Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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Effects of nasopharyngeal microbiota in respiratory infections and allergies

  • Kang, Hyun Mi (Division of Pediatric Infectious Diseases, Departments of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Kang, Jin Han (Division of Pediatric Infectious Diseases, Departments of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 투고 : 2020.08.27
  • 심사 : 2021.04.02
  • 발행 : 2021.11.15
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초록

The human microbiome, which consists of a collective cluster of commensal, symbiotic, and pathogenic microorganisms living in the human body, plays a key role in host health and immunity. The human nasal cavity harbors commensal bacteria that suppress the colonization of opportunistic pathogens. However, dysbiosis of the nasal microbial community is associated with many diseases, such as acute respiratory infections including otitis media, sinusitis and bronchitis and allergic respiratory diseases including asthma. The nasopharyngeal acquisition of pneumococcus, which exists as a pathobiont in the nasal cavity, is the initial step in virtually all pneumococcal diseases. Although the factors influencing nasal colonization and elimination are not fully understood, the adhesion of opportunistic pathogens to nasopharyngeal mucosa receptors and the eliciting of immune responses in the host are implicated in addition to bacterial microbiota properties and colonization resistance dynamics. Probiotics or synbiotic interventions may show promising and effective roles in the adjunctive treatment of dysbiosis; however, more studies are needed to characterize how these interventions can be applied in clinical practice in the future.

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참고문헌

  1. Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 2012;37:158-70. https://doi.org/10.1016/j.immuni.2012.04.011
  2. Esposito S, Principi N. Impact of nasopharyngeal microbiota on the development of respiratory tract diseases. Eur J Clin Microbiol Infect Dis 2018;37:1-7. https://doi.org/10.1007/s10096-017-3076-7
  3. Huang YJ. Nasopharyngeal microbiota: gatekeepers or fortune tellers of susceptibility to respiratory tract infections? Am J Respir Crit Care Med 2017;196:1504-5. https://doi.org/10.1164/rccm.201707-1470ed
  4. Rawls M, Ellis AK. The microbiome of the nose. Ann Allergy Asthma Immunol 2019;122:17-24. https://doi.org/10.1016/j.anai.2018.05.009
  5. Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol 2014;5:427. https://doi.org/10.3389/fimmu.2014.00427
  6. Thomas S, Izard J, Walsh E, Batich K, Chongsathidkiet P, Clarke G, et al. The host microbiome regulates and maintains human health: a primer and perspective for non-microbiologists. Cancer Res 2017;77:1783-812. https://doi.org/10.1158/0008-5472.CAN-16-2929
  7. Dimitri-Pinheiro S, Soares R, Barata P. The microbiome of the nose-friend or foe? Allergy Rhinol (Providence) 2020;11:2152656720911605.
  8. Schoos AM, Kragh M, Ahrens P, Kuhn KG, Rasmussen MA, Chawes BL, et al. Season of birth impacts the neonatal nasopharyngeal microbiota. Children (Basel) 2020;7:45. https://doi.org/10.3390/children7050045
  9. Shukla SK, Ye Z, Sandberg S, Reyes I, Fritsche TR, Keifer M. The nasal microbiota of dairy farmers is more complex than oral microbiota, reflects occupational exposure, and provides competition for staphylococci. PLoS One 2017;12:e0183898. https://doi.org/10.1371/journal.pone.0183898
  10. Manenzhe RI, Dube FS, Wright M, Lennard K, Zar HJ, Mounaud S, et al. Longitudinal changes in the nasopharyngeal resistome of South African infants using shotgun metagenomic sequencing. PLoS One 2020;15:e0231887. https://doi.org/10.1371/journal.pone.0231887
