Vaginal Microbiota and HIV Susceptibility

The composition of the vaginal microbiota can influence the transmission of pathogens such as HIV. Women colonised with optimal vaginal bacterial communities, typically dominated by beneficial Lactobacillus spp., have a decreased risk of acquiring and transmitting HIV compared to women colonised with non-optimal microbiota. A non-optimal vaginal microbiota is characterised by a depletion of beneficial Lactobacillus spp. and high relative abundance of non-beneficial bacterial species, as exemplified by bacterial vaginosis (BV), which is a common form of vaginal dysbiosis in women of reproductive age that occurs in up to 55% of women in sub-Saharan Africa where HIV predominates (McKinnon et al 2019 AIDS Res Hum Retroviruses 25(3)). Non-optimal vaginal microbiota increase local pro-inflammatory cytokines, recruit activated HIV target cells and disrupt cervicovaginal epithelial barrier integrity that together drive increased risk of HIV acquisition. While studies have described the association between the vaginal microbiota and increased susceptibility to HIV and sexually transmitted infections (STIs), relatively little is known about how the microbiota and its metabolites act on the epithelium to mediate this effect. Major distinguishing features of women colonised with optimal vaginal microbiota compared to women with BV is a dramatic increase in the levels of lactic acid and depletion of short chain fatty acids (SCFAs) suggesting a role for these metabolites as effector molecules of vaginal bacteria. Projects are available to determine the direct anti-HIV mechanism of vaginal microbiota metabolites, their immune modulatory and barrier promoting effects on cervicovaginal epithelial cells, and to examine the roles of key members of the vaginal bacterial community (Hearps et al 2017 Mucosal Immunol 10:1480; Chetwin et al 2019 Sci Rep 9:1917). These studies are underpinning an exciting program at the Burnet to advance strategies to treat and prevent genital inflammation and consequently susceptibility to HIV, other STIs as well adverse reproductive health outcomes.