The Human Microbiome and Interactions with Disease States, Medical Interventions, and the Metabolome

Ursell, Luke Kenneth

Graduate Thesis Or Dissertation

The Human Microbiome and Interactions with Disease States, Medical Interventions, and the Metabolome Public Deposited

Analytics

Citations

Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/jq085k10q

Abstract

Next generation sequencing technologies have allowed researchers to evaluate the unculturable members of the human microbiome with unprecedented precision and detail. Early studies of the human microbiome revealed the unique microbial fingerprint that we contain, as well as the fact that numerous disease states, including allergies, obesity, and gastrointestinal disorders, are associated with alterations in our human microbiome or a lack of exposure to critical microbes. This dissertation examines some common disease states and their microbial associations. Recent studies have also demonstrated how important it is to assess how medical interventions, including pharmaceutical drugs and implanted medical devices, alter our innate microbiome. Any negative alterations in microbial community structure or composition might have series deleterious consequences for the patient. Therefore, in this dissertation I assess the impact that intravaginal rings, used to deliver localized doses of acyclovir in herpes simplex positive women, have on the vaginal microbiome. I demonstrate that intravaginal rings are safe from a microbial perspective as they do not alter or aggravate the vaginal microbial community. Furthermore, this dissertation discusses the importance of assessing our ancestral microbiome to determine how modern day society has changed our evolutionary microbiome, with possible harmful consequences. I discuss several mechanisms by which researchers are exploring how to replenish our natural defensive microbes. Along this line of research, I compare the microbial communities and functional profiles of the hunter-gatherer group Matses to individuals from the United States and those from the agrarian societies of Malawi and Venezuela. This work demonstrates how our ancestral microbiome was enriched in genes related to energy metabolism, and how altered our modern day microbial community structure is from our evolutionary past. Finally, the importance of the interaction between intestinal metabolites and the microbiome is explored, focusing on how microbes can alter drug metabolism. I go on to evaluate the vast differences in the metabolite profile of potatoes that have been processed in different ways across a range of cultivar types. This work demonstrates that processing method is the dominant driver of metabolic profiles, but that cultivar and processing method interact non-linearly to produce unpredictable concentrations in the majority of potato-containing metabolites. I also show that common vitamins and antioxidants have unpredictable concentrations across processing methods and cultivars, highlighting that in the future this work might allow us manipulate our food metabolites to have maximum impact on the host.

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