Gut microbiota-derived extracellular vesicles in Alzheimer’s disease – Immunomodulatory mechanisms, biomarkers, and therapeutic opportunities: A review

Ronghua Yuan; Fei Liu; Jingang Yu

doi:10.17305/bb.2025.13213

Authors

Ronghua Yuan School of Nursing, Jiujiang University, Jiujiang, China; Center for Cognitive Science and Transdisciplinary Studies, Jiujiang University, Jiujiang, China; JiuJiang HML exploratory Healthy-tech Co., Ltd, Jiujiang University, Jiujiang, China; JiangXi XianKeLai Biotech Co., Ltd, Jiujiang, China. https://orcid.org/0000-0001-6435-9555
Fei Liu Jiujiang Emergency Medical Center, Jiujiang, China
Jingang Yu The Second Affiliated Hospital of Jiujiang University, Jiujiang, China

DOI:

https://doi.org/10.17305/bb.2025.13213

Keywords:

Gut microbiota-derived extracellular vesicles, Alzheimer’s disease, neuroinflammation, immune regulation, gut-brain axis, microbiota-immune-neuro axis

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that poses a growing global health challenge. Beyond traditional hallmarks such as amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation, the gut–brain axis (GBA) has emerged as a significant modulator of AD pathogenesis. Among gut-derived mediators, microbiota-derived extracellular vesicles (mEVs) transport bioactive cargo across epithelial and vascular barriers, thereby linking intestinal dysbiosis to neurodegeneration. This narrative review synthesizes experimental, translational, and early clinical evidence regarding the immunomodulatory roles of gut mEVs in AD. We examine how mEVs may traverse compromised intestinal and blood–brain barriers, activate microglia and astrocytes, and influence Aβ and tau metabolism, thereby integrating peripheral and central immune interactions. Based on this evidence, we propose the "microbiota–EV–immune–neuro axis" as a conceptual framework that connects gut dysbiosis with AD-related neurodegeneration. The review also highlights emerging data on mEV signatures as minimally invasive biomarkers and explores their potential as therapeutic targets or delivery vectors. While current evidence is preliminary and methodologically heterogeneous, mEVs are increasingly recognized as both indicators and potential modulators of AD pathophysiology, emphasizing the need for standardized, longitudinal, and interventional studies.

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