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HCC (Hepatocellular Carcinoma) is a critical health issue worldwide. Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside (M3G) can regulate the progression of HCC. In this study, feces samples from the same batch of mice were collected to explore the regulatory mechanism of M3G on intestinal microbiota and microbial TCA cycle metabolism KEGG pathway in HCC mice based on 16S rRNA sequencing and metagenomics. Our results showed that blueberry M3G increased the microbial diversity and regulated the structure of intestinal microbiota in mice, such as increasing the abundance of Clostridia (butyric acid-producing bacteria), Oscillospira and Ruminococcus, and reducing the abundance of pathogenic Erysipelotrichi. Compared with the group of liver cancer and 5-fluorouracil, blueberry M3G significantly regulated microbial TCA cycle KEGG pathway via improving the expression of key proteins (porA, DLAT, aceE, PC and OGDH). Additionally, we found which the abundance of Muribaculum intestinale increased by blueberry M3G may be an important factor affecting the microbial TCA cycle KEGG pathway via the pearson correlation (R) analysis of protein and microbiota. Taken together, these results demonstrate that the blueberry M3G has the potential to be an intestinal microbiota regulator and an adjuvant to HCC therapy.


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Blueberry malvidin-3-galactoside modulated gut microbial dysbiosis and microbial TCA cycle KEGG pathway disrupted in a liver cancer model induced by HepG2 cells

Show Author's information Zhen Chenga,cJie Lina,cNingxuan Gaoa,cXiyun Suna,b,cXianjun Menga,bRuihai Liua,b,dYunen LiueWeisheng WangfBin Lia,b,c,1( )Yuehua Wanga,b,c,1( )
College of Food Science, Shenyang Agricultural University, Liaoning, China
National R & D Professional Center For Berry Processing, Shenyang Agricultural University, Liaoning, China
Key Laboratory of Healthy Food Nutrition and Innovative Manufacturing of Liaoning, China
Department of food Science, Cornell University, Ithaca, NY, USA
Emergency Medicine Department of General Hospital of Shenyang Military Command, Laboratory of Rescue Center of Severe Trauma PLA, Liaoning, China
Shenyang Blueberry Industry Co. LTD., Liaoning, China

1 These authors contributed equally to this work. Peer review under responsibility of KeAi Communications Co., Ltd.]]>

Abstract

HCC (Hepatocellular Carcinoma) is a critical health issue worldwide. Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside (M3G) can regulate the progression of HCC. In this study, feces samples from the same batch of mice were collected to explore the regulatory mechanism of M3G on intestinal microbiota and microbial TCA cycle metabolism KEGG pathway in HCC mice based on 16S rRNA sequencing and metagenomics. Our results showed that blueberry M3G increased the microbial diversity and regulated the structure of intestinal microbiota in mice, such as increasing the abundance of Clostridia (butyric acid-producing bacteria), Oscillospira and Ruminococcus, and reducing the abundance of pathogenic Erysipelotrichi. Compared with the group of liver cancer and 5-fluorouracil, blueberry M3G significantly regulated microbial TCA cycle KEGG pathway via improving the expression of key proteins (porA, DLAT, aceE, PC and OGDH). Additionally, we found which the abundance of Muribaculum intestinale increased by blueberry M3G may be an important factor affecting the microbial TCA cycle KEGG pathway via the pearson correlation (R) analysis of protein and microbiota. Taken together, these results demonstrate that the blueberry M3G has the potential to be an intestinal microbiota regulator and an adjuvant to HCC therapy.

Keywords: HCC, malvidin-3-galactoside, Blueberry, metagenomics, microbial TCA cycle KEGG pathway

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Publication history

Received: 31 October 2019
Revised: 10 March 2020
Accepted: 03 April 2020
Published: 25 April 2020
Issue date: September 2020

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© 2020 "Society information". Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31972090), LiaoNing Revitalization Talents Program (XLYC1807127), Liaoning BaiQianWan Talents Program (2018-B-21), Tianzhu Mountain Scholar Support Project (2018), the Innovative Talent Support Program for Institution of Higher Learning of Liaoning Province (LR2017038) and the project of "double hundred" for major scientific and technological achievements transformating of Shenyang Science and Technology Bureau (Z19-3-012). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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