{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:05:02Z","timestamp":1791662702418,"version":"4.3.4"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"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":["82070624"],"award-info":[{"award-number":["82070624"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["ZDB202006"],"award-info":[{"award-number":["ZDB202006"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Graduate Research and Practical Innovation Program of Jiangsu Province","award":["KYCX23_3421"],"award-info":[{"award-number":["KYCX23_3421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The gut commensal bacterium Akkermansia muciniphila (AKK) has emerged as a candidate for treating liver disorders, yet its therapeutic potential in liver fibrosis remains poorly defined. Here, using a carbon tetrachloride (CCl4)-induced murine model, we show that AKK administration markedly attenuates collagen deposition, inflammation, and hepatic injury. AKK restored intestinal barrier integrity, reshaped microbial composition, and enhanced propionic acid transport from the gut to the liver, leading to suppression of hepatic stellate cell activation. Multi-omics profiling revealed that AKK enriched propionate-producing taxa and upregulated key metabolic enzymes, thereby elevating hepatic propionate levels. Supplementation with propionic acid alone recapitulated AKK\u2019s benefits, improving liver function, alleviating extracellular matrix accumulation, and activating the Keap1\u2013Nrf2 antioxidant pathway. Together, our findings identify a microbiota\u2013metabolite axis in which AKK counters liver fibrosis by enhancing propionate-mediated antioxidant regulation, highlighting its therapeutic promise for chronic liver disease.<\/jats:p>","DOI":"10.1093\/lifemeta\/loaf036","type":"journal-article","created":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T11:43:08Z","timestamp":1759664588000},"source":"Crossref","is-referenced-by-count":10,"title":["Propionic acid secreted by\n                    <i>Akkermansia muciniphila<\/i>\n                    alleviates hepatic fibrosis by antioxidant regulation across the gut\u2013liver axis"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-5941","authenticated-orcid":false,"given":"Lu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University , Nantong, Jiangsu 226001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University , Nantong, Jiangsu 226001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Jia","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University , Nantong, Jiangsu 226001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University , Nantong, Jiangsu 226001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University , Nantong, Jiangsu 226001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, Jiangsu 210008,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Hua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University , Nantong, Jiangsu 226001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"2026043010571091500_loaf036-B1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nri3623","article-title":"Liver fibrosis and repair: immune regulation of wound healing in a solid organ","volume":"14","author":"Pellicoro","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2026043010571091500_loaf036-B2","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 Rev Gastroenterol Hepatol"},{"key":"2026043010571091500_loaf036-B3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","article-title":"Fibrosis: from mechanisms to medicines","volume":"587","author":"Henderson","year":"2020","journal-title":"Nature"},{"key":"2026043010571091500_loaf036-B4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol Aspects Med"},{"key":"2026043010571091500_loaf036-B5","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1056\/NEJMoa2029349","article-title":"Prospective study of outcomes in adults with nonalcoholic fatty liver disease","volume":"385","author":"Sanyal","year":"2021","journal-title":"N Engl J Med."},{"key":"2026043010571091500_loaf036-B6","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1136\/gutjnl-2020-322786","article-title":"Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort","volume":"70","author":"Simon","year":"2021","journal-title":"Gut"},{"key":"2026043010571091500_loaf036-B7","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1007\/s10620-021-07009-y","article-title":"Liver fibrosis in the natural course of chronic hepatitis B viral infection: a systematic review with meta-analysis","volume":"67","author":"Lin","year":"2022","journal-title":"Dig Dis Sci"},{"key":"2026043010571091500_loaf036-B8","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s10482-020-01474-7","article-title":"Human gut microbiota\/microbiome in health and diseases: a review","volume":"113","author":"Gomaa","year":"2020","journal-title":"Antonie Van Leeuwenhoek."},{"key":"2026043010571091500_loaf036-B9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature13568","article-title":"Alterations of the human gut microbiome in liver cirrhosis","volume":"513","author":"Qin","year":"2014","journal-title":"Nature"},{"key":"2026043010571091500_loaf036-B10","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1111\/1751-7915.13410","article-title":"Akkermansia muciniphila is a promising probiotic","volume":"12","author":"Zhang","year":"2019","journal-title":"Microb Biotechnol"},{"key":"2026043010571091500_loaf036-B11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/gutjnl-2023-329996","article-title":"Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis","volume":"73","author":"Xie","year":"2023","journal-title":"Gut"},{"key":"2026043010571091500_loaf036-B12","doi-asserted-by":"crossref","first-page":"1218552","DOI":"10.3389\/fcimb.2023.1218552","article-title":"Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis","volume":"13","author":"Wu","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"2026043010571091500_loaf036-B13","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1002\/hep.28829","article-title":"Changes