The risk of acquiring sexual transmitted infections (STI) including HIV is modulated by the vaginal microbiota. Women colonised with optimal vaginal bacterial communities, typically dominated by a beneficial Lactobacillus spp., have a decreased risk of acquiring and transmitting HIV compared to women colonised with ‘non-optimal” microbiota (i.e. bacterial vaginosis, BV), which promote subclinical genital inflammation driving increased HIV risk. BV is characterised by a depletion of Lactobacillus spp. and a high relative abundance or polymicrobial anaerobes. While studies have focused on the association between vaginal microbiota and HIV risk, relatively little is known about the role of microbiota metabolites in modifying the vaginal microbiome and environment to help protect against STIs including HIV. Major distinguishing features between women colonised with optimal vaginal microbiota compared to women with BV includes dramatically increased vaginal levels of lactic acid (~120 mM vs £20 mM), while short chain fatty acids are elevated in women with BV. Our working hypothesis is that lactic acid, produced by optimal lactobacilli, is a bioactive that plays a key role in preventing HIV/STI acquisition. Here, data will be presented demonstrating that lactic acid has potent bactericidal activity against BV-associated bacteria but not lactobacilli, in vivo and ex vivo HIV virucidal activity, and immune modulatory properties on cervicovaginal epithelium that reduces production of soluble pro-inflammatory mediators linked with increased HIV risk. RNAseq and meta-proteomics studies show that lactic acid directly promotes epithelial barrier function by upregulating intracellular junctional molecules that could prevent paracellular penetration of pathogens. These findings highlight the multifaceted properties of a vaginal microbiota metabolite and suggest potential use of lactic acid and/or lactic acid producing bacteria to optimise the vaginal environment and microbiome to promote sexual and reproductive health including their use as adjuncts to reduce acquisition of STIs including HIV.