The gut-liver axis: how the gut promotes liver disease

Research over the last two decades has highlighted the major role played by the gut microbiota in health and disease, including chronic liver diseases. The liver and intestine communicate via the portal vein, biliary system, and mediators in the circulation (gut-liver axis). Microbes in the intestine are involved in the maintenance of liver homeostasis. Conversely, alterations in the normal composition or diversity of the gut microbiome-a condition called dysbiosis-can also serve as a source of pathogens and molecules that contribute to the onset or progression of chronic liver diseases, like non-alcoholic fatty liver disease. Through the increased production of bacteria-derived ethanol, altered bile acid metabolism, altered production of short-chain fatty acids, greater abundance of lipopolysaccharide (LPS) containing Gram-negative bacteria and an increased intestinal permeability, dysbiosis impacts metabolic pathways and inflammatory processes. However, the clinical relevance of specific gut microbial alterations associated with chronic liver diseases remains unclear. This review discusses how microbes and their products contribute to liver disease pathogenesis and how targeting the microbiota might be used for therapeutic approaches.