New TransBiota Studies Redefine Vaginal and Neovaginal Microbiome Health in Transgender Individuals

In two complementary studies published in Cell Reports (here and here), we report findings from the TransBiota study, an NIH-funded collaboration led by our group in partnership with Dr. Jessica Prodger at Western University (Canada). These studies provide the most comprehensive characterization to date of the vaginal and neovaginal microbiomes in transgender individuals and examine how microbial communities relate to symptoms and local immune responses.

The first study focuses on transmasculine individuals receiving sustained testosterone therapy. We show that fewer than 10% harbor Lactobacillus-dominant vaginal microbiota, a state traditionally considered “optimal” in cisgender women. Instead, most participants exhibit diverse, Lactobacillus-depleted communities that we classify into 11 newly defined transmasculine community state types (tmCSTs). Importantly, Lactobacillus dominance in this population was unexpectedly associated with vaginal odor and elevated inflammatory markers, while other common symptoms such as dryness and pain during sex showed no clear association with Lactobacillus status. These findings demonstrate that microbiome–symptom relationships in transmasculine individuals di>er fundamentally from those established in cisgender women and that clinical assumptions based on cis populations may not apply.

The second study examines the neovaginal microbiome of transfeminine individuals following penile inversion vaginoplasty. We find that the neovaginal microbiota more closely resembles penile skin microbiota than cisgender vaginal microbiota and is rarely dominated by Lactobacillus. Using 16S rRNA sequencing and immune profiling, we identify four distinct bacterial clusters with di>erent inflammatory signatures. Notably, one cluster characterized by Fastidiosipila, Ezakiella, and Murdochiella was stable over time and associated with lower inflammation, while other clusters were linked to elevated pro-inflammatory cytokines. These results help explain why standard diagnostic criteria and treatments for conditions such as bacterial vaginosis often fail in transfeminine patients.

Together, these studies demonstrate that there is no single “optimal” genital microbiome across genders or anatomical contexts. Instead, microbiome structure, host response, and symptoms are tightly linked to hormonal environment, tissue origin, and gender-a>irming medical care. The TransBiota findings highlight the urgent need for new, evidence-based clinical guidelines tailored specifically to transgender and gender-diverse individuals.

By centering transgender participants and integrating microbiome, immunologic, and symptom data, the TransBiota project provides a foundation for more inclusive, accurate, and e>ective approaches to genital health.

References

The neovaginal microbiota, symptoms, and local immune correlates in transfeminine individuals with penile inversion vaginoplasty.
Rojas-Vargas J, Wilcox H, Monari B, Gajer P, Zuanazzi D, Shouldice A, Parmar R, Haywood P, Tai V, Krakowsky Y, Potter E, Ravel J, Prodger JL.
Cell Rep. 2025 Dec 23; 44(12):116546. doi: 10.1016/j.celrep.2025.116546.

The vaginal microbiota, symptoms, and local immune correlates in transmasculine individuals using sustained testosterone therapy.
Monari B, Wilcox H, Haywood P, Gajer P, Rojas-Vargas J, Zuanazzi D, Rutt L, Shouldice A, Parmar R, Waetjen LE, Krakowsky Y, Potter E, Prodger JL, Ravel J.
Cell Rep. 2025 Dec 23; 44(12):116632. doi: 10.1016/j.celrep.2025.116632.