Project description:The vagina is an interactive interface with the environment, and as such is covered by a protective epithelial surface. This surface is colonized by bacteria and other microorganisms which, through a variety of mechanisms serve to further protect the host from invasion by pathogens. Alterations in the normal vaginal microflora, particularly those associated with bacterial vaginosis, are thought to contribute to risk of spontaneous pregnancy loss in the second trimester and spontaneous preterm birth. Additionally, alterations in the vaginal microbiome may increase the likelihood of transmission of certain agents including human immunodeficiency virus type 1 (HIV-1). There are physiologic alterations in host condition (e.g., menopause and pregnancy), which are beginning to be investigated as potential selective conditions for change in the "normal" flora, and their impact on disease susceptibility and transmission remains to be more definitively elucidated. The effects of chronically abnormal physiologic states (e.g., diabetes mellitus) on normal vaginal flora have not been well described or studied. Finally, an almost unexplored area of inquiry is the genetic contribution, including race/ethnicity, to the establishment and maintenance of a "normal" vaginal flora, under normal and physiologically altered circumstances. Our research will shed light on how the vaginal microbiome contributes to adverse obstetrical outcomes and sexually transmitted infections in diverse populations. This project addresses the following questions: First: Do the genes of the host contribute to the composition of the vaginal microbiome? We hypothesize that a woman's genetic composition significantly affects the ability of certain commensal, parasitic and pathogenic microbes to colonize and/or infect the genital tract. Thus, we will compare and quantify the microbial populations inhabiting the vaginas of monozygotic and dizygotic twins from the Mid Atlantic Twin Registry, and, in the process, address the question of whether there is a relationship between the microbiomes of the vagina, mouth and GI tract. Second: What changes in the vaginal microbiome are associated with common physiological perturbations or non-infectious pathological states of the host?We hypothesize that "altered" physiologic (pregnancy, menopause) and pathologic (chronic disease, hysterectomy) conditions, or environmental "exposures" (exogenous hormones, antibiotics, chronic immunosuppressant, smoking; douching) can predictably alter the vaginal microenvironment. These alterations will lead to changes in microbial populations within the vagina. Changes in the microbial populations may have impacts, positive or more likely negative, on the spontaneous and future well-being of the affected individual. We are characterizing the effects of these "altered" physiologic and pathologic conditions, and environmental exposures, on the composition of the vaginal microbiome. Third: What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions? We are testing the hypothesis that infectious diseases predictably alter the vaginal microbiome, and that these changes have an impact on the disease susceptibility, process, and outcome. A predilection for bacterial vaginosis, vaginitis, HIV infection, or other sexually transmitted diseases, is likely associated with a women's vaginal microbial composition. Thus, we will characterize samples from women with a variety of these infectious conditions to determine the contribution of their micriobiomes to the disease process and susceptibility. We are addressing these questions using a combination of high throughput 'nextgen' sequencing technologies, including the Roche 454 FLX and the upgraded Illumina Genome Analyzer II instruments currently installed in the Nucleic Acids Research Facilities at VCU. Thus, segments of the 16S rRNA genes will be amplified from the complex samples taken from various target sites in and around the vagina of each study participant. These segments will be sequenced and subjected to taxonomic classification protocols to identify and quantify the bacterial taxa present in each sample. Additionally, total DNA isolated from these samples will be subjected to shotgun sequence analysis to empirically reconstruct the metabolic potential of these microbiomes. Finally, specific bacterial clones will be completely sequenced and analyzed to associate the unavoidable strain and isolate diversity with the clinical phenotypes presented.

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Cervical cancer vaginal microbiome

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