Gut Microbiota, Oxidative Stress, and Inflammation: Pathophysiological Crosstalk in MASLD, MASH, and Hepatocellular Carcinoma

Metabolically-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is increasingly recognized as a systemic disorder at the intersection of metabolic dysregulation, inflammation, and carcinogenesis. Progression from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and hepatocellular carcinoma (HCC) reflects the interplay between metabolic overload, oxidative stress, immune activation, and gut microbiota dysbiosis. In this review, we propose the Redox-Microbiota-Inflammatory Axis as an integrative framework linking metabolic stress to fibrogenesis and hepatocarcinogenesis. Nutrient excess and insulin resistance promote mitochondrial dysfunction and reactive oxygen species (ROS) generation, which activate redox-sensitive inflammatory pathways. Concurrently, gut-derived microbial products and metabolites enhance hepatic immune signaling through the gut-liver axis, creating a self-amplifying pathogenic loop. Understanding this interconnected network highlights biologically actionable pathways and supports emerging therapeutic strategies targeting oxidative stress, inflammation, and microbiota-driven mechanisms across the MASLD spectrum.