Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non‐small cell lung cancer

Clinical and Translational Medicine

Guan‐Jun Ma¹  Xiang Qian²  Qing‐Lin Li²  Ai‐qin Zhang²  Zhuo Chen²  Hong‐Yan Zhang²  Xu‐Ming Ji³  Chang‐Yu Li³ 

[1] Department of Comprehensive Ward Affiliated Hangzhou Cancer Hospital Zhejiang University School of Medicine Hangzhou People's Republic of China;The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Hangzhou People's Republic of China;Zhejiang Chinese Medicine University Hangzhou People's Republic of China;

关键词: all‐trans‐retinoic acid;    gut microbiota;    lung cancer;    metabonomics;    nervonic acid;    proteomics;   

DOI  :  10.1002/ctm2.947

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown