EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001004728EGAEGA study EGAS0000100472816S V3-V4 sequencing of lung microbiota from 17 NSCLC patients eligible for surgery without neoadjuvant treatmentEGArestricted<h4>Background</h4>While well-characterised on its molecular base, non-small cell lung cancer (NSCLC) and its interaction with local microbiota remains scarcely explored. Moreover, current studies vary in source of lung microbiota, from bronchoalveolar lavage fluid (BAL) to tissue, introducing potentially differing results. Therefore, the objective of this study was to provide detailed characterisation of the oral and multi-source lung microbiota of direct interest in lung cancer research. Since lung tumours in lower lobes (LL) have been associated with decreased survival, characteristics of the microbiota in upper (UL) and lower tumour lobes have also been examined.<h4>Methods</h4>Using 16S rRNA gene sequencing technology, we analysed microbiota in saliva, BAL (obtained directly on excised lobe), non-malignant, peritumoural and tumour tissue from 18 NSCLC patients eligible for surgical treatment. Detailed taxonomy, diversity and core members were provided for each microbiota, with analysis of differential abundance on all taxonomical levels (zero-inflated binomial general linear model with Benjamini-Hochberg correction), between samples and lobe locations.<h4>Results</h4>Diversity and differential abundance analysis showed clear separation of oral and lung microbiota, but more importantly, of BAL and lung tissue microbiota. Phylum Proteobacteria dominated tissue samples, while Firmicutes was more abundant in BAL and saliva (with class Clostridia and Bacilli, respectively). However, all samples showed increased abundance of phylum Firmicutes in LL, with decrease in Proteobacteria. Also, clades Actinobacteria and Flavobacteriia showed inverse abundance between BAL and extratumoural tissues depending on the lobe location. While tumour microbiota seemed the least affected by location, peritumoural tissue showed the highest susceptibility with markedly increased similarity to BAL microbiota in UL. Differences between the three lung tissues were however very limited.<h4>Conclusions</h4>Our results confirm that BAL harbours unique lung microbiota and emphasise the importance of the sample choice for lung microbiota analysis. Further, limited differences between the tissues indicate that different local tumour-related factors, such as tumour type, stage or associated immunity, might be the ones responsible for microbiota-shaping effect. Finally, the "shift" towards Firmicutes in LL might be a sign of increased pathogenicity, as suggested in similar malignancies, and connected to worse prognosis of the LL tumours.<h4>Trial registration</h4>ClinicalTrials.gov ID: NCT03068663. Registered February 27, 2017.Characterisation of microbiota in saliva, bronchoalveolar lavage fluid, non-malignant, peritumoural and tumour tissue in non-small cell lung cancer patients: a cross-sectional clinical trial.Bingula Rea R, Filaire Edith E, Molnar Ioana I, Delmas Eve E, Berthon Jean-Yves JY, Vasson Marie-Paule MP, Bernalier-Donadille Annick A, Filaire Marc Mtreatment, Therapy, study, Microbial Community Composition, Community Composition, Microbiomes, Microbial Community Compositions, Microbial Community, non-small cell lung carcinoma, operative therapy, Microbial Community Structure, Community Structure, operations, intraoperative procedures, Surgery, non-small cell carcinoma of the lung, Microbial, Client, Treatments, Human, non-small cell lung cancer, Composition, non-small cell cancer of the lung, non-small cell carcinoma of lung, NSCLC, disease management., Patient, peroperative procedures, Therapeutic, Clients, Microbial Community Structures, perioperative procedures, Therapies, Microbiotas, Treatment, NSCLC - non-small cell lung cancer, operative procedures, Non-small cell lung cancer, non-small cell cancer of lung, General, preoperative