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由肠道细菌衍生的膜囊泡通过诱导结肠上皮细胞中的DNA损伤来诱导结肠失生症

Yu Miyakawa¹, Motoyuki Otsuka², Chikako Shibata¹

¹Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Cellular and molecular gastroenterology and hepatology

|February 3, 2024

概括

甲状腺菌 (Actinomyces odontolyticus) 分泌的膜囊泡会引发炎症和DNA损伤,从而引发结肠直肠癌 (CRC). 这一发现突显了肠道细菌在CRC发展中的作用.

科学领域:

微生物学微生物学
在瘤学瘤学.
细胞生物学细胞生物学

背景情况:

结肠直肠癌 (CRC) 是一个主要的全球健康问题.
肠道微生物群失生症越来越多地与CRC病变发生有关.
一种口腔细菌Actinomyces odontolyticus在早期的CRC中大量存在.

研究的目的:

为了研究Actinomyces odontolyticus在结肠瘤发生中的生物学功能.
确定A. odontolyticus有助于结直肠癌发病的机制.

主要方法:

检查了A. odontolyticus在人类结肠上皮细胞 (CEC) 中的细胞内信号诱导.
在CEC中使用人类诱导的多能干细胞衍生肠道器官和小鼠结肠组织来评估DNA损伤.

主要成果:

A. odontolyticus分泌的膜囊泡 (MVs) 诱导NF-κB信号和过度的ROS生产在CECs.
这些富含脂肪酸的MV激活TLR2,导致线粒体功能障碍,ROS生成和DNA损伤.
在有机体和小鼠模型中证实了A. odontolyticus诱导的DNA损伤.

结论:

A. odontolyticus MVs在结肠上皮细胞中促进慢性炎症和ROS的产生.
这一过程启动了结直肠癌的发展.
A. odontolyticus被确定为CRC病变的新型贡献者.

关键词:

一个牙消毒剂.大肠癌是什么意思大肠癌是什么意思 DNA 损伤 DNA 损伤线粒体中的线粒体.在 NF-κBB 中.

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