International Journal of Molecular Sciences Review Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature Ivana Milosevic 1,2, *, Ankica Vujovic 1,2 , Aleksandra Barac 1,2 , Marina Djelic 3 , Milos Korac 1,2 , Aleksandra Radovanovic Spurnic 1,2 , Ivana Gmizic 2 , Olja Stevanovic 1,2 , Vladimir Djordjevic 1,4 , Nebojsa Lekic 1,4 , Edda Russo 5 and Amedeo Amedei 5,6 1 Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; ankica.vujovic88@gmail.com (A.V.); aleksandrabarac85@gmail.com (A.B.); milos.korac@med.bg.ac.rs (M.K.); spurnic@yahoo.com (A.R.S.); stevanovicolja74@gmail.com (O.S.); vladimir.djordjevic@kcs.ac.rs (V.D.); nesalekic67@gmail.com (N.L.) 2 Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia; gmizic_ivana@yahoo.com 3 Faculty of Medicine, Universisty of Belgrade; Institute of Medical Physiology “Rihard Burijan”, 11000 Belgrade, Serbia; mdjelic011@gmail.com 4 Clinic for Digestive Surgery, Clinical Center of Serbia, 11000 Belgrade, Serbia 5 Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; edda.russo@unifi.it (E.R.); amedeo.amedei@unifi.it (A.A.) 6 Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134 Florence, Italy * Correspondence: ivana.s.milosevic@mfub.bg.ac.rs; Tel.: +381-11-2683-366 Received: 22 December 2018; Accepted: 14 January 2019; Published: 17 January 2019   Abstract: 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. Keywords: gut microbiota; gut-liver axis; chronic liver diseases; fecal transplantation; probiotics 1. Gut Microbiota The gut microbiota (GM) is a diverse ecosystem that consists of bacteria, protozoa, archaea, fungi, and viruses, which exist in a specific symbiosis between each other and the human body as well. Currently, it is well known that GM plays relevant roles in physiological and pathological conditions of human health, taking part in digestion, vitamin B synthesis, immunomodulation, and promotion of angiogenesis and nerve function. In addition, it is unavoidable that the GM has an impact on pathogenesis of gastrointestinal, hepatic, respiratory, cardiovascular, endocrine, and many other disorders, arising as “a new virtual metabolic organ” [1]. Int. J. Mol. Sci. 2019, 20, 395; doi:10.3390/ijms20020395 www.mdpi.com/journal/ijms