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Analysis of airway microbiota in adults from a Brazilian cystic fibrosis center

  • Clinical Microbiology - Research Paper
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Abstract

The application of next-generation sequencing tools revealed that the cystic fibrosis respiratory tract is a polymicrobial environment. We have characterized the airway bacterial microbiota of five adult patients with cystic fibrosis during a 14-month period by 16S rRNA tag sequencing using the Illumina technology. Microbial diversity, estimated by the Shannon index, varied among patient samples collected throughout the follow-up period. The beta diversity analysis revealed that the composition of the airway microbiota was highly specific for each patient, showing little variation among the samples of each patient analyzed over time. The composition of the bacterial microbiota did not reveal any emerging pathogen predictor of pulmonary disease in cystic fibrosis or of its unfavorable clinical progress, except for unveiling the presence of anaerobic microorganisms, even without any established clinical association. Our results could potentialy help us to translate and develop strategies in response to the pathobiology of this disease, particularly because it represents an innovative approach for CF centers in Brazil.

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References

  1. Keravec M, Jérôme M, Guilloux CA, Fangous MS, Mondot S, Vallet S, Le Berre SGR, Rault G, Férec C, Barbier G, Lepage P, Arnaud GH (2019) Porphyromonas, a potential predictive biomarker of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis. BMJ Open Resp Res 6:e000374

    Article  Google Scholar 

  2. Lipuma JJ (2010) The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev 23(2):299–323

    Article  Google Scholar 

  3. Bhagirath AY, Li Y, Somayajula D, Dadashi M, Badr S, Duan K (2016) Cystic fibrosis lung environment and Pseudomonas aeruginosa infection. BMC Pulm Med 16(1):174

    Article  Google Scholar 

  4. Hauser AR, Jain M, Bar-Meir M, McColley SA (2011) Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev 24(1):29–70

    Article  CAS  Google Scholar 

  5. Stressmann FA, Rogers GB, Van der Gast CJ, Marsh P, Vermeer LS, Carroll MP, Hoffman L, Daniels TW, Patel N, Forbes B, Bruce KD (2012) Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience. Thorax 67(10):867–873

    Article  Google Scholar 

  6. Zhao J, Schloss PD, Kalikin LM, Carmody LA, Foster BK, Petrosino JF, Cavalcoli JD, VanDevanter DR, Murray S, Li JZ, Young VB, LiPuma JJ (2012) Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A 109:5809–5814

    Article  CAS  Google Scholar 

  7. Mahboubi MA, Carmody LA, Foster BK, Kalikin LM, VanDevanter DR, JJ LP (2016) Culture-based and culture-independent bacteriologic analysis of cystic fibrosis respiratory specimens. J Clin Microbiol 54(3):613–619

    Article  CAS  Google Scholar 

  8. Sibley CD, Parkins MD, Rabin HR, Duan K, Norgaard JC, Surette MG (2008) A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients. Proc Natl Acad Sci U S A 105(39):15070–15075

    Article  CAS  Google Scholar 

  9. Carmody LA, Zhao J, Schloss PD, Petrosino JF, Murray S, Young VB, Li JZ, LiPuma JJ (2013) Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann Am Thorac Soc 10(3):179–187

    Article  Google Scholar 

  10. Whelan FJ, Heirali AA, Rossi L, Rabin HR, Parkins MD, Surette MG (2017) Longitudinal sampling of the lung microbiota in individuals with cystic fibrosis. PLoS One 12(3):e0172811

    Article  Google Scholar 

  11. Hoppe JE, Zemanick ET (2017) Lessons from the lower airway microbiome in early CF. Thorax 72(12):1063–1064

    Article  Google Scholar 

  12. O'Dwyer DN, Dickson RP, Moore BB (2016) The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol 196(12):4839–4847

    Article  CAS  Google Scholar 

  13. Cox MJ, Allgaier M, Taylor B, Baek MS, Huang YJ, Daly RA, Karaoz U, Andersen GL, Brown R, Fujimura KE, Wu B, Tran D, Koff J, Kleinhenz ME, Nielson D, Brodie EL, Lynch SV (2010) Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One 5:e11044

    Article  Google Scholar 

  14. Blainey PC, Milla CE, Cornfield DN, Quake SR (2012) Quantitative analysis of the human airway microbial ecology reveals a pervasive signature for cystic fibrosis. Sci Transl Med 4(153):153ra130

