Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct;2(10):1039-1054.
doi: 10.1038/s43018-021-00251-3. Epub 2021 Sep 27.

Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis

Noriho Iida  1 , Eishiro Mizukoshi  2 , Tatsuya Yamashita  1 , Masahiro Yutani  3 , Jun Seishima  1 , Ziyu Wang  1 , Kuniaki Arai  1 , Hikari Okada  1 , Taro Yamashita  1 , Yoshio Sakai  1 , Yusuke Masuo  4 , Rina Agustina  4 , Yukio Kato  4 , Yukako Fujinaga  3 , Masanobu Oshima  5 , Masao Honda  1 , François Lebreton  6 , Michael S Gilmore  6 , Shuichi Kaneko  1
Affiliations

Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis

Noriho Iida et al. Nat Cancer. 2021 Oct.

Abstract

Gut dysbiosis is observed in chronic hepatobiliary diseases and is frequently associated with liver carcinogenesis; however, the extent and specific mechanisms triggered by alterations in the microbiota mediating tumorigenesis in these patients remain unclear. Here we show that Enterococcus faecalis is abundant in the microbiota of patients with hepatitis C virus-related chronic liver disease. Xenotransplantation of gut microbiota from these patients increased the number of spontaneous liver tumors in mice and enhanced susceptibility to liver carcinogens. Hepatic colonization by gelE-positive E. faecalis increased liver expression of proliferative genes in a TLR4-Myd88-dependent manner, leading to liver tumorigenesis. Moreover, decreased fecal deoxycholic acid levels were associated with colonization by E. faecalis. Overall, these data identify E. faecalis as a key promoter of liver carcinogenesis.

PubMed Disclaimer

References

    1. Moeller, A. H. et al. Cospeciation of gut microbiota with hominids. Science 353, 380–382 (2016). - PubMed - PMC - DOI
    1. Lebreton, F. et al. Tracing the Enterococci from Paleozoic origins to the hospital. Cell 169, 849–861 (2017). - PubMed - PMC - DOI
    1. Garrett, W. S. Cancer and the microbiota. Science 348, 80–86 (2015). - PubMed - PMC - DOI
    1. Dapito, D. H. et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21, 504–516 (2012). - PubMed - PMC - DOI
    1. Global Burden of Disease Cancer Collaboration. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 3, 524–548 (2017). - PMC - DOI

Publication types

LinkOut - more resources