{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:46:16Z","timestamp":1792266376154,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017691","name":"Guangxi Key Research and Development Program","doi-asserted-by":"publisher","award":["AB25069068"],"award-info":[{"award-number":["AB25069068"]}],"id":[{"id":"10.13039\/501100017691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2023NSFSC1702"],"award-info":[{"award-number":["2023NSFSC1702"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271828"],"award-info":[{"award-number":["82271828"]}],"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":["82302049"],"award-info":[{"award-number":["82302049"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our study's objective is to investigate the specific role of tryptophan metabolism, especially that of microbiome\u2010derived metabolites, in the development of rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed metabolomics to profile metabolites in 53 individuals at high risk for RA (PreRA), 30 patients with established RA, and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen\u2010induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells\u2019 barrier function were assessed by flow cytometry, immunofluorescence staining, and Western blotting. Co\u2010immunoprecipitation and luciferase were applied for molecular mechanism studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dysregulated tryptophan metabolism exists in individuals with RA and PreRA, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole\u20103\u2010lactic acid (ILA) and indole\u20103\u2010acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)\u2013aryl hydrocarbon receptor nuclear translocator\u2013xenobiotic response element signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo\u20101 and occludin expression in Caco\u20102 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that tryptophan indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43430","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T11:03:42Z","timestamp":1762772622000},"page":"613-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Gut Microbiota\u2013Derived Tryptophan Indole Metabolites Ameliorate Collagen\u2010Induced Arthritis in Mice Via Aryl Hydrocarbon Receptor Activation"],"prefix":"10.1002","volume":"78","author":[{"given":"Liang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-2352","authenticated-orcid":false,"given":"Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvyi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences South\u2010Central Minzu University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Rheumatology and Immunology, West China Hospital Sichuan University  Chengdu Sichuan 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