Respiratory mycobiome and suggestion of inter-kingdom network during acute pulmonary exacerbation in cystic fibrosis.
Acute Disease
Adult
Aspergillus
/ physiology
Candida
/ physiology
Cystic Fibrosis
/ microbiology
Disease Progression
Female
High-Throughput Nucleotide Sequencing
Humans
Lung
/ microbiology
Male
Microbiota
/ genetics
Pseudomonas
/ physiology
RNA, Ribosomal, 16S
/ genetics
Respiratory Tract Infections
/ microbiology
Scedosporium
/ physiology
Sequence Analysis, DNA
Sputum
/ microbiology
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 02 2020
27 02 2020
Historique:
received:
08
01
2019
accepted:
14
10
2019
entrez:
29
2
2020
pubmed:
29
2
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Lung infections play a critical role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was associated with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly associated with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecological Climax/Attack model that opens new lines of thoughts about the physiopathology of CF lung disease and future perspectives to improve its therapeutic management.
Identifiants
pubmed: 32108159
doi: 10.1038/s41598-020-60015-4
pii: 10.1038/s41598-020-60015-4
pmc: PMC7046743
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3589Investigateurs
Magali Chabe
(M)
Christophe Audebert
(C)
Isabelle Durand-Joly
(I)
Amale Boldron
(A)
Isabelle Pin
(I)
Odile Cognet
(O)
Herve Pelloux
(H)
Anne Prevotat
(A)
Benoit Wallaert
(B)
Nathalie Wizla
(N)
Caroline Thumerelle
(C)
Dominique Turck
(D)
Références
Tipton, L. et al. Fungi stabilize connectivity in the lung and skin microbial ecosystems. Microbiome 6, 12 (2018).
pubmed: 29335027
pmcid: 5769346
doi: 10.1186/s40168-017-0393-0
O’Brien, S. & Fothergill, J. L. The role of multispecies social interactions in shaping Pseudomonas aeruginosa pathogenicity in the cystic fibrosis lung. FEMS Microbiol. Lett. 364 (2017).
Rush, S. T., Lee, C. H., Mio, W. & Kim, P. T. The Phylogenetic LASSO and the Microbiome. ArXiv160708877 Q-Bio Stat (2016).
Quinn, R. A. et al. Ecological networking of cystic fibrosis lung infections. NPJ Biofilms Microbiomes 2, 4 (2016).
pubmed: 28649398
pmcid: 5460249
doi: 10.1038/s41522-016-0002-1
Kurtz, Z. D. et al. Sparse and compositionally robust inference of microbial ecological networks. Plos Comput. Biol. 11, e1004226 (2015).
pubmed: 25950956
pmcid: 4423992
doi: 10.1371/journal.pcbi.1004226
Berry, D. & Widder, S. Deciphering microbial interactions and detecting keystone species with co-occurrence networks. Front. Microbiol. 5, 219 (2014).
pubmed: 24904535
pmcid: 4033041
doi: 10.3389/fmicb.2014.00219
Whiteson, K. L. et al. The upper respiratory tract as a microbial source for pulmonary infections in cystic fibrosis. Parallels from island biogeography. Am. J. Respir. Crit. Care Med. 189, 1309–1315 (2014).
pubmed: 24702670
pmcid: 4098084
doi: 10.1164/rccm.201312-2129PP
Bhatt, J. M. Treatment of pulmonary exacerbations in cystic fibrosis. Eur. Respir. Rev. Off. J. Eur. Respir. Soc. 22, 205–216 (2013).
doi: 10.1183/09059180.00006512
Stenbit, A. E. & Flume, P. A. Pulmonary exacerbations in cystic fibrosis. Curr. Opin. Pulm. Med. 17, 442–447 (2011).
pubmed: 21881509
Bilton, D. et al. Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J. Cyst. Fibros. Off. J. Eur. Cyst. Fibros. Soc. 10(Suppl 2), S79–81 (2011).
doi: 10.1016/S1569-1993(11)60012-X
Goss, C. H. & Burns, J. L. Exacerbations in cystic fibrosis. 1: Epidemiology and pathogenesis. Thorax 62, 360–367 (2007).
