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  2. Intestinal microbiota affects the progression of colorectal cancer by participating in the host intestinal arginine catabolism

Intestinal microbiota affects the progression of colorectal cancer by participating in the host intestinal arginine catabolism

  • Cell Rep. 2025 Mar 25;44(3):115370. doi: 10.1016/j.celrep.2025.115370.
Siyang Xu 1 Yuling Zhang 1 Xiaoqi Ding 1 Yijun Yang 1 Jinge Gao 1 Ning Zou 2 Li Lu 3 Jin He 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, P.R. China.
  • 2 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, P.R. China.
  • 3 Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, P.R. China. Electronic address: luli117@163.com.
  • 4 National Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, P.R. China. Electronic address: hejin@mail.hzau.edu.cn.
Abstract

Arginine plays a critical role in colorectal Cancer (CRC) progression. We find that arginine catabolism is reduced in the intestinal microbiota of patients with CRC but increased in tumor tissue. We further verify that Escherichia coli can consume arginine via the arginine succinyltransferase (AST) pathway, and gavaging mice with the AST-deficient E. coli Nissle 1917 (ΔacEcN) can inhibit arginine catabolism of the intestinal microbiota, thereby increasing the arginine concentration in the colon. In the azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model, reduced arginine catabolism in the intestinal microbiota increases the arginine concentration in the tumor microenvironment, thereby activating the nitric oxide (NO) synthesis pathway and polyamine synthesis pathway in tumor tissues, stimulating angiogenesis in the tumor microenvironment, inducing M2 macrophage polarization, and activating the Wingless/Integrated (Wnt)/β-catenin pathway, ultimately accelerating CRC progression. This study reveals that intestinal microbiota can affect CRC progression through arginine catabolism, providing a potential target for the prevention and therapy of CRC.

Keywords

CP: Cancer; Escherichia coli Nissle 1917; Wnt/β-catenin; angiogenesis; arginine catabolism; arginine succinyltransferase; colorectal cancer; intestinal microbiota; macrophage; nitric oxide; polyamine.

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