Profiling of Tumour-associated Microbiota in Human Hepatocellular Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 20

PMID 34012007

Citations 42

Authors

Seiga Komiyama

Takahiro Yamada

Nobuyuki Takemura

Norihiro Kokudo

Koji Hase

Yuki I Kawamura

Affiliations

Soon will be listed here.

Abstract

Liver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.

Citing Articles

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References

Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A . Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017; 25(5):1054-1062.e5. PMC: 5502730. DOI: 10.1016/j.cmet.2017.04.001. View

Pocha C, Xie C . Hepatocellular carcinoma in alcoholic and non-alcoholic fatty liver disease-one of a kind or two different enemies?. Transl Gastroenterol Hepatol. 2019; 4:72. PMC: 6851438. DOI: 10.21037/tgh.2019.09.01. View

Hall A, Yassour M, Sauk J, Garner A, Jiang X, Arthur T . A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med. 2017; 9(1):103. PMC: 5704459. DOI: 10.1186/s13073-017-0490-5. View

Glockner F, Yilmaz P, Quast C, Gerken J, Beccati A, Ciuprina A . 25 years of serving the community with ribosomal RNA gene reference databases and tools. J Biotechnol. 2017; 261:169-176. DOI: 10.1016/j.jbiotec.2017.06.1198. View

Yilmaz P, Parfrey L, Yarza P, Gerken J, Pruesse E, Quast C . The SILVA and "All-species Living Tree Project (LTP)" taxonomic frameworks. Nucleic Acids Res. 2013; 42(Database issue):D643-8. PMC: 3965112. DOI: 10.1093/nar/gkt1209. View

El-Serag H . Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012; 142(6):1264-1273.e1. PMC: 3338949. DOI: 10.1053/j.gastro.2011.12.061. View

Tripathi A, Debelius J, Brenner D, Karin M, Loomba R, Schnabl B . The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018; 15(7):397-411. PMC: 6319369. DOI: 10.1038/s41575-018-0011-z. View

Banerjee S, Tian T, Wei Z, Shih N, Feldman M, Alwine J . The ovarian cancer oncobiome. Oncotarget. 2017; 8(22):36225-36245. PMC: 5482651. DOI: 10.18632/oncotarget.16717. View

Yu L, Schwabe R . The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol. 2017; 14(9):527-539. PMC: 6467288. DOI: 10.1038/nrgastro.2017.72. View

10.

Lin R, Lee F, Lee S, Tsai Y, Lin H, Lu R . Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J Hepatol. 1995; 22(2):165-72. DOI: 10.1016/0168-8278(95)80424-2. View

11.

Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L . Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019; 575(7783):505-511. PMC: 6872939. DOI: 10.1038/s41586-019-1742-x. View

12.

Willing B, Dicksved J, Halfvarson J, Andersson A, Lucio M, Zheng Z . A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology. 2010; 139(6):1844-1854.e1. DOI: 10.1053/j.gastro.2010.08.049. View

13.

Kostic A, Chun E, Robertson L, Glickman J, Gallini C, Michaud M . Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013; 14(2):207-15. PMC: 3772512. DOI: 10.1016/j.chom.2013.07.007. View

14.

Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende D . Enterotypes of the human gut microbiome. Nature. 2011; 473(7346):174-80. PMC: 3728647. DOI: 10.1038/nature09944. View

15.

Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F . The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2015; 63(3):764-75. PMC: 4975935. DOI: 10.1002/hep.28356. View

16.

Jing Y, Sun K, Liu W, Sheng D, Zhao S, Gao L . Tumor necrosis factor-α promotes hepatocellular carcinogenesis through the activation of hepatic progenitor cells. Cancer Lett. 2018; 434:22-32. DOI: 10.1016/j.canlet.2018.07.001. View

17.

Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W . Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019; 178(4):795-806.e12. PMC: 7288240. DOI: 10.1016/j.cell.2019.07.008. View

18.

Henke M, Kenny D, Cassilly C, Vlamakis H, Xavier R, Clardy J . , a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A. 2019; 116(26):12672-12677. PMC: 6601261. DOI: 10.1073/pnas.1904099116. View

19.

Banerjee S, Tian T, Wei Z, Shih N, Feldman M, Peck K . Distinct Microbial Signatures Associated With Different Breast Cancer Types. Front Microbiol. 2018; 9:951. PMC: 5962706. DOI: 10.3389/fmicb.2018.00951. View

20.

Zeng Y, Chen S, Fu Y, Wu W, Chen T, Chen J . Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. J Viral Hepat. 2019; 27(2):143-155. DOI: 10.1111/jvh.13216. View