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Frontiers in Cellular and Infection... 2022Cervical cancer disproportionately affects women of reproductive age, with 80% of cases occurring in low- and middle-income countries. Persistent infection with... (Review)
Review
Cervical cancer disproportionately affects women of reproductive age, with 80% of cases occurring in low- and middle-income countries. Persistent infection with high-risk human papillomavirus (HPV) genotypes has been described as the most common non-systemic biological risk factor for the development of cervical cancer. The mucosal immune system plays a significant role in controlling HPV infection by acting as the first line of host defense at the mucosal surface. However, the virus can evade host immunity using various mechanisms, including inhibition of the antiviral immune response necessary for HPV clearance. Pro-inflammatory cytokines and the vaginal microbiome coordinate cell-mediated immune responses and play a pivotal role in modulating immunity. Recently, diverse vaginal microbiome (associated with bacterial vaginosis) and genital inflammation have emerged as potential drivers of high-risk HPV positivity and disease severity in women. The potential role of these risk factors on HPV recurrence and persistence remains unclear. This article reviews the role of cellular or cytokine response and vaginal microbiome dysbiosis in the clearance, persistence, and recurrence of HPV infection.
Topics: Cytokines; Female; Humans; Microbiota; Papillomavirus Infections; Uterine Cervical Neoplasms; Vagina; Vaginosis, Bacterial
PubMed: 35873158
DOI: 10.3389/fcimb.2022.927131 -
Frontiers in Cellular and Infection... 2021, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically... (Review)
Review
, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of in the vaginal microbiome was carefully explored. has the smallest genome among known and it has many probiotic characteristics, but is partly different from other major vaginal species, such as , in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.
Topics: Dysbiosis; Female; Humans; Lactobacillus; Pregnancy; Vagina; Vaginosis, Bacterial
PubMed: 34881196
DOI: 10.3389/fcimb.2021.792787 -
The New England Journal of Medicine May 2020Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis.
METHODS
We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12.
RESULTS
A total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups.
CONCLUSIONS
The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02766023.).
Topics: Administration, Intravaginal; Adolescent; Adult; Anti-Bacterial Agents; Antibiosis; Double-Blind Method; Female; Gels; Humans; Incidence; Lactobacillus crispatus; Metronidazole; Middle Aged; Secondary Prevention; Vagina; Vaginosis, Bacterial; Young Adult
PubMed: 32402161
DOI: 10.1056/NEJMoa1915254 -
Australian Prescriber Dec 2020Vulvovaginitis is a commonly encountered problem in general practice. It usually presents with irritation and vaginal discharge A thorough examination is essential in... (Review)
Review
Vulvovaginitis is a commonly encountered problem in general practice. It usually presents with irritation and vaginal discharge A thorough examination is essential in order not to miss the less common causes. Investigations may be needed to confirm the diagnosis Candidiasis and bacterial vaginosis are the most common causes. Antifungals and antibiotics are therefore used in management Not all causes are infective. Several skin disorders can affect the vulva Ongoing or recurrent symptoms require careful evaluation and further investigation
PubMed: 33363301
DOI: 10.18773/austprescr.2020.055 -
Nutrients Feb 2020The vaginal microbiota has importance in preserving vaginal health and defending the host against disease. The advent of new molecular techniques and computer science... (Review)
Review
The vaginal microbiota has importance in preserving vaginal health and defending the host against disease. The advent of new molecular techniques and computer science has allowed researchers to discover microbial composition in depth and associate the structure of vaginal microbial communities. There is a consensus that vaginal flora is grouped into a restricted number of communities, although the structure of the community is constantly changing. Certain Community-Sate Types (CSTs) are more associated with poor reproductive outcomes and sexually transmitted diseases (STDs) meanwhile, CSTs dominated by species-particularly -are more related to vaginal health. In this work, we have reviewed how modifiable and non-modifiable factors may affect normal vaginal microbiota homeostasis-including sexual behavior, race or ethnicity, and hygiene. Special interest has been given to how the use of probiotics, diet intake, and use of hormone replacement therapies (HRTs) can potentially impact vaginal microbiota composition.
Topics: Dysbiosis; Eating; Female; Homeostasis; Hormone Replacement Therapy; Humans; Lactobacillus crispatus; Microbiota; Probiotics; Risk Factors; Vaginosis, Bacterial; Vigna
PubMed: 32041107
DOI: 10.3390/nu12020419 -
Reproductive Health Jun 2022Bacterial vaginosis (BV) is one of the most common vaginal infectious diseases in female reproductive period. Although the existing view is that probiotic treatment may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bacterial vaginosis (BV) is one of the most common vaginal infectious diseases in female reproductive period. Although the existing view is that probiotic treatment may be one of the feasible methods for the treatment of BV, different intervention methods lead to different treatment results. Therefore, up-to-date and comprehensive evidence in this regard is essential for the development of intervention strategies.
