Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis

Abstract

The purpose of this study was to examine whether exercise training reduced inflammation and symptomology in a mouse model of colitis. We hypothesized that moderate forced treadmill running (FTR) or voluntary wheel running (VWR) would reduce colitis symptoms and colon inflammation in response to dextran sodium sulfate (DSS). Male C57Bl/6J mice were randomized to sedentary, moderate intensity FTR (8–12 m/min, 40 min, 6 weeks, 5x/week), or VWR (30 days access to wheels). DSS was given at 2% (w/v) in drinking water over 5 days. Mice discontinued exercise 24 h prior to and during DSS treatment. Colons were harvested on Days 6, 8 and 12 in FTR and Day 8 post-DSS in VWR experiments. Contrary to our hypothesis, we found that moderate FTR exacerbated colitis symptomology and inflammation as measured by significant (p≤0.05) increases in diarrhea and IL-6, IL-1β, IL-17 colon gene expression. We also observed higher mortality (3/10 died vs. 0/10, p = 0.07) in the FTR/DSS group. In contrast, VWR alleviated colitis symptoms and reduced inflammatory gene expression in the colons of DSS-treated mice (p≤0.05). While DSS treatment reduced food/fluid intake and body weight, there was a tendency for FTR to exacerbate, and for VWR to attenuate, this effect. FTR (in the absence of DSS) increased gene expression of the chemokine and antibacterial protein CCL6 suggesting that FTR altered gut homeostasis that may be related to the exaggerated response to DSS. In conclusion, we found that FTR exacerbated, whereas VWR attenuated, symptoms and inflammation in response to DSS.

Exercise has the guts: How physical activity may positively modulate gut microbiota in chronic and immune-based diseases

“…Other animal studies supported the exercise-induced increase in butyrate-producing bacteria [76], however results might vary according to the protocol employed (voluntary-versus controlled exercise) [77]. observed that voluntary wheel running prevented weight gain and altered microbiota, reequilibrating major-phylum levels.…”

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice

“…38 Despite these parallel results linking improvements in T2DM and obesity symptoms to any form of exercise, there are differences between forced and voluntary exercise regarding other physiological outcomes. For example, mice consuming a high-fat diet have shown reduced inflammation when given access to running-wheels; 15 conversely, forced exercise may promote inflammation 39 and differently affect the gut microbiome compared to voluntary wheel-running in rodent models. 40 Future studies investigating the effects of exercise on physiology will need to establish which parameters they wish to investigate and whether to use voluntary or forced exercise in the experiments.…”

Exercise and the microbiota

“…39 In a mouse model of colitis, forced treadmill exercise training aggravated inflammatory indices and outcomes, while voluntary wheel training displayed a protective effect. 40 This suggests a biphasic and dose-response effect of exercise on gut health that has yet to be fully explored in humans.…”