Defining the neovaginal microbiome after gender affirming vaginoplasty - Project Summary It is estimated that up to 0.6% of the US population is transgender, which describes someone whose gender identity is incompatible with their sex assigned at birth. Gender affirming medical care can include vaginoplasty, which is the surgical creation of a vulva and neovagina. Transgender women have increased odds of testing positive for sexually transmitted infections (STIs) including human immunodeficiency virus (HIV) compared to cisgender women, which is maintained after adjusting for high-risk behaviours, suggesting biological factors unique to the neovaginal microenvironment may contribute to this increased risk. Despite this, little is known about the neovaginal microenvironment, which could have important implications for both post- operative care and long-term mucosal health of people with neovaginas. The neovaginal microbiome is not well-defined, but typically has greater microbial diversity compared to the natal vaginal microbiome, and contains species that are more typically detected in the penile, intestinal and skin microbiomes. In cisgender women vaginal microbial dysbiosis has been linked to increased genital inflammation, gynecological symptoms, and an increased risk of acquisition of STIs including HIV, but it is unknown if the neovaginal microbiome has a similar impact on gynecological health. A major gap in knowledge is defining the optimal neovaginal microbiome, including an understanding of the colonization and stability, and relationship to gynecological health, which is vital for care of people with neovaginas. Indeed, current post-operative and long-term care recommendations differ greatly between surgical centers. In this proposal we will define the neovaginal microbiome in transgender women who have undergone (“post-op”) or are scheduled to undergo (“pre-op”) vaginoplasty, and investigate associations of the microbiome to genital inflammation and clinical outcomes including gynecological symptoms. This study will be the first to comprehensively profile the neovaginal microenvironment, which is critical to provide evidence-based care guidelines to people with neovaginas.