pubmed: 17387214
pmcid: 2092469
doi: 10.1136/thx.2006.060889
Nguyen, L. D. N. et al. Effects of Propidium Monoazide (PMA) Treatment on Mycobiome and Bacteriome Analysis of Cystic Fibrosis Airways during Exacerbation. Plos One 11, e0168860 (2016).
pubmed: 28030619
pmcid: 5193350
doi: 10.1371/journal.pone.0168860
Quinn, R. A. et al. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease. PeerJ 4, e2174 (2016).
pubmed: 27602256
pmcid: 4991883
doi: 10.7717/peerj.2174
Quinn, R. A. et al. A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation. ISME J. 9, 1024–1038 (2015).
pubmed: 25514533
doi: 10.1038/ismej.2014.234
Carmody, L. A. et al. Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann. Am. Thorac. Soc. 10, 179–187 (2013).
pubmed: 23802813
pmcid: 3960905
doi: 10.1513/AnnalsATS.201211-107OC
Tunney, M. M. et al. Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am. J. Respir. Crit. Care Med. 187, 1118–1126 (2013).
pubmed: 23348972
pmcid: 3734618
doi: 10.1164/rccm.201210-1937OC
Zemanick, E. T. et al. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. Plos One 8, e62917 (2013).
pubmed: 23646159
pmcid: 3639911
doi: 10.1371/journal.pone.0062917
Filkins, L. M. et al. Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability. J. Bacteriol. 194, 4709–4717 (2012).
pubmed: 22753064
pmcid: 3415522
doi: 10.1128/JB.00566-12
Fodor, A. A. et al. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. Plos One 7, e45001 (2012).
pubmed: 23049765
pmcid: 3458854
doi: 10.1371/journal.pone.0045001
Zhao, J. et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc. Natl. Acad. Sci. USA 109, 5809–5814 (2012).
pubmed: 22451929
doi: 10.1073/pnas.1120577109
Goffard, A. et al. Virus and cystic fibrosis: rhinoviruses are associated with exacerbations in adult patients. J. Clin. Virol. Off. Publ. Pan Am. Soc. Clin. Virol. 60, 147–153 (2014).
doi: 10.1016/j.jcv.2014.02.005
Willner, D. et al. Case studies of the spatial heterogeneity of DNA viruses in the cystic fibrosis lung. Am. J. Respir. Cell Mol. Biol. 46, 127–131 (2012).
pubmed: 21980056
pmcid: 3361360
doi: 10.1165/rcmb.2011-0253OC
Lysholm, F. et al. Characterization of the viral microbiome in patients with severe lower respiratory tract infections, using metagenomic sequencing. Plos One 7, e30875 (2012).
pubmed: 22355331
pmcid: 3280267
doi: 10.1371/journal.pone.0030875
Chotirmall, S. H. et al. Sputum Candida albicans presages FEV
pubmed: 20472859
doi: 10.1378/chest.09-2996
Amin, R., Dupuis, A., Aaron, S. D. & Ratjen, F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest 137, 171–176 (2010).
pubmed: 19567494
doi: 10.1378/chest.09-1103
Willger, S. D. et al. Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis. Microbiome 2, 40 (2014).
pubmed: 25408892
pmcid: 4236224
doi: 10.1186/2049-2618-2-40
Delhaes, L. et al. Prevalence, geographic risk factor, and development of a standardized protocol for fungal isolation in cystic fibrosis: Results from the international prospective study ‘MFIP’. J. Cyst. Fibros. 18, 212–220 (2018).
pubmed: 30348610
doi: 10.1016/j.jcf.2018.10.001
Armstead, J., Morris, J. & Denning, D. W. Multi-country estimate of different manifestations of aspergillosis in cystic fibrosis. Plos One 9, e98502 (2014).
pubmed: 24914809
pmcid: 4051580
doi: 10.1371/journal.pone.0098502
Middleton, P. G., Chen, S. C.-A. & Meyer, W. Fungal infections and treatment in cystic fibrosis. Curr. Opin. Pulm. Med. 19, 670–675 (2013).
