The vaginal microbiome: Associations with sexually transmitted infections and the mucosal immune response

A healthy vaginal microbiota is dominated by lactobacilli. Disturbance of the microbiological vaginal microbiota balance ("dysbiosis") is associated with an increased risk of acquisition of sexually transmitted infections including HIV, and preterm birth in pregnant women. Since 2002, studies have used molecular methods to investigate the complex relationship between vaginal microbiota and vaginal health. This thesis first reviews the findings of these studies. Furthermore, it describes original studies that explore the association between vaginal microbiota composition and demographic, behavioural, clinical, and proteomic correlates in women from Sub-Saharan Africa. Rwandan female sex workers with a L. crispatus-dominated microbiota had the lowest prevalence of viral STIs including HIV, and the prevalence of viral STIs increased with increasing bacterial diversity (L. iners-dominated microbiota, moderate dysbiosis, and severe dysbiosis, respectively). Furthermore, dominance of Lactobacillus spp. was associated with the lowest prevalence of genital HIV-1 shedding in HIV-positive Rwandan sex workers, and the lowest genital concentration of the pro-inflammatory cytokines interleukin 1 alpha and granulocyte colony stimulating factor in African women from several countries. Exploratory proteomic analyses (which characterises the full set of proteins in a sample) of cervicovaginal lavages similarly showed that women with dysbiosis had a protein profile that suggested pro-inflammatory changes to the mucosal barrier. It was concluded that moderate and severe dysbiosis of the vaginal microbiota are highly prevalent in women from Sub-Saharan Africa, and are strongly associated with the prevalence of HIV and other STIs, HIV shedding in the genital tract of HIV-positive women, and markers of mucosal inflammation and impaired mucosal barrier function.