Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women (20-56 years old) undergoing gynecologic surgeries was measured.
Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries.
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants.
Project description:Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.
Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants. Suitable RNA was extracted from ten participants which were classified into two groups, the dryness and control groups, based on diagnosis of dryness by a nurse during gynecoligical examination.
Project description:Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilized proteomic, transcriptomic and metabolomic analyses to characterize biological features underlying BV in 405 African women and explored functional mechanisms using bacterial co-culturesin vitro. We identified five major vaginal microbiome groups, (L.crispatus(21%), L.iners(18%), any non-specific Lactobacillus species(9%), Gardnerella species .vaginalis(30%), or polymicrobial(22%)). Using multi-‘omics we show that BV associated epithelial disruption and mucosal inflammation are linked to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella.vaginalis, M.mulieris, and specific metabolites including imidazole propionate. Bacterial co-culturesExperiments in vitro confirmed that type strain G.vaginalis and, M.mulieris supernatants and, as well as, and imidazole propionate, directly affect epithelial barrier function and , accompanied by activation of mTOR pathways. These results establish the microbiome-mTOR axis as a central feature of epithelial dysfunction in BV.
Project description:Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilized proteomic, transcriptomic and metabolomic analyses to characterize biological features underlying BV in 405 African women and explored functional mechanisms using bacterial co-cultures in vitro. We identified five major vaginal microbiome groups, (L.crispatus(21%), L.iners(18%), any non-specific Lactobacillus species(9%), Gardnerella species .vaginalis(30%), or polymicrobial(22%)). Using multi-‘omics we show that BV associated epithelial disruption and mucosal inflammation are linked to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella.vaginalis, Mobiluncus mulieris, and specific metabolites including imidazole propionate. Bacterial co-culture experiments in vitro confirmed that type strain G.vaginalis and, M.mulieris supernatants as well as imidazole propionate, directly affect epithelial barrier function and are accompanied by activation of mTOR pathways. These results establish the microbiome-mTOR axis as a central feature of epithelial dysfunction in BV.