosis and an increased risk of acquiring future STIs stems from the fact that bacterial vaginosis allows other vaginal pathogens to gain access to the upper genital tract. Bacterial vaginosis is also responsible for the presence of enzymes that reduce the ability of host leukocytes to fight infection and for an increased release of endotoxins that stimulate cytokine and prostaglandin production within the vagina.

• #45 Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix | npj Biofilms and Microbiomes

  https://www.nature.com/articles/s41522-021-00259-8

  We tested the hypothesis that health-associated Lactobacillus and BVAB uniquely alter the immunometabolic cervical microenvironment. […] We observed that particular BVAB infections induced a dramatic enrichment in citrulline, a key metabolite in the urea cycle. […] The levels of ornithine, another metabolite of urea cycle, was also elevated following S. amnii infection. […] Overall, this analysis demonstrated unique metabolic contributions of tested clinical isolates of common BVAB species. A. vaginae and S. amnii created metabolic environments that promote host inflammatory responses, whereas G. vaginalis and P. bivia altered mostly the physiochemical properties of the epithelial barrier (such as mucins, sialic acid, polyamines). […] These mechanistic insights on immunometabolic landscape provide better understanding of BV pathogenesis and connect BV with adverse women’s health outcomes.

• #46 Bacterial vaginosis and biofilms: Therapeutic challenges and innovations – A narrative review – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/bacterial-vaginosis-and-biofilms-therapeutic-challenges-and-innovations-a-narrative-review/

  BV biofilms can modulate the host immune response, leading to chronic inflammation and tissue damage. The presence of biofilms activates inflammatory pathways, contributing to symptoms associated with BV. […] Researchers have utilised advanced imaging techniques, molecular analyses, and patient samples to delve into the intricate nature of BV biofilms and their central role in the pathogenesis of BV, underscoring the need to address biofilms in its management. […] The matrix in which biofilm bacteria are embedded acts as a physical shield, obstructing antibiotic penetration and rendering these medications less effective. […] The bacteria within biofilms are often more resistant to antibiotics due to their altered physiological state. […] Thus women with asymptomatic BV often experience high recurrence rates due to a lack of treatment.

• #47 Bacterial Vaginosis and Vulvovaginal Candidiasis Pathophysiologic Interrelationship

  https://www.mdpi.com/2076-2607/12/1/108

  More recently, the recognition and appreciation of the BV biofilm coating the surface of the vaginal mucosa has contributed to understanding the pathogenesis of BV, especially RBV, and has improved treatment of BV. Virulent strains of Gardnerella spp. are thought to initiate biofilm production and are often the predominant species present in the biofilm. […] The vaginal environment in BV is profoundly proinflammatory, as confirmed in multiple studies. Cytokine and chemokine increase are evident with increase in IL-2, type 1 interferon. The lack of PMNs appropriately reflects the effect of chemokine or chemotaxic inhibitors preventing their accumulation. The role of vaginal inflammatory mediators in the pathogenesis of BV is largely unknown and is perhaps crucial to the loss of protective Lactobacillus species as well as to explaining clinical BV recurrence and resistance to probiotic therapy.

• #48 Bacterial Vaginosis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/11965

  Bacterial vaginosis (BV) occurs due to microbial dysbiosis, presenting a highly diverse vagina microbiome (including Gardnerella spp. and Atopobium spp.) as opposed to the healthy form, which is mainly dominated by Lactobacillus spp. […] The predominant symptom is the presence of grayish-white thin homogenous discharge with an unpleasant odor or “fishy smell,” which is more apparent during menses or after sexual intercourse due to the increased production of amines by anaerobic bacteria. […] The invasion of normal, healthy microflora by pathogens disrupt the host physiology via multiple routes, including depleting nutrients essential for the growth of other residents within the vagina, destroying the vaginal barrier via hydrolytic enzymes (e.g., sialidase and prolidase), and promoting the release of pro-inflammatory chemokines and cytokines (IL-6, IL-8, IL-1α, IL-1β, TNF-α).

