Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation
Yong-Na Wu, Lei Zhang, Tuo Chen, Xun Li, Li-Hong He, Guang-Xiu Liu
Yong-Na Wu, Tuo Chen, Guang-Xiu Liu, Key Laboratory of Desert and Desertification, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, Gansu Province, China
Yong-Na Wu, Tuo Chen, Guang-Xiu Liu, Key Laboratory of Extreme Environmental Microbial Resources and Engineering of Gansu Province, Lanzhou 730000, Gansu Province, China
Yong-Na Wu, Tuo Chen, Guang-Xiu Liu, University of Chinese Academy of Sciences, Beijing 100049, China
Yong-Na Wu, Lei Zhang, Xun Li, Li-Hong He, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
Yong-Na Wu, Lei Zhang, Xun Li, Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou 730000, Gansu Province, China
Author contributions: Wu YN, Chen T, Li X and Liu GX conceived and designed the study; Wu YN and Zhang L performed the experiments; Wu YN and He LH wrote the manuscript; all authors read and approved the final manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Supported by: The National Natural Science Foundation of China, No. 31960236 and 31770536; and the Lanzhou Talent Innovation and Entrepreneurship Project, No. 2019-RC-34.
Institutional review board statement: This study was approved by the Ethics Committee of the First Hospital of Lanzhou University, No. LLYYLL-2017-18.
Institutional animal care and use committee statement: All procedures involving animals were approved by the Ethics Committee of the First Hospital of Lanzhou University, No. LLYYLL-2017-18.
Conflict-of-interest statement: There are no conflicts of interest in this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Guang-Xiu Liu, PhD, Chairman, Research Scientist, Northwest Institute of Eco-Environment and Resources, University of Chinese Academy of Sciences, No. 320 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China. liugx@lzb.ac.cn
Received: April 1, 2020
Peer-review started: April 1, 2020
First decision: June 4, 2020
Revised: June 11, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: September 28, 2020
ARTICLE HIGHLIGHTS
Research background
Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a contributing role in the pathogenesis of hepatocellular carcinoma (HCC) progression, and GM-CSF is a critical factor in promoting intestinal immunity.
Research motivation
GM-CSF may protect against the development of HCC by regulating immunity as well as the intestinal microecology.
Research objectives
To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.
Research methods
We utilized established mouse models of HCC and overexpressed GM-CSF in HCC. Liver injury, intestinal barrier function, immune inflammation and the fecal microbiome and metabolome were studied.
Research results
Overexpression of GM-CSF had a significant impact on the gut microbiome of mice with HCC and resulted in a high abundance of organisms from the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid, along with a prominent decrease in the fecal levels of succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid. The intestinal microbiota and fecal metabolites induced by GM-CSF are primarily involved in the pathways related to the reduction in the inflammatory response, biotin metabolism and intestinal barrier dysfunction.
Research conclusions
GM-CSF protects mice against HCC by ameliorating intestinal dysbiosis and attenuating inflammation.
Research perspectives
Our findings indicate that GM-CSF can protect against the development of HCC by regulating immunity as well as by modulating the abundance of specific intestinal micro-organisms and their metabolites. This study provides new insights into the treatment of HCC.
