The gut–liver axis and the intersection with the microbiome

Abstract

<p class="first" id="P2">In the past decade, an exciting realization has been that diverse liver diseases, ranging from non-alcoholic steatohepatitis, alcoholic steatohepatitis, and cirrhosis, to hepatocellular carcinoma, are not unrelated but fall along a spectrum. Recent work on the biology of the gut-liver communication axis has assisted in understanding the basic biology of both alcoholic and nonalcoholic fatty liver disease. Of immense importance is the massive advancement in understanding of the role of the microbiome, driven by high-throughput DNA sequencing and improved computational techniques that allow the complexity of the microbiome to be interrogated, together with improved experimental designs. Here, we review the gut-liver communications of these various forms of liver disease, explore the molecular, genetic and microbiome relationships, discuss prospects for exploiting the microbiome to determine the stage of liver disease, and to predict the effects of pharmaceutical, dietary, and other interventions at a population and individual level. We conclude that although much remains to be done in understanding the relationship between the microbiome and liver disease, rapid progress towards clinical applications is being made, especially in study designs that complement human intervention studies with mechanistic work in mice that have been humanized in multiple respects, including the genetic, immunological and microbiome characteristics of individual patients. These “avatar mice” may be especially useful for guiding new microbiome-based or microbiome-informed therapies. </p>