Skip to main content

Advertisement

SpringerLink
Log in

Impact of nasopharyngeal microbiota on the development of respiratory tract diseases

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Knowledge of whether and how respiratory microbiota composition can prime the immune system and provide colonisation resistance, limiting consecutive pathobiont overgrowth and infections, is essential to improving the prevention and therapy of respiratory disorders. Modulation of dysbiotic ecosystems or reconstitution of missing microbes might be a possible measure to reduce respiratory diseases. The aim of this review is to analyse the role of nasopharyngeal microbiota in the development of respiratory tract disease in paediatric-age subjects. PubMed was used to search for all studies published over the last 15 years using the following key words: “microbiota” or “microbioma” and “nasopharyngeal” or “respiratory” or “nasal” and “children” or “paediatric” or “infant”. Analysis of the literature showed that respiratory microbiota can regulate health and disease development in the respiratory tract. Like the gut microbiota, the respiratory microbiota is established at birth, and early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Protective and dangerous bacteria have been identified, and this can be considered the base for developing new approaches to diseases that respond poorly to traditional interventions. Reconstitution of missing microbes can be achieved by the administration of pre- and probiotics. Modulation of respiratory microbiota by favouring colonisation of the upper respiratory tract by beneficial commensals can interfere with the proliferation and activity of resident pathobionts and is a possible new measure to reduce the risk of disease. However, further studies are needed because a deeper understanding of these and related issues can be transferred to clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schenck LP, Surette MG, Bowdish DM (2016) Composition and immunological significance of the upper respiratory tract microbiota. FEBS Lett 590:3705–3720

    Article  CAS  PubMed  Google Scholar 

  2. Tan TT, Morgelin M, Forsgren A, Riesbeck K (2007) Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles. J Infect Dis 195:1661–1670

    Article  CAS  PubMed  Google Scholar 

  3. Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rümke HC et al (2004) Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 363:1871–1872

    Article  CAS  PubMed  Google Scholar 

  4. Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI (1995) Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377:435–438

    Article  CAS  PubMed  Google Scholar 

  5. Bosch AA, Biesbroek G, Trzcinski K, Sanders EA, Bogaert D (2013) Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog 9:e1003057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kloepfer KM, Lee WM, Pappas TE, Kang TJ, Vrtis RF, Evans MD et al (2014) Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. J Allergy Clin Immunol 133:1301–1307

    Article  PubMed  PubMed Central  Google Scholar 

  7. de Steenhuijsen Piters WA, Sanders EA, Bogaert D (2015) The role of the local microbial ecosystem in respiratory health and disease. Philos Trans R Soc Lond B Biol Sci 370:20140294

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wang Y, Li X, Ge T, Xiao Y, Liao Y, Cui Y et al (2016) Probiotics for prevention and treatment of respiratory tract infections in children: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 95:e4509

    Article  Google Scholar 

  9. Lenoir-Wijnkoop I, Gerlier L, Bresson JL, Le Pen C, Berdeaux G (2015) Public health and budget impact of probiotics on common respiratory tract infections: a modelling study. PLoS One 10:e0122765

    Article  PubMed  PubMed Central  Google Scholar 

  10. Biesbroek G, Tsivtsivadze E, Sanders EA, Montijn R, Veenhoven RH, Keijser BJ et al (2014) Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med 190:1283–1292

    Article  PubMed  Google Scholar 

  11. Grice EA, Segre JA (2011) The skin microbiome. Nat Rev Microbiol 9:244–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mendling W (2016) Vaginal microbiota. Adv Exp Med Biol 902:83–93

    Article  PubMed  Google Scholar 

  13. Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N et al (2015) The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 17:704–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Broides A, Dagan R, Greenberg D, Givon-Lavi N, Leibovitz E (2009) Acute otitis media caused by Moraxella catarrhalis: epidemiologic and clinical characteristics. Clin Infect Dis 49:1641–1647

    Article  PubMed  Google Scholar 

  15. Aebi C (2011) Moraxella catarrhalis—pathogen or commensal? Adv Exp Med Biol 697:107–116

    Article  PubMed  Google Scholar 

  16. Armbruster CE, Hong W, Pang B, Weimer KED, Juneau RA, Turner J et al (2010) Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling. MBio 1:e00102-10

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bosch AA, Levin E, van Houten MA, Hasrat R, Kalkman G, Biesbroek G et al (2016) Development of upper respiratory tract microbiota in infancy is affected by mode of delivery. EBioMedicine 9:336–345

    Article  PubMed  PubMed Central  Google Scholar 

  18. Guibas GV, Moschonis G, Xepapadaki P, Roumpedaki E, Androutsos O, Manios Y et al (2013) Conception via in vitro fertilization and delivery by Caesarean section are associated with paediatric asthma incidence. Clin Exp Allergy 43:1058–1066

