具核梭杆菌促进肺癌发展及其对肺部微生态的影响

Fusobacterium nucleatum promotes lung cancer development and influences the lung microbiota

摘要:

目的 探究具核梭杆菌是否会促进肺癌的发展及其潜在机制。方法 通过细胞实验证实具核梭杆菌能促进肺癌细胞的增殖和转移；通过动物实验验证具核梭杆菌能促进肺癌的发展。对肺癌小鼠的肺泡灌洗液进行16S rRNA基因测序，以及对肺组织进行转录组测序，分析具核梭杆菌对肺癌小鼠肺部菌群的影响及肺组织相关通路的激活情况。结果 具核梭杆菌促进了肺癌上皮细胞A549的增殖和转移。在体内动物实验中，具核梭杆菌感染肺部后肺部结节数量增加，肺组织荧光强度增强。16S rRNA基因测序结果显示，感染小鼠肺部鼠杆状菌属(Muribaculum)、简单螺旋形菌属(Simplicispira)等富集。肺组织转录组结果显示，肺癌小鼠感染具核梭杆菌后激活了IL-17信号通路、细胞因子-细胞因子受体相互作用、金黄色葡萄球菌感染通路、TNF信号通路等与炎症或免疫相关的信号通路。结论 具核梭杆菌感染导致肺部微生物群紊乱，肺组织中多个与炎症和免疫相关的信号通路被激活，从而促进了小鼠肺癌的转移。

Abstract:

Objective To investigate whether Fusobacterium nucleatum promotes the development of lung cancer and find out the underlying mechanisms.Methods The cell experiment proved that F. nucleatum can promote the proliferation and metastasis of lung cancer cells; Animal experiments showed that F. nucleatum can promote the development of lung cancer; 16S rRNA gene sequencing of alveolar lavage fluid and transcriptome sequencing of lung tissue were performed to analyze the effects of F. nucleatum on the lung flora of mice with lung cancer and the activation of relevant pathways in lung tissue.Results The cell experiment showed that F. nucleatum significantly promoted the proliferation and metastasis of A549 cells. The animal experiments confirmed that F. nucleatum infection in the lungs increased the number of nodules and enhanced the fluorescence intensity in the lung tissue. The 16S rRNA gene sequencing revealed the enrichment of Muribaculum and Simplicispira in the lung of infected mice. The transcriptome sequencing results showed that the mouse model of lung cancer activated the interleukin-17 signaling pathway, cytokine-cytokine receptor interactions, Staphylococcus aureus infection pathway, tumor necrosis factor signaling pathway, and other signaling pathways related to inflammation or immunity after being infected with F. nucleatum.Conclusion F. nucleatum infection in mice with lung cancer disrupts the microbiota and activates the immunity- and inflammation-related signaling pathways in the lung, thereby promoting the metastasis of lung cancer in mice.