The female reproductive tract microbiotas, inflammation, and gynecological conditions: mechanisms, therapeutic advances, and future perspectives

The female reproductive tract (FRT), particularly the vagina, has traditionally been regarded as a sterile environment. However, it is now recognized that the vagina is a complex, dynamic ecosystem dominated by Lactobacillus species, which maintain internal homeostasis through acid production, competitive exclusion, and immune regulation. Microbial dysbiosis, characterized by a loss of Lactobacillus dominance, increased microbial diversity and overgrowth of pathogenic bacteria, triggers chronic low-grade inflammation by disrupting physical barriers, activating pattern recognition receptors (PRRs) and secreting pro-inflammatory metabolites. This links to various gynecological conditions, including bacterial vaginosis (BV), pelvic inflammatory disease (PID), persistent human papillomavirus (HPV) infection and cervical cancer, endometriosis, infertility, and poor outcomes of assisted reproductive technologies, as well as adverse pregnancy outcomes such as preterm birth. The microbiota of the FRT is shaped by the menstrual cycle, hormones, behavior, antibiotics, stress, and genetic factors throughout the life course. The development of microbiota-based diagnostic biomarkers and therapeutic interventions to promote female reproductive health is supported by elucidating the mechanisms of this axis, which also helps clarify the pathophysiology of these diseases.