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 

机构地区：[1]Department of Central Laboratory&Institute of Clinical Molecular Biology,Peking University People’s Hospital,Beijing 100044,China [2]State Key Laboratory of Animal Nutrition,College of Animal Science and Technology,China Agricultural University,Beijing 100193,China [3]CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《World Journal of Gastroenterology》2022年第18期1981-1995,共15页世界胃肠病学杂志（英文版）

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

摘　　要：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.However,the mechanism by which it is involved in CRC development is not fully understood.AIM To explore its potential causative role in CRC development,we evaluated the colon pathology,mucosa barrier,colon microbiota and host transcriptome profile after F.nucleatum infection in an azoxymethane/dextran sulfate sodium salt(AOM/DSS)mouse model.METHODS Three groups of mice were compared to reveal the differences,i.e.,the control,AOM/DSS-induced CRC and AOM/DSS-FUSO infection groups.RESULTS 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 F.nucleatum 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 F.nucleatum 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 vs AOM/DSSFUSO 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 F.nucleatum infection enriched eight taxa belonging to Proteobacteria,which correlates with increased expression of oncogenic genes.CONCLUSION Our study demonstrated that F.nucleatum infection

关 键 词：Fusobacterium nucleatum Mucosal microbiota TRANSCRIPTOME Colorectal cancer Inflammation-inducing bacteria 

分 类 号：R735.34[医药卫生—肿瘤]