procedures, non-small cell lung carcinoma (disease), Human Microbiomes, Microbial Communities, Community, Human Microbiome, Microbiome, invasive proceduresmixed phenotype acute leukaemia, Malignant tumor of lung, Bile salt-stimulated lipase, odd(Oz), Laboratory, A4, malignant neoplasm of the lung, sulfur, infectivity, Lung Carcinomas, parenchyma of lung, Method, RNA Genes, ten-m, 1, 2, Research Activity, Pulmonary Lavage Fluids, Laboratory Research, placement, Priorities, treatment, gamma sarcoglycan, Lung Cancer, 3-hydroxy-1, l(3)rP126, azufre, Solute carrier family 27 member 5, Tissue, Basen, S, Ribosomal RNA, Lung Cancers, procedures, BcDNA:AT25108, Lobel, decreased, Ach, sample, GOV, Microbial Community Structures, l(3)61Da, dithioglycerol, stage, purple photosynthetic bacteria and relatives, Very long-chain acyl-CoA synthetase-related protein, dimercaptopropanol, pulmo, gov, CG5723, lung parenchyma, Salivas, Research Priorities, Purple Bacteria, Procedure, Emc, CG1007, non-small cell lung cancer, Carboxyl ester lipase, Base2, Base1, Pathogenicity, malignant tumour of lung, sarcoglycan, simple tissue, relational spatial quality, Microbial Communities, 0977/09, Carcinomas, Research and Development, Lung malignant tumors, Industrial, low G+C Gram-positive bacteria, Actinobacteraeota, Industrial Arts, death rate, Microbial Community Compositions, alpha, Methodological, Lung Lavage Fluids, rRNA gene, Activities, Composition, 0587/01, hyaline, pulmonary, 35kD dystrophin-associated glycoprotein, rRNA Gene, Bronchoalveolar Lavage Fluids, BACS, AML with lymphoid markers, 2017, Purple, Cancer of the Lung, lung neoplasm, Community, Lobe, Lung, 5301, clostridial firmicutes, Neoplasms, developmental stage, lung cancer, Prognostic Factors, non-small cell carcinoma of the lung, firmicutes, Human, Odz, British antilewisite, 3-dimercaptopropanol, Firmacutes, lung, AW214463, 2-propanedithiol, bronchoalveolar lavage fluid, Pulmonary Cancer, MAM, gamma-SG, neoplasm, Technique, Pulmonary, dimercaprol, l(3)04322, odz, malignant tumour of the lung, saliva atomaris, Elemental sulfur, LNCR, mixed phenotype acute leukemia, Bacteria, l(3)rJ307, Lung Carcinoma, Study, l(3)05301, NSCLC, Bacillus/Lactobacillus/Streptococcus group, Lung Neoplasm, 2-dithioglycerol, malignant neoplasm of lung, BA-CoA ligase, Development and Research, Firmicuteota, Human Microbiome, Cancer, Ten-mc., RAD3D, Bronchial Lavage Fluids, Actinobacteriota, 35 kDa dystrophin-associated glycoprotein, Dm0688, Firmibacteria, VLACS-related, bHLHb28, Factor, Bagl, SGCG, Ten79E, actinobacteria, "Alphaproteobacteriota" Whitman et al. 2018, Ribosomal RNA Genes, British anti-Lewisite, chemical analysis, malignant lung tumour, Nonsmall cell lung cancer, Neoplasm, British anti-lewisite, background, Non-small cell lung cancer, Bronchial Lavage Fluid, susceptibility, malignant tumor of the lung, CT16449, DMDA1, Pulmonary Neoplasm, increased number, ms(3)61CD, Cancers, Actinobacteria, Bacillaeota, BALL, PARP-9, RNA Gene, Clostridium group firmicutes, air-filled, dithioglycerine, Fatty acid transport protein 5, Microbiotas, protection against, ten(m), Pulmonary Cancers, virulence, nucleobases, Actinomycetes, RAB16, CG11452, Non-Small-Cell, Proteobacteria, MGC130048, sulfactin, l(3)05592, Activity, determination, Feature, Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980), Non-Small Cell Lung Cancer, malignant tumor of lung, PRAS40, FCAALL.51, Bronchoalveolar, bronchioalveolar lavage, Pancreatic lysophospholipase, Techniques, DmelCG5723, DmelCG1007, theion, Cholate--CoA ligase, Non-Small-Cell Lung Carcinoma, 3-mercaptopropan-1-ol, Non-Small Cell Lung Carcinoma, Schwefel, present in fewer numbers in organism, Bronchial Alveolar Lavage Fluid, Pulmonary cancer, ARTD9, increased, Ribosomal, Immune Processes, Immune Responses, Prognoses, l(3)rL201, alveolar cell carcinoma, bases, Microbial Community Structure, Alveolar Lavage Fluids, 2-dimercapto-3-propanol, Pulmonary Lavage Fluid, ten-m/odz, Non-Small