Lower respiratory tract microbiome is associated with checkpoint inhibitor pneumonitis in lung cancer patients

Background: The gut microbiome is associated with the occurrence and severity of immune-related adverse events (irAEs) in cancer patients undergoing immunotherapy. However, the relationship between the lower respiratory tract (LRT) microbiome and checkpoint inhibitor pneumonitis (CIP) in lung cancer patients who underwent immunotherapy is unclear. The aim of the present study was to investigate the associations between the LRT microbiome and CIP in lung cancer patients receiving immunotherapy. Methods: This retrospective study included lung cancer patients who received immunotherapy and had metagenomic next-generation sequencing (mNGS) results of LRT specimens [bronchoalveolar lavage fluid (BALF)]. Based on their final diagnosis, the patients were allocated to either the CIP group or the non-CIP group. We conducted an exploratory analysis of the LRT microbiome in the CIP and non-CIP patients, delineating the microbial composition, and comparing the differences between the two groups. Results: In total, 52 lung patients were included in the study, of whom 33 were allocated to the CIP group and 19 to the non-CIP group. The alpha- and beta-diversity analyses revealed no significant differences between the two groups. In the CIP group, the dominant phyla were Firmicutes (41.7%), Acinetobacter (18.2%), and Proteobacteria (16.3%). In the non-CIP group, the dominant phyla were Firmicutes (38.2%), Acinetobacter (18.4%), and Proteobacteria (17.8%). Notably, the relative abundance of the Proteobacteria phylum (P<0.001) and Firmicutes phylum (P=0.01) was significantly higher in the CIP group than the non-CIP group. Conclusions: The elevated relative abundance of the Proteobacteria and Firmicutes phyla in the LRT samples is associated with CIP in lung cancer patients.