{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:40:25Z","timestamp":1792521625903,"version":"4.5.0"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"43","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI162696"],"award-info":[{"award-number":["AI162696"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI146888"],"award-info":[{"award-number":["AI146888"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T35AI060528"],"award-info":[{"award-number":["T35AI060528"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,27]]},"abstract":"<jats:p>\n                    The intestinal microbiota is a critical determinant of mucosal homeostasis, yet the functional contributions of Archaea\u2014which constitute up to 10% of the anaerobic community\u2014remain largely undefined. Here, we provide evidence that the human methanogens\n                    <jats:italic toggle=\"yes\">Methanobrevibacter smithii<\/jats:italic>\n                    (MSm) and\n                    <jats:italic toggle=\"yes\">Methanosphaera stadtmanae<\/jats:italic>\n                    (MSt) promote colonic health. Transcriptomic analysis of germ-free mice reveals that MSm and MSt induce distinct colonic programs important for epithelial integrity. Using gnotobiotic and antibiotic-treated specific-pathogen-free mouse models, we show that MSm and MSt reinforce the epithelial barrier, characterized by increased goblet cell expansion, mucus thickening, and enhanced epithelial regeneration. Furthermore, methanogens expand Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cell (T\n                    <jats:sub>reg<\/jats:sub>\n                    ) populations without inducing pro-inflammatory T\n                    <jats:sub>H<\/jats:sub>\n                    17 responses. Notably, MSm and MSt protect against dextran sodium sulfate-induced colitis. While MSt-mediated protection requires adaptive immunity, MSm retains partial efficacy in lymphocyte-deficient mice, revealing nonredundant protective mechanisms. These findings indicate that methanogenic archaea promote mucosal integrity during host association and suggest that methanogens may hold therapeutic potential for inflammatory bowel disease, though translation to human disease remains to be established.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2610622123","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:01:52Z","timestamp":1792519312000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Methanogenic archaea\n                    <i>Methanobrevibacter smithii<\/i>\n                    and\n                    <i>Methanosphaera stadtmanae<\/i>\n                    promote mucosal homeostasis and protect from colitis"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8532-3935","authenticated-orcid":false,"given":"Emily E.","family":"Byrd","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4581-908X","authenticated-orcid":false,"given":"Benjamin W.","family":"Harris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongpan","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genomic Sciences, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Elise","family":"Warren","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sree H.","family":"Kolli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-6360","authenticated-orcid":false,"given":"Audrey M.","family":"Putelo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell T.","family":"McGinty","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9148-2836","authenticated-orcid":false,"given":"Michael D.","family":"Solga","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Flow Cytometry Core Facility, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie R.","family":"Rutkowski","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7334-5347","authenticated-orcid":false,"given":"Melissa M.","family":"Kendall","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13960"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.01.017"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.007"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i43.16062"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14020196"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007063"},{"key":"e_1_3_4_7_2","first-page":"17","article-title":"Markers of dysbiosis in patients with ulcerative colitis and Crohn\u2019s disease","volume":"91","author":"Danilova N. 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