{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:03:19Z","timestamp":1789707799479,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Natural Science Foundation Project","award":["CSTB2024NSCQ-MSX0883,CSTB2024NSCQ-MSX0166"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0883,CSTB2024NSCQ-MSX0166"]}]},{"name":"Medical Research Foundation of Chongqing General Hospital","award":["Y2023YXYJZDXM01"],"award-info":[{"award-number":["Y2023YXYJZDXM01"]}]},{"DOI":"10.13039\/100016834","name":"Chongqing Municipal Health Commission","doi-asserted-by":"publisher","award":["YXQN202560"],"award-info":[{"award-number":["YXQN202560"]}],"id":[{"id":"10.13039\/100016834","id-type":"DOI","asserted-by":"publisher"}]},{"award":["YXQN202560"],"award-info":[{"award-number":["YXQN202560"]}],"id":[{"id":"https:\/\/ror.org\/04ce5fg13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The gut microbiota plays a critical role in regulating liver metabolism and immunity, significantly influencing hepatic inflammation and fibrogenesis. However, the mechanisms by which it modulates the progression of liver fibrosis remain unclear. This study investigated the interplay between the gut microbiota and bile acids in murine liver fibrosis. A mouse model of liver fibrosis was established via intraperitoneal injection of carbon tetrachloride. The gut microbiota was depleted using an antibiotic cocktail, as confirmed through 16S rRNA sequencing. Bile acid profiles were measured using ultra-performance liquid chromatography\u2013tandem mass spectrometry. The effects of secondary bile acids on macrophage polarization were assessed in vivo and in vitro. Gut commensal microbiota depletion exacerbated liver inflammation and fibrosis. Concomitantly, this depletion significantly reduced microbiota-derived secondary bile acids. Notably, supplementation with deoxycholic acid markedly attenuated liver fibrosis. This protective effect was associated with the inhibition of pro-inflammatory M1 macrophage polarization. Takeda G protein-coupled receptor 5 (TGR5) activation was identified as the mechanism underlying the effect of deoxycholic acid on macrophages, as a TGR5 antagonist reversed this inhibition. Mechanistically, TGR5 activation suppressed the NF-\u03baB pathway in macrophages via the cAMP\u2013PKA signaling cascade, thereby inhibiting hepatic stellate cell activation. Our results demonstrate that the gut microbiota\u2013secondary bile acid\u2013TGR5 signaling axis plays a critical role in liver fibrosis and represents a promising therapeutic target.<\/jats:p>","DOI":"10.3390\/microorganisms14092035","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"2035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Commensal Bacteria Ameliorate Liver Fibrosis by Inhibiting Macrophage M1 Polarization Through Secondary Bile Acids in a Murine Liver Fibrosis Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Hongyan","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanyu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyi","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chinese Ministry of Education, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Hepatopancreatobiliary Surgery, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2045-9540","authenticated-orcid":false,"given":"Zhidan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuliang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41575-023-00807-x","article-title":"Hepatic inflammatory responses in liver fibrosis","volume":"20","author":"Hammerich","year":"2023","journal-title":"Nat. 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