Analyzing lung cancer risks in patients with impaired pulmonary function through characterization of gut microbiome and metabolites

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Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Luan J, Zhang F, Suo L, Zhang W, Li Y, Yu X, Liu B, Cao H
Journal
BMC pulmonary medicine
Year
2024
Keywords:
Biomarkers, Gut microbiota, Lung cancer, Metabolomics, Pulmonary function
BACKGROUND: Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites. METHODS: Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16 S rRNA gene amplicon sequencing and metabolomics. RESULTS: The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function. CONCLUSIONS: Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.

Experiment 1


Needs review

Curated date: 2024/03/21

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Lung cancer , Chronic obstructive pulmonary disease 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,Lung cancer,Airflow Obstruction, Chronic,Airflow Obstructions, Chronic,CAFL - Chronic airflow limitation,CAL - Chronic airflow limitation,CAO - Chronic airflow obstruction,Chronic airflow limitation,Chronic Airflow Obstruction,Chronic Airflow Obstructions,Chronic airway disease,Chronic airway obstruction,chronic airway obstruction, NEC in ICD9CM_2006,chronic airway obstruction, not elsewhere classified,Chronic irreversible airway obstruction,CHRONIC OBSTRUCTIVE AIRWAY DIS,chronic obstructive airway disease,Chronic Obstructive Airways Disease,chronic obstructive airways disease,chronic obstructive airways disease NOS,chronic obstructive airways disease NOS (disorder),CHRONIC OBSTRUCTIVE LUNG DIS,Chronic Obstructive Lung Disease,chronic obstructive lung disease,chronic obstructive lung disease (disorder),chronic obstructive lung disease [Ambiguous],Chronic obstructive lung disease, NEC,Chronic obstructive lung disease, NOS,CHRONIC OBSTRUCTIVE PULM DIS,chronic obstructive pulmonary disease,Chronic Obstructive Pulmonary Disease (COPD),chronic obstructive pulmonary disease (COPD),chronic obstructive pulmonary disease and allied conditions,Chronic obstructive pulmonary disease finding,Chronic obstructive pulmonary disease finding (finding),Chronic obstructive pulmonary disease NOS,CHRONIC OBSTRUCTIVE PULMONARY DISEASE, (COPD),chronic obstructive pulmonary disease, (COPD),COAD,COAD - Chronic obstructive airways disease,COLD,cold,COLD (chronic obstructive lung disease),cold (chronic obstructive lung disease),COLD - Chronic obstructive lung disease,COPD,COPD - Chronic obstructive pulmonary disease,COPD NOS,COPD, CHRONIC OBSTRUCTIVE PULMONARY DISEASE,COPD, chronic obstructive pulmonary disease,DISEASE (COPD), CHRONIC OBSTRUCTIVE,disease (COPD), chronic obstructive,Dops,obstructive lung disease, chronic,OBSTRUCTIVE PULMONARY DISEASE (COPD), CHRONIC,obstructive pulmonary disease (COPD), chronic,PULM DIS CHRONIC OBSTRUCTIVE,PULMONARY DISEASE (COPD), CHRONIC OBSTRUCTIVE,pulmonary disease (COPD), chronic obstructive,Pulmonary Disease, Chronic Obstructive,Chronic obstructive pulmonary disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Benign pulmonary diseases
Group 1 name Corresponds to the case (exposed) group for case-control studies
lung cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A malignant neoplasm involving the lung.
Group 0 sample size Number of subjects in the control (unexposed) group
28
Group 1 sample size Number of subjects in the case (exposed) group
55
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
PLS-DA (Partial least square discriminant analysis)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/21

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Source: figure 2b

Description: Gut microbial composition in lung cancer patients(C) and benign diseases patients(N). (B) Differential taxa at the genus level analyzed by linear discriminant analysis (LDA) scores (LDA > 2.0, P < 0.05)

Abundance in Group 1: increased abundance in lung cancer

NCBI Quality ControlLinks
Anaerobutyricum hallii
Bifidobacterium
Bacteroides

Revision editor(s): Omojokunoluwatomisin

Signature 2

Needs review

Curated date: 2024/03/21

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Source: figure 2b

Description: Gut microbial composition in lung cancer patients(C) and benign diseases patients(N) Differential taxa at the genus level analyzed by linear discriminant analysis (LDA) scores (LDA > 2.0, P < 0.05).

Abundance in Group 1: decreased abundance in lung cancer

NCBI Quality ControlLinks
Blautia
Subdoligranulum
Lachnoanaerobaculum
Kurthia
Fusicatenibacter
Carnobacterium
unclassified atopobiaceaeunclassified atopobiaceae
Propionibacterium
Coprococcus
Ruminococcus gauvreauii
lachnospiraceae ND 3007lachnospiraceae ND 3007
ruminococcaceae CAG-352ruminococcaceae CAG-352

Revision editor(s): Omojokunoluwatomisin

Experiment 2


Needs review

Curated date: 2024/03/21

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Differences from previous experiment shown

Subjects

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,Lung cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
lung cancer
Group 1 name Corresponds to the case (exposed) group for case-control studies
normal pulmonary function
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Any function involved in the exchange of oxygen and carbon dioxide between the atmosphere and the cells of the body
Group 0 sample size Number of subjects in the control (unexposed) group
35
Group 1 sample size Number of subjects in the case (exposed) group
20

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
PLS-DA (Partial least square discriminant analysis)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

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

Experiment 3


Needs review

Curated date: 2024/03/21

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
mild pulmonary dysfunction
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mild pulmonary dysfunction is when the diagnosis is confirmed by spirometry and FEV1 is above 80% predicted.
Group 0 sample size Number of subjects in the control (unexposed) group
32
Group 1 sample size Number of subjects in the case (exposed) group
23

Lab analysis

Statistical Analysis

Statistical test
PLS-DA (Partial least square discriminant analysis)

Alpha Diversity

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

Experiment 4


Needs review

Curated date: 2024/03/22

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
moderate pulmonary dysfunction
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
moderate pulmonary dysfunction is when the diagnosis is confirmed by spirometry and FEV1 is between 50–79% predicted.
Group 0 sample size Number of subjects in the control (unexposed) group
43
Group 1 sample size Number of subjects in the case (exposed) group
12

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
PLS-DA (Partial least square discriminant analysis)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/22

Curator: Omojokunoluwatomisin

Revision editor(s): Omojokunoluwatomisin

Source: Figure 4C

Description: Gut microbial composition differences between ZC, QD, and ZZD patients.12 significantly different genera were showed by Kruskal wallis H test bar plot.

Abundance in Group 1: increased abundance in moderate pulmonary dysfunction

NCBI Quality ControlLinks
Eubacterium sp.
Lachnospiraceae
Lactococcus
Raoultibacter
Romboutsia
Subdoligranulum

Revision editor(s): Omojokunoluwatomisin