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.