2021年12月23日出版的《癌细胞》杂志发表了美国密歇根大学Yatrik M. Shah研究团队的最新成果，他们发现健康个体肠道微生物组中的Reuterin蛋白通过改变氧化还原平衡抑制结直肠癌(CRC)细胞生长。

研究人员分析了由不同突变造成结肠肿癌小鼠模型中相关的粪便代谢物。研究发现健康小鼠或人的微生物代谢物具有生长抑制作用，而这种反应在模型小鼠和CRC患者中减弱。微生物分析表明，罗伊氏乳杆菌及其代谢物Reuterin蛋白在小鼠和人类CRC中下调。Reuterin改变氧化还原平衡，并减少结肠癌细胞的增殖和存活。Reuterin诱导选择性蛋白质氧化并抑制核糖体生物合成和蛋白质翻译。外源性罗伊氏乳杆菌限制结肠肿瘤生长，增加肿瘤活性氧类型，并减少体内蛋白质翻译。该研究结果表明，健康个体的微生物组，特别是其含有的罗伊氏乳杆菌，通过微生物代谢物交换可预防CRC。

据介绍，微生物失调是结直肠癌的标志，会产生炎症、肿瘤生长和对治疗的反应。肠道微生物通过代谢物发出信号，但很大程度上代谢物如何影响CRC是未知的。

附：英文原文

Title: Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance

Author: Hannah N. Bell, Ryan J. Rebernick, Joshua Goyert, Rashi Singhal, Miljan Kuljanin, Samuel A. Kerk, Wesley Huang, Nupur K. Das, Anthony Andren, Sumeet Solanki, Shannon L. Miller, Peter K. Todd, Eric R. Fearon, Costas A. Lyssiotis, Steven P. Gygi, Joseph D. Mancias, Yatrik M. Shah

Issue&Volume: 2021-12-23

Abstract: Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation,tumor growth, and therapy response. Gut microbes signal via metabolites, but how themetabolites impact CRC is largely unknown. We interrogated fecal metabolites associatedwith mouse models of colon tumorigenesis with varying mutational load. We find thatmicrobial metabolites from healthy mice or humans are growth-repressive, and thisresponse is attenuated in mice and patients with CRC. Microbial profiling revealsthat Lactobacillus reuteri and its metabolite, reuterin, are downregulated in mouse and human CRC. Reuterin alters redox balance, and reduces proliferation and survival in colon cancercells. Reuterin induces selective protein oxidation and inhibits ribosomal biogenesisand protein translation. Exogenous Lactobacillus reuteri restricts colon tumor growth, increases tumor reactive oxygen species, and decreasesprotein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.

DOI: 10.1016/j.ccell.2021.12.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00613-9