OBJECTIVE
This meta-analysis aims to systematically evaluate the role of probiotics in the treatment of BV in adult women.
METHODS
We searched the databases of Embase, Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov for Randomized Controlled Trials published until November 7, 2021. Meta-analysis was performed by Revman5.3 software to systematically evaluate the clinical efficacy of probiotics adjunctive therapy in the treatment of BV. The literatures were screened and evaluated according to the inclusion and exclusion criteria. Chi-square test was used to test the heterogeneity between trials. Random or Fixed effect models were used to analyze the cure rate of BV.
RESULTS
Fourteen randomized controlled trials compared the efficacy of probiotics with antibiotic therapy (probiotics + antibiotics group) versus antibiotics alone or plus placebo (antibiotics (+ placebo) group) for BV [Risk Ratios (RR) = 1.23, 95% CI (1.05, 1.43), P = 0.009]. Three compared the efficacy of probiotics regimen (probiotics group) and antibiotics (antibiotics group) in the treatment of BV [RR = 1.12, 95% CI (0.60, 2.07), P = 0.72]. Another Three compared the efficacy of probiotics regimen (probiotics group) with placebo (placebo group) [RR = 15.20, 95% CI (3.87, 59.64), P < 0.0001].
CONCLUSION
Our meta-analysis suggests probiotics may play a positive role in the treatment of BV, but more strong evidence is needed.
Topics: Administration, Intravaginal; Adult; Anti-Bacterial Agents; Female; Humans; Probiotics; Randomized Controlled Trials as Topic; Vagina; Vaginosis, Bacterial
PubMed: 35698149
DOI: 10.1186/s12978-022-01449-z -
Microbiome Nov 2022A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence...
BACKGROUND
A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions.
RESULTS
Here, we describe an organ-on-a-chip (organ chip) microfluidic culture model of the human vaginal mucosa (vagina chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis-containing consortia, and to measure associated host innate immune responses. Co-culture and growth of the L. crispatus consortia on-chip was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis-containing consortia in the vagina chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines.
CONCLUSION
This study demonstrates the potential of applying human organ chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products. Video Abstract.
Topics: Female; Pregnancy; Humans; Lab-On-A-Chip Devices; Vagina; Microbiota; Vaginosis, Bacterial; Cytokines
PubMed: 36434666
DOI: 10.1186/s40168-022-01400-1 -
Sexually Transmitted Diseases Dec 2019A retrospective chart review characterized clinicians' use of maintenance intravaginal boric acid for women with recurrent vulvovaginal candidiasis or bacterial...
A retrospective chart review characterized clinicians' use of maintenance intravaginal boric acid for women with recurrent vulvovaginal candidiasis or bacterial vaginosis. Average length of use was 13 months with high patient satisfaction and few adverse events. Prospective studies are needed to evaluate the efficacy of maintenance boric acid for these conditions.
Topics: Administration, Intravaginal; Adult; Anti-Infective Agents, Local; Boric Acids; Candidiasis, Vulvovaginal; Drug Administration Schedule; Female; Humans; Middle Aged; Patient Satisfaction; Recurrence; Retrospective Studies; Treatment Outcome; Vaginosis, Bacterial
PubMed: 31663976
DOI: 10.1097/OLQ.0000000000001063 -
Nature Communications Feb 2022Despite the high prevalence of both cervico-vaginal human papillomavirus (HPV) infection and bacterial vaginosis (BV) worldwide, their causal relationship remains...
Despite the high prevalence of both cervico-vaginal human papillomavirus (HPV) infection and bacterial vaginosis (BV) worldwide, their causal relationship remains unclear. While BV has been presumed to be a risk factor for HPV acquisition and related carcinogenesis for a long time, here, supported by both a large retrospective follow-up study (n = 6,085) and extensive in vivo data using the K14-HPV16 transgenic mouse model, we report a novel blueprint in which the opposite association also exists. Mechanistically, by interacting with several core members (NEMO, CK1 and β-TrCP) of both NF-κB and Wnt/β-catenin signaling pathways, we show that HPV E7 oncoprotein greatly inhibits host defense peptide expression. Physiologically secreted by the squamous mucosa lining the lower female genital tract, we demonstrate that some of these latter are fundamental factors governing host-microbial interactions. More specifically, several innate molecules down-regulated in case of HPV infection are hydrolyzed, internalized and used by the predominant Lactobacillus species as amino acid source sustaining their growth/survival. Collectively, this study reveals a new viral immune evasion strategy which, by its persistent/negative impact on lactic acid bacteria, ultimately causes the dysbiosis of vaginal microbiota.
Topics: Amino Acids; Animals; Female; Follow-Up Studies; Lactobacillus; Mice; Microbiota; Mucous Membrane; Papillomavirus Infections; Peptides; Retrospective Studies; Vagina; Vaginosis, Bacterial
PubMed: 35228537
DOI: 10.1038/s41467-022-28724-8