从肠道微生物生态学到脂质稳态:解码肠道微生物群在血脂异常发病机制和干预中的作用。

IF 5.4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Jing Lv, He-Ping Zhao, Yan Yu, Ji-Han Wang, Xiao-Jun Zhang, Zhi-Qi Guo, Wen-Yan Jiang, Kai Wang, Lei Guo
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引用次数: 0

摘要

血脂异常是一种以全身脂质异常为特征的复杂疾病,影响着全球一半以上的成年人,是动脉粥样硬化性心血管疾病的主要可改变危险因素。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剂,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动脉粥样硬化脂质谱相关。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-环境串扰,包括表观遗传修饰和昼夜节律干扰。机制上,转基因扰动通过脂多糖引发的肝脏极低密度脂蛋白过量产生、短链脂肪酸-G蛋白偶联受体43/41介导的脂肪细胞脂解、胆酸-法内酯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、宿主-微生物群非编码RNA串扰调节脂肪生成基因等途径破坏脂质稳态。这篇全面的综述系统地探讨了三个关键的维度,包括转基因与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,以及通过精确益生菌、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转基因调节的转化应用。尽管取得了这些进展,但在建立微生物分类途径的因果关系和最佳干预时机方面仍然存在关键差距。未来的方向需要纵向的多组学研究,用于机制验证的生物模型,以及机器学习驱动的个性化微生物群分析。这种综合为开发以微生物群为中心的针对血脂异常病理生理的策略提供了一个框架,对精确的血脂异常管理和下一代心血管疾病预防具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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

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

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 via 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.

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来源期刊
World Journal of Gastroenterology
World Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
7.80
自引率
4.70%
发文量
464
审稿时长
2.4 months
期刊介绍: The primary aims of the WJG are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in gastroenterology and hepatology.
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