• #49 Bacterial Vaginosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459216/

  Gardnerella has the necessary virulence factors that facilitate its adherence to host epithelial cells, enabling it to compete with Lactobacillus for dominance within the vaginal environment effectively. The symptoms of bacterial vaginosis are believed to arise from the proliferation of usually dormant vaginal anaerobes that establish symbiotic relationships with Gardnerella. […] The association between bacterial vaginosis and an increased risk of acquiring future STIs stems from the fact that bacterial vaginosis allows other vaginal pathogens to gain access to the upper genital tract. Bacterial vaginosis is also responsible for the presence of enzymes that reduce the ability of host leukocytes to fight infection and for an increased release of endotoxins that stimulate cytokine and prostaglandin production within the vagina.

• #50 Bacterial Vaginosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459216/

  Gardnerella has the necessary virulence factors that facilitate its adherence to host epithelial cells, enabling it to compete with Lactobacillus for dominance within the vaginal environment effectively. The symptoms of bacterial vaginosis are believed to arise from the proliferation of usually dormant vaginal anaerobes that establish symbiotic relationships with Gardnerella. […] The association between bacterial vaginosis and an increased risk of acquiring future STIs stems from the fact that bacterial vaginosis allows other vaginal pathogens to gain access to the upper genital tract. Bacterial vaginosis is also responsible for the presence of enzymes that reduce the ability of host leukocytes to fight infection and for an increased release of endotoxins that stimulate cytokine and prostaglandin production within the vagina.

• #51 Bacterial Vaginosis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/11965

  The formation of a “new community” within the biofilm subsequently competes with Lactobacillus spp. as those living within the biofilms of G. vaginalis have a higher tolerance against lactic acid and hydrogen peroxide produced by Lactobacillus spp.; this increases their survival chances and failure to purge these opportunistic pathogens from the environment will eventually tilt the balance of the entire vaginal ecosystem. […] The role of A. vaginae in BV has always been the centre of the argument until lately, whereby researchers unveiled that the bacterium is indeed an important focal component in the abnormal microflora of BV. […] As demonstrated through in vitro experiments, A. vaginae triggered the host’s innate immune response via vaginal epithelial cells, which later increased the localized production of IL-6 and IL-8 and an antimicrobial β-defensin peptide, mediated through the toll-like receptor 2.

• #52 Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix | npj Biofilms and Microbiomes

  https://www.nature.com/articles/s41522-021-00259-8

  We tested the hypothesis that health-associated Lactobacillus and BVAB uniquely alter the immunometabolic cervical microenvironment. […] We observed that particular BVAB infections induced a dramatic enrichment in citrulline, a key metabolite in the urea cycle. […] The levels of ornithine, another metabolite of urea cycle, was also elevated following S. amnii infection. […] Overall, this analysis demonstrated unique metabolic contributions of tested clinical isolates of common BVAB species. A. vaginae and S. amnii created metabolic environments that promote host inflammatory responses, whereas G. vaginalis and P. bivia altered mostly the physiochemical properties of the epithelial barrier (such as mucins, sialic acid, polyamines). […] These mechanistic insights on immunometabolic landscape provide better understanding of BV pathogenesis and connect BV with adverse women’s health outcomes.

• #53 Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix | npj Biofilms and Microbiomes

  https://www.nature.com/articles/s41522-021-00259-8

  We tested the hypothesis that health-associated Lactobacillus and BVAB uniquely alter the immunometabolic cervical microenvironment. […] We observed that particular BVAB infections induced a dramatic enrichment in citrulline, a key metabolite in the urea cycle. […] The levels of ornithine, another metabolite of urea cycle, was also elevated following S. amnii infection. […] Overall, this analysis demonstrated unique metabolic contributions of tested clinical isolates of common BVAB species. A. vaginae and S. amnii created metabolic environments that promote host inflammatory responses, whereas G. vaginalis and P. bivia altered mostly the physiochemical properties of the epithelial barrier (such as mucins, sialic acid, polyamines). […] These mechanistic insights on immunometabolic landscape provide better understanding of BV pathogenesis and connect BV with adverse women’s health outcomes.

