Metagenomic applications and the potential for understanding chronic liver disease

Abstract

Liver fibrosis is characterized by an excessive deposition of extracellular matrix proteins that occurs in chronic liver disease of any origin. Cirrhosis occurs with the development of regenerating nodules of hepatocytes. Patients with decompensated liver cirrhosis have a poor prognosis, and liver transplantation is often necessary. There are no effective antifibrotic treatments for patients with chronic liver diseases. Intestinal dysbiosis and bacterial translocation are common in patients with liver disease, and there is strong evidence that the translocation of bacteria and their products across the epithelial barrier contributes to the progression of liver fibrosis. Supporting evidence comes from animal studies demonstrating that intestinal decontamination is associated with decreased liver fibrogenesis. Despite this strong association, the exact molecular mechanism of how intestinal bacterial overgrowth and translocation contribute to liver disease progression remains unknown. In this chapter we describe microbial changes in response to liver injury and chronic liver disease and the consequences of intestinal dysbiosis on host biology. We will initially focus on fatty liver disease associated with obesity and liver injury induced by alcohol. We then highlight how therapeutic interventions may modify the gastrointestinal microflora and prevent or reduce disease progression.