TY - JOUR
T1 - Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea
AU - Weinberger, Viktoria
AU - Darnhofer, Barbara
AU - Thapa, Himadri B.
AU - Mertelj, Polona
AU - Stentz, Régis
AU - Jones, Emily
AU - Grabmann, Gerlinde
AU - Mohammadzadeh, Rokhsareh
AU - Shinde, Tejus
AU - Karner, Christina
AU - Ober, Jennifer
AU - Juodeikis, Rokas
AU - Pernitsch, Dominique
AU - Hingerl, Kerstin
AU - Zurabishvili, Tamara
AU - Kumpitsch, Christina
AU - Kuehnast, Torben
AU - Rinner, Beate
AU - Strohmaier, Heimo
AU - Kolb, Dagmar
AU - Gotts, Kathryn
AU - Weichhart, Thomas
AU - Köcher, Thomas
AU - Köfeler, Harald
AU - Carding, Simon R.
AU - Schild, Stefan
AU - Moissl-Eichinger, Christine
N1 - 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.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105007179930
U2 - 10.1038/s41467-025-60271-w
DO - 10.1038/s41467-025-60271-w
M3 - Article
C2 - 40461460
AN - SCOPUS:105007179930
SN - 2041-1723
VL - 16
SP - 1
EP - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5094
ER -