Endogenous Ethanol Metabolism and Development of MASLD-MASH

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent liver disorder driven by metabolic dysregulation and inflammation. 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-prebiotic combination to discussing new approaches.