Correlation between gut microbiota and their metabolites and the efficacy of chemotherapy combined with immunotherapy for extensive-stage small cell lung cancer

Introduction: Gut microbiota has been reported to be associated with the host's immune system and immunotherapy response, as well as immune-related adverse events (irAEs). Additionally, gut microbial metabolites have various immunomodulatory effects. Our study focused on the differences in gut microbiota and their metabolites between long progression-free survival (PFS) and short PFS in patients with small cell lung cancer before and after chemotherapy combined with immunotherapy. Methods: The enrolled patients collected in our department were divided into long PFS and short PFS groups according to whether the PFS was ≥6 months, and the stool samples before and after treatment were analyzed using metagenomics and metabolomics. Results: (P = 0.0127) differed between the long and short PFS groups. In the analysis of differential metabolites, we found that indirubin-3'-monoxime (AUC 0.611), stearidonic acid (AUC 0.867), leukotriene B4 (AUC 0.844), trans-cinnamic acid (AUC 0.792), and L-tyrosine (AUC 0.751) could be used as potential biomarkers. Discussion: Gut microbiota and their metabolites hold broad prospects for translational applications in cancer clinical management, such as the development of microbial biomarkers and the modulation of microbiota to enhance the efficacy of chemotherapy and immunotherapy.