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

التفاصيل البيبلوغرافية
العنوان:	Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment
المؤلفون:	Schneider, Kai Markus, Mohs, Antje, Gui, Wenfang, Galvez, Eric J C, Candels, Lena Susanna, Hoenicke, Lisa, Muthukumarasamy, Uthayakumar, Holland, Christian H, Elfers, Carsten, Kilic, Konrad, Schneider, Carolin Victoria, Schierwagen, Robert, Strnad, Pavel, Wirtz, Theresa H, Marschall, Hanns-Ulrich, Latz, Eicke, Lelouvier, Benjamin, Saez-Rodriguez, Julio, de Vos, Willem, Strowig, Till, Trebicka, Jonel, Trautwein, Christian
المساهمون:	Medicine
المصدر:	Nature communications ; 13 ; 1 ; 3964 ; England
سنة النشر:	2023
المجموعة:	University of Massachusetts, Medical School: eScholarship@UMMS
مصطلحات موضوعية:	Hepatocellular carcinoma, Microbiome, Tumour immunology
الوصف:	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.
نوع الوثيقة:	article in journal/newspaper
اللغة:	English
تدمد:	2041-1723
Relation:	Nature Communications; https://doi.org/10.1038/s41467-022-31312-5; Schneider KM, Mohs A, Gui W, Galvez EJC, Candels LS, Hoenicke L, Muthukumarasamy U, Holland CH, Elfers C, Kilic K, Schneider CV, Schierwagen R, Strnad P, Wirtz TH, Marschall HU, Latz E, Lelouvier B, Saez-Rodriguez J, de Vos W, Strowig T, Trebicka J, Trautwein C. Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment. Nat Commun. 2022 Jul 8;13(1):3964. doi:10.1038/s41467-022-31312-5. PMID: 35803930; PMCID: PMC9270328.; http://hdl.handle.net/20.500.14038/52758
DOI:	10.1038/s41467-022-31312-5
الاتاحة:	https://doi.org/10.1038/s41467-022-31312-5 https://hdl.handle.net/20.500.14038/52758
Rights:	Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2022 ; Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/
رقم الانضمام:	edsbas.82CFEB76
قاعدة البيانات:	BASE

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الوصف
تدمد:	20411723
DOI:	10.1038/s41467-022-31312-5