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Urea Cycle Activation Triggered by Host-microbiota Maladaptation Driving Colorectal Tumorigenesis by Haoyan Chen; Tianying Tong; Shi-Yuan Lu; Linhua Ji; Baoqin Xuan; Gang Zhao; Yuqing Yan; Linhong Song; Licong Zhao; Yile Xie; Xiaoxu Leng; Xinyu Zhang; Yun Cui; Xiaoyu Chen; Hua Xiong; TaChung Yu; Xiaobo Li; Tiantian Sun; Zheng Wang; Jinxian Chen; Ying-Xuan Chen; Jie Hong; Jing-Yuan Fang is a Medicine article available to read on EtoBox.

What is Urea Cycle Activation Triggered by Host-microbiota Maladaptation Driving Colorectal Tumorigenesis about?

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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Author

Haoyan Chen; Tianying Tong; Shi-Yuan Lu; Linhua Ji; Baoqin Xuan; Gang Zhao; Yuqing Yan; Linhong Song; Licong Zhao; Yile Xie; Xiaoxu Leng; Xinyu Zhang; Yun Cui; Xiaoyu Chen; Hua Xiong; TaChung Yu; Xiaobo Li; Tiantian Sun; Zheng Wang; Jinxian Chen; Ying-Xuan Chen; Jie Hong; Jing-Yuan Fang

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Medicine (Life Sciences)