Gut microbiota and its derived metabolites as silent sculptors of non-alcoholic fatty liver disease development and potential guide for non-invasive clinical diagnostics.

Non-alcoholic fatty liver disease (NAFLD) has made its mark as a predominant etiology of chronic liver disease on a global scale, significantly contributing to liver-related morbidity and mortality. It is characterized by excessive hepatic fat accumulation in individuals with minimal to no alcohol intake and may advance to non-alcoholic steatohepatitis (NASH), a more stringent manifestation of the condition. The pathophysiology of NAFLD is influenced by various factors, particularly the gastrointestinal (GI) microbiota and its derived metabolites. Most studies concerning microbiomes in NAFLD have predominantly focused on the study of intestinal bacteria, resulting in a significant gap in understanding the modifications in non-bacterial intestinal microorganisms among patients suffering from NAFLD. Consequently, this article elucidates how the core gut microbiota (encompassing bacteria, archaea, viruses, and fungi) and their mechanisms pertaining to the development and progression of NAFLD. Then, we emphasized the significant role of metabolites originating from gut microbiota, including short-chain fatty acids, bile acids, endogenous ethanol, trimethylamine, and lipopolysaccharide, in the pathophysiology of NAFLD, through mechanisms associated with hepatic lipid metabolism, inflammatory processes, and insulin resistance. Furthermore, we assess the potential of metabolites as a potential non-invasive biomarker for clinical application.