Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth

Price, Christopher A., Jones, Emily J., Ilker, Nilda, Nicklin, Alicia D., Juodeikis, Rokas, McKee, Alastair M., Mitchell, Luke J., Stentz, Régis, Hall, Lindsay J. ORCID: https://orcid.org/0000-0001-8938-5709, Carding, Simon R. and Robinson, Stephen D. ORCID: https://orcid.org/0000-0002-6606-7588 (2026) Systemically delivered Bacteroides thetaiotaomicron-derived bacterial extracellular vesicles inhibit primary and metastatic melanoma growth. Microbiology Spectrum. ISSN 2165-0497

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Abstract

The gut microbiome can contribute to anti-tumor immunity and cancer therapy responses, but translating live microbe-based interventions remains challenging due to safety, controllability, and delivery constraints. Bacterial extracellular vesicles (BEVs) are an attractive cell-free alternative, as they package bacterial cargo into a nanoscale format capable of host-cell engagement, immunological activation, and systemic distribution. Here, we investigated the anti-tumor potential of BEVs derived from the human gut commensal Bacteroides thetaiotaomicron (Bt). We show that the delivery route is a major determinant of efficacy. Intravenous, but not intraperitoneal, administration produced robust anti-tumor activity in a B16F10 melanoma mouse model. Intravenously delivered Bt BEVs suppressed primary tumor growth in a dose-dependent manner and reduced metastatic outgrowth in the lung. Bt BEVs did not reduce B16F10 metabolic viability during a 24-h in vitro exposure, but they activated NF-κB and Toll-like receptor signaling in human reporter systems, and NanoLuc-associated signal from labeled BEV preparations was detected in excised tumor tissue following systemic administration. Although the host pathways responsible for tumor control remain to be defined, these findings identify naturally produced commensal-derived Bt BEVs as a candidate cell-free microbial therapeutic modality for cancer therapy.

Item Type: Article
Additional Information: Data Availability Statement: The numerical source data underlying the quantitative analyses presented in this study are provided in the supplemental material. Additional data supporting the findings of this study are available from the corresponding authors upon reasonable request.
Uncontrolled Keywords: extracellular vesicles,bacteroides thetaiotaomicron,host-microbe interactions,melanoma,microbiome-derived productsmicrobiome-derived products,das in place,the numerical source data underlying the quantitative analyses presented in this study are provided in the supplemental material. additional data supporting the findings of this study are available from the corresponding authors upon reasonable request.,2026 ,/dt/atira/pure/keyword/DAStatement/das_in_place
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Science > Research Groups > Cells and Tissues
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Depositing User: LivePure Connector
Date Deposited: 13 Oct 2026 15:20
Last Modified: 13 Oct 2026 15:20
URI: https://ueaeprints.uea.ac.uk/id/eprint/104771
DOI: 10.1128/spectrum.02512-26

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