Differences in Vaginal Microbiota, Host Transcriptome, and Proteins in Women With Bacterial Vaginosis Are Associated With Metronidazole Treatment Response
Joyce Serebrenik, Tao Wang, Richard Hunte, Sujatha Srinivasan, Jessica McWalters, Gregory K. Tharp, Steven E. Bosinger, Tina L. Fiedler, Jessica Atrio, Kerry Murphy, Rebecca Barnett, Laurie R Ray, Meighan Krows, David N. Fredricks, Elizabeth Irungu, Kenneth Ngure, Nelly Mugo, Jeanne Marrazzo, Marla J. Keller, Betsy C. Herold
Abstract
BACKGROUND: Bacterial vaginosis (BV) treatment failures and recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. METHODS: Women with BV (Bronx, New York and Thika, Kenya) received 7 days of oral metronidazole at enrollment (day 0) and underwent genital tract sampling of microbiome (16S ribosomal RNA gene sequencing), transcriptome (RNAseq), and immune mediator concentrations on day 0, 15, and 35. RESULTS: Bronx participants were more likely than Thika participants to clinically respond to metronidazole (19/20 vs 10/18, respectively, P = .0067) and by changes in microbiota composition and diversity. After dichotomizing the cohort into responders and nonresponders by change in α-diversity between day 35 and day 0, we identified that transcription differences associated with chemokine signaling (q = 0.002) and immune system process (q = 2.5 × 10-8) that differentiated responders from nonresponders were present at enrollment. Responders had significantly lower levels of CXCL9 in cervicovaginal lavage on day 0 (P < .007), and concentrations of CXCL9, CXCL10, and monocyte chemoattractant protein 1 increased significantly between day 0 and day 35 in responders vs nonresponders. CONCLUSIONS: Response to metronidazole is characterized by significant changes in chemokines and related transcripts, suggesting that treatments that promote these pathways may prove beneficial.