Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2022; 28(18): 1981-1995
Published online May 14, 2022. doi: 10.3748/wjg.v28.i18.1981
Fusobacterium nucleatum promotes colon cancer progression by changing the mucosal microbiota and colon transcriptome in a mouse model
Na Wu, Yu-Qing Feng, Na Lyu, Di Wang, Wei-Dong Yu, Yong-Fei Hu
Na Wu, Di Wang, Wei-Dong Yu, Department of Central Laboratory & Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing 100044, China
Yu-Qing Feng, Yong-Fei Hu, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Na Lyu, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Author contributions: Wu N and Feng YQ contributed equally to this work and performed the majority of experiments. Wu N, Yu WD, and Hu YF designed and coordinated the study; Wu N, Feng YQ, Lyu N, and Wang D performed the experiments; Wu N and Feng YQ analyzed and interpreted the data; Wu N, Feng YQ and Hu YF wrote the manuscript; all authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 32070116; and Open Project Program of CAS Key Laboratory of Pathogenic Microbiology and Immunology, No. CASPMI202102.
Institutional animal care and use committee statement: The study was reviewed and approved by the Institutional Animal Care Committee of the Peking University People’s Hospital. All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: The raw 16S amplicon sequencing and transcriptome data in this study have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject number PRJNA767246.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong-Fei Hu, PhD, Professor, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China. huyongfei@cau.edu.cn
Received: January 30, 2022
Peer-review started: January 30, 2022
First decision: February 24, 2022
Revised: February 28, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: May 14, 2022
Processing time: 101 Days and 23.5 Hours
ARTICLE HIGHLIGHTS
Research background

Fusobacterium nucleatum (F. nucleatum) has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer (CRC), which has attracted broad attention. Exploring the roles and underlying mechanism of F. nucleatum has important theoretical and practical significance for diagnosis and targeted therapy of CRC.

Research motivation

The aim of this study is to reveal the effect of F. nucleatum infection on the changes of mucosal microbiota, and investigate the regulatory role of F. nucleatum in the CRC progression.

Research objectives

The azoxymethane/dextran sulfate sodium salt (AOM/DSS)-induced mice were used to investigate the role of F. nucleatum in the “oncogenic microbial environment” of the colon.

Research methods

The mucosal microbial composition and RNA-seq transcriptomic analysis were used to identify the differentially expressed gene (DEG) signatures driven by F. nucleatum infection, and integrated network analysis was conducted to reveal the relationship between microbial dysbiosis and the DEGs.

Research results

We provide direct evidence that F. nucleatum interacts with other species, remodels the microbiota, and alters the tumor microenvironment. In addition, we revealed the dysbiosis signature of the colon mucosa microbiota driven by F. nucleatum and the interaction between the hub microbial taxa and the host transcriptome.

Research conclusions

Dysbiosis in the mucosal microbiota driven by F. nucleatum, in particular Enterobacteriaceae and Stenotrophomonas, occurs during F. nucleatum infection, leading to the differential expression of oncogene transcriptomes in the AOM/DSS model.

Research perspectives

Our study provides a deeper insight into CRC etiology driven by F. nucleatum infection and the mechanisms of the tumorigenic effect of F. nucleatum. Targeting F. nucleatum infection is a potential treatment for CRC.