期刊
JOURNAL OF INFECTIOUS DISEASES
卷 224, 期 12, 页码 2094-2104出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab266
关键词
bacterial vaginosis; vaginal microbiota; metronidazole; chemokines; ectocervical transcriptome
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute for Allergy and Infectious Diseases
- National Center for Advancing Translational Sciences at the National Institutes of Health [R01 HD098977, R01 AI134367, U19 AI103461, P30 AI124414, UL1 TR002556]
- ORIP/OD [P51OD011132]
This study compared the vaginal microbiota and ectocervical transcriptome of BV patients before and after oral metronidazole therapy in Bronx, New York and Thika, Kenya. Significant differences in transcription associated with chemokine signaling and immune system process were already present at enrollment between responders and nonresponders. Responders had lower levels of CXCL9 at baseline and showed increased concentrations of CXCL9, CXCL10, and monocyte chemoattractant protein 1 during treatment compared to nonresponders.
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 alpha-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 x 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.
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