Salivary Microbial Dysbiosis is Associated with Systemic Inflammatory Markers and Predicted Oral Metabolites in Non-Small Cell Lung Cancer Patients

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

31205521

DOI Digital object identifier for electronic documents.

10.7150/jca.28077

URI Uniform resource identifier for web resources.

Authors

Zhang W, Luo J, Dong X, Zhao S, Hao Y, Peng C, Shi H, Zhou Y, Shan L, Sun Q, Li Y, Zhao X

Journal

Journal of Cancer

Year

2019

An increasing number of studies have suggested the dysbiosis of salivary microbiome has been linked to the advancement of multiple diseases and proved to be helpful for the diagnosis of them. Although epidemiological studies of salivary microbiota in carcinogenesis are mounting, no systemic study exists regarding the oral microbiota of non-small cell lung cancer (NSCLC) patients. In this study, we presented the characteristics of the salivary microbiota in patients from NSCLC and healthy controls by sequencing of the 16S rRNA microbial genes. Our result revealed distinct salivary microbiota composition in patients from NSCLC compared to the healthy controls. As principal co-ordinates analysis (PCoA) showed, saliva samples clearly differed between the two groups, considering the weighted (p = 0.001, R2 = 0.17), and unweighted (p = 0.001, R2 = 0.25) UniFrac distance. Phylum Firmicutes (31.69% vs 24.25%, p < 0.05) and its two genera Veillonella (15.51%% vs 9.35%, p < 0.05) and Streptococcus (9.96% vs 6.83%, p < 0.05) were strongly increased in NSCLC group compared to the controls. Additionally, the relative abundances of Fusobacterium (3.06% vs 4.92%, p = 0.08), Prevotella (1.45% vs 3.52%, p < 0.001), Bacteroides (0.56% vs 2.24%, p < 0.001), and Faecalibacterium (0.21% vs 1.00%, p < 0.001) in NSCLC group were generally decreased. Furthermore, we investigated the correlations between systemic inflammation markers and salivary microbiota. Neutrophil-lymphocyte ratio (NLR) positively correlated with the Veillonella (r =0.350, p = 0.007) and lymphocyte-monocyte ratio (LMR) negatively correlated with Streptococcus (r =-0.340, p = 0.008). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways inferred by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that pathways related to xenobiotics biodegradation and metabolism (p < 0.05) and amino acid metabolism (p < 0.05) were enriched in the NSCLC group. Folate biosynthesis (p < 0.05) significantly decreased in NSCLC group. The specific correlations of clinical systemic inflammation markers and predicted KEGG pathways also could pronounce a broad understanding of salivary microbiota in patients with NSCLC. Moreover, our study extended the new sight into salivary microbiota-targeted interventions to clinically improve the therapeutic strategies for salivary dysbiosis in NSCLC patients. Further investigations of the potential mechanism of salivary microbiota in the progression of NSCLC are still in demand.

Experiment 1

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Curated date: 2021/01/10

Curator: WikiWorks

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Subjects

Location of subjects: China

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: lung cancer alveolar cell carcinoma,cancer of lung,lung cancer,lung cancer, protection against,lung neoplasm,malignant lung neoplasm,malignant lung tumor,malignant neoplasm of lung,malignant neoplasm of the lung,malignant tumor of lung,malignant tumor of the lung,Nonsmall cell lung cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies: NSCLC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: newly diagnosed NSCLC (non small cell lung cancer) patients
Group 0 sample size Number of subjects in the control (unexposed) group: 20
Group 1 sample size Number of subjects in the case (exposed) group: 39
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 6 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V2

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: Metastats

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Matched on Factors on which subjects have been matched on in a case-control study: age, sex, body mass index

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased
Chao1 Abundance-based estimator of species richness: unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Signature 1

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Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 2

Description: Salivary microbial dysbiosis in non-small cell lung cancer

Abundance in Group 1: increased abundance in NSCLC

NCBI	Links
Actinomycetota
Bacillota
Pseudomonadota
Aggregatibacter
Rothia
Leptotrichia
Lautropia
Streptococcus
Veillonella

Revision editor(s): WikiWorks

Signature 2

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 2

Description: Salivary microbial dysbiosis in non-small cell lung cancer

Abundance in Group 1: decreased abundance in NSCLC

NCBI	Links
Bacteroidota
Faecalibacterium
Bacteroides
Prevotella
Alloprevotella
Porphyromonas

Revision editor(s): WikiWorks

Experiment 2

Edit History Delete

Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Atrayees

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: lung cancer alveolar cell carcinoma,cancer of lung,lung cancer,lung cancer, protection against,lung neoplasm,malignant lung neoplasm,malignant lung tumor,malignant neoplasm of lung,malignant neoplasm of the lung,malignant tumor of lung,malignant tumor of the lung,Nonsmall cell lung cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies: NSCLC
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: newly diagnosed NSCLC (non small cell lung cancer) patients
Group 0 sample size Number of subjects in the control (unexposed) group: 20
Group 1 sample size Number of subjects in the case (exposed) group: 39
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 6 months

Lab analysis

Sequencing type: 16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 4

Matched on Factors on which subjects have been matched on in a case-control study: age, sex, body mass index

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased
Chao1 Abundance-based estimator of species richness: unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness: increased