The Role of the Gut Microbiome and its Derived Mediators in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become an emerging disease throughout the world. Metabolic comorbidities such as obesity (especially central obesity), diabetes, and dyslipidaemia have been established as risk factors not only for NAFLD development, but also for the disease progression. Dietary or genetic obesity has been hypothesised to induce alteration of gut microbiota, thereby causing the promotion of deoxycholic acid production in the intestinal tract. Elevated levels of deoxycholic acid can provoke senescence-associated secretory phenotype in hepatic stellate cells through enterohepatic circulation, which in turn leads to the secretion of various inflammatory and tumour-promoting factors in the liver and may further result in obesity-induced hepatocellular carcinoma. Short-chain fatty acids are mainly produced through the fermentation of indigestible carbohydrates by gut microbiota. Gut microbiota have been considered to play a role in NAFLD and its disease progression. The main end products resulting from the indigestible carbohydrate catabolism of intestinal microbes are short-chain fatty acids, constituting acetate, propionate, and butyrate. High concentrations of propionate can promote development of NAFLD, whereas acetate and butyrate can prevent the development of the disease.