Microbiota and chronic liver diseases

Liver diseases are accompanied by changes in the intestinal bacterial microbiota, mycobiota and virome. The importance of intestinal dysbiosis for liver diseases has been shown by fecal microbiota exchange. Mice transplanted with stool from patients with fatty liver disease develop increased experimental liver disease. The intestinal microbiota contributes to fatty liver disease via various mechanisms, such as increased intestinal permeability in a subset of patients, changes in tryptophan-derived indole metabolites and bile acids. Bacterial virulence factors are proteins or peptides encoded by bacterial genes that help the organisms colonize the intestine or mediate disease. We have recently demonstrated that an exotoxin secreted by Enterococcus faecalis (E. faecalis) to cause hepatocyte death and liver injury in humanized mouse models of ethanol-induced liver disease. The presence of exotoxin-positive E. faecalis correlated with liver disease severity and mortality in patients with alcoholic hepatitis. Conversely, there is no correlation between liver disease in a NAFLD cohort and positivity for exotoxin secreted from E. faecalis. Gut microbiome centered treatment approaches might be able to restore intestinal homeostasis and eubiosis. This could be achieved by using bio-engineered bacteria, supplementing metabolites or phage therapy that can target specific bacteria.