Proteomic and Metabolomic Profiling of Archaeal Extracellular Vesicles from the Human Gut

Viktoria Weinberger; Barbara Darnhofer; Himadri B Thapa; Polona Mertelj; Régis Stentz; Emily J. 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 M. Strohmaier; Dagmar Kolb; Kathryn Gotts; Thomas Weichhart; Thomas Köcher; Harald C. Köfeler; Simon Richard Carding; Stefan Schild; Christine Moissl‐Eichinger

doi:10.1038/s41467-025-60271-w

MicrobiologyNature CommunicationsJun 3, 2025

Peer-reviewed journal article

Proteomic and Metabolomic Profiling of Archaeal Extracellular Vesicles from the Human Gut

Viktoria Weinberger iD, Barbara Darnhofer iD, Himadri B Thapa iD, Polona Mertelj, Régis Stentz iD, Emily J. Jones iD, Gerlinde Grabmann iD, Rokhsareh Mohammadzadeh, Tejus Shinde iD, Christina Karner iD, Jennifer Ober, Rokas Juodeikis iD, Dominique Pernitsch, Kerstin Hingerl, Tamara Zurabishvili, Christina Kumpitsch iD, Torben Kuehnast iD, Beate Rinner iD, Heimo M. Strohmaier iD, Dagmar Kolb iD, Kathryn Gotts iD, Thomas Weichhart iD, Thomas Köcher iD, Harald C. Köfeler iD, Simon Richard Carding iD, , Christine Moissl‐Eichinger iD

Abstract

One potential mechanism for microbiome-host, and microbiome constituents interaction and communication involves extracellular vesicles (EVs). Here, for the first time, we report the capability of two M. smithii strains (ALI and GRAZ-2), Candidatus M. intestini, and Methanosphaera stadtmanae, as underrepresented components of the gut microbiome, to produce EVs. Interesting, size, morphology, and composition of AEVs were comparable to bacterial EVs, as indicated by ultrastructure, composition, proteomic and metabolomic analyses; however, EVs were substantially less prevalent in the studied Archaea. When looking at the proteomics more precisely, although AEVs from M. smithii ALI and M. intestini were found to be carrying unique proteins (n=135 and n=30, respectively), the shared proteins in AEVs within this genus (n=229), were mostly adhesins(/like) proteins, or proteins with IG-like domains. One remarkable observation was the uptake of AEVs obtained from Methanosphaera stadtmanae and the studied Methanobrevibacter species by human monocytes and the subsequent IL-8 secretion.

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