Background: Bacterial vaginosis—a condition defined by a shift from Lactobacillus dominance to a polymicrobial, anaerobic bacterial community—increases the risk of acquiring sexually transmitted infections and other complications of the female reproductive tract. Antibiotic treatment frequently fails to return the microbiome to an optimal Lactobacillus-dominated state. No criteria currently exist to identify the patients likely to experience treatment failure. Objective: We sought to identify the pretreatment community signatures associated with treatment failure through 16S ribosomal RNA gene analysis. Study Design: Twenty-eight women who were enrolled in an oral metronidazole treatment trial of bacterial vaginosis were studied. Cervicovaginal lavage samples were collected before metronidazole treatment and at 7 and 30 days posttreatment. Cervicovaginal lavage DNA was amplified and sequenced using a paired-end, V4 region 2×150 MiSeq run. Results: Of the 28 women, 25% failed to clear bacterial vaginosis; 35.7% demonstrated a transient clearance, shifting to community-type 2 (Lactobacillus iners dominant) at visit 2 only; 7.1% demonstrated a delayed clearance, reaching community-type 2 at the final visit only; and 32.1% of patients experienced sustained bacterial vaginosis clearance. Examination of the community composition and structure demonstrated that both the richness and the evenness were significantly lower for the women who experienced sustained clearance, whereas the women who failed to clear bacterial vaginosis possessed the highest median levels of richness, evenness, and diversity pretreatment. Soluble immune factors in the lower reproductive tract improved significantly following a shift from community-type 4 to a Lactobacillus-dominant microbiome, with the samples categorized as community-type 2 possessing significantly higher levels of secretory leukocyte protease inhibitor, growth-regulated alpha protein, and macrophage inflammatory protein-3 and significantly lower levels of intercellular adhesion molecule-1. Although the shifts to Lactobacillus dominance improved the markers of mucosal tissue health, these gains were only temporary among the women who experienced recurrence. Conclusion: Assemblies of highly diverse microbiota are associated with the enhanced resilience of bacterial vaginosis to standard metronidazole treatment. These communities may be foundational to treatment resistance or simply an indication of a well-established community made possible by canonical biofilm-forming taxa. Future studies must target the transcriptional activity of these communities under the pressure of antibiotic treatment to resolve the mechanisms of their resistance.
Bibliographical noteFunding Information:
These studies were supported through funding to N.R.K. via grant number R01DK112254 from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, M.G. via grant numbers R01 AI145296 and R01 AI127463, and M.A. via grant number AI138718 01. The CONRAD 115 BV study was funded by an interagency agreement between the Centers for Disease Control and Prevention and the United States Agency for International Development through a cooperative agreement with CONRAD/Eastern Virginia Medical School (GPO-A-00-08-00005-00). The views of the authors do not necessarily represent those of the funding agencies; the funding agencies played no role in submission decision.
- bacterial vaginosis recurrence
- molecular bacterial vaginosis
- mucosal immunity
- vaginal microbiome