Abstract
BACKGROUND: Excessive abundance of gut pathogens and inflammatory lung damage are potential risk factors for lung cancer. Nevertheless, the exact function of inflammatory proteins in mediating the nexus between gut microbiota and lung cancer remains elusive. METHODS: We first executed Mendelian randomization analysis with the inverse variance weighting method as the primary method, followed by a sensitivity analysis of the results. Finally, we carried out in vitro experiments and database analyses to corroborate our conclusions. RESULTS: After multiple tests, we identified that the gut genus Parasutterella and species Escherichia coli (E. coli) were tied a heightened risk of lung cancer, while Bacteroides salyersiae was a protective factor against lung cancer. Circulating STAM-binding protein (STAMBP) and C-C Motif Chemokine Ligand 23 were considered potential risk factors for lung cancer. In vitro experimental results indicated that the E. coli supernatant significantly induced lung cancer cell proliferation and cell cycle transition but suppressed cell apoptosis. Mechanistically, E. coli increases the production of STAMBP to promote lung cancer progression. CONCLUSIONS: Our results indicated that gut E. coli can potentially increase STAMBP secretion, thereby promoting lung cancer progression. This research delivers a new viewpoint for analyzing the carcinogenic mechanism of E. coli as well as the subsequent prevention and management of lung cancer.