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    Examining the potential role of biogenic amines in vaginal microbial ecology and gynecological health
    (Montana State University - Bozeman, College of Letters & Science, 2019) Borgogna, Joanna-Lynn Claire; Chairperson, Graduate Committee: Carl Yeoman; Carl J. Yeoman was a co-author of the article, 'The application of molecular methods towards an understanding of the role of the vaginal microbiome in health and disease' in the journal 'The human microbiome' which is contained within this thesis.; Michelle D. Shardell, Elisa K. Santori, Tiffanie M. Nelson, Jessica M. Rath, Elbert D. Glover, Jacques Ravel, Patti E. Gravitt, Carl J. Yeoman and Rebecca M. Brotman were co-authors of the article, 'The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis' in the journal 'British journal of obstetrics and gynecology' which is contained within this thesis.; Michelle D. Shardell, Carl J. Yeoman, Khalil G. Ghanem, Herlin Kadriu, Alexander V. Ulanov, Charlotte A. Gaydos, Justin Hardick, Courtney K. Robinson, Patrik M. Bavoil, Jacques Ravel, Rebecca M. Brotman and Susan Tuddenham were co-authors of the article, 'The association of Chlamydia trachomatis and Mycoplasma genitalium infection with the vaginal metabolome' submitted to the journal 'Scientific reports' which is contained within this thesis.; Savannah Gray, Elisa K. Santori, Ben Americus, Zhong Li, Alexander Ulanov, Jacques Ravel, Rebecca M. Brotman and Carl J. Yeoman were co-authors of the article, 'Biogenic amines affect the growth and lactic acid productin of vaginal Lactobacillus SPP.' which is contained within this thesis.
    Bacterial vaginosis is the most common vaginal disorder amongst reproductive-aged women affecting nearly 1/3 of all US women. Bacterial vaginosis is associated with an increased risk of adverse sexual and reproductive health outcomes including an increased sexually transmitted infection acquisition risk. Characteristic features of bacterial vaginosis include an increase in vaginal pH (>4.5) that is associated with a depletion of vaginal Lactobacillus spp., and replacement by various strict and facultative anaerobes. The depletion of Lactobacillus spp. is an important feature as the production of lactic acid by vaginal Lactobacillus species is considered the major barrier to infection. Women with bacterial vaginosis have reduced lactic acid and higher concentrations of biogenic amines. Biogenic amines may be important biomolecules bridging important microbiological and clinical characteristics that connect shifts in the vaginal microbiome to common features of bacterial vaginosis. Herein, we utilized 16S rRNA gene amplicon sequencing combined with metabolomics to evaluate the association between biogenic amines and the most prevalent bacterial (Chlamydia trachomatis) and viral (Human papillomavirus) sexually transmitted infection. We further assessed the effect of biogenic amines upon specific growth properties of vaginal lactobacilli. We observed that women who were HPV positive or had Chlamydia trachomatis mono- or Chlamydia trachomatis /Mycoplasma genitalium co-infection had higher concentrations of biogenic amines when compared to women who were uninfected. Growth assays demonstrated that biogenic amines adversely affected the growth of the major vaginal lactobacilli. Putrescine was associated with increased doubling times and longer lag times for all tested species, while cadaverine increased the doubling times of all except L. iners, Exposure to biogenic amines was generally associated with reduced production of lactic acid, Collectively, these data provide valuable evidence that biogenic amines negatively affect the growth of vaginal Lactobacillus species, in vitro, and are associated not only with bacterial vaginosis but also with HPV and C. trachomatis mono- and co-infection. Taken together, these data provide a more refined understanding of the potential impact of biogenic amines upon the vaginal microenvironment and increased susceptibility to bacterial vaginosis, vaginal dysbiosis, and bacterial and viral STIs.
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