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Characteristics of the Airway Microbiome of Cystic Fibrosis Patients

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Abstract

Microbiota as an integral component of human body is actively investigated, including by massively parallel sequencing. However, microbiomes of lungs and sinuses have become the object of scientific attention only in the last decade. For patients with cystic fibrosis, monitoring the state of respiratory tract microorganisms is essential for maintaining lung function. Here, we studied the role of sinuses and polyps in the formation of respiratory tract microbiome. We identified Proteobacteria in the sinuses and samples from the lower respiratory tract (even in childhood). In some cases, they were accompanied by potentially dangerous basidiomycetes. The presence of polyps did not affect formation of the sinus microbiome. Proteobacteria are decisive in reducing the biodiversity of lung and sinus microbiomes, which correlated with the worsening of the lung function indicators. Soft mutations in the CFTR gene contribute to the formation of safer microbiome even in heterozygotes with class I. mutations.

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Abbreviations

CF:

cystic fibrosis

CFTR:

cystic fibrosis transmembrane regulator

FDR:

false discovery rate

FEV1:

forced expiratory volume in one second

ITS:

internal transcribed spacer

MLST:

multilocus sequence typing

OTU:

operational taxonomic unit

PCoA:

principal coordinate analysis

PERMANOVA:

permutational multivariate analysis of variance

SRA:

sequence read archive

ST:

sequence type related to MLST

References

  1. Woese, C. R. (2004) A. new biology for a. new century, Microbiol. Mol. Biol. Rev., 68, 173–186, doi: https://doi.org/10.1128/MMBR.68.2.173-186.2004.

    Article  CAS  Google Scholar 

  2. Stackebrandt, E., and Woese, C. R. (1984) The phylogeny of prokaryotes, Microbiol. Sci., 1, 117–122.

    CAS  PubMed  Google Scholar 

  3. Land, M., Hauser, L., Jim, S. R., Nookaew, I., Leuze, M. R., Ahn, T. H., Karpinets, T., Lund, O., Kora, G., Wassenaar, T., Poudel, S., and Ussery D. W. (2015) Insights from 20 years of bacterial genome sequencing, Fund. Integr. Genomics, 15, 141–161, doi: https://doi.org/10.1007/sl0142-015-0433-4.

    Article  CAS  Google Scholar 

  4. Olsen, G. L., Larsen, N., and Woese, C. R. (1991) Theribo-somal RNA database project, Nucleic Acids Res., 19 (Suppl.), 2017–2021, doi: https://doi.org/10.1093/nar/19.suppl.2017.

    Article  CAS  Google Scholar 

  5. NIH Human Microbiome Project (https://hmpdacc.org/).

  6. Proctor, L. M. (2011) The Human Microbiome Project in 2011 and beyond, Cell Host Microbe, 10, 287–291, doi: https://doi.org/10.1016/j.chom.2011.10.001.

    Article  CAS  Google Scholar 

  7. Nichols, D. P., and Chmiel, J. F. (2015) Inflammation and its genesis in cystic fibrosis, Pediatr. Pulmonol., 50 (Suppl. 40), S39–S56, doi: https://doi.org/10.1002/ppul.23242.

    Article  Google Scholar 

  8. Salsgiver, E. L., Fink, A. K., Knapp, E. A., LiPuma, J. J., Olivier, K. N., Marshall, B. C., and Saiman, L. (2016) Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis, Chest, 149, 390–400, doi: https://doi.org/10.1378/chest.l5-0676.

    Article  Google Scholar 

  9. Dickson, R. P., Erb-Downward, J. R., Martinez, F. J., and Huffnagle, G. B. (2016) The microbiome and the respiratory tract, Annu. Rev. Physiol., 78, 481–504, doi: https://doi.org/10.1146/annurev-physiol-021115-105238.

    Article  CAS  Google Scholar 

  10. Zakharkina, T., Heinzel, E., Koczulla, R. A., Greulich, T., Rentz, K., Pauling, J. K., Baumbach, J., Herrmann, M., Grunewald, C., Dienemann, H., von Muller, L., and Bals, R. (2013) Analysis of the airway microbiota of healthy individuals and patients with chronic obstructive pulmonary disease by T-RFLP and clone sequencing, PLoS One, 8, e68302, doi: https://doi.org/10.1371/journal.pone.0068302.

    Article  CAS  Google Scholar 

  11. Voronkova, A. Yu., Amelina, E. L., Kashirskaya, N. Yu., Kondrat'eva, E. I., Krasovskiy S. A., Starinova, N. I., and Kapranov, N. I. (2019) in The Russian Federation Cystic Fibrosis Patient Registry 2017 (Voronkova, A. Yu., ed.) [in Russian], Medpraktika-M, Moscow, p. 68.

  12. European Cystic Fibrosis Society Patient Registry. Annual data report (year 2016), v. 1.2018 (www.ecfs.eu/sites/ default/files/general-content-images/working-groups/ ecfs-patient-registry/ECFSPR_Report2016_06062018.pdf).