• #54 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4957507/

  The majority of epidemiologic data support the hypothesis that BV is a STI. […] Assuming that sexual transmission plays a key role in the pathogenesis of BV, the next question concerns the transmitted pathogen(s). […] More recently it was shown that previously unrecognized, unculturable bacteria are also part of the BV flora. […] Although it is highly likely that anaerobes contribute to the symptoms of BV, there has been renewed interest in the hypothesis that G. vaginalis is the inciting pathogen, with studies confirming its virulence factors (ability to adhere to host receptor sites on vaginal epithelial cells, production of cytotoxic substances specific for host cells, and biofilm formation) as well as its concordance in sexual partners. […] In 2014, Schwebke et al presented a conceptual model for the pathogenesis of BV with G. vaginalis as the founder or keystone pathogen.

• #55 Bacterial Vaginosis – STI Treatment Guidelines

  https://www.cdc.gov/std/treatment-guidelines/bv.htm

  BV is a vaginal dysbiosis resulting from replacement of normal hydrogen peroxide and lactic-acidproducing Lactobacillus species in the vagina with high concentrations of anaerobic bacteria, including G. vaginalis, Prevotella species, Mobiluncus species, A. vaginae, and other BV-associated bacteria. […] The cause of the microbial alteration that precipitates BV is not fully understood, and whether BV results from acquisition of a single sexually transmitted pathogen is unknown. […] BV also increases HIV infection acquisition because specific BV-associated bacteria can increase susceptibility to HIV and the risk for HIV transmission to male sex partners. […] Although BV-associated bacteria can be identified on male genitalia, treatment of male sex partners has not been beneficial in preventing the recurrence of BV.

• #56 Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02077-3

  While persistence or resistance of BVAB or BV biofilm following antibiotic therapy is likely to be the dominant mechanism among some women, there is a robust body of evidence to support the exchange of both optimal and detrimental bacteria between partners during sexual activity. […] These data suggest that reinfection of women with pathogenic BVAB may be a key driver of recurrence following treatment. […] What is clear now is that there is a substantial body of epidemiological and microbiological data to support the role of sexual transmission in the BV syndrome. […] The contribution of the cutaneous penile microbiota to BV acquisition in women was evident in a large circumcision trial in sub-Saharan Africa that had a primary aim of reducing HIV transmission. […] Collectively, these data illustrate male carriage of BVAB and highlight how male partners and specific anatomical sites may contribute to BV acquisition and recurrence.

• #57

  https://link.springer.com/article/10.1007/s11908-013-0318-4

  Bacterial vaginosis (BV) is the most common cause of vaginal infection, yet its pathogenesis remains controversial. […] Although BV is characterized by its polymicrobial nature, it is highly likely that the inciting organism is Gardnerella vaginalis. […] Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. […] Adherent biofilms in bacterial vaginosis. […] Gardnerella biofilm involves females and males and is sexually transmitted.

• #58 Pathogenesis of bacterial vaginosi … | Article | H1 Connect

  https://connect.h1.co/article/726601039

  Bacterial vaginosis (BV) may be sexually transmitted; however, we still dont know whether the condition results from transmission of a single agent. […] Here, Muzny and Schwebke propose a model with Gardnerella as the keystone organism for the development of BV, with acquisition of both Gardnerella and additional anaerobes being sexual. […] Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV.

