{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:41:57Z","timestamp":1792644117359,"version":"4.5.0"},"reference-count":121,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cystic fibrosis (CF) is a genetic disease with mutational changes leading to profound dysbiosis, both pulmonary and intestinal, from a very young age. This dysbiosis plays an important role in clinical manifestations, particularly in the lungs, affected by chronic infection. The range of microbiological tools has recently been enriched by metagenomics based on next-generation sequencing (NGS). Currently applied essentially in a gene-targeted manner, metagenomics has enabled very exhaustive description of bacterial communities in the CF lung niche and, to a lesser extent, the fungi. Aided by progress in bioinformatics, this now makes it possible to envisage shotgun sequencing and opens the door to other areas of the microbial world, the virome, and the archaeome, for which almost everything remains to be described in cystic fibrosis. Paradoxically, applying NGS in microbiology has seen a rebirth of bacterial culture, but in an extended manner (culturomics), which has proved to be a perfectly complementary approach to NGS. Animal models have also proved indispensable for validating microbiome pathophysiological hypotheses. Description of pathological microbiomes and correlation with clinical status and therapeutics (antibiotic therapy, cystic fibrosis transmembrane conductance regulator (CFTR) modulators) revealed the richness of microbiome data, enabling description of predictive and follow-up biomarkers. Although monogenic, CF is a multifactorial disease, and both genotype and microbiome profiles are crucial interconnected factors in disease progression. Microbiome-genome interactions are thus important to decipher.<\/jats:p>","DOI":"10.3390\/genes11050536","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T12:26:30Z","timestamp":1589199990000},"page":"536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["The Microbiome in Cystic Fibrosis Pulmonary Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Alice","family":"Fran\u00e7oise","sequence":"first","affiliation":[{"name":"UMR 1078 GGB, University of Brest, Inserm, EFS, F-29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-9696","authenticated-orcid":false,"given":"Genevi\u00e8ve","family":"H\u00e9ry-Arnaud","sequence":"additional","affiliation":[{"name":"UMR 1078 GGB, University of Brest, Inserm, EFS, F-29200 Brest, France"},{"name":"Unit\u00e9 de Bact\u00e9riologie, P\u00f4le de Biologie-Pathologie, Centre Hospitalier R\u00e9gional et Universitaire de Brest, H\u00f4pital de la Cavale Blanche, Boulevard Tanguy Prigent, 29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fphar.2019.00121","article-title":"Emerging therapeutic approaches for cystic fibrosis. from gene editing to personalized medicine","volume":"10","author":"Pranke","year":"2019","journal-title":"Front. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.trsl.2015.04.008","article-title":"Translating the genetics of cystic fibrosis to personalized medicine","volume":"168","author":"Corvol","year":"2016","journal-title":"Transl. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Travert, G., Heeley, M., and Heeley, A. (2020). history of newborn screening for cystic fibrosis\u2014The early years. IJNS, 6.","DOI":"10.3390\/ijns6010008"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev-genom-083117-021329","article-title":"Cystic fibrosis disease modifiers: Complex genetics defines the phenotypic diversity in a monogenic disease","volume":"19","author":"Knowles","year":"2018","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.pcl.2016.04.002","article-title":"Molecular genetics of cystic fibrosis transmembrane conductance regulator","volume":"63","author":"Sosnay","year":"2016","journal-title":"Pedia. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jmoldx.2015.06.010","article-title":"Cystic Fibrosis","volume":"18","author":"Brennan","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: A global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jpeds.2015.02.049","article-title":"Associations between gut microbial colonization in early life and respiratory outcomes in cystic fibrosis","volume":"167","author":"Hoen","year":"2015","journal-title":"J. Pediatrics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13073-020-0710-2","article-title":"Interactions between the gut microbiome and host gene regulation in cystic fibrosis","volume":"12","author":"Dayama","year":"2020","journal-title":"Genome Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1164\/rccm.201901-0145OC","article-title":"Correlating cystic fibrosis transmembrane conductance regulator function with clinical features to inform precision treatment of cystic fibrosis","volume":"199","author":"McCague","year":"2019","journal-title":"Am. J. Respir Crit Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Schippa, S., Iebba, V., Santangelo, F., Gagliardi, A., De Biase, R.V., Stamato, A., Bertasi, S., Lucarelli, M., Conte, M.P., and Quattrucci, S. (2013). Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PLoS ONE, 8.","DOI":"10.1371\/annotation\/a8b06cd3-c8a8-48fa-9748-b04fded4b963"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vongthilath, R., Richaud Thiriez, B., Dehillotte, C., Lemonnier, L., Guillien, A., Degano, B., Dalphin, M.-L., Dalphin, J.-C., and Pl\u00e9siat, P. (2019). Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas aeruginosa: Analysis of the French CF registry. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210201"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1375\/136905200320565256","article-title":"Categories of \u0394F508 homozygous cystic fibrosis twin and sibling pairs with distinct phenotypic characteristics","volume":"3","author":"Mekus","year":"2000","journal-title":"Twin Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eS13","DOI":"10.1016\/S0929-693X(20)30045-2","article-title":"Variant classifications, databases and genotype-phenotype correlations","volume":"27","author":"Raynal","year":"2020","journal-title":"Arch. P\u00e9diatrie"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40168-015-0094-5","article-title":"The vocabulary of microbiome research: A proposal","volume":"3","author":"Marchesi","year":"2015","journal-title":"Microbiome"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev-physiol-021115-105238","article-title":"The microbiome and the respiratory tract","volume":"78","author":"Dickson","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00387-19","DOI":"10.1128\/mSystems.00387-19","article-title":"A metabolome- and metagenome-wide association network reveals microbial natural products and microbial biotransformation products from the human microbiota","volume":"4","author":"Cao","year":"2019","journal-title":"mSystems"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2017.10.001","article-title":"Three-dimensional microbiome and metabolome cartography of a diseased human lung","volume":"22","author":"Garg","year":"2017","journal-title":"Cell Host Microbe."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1700832","DOI":"10.1183\/13993003.00832-2017","article-title":"Airway microbiota across age and disease spectrum in cystic fibrosis","volume":"50","author":"Zemanick","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jcf.2018.12.003","article-title":"Differences in the lower airway microbiota of infants with and without cystic fibrosis","volume":"18","author":"Frayman","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1136\/thoraxjnl-2016-209279","article-title":"The lower airway microbiota in early cystic fibrosis lung disease: A longitudinal analysis","volume":"72","author":"Frayman","year":"2017","journal-title":"Thorax"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/ismej.2010.175","article-title":"Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities","volume":"5","author":"Walker","year":"2011","journal-title":"ISME J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00163-18","DOI":"10.1128\/mSystems.00163-18","article-title":"Performance of microbiome sequence inference methods in environments with varying biomass","volume":"4","author":"Caruso","year":"2019","journal-title":"mSystems"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D.R., Fernandes, G.R., Tap, J., and Bruls, T. (2011). Enterotypes of the human gut microbiome. Nature, 473, 174\u2013180.","DOI":"10.1038\/nature09944"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jcf.2018.11.003","article-title":"The lung and gut microbiome: What has to be taken into consideration for cystic fibrosis?","volume":"18","author":"Boutin","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hogan, D.A., Willger, S.D., Dolben, E.L., Hampton, T.H., Stanton, B.A., Morrison, H.G., Sogin, M.L., Czum, J., and Ashare, A. (2016). Analysis of lung microbiota in bronchoalveolar lavage, protected brush and sputum samples from subjects with mild-to-moderate cystic fibrosis lung disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149998"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1128\/JCM.02282-05","article-title":"Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with cystic fibrosis","volume":"44","author":"Rogers","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40168-020-00810-3","article-title":"Lung function and microbiota diversity in cystic fibrosis","volume":"8","author":"Cuthbertson","year":"2020","journal-title":"Microbiome"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S2213-2600(18)30171-1","article-title":"The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: A prospective internally controlled interventional trial","volume":"6","author":"Ronchetti","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1111\/j.1462-2920.2010.02173.x","article-title":"Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa: Ecology of the cystic fibrosis respiratory tract bacterial community","volume":"12","author":"Lemon","year":"2010","journal-title":"Environ. