Gut-to-Body: Regulatory Roles of Probiotic Extracellular Vesicles in Healthy Homeostasis

• Probiotics and postbiotics aid gut health and immune regulation. • Postbiotics include probiotic extracellular vesicles with promising effects. • Extracellular vesicles help mitigate NDDs by crossing the BBB. • Further research is needed to clarify their mechanisms and clinical potential. The benefits of probiotics in maintaining gut health and regulating immune responses are widely recognized. Emerging evidence has revealed the existence of bidirectional communication between the gut microbiota and the central nervous system (CNS), termed the "microbiota gut-brain-axis." This axis serves as a critical regulator of neuroglial function, which establishes it as an actionable target for mitigating the development and progression of neurodegenerative diseases (NDDs). Bacterial extracellular vesicles (BEVs) containing bioactive proteins, lipids, nucleic acids, and metabolites released by bacteria have now been identified as potential key mediators of both bacteria-bacteria and bacteria-host interactions. Postbiotics, defined as non-viable microbial preparations and/or their components that confer health benefits to the host, encompass probiotic-derived extracellular vesicles (P-EVs)— nanoscale by-products secreted by probiotics. These P-EVs may serve as novel postbiotics with potential critical roles in mitigating NDDs. Framed within the probiotic paradigm, this review systematically examines fundamental aspects of P-EVs, including their biosynthesis, core compositional profiles, and transport mechanisms. We further elucidate the underlying mechanisms through which P-EVs ameliorate NDDs. Finally, we postulate that P-EVs, as innovative postbiotics, may provide robust support for developing neuroprotective intervention strategies within functional food formulations targeting NDDs.