Effects of high-intensity treadmill training on intestinal permeability and myocardial autophagy in rats

Abstract

In this study, we investigated whether gut microbiota-derived factors contribute to the increase in intestinal permeability and the activation of left ventricular autophagy-related signaling induced by high-intensity treadmill exercise, using an antibiotic-treated rat model. Serum levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), colonic occludin, zonulin, and myocardial autophagy-related signaling were analyzed. A total of 38 specific pathogen-free male Sprague–Dawley rats aged 8 weeks were randomly assigned to four groups: control (n=9), antibiotic control (n=9), exercise (n=10), and antibiotic plus exercise (n=10). Treadmill exercise was performed for 60 min per session, 4 times per week, for 8 weeks. Eight weeks of high-intensity treadmill exercise increased intestinal permeability and elevated circulating levels of gut-derived LPS and LBP. Increased LPS and LBP levels were associated with the activation of adenosine monophosphate-activated protein kinase (AMPK) and upregulation of myocardial autophagy-related markers, including microtubule-associated protein light chain 3 and B-cell lymphoma-2-interacting myosin-like coiled-coil protein. Although increased intestinal permeability was also observed in the antibiotic-treated exercise group, circulating LPS and LBP levels did not increase significantly, nor did AMPK activation or the expression of autophagy-related markers. Prolonged high-intensity treadmill exercise may be associated with increased intestinal permeability and activation of myocardial autophagy-related signaling. The attenuation of the increases in circulating LPS/LBP levels and in myocardial autophagy-related signaling after antibiotic treatment suggests that gut microbiota-derived factors may mediate these gut-heart responses. Optimizing exercise benefits while minimizing risks may require considering both training in-tensity and gut health in the exercise program design.

The authors' abstract, as published at the source. Journal of Exercise Rehabilitation, 2026 · DOI ↗