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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Lactiplantibacillus plantarum<\/jats:italic>\n                    is a widely recognized probiotic with anti-inflammatory potential, yet its efficacy varies among strains and the underlying determinants remain poorly defined. Here, we identify methyl indole-3-acetate (MIA), a previously uncharacterized microbial metabolite, as a contributor to the strain-specific anti-inflammatory effects of\n                    <jats:italic toggle=\"yes\">L. plantarum<\/jats:italic>\n                    . Strains with higher MIA production show stronger protection against colitis in mice, whereas deletion of the key biosynthetic enzyme eliminates this protective effect. Mechanistically, MIA epigenetically activates the transcription of lncRNA\n                    <jats:italic toggle=\"yes\">Snhg9<\/jats:italic>\n                    by promoting histone H4K8 acetylation at its promoter, an effect mediated through direct inhibition of HDAC1. In turn,\n                    <jats:italic toggle=\"yes\">Snhg9<\/jats:italic>\n                    suppresses NF-\u03baB signaling by enhancing the deacetylase activity of SIRT1, thereby attenuating inflammatory responses. Together, our findings support a role for MIA in shaping strain-dependent host responses to\n                    <jats:italic toggle=\"yes\">L. plantarum<\/jats:italic>\n                    , uncover a lncRNA-mediated host\u2013microbe regulatory pathway, and provide a framework for further investigation of strain-specific probiotic function in inflammatory disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2533522123","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:26:36Z","timestamp":1788971196000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Methyl indole-3-acetate contributes to strain-specific anti-inflammatory effects of\n                    <i>Lactiplantibacillus plantarum<\/i>"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8807-1467","authenticated-orcid":false,"given":"Kailin","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00a2xv884","id-type":"ROR","asserted-by":"publisher"}],"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00a2xv884","id-type":"ROR","asserted-by":"publisher"}],"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine","place":["Hangzhou, 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