Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea

Viktoria Weinberger, Barbara Darnhofer, Himadri B. Thapa, Polona Mertelj, Régis Stentz, Emily Jones, Gerlinde Grabmann, Rokhsareh Mohammadzadeh, Tejus Shinde, Christina Karner, Jennifer Ober, Rokas Juodeikis, Dominique Pernitsch, Kerstin Hingerl, Tamara Zurabishvili, Christina Kumpitsch, Torben Kuehnast, Beate Rinner, Heimo Strohmaier, Dagmar Kolb, Kathryn Gotts, Thomas Weichhart, Thomas Köcher, Harald Köfeler, Simon R. Carding, Stefan Schild and Christine Moissl-Eichinger ()
Additional contact information
Viktoria Weinberger: Medical University of Graz
Barbara Darnhofer: Medical University of Graz
Himadri B. Thapa: University of Graz
Polona Mertelj: Medical University of Graz
Régis Stentz: Quadram Institute Bioscience
Emily Jones: Quadram Institute Bioscience
Gerlinde Grabmann: Metabolomics
Rokhsareh Mohammadzadeh: Medical University of Graz
Tejus Shinde: Medical University of Graz
Christina Karner: Medical University of Graz
Jennifer Ober: Medical University of Graz
Rokas Juodeikis: Quadram Institute Bioscience
Dominique Pernitsch: Medical University of Graz
Kerstin Hingerl: Medical University of Graz
Tamara Zurabishvili: Medical University of Graz
Christina Kumpitsch: Medical University of Graz
Torben Kuehnast: Medical University of Graz
Beate Rinner: Medical University of Graz
Heimo Strohmaier: Medical University of Graz
Dagmar Kolb: Medical University of Graz
Kathryn Gotts: Quadram Institute Bioscience
Thomas Weichhart: Medical University of Vienna
Thomas Köcher: Metabolomics
Harald Köfeler: Medical University of Graz
Simon R. Carding: Quadram Institute Bioscience
Stefan Schild: University of Graz
Christine Moissl-Eichinger: Medical University of Graz

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60271-w

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