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ToolsWeinberger, Viktoria, Darnhofer, Barbara, Thapa, Himadri B., Mertelj, Polona, Stentz, Régis, Jones, Emily, Grabmann, Gerlinde, Mohammadzadeh, Rokhsareh, Shinde, Tejus, Karner, Christina, Ober, Jennifer, Juodeikis, Rokas, Pernitsch, Dominique, Hingerl, Kerstin, Zurabishvili, Tamara, Kumpitsch, Christina, Kuehnast, Torben, Rinner, Beate, Strohmaier, Heimo, Kolb, Dagmar, Gotts, Kathryn, Weichhart, Thomas, Köcher, Thomas, Köfeler, Harald, Carding, Simon R., Schild, Stefan and Moissl-Eichinger, Christine (2025) Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea. Nature Communications, 16 (1). pp. 1-17. ISSN 2041-1723
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Abstract
Gastrointestinal bacteria interact with the host and each other through various mechanisms, including the production of extracellular vesicles (EVs). However, the composition and potential roles of EVs released by gut archaea are poorly understood. Here, we study EVs produced by four strains of human gut-derived methanogenic archaea: Methanobrevibacter smithii ALI, M. smithii GRAZ-2, M. intestini, and Methanosphaera stadtmanae. The size (~130 nm) and morphology of these EVs are comparable to those of bacterial EVs. Proteomic and metabolomic analyses reveal that the archaeal EVs are enriched in putative adhesins or adhesin-like proteins, free glutamic and aspartic acid, and choline glycerophosphate. The archaeal EVs are taken up by macrophages in vitro and elicit species-specific responses in immune and epithelial cell lines, including production of chemokines such as CXCL9, CXCL11, and CX3CL1. The EVs produced by M. intestini strongly induce pro-inflammatory cytokine IL-8 in epithelial cells. Future work should examine whether archaeal EVs play roles in the interactions of archaea with other gut microbes and with the host.
| Item Type: | Article |
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| Additional Information: | We thank Stefanie Duller for providing electron micrographs, Eliska Sedlackova for additional proof reading, and the John Innes Centre Bioimaging facility and staff for their contribution to this publication. The support for V. Weinberger through the local dissertation program MolMed is acknowledged. The authors acknowledge the support of the ZMF Galaxy Team: Core Facility Computational Bioanalytics, Medical University of Graz, funded by the Austrian Federal Ministry of Education, Science and Research, Hochschulraum-Strukturmittel 2016 grant as part of BioTechMed Graz. The Vienna BioCenter Core Facilities (VBCF) Metabolomics Facility acknowledges funding from the Austrian Federal Ministry of Education, Science & Research; and the City of Vienna. Data Availability Full proteomic data obtained from mass spectrometry are available via ProteomeXchange Consortium partner repository under dataset identifier PXD053245. Metabolomic data used in this study are available via MetaboLights under accession number MTBLS12422. Other data generated in the study are provided in the Supplementary Information, Source Data files and/or our Github repository (https://github.com/vikwein/Archaeal_extracellular_vesicles). Source data are provided with this paper. |
| Uncontrolled Keywords: | general chemistry,general biochemistry,genetics and molecular biology,general physics and astronomy ,/dk/atira/pure/subjectarea/asjc/1600/1600 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | 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 Medicine and Health Sciences > Research Centres > Metabolic Health |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 19 May 2026 12:20 |
| Last Modified: | 19 May 2026 12:20 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/103093 |
| DOI: | 10.1038/s41467-025-60271-w |
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