Vaginosis citolítica: actualización diagnóstica y terapéutica / Cytolytic vaginosis: diagnostic and therapeutic update

El objetivo es conocer el abordaje diagnóstico y terapéutico de la vaginosis citolítica. Para ello se hizo una búsqueda sistemática de la literatura médica mediante las bases de datos: PubMed, Central, etc. Se limitó a ensayos clínicos aleatorizados, metaanálisis y revisiones bibliográficas, con disponibilidad del texto completo para evaluarlos en su totalidad e incluirlos en la revisión; publicados entre 1980 y 2021. Se incluyeron 27 publicaciones. La vaginosis citolítica es un trastorno infradiagnosticado. En mujeres con síntomas y signos de candidiasis vulvovaginal, que no responden a la terapia, se debe considerar la probabilidad de estar en presencia de una vaginosis citolítica. El tratamiento obliga a elevar el pH vaginal a valores básicos y a disminuir el número excesivo de Lactobacillus, resultando de utilidad las duchas vaginales con bicarbonato de sodio y/o un tratamiento con antibióticos derivados de la penicilina junto a un inhibidor de ß-lactamasas o doxiciclina en las pacientes alérgicas a la penicilina. Finalmente, se concluye que la vaginosis citolítica es una afección común, frecuentemente se diagnostica de forma errónea porque se confunde con la candidiasis vulvovaginal; se caracteriza por producir un cuadro clínico similar. El tratamiento se enfoca en disminuir el número de Lactobacillus y la elevación del pH vaginal.

The objective is to know the diagnostic and therapeutic approach of cytolytic vaginosis. A systematic search of the medical literature was carried out using the following databases: Medline via PubMed, Central, and Cochrane Database of Systematic Reviews, among others. The search was limited to randomized clinical trials, meta-analyses, and literature reviews that had the full text available for full evaluation and inclusion in the review; published between 1980 and 2021. Twenty-seven publications were included. Cytolytic vaginosis is a frequently underdiagnosed disorder, which mimics Candida vaginitis. In women with symptoms and signs of vulvovaginal candidiasis who do not respond to antifungal therapy, the possibility of cytolytic vaginosis should be considered. The treatment of this condition requires raising the vaginal pH to basic values and reducing the excessive number of Lactobacillus, resulting in useful vaginal douches with sodium bicarbonate and/or treatment with antibiotics derived from penicillin together with a ß-lactamases inhibitor or doxycycline in patients allergic to penicillin. Finally, we conclude that cytolytic vaginosis is a common condition, frequently misdiagnosed because it is confused with vulvovaginal candidiasis, since it is characterized by producing a similar clinical picture. Treatment focuses on reducing the number of Lactobacillus and raising vaginal pH.

Microbiome and Vulvovaginitis.

Vulvovaginitis occurs in mostly reproductive aged women. Recurrent vaginitis affects overall quality of life, with a large financial burden on the patient, family, and health system. This review discusses a clinician's approach to vulvovaginitis with specific attention to the 2021 updated Center for Disease Control and Prevention guidelines. The authors discuss the role of the microbiome in vaginitis and evidence-based approaches for diagnosis and treatment of vaginitis. This review also provides updates on new considerations, diagnosis, management, and treatment of vaginitis. Desquamative inflammatory vaginitis and genitourinary syndrome of menopause are discussed as differential diagnosis of vaginitis symptoms.

Lactobacillus Probiotics Improve Vaginal Dysbiosis in Asymptomatic Women.

Vaginal dysbiosis can lead to serious infections in asymptomatic women. Lactobacillus probiotics (LBPs) are being investigated as a promising therapy for reversing vaginal microbiota dysbiosis. This study aimed to investigate whether administering LBPs could improve vaginal dysbiosis and facilitate the colonization of Lactobacillus species in asymptomatic women. 36 asymptomatic women were classified based on the Nugent score as Low-NS (n = 26) and High-NS (n = 10) groups. A combination of Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, and Lactobacillus reuteri CBT LU4 was administered orally for 6 weeks. The study found that among women with a High-NS, 60% showed improved vaginal dysbiosis with a Low-NS after LBP intake, while four retained a High-NS. Among women with a Low-NS, 11.5 % switched to a High-NS. Genera associated with vaginal dysbiosis were positively correlated with the alpha diversity or NS, while a negative correlation was observed between Lactobacillus and the alpha diversity and with the NS. Vaginal dysbiosis in asymptomatic women with an HNS improved after 6 weeks of LBP intake, and qRT-PCR revealed the colonization of Lactobacillus spp. in the vagina. These results suggested that oral administration of this LBP could improve vaginal health in asymptomatic women with an HNS.