in blood microbiota profiles associated with liver fibrosis in obese patients: a pilot analysis","volume":"64","author":"Lelouvier","year":"2016","journal-title":"Hepatology"},{"key":"2026043010571091500_loaf036-B14","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.molcel.2020.03.001","article-title":"Immune-microbiota interplay and colonization resistance in infection","volume":"78","author":"Leshem","year":"2020","journal-title":"Mol Cell"},{"key":"2026043010571091500_loaf036-B15","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1038\/ncomms3384","article-title":"Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity","volume":"4","author":"Li","year":"2013","journal-title":"Nat Commun"},{"key":"2026043010571091500_loaf036-B16","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1038\/ismej.2014.45","article-title":"Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity","volume":"8","author":"Everard","year":"2014","journal-title":"ISME J"},{"key":"2026043010571091500_loaf036-B17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nm.4236","article-title":"A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice","volume":"23","author":"Plovier","year":"2017","journal-title":"Nat Med"},{"key":"2026043010571091500_loaf036-B18","doi-asserted-by":"crossref","first-page":"e0048421","DOI":"10.1128\/Spectrum.00484-21","article-title":"The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD\/CCl4-induced liver injury","volume":"9","author":"Keshavarz Azizi Raftar","year":"2021","journal-title":"Microbiol Spectr"},{"key":"2026043010571091500_loaf036-B19","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1136\/gutjnl-2016-313432","article-title":"Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease","volume":"67","author":"Grander","year":"2018","journal-title":"Gut"},{"key":"2026043010571091500_loaf036-B20","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1080\/10408398.2016.1245650","article-title":"Short-chain fatty acids in control of energy metabolism","volume":"58","author":"Hu","year":"2018","journal-title":"Crit Rev Food Sci Nutr"},{"key":"2026043010571091500_loaf036-B21","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.jhep.2020.01.017","article-title":"Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis","volume":"72","author":"Bajaj","year":"2020","journal-title":"J Hepatol"},{"key":"2026043010571091500_loaf036-B22","doi-asserted-by":"crossref","first-page":"11005","DOI":"10.1039\/D4FO03591G","article-title":"Lacticaseibacillus plantarum postbiotics prepared by the combined technique of pasteurization and ultrasound: effective measures to alleviate obesity based on the SCFAs-GPR41\/GPR43 signaling pathway","volume":"15","author":"Miao","year":"2024","journal-title":"Food Funct"},{"key":"2026043010571091500_loaf036-B23","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nbt.2942","article-title":"An integrated catalog of reference genes in the human gut microbiome","volume":"32","author":"Li","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2026043010571091500_loaf036-B24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40168-024-02001-w","article-title":"Akkermansia muciniphila and its metabolite propionic acid maintains neuronal mitochondrial division and autophagy homeostasis during Alzheimer\u2019s disease pathologic process via GPR41 and GPR43","volume":"13","author":"Wang","year":"2025","journal-title":"Microbiome"},{"key":"2026043010571091500_loaf036-B25","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3892\/etm.2022.11545","article-title":"Riboflavin ameliorates mitochondrial dysfunction via the AMPK\/PGC1alpha\/HO\u20111 signaling pathway and attenuates carbon tetrachloride\u2011induced liver fibrosis in rats","volume":"24","author":"Tang","year":"2022","journal-title":"Exp Ther Med"},{"key":"2026043010571091500_loaf036-B26","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0014-5793(00)01748-8","article-title":"Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension","volume":"476","author":"Miralles","year":"2000","journal-title":"FEBS Lett"},{"key":"2026043010571091500_loaf036-B27","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.3390\/cells10123406","article-title":"Maresin-1 prevents liver fibrosis by targeting Nrf2 and NF-\u03baB, reducing oxidative stress and inflammation","volume":"10","author":"Rodr\u00edguez","year":"2021","journal-title":"Cells"},{"key":"2026043010571091500_loaf036-B28","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.intimp.2014.05.014","article-title":"Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin","volume":"21","author":"Al-Harbi","year":"2014","journal-title":"Int Immunopharmacol"},{"key":"2026043010571091500_loaf036-B29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12944-018-0674-z","article-title":"Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide","volume":"17","author":"Bashandy","year":"2018","journal-title":"Lipids Health Dis"}],"container-title":["Life Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/lifemeta\/advance-article-pdf\/doi\/10.1093\/lifemeta\/loaf036\/64547144\/loaf036.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lifemeta\/article-pdf\/5\/1\/loaf036\/64547144\/loaf036.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lifemeta\/article-pdf\/5\/1\/loaf036\/64547144\/loaf036.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:57:21Z","timestamp":1777561041000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/lifemeta\/article\/doi\/10.1093\/lifemeta\/loaf036\/8277574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,30]]}},"URL":"https:\/\/doi.org\/10.1093\/lifemeta\/loaf036","relation":{},"ISSN":["2755-0230"],"issn-type":[{"value":"2755-0230","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2025,10,8]]},"article-number":"loaf036"}}