适应不良
癌变
寄主(生物学)
生物
结直肠癌
细胞生物学
癌症研究
遗传学
生态学
癌症
作者
Haoyan Chen,Tianying Tong,Shiyuan Lu,Linhua Ji,Baoqin Xuan,Gang Zhao,Yuqing Yan,Linhong Song,Licong Zhao,Yile Xie,Xiao-Xu Leng,Xinyu Zhang,Yun Cui,Xiaoyu Chen,Hua Xiong,TaChung Yu,Xiaobo Li,Tiantian Sun,Zheng Wang,Jinxian Chen,Yingxuan Chen,Jie Hong,Jing‐Yuan Fang
出处
期刊:Cell Metabolism
[Elsevier]
日期:2023-03-23
卷期号:35 (4): 651-666.e7
被引量:28
标识
DOI:10.1016/j.cmet.2023.03.003
摘要
Maladaptation of host-microbiota metabolic interplay plays a critical role in colorectal cancer initiation. Here, through a combination of single-cell transcriptomics, microbiome profiling, metabonomics, and clinical analysis on colorectal adenoma and carcinoma tissues, we demonstrate that host's urea cycle metabolism is significantly activated during colorectal tumorigenesis, accompanied by the absence of beneficial bacteria with ureolytic capacity, such as Bifidobacterium, and the overabundance of pathogenic bacteria lacking ureolytic function. Urea could enter into macrophages, inhibit the binding efficiency of p-STAT1 to SAT1 promotor region, and further skew macrophages toward a pro-tumoral phenotype characterized by the accumulation of polyamines. Treating a murine model using urea cycle inhibitors or Bifidobacterium-based supplements could mitigate urea-mediated tumorigenesis. Collectively, this study highlights the utility of urea cycle inhibitors or therapeutically manipulating microbial composition using probiotics to prevent colorectal cancer.
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