  13. Einarsson, G. G., Zhao, J., LiPuma, J. J., Downey, D. G., Tunney M. M., and Elborn, J. S. (2019) Community analysis and co-occurrence patterns in airway microbial communities during health and disease, ERJ Open Res., 5, 00128–2017, doi: https://doi.org/10.1183/23120541.00128-2017.

    Article  Google Scholar 

  14. Caverly L. J., and LiPuma, J. J. (2018) Cystic fibrosis respiratory microbiota: unraveling complexity to inform clinical practice, Expert Rev. Respir. Med., 12, 857–865, doi: https://doi.org/10.1080/17476348.2018.1513331.

    Article  CAS  Google Scholar 

  15. Isles, A., Maclusky I., Corey, M., Gold, R., Prober, C., Fleming, P., and Levison, H. (1984) Pseudomonas cepacia infection in cystic fibrosis: an emerging problem, J. Pediatr., 104, 206–210, doi: https://doi.org/10.1016/s0022-3476(84)80993-2.

    Article  CAS  Google Scholar 

  16. Lobo, L. L., Tulu, Z., Aris, R. M., and Noone, P. G. (2015) Pan-resistant Achromobacter xylosoxidans and Stenotropho-monas maltophilia infection in cystic fibrosis does not reduce survival after lung transplantation, Transplantation, 99, 2196–2202, doi: https://doi.org/10.1097/TP.0000000000000709.

    Article  CAS  Google Scholar 

  17. Voronina, O., Ryzhova, N., Kunda, M., Sharapova, N., Aksenova, E., Amelina, E., Shumkova, G., Simonova, O., Egorov, M., Kondratyeva, E., Chuchalin, A., and Gintsburg, A. (2018) Changes in airways bacterial community with cystic fibrosis patients' age and lung function decline, 41st Eur. Cystic Fibrosis Conf, J. Cystic Fibrosis, 17 (Suppl. 3), S78, doi: https://doi.org/10.1016/S1569-1993(18)30366-7.

    Article  Google Scholar 

  18. Pletcher, S. D., Goldberg, A. N., and Cope, E. K. (2019) Loss of microbial niche specificity between the upper and lower airways in patients with cystic fibrosis, Laryngoscope, 129, 544–550, doi: https://doi.org/10.1002/lary.27454.

    Article  Google Scholar 

  19. Ryzhova, N. N., Voronina, O. L., Loseva, E. V., Aksenova, E. I., Kunda, M. S., Sharapova, N. E., Sherman, V. D., and Gintsburg, A. L. (2019) Respiratory tract microbiome in children with cystic fibrosis, Sib. Med. Obozrenie, 2, 19–28, doi: https://doi.org/10.20333/2500136-2019-2-19-28.

    Google Scholar 

  20. Voronina, O. L., Ryzhova, N. N., Kunda, M. S., Aksenova, E. I., Sharapova, N. E., Amelina, E. L., Lazareva, A. V., Chernevich, V. P., Simonova, O. I., Zhukhovitskiy V. G., Zhilina, S. V., Semykin, S. Yu., Polikarpova, S. V., Asherova, I. K., Orlov, A. V., and Kondratenko, O. V. (2019) Major trends in altered diversity of Burkholderia spp. infecting cystic fibrosis patients in the Russian Federation, Sib. Med. Obozrenie, 2, 80–88, doi: https://doi.org/10.20333/2500136-2019-2-80-88.

    Google Scholar 

  21. Voronina, O. L., Kunda, M. S., Ryzhova, N. N., Aksenova, E. I., Sharapova, N. E., Semenov, A. N., Amelina, E. L., Chuchalin, A. G., and Gintsburg, A. L. (2018) On Burkholderiales order microorganisms and cystic fibrosis in Russia, BMC Genomics, 19 (Suppl. 3), 74, doi: https://doi.org/10.1186/sl2864-018-4472-9.

    Article  Google Scholar 

  22. Voronina, O. L., Kunda, M. S., Ryzhova, N. N., Aksenova, E. I., Semenov, A. N., Lasareva, A. V., Amelina, E. L., Chuchalin, A. G., Lunin, V. G., and Gintsburg, A. L. (2015) The variability of the order Burkholderiales representatives in the healthcare units, BioMed Res. Int., 2015, 680210, doi: https://doi.org/10.1155/2015/68021.

    Article  Google Scholar 

  23. Voronina, O. L., Kunda, M. S., Aksenova, E. I., Orlova, A. A., Chernukha, M. Yu., Lunin, V. G., Amelina, E. L., and Chuchalin, A. G., and Gintsburg, A. L. (2013) Express test for detecting microbes infecting respiratory tract in patients with cystic fibrosis, Klin. Lab. Diag., 11, 53–57.

