Year: 2026
Type: preprint
Abstract: Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood. Mucosal-associated invariant T (MAIT) cells sense microbial metabolites through their T cell receptor and contribute to antimicrobial defence and barrier homeostasis. Key sources of the major MAIT cell antigen 5-OP-RU within the human gut microbiome are unknown. Analysing microbiomes from UK, Zambian, Kenyan and Ugandan donors, we found strong correlations between archaeal riboflavin biosynthesis and circulating MAIT cell frequency and activation. Stool 5-OP-RU levels correlated with archaeal abundance. Cultures of methanogenic archaea, including the human commensal Methanobrevibacter smithii , produced 5-OP-RU and strongly activated MAIT cells without inflammation. We demonstrate a critical role for archaea in shaping human immunity, with implications for microbiome-mediated regulation of health.
Authors: Natasha Fisher-Pearson, Martin J. Lett, Isaac W. D. Maylam, Connor J. S. Philp, Mariolina Salio, Richard J. Suckling, Robert Simmons, Keir Barnbrook, Benjamin Swift, Walter Jaoko, Freddie Kibengo, William Kilembe, Eduard J. Sanders, Mark C. Coles, Claire F. Pearson, Paola Cicconi, Tomáš Hanke, Nicholas M. Provine, Paul Klenerman, Jethro S. Johnson
Institutions: University of Oxford, Kennedy Institute of Rheumatology, Immunocore (United Kingdom), Royal Veterinary College, University of Nairobi, Kenya AIDS Vaccine Initiative, MRC/UVRI & LSHTM Uganda Research Unit, Uganda Virus Research Institute, Kenya Medical Research Institute, Aurum Institute, KEMRI-Wellcome Trust Research Programme, Jenner Institute, Centre for Human Genetics, Medawar Building for Pathogen Research
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Mechanistic investigation of vaccine immunogenicity, DTP Bid Led by University of Oxford, G2354209684, G2790579513, Mechanistic investigation of vaccine immunogenicity, Globally Relevant AIDS Vaccine Europe-Africa Trials Partnership, Innate-like T cells and integration of host defence, G4951612468, G5267706263, G5331953782, DTP Bid Led by University of Oxford, G563290157, G564868737, G7289447374, Innate-like T cells and integration of host defence, G8492079668, G8569936322, G8869923972
OpenAlex ID: W7213458400