    Article  Google Scholar 

  15. Stressmann FA, Rogers GB, Marsh P, Lilley AK, Daniels TW, Carroll MP, Hoffman LR, Jones G, Allen CE, Patel N, Forbes B, Tick A, Bruce KD (2011) Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation? J Cyst Fibros 10(5):357–365

    Article  Google Scholar 

  16. Delhaes L, Monchy S, Fréalle E, Hubans C, Salleron J, Prevotat A, Wallet F, Wallaert B, Dei-Cas E, Sime-Ngando T, Chabé M, Viscogliosi E (2012) The airway microbiota in cystic fibrosis: a complex fungal and bacterial community—implications for therapeutic management. PLoS One 7(4):e36313

    Article  CAS  Google Scholar 

  17. Zemanick ET, Wagner BD, Robertson CE, Ahrens RC, Chmiel JF, Clancy JP, Gibson RL, Harris WT, Kurland G, Laguna TA, McColley SA, McCoy K, Retsch-Bogart G, Sobush KT, Zeitlin PL, Stevens MJ, Accurso FJ, Sagel SD, Harris JK (2017) Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J 50(5):1700832

    Article  Google Scholar 

  18. Carmody LA, Caverly LJ, Foster BK, MAM R, Kalikin LM, Simon RH, DR VD, JJ LP (2018) Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis. PLoS One 13(3):e0194060

    Article  Google Scholar 

  19. Rossi GA, Morelli P, Gallieta LJ, Colin AA (2019) Airway microenvironment alterations and pathogen growth incystic fibrosis. Pediatr Pulmonol 54(4):497–506

    Article  Google Scholar 

  20. Caverly LJ, Zhao J, Li Puma JJ (2015) Cystic fibrosis lung microbiome: opportunities to reconsider management of airway infection. Pediatr Pulmonol 50(Suppl. 40):S31–S38

    Article  Google Scholar 

  21. Layeghifard M, Li H, Wang PW, Donaldson SL, Coburn B, Clark ST, Caballero JD, Zhang Y, Tullis ED, Yau YCW, Waters V, Hwang DM, Guttman D (2019) Microbiome networks and change-point analysis reveal key community changes associated with cystic fibrosis pulmonary exacerbations. NPJ Biofilms Microbiomes 5:4 Published online 2019 Jan 21

    Article  Google Scholar 

  22. Mallozi MC (1996) Valores de referência para espirometria em crianças e adolescentes, calculados a partir de uma amostra da cidade de São Paulo. I Consenso Brasileiro sobre Espirometria. J Pneumol 22(3):1–164

    Google Scholar 

  23. Pereira CA, Satro T, Rodrigues SC (2007) New reference values for forced spirometry in white adults in Brazil. J Bras Pneumol 33(4):397–406

    Article  Google Scholar 

  24. Cystic Fibrosis Foundation (2015) Cystic Fibrosis Foundation Patient Registry 2014. pp. 1–92

  25. GBEFC (2016) Registro Brasileiro de Fibrose Cística. p. 1–56. www. gbefc.org.br

  26. Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Lozupone CA, Turnbaugh PJ, Fierer N, Knight R (2011) Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. PNAS 15 108(1):4516–4522

    Article  CAS  Google Scholar 

  27. Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 75(23):7537–7541

    Article  CAS  Google Scholar 

  28. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glöckner FO (2013) Nucleic Acids Res 41(D1):D590–D596

    Article  CAS  Google Scholar 

  29. Rognes T, Flouri T, Nichols B, Quince C, Mahé F (2016) VSEARCH: a versatile open source tool for metagenomics. PeerJ 18(4):e2584

    Article  Google Scholar 

  30. The UK Cystic Fibrosis Trust (2010) Microbiology laboratory standards working group. Laboratory standards for processing microbiological samples from people with cystic fibrosis. The UK Cystic Fibrosis Trust - Microbiology laboratory standards working group- Consense Document, 1st edn, 1–40

  31. Tunney MM, Field TR, Moriarty TF, Patrick S, Doering G, Muhlebach MS, Wolfgang MC, Boucher R, Gilpin DF, McDowell A, Elborn JS (2008) Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 177:995–1001

