Non-small cell lung cancer microbiota characterization: Prevalence of enteric and potentially pathogenic bacteria in cancer tissues

Dumont-Leblond, Nathan; Veillette, Marc; Racine, Christine; Joubert, Philippe; Duchaine, Caroline

doi:10.1371/journal.pone.0249832

Cited by 21 publications

(18 citation statements)

References 41 publications

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“…We did not observe a significant difference in overall microbiome composition between paired tumor and normal lung samples in our study, with composition being more similar within than between patients. Similar overall composition for paired tumor and normal lung is consistent with our previous pilot study [ 21 ] and other studies that have compared tumor and normal lung samples [ 18 , 55 , 56 , 62 – 65 ]. Some of these studies have observed differences in specific taxa between paired tumor and normal lung samples, including a meta-analysis of 5 studies which found decreased abundance of Actinobacteria, Corynebacterium , Lachnoanaerobaculum , and Halomonas in tumor compared to adjacent normal lung [ 66 ].…”

Section: Discussionsupporting

confidence: 91%

The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer

et al. 2022

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Background Cancer recurrence after tumor resection in early-stage non-small cell lung cancer (NSCLC) is common, yet difficult to predict. The lung microbiota and systemic immunity may be important modulators of risk for lung cancer recurrence, yet biomarkers from the lung microbiome and peripheral immune environment are understudied. Such markers may hold promise for prediction as well as improved etiologic understanding of lung cancer recurrence. Methods In tumor and distant normal lung samples from 46 stage II NSCLC patients with curative resection (39 tumor samples, 41 normal lung samples), we conducted 16S rRNA gene sequencing. We also measured peripheral blood immune gene expression with nanoString®. We examined associations of lung microbiota and peripheral gene expression with recurrence-free survival (RFS) and disease-free survival (DFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression, and examined predictive accuracy using time-dependent receiver operating characteristic (ROC) curves. Results Over a median of 4.8 years of follow-up (range 0.2–12.2 years), 43% of patients experienced a recurrence, and 50% died. In normal lung tissue, a higher abundance of classes Bacteroidia and Clostridia, and orders Bacteroidales and Clostridiales, were associated with worse RFS, while a higher abundance of classes Alphaproteobacteria and Betaproteobacteria, and orders Burkholderiales and Neisseriales, were associated with better RFS. In tumor tissue, a higher abundance of orders Actinomycetales and Pseudomonadales were associated with worse DFS. Among these taxa, normal lung Clostridiales and Bacteroidales were also related to worse survival in a previous small pilot study and an additional independent validation cohort. In peripheral blood, higher expression of genes TAP1, TAPBP, CSF2RB, and IFITM2 were associated with better DFS. Analysis of ROC curves revealed that lung microbiome and peripheral gene expression biomarkers provided significant additional recurrence risk discrimination over standard demographic and clinical covariates, with microbiome biomarkers contributing more to short-term (1-year) prediction and gene biomarkers contributing to longer-term (2–5-year) prediction. Conclusions We identified compelling biomarkers in under-explored data types, the lung microbiome, and peripheral blood gene expression, which may improve risk prediction of recurrence in early-stage NSCLC patients. These findings will require validation in a larger cohort.

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Section: Discussionsupporting

confidence: 91%

The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer

et al. 2022

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“…If the intestinal microbiota increases the effect of NAD boosting drugs, their concomitant use with antimicrobial agents should be prescribed only in patients where the presence of neoplastic disease can be ruled out. Bacteria are frequently associated with tumors ( Xu et al, 2020 ; Dumont-Leblond et al, 2021 ); for instance, the bronchial environments of lung tumors bronchial is enriched in Streptococcus harboring PncA nicotine amidase ( Bello et al, 2021 ). The activity of this bacterial protein might protect neoplastic tissues from NAD-targeting anti-cancer drugs by supplying nicotinic acid to the tumor cells, feeding the deamidated biosynthesis pathway to fulfill their high demand for NAD.…”

Section: Discussion Microbiota Modulation and Drugs Acting On Nad Met...mentioning

confidence: 99%

Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials

Baquero

Campo

Martínez

2022

Front. Mol. Biosci.

