Theses and Dissertations at Montana State University (MSU)
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Item Improving small bowel visualization during Video Capsule Endoscopy (VCE): quality improvement initiative(Montana State University - Bozeman, College of Nursing, 2024) Foster, Nicole Marie; Chairperson, Graduate Committee: Molly Secor; This is a manuscript style paper that includes co-authored chapters.Background: This practice improvement project addresses the clinical challenge of suboptimal small bowel visualization during Video Capsule Endoscopy (VCE) procedures, focusing on its local manifestation at a gastroenterology clinic in urban Indiana and proposing interventions (Deding et al., 2023a). Previous studies support the use of polyethylene glycol (PEG) solutions and staff education to improve small bowel visualization, highlighting the importance of standardized protocols and continuous training (Klein et al., 2016; Deding et al., 2022a). Problem: The clinical problem stems from inconsistent bowel preparations and prolonged capsule excretion times, potentially leading to delayed diagnoses and compromised patient care (Deding et al., 2023a). Through a comprehensive literature review and the application of the Johns Hopkins Model as a conceptual framework (Moen et al., 2022a; Bjoersum-Meyer et al., 2021). The aim was to enhance small bowel visualization during VCE procedures by implementing evidence-based strategies. Methods: Methods involved assessing the context, implementing interventions, measuring outcomes, and analyzing data. Results indicated improvements in bowel preparation quality and capsule excretion times following intervention implementation (Deding et al., 2023a). Results: Key findings suggest that standardized protocols and continuous staff education are essential for achieving optimal small bowel visualization during VCE procedures (Bjoersum-Meyer et al., 2021). Conclusions: The Johns Hopkins Model guided the development, implementation, and evaluation of interventions, emphasizing systematic quality improvement processes (Moen et al., 2022a). The project's goal was to improve the quality of small bowel visualization through staff education, protocol adjustments, and process standardization at the gastroenterology clinic in urban Indiana.Item Omics approaches identify molecular mechanisms of arsenic-microbial interactions(Montana State University - Bozeman, College of Letters & Science, 2019) Rawle, Rachel Anna; Chairperson, Graduate Committee: Timothy R. McDermott and Brian Bothner (co-chair); Yoon-Suk Kang, Brian Bothner, Gejiao Wang and Timothy R. McDermott were co-authors of the article, 'Transcriptomics analysis defines global cellular response of Agrobacterium tumefaciens 5A to arsenite exposure regulated through the histidine kinases phor and aios' in the journal 'Environmental microbiology' which is contained within this dissertation.; Monika Tokmina-Lukaszewska, Zunji Shi, Brian Tripet, Fang Dang, Timothy R. McDermott, Valerie Copie, Gejiao Wang and Brian Bothner were co-authors of the article, 'Metabolic responses to arsenite exposure regulated through histidine kinases phor and aios in Agrobacterium tumefaciens 5A' submitted to the journal 'Environmental microbiology' which is contained within this dissertation.Arsenic is a class I carcinogen and causes various cancers and diseases. Its toxicity, prevalence, and potential for human exposure has classified arsenic as the number one environmental toxin according to the Environmental Protection Agency. Contamination of groundwater and soil leads to over 200 million human exposures above the health limit. In every environment where arsenic and microbes coexist, microbes are the principal drivers of arsenic speciation, which is directly related to bioavailability, toxicity, and bioaccumulation. These speciation events drive arsenic behavior in the soil, water, and as recent data suggests, human-associated microbiomes. This dissertation details arsenic-microbial interactions through an omics platform, utilizing transcriptomics, metabolomics, and proteomics profiling as a way to globally assess the impacts of arsenic exposure. This work followed two main aims: (1) characterize cell metabolism during arsenic exposure in soil bacterium Agrobacterium tumefaciens 5A, a model organism for arsenite oxidation, and (2) assess the impacts of specific arsenic-processing bacteria within the gut microbiome of mammals. The results of this work provide a foundational understanding for how arsenic speciation events are regulated and how they affect nutrient cycling in environmental systems, which is necessary for bioremediation and health initiatives.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 Investigating arsenic-microbiome interactions in the gut using murine models(Montana State University - Bozeman, College of Letters & Science, 2019) Coryell, Michael Philip; Chairperson, Graduate Committee: Seth Walk; B. A. Roggenbeck and Seth T. Walk were co-authors of the article, 'The human gut microbiome's influence on arsenic toxicity' submitted to the journal 'Current pharmacology reports' which is contained within this thesis.; M. McAlpine, N.V. Pinkham, T.R. McDermott and Seth T. Walk were co-authors of the article, 'The gut microbiome is required for full protection against acute arsenic toxicity in mouse models' in the journal 'Nature communications' which is contained within this thesis.; M. Yoshinaga, T.R. McDermott and Seth T. Walk were co-authors of the article, 'Speciation of excreted arsenicals from germ free and conventional AS3MT knockout mice exposed to inorganic arsenate' which is contained within this thesis.Drinking water contamination with arsenic is a wide-spread public health concern, potentially affecting over 140 million people across at least 40 different countries. Current understanding of biological and behavioral factors influencing clinical outcomes is insufficient to