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40168-017-0267-5","article-title":"Optimizing methods and dodging pitfalls in microbiome research","volume":"5","author":"Kim","year":"2017","journal-title":"Microbiome"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/2049-2618-2-40","article-title":"Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis","volume":"2","author":"Willger","year":"2014","journal-title":"Microbiome"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.3389\/fmicb.2019.02796","article-title":"Exploring the archaeome: Detection of archaeal signatures in the human body","volume":"10","author":"Pausan","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/1040841X.2017.1297763","article-title":"Viruses in cystic fibrosis patients\u2019 airways","volume":"43","author":"Billard","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, Z., Liu, H., Wang, F., Yang, Y., Wang, X., Chen, B., Stampfli, M.R., Zhou, H., Shu, W., and Brightling, C.E. (2020). A refined view of airway microbiome in chronic obstructive pulmonary disease at species and strain-levels. Microbiology.","DOI":"10.1101\/2020.01.18.908624"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.micinf.2017.12.002","article-title":"Airway microbial metagenomics","volume":"20","author":"Pienkowska","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bacci, G., Mengoni, A., Fiscarelli, E., Segata, N., Taccetti, G., Dolce, D., Paganin, P., Morelli, P., Tuccio, V., and De Alessandri, A. (2017). A different microbiome gene repertoire in the airways of cystic fibrosis patients with severe lung disease. IJMS, 18.","DOI":"10.3390\/ijms18081654"},{"key":"ref_39","unstructured":"Shi, X., Gao, Z., Lin, Q., Zhao, L., Ma, Q., Kang, Y., and Yu, J. (2020). Meta-analysis reveals potential influence of oxidative stress on the airway microbiomes of cystic fibrosis patients. Genom. Proteom. Bioinform., S1672022920300231."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Twomey, K.B., Alston, M., An, S.-Q., O\u2019Connell, O.J., McCarthy, Y., Swarbreck, D., Febrer, M., Dow, J.M., Plant, B.J., and Ryan, R.P. (2013). Microbiota and metabolite profiling reveal specific alterations in bacterial community structure and environment in the cystic fibrosis airway during exacerbation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082432"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cmet.2014.10.016","article-title":"Specialized metabolites from the microbiome in health and disease","volume":"20","author":"Sharon","year":"2014","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2174","DOI":"10.7717\/peerj.2174","article-title":"Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease","volume":"4","author":"Quinn","year":"2016","journal-title":"PeerJ"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16731","DOI":"10.1073\/pnas.0804812105","article-title":"Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients","volume":"105","author":"Sokol","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/1040841X.2018.1549019","article-title":"Anaerobes in cystic fibrosis patients\u2019 airways","volume":"45","author":"Lamoureux","year":"2019","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kirchner, S., Fothergill, J.L., Wright, E.A., James, C.E., Mowat, E., and Winstanley, C. (2012). Use of artificial sputum medium to test antibiotic efficacy against Pseudomonas aeruginosa in conditions more relevant to the cystic fibrosis lung. JoVE, 3857.","DOI":"10.3791\/3857-v"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Verhoeckx, K., Cotter, P., L\u00f3pez-Exp\u00f3sito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., and Wichers, H. (2015). The Impact of Food Bioactives on Health, Springer International Publishing.","DOI":"10.1007\/978-3-319-16104-4"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Comstock, W.J., Huh, E., Weekes, R., Watson, C., Xu, T., Dorrestein, P.C., and Quinn, R.A. (2017). The WinCF Model\u2014An inexpensive and tractable microcosm of a mucus plugged bronchiole to study the microbiology of lung infections. JoVE, 