Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy

Figure 3 Pathophysiology of gut-liver-axis[31]. The microbiome sets the stage for the gut-liver-axis, representing an excessive source of bacterial products and metabolites in terms of both quantity and diversity. In conditions of increased intestinal permeability, the epithelial barrier is crossed more than in healthy conditions by bacterial products (lipopolysaccharides, peptidoglycans, bacterial DNA, flagellin etc.), which stimulate the gut-associated lymphatic tissue to release pro-inflammatory cytokines (TNF, IL1, IL6 etc.), chemokines, as well as eicosanoids, leading to portal-venous P/MAMP- and cytokinemia. Moreover, bacterial metabolites (trimethylamine, ethanol and other volatile organoids, fatty acids, acetaldehyde etc.) increasingly permeate the epithelial barrier. Anything crossing the epithelial barrier faces the gut-vascular barrier, which determines the likely rate and size of molecules entering the portal-venous circulation. The intrahepatic effects of this portal-venous inflow of stimulants, as well as platelets on Kupffer cells and hepatic stellate cells, drives inflammation, fibrogenesis and carcinogenesis. LPS: Lipopolysaccharide; HSC: Hepatic stellate cell; MCP-1: Monocyte chemoattractant protein-1; CDCA: Chenodeoxycholic acid. Citation: Wiest R, Albillos A, Trauner M, Bajaj JS, Jalan R. Targeting the gut-liver axis in liver disease. J Hepatol 2017; 67: 1084-1103. Copyright © European Association for the Study of the Liver 2017. Published by Elsevier B.V.