Impact of (recurrent) bacterial vaginosis on quality of life and the need for accessible alternative treatments.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common vaginal dysbiosis in women aged 15-44 years old. METHODS: We administered a cross-sectional, single timepoint survey to women ages 18 years or older and who have had bacterial vaginosis (BV). Women completed an anonymous online survey evaluating the impact of BV on their quality of life, how effective different types of treatments were and the amount of self-diagnosed vs. provider diagnosed BV episodes they had. RESULTS: 62 participants completed the anonymous online survey. With a self-reported median number of BV episodes in the past year was 4 (IQR 1-7). Among these women 69.8% reported BV had a negative impact on their sexual health, 67.7% on their physical health, 74.6% on their mental health. More than half of the respondents had used probiotics with oral Lactobacillus sp. (53.2%), mainly by oral route, and over a third had used vaginal boric acid (37.1%). Most women were unaware of Lactobacillus crispatus. Lactobacillus probiotics were more likely to be tried by women who were negatively impacted by BV for overall quality of life (p = 0.033), sexual health (p = 0.002), and mental health (p = 0.006) while boric acid use was more likely to be used by women who were negatively impacted by BV for their sexual health (p = 0.008). CONCLUSIONS: BV is associated with negative quality of life and the women most impacted are seeking alternative treatments such as probiotics (Lactobacillus) and boric acid. There needs to be improvements in BV treatment that include alternative therapy options that have demonstrated efficacy with standardized composition, formulation and dosage.

Synthetic bacterial consortia transplantation for the treatment of Gardnerella vaginalis-induced bacterial vaginosis in mice.

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1ß and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis. Video Abstract.

Optimizing the vaginal microbiome as a potential strategy to reduce heterosexual HIV transmission.

Bacterial vaginosis (BV) is a proinflammatory genital condition characterized by high vaginal bacterial diversity and a paucity of Lactobacillus species. BV has been linked to an elevated risk of HIV acquisition among HIV-negative women and of forward HIV transmission to male sex partners among women living with HIV (adjusted hazard ratios of 1.69 and 3.17, respectively), potentially by eliciting genital inflammation in women with BV and their male sex partners. BV is also highly prevalent among women in sub-Saharan Africa, suggesting that BV treatment may have potential as an HIV prevention strategy. BV is typically treated with antibiotics but recurrence rates are high, possibly because treatment does not directly promote Lactobacillus growth. More recently, BV treatment strategies incorporating live biotherapeutic lactobacilli have led to sustained optimization of the vaginal microbiome and a decrease in inflammatory biomarkers previously associated with HIV susceptibility. Future studies are urgently needed to evaluate BV treatment strategies that can optimize the vaginal microbiome in the long term through colonization with H2 O2 -producing vaginal lactobacilli and to assess whether vaginal microbiota optimization is able to reduce the risk of HIV transmission.

Antagonistic activity of Lactiplantibacillus plantarum 6.2 extracted from cocoa fermentation and its supernatant on Gardnerella vaginalis.

Search for alternative methods for the treatment of bacterial vaginosis has been growing, and probiotics being among them. The most well-known probiotic microorganisms are lactobacilli, which are naturally present in the vaginal microenvironment. Cocoa fermentation is a source of lactic acid bacteria, with lactobacilli being the most prominent. The aim of this study was to evaluate the antagonistic activity of Lactiplantibacillus plantarum 6.2 a strain of lactobacilli isolated from cocoa fermentation, and its cell-free supernatant on Gardnerella vaginalis. It was shown that Lpb. plantarum 6.2 and its supernatant, used at three concentrations, i.e., 40, 20 and 10 mg/mL, have a strong antagonistic activity against G. vaginalis, with a probable action of proteinaceous bacteriocins; the activity was lost after heat treatment. The ability to exclude and displace G. vaginalis from the adhesion site to vaginal HMVII epithelial cells was also demonstrated by the lactobacilli and the supernatant, with the latter showing a bactericidal effect. Thus, the Lpb. plantarum 6.2 strain presents itself as a good probiotic with potential to be used not only as a therapeutic alternative for vaginosis but also as a complement to existing therapies.

[Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review].

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.

Probiotic lactobacilli in formulas and hygiene products for the health of the urogenital tract.

Lactobacilli are the predominant microorganisms of the healthy human vagina. A novel alternative for the prevention and treatment of female urogenital tract infections (UGTI) is the inclusion of these microorganisms as active pharmaceutical ingredients in probiotic formulas, and more recently in female hygienic products. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host." A list of requirements must be considered during the development of probiotic product/formula for the female urogenital tract (UGT). This review aims to resume the requirements, probiotic characteristics, and clinical trial applied to determine the effect of probiotic and potentially probiotic strains on different woman's physiological and pathological conditions, and in preterm birth prevention. A revision of female hygienic products available in the world market is included, together with novel studies applying nanotechnology for Lactobacillus incorporation in hygienic products. Further studies and well-designed clinical trials are urgently required to complement the current knowledge and applications of probiotics in the female UGT. The use of probiotic formulas and products will improve and restore the ecological equilibrium of the UGT microbiome to prevent and treat UGTI in women under different conditions.

Lactobacillus plantarum Lp62 exerts probiotic effects against Gardnerella vaginalis ATCC 49154 in bacterial vaginosis.

The severe side-effects elicited by conventional antibiotic therapy and the recurrence of Bacterial vaginosis-associated bacteria and bacterial resistance have led to the development of novel alternative therapies, among which genital probiotics are widely used. In this study, we aimed to evaluate the antimicrobial activities of Lactobacillus plantarum Lp62 and its supernatant against Gardnerella vaginalis, using both in vitro and in vivo approaches. In vitro assays were used to evaluate the viability of the strain and the antimicrobial activities of the supernatant in different pH ranges. An in vivo assay was performed on female BALB/c mice, wherein the animals were divided into eight groups: four control groups and four treated groups (for curative and preventive therapies). After infecting and treating the mice, the animals were killed to quantify the bacterial load using qPCR, evaluate leucocyte cellular response, determine vaginal cytokine levels and perform cytokine tissue gene expression. Our analyses revealed significant activity of the strain and its supernatant against G. vaginalis. Preliminary in vitro tests showed that the strain grew with equal efficiency in different pH ranges. Meanwhile, the presence of halo and inhibition of pathogen growth established the significant activity of the supernatant against G. vaginalis. We observed that both micro-organisms are resident bacteria of mouse microbiota and that the lactobacilli population growth was affected by G. vaginalis and vice versa. We also observed that the treated groups, with their low bacterial load, absence of leucocyte recruitment, reduced cytokine levels in the vaginal lavage and normalized cytokine gene expression, successfully controlled the infection.

The reproductive tract microbiota in pregnancy.

The reproductive tract microbiota plays a crucial role in maintenance of normal pregnancy and influences reproductive outcomes. Microbe-host interactions in pregnancy remain poorly understood and their role in shaping immune modulation is still being uncovered. In this review, we describe the composition of vaginal microbial communities in the reproductive tract and their association with reproductive outcomes. We also consider strategies for manipulating microbiota composition by using live biotherapeutics, selective eradication of pathogenic bacteria with antibiotics and vaginal microbiota transplantation. Finally, future developments in this field and the need for mechanistic studies to explore the functional significance of reproductive tract microbial communities are highlighted.

Microbial mismanagement: how inadequate treatments for vaginal dysbiosis drive the HIV epidemic in women.

