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酒精加速食道状细胞癌的发展,原因是周围循环中高的阴性细菌在周围循环中
Zehua Zhang1, Le Kang2, Yanfen Gu1
1Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong New District, Shanghai, 200120, China.
Experimental hematology & oncology
|February 26, 2025
概括
酒精消费通过改变肠道微生物来增加食道癌症的风险,导致脂多糖 (LPS) 的升高. 这促进了炎症和细胞增殖,表明LPS和阴性细菌是与酒精有关的食道状细胞癌 (ESCC) 的治疗点.
科学领域:
- 微生物学 微生物学
- 在瘤学瘤学.
- 胃肠病学 胃肠病学
背景情况:
- 饮酒是食道状细胞癌 (ESCC) 的重要危险因素.
- 酒精诱导的微生物失生症在ESCC病原体中的作用仍然不完全理解.
研究的目的:
- 研究酒精消费对微生物群的影响及其对ESCC发展的贡献.
- 阐明酒精诱导的微生物变化促进ESCC进展的机制.
主要方法:
- 对328名ESCC患者的回顾性分析.
- 饮酒和ESCC的小鼠模型.
- 血液和组织微生物组组成的分析.
- 测量血清脂多糖酸盐 (LPS) 的水平.
- 研究炎症通路激活 (TNF,TLR,NF-κB,MAPK) 和亡.
主要成果:
- 酒精消费显著增加ESCC风险和Ki67表达.
- 与酒精相关的ESCC患者表现出血液微生物群多样性增加,其中格兰氏阴性细菌占主导地位,血清LPS升高.
- 在小鼠中,酒精摄入增加了瘤负担,损害了肠道屏障的完整性,并促进了细菌转移.
- 在血液和食道组织中发现了高水平的阴性细菌 (Bacteroidales,Escherichia coli).
- 酒精和LPS协同激活了促炎途径,在正常食道细胞中驱动ESCC细胞增殖和LPS诱导的亡.
结论:
- 酒精诱导的微生物失生症和LPS介导的炎症代表了ESCC病变发生的新机制.
- 准Gram阴性细菌和LPS为与酒精有关的ESCC提供了潜在的治疗策略.
- 对微生物变化和瘤微环境的进一步研究是有必要的.
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