55532.","DOI":"10.3791\/55532-v"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/1469-0691.12023","article-title":"Microbial culturomics: Paradigm shift in the human gut microbiome study","volume":"18","author":"Lagier","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12859","DOI":"10.1038\/s41598-019-49371-y","article-title":"In vitro evolution of Pseudomonas aeruginosa AA2 biofilms in the presence of cystic fibrosis lung microbiome members","volume":"9","author":"Vandeplassche","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00115-19","DOI":"10.1128\/JB.00115-19","article-title":"The Yin and Yang of Streptococcus Lung infections in cystic fibrosis: A model for studying polymicrobial interactions","volume":"201","author":"Scott","year":"2019","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1139\/cjm-2016-0705","article-title":"Synthetic cystic fibrosis sputum medium diminishes Burkholderia cenocepacia antifungal activity against Aspergillus fumigatus independently of phenylacetic acid production","volume":"63","author":"Lightly","year":"2017","journal-title":"Can. J. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sibley, C.D., Grinwis, M.E., Field, T.R., Eshaghurshan, C.S., Faria, M.M., Dowd, S.E., Parkins, M.D., Rabin, H.R., and Surette, M.G. (2011). Culture enriched molecular profiling of the cystic fibrosis airway microbiome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022702"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1164\/rccm.201711-2180OC","article-title":"The lung microbiota of healthy mice are highly variable, cluster by environment, and reflect variation in baseline lung innate immunity","volume":"198","author":"Dickson","year":"2018","journal-title":"Am. J. Respir. Crit Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/femsre\/fuv036","article-title":"Heterogeneity of the gut microbiome in mice: Guidelines for optimizing experimental design","volume":"40","author":"Laukens","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12931-018-0750-y","article-title":"Airway disease phenotypes in animal models of cystic fibrosis","volume":"19","author":"McCarron","year":"2018","journal-title":"Respir. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.bbadis.2018.07.026","article-title":"Animal models for cystic fibrosis liver disease (CFLD)","volume":"1865","author":"Fiorotto","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1165\/rcmb.2013-0261OC","article-title":"Gastrointestinal pathology in juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets","volume":"50","author":"Sun","year":"2014","journal-title":"Am. J.Respir. Cell. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3389\/fcimb.2017.00540","article-title":"Sinus microanatomy and microbiota in a rabbit model of rhinosinusitis","volume":"7","author":"Cho","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMra1300109","article-title":"Origins of cystic fibrosis lung disease","volume":"372","author":"Stoltz","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e123529","DOI":"10.1172\/jci.insight.123529","article-title":"A sheep model of cystic fibrosis generated by CRISPR\/Cas9 disruption of the CFTR gene","volume":"3","author":"Fan","year":"2018","journal-title":"JCI Insight"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e97199","DOI":"10.1172\/jci.insight.97199","article-title":"Development of an airway mucus defect in the cystic fibrosis rat","volume":"3","author":"Birket","year":"2018","journal-title":"JCI Insight"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.1128\/IAI.72.10.6040-6049.2004","article-title":"Bacterial overgrowth in the cystic fibrosis transmembrane conductance regulator null mouse small intestine","volume":"72","author":"Norkina","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19189","DOI":"10.1038\/srep19189","article-title":"Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model","volume":"6","author":"Bazett","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s00335-015-9560-4","article-title":"Cystic fibrosis mouse model-dependent intestinal structure and gut microbiome","volume":"26","author":"Bazett","year":"2015","journal-title":"Mamm Genome"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4161\/gmic.22430","article-title":"Cystic fibrosis transmembrane conductance regulator knockout mice exhibit aberrant gastrointestinal microbiota","volume":"4","author":"Lynch","year":"2013","journal-title":"Gut Microbes"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Meeker, S.M., Mears, K.S., Sangwan, N., Brittnacher, M.J., Weiss, E.J., Treuting, P.M., Tolley, N., Pope, C.E., Hager, K.R., and Vo, A.T. (2020). CFTR dysregulation drives active selection of the gut microbiome. