Interventions for non-alcoholic liver disease: a gut microbial metabolites perspective

Over the past two decades, non-alcoholic fatty liver disease (NAFLD) has become a leading burden of hepatocellular carcinoma and liver transplantation. Although the exact pathogenesis of NAFLD has not been fully elucidated, recent hypotheses placed more emphasis on the crucial role of the gut microbiome and its derivatives. Reportedly, microbial metabolites such as short-chain fatty acids, amino acid metabolites (indole and its derivatives), bile acids (BAs), trimethylamine N-oxide (TMAO), and endogenous ethanol exhibit sophisticated bioactive properties. These molecules regulate host lipid, glucose, and BAs metabolic homeostasis via modulating nutrient absorption, energy expenditure, inflammation, and the neuroendocrine axis. Consequently, a broad range of research has studied the therapeutic effects of microbiota-derived metabolites. In this review, we explore the interaction of microbial products and NAFLD. We also discuss the regulatory role of existing NAFLD therapies on metabolite levels and investigate the potential of targeting those metabolites to relieve NAFLD.

Automated summary

This review explores the interaction between microbial products and non-alcoholic fatty liver disease (NAFLD), as well as the regulatory role of existing NAFLD therapies on metabolite levels. It is found that microbial metabolites can regulate host lipid, glucose, and bile acid metabolic homeostasis through various pathways, and have the potential to alleviate NAFLD. Therefore, targeting these metabolites may be beneficial in relieving NAFLD.