{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:54:34Z","timestamp":1791914074880,"version":"4.3.4"},"reference-count":91,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MUR","award":["PRIN_2022PNRR_P2022KCHLN_002"],"award-info":[{"award-number":["PRIN_2022PNRR_P2022KCHLN_002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most prevalent cause of chronic liver disease worldwide. Its pathogenesis is complex and not yet fully elucidated but is commonly explained by the \u201cmultiple hit\u201d hypothesis, which suggests that pathological behaviours interact with an unfavourable genetic background and the presence of cardiovascular comorbidities. Recent evidence has highlighted a potential role of the gut microbiota in the onset and progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), potentially driven by epigenetic modifications mediated by microRNAs (miRNAs). MiRNAs are small, non-coding RNAs that regulate gene expression both intra- and extracellularly. Notably, emerging data suggests a bidirectional communication between the gut microbiota and the host, mediated by miRNAs via exosomes and outer membrane vesicles. The primary aim of this review is to explore the epigenetic crosstalk between the host and the gut microbiota through miRNA expression, with the goal of identifying specific pathways involved in MASLD development and natural history. A secondary objective is to evaluate the potential applications of artificial intelligence in the analysis of these complex host\u2013microbiota interactions, to standardize the evaluation of microbiota and to create a model of the epigenetic changes in metabolic liver disease.<\/jats:p>","DOI":"10.3390\/ijms26178633","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T07:46:17Z","timestamp":1757058377000},"page":"8633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MASLD Under the Microscope: How microRNAs and Microbiota Shape Hepatic Metabolic Disease Progression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-6963","authenticated-orcid":false,"given":"Clelia","family":"Asero","sequence":"first","affiliation":[{"name":"Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9815-5275","authenticated-orcid":false,"given":"Maria Stella","family":"Franz\u00e8","sequence":"additional","affiliation":[{"name":"Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-6799","authenticated-orcid":false,"given":"Irene","family":"Cacciola","sequence":"additional","affiliation":[{"name":"Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Gangemi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"},{"name":"Division of Allergy and Clinical Immunology, University Hospital of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.jhep.2024.04.031","article-title":"EASL\u2013EASD\u2013EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)","volume":"81","author":"Tacke","year":"2024","journal-title":"J. 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