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008251"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/hep4.1266","article-title":"Diet-induced dysbiosis and genetic background synergize with cystic fibrosis transmembrane conductance regulator deficiency to promote cholangiopathy in mice","volume":"2","author":"Debray","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.3389\/fmicb.2019.02880","article-title":"Despite antagonism in vitro, Pseudomonas aeruginosa enhances Staphylococcus aureus colonization in a murine lung infection model","volume":"10","author":"Millette","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nri3769","article-title":"Host\u2013microorganism interactions in lung diseases","volume":"14","author":"Marsland","year":"2014","journal-title":"Nat. Rev Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"eaav3488","DOI":"10.1126\/scitranslmed.aav3488","article-title":"Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis","volume":"11","author":"Esther","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S2213-2600(16)30081-9","article-title":"The nasal microbiota in infants with cystic fibrosis in the first year of life: A prospective cohort study","volume":"4","author":"Mika","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_72","first-page":"00096","article-title":"The cystic fibrosis lower airways microbial metagenome","volume":"2","author":"Chouvarine","year":"2016","journal-title":"ERJ Open Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1164\/rccm.201104-0655OC","article-title":"Topographical continuity of bacterial populations in the healthy human respiratory tract","volume":"184","author":"Charlson","year":"2011","journal-title":"Am. J. Respir Crit Care Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Boutin, S., Graeber, S.Y., Weitnauer, M., Panitz, J., Stahl, M., Clausznitzer, D., Kaderali, L., Einarsson, G., Tunney, M.M., and Elborn, J.S. (2015). Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116029"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1602235","DOI":"10.1183\/13993003.02235-2016","article-title":"Concordance between upper and lower airway microbiota in infants with cystic fibrosis","volume":"49","author":"Prevaes","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bernarde, C., Keravec, M., Mounier, J., Gouriou, S., Rault, G., F\u00e9rec, C., Barbier, G., and H\u00e9ry-Arnaud, G. (2015). Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124124"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1186\/s40064-015-1207-0","article-title":"Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization","volume":"4","author":"Keravec","year":"2015","journal-title":"SpringerPlus"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e000374","DOI":"10.1136\/bmjresp-2018-000374","article-title":"Porphyromonas, a potential predictive biomarker of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis","volume":"6","author":"Keravec","year":"2019","journal-title":"BMJ Open Resp. Res."},{"key":"ref_79","first-page":"112","article-title":"Prediction of the intestinal resistome by a three-dimensional structure-based method","volume":"4","author":"Ghozlane","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Jankauskait\u0117, L., Misevi\u010dien\u0117, V., Vaidelien\u0117, L., and K\u0117valas, R. (2018). Lower airway virology in health and disease\u2014From invaders to symbionts. Medicina, 54.","DOI":"10.3390\/medicina54050072"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1093\/jac\/dkr318","article-title":"Bacteriophages as vehicles of the resistome in cystic fibrosis","volume":"66","author":"Rolain","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1128\/JCM.01094-15","article-title":"Cohort study of airway mycobiome in adult cystic fibrosis patients: Differences in community structure between fungi and bacteria reveal predominance of transient fungal elements","volume":"53","author":"Kramer","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Delhaes, L., Monchy, S., Fr\u00e9alle, E., Hubans, C., Salleron, J., Leroy, S., Prevotat, A., Wallet, F., Wallaert, B., and Dei-Cas, E. (2012). The airway microbiota in cystic fibrosis: A complex fungal and bacterial community\u2014Implications for therapeutic management. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036313"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"The Mucofong Investigation Group, Soret, P., Vandenborght, L.