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

Microorganisms thriving in the human gastrointestinal microbiome have developed numerous mechanisms for microbiome-host and microbe-microbe interaction, including the formation of extracellular vesicles (EVs). However, the interactive mechanisms of members of the human archaeome remained largely unexplored. Here, we report the capability of two Methanobrevibacter strains M. smithii, Cand. M. intestini and Methanosphaera stadtmanae, to produce EVs. While the size (~ 130 nm) and morphology of these archaeal EVs were comparable to bacterial EVs, proteomic and metabolomic analyses revealed unique traits. The proteins found in both the EVs of M. smithii and Cand. M. intestini (n = 229) predominantly included adhesin and adhesin-like proteins, involved in archaea-surface and archaea-bacteria interaction. Additionally, the archaeal EVs contained glutamic acid and choline glycerophosphate, which could be involved in gut-brain signalling. Vesicles from all studied species were efficiently taken up by human monocytes and induced IL-8 production in epithelial HT-29 cells. The identification of archaeal EVs and their components provides novel insights into the complex interactions between the archaeal and bacterial microbiome and the host, potentially offering new paths to modulate vesicle-mediated impacts on host health.