• #59

  https://www-.grantome.com/grant/NIH/K23-AI106957-02

  Bacterial vaginosis (BV) is the most common vaginal infection in the United States, with an estimated prevalence of 30%. It is associated with adverse outcomes including preterm birth, pelvic inflammatory disease, and increased risk for sexually transmitted infections (STIs), including HIV. BV represents a shift in the vaginal microbiota from Lactobacillus-predominate species to facultative (Gardnerella vaginalis; GV) and strict anaerobic bacteria. […] However, the pathogenesis of BV remains unclear. It remains controversial as to whether BV results from acquisition of GV as the founder organism which subsequently leads to the complex changes in the vaginal microbiota associated with BV, whether BV is transmitted as a polymicrobial consortium, […] GV, as a facultative anaerobe, may be able to tolerate the high oxidation-reduction (redox) potential of a healthy vaginal microbiome, unlike strict anaerobes (i.e. other BV-associated bacteria: BVAB).

• #60

  https://www.who.int/news-room/fact-sheets/detail/bacterial-vaginosis

  Bacterial vaginosis (BV) results from an imbalance between good and harmful bacteria micro-organisms. More specifically, an overgrowth of pathogens such as Gardnerella spp., Prevotella spp., Mobilincus spp., Megaspahera spp., Sneathea spp. and mixed vaginal anaerobes species would eventually replace the beneficial lactobacilli that helps maintain a healthy vaginal environment. […] The exact cause of this imbalance is not known but has been attributed to douching and having unprotected sex with a new or several sex partners. […] Vaginal cleansing and douching can increase the risk of developing BV. Intravaginal practice, e.g. insertion of herbs or other products into the vagina, is another risk factor.

• #61 Bacterial Vaginosis: A Review

  https://www.uspharmacist.com/article/bacterial-vaginosis-a-review

  Patients with BV have a dense biofilm consisting of a matrix of polysaccharides, proteins, extracellular DNA, and embedded bacteria that is tightly attached to the vaginal epithelial surface.11,12 The biofilm is polymicrobial and consists mainly of G vaginalis, with 80% of G vaginalis containing biofilms also containing A vaginae.11 Bacteria residing within a biofilm enjoy relative protection from antimicrobial agents and the host immune system, as well as high resistance to lactobacilli-produced defense factors (such as lactic acid, hydrogen peroxide, and bacteriocins), which may be due in part to differences in gene expression.10,13-15 Therefore, infections involving biofilm, such as BV, are difficult to clear and often have high rates of recurrence.13,16 […] It is unknown whether one pathogen transmitted through sexual exposure causes BV, and the mechanism that causes the disruption of lactobacilli that leads to BV is not completely understood.4 Sexual exposure (particularly having multiple or new sex partners) increases the risk of BV, and this condition rarely occurs in women who have never had sex. Additionally, regular douching and the absence of vaginal lactobacilli or protection during sex are related to the development of BV.4

• #62 Diet for Preventing Bacterial Vaginosis

  https://nutritionfacts.org/video/bacterial-vaginosis-and-diet/

  And the more nutrient-rich ones diet, the lower ones apparent risk for bacterial vaginosis. […] Well, its thought that high fat intakeparticularly saturated fat, which comes mostly from like, dairy, doughnuts, and chicken in this countrymay increase vaginal pH, thereby increasing the risk of bacterial vaginosis.

• #63 Diet for Preventing Bacterial Vaginosis

  https://nutritionfacts.org/video/bacterial-vaginosis-and-diet/

  In the same way fermented pickles, kimchi, and sauerkraut foster the growth of good bacteria (like lactobacillus) by maintaining an acidic environment, so does the human vagina. The normal pH of ones vagina is that of tomato juice. Once it starts creeping up to that of coffee, though, an overgrowth of bad bacteria can take hold, and cause bacterial vaginosiswhich affects an astounding 29% of American women; thats nearly one in three women in the United States. That makes it the most frequent cause of vaginal complaints among younger women, affecting tens of millions. Its commonly diagnosed with the so-called whiff test, where the doctor takes a whiff of the vaginal discharge, sniffing for the characteristic fishy odor. […] Recently, poor nutrition has been added to the list of risk factors. You appear more likely to get bacterial vaginosis if you have lower levels circulating in your bloodstream of phytonutrients, like vitamin C and beta-carotene, indicating a lower intake of fruits and vegetables.

