Abnormal bile acid-microbiota crosstalk promotes the development of hepatocellular carcinoma.

Content Provider	Europe PMC
Author	Shen, Rui Ke, Lixin Li, Qiao Dang, Xi Shen, Shunli Shen, Jianming Li, Shaoqiang Liang, Lijian Peng, Baogang Kuang, Ming Ma, Yi Yang, Zhonghan Hua, Yunpeng
Abstract	BackgroundGut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules.MethodsWe tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro.ResultsWe found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro.ConclusionsWe conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12072-022-10299-7.
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ISSN	19360533
Journal	Hepatology International [Hepatol Int]
Volume Number	16
DOI	10.1007/s12072-022-10299-7
PubMed Central reference number	PMC9013324
Issue Number	2
PubMed reference number	35211843
e-ISSN	19360541
Language	English
Publisher	Springer India
Publisher Date	2022-02-24
Publisher Place	New Delhi
Access Restriction	Open
Rights License	Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022
Subject Keyword	Primary bile acids Secondary bile acids Gut microbiota Bile salt hydrolase Glyco-deoxycholic acid Bifidobacteriales Lactobacillales Bacteroidales Clostridiales Tumorigenesis
Content Type	Text
Resource Type	Article
Subject	Hepatology