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从肠道微生物生态到脂质稳态:解读肠道微生物群在血脂异常发病机制及干预中的作用

From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.

作者信息

Lv Jing, Zhao He-Ping, Yu Yan, Wang Ji-Han, Zhang Xiao-Jun, Guo Zhi-Qi, Jiang Wen-Yan, Wang Kai, Guo Lei

机构信息

Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China.

Yan'an Medical College, Yan'an University, Yan'an 716000, Shaanxi Province, China.

出版信息

World J Gastroenterol. 2025 Aug 14;31(30):108680. doi: 10.3748/wjg.v31.i30.108680.


DOI:10.3748/wjg.v31.i30.108680
PMID:40904889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12404133/
Abstract

Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.

摘要

血脂异常是一种以全身脂质谱异常为特征的复杂疾病,全球超过一半的成年人受其影响,是动脉粥样硬化性心血管疾病的一个主要可改变风险因素。越来越多的证据表明,肠道微生物群(GM)是一种关键的代谢调节因子,通过饮食生物转化、免疫代谢调节和生物活性代谢物信号传导与致动脉粥样硬化的脂质谱相关。然而,驱动血脂异常发病机制的宿主-微生物相互作用涉及复杂的基因-环境相互作用,涵盖从表观遗传修饰到昼夜节律调节。从机制上讲,GM扰动会破坏脂质稳态,包括脂多糖引发的肝脏极低密度脂蛋白过度产生、短链脂肪酸-G蛋白偶联受体43/41介导的脂肪细胞脂解、胆汁酸-法尼酯X受体/武田G蛋白偶联受体5轴功能障碍改变胆固醇通量、微生物β-氧化中间体损害线粒体能量代谢,以及宿主-微生物群非编码RNA相互作用调节脂肪生成基因。这篇综述系统地研究了三个关键方面,包括GM-脂质轴的双向相互作用、连接微生物生态与代谢功能障碍的分子级联反应,以及通过精准益生菌、结构特异性益生元和代谢优化的粪便微生物群移植方案进行GM调节的转化应用。尽管取得了这些进展,但在建立因果微生物分类群-途径关系和最佳干预时机方面仍存在关键差距。未来的方向需要纵向多组学研究、用于机制验证的悉生生物模型,以及机器学习驱动的个性化微生物群分析。这一综述为制定以微生物群为中心的策略以针对血脂异常病理生理学提供了一个框架,对精准血脂异常管理和下一代心血管疾病预防具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/f60edff56819/wjg-31-30-108680-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/6c5c56c12783/wjg-31-30-108680-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/4f3dcd3cac78/wjg-31-30-108680-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/f60edff56819/wjg-31-30-108680-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/6c5c56c12783/wjg-31-30-108680-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/4f3dcd3cac78/wjg-31-30-108680-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09e9/12404133/f60edff56819/wjg-31-30-108680-g003.jpg

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From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.

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本文引用的文献

[1]
Probiotics for the treatment of hyperlipidemia: Focus on gut-liver axis and lipid metabolism.

Pharmacol Res. 2025-4

[2]
The synergistic role of gut microbiota and RNA in metabolic diseases: mechanisms and therapeutic insights.

Front Microbiol. 2025-1-29

[3]
Bile acid derivatives from gut microbiota promote GBPs-mediated activation of caspase-4/11 by LPS through .

Int J Biol Sci. 2024-10-28

[4]
Impact of () sup. TISTR 2593 Probiotic Supplementation on the Gut Microbiome of Hypercholesterolemia Patients: A Randomized Controlled Trial.

Nutrients. 2024-9-1

[5]
Day and Night Reversed Feeding Aggravates High-Fat Diet-Induced Abnormalities in Intestinal Flora and Lipid Metabolism in Adipose Tissue of Mice.

J Nutr. 2024-9

[6]
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Ann Med Surg (Lond). 2024-1-18

[7]
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Biomed Rep. 2024-2-1

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Int J Biol Macromol. 2024-2

[9]
The gut-Snhg9 interplay as a new path to metabolic health.

Trends Endocrinol Metab. 2024-1

[10]
An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism.

Cell Host Microbe. 2023-10-11

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