pubmed: 24060984
doi: 10.1097/MCP.0b013e328365ab74
Speirs, J. J., van der Ent, C. K. & Beekman, J. M. Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis. Curr. Opin. Pulm. Med. 18, 632–638 (2012).
pubmed: 22965276
doi: 10.1097/MCP.0b013e328358d50b
Conrad, D. et al. Cystic fibrosis therapy: a community ecology perspective. Am. J. Respir. Cell Mol. Biol. 48, 150–156 (2013).
pubmed: 23103995
pmcid: 3604065
doi: 10.1165/rcmb.2012-0059PS
Lim, Y. W. et al. Clinical insights from metagenomic analysis of sputum samples from patients with cystic fibrosis. J. Clin. Microbiol. 52, 425–437 (2014).
pubmed: 24478471
pmcid: 3911355
doi: 10.1128/JCM.02204-13
Stevens, D. A. et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis–state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 37(Suppl 3), S225–264 (2003).
doi: 10.1086/376525
Galand, P. E., Casamayor, E. O., Kirchman, D. L. & Lovejoy, C. Ecology of the rare microbial biosphere of the Arctic Ocean. Proc. Natl. Acad. Sci. USA 106, 22427–22432 (2009).
pubmed: 20018741
doi: 10.1073/pnas.0908284106
Sokol, H. et al. Fungal microbiota dysbiosis in IBD. Gut 66, 1039–1048 (2017).
pubmed: 26843508
doi: 10.1136/gutjnl-2015-310746
Kramer, R. et al. Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements. J. Clin. Microbiol. 53, 2900–2907 (2015).
pubmed: 26135861
pmcid: 4540938
doi: 10.1128/JCM.01094-15
Delhaes, L. et al. The airway microbiota in cystic fibrosis: a complex fungal and bacterial community–implications for therapeutic management. Plos One 7, e36313 (2012).
pubmed: 22558432
pmcid: 3338676
doi: 10.1371/journal.pone.0036313
Sanders, D. B. et al. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am. J. Respir. Crit. Care Med. 182, 627–632 (2010).
pubmed: 20463179
pmcid: 5450763
doi: 10.1164/rccm.200909-1421OC
Heirali, A. A. et al. The effects of inhaled aztreonam on the cystic fibrosis lung microbiome. Microbiome 5, 51 (2017).
pubmed: 28476135
pmcid: 5420135
doi: 10.1186/s40168-017-0265-7
Bacci, G. et al. Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline. PloS One 11, e0156807 (2016).
pubmed: 27355625
pmcid: 4927098
doi: 10.1371/journal.pone.0156807
Hogan, D. A. et al. 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, e0149998 (2016).
pubmed: 26943329
pmcid: 4778801
doi: 10.1371/journal.pone.0149998
Cuthbertson, L. et al. Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. ISME J. 10, 1081–1091 (2016).
pubmed: 26555248
doi: 10.1038/ismej.2015.198
Bos, L. D. J., Meinardi, S., Blake, D. & Whiteson, K. Bacteria in the airways of patients with cystic fibrosis are genetically capable of producing VOCs in breath. J. Breath Res. 10, 047103 (2016).
pubmed: 27991430
doi: 10.1088/1752-7163/10/4/047103
Botterel, F. et al. Fungal and Bacterial Diversity of Airway Microbiota in Adults with Cystic Fibrosis: Concordance Between Conventional Methods and Ultra-Deep Sequencing, and Their Practical use in the Clinical Laboratory. Mycopathologia 183, 171–183 (2018).
pubmed: 28766039
doi: 10.1007/s11046-017-0185-x
Richardson, M., Bowyer, P. & Sabino, R. The human lung and Aspergillus: You are what you breathe in? Med. Mycol. 57, S145–S154 (2019).