Women and girls represent a key population driving new HIV infections and persistence of the HIV pandemic. A key determinant of HIV susceptibility is the composition of the vaginal microbiome, which can influence the local immune cell population, inflammation status, and HIV prevention drug levels. While a low-diversity composition dominated by Lactobacillus crispatus is associated with a decreased risk of HIV acquisition, high diversity environments associated with bacterial vaginosis increase risk of HIV. Given the important role of the vaginal microbiome in determining HIV susceptibility, altering the microbiome towards a Lactobacillus-dominated state is an attractive complementary strategy to reduce HIV incidence rates. Here, we provide an overview of the mechanisms by which the vaginal microbiome may contribute to HIV acquisition risk. Furthermore, we address the advantages and limitations of historical treatments and emerging technologies under investigation to modify the vaginal microbiome, including: antibiotics, bacteriophages, probiotics, topicals, and engineered bacteria. By addressing the current state of vaginal microbiome knowledge and strategies for manipulation, we hope to amplify the growing calls for increased resources and research into vaginal microbial health, which will be essential to accelerating preventative efforts amongst the world's most vulnerable populations.

Perspectives on Existing and Novel Alternative Intravaginal Probiotic Delivery Methods in the Context of Bacterial Vaginosis Infection.

Bacterial vaginosis (BV) is one of the most common vaginal infections that affects hundreds of millions of women of reproductive age, worldwide. Traditional treatment strategies, such as oral and topical antibiotics, have shown efficacy against BV, but frequent recurrence of infection and the development of antibiotic-resistant bacteria remain as significant challenges. Alternatively, recent progress in understanding immune, microbiological, and metabolic interactions in the vaginal microbiota has prompted the consideration of administering probiotic organisms to restore and maintain vaginal health within the context of BV prevention and treatment. Given this, the objective of this review is to discuss existing and potential alternative approaches to deliver, and to potentially sustain the delivery of probiotics, to prevent and/or treat BV infections. First, a brief overview is provided regarding the probiotic species and combinatorial probiotic strategies that have shown promise in the treatment of BV and in restoring female reproductive health. Additionally, the advantages and challenges associated with current oral and intravaginal probiotic delivery platforms are discussed. Lastly, we present emerging and promising alternative dosage forms, such as electrospun fibers and 3D bioprinted scaffolds, that may be adapted as new strategies to intravaginally deliver probiotic organisms. Graphical abstract.

Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review.

The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.

Dysbiosis of the rat vagina is efficiently rescued by vaginal microbiota transplantation or probiotic combination.

Vaginal dysbiosis is characterised by a disturbed vaginal microbiota and is associated with various gynaecological diseases. Owing to its high recurrence rate, there is an urgent need for the development of effective therapeutic agents. In the present study, a vaginal dysbiosis model was developed to study the effect of vaginal microbiota transplantation (VMT) or probiotic combination (containing Lactobacillus helveticus, Lactobacillus crispatus, Lactobacillus acidophilus, Lactobacillus gasseri and Lactobacillus salivarius) on vaginal dysbiosis. Our results indicated that VMT or probiotic combination significantly reduced bacterial-induced inflammation (infiltration of neutrophils, lymphocytes and monocytes) in the uterine wall and the enrichment of pro-inflammatory cytokines [interleukin-1ß (IL-1ß) and tumour necrosis factor-alpha (TNFα)] in vaginal tissue, and restored the disturbed vaginal microbiota to normal levels (increased numbers of Lactobacillus and decreased numbers of Enterobacter and Enterococcus), thus it should be beneficial for avoiding the recurrence of vaginal dysbiosis. Therefore, VMT or probiotic combination might be an effective agent for the treatment of bacterial-induced vaginosis.

A clinical pilot study on the effect of the probiotic Lacticaseibacillus rhamnosus TOM 22.8 strain in women with vaginal dysbiosis.

Lactobacilli with probiotic features play an essential role in maintaining a balanced vaginal microbiota and their administration has been suggested for the treatment and prevention of vaginal dysbiosis. The present study was aimed to in vitro and in vivo investigate the probiotic potential of the Lacticaseibacillus rhamnosus TOM 22.8 strain, isolated from the vaginal ecosystem of a healthy woman. For this purpose, safety and functional properties were in depth evaluated. The strain exhibited a broad spectrum of antagonistic activity against vaginal pathogens; adhesion capacity to both the vaginal VK2/E6E7 and the intestinal Caco-2 cells; anti-inflammatory and antioxidant activities, suggesting its promising probiotic features. In addition, an in vivo pilot-study was planned. Based on both clinical and microbiological parameters, the oral or vaginal strain administration, determined a significant pathogens reduction after 10 days of administration and a maintenance of eubiosis up to 30 days after the end of the treatment. Therefore, the L. rhamnosus TOM 22.8 strain can be proposed as valuable oral and/or vaginal treatment for vaginal dysbiosis.