Cell Lung, ten[m], Non Small Cell Lung Carcinoma, Alveolar, Lung Lavage Fluid, resistance to, proteobacteria, Immune, Malignant neoplasm of lung, Methodological Studies, acute leukaemia of undetermined lineage, disease management, soufre, Therapies, gamma-sarcoglycan, BSSL, Research Priority, associated, 1110012J22Rik, somatic mutation, Therapy, dimercaprolum, Carcinoma, Lung cancer, Process, Nucleobase, D2-2, Arts, SG-gamma, Cancer of Lung, Bssl, Microbial, somatic, l(3)05309, results, cancer of lung, Lavage Fluid, ALL with myeloid markers, 3-Mercaptopropanol, Malignant lung tumor, VLACSR, non-small cell lung carcinoma (disease), AI227026, neoplasms, Lavage Fluids, Cholesterol esterase, malignant lung neoplasm, Factors, adenocarcinoma of lung, 16S, Prognostic, susceptibility to, Firmicutes, DL4475C, Low G+C firmicutes, Features, gamma (35kDa dystrophin-associated glycoprotein), Methodological Study, Treatments, Non Small Cell Lung, non-small cell carcinoma of lung, response to tyrosine kinase inhibitor in, sulphur, Terrabacteria, DMDA, Patient, acute leukemia of undetermined lineage, Base, 3-Dimercapto-1-propanol, location, Human Microbiomes, accessory, base, Prognostic Factor, Cancer of the lung, Microbial Community Composition, Sterol esterase, SGCG_HUMAN, Procedures, non-small cell lung carcinoma, malignant lung tumor, Gene, Non-Small-Cell Lung, Ten[m], autosomal dominant, supernumerary, TYPE, DAGA4, non-small cell cancer of the lung, 3-dithiopropanol, reduced, CONSTITUTIVE 1, subnumerary, 35DAG, Studies, saliva molecularis, SUPPRESSOR OF NPR1-1, rRNA Genes, NSCLC - non-small cell lung cancer, Proteobacteriota, SCG3, 3-dimercaptol-1-propanol, study, Ribosomal RNA Gene, Research, High G+C Gram-Positive Bacteria, Bacillus/Clostridium group, rBAL-1, decreased number, l(3)j4E11, Actinomycete, Immune Response, time of survival, Gram-Positive Bacteria, Clients, odz/ten-m, Nonsmall Cell Lung Cancer, FATP-5, rDNA, Characteristics, Immune Process, Non-Small-Cell Lung Carcinomas, Terrabacterida, Community Composition, Pulmonary Neoplasms, BAL cell, beta-dithioglycerol, biphenotypic acute leukemia, Client, 1810036E18Rik, LGMD2C, 6.2.1.7, Alphaproteobacteriota, Priority, survival, Characteristic, Research Activities, core, 3-dimercapto-1-propanol, techniques, Microbiome, 3.1.1.13, Bile acid-CoA ligase, Genes, Microbiomes, Microbial Community, biphenotypic acute leukaemia, 0203/10, Community Structure, Bacillota corrig. Gibbons and Murray 2021, 3.1.1.3, sample population, introduction, present in greater numbers in organism, nonsmall cell lung cancer, rRNA, clear, Therapeutic, Bal, BAL, BC003281, High G+C, SCARMD2, Alveolar Lavage Fluid, Response, Treatment, Lungs, sailva normalis, assay, non-small cell cancer of lung, Bronchial, 0094/26, l(3)00844, methodologyMicrobial Community Composition, Carcinoma, Community Composition, Lung, Bronchial Lavage Fluids, non-small cell lung carcinoma, BAL cell, Salivas, Non-Small Cell Lung Cancer, Non-Small-Cell Lung, non-small cell carcinoma of the lung, Microbial, Bronchoalveolar, Client, bronchioalveolar lavage, Intervention Study., Human, non-small cell lung cancer, non-small cell cancer of the lung, Lung Carcinomas, Lavage Fluid, saliva molecularis, Non-Small-Cell Lung Carcinoma, simple tissue, NSCLC - non-small cell lung cancer, Non-small cell lung cancer, Non-Small Cell Lung Carcinoma, bronchoalveolar lavage fluid, Bronchial Lavage Fluid, Pulmonary Lavage Fluids, non-small cell lung carcinoma (disease), Bronchial Alveolar Lavage Fluid, Microbial Communities, Lavage Fluids, Pulmonary, Microbiome, Carcinomas, Microbiomes, Microbial Community Compositions, Microbial Community, Microbial Community Structure, saliva atomaris, Alveolar Lavage Fluids, Tissue, Community Structure, 2-D projection, Pulmonary Lavage Fluid, Non-Small Cell Lung, Lung Lavage Fluids, Non Small Cell Lung Carcinoma, Lung Carcinoma, Non Small Cell Lung, Composition, non-small cell carcinoma of lung, Alveolar, NSCLC, Lung