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Item Diet-induced alterations to postprandial metabolism and the gut microbiota(Montana State University - Bozeman, The Graduate School, 2022) Wilson, Stephanie Michelle-Gandia; Chairperson, Graduate Committee: Mary P. Miles; This is a manuscript style paper that includes co-authored chapters.Obesity is a key component of a cluster of metabolic risk factors for chronic disease which include dyslipidemia, hyperglycemia, and hypertension. Stark changes in diet and lifestyle contribute to growing metabolic disorder prevalence. Many Americans regularly consume foods low in fiber and rich in fat and sugar, which can negatively influence glucose and lipid metabolism over time. A nutritionally poor diet exerts deleterious effects on the gastrointestinal microbial community which has larger host health implications. As a modifiable risk factor, diet can be part of the solution to counter the rise of chronic disease. However, dietary responses as it pertains to glucose and lipid metabolism display high interindividual variability. This interindividual variability with diet can also be observed at the microbial level in our gastrointestinal system. In metabolically at-risk adults, we examined postprandial responses and the efficacy of a long-term lentil dietary intervention in improving postprandial glycemic responses. We further assessed the effect of an antioxidant-rich juice from the Aronia melanocarpa berry and its anti-inflammatory potential against a high fat diet in a gnotobiotic mouse model to evaluate how specific gut microbial communities transferred from metabolically at-risk adults with different inflammatory profiles may impact dietary responses. Postprandial triglyceride responses in adults with overweight and obesity can be partially explained by central adiposity, insulin resistance, and the ability to switch between glucose and fat metabolism to a metabolic stress. A long-term dietary intervention with lentils, a fiber-rich pulse crop, worked in a dose-dependent manner to reduce insulin resistance in adults with increased central adiposity without an increase in gastrointestinal symptoms, a common deterrent to incorporating fiber-foods in the diet. Our gnotobiotic mouse experiments revealed donor- dependent changes in dietary responses. We observed protective effects of Aronia juice in mice, particularly in mice from the low inflammation stool donor. Metabolomic changes in phospholipids such as phosphatidylcholine and sphingomyelin were further detected, with changes respectively unique to Aronia juice and high-fat diet. Taken together, this dissertation provides an improved understanding of our metabolic responses and microbial alterations to the foods we consume, and how these responses influence the progression of metabolic diseases.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 Managing antipsychotic induced metabolic syndrome to improve treatment adherence and quality of life in Gallatin County(Montana State University - Bozeman, College of Nursing, 2015) Frye, Shelby Leigh; Chairperson, Graduate Committee: Laura LarssonAtypical antipsychotics are prescribed for patients suffering from serious mental illnesses. As these medications have become more widely used over the past 3 decades, practitioners have started to become more aware of metabolic side effects caused by them. Metabolic syndrome is a term for alterations in baseline metabolic functioning which result in weight gain, hyperlipidemia, hypertension, insulin resistance, diabetes, and cardiovascular disease. A correlation between obesity and mortality exists within the population of individuals diagnosed with a severe mental illness taking atypical antipsychotics and has been reported as responsible for decreased life expectancy of up to 30 years. However, monitoring the physical side effects has been a significant barrier to successful management for these patients, often due to unclear practice direction between psychiatric and primary care providers. Many patients with metabolic syndrome experience exacerbations in their mental illness such as increased depression, anxiety, and isolation related to discomfort and decreased self-esteem, which can lead to medication nonadherence causing further complications. Patients experiencing emotional decline may be unable to participate in necessary lifestyle modifications without assistance, leading to the progression of metabolic syndrome. Such health related spirals contribute to the development of treatment resistance and poor patient outcomes. At the Gallatin Mental Health Center in Bozeman, MT, 23 patients taking atypical antipsychotics were provided a qualitative satisfaction survey about medications, treatment plans, and adherence, in addition to being offered an opportunity to make recommendations that could improve their overall health. In accordance with research and successful interventions internationally, a significant number of the patients in Bozeman have experienced metabolic changes, have difficulty remembering or understanding treatment goals, and would like assistance with lifestyle interventions. Using evidence based research and recommendations for metabolic syndrome prevention assessments and interventions a physical health assessment checklist for psychiatric nurses at Gallatin Mental Health was created. An assessment key to assist the nurse with the checklist, a prefabricated order set of interventions, and a simple care plan to guide best practice policy implementation will provide for better treatment adherence and improved quality of life for patients taking atypical antipsychotics in Gallatin County.