-derived metabolites may influence cardiometabolic pathways in .
Diabetic cardiomyopathy is characterized by heart muscle changes without the presence of coronary artery disease or hypertension.
Gut microbiota and its metabolites are linked to systemic metabolic balance, affecting energy use, inflammation, and oxidative stress.
Specific metabolites from gut bacteria, such as short-chain fatty acids and trimethylamine N-oxide, may regulate heart-related metabolic processes.
These metabolites can impact insulin resistance, fat buildup, and heart tissue scarring.
Potential therapies targeting gut microbiota include dietary changes, probiotics, and certain medications, showing promise in animal studies.
Clinical evidence for these microbiota-focused therapies in humans is currently limited.
Simplified
(DCM) is a major cardiovascular complication of diabetes mellitus, characterized by myocardial structural and functional abnormalities in the absence of overt coronary artery disease or hypertension. A growing body of evidence implicates the and its metabolites as key modulators of systemic metabolic homeostasis, influencing energy metabolism, inflammation, and oxidative stress. The gut microbiota emerges as a novel regulator of cardiac remodeling and in DCM through the gut-heart axis. This review aims to synthesize current mechanistic insights into how gut microbiota and its bioactive metabolites contribute to metabolic reprogramming in DCM. It further evaluates the potential of microbiota-targeted interventions as emerging therapeutic strategies to mitigate disease progression and restore cardiac homeostasis. A narrative, mechanistically focused literature review was conducted using PubMed and Web of Science databases. It covered experimental, preclinical, and translational studies up to April 2025. Articles were selected based on relevance to gut microbial metabolism, host cardiac metabolic pathways, and therapeutic interventions linked to DCM. Gut microbiota-derived metabolites-including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids, lipopolysaccharides (LPS), tryptophan catabolites, and hydrogen sulfide-modulate cardiometabolic pathways via epigenetic regulation, altered energy substrate utilization, inflammatory signaling, and mitochondrial oxidative stress. These metabolites influence insulin resistance, lipid accumulation, mitochondrial dynamics, and cardiac fibrosis. Therapeutic strategies such as dietary modulation, probiotics, prebiotics, fecal microbiota transplantation, and drugs like SGLT2 inhibitors and GLP-1 receptor agonists have shown promising effects in modulating gut microbiota composition and alleviating DCM phenotypes in animal models. However, clinical evidence remains limited. The gut microbiota plays a pivotal role in the pathogenesis and potential treatment of DCM through its ability to reprogram host metabolism and inflammation. While preclinical data are compelling, further translational research-including humanized models and multi-omics integration-is required to validate microbiota-targeted therapies for cardiovascular applications. Targeting the microbiota-metabolite axis offers an innovative therapeutic avenue for personalized intervention in diabetic heart disease.
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