• #64 Bacterial Vaginosis (BV) – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis-cervicitis-and-pelvic-inflammatory-disease/bacterial-vaginosis-bv

  Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. […] The pathogenesis is unclear but involves the overgrowth of multiple bacterial pathogens and a decrease in the usual lactobacillus-predominant vaginal flora. […] Anaerobic pathogens that overgrow include Prevotella species, Peptostreptococcus species, Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis, which increase in concentration by 10- to 100-fold and replace the lactobacilli that usually maintain a normal vaginal environment. […] Bacterial vaginosis appears to increase the risk of pelvic inflammatory disease, postabortion and postpartum endometritis, and posthysterectomy vaginal cuff infection. […] BV increases the risk of pelvic inflammatory disease, postpartum endometritis, and some pregnancy complications, including prelabor rupture of membranes and preterm birth.

• #65 Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix | npj Biofilms and Microbiomes

  https://www.nature.com/articles/s41522-021-00259-8

  Bacterial vaginosis (BV) is an enigmatic polymicrobial condition characterized by a depletion of health-associated Lactobacillus and an overgrowth of anaerobes. Importantly, BV is linked to adverse gynecologic and obstetric outcomes: an increased risk of sexually transmitted infections, preterm birth, and cancer. […] The etiology of this polymicrobial disorder is poorly understood. […] Multiple epidemiological studies have shown that BV is a risk factor for gynecologic, reproductive, and obstetric sequelae, such as endometritis, pelvic inflammatory disease, infertility, cervicitis, and preterm birth. […] Women with BV also exhibit an increased risk of acquiring sexually transmitted infections (STIs) caused by viruses, bacteria, and protozoan parasites. […] Our study demonstrated that 3D cervical epithelial cell colonized with cervicovaginal microbiota faithfully reproduce the immunometabolic microenvironment previously observed in clinical studies and can successfully be used as a robust tool to evaluate host responses to commensal and pathogenic bacteria in the female reproductive tract.

• #66 Bacterial Vaginosis – STI Treatment Guidelines

  https://www.cdc.gov/std/treatment-guidelines/bv.htm

  BV is a vaginal dysbiosis resulting from replacement of normal hydrogen peroxide and lactic-acidproducing Lactobacillus species in the vagina with high concentrations of anaerobic bacteria, including G. vaginalis, Prevotella species, Mobiluncus species, A. vaginae, and other BV-associated bacteria. […] The cause of the microbial alteration that precipitates BV is not fully understood, and whether BV results from acquisition of a single sexually transmitted pathogen is unknown. […] BV also increases HIV infection acquisition because specific BV-associated bacteria can increase susceptibility to HIV and the risk for HIV transmission to male sex partners. […] Although BV-associated bacteria can be identified on male genitalia, treatment of male sex partners has not been beneficial in preventing the recurrence of BV.

• #67 Bacterial Vaginosis and Sexually Transmitted Diseases: Relationship and Management | IntechOpen

  https://www.intechopen.com/chapters/56549

  Furthermore, the loss of lactobacilli dominance is linked to bacterial vaginosis (BV), which is associated with an overgrowth of anaerobic bacteria, relatively high vaginal pH (4.5) infertility, preterm birth, maternal infections, and increased risk of STDs. […] The relationship between genital epithelial cells in the vagina and vaginal microbiota seems to strongly influence the innate immune response suggesting a pivotal role of the reproductive tract immune response in determining BV and its compliances: vaginal microbiota derangement could decrease local immunity with a consequent increase of STDs risks in the women urogenital tract. […] An increasing number of evidences provide a strong foundation for a biologic relationship between BV and increased STIs susceptibility. […] BV may predispose to acquisition of STDs upon exposure because local cytokine production associated with BV may facilitate the acquisition of STDs.

