Microbiota and Small Cell Lung Cancer: A casual bystander or a hidden culprit?

The tumor-associated microbiome is a key player in cancer development, progression, prognosis, and therapeutic response. Notably, distinct microbial signatures have been identified across cancer types. Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancer, yet its microbiome remains unclear. Analyzing the bacteriome composition in tissue from ten SCLC cases and in 10 cases of a heterogenous lung pathology group, we found a distinct microbial signature associated with SCLC with significantly lower diversity and higher dissimilarity, characterized by a higher relative abundance of Firmicutes and Bacteroidota, and a markedly different set of dominant genera ( Pseudomonas, Streptococcus and Haemophilus ) resulting in an increased Proteobacteria-to-Actinobacteria ratio. Unexpectedly, mycobiome analysis comparing pooled samples of these SCLC cases with ten pooled lung adenocarcinoma (LUAD) cases revealed that the fungal genus Taphrina was uniquely represented in SCLC. Strikingly, mycobiome individual analysis of twenty-one additional SCLC cases compared with 10 LUAD cases showed an increased prevalence of Taphrina sp. in SLCL tissue. Overall, the results suggest that SCLC microbiome is distinct from other lung pathologies and uncovers a novel link between the biotrophic plant pathogenic Taphrina and human cancer.