Abstract:Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared to 62 control subjects with respect to CA and MN fre… Show more
“…With our established metaproteomics platform, we identified several lung cancer-associated bacteria from the genus to the class level that is consistent with previous sequencingbased studies [9,[61][62][63][64][65][66] and revealed novel lung cancerrelated bacteria that were underestimated by conventional methods. Through an independent cohort validation, 7 species were confirmed to be lung cancer associated.…”
Section: Discussionsupporting
confidence: 86%
“…We then conducted the linear discriminant effect size (LEfSe) analysis to explore marked differences of bacteria between the two groups (Figure 5(b)). Genus Fusobacterium and Neisseria, family Neisseriaceae and Actinomycetaceae, and order Burkholderiales were characteristic bacteria in lung cancer, while decreased genus Actinomyces and class Spirochaetia was found in lung cancer, which corroborates the findings in previous sequencing-based studies [9,[61][62][63][64][65][66].…”
The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced Fusobacterium nucleatum and Prevotella histicola and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.
“…With our established metaproteomics platform, we identified several lung cancer-associated bacteria from the genus to the class level that is consistent with previous sequencingbased studies [9,[61][62][63][64][65][66] and revealed novel lung cancerrelated bacteria that were underestimated by conventional methods. Through an independent cohort validation, 7 species were confirmed to be lung cancer associated.…”
Section: Discussionsupporting
confidence: 86%
“…We then conducted the linear discriminant effect size (LEfSe) analysis to explore marked differences of bacteria between the two groups (Figure 5(b)). Genus Fusobacterium and Neisseria, family Neisseriaceae and Actinomycetaceae, and order Burkholderiales were characteristic bacteria in lung cancer, while decreased genus Actinomyces and class Spirochaetia was found in lung cancer, which corroborates the findings in previous sequencing-based studies [9,[61][62][63][64][65][66].…”
The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced Fusobacterium nucleatum and Prevotella histicola and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.
“… 4 , 27 The relative abundance of a lung cancer-associated oral-related bacteria, Streptococcus , tended to be reduced in the subset of patients who took CBM588 compared with the subset who did not. 29 , 32 These results suggest that the presence of a live biotherapeutic bacterium CBM588 in the gut of cancer patients may provide a beneficial impact on gut commensals. Figure 7.…”
Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing.
Clostridium butyricum
therapy using
C. butyricum
MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.
“…Since pneumoconiosis is associated with the risk of cancer [ 7 ], it is interesting to consider the presence of Streptococcus in the respiratory tract of lung cancer patients. We recently reported a significant increase in the representation of Streptococcus , Bacillus , Gemella, and Haemophilus in the sputum of lung cancer patients compared to control subjects [ 48 ]. In addition to a significant increase in Streptococcus , we also observe an increase in the representation of the genera Bacillus and Gemella in the sputum of miners with CWP compared to control subjects ( Table 3 ).…”
Coal worker’s pneumoconiosis (CWP) is an occupationally induced progressive fibrotic lung disease. This irreversible but preventable disease currently affects millions across the world, mainly in countries with developed coal mining industries. Here, we report a pilot study that explores the sputum microbiome as a potential non-invasive bacterial biomarker of CWP status. Sputum samples were collected from 35 former and active coal miners diagnosed with CWP and 35 healthy controls. Sequencing of bacterial 16S rRNA genes was used to study the taxonomic composition of the respiratory microbiome. There was no difference in alpha diversity between CWP and controls. The structure of bacterial communities in sputum samples (β diversity) differed significantly between cases and controls (pseudo-F = 3.61; p = 0.004). A significant increase in the abundance of Streptococcus (25.12 ± 11.37 vs. 16.85 ± 11.35%; p = 0.0003) was detected in samples from CWP subjects as compared to controls. The increased representation of Streptococcus in sputum from CWP patients was associated only with the presence of occupational pulmonary fibrosis, but did not depend on age, and did not differ between former and current miners. The study shows, for the first time, that the sputum microbiota of CWP subjects differs from that of controls. The results of our present exploratory study warrant further investigations on a larger cohort.
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