• #68 Bacterial Vaginosis (BV) – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis-cervicitis-and-pelvic-inflammatory-disease/bacterial-vaginosis-bv

  Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. […] The pathogenesis is unclear but involves the overgrowth of multiple bacterial pathogens and a decrease in the usual lactobacillus-predominant vaginal flora. […] Anaerobic pathogens that overgrow include Prevotella species, Peptostreptococcus species, Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis, which increase in concentration by 10- to 100-fold and replace the lactobacilli that usually maintain a normal vaginal environment. […] Bacterial vaginosis appears to increase the risk of pelvic inflammatory disease, postabortion and postpartum endometritis, and posthysterectomy vaginal cuff infection. […] BV increases the risk of pelvic inflammatory disease, postpartum endometritis, and some pregnancy complications, including prelabor rupture of membranes and preterm birth.

• #69 Bacterial Vaginosis (BV) – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis-cervicitis-and-pelvic-inflammatory-disease/bacterial-vaginosis-bv

  Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. […] The pathogenesis is unclear but involves the overgrowth of multiple bacterial pathogens and a decrease in the usual lactobacillus-predominant vaginal flora. […] Anaerobic pathogens that overgrow include Prevotella species, Peptostreptococcus species, Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis, which increase in concentration by 10- to 100-fold and replace the lactobacilli that usually maintain a normal vaginal environment. […] Bacterial vaginosis appears to increase the risk of pelvic inflammatory disease, postabortion and postpartum endometritis, and posthysterectomy vaginal cuff infection. […] BV increases the risk of pelvic inflammatory disease, postpartum endometritis, and some pregnancy complications, including prelabor rupture of membranes and preterm birth.

• #70 Current Concept of Bacterial Vaginosis in Cervical Cancer | Biswal | Journal of Clinical Gynecology and Obstetrics

  https://jcgo.org/index.php/jcgo/article/view/175/89

  The pathogenesis of BV in cervical cancer is complex. BV is not attributable to a single causative organism but its due to immense overgrowth of composite of flora including G. vaginalis, Peptostreptococci, Bacterioides spp., Mobiluncus spp., Mycoplasma and Ureaplasma urealyticum. Fusobacterium and Atopobium vagina are also commonly found in BV. Inflammation plays a little role since this disease is due to the disruption of the vaginal microenvironment rather than a true tissues infective state. This overgrowth shifts the balance from Lactobacillus-predominated vaginal ecosystem to microenvironment with anaerobic bacteria dominance. This conclusion is corroborated by experimental studies conducted in humans and animal models that demonstrated upon vaginal inoculation with a single vaginosis-causing bacterial species, BV will rarely occur.

• #71

  https://www.jcdr.net/article_fulltext.asp?id=1437

  High titres of the sialidase enzyme and low titres of sIgA correlated with an adverse pregnancy outcome, especially preterm delivery and low birth weight. […] It is not certain whether women with intermediate flora can revert back to the normal flora or complicate into bacterial vaginosis. […] Further studies are needed to prove this aspect of the pathogenesis of bacterial vaginosis. […] All women with bacterial vaginosis or with intermediate flora do not show significant titres of the sIgA antibodies to G.vaginalis. So, the detection of sIgA to G.vaginalis in the vaginal discharge cannot be used as a means for the diagnosis of bacterial vaginosis.

• #72 Current Concept of Bacterial Vaginosis in Cervical Cancer | Biswal | Journal of Clinical Gynecology and Obstetrics

  https://jcgo.org/index.php/jcgo/article/view/175/89

  It has been hypothesized that BV results in cervical cancer through an increase in vaginal nitrosamines and altered cytokine profiles. The presence of raise nitrosamines in vagina will lead to higher probability of DNA damage and change in cytokine profiles will cause altered response of immune system to clear up HPV infection. Therefore, BV will interact with HPV infection with the consequence of higher risk of developing cervical cancer among those with BV and HPV co-infection than those with a mono-infection. However, other infections for instance Candida was not associated with the development of CIN or cervical carcinoma. […] Nevertheless, the causal relationship between BV-HPV interaction and cervical cancer development may not be entirely infallible since the causation may be bidirectional due to reverse causality. Owing to the relative immunodeficiency state in advanced cancer stage, BV thrives and therefore seems to be antecedent factor of cervical carcinoma whilst in fact the opposite is true. Its equally coherent to postulate that BV-HPV infection is a bona-fide cause of cervical carcinoma. Unless theres a properly executed and methodologically sound cohort study, the temporal order between BV-HPV and cervical carcinoma cannot be fully ascertained.

