Publication Date
2017
Document Type
Thesis
Committee Members
Oleg Paliy, Ph.D. (Advisor); Nancy Bigley, Ph.D. (Committee Member); Dawn Wooley, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Allergy is a global health problem, affecting more than 40% of the world population. Allergy is often associated with a dysregulation of the immune system that becomes overactive against allergens. Several genes are known to be important for the proper homeostasis of the immune system in the epithelial tissues, and the loss of function of genes such as IKKß or SOX9 impacts the interaction between external stimuli and the host. Many of the allergic responses are triggered through the regulatory cascade governed by transcriptional factor NF-κB. Regulation of NF-κB activity is complex, involves several alternative routes, and is also influenced by metabolites produced in the gut by resident microbes. In this study, we aimed to profile small and large intestinal metabolite profiles in two mouse models of allergic disease, and compare these profiles to those of wild type mice. Proton nuclear magnetic resonance was used to acquire metabolite signatures of all samples. Multivariate statistical analyses of the binned NMR data revealed that samples separated into distinct groups corresponding to the gastrointestinal tract sections, and partially into groups based on mouse model. Using NMR spectrum deconvolution, we also quantified levels of twelve different metabolites known to be abundant in the gut lumen. Several quantified metabolites such as butyrate, propionate, tryptophan, and threonine were significantly less abundant in the gut of allergy disease mouse models compared to the wildtype mice. These metabolites were previously shown to regulate the signaling pathways of NF-κB. Knocked out the genes of IKKß or SOX9 in allergic mice models lowered the allergic responses in the airways by increasing the production of immunoglobulin A.
Page Count
58
Department or Program
Microbiology and Immunology
Year Degree Awarded
2017
Copyright
Copyright 2017, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
ORCID ID
0000-0001-9690-1409