    Article  CAS  PubMed  Google Scholar 

  19. Kristensen K, Fisker N, Haerskjold A, Ravn H, Simões EAF, Stensballe L (2015) Caesarean section and hospitalization for respiratory syncytial virus infection: a population-based study. Pediatr Infect Dis J 34:145–148

    Article  PubMed  Google Scholar 

  20. Biesbroek G, Bosch AA, Wang X, Keijser BJ, Veenhoven RH, Sanders EA et al (2014) The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med 190:298–308

    Article  PubMed  Google Scholar 

  21. Laufer AS, Metlay JP, Gent JF, Fennie KP, Kong Y, Pettigrew MM (2011) Microbial communities of the upper respiratory tract and otitis media in children. MBio 2:e00245-10

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tarrant M, Kwok M-K, Lam T-H, Leung GM, Schooling CM (2010) Breast-feeding and childhood hospitalizations for infections. Epidemiology 21:847–854

    Article  PubMed  Google Scholar 

  23. Duijts L, Jaddoe VWV, Hofman A, Moll HA (2010) Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics 126:e18–e25

    Article  PubMed  Google Scholar 

  24. Duijts L, Ramadhani MK, Moll HA (2009) Breastfeeding protects against infectious diseases during infancy in industrialized countries. A systematic review. Matern Child Nutr 5:199–210

    Article  PubMed  Google Scholar 

  25. Hunt KM, Foster JA, Forney LJ, Schütte UME, Beck DL, Abdo Z et al (2011) Characterization of the diversity and temporal stability of bacterial communities in human milk. PLoS One 6:e21313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R et al (2011) Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A 108(Suppl 1):4578–4585

    Article  CAS  PubMed  Google Scholar 

  27. Everard ML (2016) Paediatric respiratory infections. Eur Respir Rev 25:36–40

    Article  PubMed  Google Scholar 

  28. Teele DW, Klein JO, Rosner B (1989) Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J Infect Dis 160:83–94

    Article  CAS  PubMed  Google Scholar 

  29. Pichichero ME (2013) Otitis media. Pediatr Clin North Am 60:391–407

    Article  PubMed  Google Scholar 

  30. Marchisio P, Claut L, Rognoni A, Esposito S, Passali D, Bellussi L et al (2003) Differences in nasopharyngeal bacterial flora in children with nonsevere recurrent acute otitis media and chronic otitis media with effusion: implications for management. Pediatr Infect Dis J 22:262–268

    PubMed  Google Scholar 

  31. Tano K, Olofsson C, Grahn-Håkansson E, Holm SE (1999) In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis by alpha-hemolytic streptococci from healthy children. Int J Pediatr Otorhinolaryngol 47:49–56

    Article  CAS  PubMed  Google Scholar 

  32. Hilty M, Qi W, Brugger SD, Frei L, Agyeman P, Frey PM et al (2012) Nasopharyngeal microbiota in infants with acute otitis media. J Infect Dis 205:1048–1055

    Article  CAS  PubMed  Google Scholar 

  33. Marchisio P, Nazzari E, Torretta S, Esposito S, Principi N (2014) Medical prevention of recurrent acute otitis media: an updated overview. Expert Rev Anti Infect Ther 12:611–620

    Article  CAS  PubMed  Google Scholar 

  34. Hasegawa K, Linnemann RW, Mansbach JM, Ajami NJ, Espinola JA, Petrosino JF et al (2016) Nasal airway microbiota profile and severe bronchiolitis in infants: a case–control study. Pediatr Infect Dis J

  35. Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA et al (2014) Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science 345:818–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP, Davis GJ et al (2010) Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2:29ra31

    Article  PubMed  PubMed Central  Google Scholar 

  37. Abou Alaiwa MH, Reznikov LR, Gansemer ND, Sheets KA, Horswill AR, Stoltz DA et al (2014) pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37. Proc Natl Acad Sci U S A 111:18703–18708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  39. Stressmann FA, Rogers GB, Marsh P, Lilley AK, Daniels TW, Carroll MP et al (2011) Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation? J Cyst Fibros 10:357–365

    Article  PubMed  Google Scholar 

  40. Prevaes SM, de Winter-de Groot KM, Janssens HM, de Steenhuijsen Piters WA, Tramper-Stranders GA, Wyllie AL et al (2016) Development of the nasopharyngeal microbiota in infants with cystic fibrosis. Am J Respir Crit Care Med 193:504–515

    Article  CAS  PubMed  Google Scholar 

  41. Kahl BC (2010) Impact of Staphylococcus aureus on the pathogenesis of chronic cystic fibrosis lung disease. Int J Med Microbiol 300:514–519

    Article  PubMed  Google Scholar 

  42. Melter O, Radojevič B (2010) Small colony variants of Staphylococcus aureus—review. Folia Microbiol (Praha) 55:548–558

