微生物群-先天免疫相互作用驱动动脉粥样硬化：机制、疾病进展和新兴治疗策略
Microbiota-innate immune crosstalk drives atherosclerosis: mechanisms, disease progression, and emerging therapeutic strategies.
摘要(中文译文)
动脉粥样硬化（AS）是一种由脂质代谢失调、慢性炎症和免疫功能障碍相互作用驱动的复杂心血管疾病。越来越多的证据表明，肠道微生物群不仅调节宿主代谢稳态，还通过与先天免疫系统的复杂相互作用积极参与AS的发生和进展。微生物来源的信号分子，包括脂多糖、外膜囊泡、胞外核酸和TMAO，可激活Toll样受体、NLRP3炎症小体和核酸感知通路，从而促进炎性细胞因子产生、内皮功能障碍和泡沫细胞形成。相反，有益微生物代谢物如短链脂肪酸、胆汁酸和色氨酸衍生代谢物，通过涉及FFAR2/3、AhR、FXR和TGR5的信号通路发挥免疫调节和血管保护作用。反之，先天免疫系统通过屏障防御、吞噬清除和抗菌因子产生来塑造微生物组成和功能，建立起动态且互惠的微生物群-免疫相互作用网络。本综述系统总结了与动脉粥样硬化相关的微生物生态和先天免疫稳态的改变，阐明了微生物群-先天免疫串扰的关键分子机制，并考察了其在疾病演变的四个关键阶段（内皮功能障碍、泡沫细胞形成、斑块进展以及斑块失稳定和破裂）中的动态参与。此外，还全面讨论了新兴治疗策略，包括微生物群重塑、微生物代谢途径调节和基于精准微生物组的干预。微生物群-先天免疫轴为理解动脉粥样硬化发病机制提供了新的概念框架，并代表了未来疾病预防、风险分层和精准治疗的有前景的靶点。
Abstract
Atherosclerosis (AS) is a complex cardiovascular disease driven by the interplay of dysregulated lipid metabolism, chronic inflammation, and immune dysfunction. Increasing evidence has revealed that the gut microbiota not only regulates host metabolic homeostasis but also actively contributes to the initiation and progression of AS through intricate interactions with the innate immune system. Microbial-derived signaling molecules, including lipopolysaccharides, outer membrane vesicles, extracellular nucleic acids, and TMAO, can activate Toll-like receptors, the NLRP3 inflammasome, and nucleic acid-sensing pathways, thereby promoting inflammatory cytokine production, endothelial dysfunction, and foam cell formation. In contrast, beneficial microbial metabolites such as short-chain fatty acids, bile acids, and tryptophan-derived metabolites exert immunomodulatory and vasculoprotective effects through signaling pathways involving FFAR2/3, the AhR, the FXR, and TGR5. Conversely, the innate immune system shapes microbial composition and function through barrier defense, phagocytic clearance, and antimicrobial factor production, establishing a dynamic and reciprocal microbiota-immune interaction network. This review systematically summarizes alterations in microbial ecology and innate immune homeostasis associated with atherosclerosis, elucidates the key molecular mechanisms underlying microbiota-innate immune crosstalk, and examines its dynamic involvement across four critical stages of disease evolution: endothelial dysfunction, foam cell formation, plaque progression, and plaque destabilization and rupture. In addition, emerging therapeutic approaches, including microbiota remodeling, modulation of microbial metabolic pathways, and precision microbiome-based interventions, are comprehensively discussed. The microbiota-innate immune axis provides a novel conceptual framework for understanding atherosclerosis pathogenesis and represents a promising target for future disease prevention, risk stratification, and precision therapeutics.
如何引用
AMA
Yongang Li, Jinheng Zhu, Mingkui Huang, Xuan Liu, Liezhi Wang. Microbiota-innate immune crosstalk drives atherosclerosis: mechanisms, disease progression, and emerging therapeutic strategies.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1900899.
APA
Yongang Li, Jinheng Zhu, Mingkui Huang, Xuan Liu, Liezhi Wang (2026). Microbiota-innate immune crosstalk drives atherosclerosis: mechanisms, disease progression, and emerging therapeutic strategies.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1900899
GB/T 7714
Yongang Li, Jinheng Zhu, Mingkui Huang, Xuan Liu, Liezhi Wang. Microbiota-innate immune crosstalk drives atherosclerosis: mechanisms, disease progression, and emerging therapeutic strategies.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1900899.
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