Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment.

Autor: Schneider KM; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Mohs A; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Gui W; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Galvez EJC; Helmholtz Centre for Infection Research, Braunschweig, Germany and Hannover Medical School, Hannover, Germany., Candels LS; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Hoenicke L; Helmholtz Centre for Infection Research, Braunschweig, Germany and Hannover Medical School, Hannover, Germany., Muthukumarasamy U; Helmholtz Centre for Infection Research, Braunschweig, Germany and Hannover Medical School, Hannover, Germany., Holland CH; Institute for Computational Biomedicine, Bioquant, Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Heidelberg, Germany.; Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Faculty of Medicine, Aachen, Germany., Elfers C; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Kilic K; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Schneider CV; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.; The Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Schierwagen R; European Foundation for the Study of Chronic Liver Failure (EF-CLIF), 08021, Barcelona, Spain.; Translational Hepatology, Department of Internal Medicine I, Goethe University Frankfurt, 60323, Frankfurt, Germany., Strnad P; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Wirtz TH; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany., Marschall HU; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Latz E; Institute of Innate Immunity, Medical Faculty, University of Bonn, 53127, Bonn, Germany.; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.; German Center for Neurodegenerative Diseases, 53127, Bonn, Germany., Lelouvier B; Vaiomer SAS, Labège, France., Saez-Rodriguez J; Institute for Computational Biomedicine, Bioquant, Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Heidelberg, Germany.; Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Faculty of Medicine, Aachen, Germany., de Vos W; Laboratory of Microbiology, Wageningen University, 6708 WE, Wageningen, The Netherlands.; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland., Strowig T; Helmholtz Centre for Infection Research, Braunschweig, Germany and Hannover Medical School, Hannover, Germany., Trebicka J; European Foundation for the Study of Chronic Liver Failure (EF-CLIF), 08021, Barcelona, Spain.; Translational Hepatology, Department of Internal Medicine I, Goethe University Frankfurt, 60323, Frankfurt, Germany., Trautwein C; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany. ctrautwein@ukaachen.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jul 08; Vol. 13 (1), pp. 3964. Date of Electronic Publication: 2022 Jul 08.
DOI: 10.1038/s41467-022-31312-5
Abstrakt: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance and drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6 -/- mice, induces a Toll-like receptor 4 dependent expansion of hepatic monocytic myeloid-derived suppressor cells (mMDSC) and suppression of T-cell abundance. This phenotype is transmissible via fecal microbiota transfer and reversible upon antibiotic treatment, pointing to the high plasticity of the tumor microenvironment. While loss of Akkermansia muciniphila correlates with mMDSC abundance, its reintroduction restores intestinal barrier function and strongly reduces liver inflammation and fibrosis. Cirrhosis patients display increased bacterial abundance in hepatic tissue, which induces pronounced transcriptional changes, including activation of fibro-inflammatory pathways as well as circuits mediating cancer immunosuppression. This study demonstrates that gut microbiota closely shapes the hepatic inflammatory microenvironment opening approaches for cancer prevention and therapy.
(© 2022. The Author(s).)
Databáze: MEDLINE
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