In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide

Abstract

BackgroundHydrogen peroxide (H2O2) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H2O2 are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H2O2. Here we used conditions more like those in vivo to compare the effects of physiologically plausible concentrations of H2O2 and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli.MethodsAnaerobic cultures of seventeen species of BV-associated bacteria and four species of vaginal lactobacilli were exposed to H2O2, lactic acid, or acetic acid at pH 7.0 and pH 4.5. After two hours, the remaining viable bacteria were enumerated by growth on agar media plates. The effect of vaginal fluid (VF) on the microbicidal activities of H2O2 and lactic acid was also measured.ResultsPhysiological concentrations of H2O2 (< 100 μM) failed to inactivate any of the BV-associated bacteria tested, even in the presence of human myeloperoxidase (MPO) that increases the microbicidal activity of H2O2. At 10 mM, H2O2 inactivated all four species of vaginal lactobacilli but only one of seventeen species of BV-associated bacteria. Moreover, the addition of just 1% vaginal fluid (VF) blocked the microbicidal activity of 1 M H2O2. In contrast, lactic acid at physiological concentrations (55-111 mM) and pH (4.5) inactivated all the BV-associated bacteria tested, and had no detectable effect on the vaginal lactobacilli. Also, the addition of 10% VF did not block the microbicidal activity of lactic acid.ConclusionsUnder optimal, anaerobic growth conditions, physiological concentrations of lactic acid inactivated BV-associated bacteria without affecting vaginal lactobacilli, whereas physiological concentrations of H2O2 produced no detectable inactivation of either BV-associated bacteria or vaginal lactobacilli. Moreover, at very high concentrations, H2O2 was more toxic to vaginal lactobacilli than to BV-associated bacteria. On the basis of these in vitro observations, we conclude that lactic acid, not H2O2, is likely to suppress BV-associated bacteria in vivo.

Vaginal microbiome and sexually transmitted infections: an epidemiologic perspective

“…Furthermore, O'Hanlon et al presented compelling evidence suggesting that if measurements of vaginal secretions are made under hypoxic conditions that mimic the vagina, pH is lower and lactic acid concentrations are higher than in data previously reported under aerobic conditions (76). Lactic acid may also prove to be more effective than acidity alone in preventing overgrowth of bacteria and acquisition of sexually transmitted organisms (77,78). Under aerobic conditions, some lactobacilli can produce hydrogen peroxide (another inhibitor of anaerobes and other organisms), but little if any hydrogen peroxide is detectable in vaginal secretions due to the hypoxic environment and the high antioxidant capacity of vaginal secretions (78,79).…”

Genomic Comparisons of Lactobacillus crispatus and Lactobacillus iners Reveal Potential Ecological Drivers of Community Composition in the Vagina

“…Studies have shown that these communities can be divided into five different types, four of which are dominated by either Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri, or Lactobacillus jensenii (2). These four species are closely related and are thought to perform similar ecological functions in the vaginal environment (namely, the production of lactic acid) (3,4). Instances of cooccurrence among these species are rare, and temporal data have demonstrated that shifts in the dominant Lactobacillus are common (5), suggesting that the species compete for shared niche space in the vagina.…”

MIG1Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids

“…Weak organic acids (WOAs), primarily produced by anaerobic bacteria via fermentation of undigested complex carbohydrates, are among the most abundant metabolites found on mucosal surfaces and the lumen of the gut (16). Vaginal lactobacilli secrete large amounts of lactic acid (ϳ55 to 111 mM), concomitantly lowering the mucosal pH to ϳ4.5 (17,18). Short-chain fatty acids (SCFAs), such as acetic, propionic, and butyric acid, are produced by a large spectrum of GI bacteria and reach total concentrations of up to 140 mM (16,19).…”