{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:52Z","timestamp":1792790392716,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,16]]},"group-title":"Immunology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Kennedy Trust for Rheumatology Research"},{"name":"Medical Research Council","award":["MR\/N013468\/1"],"award-info":[{"award-number":["MR\/N013468\/1"]}]},{"name":"Medical Research Council","award":["MR\/W006731\/1"],"award-info":[{"award-number":["MR\/W006731\/1"]}]},{"name":"Medical Research Council","award":["UKRI935"],"award-info":[{"award-number":["UKRI935"]}]},{"name":"Oxford-Radcliffe Graduate Scholarship","award":["SFF2526-RAD-1429369"],"award-info":[{"award-number":["SFF2526-RAD-1429369"]}]},{"name":"European & Developing Countries Clinical Trials Partnership","award":["SRIA2015-1066"],"award-info":[{"award-number":["SRIA2015-1066"]}],"id":[{"id":"https:\/\/ror.org\/031jv9v19","id-type":"ROR","asserted-by":"crossref"}]},{"name":"EU Horizon 2020","award":["681137-EAVI2020"],"award-info":[{"award-number":["681137-EAVI2020"]}]},{"name":"Wellcome Trust","award":["227217\/Z\/23\/Z"],"award-info":[{"award-number":["227217\/Z\/23\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["222426\/Z\/21\/Z"],"award-info":[{"award-number":["222426\/Z\/21\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Cancer Research UK","award":["DRCNPG-Nov22\/100005"],"award-info":[{"award-number":["DRCNPG-Nov22\/100005"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fondation Leducq","award":["RHD23VAC02"],"award-info":[{"award-number":["RHD23VAC02"]}],"id":[{"id":"https:\/\/ror.org\/01czwga19","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:italic>Methanobrevibacter smithii<\/jats:italic>\n                  , 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.\n                <\/jats:p>","DOI":"10.64898\/2026.09.11.750638","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:30:14Z","timestamp":1789619414000},"source":"Crossref","is-referenced-by-count":0,"title":["Gut archaea drive human MAIT cell responses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2285-1220","authenticated-orcid":false,"given":"Natasha","family":"Fisher-Pearson","sequence":"first","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7230-9264","authenticated-orcid":false,"given":"Martin J.","family":"Lett","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine (NDM), University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4684-6165","authenticated-orcid":false,"given":"Isaac W. D.","family":"Maylam","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4190-732X","authenticated-orcid":false,"given":"Connor J. S.","family":"Philp","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine (NDM), University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4821-3801","authenticated-orcid":false,"given":"Mariolina","family":"Salio","sequence":"additional","affiliation":[{"name":"Immunocore Ltd.; Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6962-6533","authenticated-orcid":false,"given":"Richard J.","family":"Suckling","sequence":"additional","affiliation":[{"name":"Immunocore Ltd.; Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Simmons","sequence":"additional","affiliation":[{"name":"Immunocore Ltd.; Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9733-3551","authenticated-orcid":false,"given":"Keir","family":"Barnbrook","sequence":"additional","affiliation":[{"name":"Immunocore Ltd.; Abingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Swift","sequence":"additional","affiliation":[{"name":"Carus Animal Health; Stevenage, UK"},{"name":"Royal Veterinary College; London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Jaoko","sequence":"additional","affiliation":[{"name":"KAVI-Institute of Clinical Research (KAVI-ICR), University of Nairobi; Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddie","family":"Kibengo","sequence":"additional","affiliation":[{"name":"MRC\/UVRI & LSHTM Uganda Research Unit (MUL); Entebbe, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Kilembe","sequence":"additional","affiliation":[{"name":"Center for Family Health Research Zambia (CFHRZ); Lusaka, Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard J.","family":"Sanders","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme (KWTRP); Kilifi, Kenya"},{"name":"The Aurum Institute; Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8079-9358","authenticated-orcid":false,"given":"Mark C.","family":"Coles","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire F.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cicconi","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford; Oxford, UK"},{"name":"Oxford Vaccine Group, Department of Paediatrics, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-9546","authenticated-orcid":false,"given":"Tom\u00e1\u0161","family":"Hanke","sequence":"additional","affiliation":[{"name":"The Jenner Institute, Nuffield Department of Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9694-2216","authenticated-orcid":false,"given":"Nicholas M.","family":"Provine","sequence":"additional","affiliation":[{"name":"Pandemic Sciences Institute, NDM, University of Oxford; Oxford, UK"},{"name":"Centre for Human Genetics, NDM, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-9161","authenticated-orcid":false,"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine (NDM), University of Oxford; Oxford, UK"},{"name":"Peter Medawar Building for Pathogen Research, NDM, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-054X","authenticated-orcid":false,"given":"Jethro S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, University of Oxford; Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091912450622000_2026.09.11.750638v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-0407-y"},{"key":"2026091912450622000_2026.09.11.750638v1.