Project description:The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
Project description:Bacterial vaginosis (BV) treatment failures or recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. Response to metronidazole is characterized by significant changes in chemokines and related transcripts suggesting that strategies to promote these pathways may prove beneficial.
Project description:Use of hormonal contraceptives (HC) could alter the bacterial community, immune response and epithelial barrier integrity of the female genital tract (FGT) mucosal environment, leading to increased susceptibility to sexually transmitted infections (STIs), including HIV. Here, we tested whether use of three types of HCs, injectable Net-En, combined oral contraceptives (COC) and NuvaRing, a combined contraceptive vaginal ring (CCVR), led to distinct patterns in FGT host transcriptomics transcriptome in South African adolescent females. In an intention-to-treat analysis, we observed few changes in endocervical gene expression in the Net-En and COC groups. Relative to the COC and Net-En arms, samples from the CCVR arm had significant elevation of transcriptional networks driven by IL-6, IL-1 and NFKB, and lower expression of genes supporting epithelial barrier integrity. An integrated multivariate analysis of the cervicovaginal microbiome, transcriptome and cytokines demonstrated that networks of microbial dysbiosis and inflammation accurately discriminated the CCVR arm from the other contraceptive groups, while genes involved in epithelial cell differentiation were predictive of the Net-En and COC arms.
