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肠道微生物群衍生代谢物调控糖尿病心肌病中的代谢重编程:机制与治疗前沿

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

作者信息

Jin Jing-Yu, Yang Xin-Yu, Feng Ru, Ye Meng-Liang, Xu Hui, Wang Jing-Yue, Hu Jia-Chun, Zuo Heng-Tong, Lu Jin-Yue, Song Jian-Ye, Zhao Yi, Wang Yan, Tong Qian

机构信息

Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

FASEB J. 2025 Sep 15;39(17):e71004. doi: 10.1096/fj.202501579RR.


DOI:10.1096/fj.202501579RR
PMID:40899744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12406765/
Abstract

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.

摘要

糖尿病性心肌病(DCM)是糖尿病的一种主要心血管并发症,其特征是在没有明显冠状动脉疾病或高血压的情况下出现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产物是全身代谢稳态的关键调节因子,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型调节因子。本综述旨在综合当前关于肠道微生物群及其生物活性代谢产物如何促进DCM中代谢重编程的机制见解。它还进一步评估了以微生物群为靶点的干预措施作为减轻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数据库进行了一篇以机制为重点的叙述性文献综述。涵盖了截至2025年4月的实验、临床前和转化研究。根据与肠道微生物代谢、宿主心脏代谢途径以及与DCM相关的治疗干预措施的相关性选择文章。肠道微生物群衍生的代谢产物,包括短链脂肪酸(SCFAs)、氧化三甲胺(TMAO)、胆汁酸、脂多糖(LPS)、色氨酸分解代谢产物和硫化氢,通过表观遗传调控、改变能量底物利用、炎症信号传导和线粒体氧化应激来调节心脏代谢途径。这些代谢产物影响胰岛素抵抗、脂质积累、线粒体动力学和心脏纤维化。饮食调节、益生菌、益生元、粪便微生物群移植等治疗策略以及SGLT2抑制剂和GLP-1受体激动剂等药物在调节肠道微生物群组成和减轻动物模型中的DCM表型方面已显示出有前景的效果。然而,临床证据仍然有限。肠道微生物群通过其重新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。虽然临床前数据很有说服力,但需要进一步的转化研究,包括人源化模型和多组学整合,以验证针对心血管应用的以微生物群为靶点的疗法。靶向微生物群-代谢产物轴为糖尿病性心脏病的个性化干预提供了一条创新的治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/be2c251a6fe8/FSB2-39-e71004-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/6c017548071f/FSB2-39-e71004-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/cb45ef633e68/FSB2-39-e71004-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/be2c251a6fe8/FSB2-39-e71004-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/6c017548071f/FSB2-39-e71004-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/cb45ef633e68/FSB2-39-e71004-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc2/12406765/be2c251a6fe8/FSB2-39-e71004-g002.jpg

相似文献

[1]
Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.

FASEB J. 2025-9-15

[2]
Type 2 Diabetes and the Multifaceted Gut-X Axes.

Nutrients. 2025-8-21

[3]
Exploring the gut microbiome's influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies.

World J Gastrointest Pharmacol Ther. 2025-6-5

[4]
Gut Microbiota-Targeted Therapeutics for Metabolic Disorders: Mechanistic Insights into the Synergy of Probiotic-Fermented Herbal Bioactives.

Int J Mol Sci. 2025-6-7

[5]
Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years.

Cochrane Database Syst Rev. 2025-7-10

[6]
Mitochondrial ultrastructural pathology in diabetic cardiomyopathy: integrated analysis via scanning electron microscopy and 3D visualization imaging.

Cardiovasc Diabetol. 2025-8-13

[7]
Microbiota in Gut-Heart Axis: Metabolites and Mechanisms in Cardiovascular Disease.

Compr Physiol. 2025-6

[8]
Gut microbiota and cardiac arrhythmogenesis: Unveiling the gut-heart axis.

Pathol Res Pract. 2025-7-15

[9]
The Oral-Gut Microbiota Axis as a Mediator of Frailty and Sarcopenia.

Nutrients. 2025-7-23

[10]
Multi-strain probiotics attenuate carbohydrate-lipid metabolic dysregulation in type 2 diabetic rats via gut-liver axis modulation.

mSystems. 2025-7-22

本文引用的文献

[1]
Exerkines: Potential regulators of diabetic cardiomyopathy.

Ageing Res Rev. 2025-8

[2]
Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF.

Cardiovasc Diabetol. 2025-4-4

[3]
Ferroptosis: mechanism and role in diabetes-related cardiovascular diseases.

Cardiovasc Diabetol. 2025-2-7

[4]
Exercised gut microbiota improves vascular and metabolic abnormalities in sedentary diabetic mice through gut‒vascular connection.

J Sport Health Sci. 2025-1-17

[5]
Revisiting the Concepts of Prebiotic and Prebiotic Effect in Light of Scientific and Regulatory Progress-A Consensus Paper From the Global Prebiotic Association.

Adv Nutr. 2024-12

[6]
BCKDH kinase promotes hepatic gluconeogenesis independent of BCKDHA.

Cell Death Dis. 2024-10-10

[7]
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Int J Biol Macromol. 2024-11

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Resveratrol stimulates brown of white adipose via regulating ERK/DRP1-mediated mitochondrial fission and improves systemic glucose homeostasis.

Endocrine. 2025-1

[9]
BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21.

Microbiome. 2024-8-24

[10]
Western diets and chronic diseases.

Nat Med. 2024-8

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