Date of Award
Fall 2025
Document Type
Open Access Dissertation
Department
Biomedical Science
First Advisor
Phillip Brandon Busbee
Abstract
Inflammatory bowel disease (IBD) is a presently incurable chronic condition of the gastrointestinal (GI) tract characterized by inflammation, increased gut permeability, impaired quality of life, and significant financial burden. Epidemiological investigations also note an increased incidence of major depressive disorder (MDD) in the IBD population. This project aimed to establish a causal thread between both conditions by first identifying discrete metabolome profiles in experimental colitis models. Untargeted fecal metabolomics identified elevations of quinolinic acid (QA), a neurotoxic intermediate of the kynurenine pathway (KP), in the gut of colitis animals. Single cell RNA sequencing of colons labeled dendritic cells (DCs) as primary producers of key KP enzymes required for production of QA. Activation of the aryl hydrocarbon receptor (AhR) using the natural agonist indole-3-carbinol (I3C) resulted in the amelioration of colitis symptoms, inhibition of KP enzymes, and reduction of gut-derived QA. Subsequent inquiries identified the presence of depressive-like behavior and increased blood brain barrier permeability in colitis animals largely prevented by I3C treatment. Select inhibition of a KP enzyme resulted in the abrogation of depressive-like behavior as well. Collectively, these studies provide evidence that use of AhR agonist I3C can regulate QA production in the gut during colitis and impact depressive-like behavior associated with intestinal inflammation.
Rights
© 2025, Raymond Kennith Bogdon
Recommended Citation
Bogdon, R. K.(2025). Aryl Hydrocarbon Receptor Ligand Indole-3-Carbinol Attenuates Colitis-Associated Depression: Implications of Quinolinic Acid Regulation. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/8699