Samaneh Mazinani, Mohammad Aghazadeh, Vahid Arefi, Sepehr Taghizadeh, Bahareh Mehramuz, Hossein Samadi Kafil
The maintenance of vaginal microbial homeostasis is essential for women's reproductive health, serving as a primary defense against genital tract infections. Disruption of this ecosystem (dysbiosis) is associated with chronic inflammation, recurrent infections, adverse pregnancy outcomes, and increased susceptibility to sexually transmitted infections. This comprehensive review examines the consequences of this disruption, addressing all categories of vaginal infections, including bacterial, viral, parasitic, and fungal. A specific focus is placed on Bacterial Vaginosis (BV), Vulvovaginal Candidiasis (VVC), and Trichomoniasis, which collectively account for approximately 70% of vaginitis cases. The article provides an integrated analysis structured across three critical dimensions: Microbial Pathogenesis, detailing the mechanisms of virulence, polymicrobial biofilm formation (eg, Gardnerella vaginalis), and the development of antimicrobial resistance (AMR); Host-Microbe-Immune Interface, which explores the chronic inflammatory state and the heightened susceptibility to ascending infections (PID) and viral coinfections (HPV, HIV); and Therapeutic Innovation. Concluding with a forward-looking perspective, we discuss emerging microbiota-targeted therapeutic approaches and the potential transition toward precision medicine, including CRISPR-based genomic editing, phage therapy, and nanomedicine, which represent promising avenues for future research and clinical translation. Overall, this review integrates current evidence on vaginal dysbiosis and microbiota-targeted therapies, providing a comprehensive perspective that may support future research and precision-based clinical management.