    Article  CAS  Google Scholar 

  43. Fuchs S, Pané-Farré J, Kohler C, Hecker M, Engelmann S (2007) Anaerobic gene expression in Staphylococcus aureus. J Bacteriol 189:4275–4289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mika M, Korten I, Qi W, Regamey N, Frey U, Casaulta C et al (2016) The nasal microbiota in infants with cystic fibrosis in the first year of life: a prospective cohort study. Lancet Respir Med 4:627–635

    Article  PubMed  Google Scholar 

  45. Zemanick ET, Wagner BD, Robertson CE, Stevens MJ, Szefler SJ, Accurso FJ et al (2015) Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods. Ann Am Thorac Soc 12:221–229

    Article  PubMed  PubMed Central  Google Scholar 

  46. Cuthbertson L, Rogers GB, Walker AW, Oliver A, Green LE, Daniels TW et al (2016) Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. ISME J 10:1081–1091

    Article  CAS  PubMed  Google Scholar 

  47. de Benedictis FM, Attanasi M (2016) Asthma in childhood. Eur Respir Rev 25:41–47

    Article  PubMed  Google Scholar 

  48. Kusel MM, de Klerk NH, Kebadze T, Vohma V, Holt PG, Johnston SL et al (2007) Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol 119:1105–1110

    Article  PubMed  Google Scholar 

  49. Wu P, Hartert TV (2011) Evidence for a causal relationship between respiratory syncytial virus infection and asthma. Expert Rev Anti Infect Ther 9:731–745

    Article  PubMed  PubMed Central  Google Scholar 

  50. Bisgaard H, Hermansen MN, Buchvald F, Loland L, Halkjaer LB, Bønnelykke K et al (2007) Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 357:1487–1495

    Article  CAS  PubMed  Google Scholar 

  51. Hales BJ, Pearce LJ, Kusel MM, Holt PG, Sly PD, Thomas WR (2008) Differences in the antibody response to a mucosal bacterial antigen between allergic and non-allergic subjects. Thorax 63:221–227

    Article  CAS  PubMed  Google Scholar 

  52. Hollams EM, Hales BJ, Bachert C, Huvenne W, Parsons F, de Klerk NH et al (2010) Th2-associated immunity to bacteria in teenagers and susceptibility to asthma. Eur Respir J 36:509–516

    Article  CAS  PubMed  Google Scholar 

  53. Holt PG, Sly PD (2012) Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Nat Med 18:726–735

    Article  CAS  PubMed  Google Scholar 

  54. Zhang L, Gao H, Yang T, Yang B, Jiang X, Wang L et al (2014) Infant 7-valent pneumococcal conjugate vaccine immunization alters young adulthood CD4(+)T cell subsets in allergic airway disease mouse model. Vaccine 32:2079–2085

    Article  CAS  PubMed  Google Scholar 

  55. Principi N, Esposito S (2016) Gut microbiota and central nervous system development. J Infect 73:536–546

    Article  PubMed  Google Scholar 

  56. Principi N, Esposito S (2016) Antibiotic administration and the development of obesity in children. Int J Antimicrob Agents 47:171–177

    Article  CAS  PubMed  Google Scholar 

  57. Shukla SD, Budden KF, Neal R, Hansbro PM (2017) Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunology 6:e133

    Article  PubMed  PubMed Central  Google Scholar 

  58. Fung TC, Olson CA, Hsiao EY (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 20:145–155

    Article  CAS  PubMed  Google Scholar 

  59. Blacher E, Levy M, Tatirovsky E, Elinav E (2017) Microbiome-modulated metabolites at the interface of host immunity. J Immunol 198:572–580

    Article  CAS  PubMed  Google Scholar 

  60. Lin L, Zhang J (2017) Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC Immunol 18:2

    Article  PubMed  PubMed Central  Google Scholar 

  61. Marchisio P, Santagati M, Scillato M, Baggi E, Fattizzo M, Rosazza C et al (2015) Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur J Clin Microbiol Infect Dis 34:2377–2383

    Article  CAS  PubMed  Google Scholar 

  62. Santagati M, Scillato M, Patanè F, Aiello C, Stefani S (2012) Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol Med Microbiol 65:23–31

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This review was supported by a grant from the Italian Ministry of Health (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Fondi di Ricerca Corrente 2017 850/02).

Author information

Authors and Affiliations

  1. Pediatric Clinic, Università degli Studi di Perugia, Piazza Menghini 1, 06129, Perugia, Italy

    S. Esposito

  2. Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

    N. Principi

Authors
  1. S. Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Principi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Esposito.

Ethics declarations

Conflict of interest

The authors have no potential conflict of interest to declare.

Ethical approval

Not required for a review article.

Informed consent

Not required for a review article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Esposito, S., Principi, N. Impact of nasopharyngeal microbiota on the development of respiratory tract diseases. Eur J Clin Microbiol Infect Dis 37, 1–7 (2018). https://doi.org/10.1007/s10096-017-3076-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-017-3076-7

Keywords

Search

Navigation