Special delivery extracellular vesicles released by commensal gut bacteria deliver bioactive protein to distal organs

Jones E, Juodeikis R, Parker A, Blackshaw LA, Brion A, Carding SR. (2025)

Extracellular Vesicles and Circulating Nucleic Acids


Aim: The intestinal microbiota is an essential component of human health, yet the pathways and mediators of microbiota-host interactions are unclear. Considering the mucus coating of the healthy intestinal epithelium excludes direct interactions, indirect interactions via microbial products such as nanoscale bacterial extracellular vesicles (BEVs) are promising mediators of microbiota-host interactions. Due to their low abundance, investigating BEVs in vivo is challenging.

Methods: We describe the development of a highly sensitive Nanoluciferase system for luminescence-based detection of BEVs produced by the model human commensal bacterium Bacteroides thetaiotaomicron, demonstrating advantages in its use for BEV labelling over conventional lipophilic dyes.

Results: We have used this system to demonstrate BEV translocation and active protein delivery from the intestine of mice to a range of tissues, including the central nervous system. This establishes the ability of BEVs produced in the gastrointestinal tract (GIT) to traverse several physical host barriers including the intestinal epithelium, vascular endothelium, and the blood-brain-barrier to access tissues including the brain and eyes.

Conclusion: These findings both increase our understanding of the scale of BEV-mediated microbe-host interactions and demonstrate their potential use as a long-distance bioactive therapeutic delivery system. 


Extracellular Vesicles and Circulating Nucleic Acids


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