  11. Lee JT, Frank DN, Ramakrishnan V. Microbiome of the paranasal sinuses: update and literature review. Am J Rhinol Allergy 2016;30:3-16. https://doi.org/10.2500/ajra.2016.30.4255
  12. Mika M, Mack I, Korten I, Qi W, Aebi S, Frey U, et al. Dynamics of the nasal microbiota in infancy: a prospective cohort study. J Allergy Clin Immunol 2015;135:905-12.e11. https://doi.org/10.1016/j.jaci.2014.12.1909
  13. Yan M, Pamp SJ, Fukuyama J, Hwang PH, Cho DY, Holmes S, et al. Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage. Cell Host Microbe 2013;14:631-40. https://doi.org/10.1016/j.chom.2013.11.005
  14. Garcia-Rodriguez JA, Fresnadillo Martinez MJ. Dynamics of nasopharyngeal colonization by potential respiratory pathogens. J Antimicrob Chemother 2002;50 Suppl S2:59-73. https://doi.org/10.1093/jac/dkf506
  15. Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y. Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics. J Infect Dis 1997;175:1440-5. https://doi.org/10.1086/516477
  16. Faden H, Waz MJ, Bernstein JM, Brodsky L, Stanievich J, Ogra PL. Nasopharyngeal flora in the first three years of life in normal and otitisprone children. Ann Otol Rhinol Laryngol 1991;100:612-5. https://doi.org/10.1177/000348949110000802
  17. Hare KM, Singleton RJ, Grimwood K, Valery PC, Cheng AC, Morris PS, et al. Longitudinal nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in indigenous Australian and Alaska native children with bronchiectasis. PLoS One 2013;8:e70478. https://doi.org/10.1371/journal.pone.0070478
  18. Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol 2005;560:11-8. https://doi.org/10.1007/0-387-24180-9_2
  19. Jacoby P, Watson K, Bowman J, Taylor A, Riley TV, Smith DW, et al. Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract. Vaccine 2007;25:2458-64. https://doi.org/10.1016/j.vaccine.2006.09.020
  20. Kao JY, Zhang M, Miller MJ, Mills JC, Wang B, Liu M, et al. Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology 2010;138:1046-54. https://doi.org/10.1053/j.gastro.2009.11.043
  21. Gisselsson-Solen M, Hermansson A, Melhus A, Brodszki N. Immunologic findings in young children with early onset of acute otitis media. Acta Otolaryngol 2014;134:1022-8. https://doi.org/10.3109/00016489.2014.902539
  22. Browne JJ, Matthews EH, Taylor-Robinson AW, Kyd JM. Regulatory T lymphocytes are associated with increased nasopharyngeal colonization in children. Int J Pediatr Otorhinolaryngol 2019;120:51-7. https://doi.org/10.1016/j.ijporl.2019.02.011
  23. Guiducci C, Valzasina B, Dislich H, Colombo MP. CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell-produced IL-2. Eur J Immunol 2005;35:557-67. https://doi.org/10.1002/eji.200425810
  24. Meiler F, Zumkehr J, Klunker S, Ruckert B, Akdis CA, Akdis M. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J Exp Med 2008;205:2887-98. https://doi.org/10.1084/jem.20080193
  25. Lee KH, Gordon A, Foxman B. The role of respiratory viruses in the etiology of bacterial pneumonia: an ecological perspective. Evol Med Public Health 2016;2016:95-109. https://doi.org/10.1093/emph/eow007
  26. DE Lastours V, Malosh R, Ramadugu K, Srinivasan U, Dawid S, Ohmit S, et al. Co-colonization by Streptococcus pneumoniae and Staphylococcus aureus in the throat during acute respiratory illnesses. Epidemiol Infect 2016;144:3507-19. https://doi.org/10.1017/S0950268816001473
  27. Wen Z, Xie G, Zhou Q, Qiu C, Li J, Hu Q, et al. Distinct nasopharyngeal and oropharyngeal microbiota of children with influenza a virus compared with healthy children. Biomed Res Int 2018;2018:6362716. https://doi.org/10.1155/2018/6362716
