Theses and Dissertations at Montana State University (MSU)
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Item Human gut phages in health and disease(Montana State University - Bozeman, College of Letters & Science, 2018) Manrique Ronquillo, Maria del Pilar; Chairperson, Graduate Committee: Mark J. Young; Michael S. Dills and Mark J. Young were co-authors of the article, 'The human gut phage community and its implications for health and disease' in the journal 'Viruses' which is contained within this dissertation.; Benjamin Bolduc, Seth T. Walk, John van der Oost, Willem M. de Vos and Mark J. Young were co-authors of the article, 'Healthy human gut phageome' in the journal 'Proceedings of the National Academy of Sciences of the United States of America' which is contained within this dissertation.; Mark J. Young was a co-author of the article, 'Interactions of the healthy gut phage community (HGP) with the core gut bacterial community' submitted to the journal 'PLOS computational biology' which is contained within this dissertation.; Yifan Zhu, John van der Oost, Willem M. de Vos and Mark J. Young were co-authors of the article, 'Gut bacteriophages and fecal microbial transplantation outcome in subjects with metabolic syndrome' which is contained within this dissertation.; Seth T. Walk and Mark J. Young were co-authors of the article, 'Bacteriophage-enriched filtrates: a potential tool to modify the structure of the gut-associated bacterial community' which is contained within this dissertation.The human body is colonized by a diverse microbial community known as the human microbiota. Most of these microbes, reside in the human intestinal tract. The gut microbiota has coevolved with humans and has become essential for multiple physiological functions that range from digestion, to development of the immune system, protection for pathogens, and even behavior. The gut microbial community is primarily dominated by Bacteria and their viruses- bacteriophages (or phages for short). Even though our knowledge of the contribution of the former to human health is extensive, the role of bacteriophages in human health and disease has been explored considerably less. Study of bacteriophages in other microbial environments has highlighted their importance in influencing the structure and function of their host community. Therefore, understanding the role of bacteriophages in the human gut ecosystem, and overall, in human health, has become a focus of current research. The main overarching hypothesis of this thesis is that human gut bacteriophages contribute to human health. To test this hypothesis, viral metagenomic surveys of healthy and disease individuals, together with experiments in a gnotobiotic mouse model system were performed. A group of bacteriophages shared among healthy individuals and significantly depleted in individuals with IBD was identified. Moreover, a host reservoir for these phages was identified in the core gut bacterial community of healthy subjects. Study of phage dynamics during an FMT treatment in patients with metabolic syndrome further highlighted the association of bacteriophages with human health. Patients that showed significant clinical improvement harbored a richer community, and a community more similar to healthy donors than patients that did not respond to the treatment. Moreover, a set of potential phage biomarkers associated with health and treatment outcome were identified. Lastly, experiments in gnotobiotic mice demonstrated the ability of bacteriophage-enriched filtrates to modify the microbial community structure. This result highlights the potential use of bacteriophages to manipulate the human gut microbiota, and potentially restore human health.Item 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.Item Microbial studies of a high alpine water supply used for recreation(Montana State University - Bozeman, College of Agriculture, 1975) Stuart, Sidney Arthur