{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:49:06Z","timestamp":1777988946033,"version":"3.51.4"},"posted":{"date-parts":[[2026,3,19]]},"group-title":"Microbiology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA255116"],"award-info":[{"award-number":["R01CA255116"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK114034"],"award-info":[{"award-number":["R01DK114034"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL122593"],"award-info":[{"award-number":["R01HL122593"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5T32DK007418"],"award-info":[{"award-number":["5T32DK007418"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["PCEFP3_194609"],"award-info":[{"award-number":["PCEFP3_194609"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["TMSGI3_211318"],"award-info":[{"award-number":["TMSGI3_211318"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Multiple Sclerosis Society","award":["FG-1708-2887"],"award-info":[{"award-number":["FG-1708-2887"]}]},{"name":"The Propatient Foundation"},{"name":"The Gottfried and Julia Bangerter Rhyner Foundation"},{"name":"ational Science Foundation Graduate Research Fellowship Program","award":["2038436"],"award-info":[{"award-number":["2038436"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,23]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Women are at increased risk of autoimmune diseases, including multiple sclerosis (MS); however, the degree to which sex differences in the gut microbiota impact autoimmunity remains largely unexplored. Our 27-cohort meta-analysis revealed 60 sex-associated gut bacterial species. Leveraging an independent clinical cohort, we demonstrate that female-enriched species significantly associate with MS status and clinical disability (EDSS). Top female-enriched species\n                  <jats:italic>Eggerthella lenta<\/jats:italic>\n                  drove disease in the experimental autoimmune encephalomyelitis (EAE) MS model, consistent with brain and gut lamina propria T cell infiltration and MS-associated T helper (Th) signatures.\n                  <jats:italic>E. lenta<\/jats:italic>\n                  induced intestinal Th1 and Th17 in healthy mice, independent of bacterial viability. Mechanistically, we demonstrate that TLR2 directly drives\n                  <jats:italic>E. lenta<\/jats:italic>\n                  -induced IFN-\u03b3 production in Th cells and is necessary for exacerbation of EAE. Together, we identify a causal host-microbe axis contributing to sex differences in autoimmunity and provide a framework for evaluating sex as a biological variable in human microbiome research.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>27-cohort meta-analysis identifies a robust sex-signature in human gut microbiota.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Female-enriched species are associated with MS risk and severity.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Female-enriched\n                        <jats:italic>Eggerthella lenta<\/jats:italic>\n                        exacerbates the EAE model.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        <jats:italic>E. lenta<\/jats:italic>\n                        impacts neuroinflammation via toll-like receptor 2.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.16.711194","type":"posted-content","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:05:12Z","timestamp":1773914712000},"source":"Crossref","is-referenced-by-count":1,"title":["Female-enriched\n                  <i>Eggerthella lenta<\/i>\n                  drives neuroinflammation and IFN-\u03b3 via host receptor TLR2"],"prefix":"10.64898","author":[{"given":"Rachel R.","family":"Rock","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 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