Exercise and Inflammation in cancer survivorship care

Abstract

Cancer represents a significant global health burden. With improvements in detection and treatment survivors represent a growing population with complex health needs. increased late-effects, such as pain and cardio-metabolic diseases, have been attributed to systemic inflammation, however, the underlying mechanisms are yet to be fully elucidated. Exercise has been shown to ameliorate many of the adverse impacts due to cancer and its treatment, including reducing systemic inflammation, yet few cancer survivors meet the recommended physical activity (PA) guidelines. Additionally, the optimal characteristics of exercise to reverse the adverse effects of cancer treatments remain to be determined. The aim was to investigate the barriers to and facilitators of exercise for cancer survivors. I then tested the impact of exercise intensity on systemic inflammation and common inflammation-associated side effect, pain. Finally, I investigated a potential mechanism linking chemotherapy and irradiation to systemic inflammation in an animal model. A mixed-methods systematic review determined that treatment-related side effects, lack of time and fatigue were the most substantial barriers to exercise for survivors. I investigated the effect of exercise intensity on pain thresholds before and after a short training period in 14 adult survivors of cancer. I found that high intensity exercise increased acute pain thresholds with no change after low intensity, but that this difference between intensities was lost after a short training period. I then investigated the effect of high and low intensity exercise on systemic markers of inflammation. Exercise at either intensity had no effect on common markers of inflammation, however, low intensity exercise decreased chemokine CCL2, a pro-inflammatory chemokine, with no response to high intensity exercise. In C57BL/6J mice, I found that chemotherapy and total body irradiation (TBI) significantly altered gut microbiota diversity and increased abundance of genera associated with inflammation. This thesis found that low intensity exercise training may be effective at reducing pain and some markers of inflammation in cancer survivors, which may be a viable exercise option for survivors with significant barriers to exercise. Furthermore, persisting disruption of the gut microbiota after treatment results in a shift towards a more inflammatory microbiota composition, which may impact on systemic inflammation.