Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4: Influence Statistics

Expert Impact

Concepts for which they have has direct influence: Intestinal microbiota , Hepatocellular carcinoma , Tlr4 intestinal microbiota , Intestinal microbiota tlr4 , Liver neoplasms , Experimental mice mice , Hcc promotion .

Key People For Intestinal Microbiota

Top KOLs in the world
#1
Jeffrey I Gordon
fatty acid transgenic mice gut microbiota
#2
Robin D Knight
gut microbiome microbial communities sequence analysis
#3
Ruth E Ley
gut microbiota metabolic syndrome archaeal diversity
#4
Peter James Turnbaugh
gut microbiome drug metabolism nutrient absorption
#5
Willem Meindert de Vos
intestinal microbiota lactococcus lactis lactic acid bacteria
#6
Fredrik Bäckhed
gut microbiota host metabolism bile acids

Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4

Abstract

. Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.