Liver diseases: The pathogenetic role of the gut microbiome and the potential of treatment for its modulation

The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.