Targeting Dysbiosis for the Treatment of Liver Disease

Abstract

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets.

Fig. 1

Mechanisms of liver disease in dysbiosis. Under normal conditions, gut integrity is preserved with minimal entry of bacterial products into the portal circulation. In the liver, hepatocytes and Kupffer cells rapidly clear microbial products and maintain immunotolerance without inflammation. In dysbiosis, intestinal permeability is increased, resulting in increased translocation of bacteria, metabolites, and microbial products. Metabolites have direct toxic effects on the liver. Activation of the innate immune system via toll-like receptors and inflammasomes by bacteria and bacterial products produces large amounts of inflammatory cytokines and subsequent liver damage.