Feigelman, R. et al. Sputum DNA sequencing in cystic fibrosis: non-invasive access to the lung microbiome and to pathogen details. Microbiome 5, 20 (2017).
pubmed: 28187782
pmcid: 5303297
doi: 10.1186/s40168-017-0234-1
Kim, S. H. et al. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation. Plos Pathog. 11, e1005308 (2015).
pubmed: 26588216
pmcid: 4654494
doi: 10.1371/journal.ppat.1005308
Boutin, S. & Dalpke, A. H. Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients. Mol. Cell. Pediatr. 4, 1 (2017).
pubmed: 28097632
pmcid: 5241261
doi: 10.1186/s40348-016-0067-1
Dickson, R. P. et al. Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography. Ann. Am. Thorac. Soc. 12, 821–830 (2015).
pubmed: 25803243
pmcid: 4590020
doi: 10.1513/AnnalsATS.201501-029OC
Venkataraman, A. et al. Application of a neutral community model to assess structuring of the human lung microbiome. mBio 6 (2015).
Lamoureux, C., Guilloux, C.-A., Beauruelle, C., Jolivet-Gougeon, A. & Héry-Arnaud, G. Anaerobes in cystic fibrosis patients’ airways. Crit. Rev. Microbiol. 1–15, https://doi.org/10.1080/1040841X.2018.1549019 (2019).
pubmed: 30663924
doi: 10.1080/1040841X.2018.1549019
Caverly, L. J. & LiPuma, J. J. Good cop, bad cop: anaerobes in cystic fibrosis airways. Eur. Respir. J. 52 (2018).
Rogers, G. B., Hoffman, L. R., Carroll, M. P. & Bruce, K. D. Interpreting infective microbiota: the importance of an ecological perspective. Trends Microbiol. 21, 271–276 (2013).
pubmed: 23598051
doi: 10.1016/j.tim.2013.03.004
Hurley, M. N. & Smyth, A. R. Staphylococcus aureus in cystic fibrosis: pivotal role or bit part actor? Curr. Opin. Pulm. Med. 24, 586–591 (2018).
pubmed: 30113336
doi: 10.1097/MCP.0000000000000518
Hector, A. et al. Microbial colonization and lung function in adolescents with cystic fibrosis. J. Cyst. Fibros. Off. J. Eur. Cyst. Fibros. Soc. 15, 340–349 (2016).
doi: 10.1016/j.jcf.2016.01.004
Zemanick, E. T. et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur. Respir. J. 50 (2017).
pubmed: 29146601
doi: 10.1183/13993003.00832-2017
van Woerden, H. C. et al. Differences in fungi present in induced sputum samples from asthma patients and non-atopic controls: a community based case control study. BMC Infect. Dis. 13, 69 (2013).
pubmed: 23384395
pmcid: 3570489
doi: 10.1186/1471-2334-13-69
Guillot, J., Hadina, S. & Guého, E. The genus Malassezia: old facts and new concepts. Parassitologia 50, 77–79 (2008).
pubmed: 18693563
Kerem, E. et al. Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS patient registry. Eur. Respir. J. 43, 125–133 (2014).
pubmed: 23598952
doi: 10.1183/09031936.00166412
Pages-Monteiro, L. et al. Strong incidence of Pseudomonas aeruginosa on bacterial rrs and ITS genetic structures of cystic fibrosis sputa. Plos One 12, e0173022 (2017).
pubmed: 28282386
pmcid: 5345789
doi: 10.1371/journal.pone.0173022
Whelan, F. J. et al. Longitudinal sampling of the lung microbiota in individuals with cystic fibrosis. Plos One 12, e0172811 (2017).
pubmed: 28253277
pmcid: 5333848
doi: 10.1371/journal.pone.0172811
Somayaji, R. et al. Long-term clinical outcomes of ‘Prairie Epidemic Strain’ Pseudomonas aeruginosa infection in adults with cystic fibrosis. Thorax 72, 333–339 (2017).
pubmed: 27682327
doi: 10.1136/thoraxjnl-2015-208083
Russell, G. K., Gadhok, R. & Simmonds, N. J. The destructive combination of Scediosporium apiosperum lung disease and exuberant inflammation in cystic fibrosis. Paediatr. Respir. Rev. 14(Suppl 1), 22–25 (2013).
pubmed: 23518310
doi: 10.1016/j.prrv.2013.02.004
Staerck, C. et al. The secreted polyketide boydone A is responsible for the anti-Staphylococcus aureus activity of Scedosporium boydii. FEMS Microbiol. Lett. 364 (2017).
