The Human Respiratory Microbiome: The End of the Beginning?

  • Alicia B. Mitchell
  • Allan R. GlanvilleEmail author


The human respiratory microbiome is a subset of the human microbiome which comprises all organisms that live on and in the human body, including bacteria, fungi, viruses, bacteriophages and archaea. Once considered sterile, we now know that the lungs harbour a rich diversity of organisms which may vary temporally and spatially within the lungs, the so called pulmonary microbiome. Perturbations of which, occasioned by acute infections and immune suppression, may lead to a state of dysbiosis, the full implications of which are not yet known. So, it is a most engaging time to be involved in the exploration of the diversity and richness of this part of the respiratory microbiome in particular, especially as new tools, including next generation sequencing are beginning to answer fundamental questions. Much work remains to be done but we are in sight of the end of the beginning.


Pulmonary microbiome Lung transplantation Virome Next generation sequencing 


  1. 1.
    Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–20.CrossRefPubMedGoogle Scholar
  3. 3.
    Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–10.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Dickson RP, Erb-Downward JR, Huffnagle GB. The role of the bacterial microbiome in lung disease. Expert Rev Respir Med. 2013;7:245–57.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    The Lung HIV Microbiome Project (LHMP). National Heart, Lung and Blood Institute. 2015. Accessed 30 June 2017.
  6. 6.
    Gollwitzer ES, Saglani S, Trompette A, et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat Med. 2014;20:642–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Teo SM, Mok D, Pham K, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17:704–15.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Biesbroek G, Tsivtsivadze E, Sanders EA, et al. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med. 2014;190:1283–92.CrossRefPubMedGoogle Scholar
  9. 9.
    Trompette A, Gollwitzer ES, Yadava K, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014;20:159–66.CrossRefPubMedGoogle Scholar
  10. 10.
    Bruzzese E, Callegari ML, Raia V, et al. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial. PLoS One. 2014;9:e87796.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bisgaard H, Li N, Bonnelykke K, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol. 2011;128:646–52.e1-5.CrossRefPubMedGoogle Scholar
  12. 12.
    Inagaki H, Suzuki T, Nomoto K, Yoshikai Y. Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in sites of inflammation. Infect Immun. 1996;64:3280–7.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Rogers GB, van der Gast CJ, Cuthbertson L, et al. Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition. Thorax. 2013;68:731–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Rogers GB, Zain NM, Bruce KD, et al. A novel microbiota stratification system predicts future exacerbations in bronchiectasis. Ann Am Thorac Soc. 2014;11:496–503.CrossRefPubMedGoogle Scholar
  15. 15.
    Molyneaux PL, Mallia P, Cox MJ, et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:1224–31.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bassis CM, Erb-Downward JR, Dickson RP, et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio. 2015;6:e00037.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Segal LN, Alekseyenko AV, Clemente JC, et al. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013;1:19.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sze MA, Dimitriu PA, Hayashi S, et al. The lung tissue microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185:1073–80.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    West JB. Regional differences in the lung. Chest. 1978;74:426–37.PubMedGoogle Scholar
  20. 20.
    O’Dwyer DN, Dickson RP, Moore BB. The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol. 2016;196:4839–47.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. The microbiome and the respiratory tract. Annu Rev Physiol. 2016;78:481–504.CrossRefPubMedGoogle Scholar
  22. 22.
    Bidan CM, Veldsink AC, Meurs H, Gosens R. Airway and extracellular matrix mechanics in COPD. Front Physiol. 2015;6:346.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gleeson K, Eggli DF, Maxwell SL. Quantitative aspiration during sleep in normal subjects. Chest. 1997;111:1266–72.CrossRefPubMedGoogle Scholar
  24. 24.
    Huxley EJ, Viroslav J, Gray WR, Pierce AK. Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am J Med. 1978;64:564–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Rana A, Gruessner A, Agopian VG, et al. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 2015;150:252–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Borewicz K, Pragman AA, Kim HB, Hertz M, Wendt C, Isaacson RE. Longitudinal analysis of the lung microbiome in lung transplantation. FEMS Microbiol Lett. 2013;339:57–65.CrossRefPubMedGoogle Scholar
  27. 27.
    Luna R, Sagar M, Crabtree S, et al. Characterization of the lung microbiome in pediatric lung transplant recipients. J Heart Lung Transplant. 2013;32:S291.CrossRefGoogle Scholar
  28. 28.
    Willner DL, Hugenholtz P, Yerkovich ST, et al. Reestablishment of recipient-associated microbiota in the lung allograft is linked to reduced risk of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2013;187:640–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Ison MG, Hager J, Blumberg E, et al. Donor-derived disease transmission events in the United States: data reviewed by the OPTN/UNOS Disease Transmission Advisory Committee. Am J Transplant. 2009;9:1929–35.CrossRefPubMedGoogle Scholar
  30. 30.