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-080719-015428"},{"key":"2026091912450622000_2026.09.11.750638v1.3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.12.1907"},{"key":"2026091912450622000_2026.09.11.750638v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4866"},{"key":"2026091912450622000_2026.09.11.750638v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature11605"},{"key":"2026091912450622000_2026.09.11.750638v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature13160"},{"key":"2026091912450622000_2026.09.11.750638v1.7","doi-asserted-by":"crossref","first-page":"eadi8954","DOI":"10.1126\/sciimmunol.adi8954","article-title":"MAIT cells monitor intestinal dysbiosis and contribute to host protection during colitis","volume":"9","year":"2024","journal-title":"Sci. Immunol"},{"key":"2026091912450622000_2026.09.11.750638v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw2719"},{"key":"2026091912450622000_2026.09.11.750638v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax6624"},{"key":"2026091912450622000_2026.09.11.750638v1.10","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-016-0927-9"},{"key":"2026091912450622000_2026.09.11.750638v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.009"},{"key":"2026091912450622000_2026.09.11.750638v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343509"},{"key":"2026091912450622000_2026.09.11.750638v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11653"},{"key":"2026091912450622000_2026.09.11.750638v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01575-1"},{"key":"2026091912450622000_2026.09.11.750638v1.15","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00279-12"},{"key":"2026091912450622000_2026.09.11.750638v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302799110"},{"key":"2026091912450622000_2026.09.11.750638v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003681"},{"key":"2026091912450622000_2026.09.11.750638v1.18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160637"},{"key":"2026091912450622000_2026.09.11.750638v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.39"},{"key":"2026091912450622000_2026.09.11.750638v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05202-8"},{"key":"2026091912450622000_2026.09.11.750638v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24570-2"},{"key":"2026091912450622000_2026.09.11.750638v1.22","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1016\/j.celrep.2019.08.050","article-title":"TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions","volume":"28","year":"2019","journal-title":"Cell Rep"},{"key":"2026091912450622000_2026.09.11.750638v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3854"},{"key":"2026091912450622000_2026.09.11.750638v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12021"},{"key":"2026091912450622000_2026.09.11.750638v1.25","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324478"},{"key":"2026091912450622000_2026.09.11.750638v1.26","doi-asserted-by":"crossref","unstructured":"A. J. Corbett , W. Awad , H. Wang , Z. Chen , Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries. Front. Immunol. 11 (2020).","DOI":"10.3389\/fimmu.2020.01961"},{"key":"2026091912450622000_2026.09.11.750638v1.27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001536"},{"key":"2026091912450622000_2026.09.11.750638v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature11053"},{"key":"2026091912450622000_2026.09.11.750638v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.12.017"},{"key":"2026091912450622000_2026.09.11.750638v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1103"},{"key":"2026091912450622000_2026.09.11.750638v1.31","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12193"},{"key":"2026091912450622000_2026.09.11.750638v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3416"},{"key":"2026091912450622000_2026.09.11.750638v1.33","doi-asserted-by":"publisher","DOI":"10.1042\/ETLS20180037"},{"key":"2026091912450622000_2026.09.11.750638v1.34","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.12.4042-4049.1992"},{"key":"2026091912450622000_2026.09.11.750638v1.35","doi-asserted-by":"crossref","first-page":"fuab021","DOI":"10.1093\/femsre\/fuab021","article-title":"Cofactor F420: an expanded view of its distribution, biosynthesis and roles in bacteria and archaea","volume":"45","year":"2021","journal-title":"FEMS Microbiol. Rev"},{"key":"2026091912450622000_2026.09.11.750638v1.36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099411"},{"key":"2026091912450622000_2026.09.11.750638v1.37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01535"},{"key":"2026091912450622000_2026.09.11.750638v1.38","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax8819"},{"key":"2026091912450622000_2026.09.11.750638v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17307-0"},{"key":"2026091912450622000_2026.09.11.750638v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3854"},{"key":"2026091912450622000_2026.09.11.750638v1.41","doi-asserted-by":"crossref","unstructured":"H. den Braanker , M. Bongenaar , E. Lubberts , How to Prepare Spectral Flow Cytometry Datasets for High Dimensional Data Analysis: A Practical Workflow. Front. Immunol. 12 (2021).","DOI":"10.3389\/fimmu.2021.768113"},{"key":"2026091912450622000_2026.09.11.750638v1.42","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-13-104"},{"key":"2026091912450622000_2026.09.11.750638v1.43","doi-asserted-by":"publisher","DOI":"10.5281\/ZENODO.15017011"},{"key":"2026091912450622000_2026.09.11.750638v1.44","doi-asserted-by":"crossref","first-page":"D734","DOI":"10.1093\/nar\/gkaa996","article-title":"HMPDACC: a Human Microbiome Project Multi-omic data resource","volume":"49","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2026091912450622000_2026.09.11.750638v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-021-01153-z"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.11.750638","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:45:16Z","timestamp":1789847116000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.11.750638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":45,"URL":"https:\/\/doi.org\/10.64898\/2026.09.11.750638","relation":{},"subject":[],"published":{"date-parts":[[2026,9,16]]},"subtype":"preprint"}}