    Article  Google Scholar 

  32. Carmody LA, Zhao J, Kalikin LM, LeBar W, Simon RH, Venkataraman A, Schmidt TM, Abdo Z, Schloss PD, JJ LP (2015) The daily dynamics of cystic fibrosis airway microbiota during clinical stability and at exacerbation. Microbiome 3:12

    Article  Google Scholar 

  33. Fodor AA, Klem ER, Gilpin DF, Elborn JS, Boucher RC, Tunney MM, Wolfgang MC (2012) The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS One 7(9):e45001

    Article  CAS  Google Scholar 

  34. Field TR, Sibley CD, Parkins MD, Rabin HR, Surette MG (2010) The genus Prevotella in cystic fibrosis airways. Anaerobe 16(4):337–344

    Article  CAS  Google Scholar 

  35. Duan K, Dammel C, Stein J, Rabin H, Surette MG (2003) Modulation of Pseudomonas aeruginosa gene expression by host microflora through interspecies communication. Mol Microbiol 50(5):1477–1491

    Article  CAS  Google Scholar 

  36. Filkins LM, O'Toole GA (2015) Cystic fibrosis lung infections: polymicrobial, complex, and hard to treat. PLoS Pathog 11(12):e1005258

    Article  Google Scholar 

  37. Frayman KB, Armstrong DS, Carzino R, Ferkol TW, Grimwood K, Storch GA, Teo SM, Wylie KM, Ranganathan SC (2017) The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis. Thorax 72(12):1104–1112

    Article  Google Scholar 

  38. Ahmed B, Cox MJ, Cuthbertson L, James P, Cookson WOC, Davies JC, Mofatt MF, Bush A (2019) Longitudinal development of the airway microbiota in infants with cystic fibrosis. Sci Rep 9:5143

    Article  Google Scholar 

  39. Krause R, Moissl-Eichinger C, Halwachs B, Gorkiewicz G, Berg G, Valentin T, Prattes J, Högenauer C, Zollner-Schwetz I (2017) Mycobiome in the lower respiratory tract—a clinical perspective. Front Microbiol 10(7):2169

    Google Scholar 

  40. da Costa Ferreira Leite C, de Freitas FAD, Leão RS, de Cássia Firmida M, Albano RM, Marques EA (2017) Case report: airway microbiome in CF patients and clinical evolution. Poster presentation at VI Brazilian Congress of Cystic Fibrosis

  41. da Costa Ferreira Leite C, Folescu TW, de Cássia FM, Cohen RWF, Leão RS, de Freitas FAD, Albano RM, da Costa CH, Marques EA (2017) Monitoring clinical and microbiological evolution of a cystic fibrosis patient over 26 years: experience of a Brazilian CF centre. BMC Pulm Med 17(1):100

    Article  Google Scholar 

  42. Kramer R, Sauer-Heilborn A, Welte T, Jauregui R, Brettar I, Guzman CA, Höfle MG (2015) High individuality of respiratory bacterial communities in a large cohort of adult cystic fibrosis patients under continuous antibiotic treatment. PLoS One 10(2):e0117436

    Article  Google Scholar 

  43. Coburn B, Wang PW, Diaz Caballero J, Clark ST, Brahma V, Donaldson S, Zhang Y, Surendra A, Gong Y, Elizabeth Tullis D, Yau YC, Waters VJ, Hwang DM, Guttman DS (2015) Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 5:10241

    Article  CAS  Google Scholar 

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Acknowledgments

We gratefully acknowledge the medical staff and patients from Policlínica Piquet Carneiro/ Pedro Ernesto University Hospital (PPC-HUPE), a reference center for adult patients in Rio de Janeiro, Brazil. We thank the Bacteriology laboratory from HUPE for generous assistance in obtaining sputum samples for this study.

Funding

FAPERJ-Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro–Grant E-26/110.742/2013.

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Correspondence to Elizabeth Andrade Marques.

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This study was approved by the Ethics Committee of the Pedro Ernesto University Hospital: CAAE 78893515.1.0000.5259.

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The authors declare that they have no conflict of interest.

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Responsible Editor: Mariana X. Byndloss

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Leite, C.C.F., de Freitas, F.A.D., de Cássia Firmida, M. et al. Analysis of airway microbiota in adults from a Brazilian cystic fibrosis center. Braz J Microbiol 51, 1747–1755 (2020). https://doi.org/10.1007/s42770-020-00381-3

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  • DOI: https://doi.org/10.1007/s42770-020-00381-3

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