-E., Francis, F., Coron, N., Enaud, R., Avalos, M., Schaeverbeke, T., Berger, P., and Fayon, M. (2020). Respiratory mycobiome and suggestion of inter-kingdom network during acute pulmonary exacerbation in cystic fibrosis. Sci. Rep., 10, 3589.","DOI":"10.1038\/s41598-020-60015-4"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e00824-17","DOI":"10.1128\/mBio.00824-17","article-title":"First insights into the diverse human archaeome: Specific detection of archaea in the gastrointestinal tract, lung, and nose and on skin","volume":"8","author":"Koskinen","year":"2017","journal-title":"mBio"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Cox, M.J., Allgaier, M., Taylor, B., Baek, M.S., Huang, Y.J., Daly, R.A., Karaoz, U., Andersen, G.L., Brown, R., and Fujimura, K.E. (2010). Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011044"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.1073\/pnas.1120577109","article-title":"Decade-long bacterial community dynamics in cystic fibrosis airways","volume":"109","author":"Zhao","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1016\/j.celrep.2019.03.086","article-title":"Direct lung sampling indicates that established pathogens dominate early infections in children with cystic fibrosis","volume":"27","author":"Jorth","year":"2019","journal-title":"Cell Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/MCP.0000000000000316","article-title":"Development of the respiratory tract microbiota in cystic fibrosis","volume":"22","author":"Bogaert","year":"2016","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Zemanick, E.T., Harris, J.K., Wagner, B.D., Robertson, C.E., Sagel, S.D., Stevens, M.J., Accurso, F.J., and Laguna, T.A. (2013). Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062917"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/ismej.2015.198","article-title":"Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention","volume":"10","author":"Cuthbertson","year":"2016","journal-title":"ISME J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Li, J., Hao, C., Ren, L., Xiao, Y., Wang, J., and Qin, X. (2016). Data mining of lung microbiota in cystic fibrosis patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164510"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.3389\/fmicb.2018.02147","article-title":"Diet, microbiota and gut-lung connection","volume":"9","author":"Anand","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3389\/fmicb.2020.00301","article-title":"The cross-talk between gut microbiota and lungs in common lung diseases","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"24857","DOI":"10.1038\/srep24857","article-title":"Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis","volume":"6","author":"Nielsen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-genet-110711-155532","article-title":"The relationship between the human genome and microbiome comes into view","volume":"51","author":"Goodrich","year":"2017","journal-title":"Annu. Rev. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2014.09.053","article-title":"Human genetics shape the gut microbiome","volume":"159","author":"Goodrich","year":"2014","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Vernocchi, P., Del Chierico, F., Quagliariello, A., Ercolini, D., Lucidi, V., and Putignani, L. (2017). A Metagenomic and in silico functional prediction of gut microbiota profiles may concur in discovering new cystic fibrosis patient-targeted probiotics. Nutrients, 9.","DOI":"10.3390\/nu9121342"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1800242","DOI":"10.1183\/13993003.00242-2018","article-title":"Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: A multisite study","volume":"52","author":"Muhlebach","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"fiw230","DOI":"10.1093\/femsec\/fiw230","article-title":"Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota","volume":"93","author":"Miragoli","year":"2017","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.ygeno.2019.06.028","article-title":"Transcriptome analysis of the distal small intestine of Cftr null mice","volume":"112","author":"Ikpa","year":"2020","journal-title":"Genomics"},{"key":"ref_102","unstructured":"Rogers, G.B., Taylor, S.L., Hoffman, L.R., and Burr, L.D. (2019). The impact of CFTR modulator therapies on CF airway microbiology. J. Cyst. Fibros., S156919931930829X."