Farver, C. | Search bioRxiv

bioRxiv2025

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.

cancer biology↗

bioRxiv2021

Ineffectual AEC1 Differentiation from KRT8hi Transitional Cells without Fibrosis Associated with Fatal Acute Respiratory Failure in COVID-19 ARDS

ARDS due to COVID-19 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; clinical recovery requires epithelial regeneration. During physiologic regeneration in mice, AEC2s proliferate, exit the cell cycle, and transiently assume a transitional state before differentiating into AEC1s; persistence of the transitional state is associated with pulmonary fibrosis in humans. It is unknown whether transitional cells emerge and differentiate into AEC1s without fibrosis in human ARDS and why transitional cells differentiate into AEC1s during physiologic regeneration but persist in fibrosis. We hypothesized that incomplete but ongoing AEC1 differentiation from transitional cells without fibrosis may underlie persistent barrier permeability and fatal acute respiratory failure in ARDS. Immunostaining of postmortem ARDS lungs revealed abundant transitional cells in organized monolayers on alveolar septa without fibrosis. They were typically cuboidal or partially spread, sometimes flat, and occasionally expressed AEC1 markers. Immunostaining and/or interrogation of scRNAseq datasets revealed that transitional cells in mouse models of physiologic regeneration, ARDS, and fibrosis express markers of cell cycle exit but only in fibrosis express a specific senescence marker. Thus, in severe, fatal early ARDS, AEC1 differentiation from transitional cells is incomplete, underlying persistent barrier permeability and respiratory failure, but ongoing without fibrosis; senescence of transitional cells may be associated with pulmonary fibrosis.

pathology↗