Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis. Bajaj Jasmohan S,Khoruts Alexander Journal of hepatology Patients with chronic liver disease and cirrhosis demonstrate a global mucosal immune impairment, which is associated with altered gut microbiota composition and functionality. These changes progress along with the advancing degree of cirrhosis and can be linked with hepatic encephalopathy, infections and even prognostication independent of clinical biomarkers. Along with compositional changes, functional alterations to the microbiota, related to short-chain fatty acids, bioenergetics and bile acid metabolism, are also associated with cirrhosis progression and outcomes. Altering the functional and structural profile of the microbiota is partly achieved by medications used in patients with cirrhosis such as rifaximin, lactulose, proton pump inhibitors and other antibiotics. However, the role of faecal or intestinal microbiota transplantation is increasingly being recognised. Herein, we review the challenges, opportunities and road ahead for the appropriate and safe use of intestinal microbiota transplantation in liver disease. 10.1016/j.jhep.2020.01.017

The gut-liver axis in liver disease: Pathophysiological basis for therapy. Albillos Agustín,de Gottardi Andrea,Rescigno María Journal of hepatology The gut-liver axis refers to the bidirectional relationship between the gut and its microbiota, and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. This reciprocal interaction is established by the portal vein which enables transport of gut-derived products directly to the liver, and the liver feedback route of bile and antibody secretion to the intestine. The intestinal mucosal and vascular barrier is the functional and anatomical structure that serves as a playground for the interactions between the gut and the liver, limiting the systemic dissemination of microbes and toxins while allowing nutrients to access the circulation and to reach the liver. The control of microbial communities is critical to maintaining homeostasis of the gut-liver axis, and as part of this bidirectional communication the liver shapes intestinal microbial communities. Alcohol disrupts the gut-liver axis at multiple interconnected levels, including the gut microbiome, mucus barrier, epithelial barrier and at the level of antimicrobial peptide production, which increases microbial exposure and the proinflammatory environment of the liver. Growing evidence indicates the pathogenetic role of microbe-derived metabolites, such as trimethylamine, secondary bile acids, short-chain fatty acids and ethanol, in the pathogenesis of non-alcoholic fatty liver disease. Cirrhosis by itself is associated with profound alterations in gut microbiota and damage at the different levels of defence of the intestinal barrier, including the epithelial, vascular and immune barriers. The relevance of the severe disturbance of the intestinal barrier in cirrhosis has been linked to translocation of live bacteria, bacterial infections and disease progression. The identification of the elements of the gut-liver axis primarily damaged in each chronic liver disease offers possibilities for intervention. Beyond antibiotics, upcoming therapies centred on the gut include new generations of probiotics, bacterial metabolites (postbiotics), faecal microbial transplantation, and carbon nanoparticles. FXR-agonists target both the gut and the liver and are currently being tested in different liver diseases. Finally, synthetic biotic medicines, phages that target specific bacteria or therapies that create physical barriers between the gut and the liver offer new therapeutic approaches. 10.1016/j.jhep.2019.10.003

Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Milosevic Ivana,Vujovic Ankica,Barac Aleksandra,Djelic Marina,Korac Milos,Radovanovic Spurnic Aleksandra,Gmizic Ivana,Stevanovic Olja,Djordjevic Vladimir,Lekic Nebojsa,Russo Edda,Amedei Amedeo International journal of molecular sciences The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called "the new virtual metabolic organ", makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of "ancient" microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies. 10.3390/ijms20020395