Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non‐small cell lung cancer. Issue 6 (23rd June 2022)

• Record Type: Journal Article
• Authors: Qian, Xiang; Zhang, Hong‐Yan; Li, Qing‐Lin; Ma, Guan‐Jun; Chen, Zhuo; Ji, Xu‐Ming; Li, Chang‐Yu; Zhang, Ai‐qin
• Is Part Of: Clinical and translational medicine. Volume 12:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-23
• Subjects: all‐trans‐retinoic acid -- gut microbiota -- lung cancer -- metabonomics -- nervonic acid -- proteomics; Clinical medicine -- Periodicals; Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 616.027
• DOI: 10.1002/ctm2.947
• Languages: English
• ISSNs: 2001-1326

Abstract

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. Abstract : Prevotella, Gemmiger, and Roseburia were significantly upregulated at the genus level in NSCLC patients. Nervonic acid/all‐trans‐retinoic acid was negatively related to Prevotella . CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri ‐colonized recipient mice caused inflammation and immune dysregulation in Lewis lung cancer (LLC) cells‐bearing C57BL/6 mice. Nervonic acid/all‐trans‐retinoic acid improved the Prevotella copri ‐treated LLC cells‐bearing C57BL/6 mice phenotype.