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"17834","DOI":"10.1038\/s41598-018-36364-6","article-title":"Impact of CFTR modulation with ivacaftor on gut microbiota and intestinal inflammation","volume":"8","author":"Ooi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1164\/rccm.201404-0703OC","article-title":"Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis","volume":"190","author":"Rowe","year":"2014","journal-title":"Am. J. Respir Crit Care Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jcf.2017.08.002","article-title":"Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on respiratory microbiota composition","volume":"17","author":"Peleg","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1513\/AnnalsATS.201907-493OC","article-title":"Changes in airway microbiome and inflammation with ivacaftor treatment in patients with cystic fibrosis and the G551D mutation","volume":"17","author":"Harris","year":"2020","journal-title":"Ann. ATS"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jcf.2012.10.003","article-title":"Dysbiosis of bifidobacteria and Clostridium cluster XIVa in the cystic fibrosis fecal microbiota","volume":"12","author":"Duytschaever","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Muhlebach, M.S., Zorn, B.T., Esther, C.R., Hatch, J.E., Murray, C.P., Turkovic, L., Ranganathan, S.C., Boucher, R.C., Stick, S.M., and Wolfgang, M.C. (2018). Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006798"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1136\/thoraxjnl-2018-211510","article-title":"Sputum microbiota is predictive of long-term clinical outcomes in young adults with cystic fibrosis","volume":"73","author":"Acosta","year":"2018","journal-title":"Thorax"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1136\/thoraxjnl-2018-212165","article-title":"Lower airway microbiota for \u2018biomarker\u2019 measurements of cystic fibrosis disease progression?","volume":"73","author":"Sherrard","year":"2018","journal-title":"Thorax"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e00431-19","DOI":"10.1128\/mBio.00431-19","article-title":"Cystic fibrosis rapid response: Translating multi-omics data into clinically relevant information","volume":"10","author":"Lim","year":"2019","journal-title":"mBio"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.jcf.2019.02.010","article-title":"The effects of cycled inhaled aztreonam on the cystic fibrosis (CF) lung microbiome","volume":"18","author":"Heirali","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.medmal.2013.05.001","article-title":"Probiotics: A new way to fight bacterial pulmonary infections?","volume":"44","author":"Alexandre","year":"2014","journal-title":"M\u00e9d. Mal. Infect."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Cho, D., Skinner, D., Lim, D.J., Mclemore, J.G., Koch, C.G., Zhang, S., Swords, W.E., Hunter, R., Crossman, D.K., and Crowley, M.R. (2020). The impact of Lactococcus lactis (probiotic nasal rinse) co-culture on growth of patient-derived strains of Pseudomonas aeruginosa. Int. Forum. Allergy Rhinol., alr.22521.","DOI":"10.1002\/alr.22521"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e00274-19","DOI":"10.1128\/JB.00274-19","article-title":"Altered stool microbiota of infants with cystic fibrosis shows a reduction in genera associated with immune programming from birth","volume":"201","author":"Antosca","year":"2019","journal-title":"J. Bacteriol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.4315\/0362-028X-64.11.1768","article-title":"Effect of Lactobacillus casei and Yogurt Administration on Prevention of Pseudomonas aeruginosa Infection in Young Mice","volume":"64","author":"Alvarez","year":"2001","journal-title":"J. Food Prot."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"110934","DOI":"10.1016\/j.fct.2019.110934","article-title":"Preliminary safety assessment of a new Bacteroides fragilis isolate","volume":"135","author":"Tan","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.2174\/138161208784480180","article-title":"Non-invasive tests in animal models and humans: A new paradigm for assessing efficacy of biologics including prebiotics and probiotics","volume":"14","author":"Butler","year":"2008","journal-title":"CPD"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Portal, C., Gouyer, V., L\u00e9onard, R., Husson, M.-O., Gottrand, F., and Desseyn, J.-L. (2018). Long-term dietary (n-3) polyunsaturated fatty acids show benefits to the lungs of Cftr F508del mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197808"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Paoli, A., Mancin, L., Bianco, A., Thomas, E., Mota, J.F., and Piccini, F. (2019). Ketogenic diet and microbiota: Friends or enemies?. Genes, 10.","DOI":"10.3390\/genes10070534"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jsbmb.2016.11.001","article-title":"Role of vitamin D on gut microbiota in cystic fibrosis","volume":"175","author":"Kanhere","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/5\/536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:27:40Z","timestamp":1760174860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/5\/536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,11]]},"references-count":121,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["genes11050536"],"URL":"https:\/\/doi.org\/10.3390\/genes11050536","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,11]]}}}