Microbial regulation of the small intestinal epithelium under homeostasis and restitution: Implications for inflammatory bowel disease
Year: 2025
Type: dissertation
Abstract: The gut microbiota are a diverse ecosystem of trillions of microbes that reside within the lumen of the gastrointestinal tract. Bacteria are the largest contributor to the microbiota and several studies have demonstrated that this complex community of microbes plays a critical role in regulating host physiology and susceptibility to disease. This is supported by observations of dysbiosis, disorder-associated changes in microbiota composition, in conditions such as multiple sclerosis, diabetes, malnutrition, cardiovascular disease, cancer, and inflammatory bowel disease (IBD). However, the mechanisms by which microbiota exert these influences remain unclear.Within the gastrointestinal tract, the gut microbiota exist in direct contact with the small intestinal epithelium, which is the largest mucosal surface of the human body. The small intestinal epithelium is comprised of multiple cell types that mediate crucial processes such as nutrient absorption and metabolism, enteroendocrine signaling, immunoregulation, barrier functions against environmental stimuli, and epithelial repair. Given that the small intestinal epithelium is one of the first and largest points of contact between the host and gut microbiota, understanding these interactions are critical to determining how microbiota mechanistically impact human risk for diseases such as IBD. Herein, I aimed to delineate how microbiota and microbial detection impact the small intestinal epithelium under homeostasis and during epithelial restitution. Using germ-free (GF) and specific-pathogen free (SPF) mice, I demonstrated that under homeostasis, microbiota increased the expression of key host-defense associated genes and suppressed nutrient starvation-induced stress in an epithelial cell subset-specific manner. Using a model of irradiation (IR) enteritis, I showed that microbiota accelerated epithelial restitution and that epithelial Nod2 signaling further promotes epithelial repair. Collectively, the work in this thesis characterizes novel host-microbiota interactions with respect to key small intestinal epithelial cell subsets that play critical roles in host defense and damage-induced epithelial restitution. The characterization of these interactions further demonstrates how microbiota and Nod2 may increase risk for IBD development through interactions with the intestinal epithelium.
Source: TSpace (University of Toronto)
Author: Tsang, Derek Ka Long
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7133018139