USE of NMR-based metabonomics to study animal models and human disease
Abstract
This dissertation describes the effects that both antibiotics and opportunistic pathogens had on the host and gut metabolome, as well as the physical effects that these experimental factors had on the distal ileum of the study mice.The dissertation also presents urinary metabolic profiles in order to identify statistically significant changes in metabolites that could be used as a biomarker for early disease diagnosis and treatment.In chapter 1 a background of both human and animal model metabonomics studies is presented, including an overview of NMR and the multivariate statistical analysis method, PCA, which was utilized in all work in this dissertation.Chapter 2 illustrates the effects that a broad spectrum antibiotic, Baytril, has on the urinary and fecal metabolic profiles of Balb/c mice.It was found that eliminating bacterial species from the gut caused significant changes in metabolic profiles of study mice.Many of the metabolic changes were a direct result of bacterial cell death and a lack of bacterial processes that naturally occur in the host intestinal tract.Chapter 3 takes the study design in Chapter 2 a few steps further and following antibiotic treatment an opportunistic pathogen, Clostridium butyricum was introduced to the mice by an intragastric gavage procedure.C. butyricum has been linked to necrotizing enterocolitis (NEC) in past studies and has been isolated from the blood and fecal cultures of neonates diagnosed with NEC.It was determined that…
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