The Complex Interplay Between Cancer and the Lung Microbiome

Background: The lung fosters a diverse microbiome that may have a complex interplay with underlying diseases, such as lung cancer. However, existing literature has revealed diverse results, likely owing to small sample sizes and diverse sampling methods. In this context, we aim to characterize the lung microbiome and its association with malignancy via multiple sampling methods during lung resection. Methods: Patients undergoing lung resection for confirmed malignancy were prospectively included in the study. During the operation, a bronchial swab and a parenchymal biopsy of lung tissue were collected from the resected specimen and sent for analysis via 16S rRNA gene amplicon (V4) sequencing. An established bioinformatics pipeline was used to determine taxonomic identification and compare these results to clinical and tumor data. Results: There were 83 participants included, with 75 (90.4%) patients having primary lung tumors and 8 (9.6%) having metastatic lesions. Resections included lobectomy (69.9%), wedge (25.3%), and segmentectomy (4.8%). Lung microbiome composition differed by primary malignancy site (lung vs metastatic; p=0.014) and tumor mutations (TP53, p=0.040; KRAS, p=0.054). For primary lung cancer, there was no difference in microbiome composition by tumor histology. A near-significant association was noted for patients with prolonged air leaks and alpha diversity of the lung microbiome (p=0.070). Conclusions: In this study, we demonstrate associations between the lung microbiome and underlying malignancy and tumor characteristics. Validation of these results may assist with diagnostic, prognostic, and therapeutic interventions in the operative and peri-operative management of lung cancer.