Gut microbiota-derived extracellular vesicles as autonomous regulators of host immunity and gut-organ axes: Cellular mechanisms of cross-kingdom communication in inflammatory, metabolic, and neurodegenerative diseases.
越来越多的实证证据表明，来源于肠道菌群的细胞外囊泡（GM-EVs）作为独立的生物学实体，促进微生物与宿主细胞之间的跨王国通讯。除反映微生物群落的组成外，GM-EVs还传递蛋白质、脂质、代谢物和调节性核酸等生物活性成分，使其能够穿越生物屏障并调控宿主的免疫、代谢和神经元信号级联。在本叙述性综述中，我们系统阐述了GM-EVs影响宿主免疫并协调肠-器官轴的最新细胞和分子机制进展，特别侧重于炎症性、代谢性和神经退行性病理。尤其关注肠-脑轴，强调新出现的证据表明微生物群来源的EVs影响小胶质细胞活化、神经炎症、突触可塑性和淀粉样蛋白-β病理，从而在认知衰退和阿尔茨海默病进展中发挥作用。我们进一步审视致病性与益生菌来源的EVs在调节宿主反应中的双功能作用，强调其对上皮屏障完整性、免疫极化和神经稳态的背景依赖性影响。最后，我们探讨肠道菌群来源的EVs作为新型生物标志物、后生元治疗剂和药物递送系统的转化应用前景，同时面对与EV异质性、分离方案标准化和机制特异性相关的现有挑战。我们还讨论了新出现的证据，即微生物群来源的EVs通过传递影响胎儿免疫成熟和发育稳态的微生物及免疫调节信号，参与母胎通讯和产前免疫编程。总之，本综述将肠道菌群来源的细胞外囊泡描述为跨王国信号传导的关键调控因子，以及复杂慢性疾病精准干预管理中有前景的靶点。
Accumulating empirical evidence suggests that extracellular vesicles derived from gut microbiota (GM-EVs) function as independent biological entities that facilitate inter-kingdom communication between microorganisms and host cells. In addition to reflecting the composition of microbial communities, GM-EVs convey bioactive components including proteins, lipids, metabolites, and regulatory nucleic acids, which empower them to traverse biological barriers and modulate host immune, metabolic, and neuronal signaling cascades. In this narrative review, we systematically elucidate contemporary advancements in the cellular and molecular mechanisms by which GM-EVs influence host immunity and orchestrate gut-organ axes, with a specific emphasis on inflammatory, metabolic, and neurodegenerative pathologies. Particular focus is directed toward the gut-brain axis, underscoring emerging evidence that microbiota-derived EVs impact microglial activation, neuroinflammation, synaptic plasticity, and amyloid-β pathology, thereby playing a role in cognitive decline and the progression of Alzheimer's disease. We further examine the bifunctional roles of pathogenic versus probiotic-derived EVs in modulating host responses, underscoring their context-dependent influences on epithelial barrier integrity, immune polarization, and neural homeostasis. Ultimately, we investigate the translational applicability of gut microbiota-derived EVs as innovative biomarkers, postbiotic therapeutics, and drug-delivery systems, while confronting existing challenges pertaining to EV heterogeneity, standardization of isolation protocols, and mechanistic specificity. We additionally discuss emerging evidence that microbiota-derived EVs participate in maternal-fetal communication and prenatal immune programming by transmitting microbial and immunomodulatory signals that influence fetal immune maturation and developmental homeostasis. Collectively, this review delineates gut microbiota-derived extracellular vesicles as pivotal regulators of interkingdom signaling and as promising targets for precision interventions in the management of complex chronic diseases.
Yong Wang, Qingzhi Wang. Gut microbiota-derived extracellular vesicles as autonomous regulators of host immunity and gut-organ axes: Cellular mechanisms of cross-kingdom communication in inflammatory, metabolic, and neurodegenerative diseases.. International immunopharmacology. 2026; doi:10.1016/j.intimp.2026.116964.
Yong Wang, Qingzhi Wang (2026). Gut microbiota-derived extracellular vesicles as autonomous regulators of host immunity and gut-organ axes: Cellular mechanisms of cross-kingdom communication in inflammatory, metabolic, and neurodegenerative diseases.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116964
Yong Wang, Qingzhi Wang. Gut microbiota-derived extracellular vesicles as autonomous regulators of host immunity and gut-organ axes: Cellular mechanisms of cross-kingdom communication in inflammatory, metabolic, and neurodegenerative diseases.[J]. International immunopharmacology, 2026 doi:10.1016/j.intimp.2026.116964.
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