{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:49:26Z","timestamp":1790704166015,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Infection with <jats:italic>Clonorchis sinensis<\/jats:italic> (<jats:italic>C. sinensis<\/jats:italic>) has the potential to induce liver fibrosis and significantly alter the gut microbiota. However, it remains unclear how these changes in the gut microbiota, through the gut-liver axis, influence the progression of liver fibrosis. Furthermore, it is uncertain whether targeting the gut microbiota, based on the concept of the gut-liver axis, could be a potential therapeutic strategy for alleviating liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The gut microbiota alterations in <jats:italic>C. sinensis<\/jats:italic>-infected mice at multiple time points were analyzed through 16S rDNA high-throughput sequencing. <jats:italic>Ruminococcus bromii (R.bromii)<\/jats:italic> therapeutic effect on <jats:italic>C. sinensis<\/jats:italic> infected mice was evaluated. Metabolic changes following produced by <jats:italic>R. bromii<\/jats:italic> were analyzed using short-chain fatty acids (SCFAs) metabolomics. Additionally, <jats:italic>R. bromii<\/jats:italic> conditioned medium (R.b CM) or its metabolites were co-cultured with two hepatic stellate cell lines (LX2 and JS1) <jats:italic>in vitro<\/jats:italic> to assess their anti-fibrotic effects. Finally, RNA sequencing was employed to investigate the specific mechanism by which acetate inhibits hepatic stellate cells (HSCs) activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The abundance of <jats:italic>R. bromii<\/jats:italic> increased during the inflammatory stage of <jats:italic>C. sinensis<\/jats:italic> infection and decreased significantly during the fibrosis stage. Oral gavage of <jats:italic>R. bromii<\/jats:italic> significantly inhibited <jats:italic>C. sinensis<\/jats:italic>-induced liver fibrosis while restoring the intestinal barrier. The activation of HSCs was significantly inhibited <jats:italic>in vitro<\/jats:italic> upon incubation with <jats:italic>R.b<\/jats:italic> CM. Acetate was identified as a key metabolite generated from <jats:italic>R. bromii<\/jats:italic> in <jats:italic>R.b<\/jats:italic> CM, and acetate attenuated <jats:italic>C. sinensis<\/jats:italic>-induced liver fibrosis <jats:italic>in vitro<\/jats:italic> and in vivo. Mechanistically, acetate inhibited the activation of HSCs by activating the PI3K\/AKT signaling pathway to prevent the progression of liver fibrosis in mice infected with <jats:italic>C. sinensis<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p><jats:italic>R. bromii<\/jats:italic> exerted a protective effect on hepatic fibrosis by delivering acetate via the gut-liver axis to active the PI3K\/AKT signaling pathway in HSCs. Furthermore, <jats:italic>R. bromii<\/jats:italic> can be used as a probiotic therapy to alleviate hepatic fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1532599","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:21:06Z","timestamp":1742196066000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Ruminococcus bromii-generated acetate alleviated Clonorchis sinensis-induced liver fibrosis in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Chun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deping","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e02566","DOI":"10.1128\/mBio.02566-18","article-title":"Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers","volume":"10","author":"Baxter","year":"2019","journal-title":"MBio"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1126\/science.aaf7419","article-title":"A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion","volume":"352","author":"Birchenough","year":"2017","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S1470-2045(09)70096-8","article-title":"A review of human carcinogens\u2014part B: biological agents","volume":"10","author":"Bouvard","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrendo.2015.128","article-title":"Short-chain fatty acids in control of body weight and insulin sensitivity","volume":"11","author":"Canfora","year":"2015","journal-title":"Nat. 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