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上海交通大学房静远研究组发现了尿素循环激活触发宿主-微生物群适应不良驱动结直肠肿瘤发生。该项研究成果发表在2023年3月23日出版的《细胞—代谢》上。

本研究结合单细胞转录组学、微生物组谱、代谢组学以及结直肠腺瘤和癌组织的临床分析，发现结直肠肿瘤发生过程中，宿主的尿素循环代谢显著激活，伴有具有溶尿能力的有益菌如双歧杆菌缺失，而缺乏溶尿功能的致病菌过多。尿素可进入巨噬细胞，抑制p-STAT1与SAT1启动子区域的结合效率，进一步使巨噬细胞偏向以多胺积累为特征的促肿瘤表型。使用尿素循环抑制剂或双歧杆菌补充剂治疗小鼠模型可以减轻尿素介导的肿瘤发生。

总的来说，这项研究强调了尿素循环抑制剂或使用益生菌治疗性地控制微生物成分以预防结直肠癌的效用。

据介绍，宿主-微生物代谢相互作用的不适应在结直肠癌发病中起着关键作用。

附：英文原文

Title: Urea cycle activation triggered by host-microbiota maladaptation driving colorectal tumorigenesis

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

Issue&Volume: 2023-03-23

Abstract: Maladaptation of host-microbiota metabolic interplay plays a critical role in colorectalcancer initiation. Here, through a combination of single-cell transcriptomics, microbiomeprofiling, metabonomics, and clinical analysis on colorectal adenoma and carcinomatissues, we demonstrate that host’s urea cycle metabolism is significantly activatedduring colorectal tumorigenesis, accompanied by the absence of beneficial bacteriawith ureolytic capacity, such as Bifidobacterium, and the overabundance of pathogenic bacteria lacking ureolytic function. Urea couldenter into macrophages, inhibit the binding efficiency of p-STAT1 to SAT1 promotor region, and further skew macrophages toward a pro-tumoral phenotype characterizedby the accumulation of polyamines. Treating a murine model using urea cycle inhibitorsor Bifidobacterium-based supplements could mitigate urea-mediated tumorigenesis. Collectively, this studyhighlights the utility of urea cycle inhibitors or therapeutically manipulating microbialcomposition using probiotics to prevent colorectal cancer.

DOI: 10.1016/j.cmet.2023.03.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00081-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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