Vaginal Microbiome Composition, Diversity and Dysbiosis: The ORCHiD Study

Background Vaginal dysbiosis may contribute to ovarian cancer (OC) outcomes, but comprehensive microbiome characterization remains limited. Here, we characterize the prevalence and predictors of vaginal microbiome dysbiosis among diverse OC patients in the US. Methods We performed 16S rRNA gene sequencing on vaginal samples from 132 OC patients recruited as part of the population-based ORCHiD study. We applied topic modeling using Latent Dirichlet Allocation (LDA), a computational approach for identifying latent microbial community patterns, to identify distinct microbial signatures representing co-occurring bacterial taxa. Results Widespread dysbiosis was observed with Lactobacillus detected in only 47.7% of patients. Topic modeling identified seven distinct microbial signatures from Lactobacillus -dominated to pathogenic communities. Patients ≥ 50 years showed significant anaerobic bacterial enrichment (log₂FC = 1.31, FDR q < 0.001). Striking racial disparities emerged: Non Hispanic-Black patients had 5-fold higher Actinomycetaceae prevalence (40.9% vs 8.2%, FDR q = 0.005), while protective L. crispatus was detected exclusively in Non Hispanic-White patients (6.4% vs 0%). Conclusions This study revealed widespread vaginal microbiome dysbiosis among OC patients with clinically significant age and racial patterns that may contribute to outcome disparities.