Date of Award

Spring 2020

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Traci Testerman

Abstract

Enterohepatic Helicobacter (EHH) species are gram-negative bacteria, which are poorly studied. Several studies suggest that EHH species contribute to inflammatory bowel disease IBD in humans. IBD and colorectal cancer (CRC) has emerged as a public health challenge worldwide. Indole-3-carbinol (I3C) is one of the natural dietary indoles abundant in Brassica (cruciferous) vegetables. The aryl hydrocarbon receptor (AhR) plays an essential role as a regulator by controlling the balance between Tregs and Th17 cells. The activation of AhR by ligands derived from food or intestinal microbiota is an essential control mechanism in that balance. Moreover, many studies showed indoles achieving chemo-preventive effects against cancer.

We used the dextran sulfate sodium (DSS)-induced colitis mouse model to study the role of Helicobacter muridarum (Hm) bacteria with and without I3C treatment. We focused on the pathology outcomes after the bacterial infection and the I3C treatment during the DSS course. Weight loss, diarrhea, blood in the stool, and histopathology were measured. Inflammation markers were also measured in the plasma and the colon. We then studied the miRNA response. miRNAs are non-coding RNAs that can regulate genes involved in the immune responses.

The purpose of the second study was to study the role of Helicobacter hepaticus (Hh). (Hh) can cause colitis in genetic or pharmacologically induced deficiencies of the Interleukin-10/Interleukin-10 receptor. We studied (Hh) infection role, in the DSS colitis model and AOM (Azoxymethane) /DSS colon cancer model in wild-type mice.

Finally, the last study's purpose was to examine the effects of different species of Helicobacter on developing acute gut injury in male and female mice with and without DSS treatment. The species used are known to infect humans: H. cinaedi, H. fennelliae, H. hepaticus, and H. pullorum. Similar pathology and immune response measurements were done for this study, as was done for the other studies.

Rights

© 2020, Rasha Raheem Abdulhamza Alkarkoushi

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