Disrupted Cervicovaginal Microbiota: Its Role in Chlamydia trachomatis Genital Infection and Associated Reproductive Outcomes.

Chlamydia trachomatis (CT) remains the most commonly reported bacterial sexually transmitted infection (STI) globally, with particularly high incidence among adolescents and young adults. In Europe, CT cases have continued to rise over the past decade, despite ongoing public health efforts in prevention and screening. Screening coverage, however, remains inconsistent across countries. CT infections are often asymptomatic, especially in women, yet can lead to serious CT-related reproductive complications if left untreated, including pelvic inflammatory disease (PID), tubal factor infertility, and ectopic pregnancy. Emerging evidence highlights the cervicovaginal microbiota as a key factor influencing susceptibility to STIs, including CT infection, its progression, and associated outcomes. A Lactobacillus-dominated microbiota, particularly L. crispatus, is well-known to be a protective factor against CT acquisition, whereas vaginal dysbiosis, characterized by a depletion of these species and an overgrowth of anaerobes, such as Gardnerella vaginalis, Atopobium vaginae, and Prevotella spp., has been linked to increased CT acquisition risk, reduced immune control, and impaired infection resolution. Interaction between microbial communities and host immunity may modulate whether CT infections spontaneously clear, persist, or progress into pathological conditions. This review explores the natural history of CT genital infection in women, emphasizing the role of cervicovaginal dysbiosis in disease progression and reproductive sequelae. By integrating current knowledge about resident cervicovaginal microbes, host-microbe interaction, and CT-related reproductive outcomes, we discuss how microbiota-targeted strategies, including probiotic or microbiome-modulating strategies, may complement current CT prevention, diagnosis, and treatment approaches.