Gut microbiota and metabolites associated with immunotherapy efficacy in extensive-stage small cell lung cancer: a pilot study

Background: The gut microbiota and its associated metabolites play a critical role in shaping the systemic immune response and influencing the efficacy of immunotherapy. In this study, patients with extensive-stage small cell lung cancer (ES-SCLC) were included to explore the correlation between gut microbiota and metabolites and immunotherapy efficacy in patients with ES-SCLC. Methods: Pre- and post-treatment, we collected stool samples from 49 ES-SCLC patients treated with an anti-programmed death-ligand 1 (PD-L1) antibody. We then applied 16S ribosomal RNA (rRNA) sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolomics technology. Subsequently, the gut microbiota and metabolites were identified and classified. Results: The results showed no statistical difference in gut microbiota alpha and beta diversity between the responder (R) and non-responder (NR) patients at baseline. However, the alpha diversity of the R patients was significantly higher than that of the NR patients after treatment. There were also differences in the microbiome composition at the baseline and post-treatment. Notably, after treatment, Faecalibacterium, Clostridium_sensu_stricto_1, and [Ruminococcus]_torques were enriched in the R group, while Dubosiella, coriobacteriaceae_UCG-002 was enriched in the NR group. The non-targeted metabolomics results also indicated that short-chain fatty acids (SCFAs) were up-regulated in the R group after treatment. More, differential metabolites were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the PD-L1 expression and programmed death 1 (PD-1) checkpoint pathway in cancer. Conclusions: These findings are anticipated to provide novel markers for predicting the efficacy of immune checkpoint inhibitors (ICIs) in patients with ES-SCLC, and offer new directions for further research on molecular mechanisms.