Targeting the Gut-Liver Mitochondria Axis in MASLD: Mechanisms and Therapeutic Perspectives

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing continuously, posing a substantial threat to public health. This study examines the critical role of imbalanced interactions within the gut‒liver-mitochondrial axis in MASLD pathogenesis. Dysregulation of mitochondrial homeostasis, including metabolic disturbances, impaired quality control, and disrupted interorganelle interactions, significantly contributes to MASLD progression. Through the gut‒liver axis, the gut microbiota establishes a bidirectional regulatory network with mitochondria. Dysbiosis disrupts mitochondrial homeostasis via multiple pathways, while mitochondrial dysfunction aggravates imbalances in the gut microbiota, creating a vicious cycle. Therefore, in this study, the molecular basis of mitochondrial abnormalities was investigated, and the mechanisms of reciprocal regulation were clarified. Additionally, targeted intervention strategies, including the modulation of mitochondrial homeostasis and the regulation of the gut microbiota, are explored to provide novel therapeutic perspectives for MASLD.