Jing-yu Jin, Xin-yu Yang, Ru Feng, Meng-liang Ye, Hui Xu, Jing-yue Wang, Jia-chun Hu, Heng-tong Zuo, Jin-yue Lu, Jian-ye Song, Yi Zhao, Yan Wang, Qian Tong
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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. 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引用次数: 0
摘要
糖尿病性心肌病(DCM)是糖尿病的主要心血管并发症,其特征是在没有明显冠状动脉疾病或高血压的情况下心肌结构和功能异常。越来越多的证据表明,肠道微生物群及其代谢物是全身代谢稳态的关键调节剂,影响能量代谢、炎症和氧化应激。肠道微生物群通过肠-心轴成为DCM中心脏重塑和代谢重编程的新调节器。这篇综述旨在综合目前关于肠道微生物群及其生物活性代谢物如何促进DCM代谢重编程的机制见解。它进一步评估了以微生物群为目标的干预措施作为减缓疾病进展和恢复心脏稳态的新兴治疗策略的潜力。使用PubMed和Web of Science数据库进行了一项叙述性的、以机械为重点的文献综述。它涵盖了截至2025年4月的实验、临床前和转化研究。文章的选择基于与肠道微生物代谢、宿主心脏代谢途径和与DCM相关的治疗干预的相关性。肠道微生物衍生的代谢物——包括短链脂肪酸(SCFAs)、三甲胺n -氧化物(TMAO)、胆汁酸、脂多糖(LPS)、色氨酸分解代谢物和硫化氢——通过表观遗传调控、改变的能量底物利用、炎症信号和线粒体氧化应激来调节心脏代谢途径。这些代谢物影响胰岛素抵抗、脂质积累、线粒体动力学和心脏纤维化。在动物模型中,饮食调节、益生菌、益生元、粪便微生物群移植以及SGLT2抑制剂和GLP-1受体激动剂等治疗策略在调节肠道微生物群组成和缓解DCM表型方面显示出了良好的效果。然而,临床证据仍然有限。肠道微生物群通过其重编程宿主代谢和炎症的能力,在DCM的发病机制和潜在治疗中起着关键作用。虽然临床前数据令人信服,但需要进一步的转化研究,包括人性化模型和多组学整合,以验证微生物群靶向治疗心血管应用。针对微生物代谢物轴为糖尿病性心脏病的个性化干预提供了一种创新的治疗途径。
Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers
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 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.
期刊介绍:
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.