Validation of probiotics as microbiome-targeted intervention for Vulvovaginal Candidiasis (VVC)

What was reviewed?

This paper reviewed the vaginal microbiota (VMB) and its relationship with vulvovaginal candidiasis (VVC), focusing on how disruptions in the vaginal microbial community contribute to the disease. It explored current antifungal treatment challenges, such as drug resistance and recurrence, and assessed emerging microbiome-based therapies including probiotics, postbiotics, synbiotics, and vaginal microbiota transplantation (VMT). The review synthesized findings from clinical trials, microbiome sequencing studies, and in vitro and animal research to evaluate how these interventions might restore vaginal microbial balance and improve VVC outcomes.

Who was reviewed?

The review drew on data from reproductive-age women, especially those affected by VVC or vaginal dysbiosis. It incorporated studies analyzing the vaginal microbial communities dominated by Lactobacillus species in healthy women versus dysbiotic communities associated with VVC. Clinical trials evaluating probiotic and postbiotic therapies and early-stage research on VMT were also included. The review highlighted key microbial signatures linked to vaginal health and infection, emphasizing the role of Candida species and the loss of protective Lactobacillus strains in disease progression.

Most important findings

The review identified that a healthy vaginal microbiota is dominated by Lactobacillus species, which produce lactic acid to maintain an acidic environment that suppresses Candida growth and modulates immune responses. Disruptions to this balance, through factors like antibiotics or hormonal changes, reduce Lactobacillus levels and raise vaginal pH, facilitating Candida overgrowth and VVC development. Conventional antifungal treatments face limitations due to resistance and recurrence. Probiotics, particularly Lactobacillus strains, demonstrated antifungal and immunomodulatory effects by competing with Candida, producing antimicrobial compounds, and supporting mucosal defenses. Postbiotics offer similar benefits without risks related to live microbes, while synbiotics enhance probiotic survival and activity. Vaginal microbiota transplantation is a promising but still experimental approach to restore microbial balance more effectively.

Greatest implications of this review

This review highlights the need to shift VVC management from solely antifungal drugs toward therapies that restore vaginal microbiota balance, aiming to reduce recurrence and drug resistance. Probiotics, postbiotics, synbiotics, and vaginal microbiota transplantation represent promising adjuncts or alternatives but require further high-quality clinical trials to confirm their safety, optimal protocols, and long-term efficacy. Integrating microbiome-focused treatments into clinical practice could improve patient outcomes by targeting the ecosystem dynamics underlying VVC rather than just the pathogen.

What was studied?

This study investigated the dual anti-Candida and anti-inflammatory effects of VAGINNE®, a fermentation broth derived from Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus jensenii, in treating vulvovaginal candidiasis (VVC). Using a controlled mouse model of Candida albicans-induced vaginal infection, the researchers examined the microbiome composition, cytokine levels, and tissue integrity following treatment with VAGINNE® compared to a standard antifungal agent (nystatin) and untreated controls.

Who was studied?

The experimental subjects were female BALB/c mice, aged seven weeks. The researchers inoculated the mice with Candida albicans to mimic human VVC and then divided them into four groups: a healthy control group, an infected group, a nystatin-treated group, and a group treated with VAGINNE®. They conducted microbiological, immunological, and histological analyses on vaginal lavage samples, plasma, and vaginal tissues.

Most Important Findings

VAGINNE® demonstrated a dual mechanism of action in combating Candida albicans. It significantly reduced the fungal burden in the vagina (from 1.67 × 10⁷ CFU/mL in infected controls to 6.15 × 10⁶ CFU/mL) and simultaneously restored beneficial Lactobacillus populations, reaching 1.19 × 10⁸ CFU/mL compared to just 1.20 × 10⁷ CFU/mL in infected animals. Histologically, mice treated with VAGINNE® exhibited preserved vaginal epithelial structure and reduced tissue invasion by fungal hyphae. Immunologically, VAGINNE® decreased levels of key proinflammatory cytokines associated with Th17-mediated immunity. Specifically, IL-17A, IL-22, and IL-23 were significantly reduced in vaginal tissues, while systemic inflammation markers IL-6 and IL-1β were also suppressed in plasma. These cytokines are crucial in fungal immunity but also contribute to excessive inflammation and tissue damage in VVC.

Thus, VAGINNE® not only restored microbiome balance and modulated the immune response, reducing local and systemic inflammation. This combination of microbial suppression and immune regulation reflects a targeted and multifaceted therapeutic strategy, contrasting the fungistatic nature of conventional azoles, which often leads to recurrence and resistance.

Greatest Implications of the Study

This study offers compelling evidence that microbiome-modulating therapies, particularly those using Lactobacillus-derived products, can effectively treat vulvovaginal candidiasis through both antifungal and anti-inflammatory mechanisms. VAGINNE® holds promise as a probiotic-based alternative to azole antifungals, especially in light of increasing drug resistance and recurrence rates in VVC. By promoting Lactobacillus regrowth, reducing fungal load, and downregulating cytokine-driven inflammation, VAGINNE® could support a paradigm shift in VVC management toward microbiome-friendly interventions. However, further clinical trials in human populations are necessary to confirm its safety and efficacy before widespread application.

What was reviewed?

This review analyzed existing knowledge of vaginal microbiota (VMB) in relation to vaginal health and recurrent vulvovaginal infections (RVVI), focusing specifically on bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis (TV). The authors critically assessed current insights derived from advanced molecular techniques, highlighting how both bacterial and fungal communities influence vaginal health, and discussed the interactions among these communities and their role in the pathogenesis of recurrent infections.

Who was reviewed?

This critical review evaluated literature from diverse sources, including peer-reviewed studies identified through databases such as PubMed and Google Scholar. Included were studies employing both culture-dependent and culture-independent methods to characterize vaginal microbial communities in healthy women and those suffering from recurrent vaginal infections, including bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis.

What were the most important findings?

The review highlights the complexity and variability of vaginal microbiota, challenging the traditional view that Lactobacillus dominance universally signifies vaginal health. While Lactobacilli typically protect vaginal health by producing lactic acid, maintaining acidic conditions that prevent infections, certain species such as L. iners can instead contribute to instability and disease susceptibility. In bacterial vaginosis, reduced Lactobacilli and increased anaerobes, especially Gardnerella vaginalis, play a critical role. G. vaginalis contributes significantly to disease through biofilm formation and secretion of virulence factors, including vaginolysin and sialidases.

For vulvovaginal candidiasis and trichomoniasis, microbial interactions are key determinants of disease progression. Candida albicans, usually harmless in its yeast form, can shift to a pathogenic hyphal state under elevated pH or disrupted microbiota, highlighting crucial interactions between bacteria and fungi in maintaining health. In trichomoniasis, Trichomonas vaginalis actively damages vaginal epithelial cells and suppresses beneficial Lactobacilli through mechanisms including protease secretion and biofilm formation, exacerbated by symbiotic interactions with mycoplasmas and dsRNA viruses that further enhance virulence.

What are the greatest implications of this review?

This review stresses the importance of understanding individual variability and complex interactions within the vaginal microbiota when managing recurrent vulvovaginal infections. It emphasizes that traditional beliefs, such as universal Lactobacillus dominance indicating vaginal health, are oversimplifications. This knowledge demands that clinicians adopt more nuanced diagnostics and personalized approaches to treatment. Furthermore, the authors highlight critical gaps in our understanding of the fungal and parasitic components of the vaginal microbiota, suggesting a need for further research utilizing comparative genomics and longitudinal microbiome profiling to guide improved clinical management strategies for RVVI.