Lower Airway Dysbiosis Affects Lung Cancer Progression

Abstract

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in group IIIB-IV TNM stage lung cancer and is associated with poor prognosis, as shown by decreased survival among subjects with early stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with IIIB-IV stage disease. In addition, this lower airway microbiota signature was associated with upregulation of IL-17, PI3K, MAPK and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL-17 inflammatory phenotype and activation of checkpoint inhibitor markers. Statement of Significance (50 word limit)Multiple lines of investigations have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here we support that the local airway microbiota modulates the host immune tone in lung cancer affecting tumor progression and prognosis.Research.

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome

“…Interestingly, the bacterial signatures also identi ed Mycoplasma salivarium, a known oral commensal that has previously been associated with ventilator-acquired pneumonia 63 , as differentially active in those who died and those who were ventilated for more than 28 days when compared to those ventilated less than 28 days. From previous data published by us, enrichment of the lower airway microbiota with oral commensals was seen to be associated with a pro-in ammatory state in several diseases including lung cancer 64,65 and nontuberculosis mycobacterium related bronchiectasis 66 .…”

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome

“…Interestingly, the bacterial signatures also identified Mycoplasma salivarium , a known oral commensal that has previously been associated with ventilator-acquired pneumonia 61 , as differentially active in those who died and those who were ventilated for more than 28 days when compared to those ventilated less than 28 days. From previous data published by us, enrichment of the lower airway microbiota with oral commensals was seen to be associated with a pro-inflammatory state in several diseases including lung cancer 62,63 and non-tuberculosis mycobacterium related bronchiectasis 64 .…”

Host-Microbiome Interaction in Lung Cancer

“…Tsay et al showed that Veillonella parvula was the most abundant taxon driving this dysbiotic association, leading to upregulation of the IL17, PI3K, MAPK, and ERK pathways in the airway transcriptome. They then used V. parvula in the murine KP lung cancer model, characterizing the mechanistic effects on lower airway CD4+ and CD8+, neutrophils, and Th17 recruitment (59). Also, Peters et al recently demonstrated through 16s rRNA gene sequencing of lung samples from NSCLC patients that lung tumor tissue was correlated with significantly lower bacterial richness and diversity, and that alterations in the relative abundance of families such as Koribacteraceae, Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with increased or decreased recurrence-free and disease-free survival (60).…”

“…showed that Veillonella parvula was the most abundant taxon driving this dysbiotic association, leading to upregulation of the IL17, PI3K, MAPK, and ERK pathways in the airway transcriptome. They then used V. parvula in the murine KP lung cancer model, characterizing the mechanistic effects on lower airway CD4+ and CD8+, neutrophils, and Th17 recruitment ( 59 ). Also, Peters et al.…”