Modulation of the gut-heart axis by exercise in diabetic cardiomyopathy: Microbial mechanisms and clinical implications

Figures

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  Figure 1. Mechanisms by which exercise modulates gut microbiota-derived metabolites to prevent and treat DCM By reshaping gut microbiota composition, exercise enhances the production of SCFAs, secondary BAs, H2S, and indole derivatives, while reducing the generation of TMAO, LPS, and BCAAs. On one hand, these metabolites act on peripheral metabolic organs, such as the gut (e.g., increased GLP-1 and FGF15/19 secretion), liver (e.g., reduced FGF21 secretion), and adipose tissue (e.g., elevated APN production), thereby indirectly improving cardiac metabolic health. On the other hand, these metabolites directly influence the myocardium via the gut-heart axis by suppressing inflammation, oxidative stress, and mitochondrial injury, as well as reducing cardiac lipotoxicity and apoptosis, ultimately contributing to the prevention and amelioration of DCM. GPR41/43, G protein-coupled receptor 41/43; APN, adiponectin; FGF15/19, fibroblast growth factor 15/19; S6K1, ribosomal protein S6 kinase 1; MyD88, myeloid differentiation primary response 88; TCA, tricarboxylic acid cycle. Created in BioRender. Chen, J. (2025) https://BioRender.com/pimqwf7.

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  Figure 2. Mechanism of exercise enhances intestinal barrier function prevent and treat DCM Regular exercise suppresses the overgrowth of intestinal fungi (e.g., Candida albicans, Mycetes spp.) and decreases NET formation, thereby reducing mucosal immune-inflammatory responses and limiting LPS translocation into the circulation. Exercise also increases the abundance of beneficial bacteria, such as A. muciniphila, Bacteroides dorei, and Bacteroides vulgatus, which promote tight-junction protein expression, preserve epithelial cohesion, and attenuate metabolic endotoxemia. Additionally, exercise elevates gut butyrate production, which stimulates epithelial proliferation, strengthens tight-junction assembly, and induces colonic Treg cell differentiation to support anti-inflammatory signaling. Together, these adaptations enhance intestinal barrier function and reduce systemic inflammation, indirectly contributing to cardioprotection in diabetes. ZO-1, zonula occludens-1. Created in BioRender. Chen, J. (2025) https://BioRender.com/7g0c616.