A new article published in the Journal of Reproductive Immunology reported that Mycoplasma genitalium is a sexually transmitted infection (STI) that causes pelvic inflammatory disease (PID) in women, among other complications. Meanwhile, Chlamydia trachomatis is an STI that can lead to infertility in women. The authors discussed that both C. trachomatis and M. genitalium have similar clinical aspects. Potential factors for pathogeneses of C. trachomatis and M. genitalium infections are preexisting vaginal microbiome and other STIs. The healthy vaginal microbiome, dominated by Lactobacillus spp, protects the host against invading bacteria like C. trachomatis and M. genitalium by producing antibacterial compounds and providing a mechanical barrier. Meanwhile, dysbiosis in the vagina is described as a non-Lactobacillus dominated microbiome or bacterial vaginosis (BV). Thus, BV and its associated bacteria play a major role in the pathogenesis of STIs such as C. trachomatis and M. genitalium. Additionally, different species of BV-associated bacteria have distinct characteristics that have a part in C. trachomatis and M. genitalium infections. Furthermore, host factors could be implicated in the interaction between C. trachomatis and M. genitalium, and the microbiome. It was stated that another important factor which should be considered is the hormonal homeostasis - oral hormonal contraception influences the vaginal milieu and could influence the infection process of STIs.