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UBC Theses and Dissertations

Physical activity as a modulator of intestinal health and its implications in inflammatory bowel diseases Estaki, Mehrbod

Abstract

The interactions between humans, the environment, and intestinal microbiota form a tripartite relationship that is fundamental to the overall health of the host. Disruptions in this delicate balance between the microbiota and host immunity are implicated in various chronic diseases including inflammatory bowel disease (IBD). IBD encompassing ulcerative colitis and Crohn’s disease are idiopathic, relapsing chronic inflammatory disorders of the intestinal tract with annual health care burdens of over $1.8 billion in Canada. There is no known cure for IBD, as so, novel therapeutic in its prevention and management are of great interest. Recently, physical activity (PA) has been proposed as a potential therapy in combating IBD. Here we show that higher aerobic fitness in humans is associated with increased bacterial diversity in the gut and higher abundances of butyrate, a type of short-chain fatty acid produced by resident bacteria with known anti-inflammatory properties. We confirm these findings in animal models showing that voluntary wheel running (VWR) in mice increases butyrate production. Additionally, VWR mice show increased microbial diversity, decreased expression of pro-inflammatory (TNF-α, TGF-β, and IFN-γ) and increased expression of anti-inflammatory (IL-10) cytokines suggestive of the potential to be primed against the damaging effects of chronic inflammation. These enhancements however were absent in a life-long model of mucin2 deficient (MUC2-/-) murine colitis and VWR offered no protection in these mice against disease symptoms. Taken together, these suggest that the benefits of PA against IBD are preventative in nature and cannot reverse existing disease states like those found in IBD. We further showed that certain PA-derived changes in the intestines such as microbial community changes, upregulation of IL-10, and attenuation of IFN-γ are dependent on the amount of PA while reduction of anti-inflammatory cytokines TNF-α and TGF-β can occur even under low running conditions. In summary, we showed that PA can beneficially modulate the intestinal environment in healthy hosts, leading to a primed anti-inflammatory state likely effective in IBD management during remission.

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Attribution-NonCommercial-NoDerivatives 4.0 International