The Neovaginal Microbiota, Symptoms, and Local Immune Correlates in Transfeminine Individuals with Penile Inversion Vaginoplasty

Transfeminine people (assigned male at birth) often undergo penile inversion vaginoplasty to create vulva, a clitoris and a vaginal canal (referred to as a neovagina). After vaginoplasty, transfeminine people frequently experience gynecological concerns but their etiology is unknown due to a lack of knowledge of the neovaginal microenvironment. We characterized neovaginal microbiota and cytokines in 47 transfeminine participants. Participants self-reported sexual behaviors and symptoms, enabling correlation with bacterial (16S rRNA) and immune profiles. Four distinct clusters of co-occurring bacteria with unique immune profiles were identified. One cluster, which included Fastidiosipila , Ezakiella , and Murdochiella , was abundant, stable, and correlated with lower cytokines. Conversely, another cluster containing Howardella , Parvimonas , Fusobacterium , and Lawsonella was linked to higher cytokines. Although Lactobacillus was detected, Lactobacillus -dominance was rare. These findings underscore the need for evidence-based clinical guidelines tailored to transfeminine gynecologic care, emphasizing the vital role of the neovaginal microbiome in symptom management and sexual health.