{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:54:51Z","timestamp":1792130091300,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571536"],"award-info":[{"award-number":["82571536"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371352"],"award-info":[{"award-number":["82371352"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401478"],"award-info":[{"award-number":["82401478"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Multiple sclerosis (MS) is a central nervous system autoimmune disease primarily driven by Th1 and Th17 cells, whose onset and progression are closely associated with gut microbiota. Kurarinone (KU), an active component from\n                    <jats:italic>Radix Sophora Flavescens<\/jats:italic>\n                    , exhibits anti\u2010inflammatory, immunoregulatory and gut microbiota\u2010modulating properties. However, whether KU alleviates MS severity via a gut microbiota\u2010mediated mechanism remains unclear. Here, we demonstrate that KU ameliorates experimental autoimmune encephalomyelitis (EAE)\u2010an animal model of MS\u2010by modulating the gut microbiota, particularly via enriching\n                    <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    , and\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    is essential for the protective effects of KU in EAE. Furthermore, KU elevates levels of the tryptophan metabolite indole\u20103\u2010acetaldehyde (IAAld). IAAld levels are positively correlated with the relative abundance of\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    and negatively correlated with EAE severity. In vitro,\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    alone is sufficient to facilitate tryptophan metabolism to produce IAAld. IAAld treatment ameliorates EAE and reduces the frequencies of pathogenic Th1 and Th17 cells in mice. Mechanistically, IAAld activates the aryl hydrocarbon receptor (AhR) and suppresses JAK\/STAT signaling, thereby dampening Th1 and Th17 differentiation; these effects are abolished following AhR blockade. Collectively, this study identifies a novel mechanism by which KU mitigates EAE via the gut metabolite IAAld\u2010AhR\u2010immune axis and unveils potential therapeutic targets for MS.\n                  <\/jats:p>","DOI":"10.1002\/advs.78358","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:38:32Z","timestamp":1792129112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota\u2010Derived Indole\u20103\u2010Acetaldehyde Contributes to the Disease\u2010Alleviating Effects of Kurarinone in Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8071-4131","authenticated-orcid":false,"given":"Xinyan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1330-6765","authenticated-orcid":false,"given":"Jiaqi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonghao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0157-5168","authenticated-orcid":false,"given":"Xue","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6678-2602","authenticated-orcid":false,"given":"Cong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology Airforce Medical Center of PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-2389","authenticated-orcid":false,"given":"Jiaji","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-881X","authenticated-orcid":false,"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology Tangdu Hospital The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02415-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202106150"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029025"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.09.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1651"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14181408"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14905"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00460-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2024.05.013"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1128\/CMR.00338-20","article-title":"A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders","volume":"35","author":"Sorboni S. 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D.","year":"2026","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_10_51_1","doi-asserted-by":"crossref","first-page":"0662","DOI":"10.34133\/research.0662","article-title":"Early Growth Response Gene 1 Benefits Autoimmune Disease by Promoting Regulatory T Cell Differentiation as a Regulator of Foxp3","volume":"8","author":"Yang L.","year":"2025","journal-title":"Research"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155239"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.78358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.78358","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.78358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:38:35Z","timestamp":1792129115000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.78358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":51,"alternative-id":["10.1002\/advs.78358"],"URL":"https:\/\/doi.org\/10.1002\/advs.78358","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"2026-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e78358"}}