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

Dec 4, 2025Biomolecules & biomedicine

Gut bacteria particles in Alzheimer's disease: immune effects, potential markers, and treatment options

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Abstract

Gut-derived extracellular vesicles (mEVs) may play a significant role in the progression of Alzheimer's disease.

The gut-brain axis has emerged as a key factor in Alzheimer's disease pathogenesis.
Microbiota-derived extracellular vesicles can transport bioactive substances across barriers, linking gut health to neurodegeneration.
mEVs may activate brain immune cells and influence the metabolism of amyloid-β and tau proteins.
The proposed 'microbiota-EV-immune-neuro axis' connects gut dysbiosis with neurodegenerative processes.
Emerging data suggest mEV signatures could serve as minimally invasive biomarkers for Alzheimer's disease.
Current findings regarding mEVs are preliminary and highlight the need for further standardized studies.

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

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