整合微生物组、代谢组和蛋白质组分析鉴定非小细胞肺癌中共生菌、代谢物和候选靶标之间的新相互作用。
Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.
机构信息
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, People's Republic of China.
Zhejiang Provincial Key Laboratory of Thoracic Tumor, Hangzhou, People's Republic of China.
出版信息
Clin Transl Med. 2022 Jun;12(6):e947. doi: 10.1002/ctm2.947.
BACKGROUND
Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation.
METHODS
We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice.
RESULTS
Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC).
CONCLUSIONS
Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.
背景
越来越多的证据表明，肠道微生物群、其特定代谢物和差异表达蛋白（DEP）与非小细胞肺癌（NSCLC）的发病机制有关。我们现在报告肠道微生物群、代谢物和 DEP 对 NSCLC 慢性炎症和免疫失调的介导作用。
方法
我们对健康志愿者和 NSCLC 患者的肠道微生物组进行了 16S 核糖体 RNA 测序。采用液相色谱-质谱（LC-MS）分析方法探索血清样本中代谢物和 DEP 的差异。此外，还对 40 例 NSCLC 组织和 40 例相邻组织进行了基于 LC-MS 的代谢组学分析。分别采用 Spearman 相关系数对组学数据进行分析和整合。然后，采用粪便微生物群移植（FMT）试验评估肠道微生物群和特定代谢物在小鼠中的作用。
结果
粪便微生物组分析显示 NSCLC 患者肠道微生物群失调，属水平上普雷沃氏菌、真杆菌和罗氏菌显著上调。然后，我们发现神经酸/全反式视黄酸水平与普雷沃氏菌呈负相关。此外，在蛋白质组分析中选择了总共 8 个核心 DEP，它们主要参与了 IL-8 和 NF-κB 途径的产生。CRP、LBP 和 CD14 被确定为 NSCLC 的潜在生物标志物。将 NSCLC 患者或普雷沃氏菌定植受体的粪便微生物群移植到小鼠体内，导致炎症和免疫失调。相反，神经酸/全反式视黄酸治疗改善了携带普雷沃氏菌处理的 Lewis 肺癌（LLC）的 C57BL/6 小鼠的表型。
结论
总的来说，这些结果表明 P. copri-神经酸/全反式视黄酸轴可能有助于 NSCLC 的发病机制。
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