Cancer Cell:肠道菌群立功,通过代谢物罗伊氏菌素抑制结直肠癌

2022-01-09 Mia “生物世界”公众号

结直肠癌(CRC)是第三大常见癌症,也是癌症死亡的第四大常见原因。未发生转移结直肠癌预后较好。一旦发生转移,临床上缺乏有效的治疗办法,且大多数病例对免疫治疗无效。

结直肠癌CRC)是第三大常见癌症,也是癌症死亡的第四大常见原因。未发生转移结直肠癌预后较好。一旦发生转移,临床上缺乏有效的治疗办法,且大多数病例对免疫治疗无效。除了一部分患者是由于遗传突变外,生活方式、饮食、炎症和肠道菌群的改变也会影响结直肠癌的发生和发展。揭示肠道菌群失调在参与影响炎症、肿瘤生长和治疗中的机制,有助于更好的预防和治疗结直肠癌。

近日,美国密歇根大学 Yatrik M. Shah 团队在 Cancer Cell 期刊在线发表了一篇题为:Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance 的研究论文。

该研究发现,健康个体的肠道菌群中的益生菌罗伊氏乳杆菌所产生的的罗伊氏菌素(Reuterin)能够通过改变氧化还原平衡抑制结直肠癌细胞的生长。

研究人员首先分析了由不同突变造成结直肠癌小鼠模型中相关的粪便代谢物,发现健康小鼠或人的肠道菌群代谢物对结直肠癌细胞系具有生长抑制作用,而结直肠癌疾病模型小鼠或结直肠癌患者的肠道菌群代谢物对结直肠癌细胞系的抑制作用则表现较弱。

通过进一步的微生物分析,研究团队发现结直肠癌疾病模型小鼠或结直肠癌患者的肠道菌群中罗伊氏乳杆菌(Lactobacillus reuteri)及其代谢物罗伊氏菌素(Reuterin)的水平较正常均有明显下调。

罗伊氏乳杆菌是几乎天然存在于所有脊椎动物和哺乳动物肠道内的乳酸菌,对肠黏膜具有很强的黏附能力,其代谢物罗伊氏菌素(Reuterin)是一种广谱抗菌物质,能广泛抑制革兰氏阳性菌、革兰氏阴性菌、酵母、真菌和病原虫等的生长。

更重要的是,研究团队发现了罗伊氏菌素(Reuterin)的细胞毒性和生长抑制作用,向培养基内添加罗伊氏菌素(Reuterin)可以很大程度的抑制细胞增殖,该作用对结直肠癌细胞尤为明显。

为了进一步解释罗伊氏菌素(Reuterin)抑制结直肠癌细胞生长的分子机制,研究团队结合了代谢组学、转录学和蛋白质组学分析发现,在这一过程中,氧化应激反应所必须的基因以及核因子红细胞2相关因子2(NRF2)的下游基因上调,且谷胱甘肽代谢被确定是一个明显的富集途径。因而,研究人员推测氧化应激是一个潜在的机制,即罗伊氏菌素(Reuterin)改变了氧化还原平衡,并减少结直肠癌细胞的增殖和存活。

随后,研究人员对该氧化应激机制做了进一步分析,说明罗伊氏菌素(Reuterin)是通过诱导蛋白质的氧化抑制核糖体生物合成和下游蛋白质翻译,从而抑制结直肠癌细胞的生长。

最后,研究团队在模型小鼠体内将罗伊氏菌素(Reuterin)对结直肠癌的这一抑制作用进行了验证。将HCT116和SW480这两种人结肠癌细胞系皮下植入裸鼠体内,每天给小鼠灌服正常的罗伊氏乳杆菌,或基因工程改造的不产生罗伊氏菌素(Reuterin)的罗伊氏乳杆菌。结果发现,接受正常罗伊氏乳杆菌的小鼠的肿瘤生长明显降低。且在这一过程中,肿瘤活性氧(ROS)的水平和种类均有显着增加。这些结果表明,外源移植性罗伊氏乳杆菌可抑制结直肠癌的体内生长,增加肿瘤活性氧类型,并减少体内蛋白质翻译。

总而言之,该研究表明,健康个体的肠道菌群,特别是其中的罗伊氏乳杆菌,可通过代谢产物罗伊氏菌素(Reuterin)预防结直肠癌的发生发展。该研究帮助人们更好的理解了肠道菌群在结直肠癌中的作用,突出了罗伊氏菌素(Reuterin)在预防和治疗结肠癌中的潜力,为临床上结直肠癌的防治提供了新的思路。

原始出处:

Hannah N. Bell, Ryan J. Rebernick, Joshua Goyert, et al. Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance. Cancer Cell, 2022.

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    2022-11-04 维他命
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    2022-01-15 ms5000000518166734

    学习学习学习学习学习学习学习学习学习学习学习学习学习学习

    0

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