    Google Scholar 

  24. Curran, B., Jonas, D., Grundmann, H., Pitt, T., and Dowson, C. G. (2004) Development of a. multilocus sequence typing scheme for the opportunistic pathogen Pseudomonas aeruginosa, J. Clin. Microbiol., 42, 5644–5649, doi: https://doi.org/10.1128/JCM.42.12.5644-5649.2004.

    Article  CAS  Google Scholar 

  25. Voronina, O. L., Ryzhova, N. N., Kunda, M. S., Aksenova, E. I., Ovchinnikov, R. S., Fedosova, N. E., Amelina, E. L., Lunin, V. G., Chuchalin, A. G., and Gintsburg, A. L. (2015) Developing approaches to identify lung mycosis pathogens directly in respiratory tract clinical samples from patients with cystic fibrosis, Lab. Sluzhba, 4, 11–17.

    Article  Google Scholar 

  26. Chen, J., Bittinger, K., Charlson, E. S., Hoffmann, C., Lewis, J., Wu, G. D., Collman, R. G., Bushman, F. D., and Li, H. (2012) Associating microbiome composition with environmental covariates using generalized UniFrac distances, Bioinformatics, 28, 2106–2113, doi: https://doi.org/10.1093/bioinformatics/bts342.

    Article  CAS  Google Scholar 

  27. A consensus report on clinical effects of genetic variants in the Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics” [in Russian], Leiden Open Variation Database, v. 3.0 (http://seqdb.med-gen.ru/).

  28. Clustering and Classification Methods for Biologists, Manchester Metropolitan University (http://www.angelfire.com/planet/biostats/upload.htm).

  29. Anderson, M. J. (2001) A. new method for non-parametric multivariate analysis of variance, Austral. Ecol, 26, 32–46, doi: https://doi.org/10.1111/j.l442-9993.2001.01070.pp.x.

    Google Scholar 

  30. Ginsburg, G. S., and Willard, H. F. (2009) Genomic and personalized medicine: foundations and applications, Transl. Res., 154, 277–287, doi: https://doi.org/10.1016/j.trsl.2009.09.005.

    Article  Google Scholar 

  31. Chowdhary A., Randhawa, H. S., Gaur, S. N., Agarwal, K., Kathuria, S., Roy, P., Klaassen, C. H., and Meis, J. F. (2013) Schizophyllum commune as an emerging fungal pathogen: a. review and report of two cases, Mycoses, 56, 1–10, doi: https://doi.org/10.1111/j.1439-0507.2012.02190.x.

    Article  CAS  Google Scholar 

  32. Biswas, K., Cavubati, R., Gunaratna, S., Hoggard, M., Waldvogel-Thurlow, S., Hong, J., Chang, K., Wagner Mackenzie, B., Taylor, M. W., and Douglas, R. G. (2019) Comparison of subtyping approaches and the underlying drivers of microbial signatures for chronic rhinosinusitis, mSphere, 4, e00679–18, doi: https://doi.org/10.1128/mSphere.00679-18.

    Article  CAS  Google Scholar 

  33. Lucas, S. K., Yang, R., Dunitz, J. M., Boyer, H. C., and Hunter, R. C. (2018) 16S rRNA gene sequencing reveals site-specific signatures of the upper and lower airways of cystic fibrosis patients, J. Cyst. Fibros., 17, 204–212, doi: https://doi.org/10.1016/j.jcf.2017.08.007.

    Article  CAS  Google Scholar 

  34. Fothergill, J. L., Neill, D. R., Loman, N., Winstanley C., and Kadioglu, A. (2014) Pseudomonas aeruginosa adaptation in the nasopharyngeal reservoir leads to migration and persistence in the lungs, Nat. Commun., 5, 4780, doi: https://doi.org/10.1038/ncomms5780.

    Article  CAS  Google Scholar 

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Funding

Funding. The study was conducted within the framework of the 2018 State Assignment no. 056-00108-18-00 and 2019–2020 Planning Period and the 2019 State Assignment no. 056-00078-19-00 and 2020–2021 Planning Period for the Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation.

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Correspondence to O. L. Voronina.

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This study is dedicated to the 80th anniversary of the Department of Biochemistry, Lomonosov Moscow State University (see vol. 84, no. 11, 2019).

Conflict of interest. The authors declare no conflict of interest.

Compliance with ethical standards. An informed consent was obtained from adult and CF patients over 15 years old; parental or guardian consent was obtained for pediatric patients under 15 years old. All procedures used to examine biological samples from the patients with CF and congenital lung malformation were approved by the Biomedical Ethics Committee at the Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation (Protocol no. 1, 17.05.2012).

Russian Text © The Author(s), 2020, published in Biokhimiya, 2020, Vol. 85, No. 1, pp. 3–14.

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Voronina, O.L., Ryzhova, N.N., Kunda, M.S. et al. Characteristics of the Airway Microbiome of Cystic Fibrosis Patients. Biochemistry Moscow 85, 1–10 (2020). https://doi.org/10.1134/S0006297920010010

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