Recurrent bacterial vaginosis following metronidazole treatment is associated with microbiota richness at diagnosis.

ABSTRACT 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 patients likely to experience treatment failure. Objective(s) We sought to identify pre-treatment community signatures associated with treatment failure through 16S rRNA gene analysis. Study Design Twenty-eight women enrolled in an oral metronidazole treatment trial of BV were studied. Cervicovaginal lavage samples were collected prior to metronidazole treatment, and again at 7 and 30-days post-treatment. Cervicovaginal lavage DNA was amplified and sequenced using a paired-end, V4 region, 2x150 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, CT2) at visit 2 only; 7.1% demonstrated delayed clearance - reaching CT2 at the final visit only; and 32.1% of patients experienced sustained bacterial vaginosis clearance. Examination of community composition and structure demonstrated that both richness and evenness were significantly lower for women who sustained clearance, while women who failed to clear bacterial vaginosis possessed the highest median levels of richness, evenness, and diversity pre-treatment. Soluble immune factors in the lower reproductive improved significantly following a shift from CT4 to a Lactobacillus-dominant microbiome, with samples categorized as CT2 possessing significantly higher levels of SLPI, GROa, and MIP3a and significantly lower levels of ICAM-1. While shifts to Lactobacillus-dominance improved markers of mucosal tissue health, these gains were only temporary amongst women who experienced recurrence. Conclusions 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.