Bacterial Indole Production and Epithelial Barrier Function in Colorectal Cancer




Tremble, Kaitlyn A.

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Colorectal cancer (CRC) is the third most diagnosed cancer globally and second leading cause of cancer mortality, accounting for approximately 10% of annual cancer diagnoses and related deaths, with early onset CRC on the rise. The intestinal epithelial barrier is the link between external processes of the microbiome and internal processes of the host system. Therefore, the development of intestinal diseases such as CRC spark questions as to the specific contributions and interplay between each side of this barrier; among them, what microbial metabolites might increase cancer risk and how the body’s response might further contribute to carcinogenesis. This thesis explores the role of Fusobacterium nucleatum—a common member of the gut microbiome in both healthy and diseased states—in CRC pathogenesis through the action of indole metabolites. First, the nature and quantity of indole production by F. nucleatum is explored. Then, the response of human colonic epithelial cells is assessed via changes in proliferation and gene expression. Further elucidation of the relationship between F. nucleatum, indole metabolites, and the colonic epithelium could advance our understanding of the mechanisms behind pathogen behavior and its contribution to CRC pathogenesis.



Biology, Cancer, Microbiome, Colorectal Cancer