{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:55:09Z","timestamp":1781693709280,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation of Hubei Hongshan Laboratory","award":["2021hszd022"],"award-info":[{"award-number":["2021hszd022"]}]},{"name":"Natural Science Foundation of Shandong Province, China","award":["SZR2564"],"award-info":[{"award-number":["SZR2564"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytolysin-positive Enterococcus faecalis is a key pathogen in severe alcoholic hepatitis, yet the mechanisms through which it worsens disease and possible therapeutic strategies remain poorly understood. This study aimed to clarify the pathogenic effects of E. faecalis in acute alcohol-associated liver disease (ALD) and to assess the protective potential of Akkermansia muciniphila (Akk11) against this pathogen. Using a mouse model of acute ethanol gavage, animals received E. faecalis and\/or Akk11 under prophylactic or therapeutic regimens. Assessments included liver injury markers, histopathology, lipid profiles, inflammatory cytokines, gut barrier integrity, and gut microbiota composition. E. faecalis exacerbated ethanol-induced hepatic steatosis and injury, showing a paradoxical effect: it increased histological damage while lowering circulating LPS and transaminases. This was linked to upregulated hepatic autophagy (increased Atg7) and reduced cholesterol, yet it promoted neutral lipid accumulation. Importantly, E. faecalis aggravated gut dysbiosis by markedly enriching the pro-inflammatory pathobiont Helicobacter typhlonius and impairing colonic barrier function. Intervention with Akk11 alleviated liver injury, reduced lipid accumulation and oxidative stress, and restored cytokine balance. Akk11 also strengthened gut barrier integrity, lowered serum endotoxin, and beneficially reshaped the microbiota. Prophylactic administration was particularly effective, normalizing the Firmicutes\/Bacteroidota ratio, suppressing H. typhlonius, and enriching beneficial Bacteroides sartorii. This study confirms the pathogenic role of E. faecalis in acute ALD and establishes A. muciniphila (Akk11) as a promising microbiota-targeted therapy, which protects against liver injury by reinforcing the gut barrier, selectively modulating microbiota, and reducing inflammation, with prophylactic administration showing superior efficacy.<\/jats:p>","DOI":"10.3390\/ijms27125474","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:19:53Z","timestamp":1781691593000},"page":"5474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Akkermansia muciniphila Alleviates Enterococcus faecalis-Exacerbated Alcoholic Liver Injury by Modulating Gut Microbiota and Barrier Function"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5184-6212","authenticated-orcid":false,"given":"Xin","family":"Sui","sequence":"first","affiliation":[{"name":"School of Biological Science and Technology, University of Jinan, Jinan 250022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhui","family":"Feng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitao","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Peng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41572-018-0014-7","article-title":"Alcoholic liver disease","volume":"4","author":"Seitz","year":"2018","journal-title":"Nat. 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