Metronidazole treatment rapidly reduces genital inflammation through effects on bacterial vaginosis-associated bacteria rather than lactobacilli

Bacterial vaginosis (BV) causes genital inflammation and increases HIV risk, while a vaginal microbiome dominated by Lactobacillus species is associated with immune quiescence and relative HIV protection. BV treatment reduces genital inflammation, but it is unclear whether this is driven by a decrease in BV-associated bacteria or an increase in Lactobacillus species. We evaluated the short-term impact of standard BV treatment on genital immunology and the vaginal microbiota. Topical metronidazole treatment rapidly reduced vaginal levels of proinflammatory cytokines, chemokines, and soluble immune markers of epithelial barrier disruption. Although the vaginal microbiota shifted to dominance by L. iners or L. jensenii, this proportional shift was primarily driven by a 2-4 log10 fold reduction in BV-associated bacteria absolute abundance; BV treatment induced no change in the absolute abundance of L. crispatus or L. iners, and only minor (<1 log10 fold) increases in L. gasseri and L. jensenii that were not independently associated with reduced inflammation in multivariable models. Therefore, the profound genital immune benefits that are associated with Lactobacillus dominance following BV treatment were not directly attributable to an absolute increase in lactobacilli, but rather to the loss of BV-associated bacteria.