Gut Microbiota‐Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers

作者：Jing‐yu Jin, Xinyu Yang, Ru Feng, Meng-Liang Ye, Hui Xu, Jingyue Wang, Jiachun Hu, Hengtong Zuo, Jin‐Yue Lu, Jian‐Ye Song, Yi Zhao, Yan Wang, Qian Tong · 发表于：The FASEB Journal · 年份：2025 · DOI：10.1096/fj.202501579rr · 被引用次数：14 · 研究领域：Diet and metabolism studies、Cardiovascular Function and Risk Factors、Pancreatic function and diabetes

Diabetic cardiomyopathy (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 gut microbiota 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 metabolic reprogramming 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 su...