Abstract
Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3–V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.
Highlights
Recent studies have reported the presence of circulating bacterial contents in healthy human blood by sequencing 16S ribosomal deoxyribonucleic acid genes[3]
Changes in blood-microbiome signatures associated with a shift in the metabolic functions has been reported in heavy alcohol drinkers without significant liver disease and those with alcoholic hepatitis[7]
It has not been known yet whether alteration in the blood microbiome is just a bystander of dysbiosis or a true player in the pathophysiology of disease, these findings collectively suggest that blood microbiota profiles might be used as a potential noninvasive biomarker
Summary
Recent studies have reported the presence of circulating bacterial contents in healthy human blood by sequencing 16S ribosomal deoxyribonucleic acid (rDNA) genes[3]. Changes in blood-microbiome signatures associated with a shift in the metabolic functions has been reported in heavy alcohol drinkers without significant liver disease and those with alcoholic hepatitis[7]. It has not been known yet whether alteration in the blood microbiome is just a bystander of dysbiosis or a true player in the pathophysiology of disease, these findings collectively suggest that blood microbiota profiles might be used as a potential noninvasive biomarker. We evaluated whether disease-specific microbiome alterations are present in the blood microbiome from patients with cirrhosis and HCC, and their potential as diagnostic biomarkers for HCC
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