{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:34:05Z","timestamp":1793126045953,"version":"4.5.0"},"posted":{"date-parts":[[2025,12,6]]},"group-title":"Immunology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["EY000184"],"award-info":[{"award-number":["EY000184"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The gut microbiome influences the development of immune-mediated inflammatory diseases, including autoimmune uveitis, a sight-threatening ocular inflammation driven by retina-specific T cells\n                  <jats:sup>1<\/jats:sup>\n                  . Using a model of spontaneous autoimmune uveitis (sEAU) we showed that gut commensals provide immune stimuli that trigger disease\n                  <jats:sup>2<\/jats:sup>\n                  . Here we report that uveitis-promoting microbes are present in human gut flora and that colonization of germ-free (GF) mice with commensals from healthy human donors was sufficient to provoke disease. Severity of sEAU correlated with expansion of Akkermansia and contraction of short-chain fatty acid (SCFA)-producing Firmicutes, accompanied by decreased SCFA levels and a dominant gut Th1 effector response. Mechanistic gain-of-function experiments, enriching GF sEAU mice with\n                  <jats:italic>A. muciniphila<\/jats:italic>\n                  , reproduced these microbiome, metabolite and immune phenotype shifts, and exacerbated disease. We propose that Akkermansia promotes autoimmunity by outcompeting SCFA producers and enhancing Th1-type responses. An inverse correlation between Akkermansia (Verrucomicrobia) and Firmicutes was also present in fecal microbiota from patients with uveitis; related Verrucomicrobia\/Firmicutes shifts were observed in multiple sclerosis and Crohn\u2019s disease datasets. These findings reveal a stereotypic gut microbial interaction network that regulates systemic immune balance, and may represent an ecologically conserved mechanism through which the gut microbiome modulates autoimmune and inflammatory diseases.\n                <\/jats:p>","DOI":"10.64898\/2025.12.04.691931","type":"posted-content","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:43:13Z","timestamp":1765197793000},"source":"Crossref","is-referenced-by-count":1,"title":["Gut microbial interaction networks control autoimmunity to neuroretina"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-5169","authenticated-orcid":false,"given":"Amy","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-4444","authenticated-orcid":false,"given":"Reiko","family":"Horai","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6977-2728","authenticated-orcid":false,"given":"Yingyos","family":"Jittayasothorn","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Badger","sequence":"additional","affiliation":[{"name":"Genetics and Microbiome Core, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 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