Deciphering the role of dietary modifications and gut dysbiosis in Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is emerging as a major health concern and economic burden worldwide. Approximately one-third of the total population is affected by NAFLD. The more aggressive form of NAFLD, non-alcoholic steatohepatitis (NASH) could progress to liver failure, fibrosis, cirrhosis, hepatocellular carcinoma and even death. NAFLD is multifactorial in origin and the gut microbiota dysregulation is one of the key features of NAFLD. Dietary alterations or nutritional interventions have a huge impact on gut microbiota composition and functions. An association between the type of diet, altered gut microbiota, and NAFLD is now being appreciated. The gut dysbiosis characterized by the changes in gut microbiota composition and its metabolites contribute to the development and progression of NAFLD through multiple mechanisms. The gut dysbiosis affects the intestinal permeability by generating endogenous ethanol, increased level of toxins such as lipopolysaccharides, and also influences the amino acid metabolism particularly tryptophan which activates the pro-inflammatory cytokines promoting hepatic inflammation. Altered microbial composition also disturbs the bile acids homeostasis which affects the energy balance and lipid metabolism through signaling via bile acid receptors. Therefore gut microbiota profiling in NAFLD patients may provide valuable information in predicting disease severity. Also, finding the key metabolites and markers of gut dysbiosis and their role in the pathogenesis of liver disease might prove helpful in designing novel and effective therapies for NAFLD. The present review succinctly summarizes gut dysbiosis triggered by various dietary factors especially macronutrients including proteins, fats and carbohydrates leading to the development and progression of NAFLD. We also address the gaps in the present studies as well as future prospects of manipulating gut microbiota for improved therapeutic and diagnostic applications in NAFLD.