A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma.


Maria Effenberger, Silvio Waschina, Christina Bronowski, Gregor Sturm, Oronzo Tassiello, Felix Sommer, Andreas Zollner, Christina Watschinger, Felix Grabherr, Ronald Gstir, Christoph Grander, Barbara Enrich, Reto Bale, Daniel Putzer, Angela Djanani, Alexander R Moschen, Heinz Zoller, Jan Rupp, Stefan Schreiber, Remy Burcelin, Cornelia Lass-Flörl, Zlatko Trajanoski, Georg Oberhuber, Philip Rosenstiel, Timon E Adolph, Konrad Aden, Herbert Tilg

Year of publication



Hepatol Commun







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HCC is the leading cause of cancer in chronic liver disease. A growing body of experimental mouse models supports the notion that gut-resident and liver-resident microbes control hepatic immune responses and, thereby, crucially contribute to liver tumorigenesis. However, a comprehensive characterization of the intestinal microbiome in fueling the transition from chronic liver disease to HCC in humans is currently missing.


Here, we profiled the fecal, blood, and liver tissue microbiome of patients with HCC by 16S rRNA sequencing and compared profiles to nonmalignant cirrhotic and noncirrhotic NAFLD patients.


We report a distinct bacterial profile, defined from 16S rRNA gene sequences, with reduced α-and β-diversity in the feces of patients with HCC and cirrhosis compared to NAFLD. Patients with HCC and cirrhosis exhibited an increased proportion of fecal bacterial gene signatures in the blood and liver compared to NAFLD. Differential analysis of the relative abundance of bacterial genera identified an increased abundance of Ruminococcaceae and Bacteroidaceae in blood and liver tissue from both HCC and cirrhosis patients compared to NAFLD. Fecal samples from cirrhosis and HCC patients both showed a reduced abundance for several taxa, including short-chain fatty acid-producing genera, such as Blautia and Agathobacter. Using paired 16S rRNA and transcriptome sequencing, we identified a direct association between gut bacterial genus abundance and host transcriptome response within the liver tissue.


Our study indicates perturbations of the intestinal and liver-resident microbiome as a critical determinant of patients with cirrhosis and HCC.