• #73 The ABCDs of bacterial vaginosis: Abnormal flora, Bothersome symptoms, Chronicity, and Differential diagnosis – Women’s Healthcare

  https://www.npwomenshealthcare.com/bacterial-vaginosis-abnormal-flora/

  Alterations in vaginal microflora cause a vaginal dysbiosis that can lead to asymptomatic or symptomatic bacterial vaginosis (BV). […] Bacterial vaginosis (BV) is a common condition that results from a shift in the balance of a womans vaginal microflora. BV is manifested by a decrease in predominantly hydrogen peroxide-producing lactobacilli and an increase in anaerobic bacteria. The depletion of lactobacilli leads to a rise in vaginal pH, and enzymes produced by the anaerobes lead to some of the classic symptoms associated with BV. […] The underlying mechanism of BV is not well understood and long-term restoration of the normal vaginal flora can be challenging, BV often recurs or becomes chronic despite initially successful treatment. […] The recurrence rate may be as high as 80% in some populations.

• #74 Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02077-3

  Bacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners. […] Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.

• #75 Bacterial vaginosis and biofilms: Therapeutic challenges and innovations – A narrative review – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/bacterial-vaginosis-and-biofilms-therapeutic-challenges-and-innovations-a-narrative-review/

  Bacterial vaginosis (BV), characterised by an imbalance in vaginal microbiota, frequently leading to recurrent episodes, has garnered recent research attention due to the significance of biofilms in its pathogenesis. […] Recent research has unveiled the existence and significance of biofilms formed by BV-associated bacteria, particularly Gardnerella vaginalis, within the vaginal environment. […] These biofilms pose challenges to treatment and may contribute to the recurrent nature of BV. […] One of the most concerning aspects of BV biofilms is their ability to hinder the effectiveness of antibiotics. The biofilms protective matrix shields BV-associated bacteria from antibiotics, making it difficult for these drugs to reach and kill them, resulting in treatment resistance and recurrent BV.

• #76 Vaginitis, TSS, and other Genitourinary Tract Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/stdd.htm

  Atopobium vaginae is at very low concentrations in the vaginal fluid of healthy women vaginal fluid. […] However, Atopobium vaginae is commonly found in the vaginal fluid of patients with BV (50%-95%). […] The presence of the biofilm enables the bacterial cells to reach higher concentrations (up to 1011 bacteria/mL) than in vaginal fluid and boosts their resistance to both the host immune system and the antimicrobials. […] It requires higher concentrations of antimicrobial agent to kill the organisms in these biofilms. […] It has also been shown that Atopobium vaginae is quite resistant to drugs commonly used to treat BV (metronidazole). […] This might explain why there is a high rate of relapse following treatment of BV.

• #77 Vaginitis, TSS, and other Genitourinary Tract Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/stdd.htm

  Atopobium vaginae is at very low concentrations in the vaginal fluid of healthy women vaginal fluid. […] However, Atopobium vaginae is commonly found in the vaginal fluid of patients with BV (50%-95%). […] The presence of the biofilm enables the bacterial cells to reach higher concentrations (up to 1011 bacteria/mL) than in vaginal fluid and boosts their resistance to both the host immune system and the antimicrobials. […] It requires higher concentrations of antimicrobial agent to kill the organisms in these biofilms. […] It has also been shown that Atopobium vaginae is quite resistant to drugs commonly used to treat BV (metronidazole). […] This might explain why there is a high rate of relapse following treatment of BV.

