Multi-Omics Nutritional Approaches Targeting Metabolic-Associated Fatty Liver Disease

Currently, metabolic-associated fatty liver disease (MAFLD) is a leading global cause of chronic liver disease, and is expected to become one of the most common indications of liver transplantation. MAFLD is associated with obesity, involving multiple mechanisms such as alterations in lipid metabolism, insulin resistance, hyperinflammation, mitochondrial dysfunction, cell apoptosis, oxidative stress, and extracellular matrix formation. However, the onset and progression of MAFLD is variable among individuals, being influenced by intrinsic (personal) and external environmental factors. In this context, sequence structural variants across the human genome, epigenetic phenomena (i.e., DNA methylation, histone modifications, and long non-coding RNAs) affecting gene expression, gut microbiota dysbiosis, and metabolomics/lipidomic fingerprints may account for differences in MAFLD outcomes through interactions with nutritional features. This knowledge may contribute to gaining a deeper understanding of the molecular and physiological processes underlying MAFLD pathogenesis and phenotype heterogeneity, as well as facilitating the identification of biomarkers of disease progression and therapeutic targets for the implementation of tailored nutritional strategies. This comprehensive literature review highlights the potential of nutrigenetic, nutriepigenetic, nutrimetagenomic, nutritranscriptomics, and nutrimetabolomic approaches for the prevention and management of MAFLD in humans through the lens of precision nutrition.

Automated summary

Currently, metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease globally and is anticipated to become a common indication for liver transplantation. MAFLD is closely associated with obesity and involves multiple mechanisms. The onset and progression of MAFLD vary among individuals due to intrinsic and extrinsic factors. Structural variants in the human genome, epigenetic phenomena, gut microbiota dysbiosis, and metabolomics/lipidomic fingerprints may contribute to differences in MAFLD outcomes through interactions with nutritional features. This knowledge enhances our understanding of the molecular and physiological processes underlying MAFLD pathogenesis and heterogeneity and aids in the identification of biomarkers for disease progression and therapeutic targets for tailored nutritional strategies.