Lavage Fluid, cross-sectional, Patient, Clients, Bronchoalveolar Lavage Fluids, Nonsmall Cell Lung Cancer, Microbial Community Structures, Alveolar Lavage Fluid, Microbiotas, sailva normalis, Bronchial, non-small cell cancer of lung, other neoplasm, Non-Small-Cell Lung Carcinomas, Human Microbiomes, Community, Human Microbiome, Non-Small-CellLobe, Microbial Community Composition, antibiotique, antimicrobials, non-small cell lung carcinoma, Compounds, Ref(2)P, Non-Small Cell Lung Cancer, antimicrobial agents, Surgery, PRAS40, Non-Small-Cell Lung, non-small cell carcinoma of the lung, fluid, Human, Agent, non-small cell cancer of the lung, Lung Carcinomas, ref2p, microbicides, Anti Mycobacterial Agent, parenchyma of lung, Ref(2)p, p62, THOC4, Miquelon and St. Pierre, pulmones, Non-Small-Cell Lung Carcinoma, lung, Antibiotic, lungs pair, Bacteriocidal, NSCLC - non-small cell lung cancer, Non-Small Cell Lung Carcinoma, Bacteriocide, preoperative procedures, neoplasm, antibiotics, ALY|REF, treatment, antimicrobial, Irrigation, study, Antimycobacterial Agents, Therapeutic Irrigations, ref(2)Pn., airways, Antibiotika, Microbial Community Structure, ALY/REF, Tissue, Anti Bacterial Compounds, Anti Bacterial Compound, Non-Small Cell Lung, Non Small Cell Lung Carcinoma, Lung Carcinoma, Anti-Mycobacterial, Anti-Bacterial Compounds, Miquelon and Saint Pierre, BEF, NSCLC, Anti-Bacterial, Lobel, Anti-Mycobacterial Agents, Clients, sample, Nonsmall Cell Lung Cancer, disease management, Therapies, Microbial Community Structures, Antimycobacterial Agent, REF, Antibiotics, operative procedures, 1110012J22Rik, Irrigations, Non-Small-Cell Lung Carcinomas, Human Microbiome, Antibiotikum, antibiotic, Therapy, Carcinoma, Douchings, Community Composition, pulmo, DmelCG10360, ALY, lung parenchyma, ref, ref(2)p, intraoperative procedures, Antibacterial Agent, lungs, Microbial, Client, Douching, non-small cell lung cancer, Anti Mycobacterial Agents, Ref2P, ref(2)Po2, peroperative procedures, microbicide, simple tissue, Non-small cell lung cancer, Bacteriocidal Agents, General, Anti Bacterial Agent, non-small cell lung carcinoma (disease), AI227026, Bacteriocides, Foods, Anti-Mycobacterial Agent, neoplasms, Microbial Communities, Corsica, Antimycobacterial, Microbiome, Carcinomas, Anti Bacterial Agents, Microbiomes, Microbial Community Compositions, Antibacterial, Microbial Community, operative therapy, Community Structure, operations, set of lungs, Lavages, Treatments, Saint Pierre and Miquelon, sample population, Non Small Cell Lung, Bacteriocidal Agent, Antibacterial Agents, Lavage, Anti-Bacterial Agent, non-small cell carcinoma of lung, Composition, airway, Agents, Patient, Therapeutic, pulmonary, Compound, perioperative procedures, Microbiotas, Treatment, St. Pierre and Miquelon, Lungs, non-small cell cancer of lung, Anti-Bacterial Compound, CG10360, other neoplasm, Human Microbiomes, Community, Non-Small-Cell, invasive proceduresfalseMicrobiota 16S sequencing study in NSCLC patients eligible for surgery without neoadjuvant treatment18 non-small cell lung cancer patients eligible for surgery without neaodjuvant treatment were included in the study at Centre Jean Perrin (France). Patients did not take any antibiotics, food supplements or immunostimulants 2 months prior to inclusion. During surgery, patients underwent partial or complete lobectomy where samples of non-malignant lung tissue, peritumoural tissue and tumour were resected from the removed lobe. This was preceeded by the washing of the removed lobe and obtaining the broncho-alveolar lavage fluid. These four sample types were analysed by 16S sequencing in 17 from 18 patients. The study is a part of the project "Characterization of Microbiota (Intestinal, From Lungs, and Upper Airways) in Patients With Non-small Cell Lung Carcinoma: Exploratory Study " which is registered under ref. NCT03068663 (clinicaltrials.gov).2020-11-10 09:05:23EGAS00001004728960632450847EGAD00001006567EGAC00001001794