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Recent studies highlight the importance of the gut microbiome as a key contributor to this pathology through its ability to ferment dietary sugars into ethanol, a metabolite previously overlooked in MASLD. In this review, we discuss the role of the gut microbiome in MASLD, covering functional and compositional shifts observed in the disease; we dive into the different microbial pathways of ethanol synthesis, hepatic mechanisms of ethanol clearance, and pathological consequences. We also discuss the role of a healthy microbiome in the clearance of ethanol in the gut and how microbiome-based strategies could be beneficial in targeting endogenous production of ethanol, going from the traditional probiotic\u2013prebiotic combination to discussing new approaches.<\/jats:p>","DOI":"10.3390\/ijms26178609","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T07:46:17Z","timestamp":1757058377000},"page":"8609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Endogenous Ethanol Metabolism and Development of MASLD-MASH"],"prefix":"10.3390","volume":"26","author":[{"given":"N\u00faria","family":"Farr\u00e0s Sol\u00e9","sequence":"first","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6056-4943","authenticated-orcid":false,"given":"Sander","family":"Wydh","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-6261","authenticated-orcid":false,"given":"Amir Hossein","family":"Alizadeh Bahmani","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-5960","authenticated-orcid":false,"given":"Thi Phuong Nam","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Internal and Vascular Medicine, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Diabeter Center Amsterdam, 1066 EC Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. 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