• #78 Bacterial Vaginosis – STI Treatment Guidelines

  https://www.cdc.gov/std/treatment-guidelines/bv.htm

  BV biofilm disrupting agents (i.e., TOL-463) are being investigated to determine their role in enhancing the likelihood of BV cure relative to approved therapies. […] Studies have evaluated the clinical and microbiologic efficacy of intravaginal Lactobacillus and other probiotic formulations to treat BV and restore normal vaginal microbiota; overall, no studies support these products as an adjunctive or replacement therapy for women with BV.

• #79 The ABCDs of bacterial vaginosis: Abnormal flora, Bothersome symptoms, Chronicity, and Differential diagnosis – Women’s Healthcare

  https://www.npwomenshealthcare.com/bacterial-vaginosis-abnormal-flora/

  The underlying mechanism of the shift to abnormal flora in BV is not well understood. […] Until novel treatment options come along, treatment regimens for recurrent BV aim to first treat the current infection and then suppress recurrence(s). […] Novel agents that disrupt the vaginal biofilm, including antiseptics, probiotics/prebiotics, plant-derived compounds, natural antimicrobials, acidifying/buffering agents, and DNases, are being investigated as treatments for recurrent BV. […] More research is needed for both better understanding of BV pathogenesis and new and novel treatment options.

• #80 Bacterial vaginosis and biofilms: Therapeutic challenges and innovations – A narrative review – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/bacterial-vaginosis-and-biofilms-therapeutic-challenges-and-innovations-a-narrative-review/

  Biofilm-focused treatments, including biofilm-disrupting agents and probiotics, offer the potential to reduce BV recurrence substantially. By targeting the protective biofilm matrix, these treatments aim to enhance the efficacy of antibiotic therapy, making embedded bacteria more susceptible to eradication. […] Addressing BV biofilms requires a holistic strategy that encompasses prevention, patient education, and innovative treatments, working towards improving the quality of life of women affected by BV and reducing the burden of this common condition.

• #81

  https://journals.lww.com/co-infectiousdiseases/fulltext/2020/02000/host_vaginal_microbiota_interactions_in_the.9.aspx

  The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. […] We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. […] Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. […] These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. […] Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes. […] Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.

• #82

  https://journals.lww.com/jlgtd/fulltext/2022/01000/the_vaginal_microbiome__ii__vaginal_dysbiotic.16.aspx

  Gardnerella vaginalis, present in 95%100% of BV cases, was originally thought to be the primary BV pathogen. […] However, G. vaginalis is found in many women without BV in lower abundances. […] It is possible that women who are colonized by Gardnerella species or clades with low virulence potential do not develop BV, whereas acquisition of virulent strains results in BV. […] In a model suggested recently, it was proposed that BV development is triggered by sexual transmission of virulent strains of G. vaginalis, which displaces healthy vaginal lactobacilli, and initiates BV biofilm formation on the vaginal epithelium. […] The loss of the protective mucous layer leads to increased adherence of secondary colonizers to the mature, polymicrobial BV biofilm. […] Overall, these data suggest that the pathogenic potentials of many BV-associated bacteria are strain or species specific.

• #83 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4957507/

  This alteration would then cause a marked decrease in lactobacilli and an increase in other BVAB, acquired shortly after birth from maternal and environmental sources and normally present in very low concentrations, leading to the BV syndrome. […] This model is in keeping with the current model for periodontal disease in which keystone pathogens are aided by accessory pathogens (commensal bacteria that are not pathogenic by themselves in a given niche but can enhance the virulence of keystone pathogens). […] Unraveling the mystery of BV pathogenesis is essential if we are to make progress in the control and prevention of this common, important condition.

• #84 Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses | CoLab

  https://colab.ws/articles/10.1093%2Finfdis%2Fjiw121

  In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. […] The discussion on the epidemiology and pathogenesis of BV is presented here, and several hypotheses on its pathogenesis are critiqued. […] Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV. […] This information is vital for the prevention and control of this important infection and its adverse public health consequences.

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