A Member of the Mycobiome Modulates a Host Metabolite to Increase Intestinal Permeability and Disease

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Publication Type thesis
School or College School of Medicine
Department Pathology
Author Chiaro, Tyson Richard
Title A Member of the Mycobiome Modulates a Host Metabolite to Increase Intestinal Permeability and Disease
Date 2015-05
Description The human body is a fascinating arrangement of cellular organization necessary to support life; it is also home to trillions of microorganisms. The largest concentration of these commensal microbes exists within the gastrointestinal tract (GI) where bacteria dominate the landscape. Accordingly, the vast majority of research performed thus far has been to elucidate the role of bacteria; however, commensal fungal species are known to colonize every mucosal surface, including the GI of humans. Moreover, humoral responses to fungal cell walls have been shown to be a specific diagnostic marker for Crohn's disease and not ulcerative colitis. However, the role of yeast within the GI both metabolically and immunologically remains largely unexplored. For this reason, we set out to investigate how a known commensal yeast species, Saccharomyces cerevisiae , and a newly described yeast species in the context of human disease, Rhodotorula aurantiaca , influence immune system development and modulate disease. Also, given the role of environmental fungi in nutrient cycling on the planet, we were interested in how these two species may impact the metabolism of the host. To address these questions, we used two common mouse models of colitis. In addition, we performed a microarray on colonic RNA from germfree mice mono-colonized with our two yeast species and LC/MS on the serum of these animals. Here we report that mono-colonization with S. cerevisiae but not R. aurantiaca results in a significant increase in products of the purine degradation pathway, including uric acid. Surprisingly, yeast did not induce a robust inflammatory response; however, we observed multiple pathways associated with both digestion and epithelial barrier integrity. We demonstrate that animals treated with S. cerevisiae during DSS colitis have worse colonic histology, increased serum uric acid levels, and intestinal permeability. Furthermore, we determined that supplementing uric acid alone during DSS colitis recapitulates these effects. We postulate that S. cerevisiae alters the colonic histology and intestinal permeability through enterocytes and shunted into the purine salvage pathway, resulting in conversion to uric acid and reabsorption into the bloodstream.
Type Text
Publisher University of Utah
Subject MESH Mycobiome; Saccharomyces cerevisiae; Uric Acid; Colonic Diseases; Crohn Disease; Colitis, Ulcerative; Colitis; Receptors, Pattern Recognition; Toll-Like Receptors; Gastrointestinal Microbiome; Intestinal Mucosa; Intestinal Absorption; Homeostasis; Microarray Analysis
Dissertation Institution University of Utah
Dissertation Name Master of Science
Language eng
Relation is Version of Digital version of A Member of the Mycobiome Modulates a Host Metabolite to Increase Intestinal Permeability and Disease
Rights Management Copyright © Tyson Richard Chiaro 2015
Format Medium application/pdf
Format Extent 19,705,556 bytes
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6cp1nc0
Setname ir_etd
Date Created 2019-07-19
Date Modified 2021-05-06
ID 1432556
Reference URL https://collections.lib.utah.edu/ark:/87278/s6cp1nc0