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Herein, the efficacy of heat\u2010killed <jats:italic>Lactobacillus johnsonii<\/jats:italic> (HKLJ) in mitigating alcoholic liver damage is demonstrated in mouse models of ALD. The gut\u2010liver axis is identified as a pivotal pathway for the protective effects of <jats:italic>L. johnsonii<\/jats:italic> against ALD. Specifically, HKLJ is found to upregulate the expression of intestinal lysozymes, thereby enhancing the production of immunoregulatory substances from gut bacteria, which subsequently activated the Nucleotide\u2010binding oligomerization domain 2 (NOD2)\u2010interleukin (IL\u201023)\u2010IL\u201022 innate immune axis. The elevated IL\u201022 upregulated the antimicrobial peptide synthesis to maintain intestinal homeostasis and moreover activated the Signal transducer and activator of Transcription3 (STAT3) pathway in the liver to facilitate the repair of hepatic injuries. The heat\u2010killed <jats:italic>L. johnsonii<\/jats:italic> provoked immunity helps correct the gut microbiota dysbiosis, specifically by reversing the reduction of butyrate\u2010producing bacteria (such as <jats:italic>Faecalibaculum rodentium<\/jats:italic>) and the expansion of opportunistic pathogens (such as <jats:italic>Helicobacter<\/jats:italic> sp. and <jats:italic>Pichia kudriavzevii<\/jats:italic>) induced by ethanol. The findings provide novel insights into the gut microbiota\u2010liver axis that may be leveraged to enhance the treatment of ALD.<\/jats:p>","DOI":"10.1002\/advs.202405781","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T04:08:39Z","timestamp":1732248519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Postbiotics From <i>Lactobacillus Johnsonii<\/i> Activates Gut Innate Immunity to Mitigate Alcohol\u2010Associated Liver Disease"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1195-418X","authenticated-orcid":false,"given":"Ruopeng","family":"Yin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"},{"name":"Medical School University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzu","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanqin","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"},{"name":"Medical School University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"},{"name":"Medical School University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6471-131X","authenticated-orcid":false,"given":"Hongwei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"},{"name":"Medical School University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00279-5"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00688-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.029"},{"key":"e_1_2_9_4_1","first-page":"220","volume":"33","author":"Szabo G.","year":"2009","journal-title":"Exp. 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