Date of Award

Spring 2025

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

E. Angela Murphy

Abstract

It is well understood that intestinal inflammation is a main driving factor in various diseases and is strongly associated with 20% of all human cancers. The burden and prevalence of inflammatory bowel disease (IBD), which includes both Ulcerative colitis (UC) and Crohn’s disease (CD), is rising globally and may be as high as 1% by 2030 in the Western world. Not only is IBD problematic on its own, but the chronic inflammation ensuing from IBD leads to an increased risk for developing colorectal cancer (CRC), which is the third most common cancer worldwide. Moreover, 60-100% of cancer patients requiring treatment and undergoing chemotherapy will experience negative gastrointestinal (GI) side-effects, one of these being chemotherapy-induced mucositis (CIM). CIM causes various GI perturbations, including intestinal ulcerations, impaired gut integrity, altered mucosal immunology, and shifts in microbial populations, all of which can reduce quality of life (QOL) and, in some cases, survival. With the understanding that intestinal inflammatory diseases, cancers, and cancer-associated toxicities remain prevalent and are unlikely to abate in the near future, scientific efforts continue to be directed towards identifying new measures of disease prevention and treatment to mitigate disease progression and improve patient QOL and survival. Nonpharmaceutical strategies (e.g., natural compounds, diet, exercise/physical activity, sleep, therapy, etc.) have shown promise in the treatment of intestinal diseases. While various natural compounds have been investigated for their anti-inflammatory properties and immune-modulating potential, our group has focused heavily on American ginseng (AG). We fractioned AG to determine the most potent, bioavailable, and anti-inflammatory compound in AG, which is known as panaxynol. Panaxynol has been shown to alleviate colitis, although the precise mechanism by which it alleviates intestinal inflammation remains largely unknown. Additionally, we know that diet plays a key role in the modulation of intestinal inflammation. Typically, a high fat diet (HFD) has been widely contraindicated for the treatment of most diseases, as it has various deleterious effects on intestinal health and perpetuates chronic inflammation in the body. Whether a HFD explicitly exacerbates cancer-associated and chemotherapy-induced mucositis, however, has yet to be established in a murine model. The overarching goal of this dissertation is to determine if and how dietary interventions (i.e., natural compounds and dietary patterns) alter the immune response and intestinal environment following an inflammatory insult (i.e., ulcerative colitis, mucositis, or cancer) to improve disease severity and outcomes. This will be accomplished with the following three aims: Aim 1: Determine potential mechanisms by which panaxynol protects against murine ulcerative colitis. Aim 2: Examine whether panaxynol protects against murine chemotherapy-induced intestinal mucositis. Aim 3: Investigate whether a high fat diet exacerbates murine chemotherapy-induced intestinal mucositis. My central hypothesis is that dietary interventions alter intestinal inflammation and architecture through the modulation of both innate and adaptive immune cell populations within the intestinal microenvironment.

Rights

© 2025, Brooke Morgan Bullard

Download

Included in

Biology Commons

Share

COinS