Host-microbe interactions characterized by gene expression of cervical adhesion molecules, cytokines, and growth factors define the recurrence of bacterial vaginosis

Abstract Bacterial vaginosis (BV) is a common vaginal condition with a high recurrence rate after treatment. In this longitudinal multi-omics study, we integrated cervical microbial metatranscriptomics, host transcriptomics, cytokine profiles, and behavioral data to investigate factors driving BV recurrence in women from Miami-Dade county (N24). Recurrence at 6 months occurred in 46% of participants after metronidazole treatment. Recurrence was preceded by increased transcriptional activity of Gardnerella and Fannyhessea, enriched for glycogen and maltose metabolism and iron scavenging. Host transcriptomic analysis of cervical tissue revealed reduced CEACAM5-7 expression and increased IL6 and EREG, indicating impaired epithelial integrity and persistent inflammation. Cytokine–gene correlations and Bayesian mediation models identified CEACAM7 as a key mediator linking inflammation and microbial activity to recurrence. Intravaginal practices further amplified risk. These findings uncover for the first time dynamic host–microbiome disruptions that persist after treatment and reveals new targets for diagnostic and therapeutic strategies to reduce BV recurrence.