Inflammatory and carcinogenic features of gut microbiota in hepatocellular carcinoma patientsOutstanding Poster Award

Recently it has been recognized from animal studies that dysbiosis of gut microbiota is a cause of liver carcinogenesis. However, character of cancer-prone gut microbiota in human liver cancer patients remains unclear. We previously reported that intestinal microflora augment inflammation in extra-intestinal organ (Science 2013). In this study we hypothesized that metabolic activity in the human intestinal microbiota causes inflammation-associated carcinogenesis in liver. At first we found that mice transplanted with feces of hepatocellular carcinoma patients (HCC) highly bear liver tumors after induction with diethylnitrosamine and CCl4 (tumor incidence 91%, 22/24 mice). In contrast, feces from chronic hepatitis C patients without HCC (CLD) or healthy donors (HD) induced less liver tumors (66% or 18%, respectively). To address characteristics of the carcinogenic feces in HCC, whole genome sequencing was done with fecal DNA of 25 samples. Total 57,259,209 sequences were analyzed to know taxonomic profile or presence of genes. In the comparison of HCC vs HD, 8 taxa were increased in HCC (P<0.05). Of those, Streptococcaceae family was also increased in HCC compared with CLD (P<0.05). Metabolic pathway of peptidoglycan biosynthesis and secondary bile acids biosynthesis were increased in HCC compared with HD or CLD (P<0.05), both of which can induce inflammation according to the previous reports. In conclusion HCC patients have taxonomically and functionally unique microbiota. Inflammatory features of gut bacteria in HCC patients might promote liver carcinogenesis.