Vandeputte, P. et al. Draft Genome Sequence of the Pathogenic Fungus Scedosporium apiospermum. Genome Announc. 2 (2014).
Han, Z., Kautto, L. & Nevalainen, H. Secretion of Proteases by an Opportunistic Fungal Pathogen Scedosporium aurantiacum. Plos One 12, e0169403 (2017).
pubmed: 28060882
pmcid: 5218550
doi: 10.1371/journal.pone.0169403
Krüger, W., Vielreicher, S., Kapitan, M., Jacobsen, I. D. & Niemiec, M. J. Fungal-Bacterial Interactions in Health and Disease. Pathog. Basel Switz. 8 (2019).
Budden, K. F. et al. Functional effects of the microbiota in chronic respiratory disease. Lancet Respir. Med., https://doi.org/10.1016/S2213-2600(18)30510-1 (2019).
pubmed: 30975495
doi: 10.1016/S2213-2600(18)30510-1
Chiu, L. et al. Protective Microbiota: From Localized to Long-Reaching Co-Immunity. Front. Immunol. 8 1678 (2017).
Coron, N. et al. Toward the Standardization of Mycological Examination of Sputum Samples in Cystic Fibrosis: Results from a French Multicenter Prospective Study. Mycopathologia 183, 101–117 (2018).
pubmed: 28748285
doi: 10.1007/s11046-017-0173-1
Abbott, J. et al. What defines a pulmonary exacerbation? The perceptions of adults with cystic fibrosis. J. Cyst. Fibros. Off. J. Eur. Cyst. Fibros. Soc. 8, 356–359 (2009).
doi: 10.1016/j.jcf.2009.07.003
Paulson, J. N., Stine, O. C., Bravo, H. C. & Pop, M. Differential abundance analysis for microbial marker-gene surveys. Nat. Methods 10, 1200–1202 (2013).
pubmed: 24076764
pmcid: 4010126
doi: 10.1038/nmeth.2658
Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).
pubmed: 4059512
pmcid: 4059512
doi: 10.1016/j.chom.2014.02.005
Enaud, R. et al. Intestinal Inflammation in Children with Cystic Fibrosis Is Associated with Crohn’s-Like Microbiota Disturbances. J. Clin. Med. 8 (2019).
pmcid: 6572243
doi: 10.3390/jcm8050645
pubmed: 6572243
Prevaes, S. M. P. J. et al. Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis. Am. J. Respir. Crit. Care Med. 193, 504–515 (2016).
pubmed: 26492486
doi: 10.1164/rccm.201509-1759OC
Bernarde, C. et al. Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation. Plos One 10, e0124124 (2015).
pubmed: 25853698
pmcid: 4390299
doi: 10.1371/journal.pone.0124124
Maeda, Y. et al. Population structure and characterization of viridans group streptococci (VGS) including Streptococcus pneumoniae isolated from adult patients with cystic fibrosis (CF). J. Cyst. Fibros. Off. J. Eur. Cyst. Fibros. Soc. 10, 133–139 (2011).
doi: 10.1016/j.jcf.2010.11.003
Tibshirani, R. The lasso method for variable selection in the Cox model. Stat. Med. 16, 385–395 (1997).
pubmed: 9044528
doi: 10.1002/(SICI)1097-0258(19970228)16:4<385::AID-SIM380>3.0.CO;2-3
Rush, S. T. A. The Phylogenetic LASSO and the Microbiome: Metagenomic Modeling in Fecal Microbiota Transplantation. (2017).
Bach, F. R. Bolasso: model consistent Lasso estimation through the bootstrap. in Proceedings of the 25th international conference on Machine learning - ICML’08 33–40 (ACM Press), https://doi.org/10.1145/1390156.1390161 (2008).