Non-antibiotic treatment of bacterial vaginosis-a systematic review.

PURPOSE: Bacterial vaginosis (BV) is one of the most common vaginal complaints of women of reproductive age, characterized by a shift from a Lactobacillus-dominated vaginal microbiome towards a more diverse flora of facultative and obligately anaerobic bacteria. BV can increase the risk of preterm births, contracting sexually transmitted infections and developing other chronic health issues. Standard treatment for BV are antibiotics, however despite initial efficacy, they do not provide effective long-term treatment and recurrence or persistence prevention. This systematic review focuses on describing the current study situation and summarizing the newest data on the efficacy of alternative non-antibiotic options, namely probiotic products containing lactobacilli, lactic acid, sucrose gel, combination products with estriol, and supplementation of antibiotics. METHODS: We conducted a systematic literature search using the MEDLINE database and evaluated the 33 trials which met our inclusion criteria. CONCLUSION: The diverse study designs produced extremely varied outcomes, but so far the results are promising. Furthermore, these alternatives have shown little to no adverse effects and are consequently generally considered safe to use. In general, the results of this review warrant more thorough trials with larger cohort sizes to provide sufficient evidence for these alternatives to be a part of official treatment recommendations.

Connecting the Dots: Translating the Vaginal Microbiome Into a Drug.

A Lactobacillus-dominated vaginal microbiota (VMB) has been associated with health and considered an important host defense mechanism against urogenital infections. Conversely, depletion of lactobacilli and increased microbial diversity, amplifies the risk of adverse gynecologic and obstetric outcomes. A common clinical condition that exemplifies dysbiosis is bacterial vaginosis (BV). BV is currently treated with antibiotics, but frequently recurs, due in part to persistent dysbiosis and failure of lactobacilli to repopulate the vagina. New treatment options are needed to address BV. The VMB is relatively simple and optimally dominated by one or several species of Lactobacillus. Lactobacillus crispatus is strongly associated with vaginal health and depleted in dysbiosis. Replenishing the dysbiotic VMB with protective L. crispatus CTV-05 is a promising approach to prevent recurrent infections and improve women's health. Here we discuss confirmation of this approach with the microbiome-based biologic drug, LACTIN-V (L. crispatus CTV-05), focusing on prevention of BV recurrence.

Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review / 生物工程学报

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health.

Human vagina is colonised by a diverse array of microorganisms that make up the normal microbiota and mycobiota. Lactobacillus is the most frequently isolated microorganism from the healthy human vagina, this includes Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii. These vaginal lactobacilli have been touted to prevent invasion of pathogens by keeping their population in check. However, the disruption of vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis (BV), sexually transmitted infections (STIs), and vulvovaginal candidiasis (VVC). Predisposing factors such as menses, pregnancy, sexual practice, uncontrolled usage of antibiotics, and vaginal douching can alter the microbial community. Therefore, the composition of vaginal microbiota serves an important role in determining vagina health. Owing to their Generally Recognised as Safe (GRAS) status, lactobacilli have been widely utilised as one of the alternatives besides conventional antimicrobial treatment against vaginal pathogens for the prevention of chronic vaginitis and the restoration of vaginal ecosystem. In addition, the effectiveness of Lactobacillus as prophylaxis has also been well-founded in long-term administration. This review aimed to highlight the beneficial effects of lactobacilli derivatives (i.e. surface-active molecules) with anti-biofilm, antioxidant, pathogen-inhibition, and immunomodulation activities in developing remedies for vaginal infections. We also discuss the current challenges in the implementation of the use of lactobacilli derivatives in promotion of human health. In the current review, we intend to provide insights for the development of lactobacilli derivatives as a complementary or alternative medicine to conventional probiotic therapy in vaginal health.