{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:23:11Z","timestamp":1785424991059,"version":"3.56.0"},"reference-count":100,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81704055"],"award-info":[{"award-number":["81704055"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["81704055"],"award-info":[{"award-number":["81704055"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Beyond their established role in lipid digestion, bile acids function as key metabolic and immune signaling molecules. This review synthesizes recent advances in bile acid metabolism within the context of gout and hyperuricemia, proposing a gut\u2013liver\u2013joint crosstalk framework. Dysregulated bile acid metabolism\u2014characterized by a reduced total bile acid pool, decreased hydrophobic secondary bile acids, elevated 12\u03b1-hydroxy bile acids, and impaired enterohepatic circulation\u2014has been mechanistically linked to both hepatic urate overproduction via the PPAR-\u03b1\/xanthine oxidase pathway and monosodium urate crystal-induced NLRP3 inflammasome activation, although human causal evidence remains to be established. The nuclear receptor FXR suppresses NLRP3 at the transcriptional level, while the membrane receptor TGR5 acts post-translationally through Cyclic adenosine monophosphate\/Protein Kinase A (cAMP\/PKA) and Glucagon-like peptide-1 (GLP-1) signaling. Gut microbiota dysbiosis amplifies these abnormalities through a vicious cycle of reduced bile acid signaling, increased intestinal permeability, and systemic endotoxemia. Based on these insights, we summarize five therapeutic strategies: FXR modulators, TGR5 agonists, microbiota-based interventions, natural products, and ursodeoxycholic acid replacement therapy. Future research should prioritize gout-specific preclinical models, clinical trials of TGR5 agonists, standardized microbiota-based therapies, dual-target molecules, and personalized patient stratification based on bile acid profiles.<\/jats:p>","DOI":"10.3390\/metabo16070464","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:43:14Z","timestamp":1783003394000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bile Acid Metabolism in Gout Pathogenesis from Gut\u2013Liver\u2013Joint Crosstalk to Therapeutic Opportunities"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2534-3050","authenticated-orcid":false,"given":"Beiyan","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate School, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8445-0120","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Gao","sequence":"additional","affiliation":[{"name":"Graduate School, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhu","family":"Wang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6426-4155","authenticated-orcid":false,"given":"Jieru","family":"Han","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4078\/jrd.2024.0054","article-title":"The Pathogenesis of Gout","volume":"32","author":"Ahn","year":"2025","journal-title":"J. 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