Role of the Intestinal Microbiome in Cholestatic Liver Disease

Abstract

Hepatobiliary health and disease is influenced by multiple factors including genetics, epigenetics, and the environment. Recently, multiple lines of evidence suggest that the microbiome also plays a central role in the initiation and/or progression of several liver diseases. Our current understanding of the dynamic interplay between microbes, microbial products and liver health and pathophysiology is incomplete. However, exciting insights are continually being made that support both a central role of the microbiome and a need for further interrogation of the microbes or microbe-associated molecules involved in the initiation and progression of select liver diseases.

Fig. 1

The gut liver axis is influenced by multiple factors. Broadly, liver and intestinal homeostasis is influenced by the genome, the environment, and the microbiome. While our current understanding of this dynamic is incomplete, exciting insights continue to support this complex network in the initiation and/or progression of liver disease.

Fig. 2

Hepatobiliary health and disease is influenced by the balance of microbe-derived cytoprotective and cytodestructive molecules. In this model, an individual’s genetic signature, environment, and microbiota are central to the maintenance of hepatobiliary health. Liver homeostasis may be associated with an increase in cytoprotective molecules, or a decrease in cytodestructive molecules derived in the gut. In contrast, liver injury’ may be the result of increased production of cytodestructive molecules or loss of cytoprotective molecules.