Du Yang, Fan Chengjuan, Song Xiaowei, Teng Chong, Zhang Zhichao, Zhang Jing, Zhao Tianjiao, Xin Tao
Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Cell Infect Microbiol. 2025 Jun 27;15:1616695. doi: 10.3389/fcimb.2025.1616695. eCollection 2025.
The incidence and mortality rates of lung cancer are both elevated. In lung cancer, leptomeningeal metastasis (LM) is a serious consequence. Patients suffering from LM have severe symptoms and a short survival time. Numerous studies have shown a connection between the prognosis of lung cancer and the composition of the gut microbiota. However, Current knowledge regarding the gut microbiota and metabolites in lung cancer patients with LM, as well as their potential impacts on LM pathogenesis, remains remarkably limited.
We established a mouse model of LM from lung cancer and a subcutaneous metastatic model, using wild-type mice as controls. Each of the three groups above contained six mice. We examined the fecal microbiota and metabolites of three groups of mice utilizing 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) technologies. Conducting correlation analysis on microbiome and metabolome data concurrently to identify significant relationships.
Mice with LM had a different gut microbiota and metabolite composition than wild-type and subcutaneous metastatic mice; the LM group had a higher ratio of Firmicutes to Bacteroidetes. Differential metabolites are primarily seen in pathways such as Nicotinate and nicotinamide metabolism, Tryptophan metabolism; Association analysis reveals that some changes in gut microbiota are linked to metabolites, such as a positive association between Eubacteria and N-Acetylsorotonin.
Some microbiota and metabolites may act as biomarkers for LM, controlling gut microbiota and metabolites or giving a novel option for research into lung cancer leptomeningeal metastases.
肺癌的发病率和死亡率均有所上升。在肺癌中，软脑膜转移（LM）是一个严重的后果。患有LM的患者症状严重且生存时间短。众多研究表明肺癌的预后与肠道微生物群的组成之间存在关联。然而，目前关于患有LM的肺癌患者的肠道微生物群和代谢物，以及它们对LM发病机制的潜在影响的知识仍然非常有限。
我们建立了肺癌软脑膜转移小鼠模型和皮下转移模型，以野生型小鼠作为对照。上述三组每组包含六只小鼠。我们利用16S rRNA基因测序和液相色谱 - 质谱（LC-MS）技术检测了三组小鼠的粪便微生物群和代谢物。同时对微生物组和代谢组数据进行相关性分析以确定显著关系。
患有LM的小鼠与野生型和皮下转移小鼠的肠道微生物群和代谢物组成不同；LM组厚壁菌门与拟杆菌门的比例更高。差异代谢物主要出现在烟酸和烟酰胺代谢、色氨酸代谢等途径中；关联分析表明肠道微生物群的一些变化与代谢物有关，例如真细菌与N-乙酰血清素之间呈正相关。
一些微生物群和代谢物可能作为LM的生物标志物，控制肠道微生物群和代谢物或为肺癌软脑膜转移的研究提供新的选择。
