Fusobacterium nucleatum promotes colon cancer progression by changing the mucosal microbiota and colon transcriptome in a mouse model

作     者：Na Wu Yu-Qing Feng Na Lyu Di Wang Wei-Dong Yu Yong-Fei Hu 

作者机构：Department of Central Laboratory&Institute of Clinical Molecular BiologyPeking University People’s HospitalBeijing 100044China State Key Laboratory of Animal NutritionCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China CAS Key Laboratory of Pathogenic Microbiology and ImmunologyInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2022年第28卷第18期

页      面：1981-1995页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China,No. 32070116 Open Project Program of CAS Key Laboratory of Pathogenic Microbiology and Immunology,No. CASPMI202102 

主　　题：Fusobacterium nucleatum Mucosal microbiota Transcriptome Colorectal cancer Inflammation-inducing bacteria 

摘      要：BACKGROUND Fusobacterium nucleatum(***)has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer(CRC),which has attracted broad ***,the mechanism by which it is involved in CRC development is not fully *** 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 *** Three groups of mice were compared to reveal the differences,i.e.,the control,AOM/DSS-induced CRC and AOM/DSS-FUSO infection *** 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 ***,the colon pathology was the most serious in the AOM/DSS-FUSO *** 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 *** comparing intestinal transcriptomics data from AOM vs AOM/DSSFUSO mice,we showed that transcriptional activity was strongly affected by dysbiosis of the gut *** 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 ***,we showed that microbial dysbiosis driven by *** infection enriched eight taxa belonging to Proteobacteria,which correlates with increased expression of oncogenic *** Our