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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.