Fusobacterium nucleatum promotes colon cancer progression by changing the mucosal microbiota and colon transcriptome in a mouse model
( ) has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer (CRC), which has attracted broad attention. However, the mechanism by which it is involved in CRC development is not fully understood. To explore its potential causative role in CRC develo...
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Published in | World journal of gastroenterology : WJG Vol. 28; no. 18; pp. 1981 - 1995 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Baishideng Publishing Group Inc
14.05.2022
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Subjects | |
Online Access | Get full text |
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Summary: | (
) has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer (CRC), which has attracted broad attention. However, the mechanism by which it is involved in CRC development is not fully understood.
To explore its potential causative role in CRC development, we evaluated the colon pathology, mucosa barrier, colon microbiota and host transcriptome profile after
infection in an azoxymethane/dextran sulfate sodium salt (AOM/DSS) mouse model.
Three groups of mice were compared to reveal the differences,
, the control, AOM/DSS-induced CRC and AOM/DSS-FUSO infection groups.
Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group, and AOM/DSS mice with
infection showed the highest tumor formation ratio among the three groups. Moreover, the colon pathology was the most serious in the AOM/DSS-FUSO group. We found that the structure of the colon microbiota changed considerably after
infection; striking differences in mucosal microbial population patterns were observed between the AOM/DSS-FUSO and AOM/DSS groups, and inflammation-inducing bacteria were enriched in the mucosal microbiota in the AOM/DSS-FUSO group. By comparing intestinal transcriptomics data from AOM
AOM/DSS-FUSO mice, we showed that transcriptional activity was strongly affected by dysbiosis of the gut microbiota. The most microbiota-sensitive genes were oncogenes in the intestine, and the cyclic adenosine monophosphate signaling pathway, neuroactive ligand-receptor interaction, PPAR signaling pathway, retinol metabolism, mineral absorption and drug metabolism were highly enriched in the AOM/DSS-FUSO group. Additionally, we showed that microbial dysbiosis driven by
infection enriched eight taxa belonging to Proteobacteria
which correlates with increased expression of oncogenic genes.
Our study demonstrated that
infection altered the colon mucosal microbiota by enriching pathogens related to the development of CRC, providing new insights into the role of
in the oncogenic microbial environment of the colon. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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. 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 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. |
ISSN: | 1007-9327 2219-2840 |
DOI: | 10.3748/wjg.v28.i18.1981 |