explain the variation observed in arsenic-related disease prevalence and severity. The intestinal microbiome in humans is a dynamic and active ecosystem with demonstrated potential to mediate arsenic metabolism in vitro and distinct variability between individuals. This dissertation investigates arsenic-microbiome interactions, with a focus on determining how microbiome activity influences host-response and toxicity from arsenic exposures. Chapter 2 overviews common exposure routes, important metabolic pathways, and current evidence of arsenic-microbiome interactions in humans or experimental animal models. Chapter 3, the initial approach was to experimentally perturb the microbiome of common laboratory mice during arsenic exposure, measuring arsenic excretion in the stool and accumulation in host tissues. Arsenic sensitive gene-knockout mice were used to determine the microbiome's influence on subacute arsenic-induced mortality. Disrupting microbiome function--first by antibiotic treatment, then by deriving mice germ free--dramatically reduced survival times during severe arsenic exposures. Transplantation of human fecal communities into germ free mice effectively complemented the loss of function from microbiome disruption in these mice. Chapter 4 examines microbiome's impact on arsenic metabolism in germ free and conventional mice from this same arsenic-sensitive genetic background. These mice are deficient for the primary metabolic pathway involved in arsenic detoxification in both humans and mice, facilitating a more complete experimental isolation of microbiome and host metabolisms. This study provides evidence of microbiome-dependent changes in the elimination routes and metabolic transformation of ingested arsenic and provides a new experimental model for studying arsenic metabolism in the gut.Item Validating Salmonella typhimurium virulence modulation by ecto-5'-nucleotidase (CD73) in intestinal epithelial cells(Montana State University - Bozeman, College of Letters & Science, 2017) Schneider, Stephanie Lorain; Chairperson, Graduate Committee: Douglas KominskyExtracellular ATP is a pro-inflammatory molecule released during intestinal insult and must be converted to adenosine by ecto-5'-nucleotidase (CD73) for the resolution of intestinal inflammation [1]. Along with its anti-inflammatory role in the intestinal mucosa, CD73-generated adenosine contributes to host-microbe interactions at the mucosal surface by modulating pathogen replication and virulence, including that of Salmonella enterica serovar Typhimurium (S. Typhimurium) [2], [3]. It has been shown, in the absence of intestinal epithelial cell-specific CD73, S. Typhimurium virulence is attenuated in vivo and in vitro, implicating the intestinal epithelium as an underappreciated source for the development of novel antimicrobial therapies. Since direct modulation of extracellular adenosine leads to pleiotropic effects, the aim of this research was to determine the mechanism(s) of S. Typhimurium virulence modulation by CD73 in intestinal epithelial cells to identify specific molecular targets that modulate pathogenesis [4], [5]Item The human intestinal organoid as a model system for enteropathogenic Escherichia coli pathogenesis(Montana State University - Bozeman, College of Letters & Science, 2015) Olshefsky, Stephen Christopher (Skip); Chairperson, Graduate Committee: Seth WalkEscherichia coli are Gram-negative, facultative anaerobic bacteria commonly found in the intestine of humans and warm-blooded animals. E. coli can be mutualistic or pathogenic that cause diarrheal disease (diarrheagenic E. coli, DEC). The colonization of E. coli begins with the successful adherence to intestinal epithelial cell (IECs); which is mediated by a variety of colonization factors on the bacterial cell surface. This is the first and most crucial step for E. coli colonization. Therefore, valuable model systems to study E. coli should recapitulate this adherence. Several model systems have been developed and successful reproduce adherence and other important aspects of EPEC pathogenesis, but have significant limitations. However, human intestinal organoids (HIOs) are a 3-dimensional tissue culture composed of a single layer of mature, differentiated, columnar epithelial cells that surround a lumen. When compared to traditional cell cultures, animal models and ligated intestines, HIOs have the potential to be more representative human physiology. Here, we begin to demonstrate the use of HIOs as an in vitro model to study E. coli. We hypothesized that HIOs could be used to study epithelial colonization dynamics of E. coli. In this study, we established working protocols for a novel experimental approach for investigating attachment factors involved in E. coli attachment. HIOs are generated from embryonic or pluripotent stem cells into definitive endoderm that gives rise to 3-dimensional structures. These structures were routinely cultured to a diameter of approximately 3.0 mm and embedding in matrigel. An overnight culture of the prototypic EPEC strain, e2348/69 (O127:H6) was transfected with a plasmid carrying a green fluorescent protein that provided visualization by fluorescent microscopy. Approximately, 2.4 x 10 6 CFU was injected into individual HIOs using a microinjector and incubated for 12 hours at 35°C and 5% CO 2. HIOs were then fixed and either stained for fluorescence imaging or processed in 1% osmium tetroxide for examination by field emission scanning electron microscopy (FE SEM). The observations that EPEC was intimately associated with the intestinal epithelium, supports the use HIO for E. coli colonization investigations.Item The bacteriology of the porcupine caecum(Montana State University - Bozeman, College of Agriculture, 1964) Johnson, John LeRoyItem Visceral mass and reticulorumen volume of differing biological types of beef cattle(Montana State University - Bozeman, College of Agriculture, 1987) Fredrickson, Eddie L.