Gut dysbiosis promote distant metastasis of NSCLC via regulating the host plasma metabolism

Metastasis are the main causes of death in Non-small cell lung cancer (NSCLC). Gut dysbiosis accelerated the progression of NSCLC. However, the specific role on distant metastasis of NSCLC is still unclear. 16s-rRNA gene sequencing was used to analyze the gut microbiota (GM) structure and diversity in NSCLC with non-distant metastasis (NM, n = 81) and with distant metastasis (M, n = 71). Metabonomics was conducted to determine plasma metabolic profiling of NM (n = 72) and M (42). Fecal microbiota transplantation (FMT) to transplant feces from M into animal models was applied to investigate the influence of GM on tumor metastasis, host metabolism, and gene expression. The α and β diversity demonstrated the gut dysbiosis between the M and NM group. 98 Differential expressed metabolites (DEM) identified and mainly involved in 10 metabolic pathways, such as Tryptophan metabolism. The mouse models evidenced FMT increased the the number of metastasis nodules. In addition, FMT changed the plasma metabolic profiling of mouse models and gene expression. Gut dysbiosis between NSCLC with and without distant metastasis may facilitate distant metastasis of tumors via regulating the host plasma metabolism, especially Tryptophan metabolism.