Interplay of Liver Disease and Gut Microbiota in the Development of Colorectal Neoplasia.

Abstract

Liver disease, colon cancer, and the gut microbiome are intimately interrelated; however, the connections linking liver disease and colorectal neoplasia via the gut microbiota remain poorly understood and rarely addressed in a single space. The goal of this review is to take a broad perspective on the clinical problem of colorectal neoplasia in the liver disease population, recognize the significance of the clinical study findings, and delve into the evidence supporting putative molecular mechanisms connecting dysbiosis in the progression of liver disease to the development of colorectal neoplasia. Clinical studies have recently reported increased risk of colorectal neoplasia in patients with fatty liver disease, and risk increases with liver disease severity. Concurrently, the evolution of -omics technology has shown dysregulation of the gut microbial community, termed dysbiosis, in the progression of liver disease. Specific microbes enriched in the gut flora of liver disease patients have been linked to colon cancer and adenomatous precursor lesions. The gut microbiome of liver disease patients generates a pro-neoplastic environment, mediated via altered bile acid signaling and a dysregulated inflammatory response that suppresses immune surveillance. Research focused on the mechanisms linking liver disease to colorectal neoplasia via the gut microbiome is needed to help us prepare for the rising tide of colon cancer in young patients with an increasing prevalence of liver disease.