Differences in Vaginal Microbiota, Host Transcriptome, and Proteins in Women With Bacterial Vaginosis Are Associated With Metronidazole Treatment Response
Autor: | Jessica Atrio, Nelly Mugo, Tina L. Fiedler, Gregory K. Tharp, Jessica McWalters, Laurie R Ray, Tao Wang, Steven E. Bosinger, Jeanne M. Marrazzo, Kenneth Ngure, Sujatha Srinivasan, Joyce Serebrenik Sultan, Marla J. Keller, Rebecca Barnett, David N. Fredricks, Elizabeth Irungu, Betsy C. Herold, Richard Hunte, Kerry Murphy, Meighan Krows |
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Rok vydání: | 2021 |
Předmět: |
Adult
DNA Bacterial 0301 basic medicine Chemokine Adolescent Physiology Cervix Uteri Polymerase Chain Reaction Transcriptome Major Articles and Brief Reports 03 medical and health sciences 0302 clinical medicine Immune system Metronidazole RNA Ribosomal 16S medicine Humans Immunology and Allergy CXCL10 030212 general & internal medicine Microbiome Bacteria biology business.industry Microbiota Sequence Analysis DNA Vaginosis Bacterial Middle Aged medicine.disease Kenya Treatment Outcome 030104 developmental biology Infectious Diseases Vagina biology.protein Cytokines CXCL9 Female Bacterial vaginosis business medicine.drug |
Zdroj: | J Infect Dis |
ISSN: | 1537-6613 0022-1899 |
Popis: | 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. |
Databáze: | OpenAIRE |
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