{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:09:58Z","timestamp":1793329798322,"version":"4.5.0"},"reference-count":195,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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 the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["82405310"],"award-info":[{"award-number":["82405310"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82405310"],"award-info":[{"award-number":["82405310"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["1020241792"],"award-info":[{"award-number":["1020241792"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut\u2013X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota\u2013BA\u2013host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut\u2013heart, gut\u2013kidney, gut\u2013liver, gut\u2013bone, and gut\u2013endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM\u2019s benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota\u2013BA\u2013organ axis thus provides a potential framework for understanding TCM\u2019s systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM\u2019s ecological modulation strategies.<\/jats:p>","DOI":"10.3390\/metabo16060366","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bile Acids and the Gut\u2013X Axis: TCM-Mediated Systemic Protection and Therapeutic Opportunities for Multi-Organ Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Jialu","family":"He","sequence":"first","affiliation":[{"name":"School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-pathol-030320-095722","article-title":"Gut Microbiota in Intestinal and Liver Disease","volume":"16","author":"Jones","year":"2021","journal-title":"Annu. 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