{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:18:36Z","timestamp":1794367116081,"version":"4.9.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Progranulin (PGRN) has been shown to play a protective role in the development of a variety of immune-mediated diseases, and the gut microbiome has been implicated in the pathogenesis of autoimmune diseases. In this study, we investigate the changes in the gut microbiota and their association with the severity of experimental autoimmune uveitis (EAU) in PGRN-deficient mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WT and PGRN-deficient C57BL\/6 mice were used to induce EAU using interphotoreceptor-binding protein peptide. Gastrointestinal (GI) contents collected from both groups of induced EAU were subjected to 16S rRNA gene sequencing analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PGRN-deficient mice developed exacerbated EAU compared to wild-type (WT) mice. The microbial richness of the GI contents in PGRN-deficient EAU\u00a0mice was significantly lower than in WT mice. The PGRN-deficient EAU mice\u00a0showed a significantly reduced microbial abundance in five phyla, namely,\n                      <jats:italic>Cyanobacteria<\/jats:italic>\n                      ,\n                      <jats:italic>Epsilonbacteraeota<\/jats:italic>\n                      ,\n                      <jats:italic>Firmicutes<\/jats:italic>\n                      ,\n                      <jats:italic>Nitrospirae<\/jats:italic>\n                      , and\n                      <jats:italic>Patescibacteria<\/jats:italic>\n                      , and a significantly increased abundance in the other four phyla, namely,\n                      <jats:italic>Deferribacteres<\/jats:italic>\n                      ,\n                      <jats:italic>Proteobacteria<\/jats:italic>\n                      ,\n                      <jats:italic>Spirochaetes<\/jats:italic>\n                      , and\n                      <jats:italic>Tenericutes<\/jats:italic>\n                      . More importantly, a newly emerged phylum named\n                      <jats:italic>Chlamydiae<\/jats:italic>\n                      was detected in the gut microbial community of PGRN-deficient EAU mice. The histopathological scores were significantly negatively correlated with gut microbial abundance and significantly positively correlated with chlamydial abundance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results showed that PGRN plays a protective role in EAU, and the significant changes in the gut microbiome may be associated with the exacerbation of inflammation in the PGRN-deficient EAU mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1641755","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:48:25Z","timestamp":1769150905000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbial alterations associated with the exacerbation of experimental autoimmune uveitis in PGRN-deficient 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