    Davis CS, Shankaran V, Kovacs EJ, et al. Gastroesophageal reflux disease after lung transplantation: pathophysiology and implications for treatment. Surgery. 2010;148:737–44; discussion 44-5.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ferdinande P, Bruyninckx F, Van Raemdonck D, Daenen W, Verleden G, Leuven Lung Transplant G. Phrenic nerve dysfunction after heart-lung and lung transplantation. J Heart Lung Transplant. 2004;23:105–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Bhorade SM, Villanueva J, Jordan A, Garrity ER. Immunosuppressive regimens in lung transplant recipients. Drugs Today (Barc). 2004;40:1003–12.CrossRefGoogle Scholar
  33. 33.
    Martinu T, Chen DF, Palmer SM. Acute rejection and humoral sensitization in lung transplant recipients. Proc Am Thorac Soc. 2009;6:54–65.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Glanville AR, Gencay M, Tamm M, et al. Chlamydia pneumoniae infection after lung transplantation. J Heart Lung Transplant. 2005;24:131–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Vilchez RA, McCurry K, Dauber J, et al. The epidemiology of parainfluenza virus infection in lung transplant recipients. Clin Infect Dis. 2001;33:2004–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Ahya VN, Douglas LP, Andreadis C, et al. Association between elevated whole blood Epstein-Barr virus (EBV)-encoded RNA EBV polymerase chain reaction and reduced incidence of acute lung allograft rejection. J Heart Lung Transplant. 2007;26:839–44.CrossRefPubMedGoogle Scholar
  37. 37.
    Thompson BR, Hodgson YM, Kotsimbos T, et al. Bronchiolitis obliterans syndrome leads to a functional deterioration of the acinus post lung transplant. Thorax. 2014;69:487–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Dickson RP, Erb-Downward JR, Freeman CM, et al. Changes in the lung microbiome following lung transplantation include the emergence of two distinct Pseudomonas species with distinct clinical associations. PLoS One. 2014;9:e97214.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Charlson ES, Diamond JM, Bittinger K, et al. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am J Respir Crit Care Med. 2012;186:536–45.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Gottlieb J, Mattner F, Weissbrodt H, et al. Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis. Respir Med. 2009;103:743–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Vos R, Vanaudenaerde BM, Geudens N, Dupont LJ, Van Raemdonck DE, Verleden GM. Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation? Eur Respir J. 2008;31:1037–45.CrossRefPubMedGoogle Scholar
  42. 42.
    Botha P, Archer L, Anderson RL, et al. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation. 2008;85:771–4.CrossRefPubMedGoogle Scholar
  43. 43.
    Delhaes L, Monchy S, Frealle E, et al. The airway microbiota in cystic fibrosis: a complex fungal and bacterial community—implications for therapeutic management. PLoS One. 2012;7:e36313.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Harrison M, Twomey K, Mccarthy Y, et al. The role of second-generation sequencing to characterize the fungal microbiota in the adult cystic fibrosis airway, and its correlation with standard culture-based methods and clinical phenotype. Pediatr Pulmonol. 2012;47:322.Google Scholar
  45. 45.
    Weigt SS, Elashoff RM, Huang C, et al. Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome. Am J Transplant. 2009;9:1903–11.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Young JC, Chehoud C, Bittinger K, et al. Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients. Am J Transplant. 2015;15:200–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Abbas AA, Diamond JM, Chehoud C, et al. The perioperative lung transplant virome: torque teno viruses are elevated in donor lungs and show divergent dynamics in primary graft dysfunction. Am J Transplant. 2017;17:1313.CrossRefPubMedGoogle Scholar
  48. 48.
    Garantziotis S, Howell DN, McAdams HP, Davis RD, Henshaw NG, Palmer SM. Influenza pneumonia in lung transplant recipients: clinical features and association with bronchiolitis obliterans syndrome. Chest. 2001;119:1277–80.CrossRefPubMedGoogle Scholar
  49. 49.
    Gottlieb J, Schulz TF, Welte T, et al. Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study. Transplantation. 2009;87:1530–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Kumar D, Erdman D, Keshavjee S, et al. Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant. 2005;5:2031–6.CrossRefPubMedGoogle Scholar
  51. 51.
    Khalifah AP, Hachem RR, Chakinala MM, et al. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med. 2004;170:181–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Bakker NA, Verschuuren EA, Erasmus ME, et al. Epstein-Barr virus-DNA load monitoring late after lung transplantation: a surrogate marker of the degree of immunosuppression and a safe guide to reduce immunosuppression. Transplantation. 2007;83:433–8.CrossRefPubMedGoogle Scholar
  53. 53.
    Engelmann I, Welte T, Fuhner T, et al. Detection of Epstein-Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation. J Clin Virol. 2009;45:47–53.CrossRefPubMedGoogle Scholar
  54. 54.
    Finlen Copeland CA, Davis WA, Snyder LD, et al. Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial. J Heart Lung Transplant. 2011;30:990–6.CrossRefPubMedGoogle Scholar
  55. 55.
    Hammond SP, Martin ST, Roberts K, et al. Cytomegalovirus disease in lung transplantation: impact of recipient seropositivity and duration of antiviral prophylaxis. Transpl Infect Dis. 2013;15:163–70.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Lung Transplant Unit, Department of Thoracic MedicineSt Vincent’s HospitalSydneyAustralia
  2. 2.The Woolcock Institute of Medical ResearchSydneyAustralia
  3. 3.School of Medical and Molecular BiosciencesUniversity of Technology SydneyUltimoAustralia

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