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Here, we show that LA markedly and dose\u2010dependently attenuates disease severity in collagen\u2010induced arthritis mice, as evidenced by reduced clinical arthritis scores, systemic inflammatory cytokines, and synovial tissue damage. LA reshaped the gut microbiota, and fecal microbiota transplantation from LA\u2010treated donors partially reproduced its protective effects, indicating a causal contribution of the altered microbial community. In particular, LA selectively enriched OTUs annotated as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Lactobacillus murinus<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>L. murinus<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) and increased levels of the microbial tryptophan metabolite indole\u20103\u2010acetic acid (IAA). Both LA and IAA activated aryl hydrocarbon receptor (AhR) signaling, suppressed tumor necrosis factor\u2010\u03b1\u2010induced inflammatory responses in human synoviocytes, and, in\u00a0vivo, enhanced IAA\u2013AhR\u2013interleukin\u201010 (IL\u201010) signaling in arthritic joints. Pharmacological inhibition of AhR with CH223191 substantially reversed LA's therapeutic effects, demonstrating that AhR signaling plays a critical role in its anti\u2010arthritic activity. Collectively, these findings demonstrate that LA protects against RA through a dual mechanism: direct activation of AhR in joint tissues and indirect reinforcement of AhR signaling through an\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>L. murinus<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u2010associated microbial IAA axis. This study highlights a gut microbiota\u2013metabolite\u2013AhR pathway as a key mediator of LA's anti\u2010arthritic effects and supports LA as a promising microbiota\u2010informed therapeutic candidate for RA.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70316","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:59:41Z","timestamp":1774699181000},"page":"3336-3353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loganic Acid Ameliorates Rheumatoid Arthritis via the\n                    <scp>\n                      <i>Lactobacillus murinus<\/i>\n                    <\/scp>\n                    \u2010Inodole\u20103\u2010Acetic Acid\u2013\n                    <scp>AhR<\/scp>\n                    \u2013\n                    <scp>IL<\/scp>\n                    \u201010 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Laboratory of New Drug Screening School of Pharmaceutical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Lin","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingni","family":"Cai","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelin","family":"Huang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug 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