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A proper NADH/NAD + balance allows for the flow of metabolic and catabolic activities determining cellular growth. In Escherichia coli, more than 80 NAD + dependent enzymes are involved in all major metabolic pathways, including the post-transcriptional build-up of thiazole and oxazole rings from small linear peptides, which is a critical step for the antibiotic activity of some microcins. In recent years, NAD metabolism boosting drugs have been explored, mostly precursors of NAD + synthesis in human cells, with beneficial effects on the aging process and in preventing oncological and neurological diseases. These compounds also enhance NAD + metabolism in the human microbiota, which contributes to these beneficial effects. On the other hand, inhibition of NAD + metabolism has been proposed as a therapeutic approach to reduce the growth and propagation of tumor cells and mitigating inflammatory bowel diseases; in this case, the activity of the microbiota might mitigate therapeutic efficacy. Antibiotics, which reduce the effect of microbiota, should synergize with NAD + metabolism inhibitors, but these drugs might increase the proportion of antibiotic persistent populations. Conversely, antibiotics might have a stronger killing effect on bacteria with active NAD + production and reduce the cooperation of NAD + producing bacteria with tumoral cells. The use of NADH/NAD + modulators should take into consideration the use of antibiotics and the population structure of the microbiota.

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“…Tissue resident microbes have been found to be both cancer promoting and cancer preventing. − In addition to their role in cancer progression, the microbiota is also critical for the metabolism of multiple drugs and xenobiotics, thus determining therapy response and prognosis in cancer patients. − Gut microbes mediate the biotransformation of drugs via multiple chemical reactions including modification and removal of functional groups, proteolysis, denitration, deconjugation, amine metabolism, acetylation, and isoxazole scission. , They can affect the absorption of drugs as well as hinder radiotherapy. , Phylogenetic stratification of tissue resident microbiota reveals greater variability in less abundant microbes at species and strain levels rather than differences at class and phylum levels between breast cancer patients and healthy individuals. , This suggests the involvement of a few specific microbes in carcinogenesis. Certain pathogenic microbes are known to synthesize potent small molecules or genotoxins capable of inducing oncogenic signaling cascades in eukaryotic cells and metabolically rewire them.…”

Section: Discussionmentioning

confidence: 99%

Label-Free Vibrational and Quantitative Phase Microscopy Reveals Remarkable Pathogen-Induced Morphomolecular Divergence in Tumor-Derived Cells

Liu

Parida

et al. 2022

ACS Sens.

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Delineating the molecular and morphological changes that cancer cells undergo in response to extracellular stimuli is crucial for identifying factors that promote tumor progression. Label-free optical imaging offers a potentially promising route for retrieving such single-cell information by generating detailed visualization of the morphology and determining alterations in biomolecular composition. The potential of such nonperturbative morphomolecular microscopy for analyzing microbiota−cancer cell interactions has been surprisingly underappreciated, despite the growing evidence of the critical role of dysbiosis in malignant transformations. Here, using a model system of breast cancer cells, we show that label-free Raman microspectroscopy and quantitative phase microscopy can detect biomolecular and morphological changes in single cells exposed to Bacteroides fragilis toxin (BFT), a toxin secreted by enterotoxigenicB. fragilis. Remarkably, using machine learning to elucidate subtle, but consistent, cellular differences, we found that the morphomolecular differences between BFT-exposed and control breast cancer cells became more accentuated after in vivo passage, corroborating our findings that a short-term BFT exposure imparts a long-term effect on cancer cells and promotes a more invasive phenotype. Complementing more classical labeling techniques, our label-free platform offers a global detection approach with measurements representative of the overall cellular phenotype, paving the way for further investigations into the multifaceted interactions between the cancer cell and the microbiota.

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Non-small cell lung cancer microbiota characterization: Prevalence of enteric and potentially pathogenic bacteria in cancer tissues

Cited by 21 publications

References 41 publications

The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer

The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer

Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials

Label-Free Vibrational and Quantitative Phase Microscopy Reveals Remarkable Pathogen-Induced Morphomolecular Divergence in Tumor-Derived Cells

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