The use of a multicellular in vitro model to investigate uptake and migration of bacterial extracellular vesicles derived from the human gut commensal Bacteroides thetaiotaomicron

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Modasia, Amisha A., Jones, Emily J., Martel, L. Marie Pascale, Louvel, Hélène, Couraud, Pierre Olivier, Blackshaw, L. Ashley and Carding, Simon R. (2023) The use of a multicellular in vitro model to investigate uptake and migration of bacterial extracellular vesicles derived from the human gut commensal Bacteroides thetaiotaomicron. Journal of Extracellular Biology, 2 (7). ISSN 2768-2811

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Abstract

Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence of BEVs ability to transmigrate across cellular barriers to elicit responses in other tissues, such as the central nervous system (CNS). Here we use a combination of single-, two- and three-cell culture systems to demonstrate the transmigration of Bacteroides thetaiotaomicron derived BEVs (Bt-BEVs) across gut epithelium and blood brain barrier (BBB) endothelium, and their subsequent acquisition and downstream effects in neuronal cells. Bt-BEVs were shown to traffic to the CNS in vivo after intravenous administration to mice, and in multi-cell in vitro culture systems to transmigrate across gut epithelial and BBB endothelial cell barriers, where they were acquired by both microglia and immature neuronal cells. No significant activation/inflammatory effects were induced in non-differentiated neurons, in contrast to that observed in microglia cells, although this was notably less than that induced by lipopolysaccharide (LPS). Overall, our findings provide evidence for transmigration of Bt-BEVs across gut-epithelial and BBB endothelial cell barriers in vivo and in vitro, and their downstream responses in neural cells. This study sheds light onto how commensal bacteria-derived BEV transport across the gut-brain axis and can be exploited for the development of targeted drug delivery.

Item Type: Article
Additional Information: Publisher Copyright: © 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
Uncontrolled Keywords: bacterial extracellular vesicles,brain,cell culture models,gut,trafficking,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 01 Jun 2026 08:43
Last Modified: 06 Jun 2026 13:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/103206
DOI: 10.1002/jex2.93

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