  28. Fan RR, Howard LM, Griffin MR, Edwards KM, Zhu Y, Williams JV, et al. Nasopharyngeal pneumococcal density and evolution of acute respiratory illnesses in young children, Peru, 2009-2011. Emerg Infect Dis 2016;22:1996-9. https://doi.org/10.3201/eid2211.160902
  29. Rosas-Salazar C, Shilts MH, Tovchigrechko A, Schobel S, Chappell JD, Larkin EK, et al. Differences in the nasopharyngeal microbiome during acute respiratory tract infection with human rhinovirus and respiratory syncytial virus in infancy. J Infect Dis 2016;214:1924-8. https://doi.org/10.1093/infdis/jiw456
  30. Toivonen L, Camargo CA Jr, Gern JE, Bochkov YA, Mansbach JM, Piedra PA, et al. Association between rhinovirus species and nasopharyngeal microbiota in infants with severe bronchiolitis. J Allergy Clin Immunol 2019;143:1925-8.e7. https://doi.org/10.1016/j.jaci.2018.12.1004
  31. Mansbach JM, Hasegawa K, Piedra PA, Avadhanula V, Petrosino JF, Sullivan AF, et al. Haemophilus-dominant nasopharyngeal microbiota is associated with delayed clearance of respiratory syncytial virus in infants hospitalized for bronchiolitis. J Infect Dis 2019;219:1804-8. https://doi.org/10.1093/infdis/jiy741
  32. von Linstow ML, Schonning K, Hoegh AM, Sevelsted A, Vissing NH, Bisgaard H. Neonatal airway colonization is associated with troublesome lung symptoms in infants. Am J Respir Crit Care Med 2013;188:1041-2. https://doi.org/10.1164/rccm.201302-0395LE
  33. Bisgaard H, Hermansen MN, Buchvald F, Loland L, Halkjaer LB, Bonnelykke K, et al. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 2007;357:1487-95. https://doi.org/10.1056/NEJMoa052632
  34. Harrison LM, Morris JA, Telford DR, Brown SM, Jones K. The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position. FEMS Immunol Med Microbiol 1999;25:19-28. https://doi.org/10.1016/S0928-8244(99)00068-1
  35. Syrjanen RK, Auranen KJ, Leino TM, Kilpi TM, Makela PH. Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage. Pediatr Infect Dis J 2005;24:801-6. https://doi.org/10.1097/01.inf.0000178072.83531.4f
  36. Revai K, Mamidi D, Chonmaitree T. Association of nasopharyngeal bacterial colonization during upper respiratory tract infection and the development of acute otitis media. Clin Infect Dis 2008;46:e34-7. https://doi.org/10.1086/525856
  37. Minovi A, Dazert S. Diseases of the middle ear in childhood. GMS Curr Top Otorhinolaryngol Head Neck Surg 2014;13:Doc11.
  38. Jervis-Bardy J, Rogers GB, Morris PS, Smith-Vaughan HC, Nosworthy E, Leong LE, et al. The microbiome of otitis media with effusion in Indigenous Australian children. Int J Pediatr Otorhinolaryngol 2015;79:1548-55. https://doi.org/10.1016/j.ijporl.2015.07.013
  39. Leskinen K, Hendolin P, Virolainen-Julkunen A, Ylikoski J, Jero J. The clinical role of Alloiococcus otitidis in otitis media with effusion. Int J Pediatr Otorhinolaryngol 2002;66:41-8. https://doi.org/10.1016/S0165-5876(02)00186-6
  40. Guvenc MG, Midilli K, Inci E, Kuskucu M, Tahamiler R, Ozergil E, et al. Lack of Chlamydophila pneumoniae and predominance of Alloiococcus otitidis in middle ear fluids of children with otitis media with effusion. Auris Nasus Larynx 2010;37:269-73. https://doi.org/10.1016/j.anl.2009.09.002
  41. Marsh RL, Binks MJ, Beissbarth J, Christensen P, Morris PS, Leach AJ, et al. Quantitative PCR of ear discharge from Indigenous Australian children with acute otitis media with perforation supports a role for Alloiococcus otitidis as a secondary pathogen. BMC Ear Nose Throat Disord 2012;12:11. https://doi.org/10.1186/1472-6815-12-11
  42. Chan CL, Wabnitz D, Bardy JJ, Bassiouni A, Wormald PJ, Vreugde S, et al. The microbiome of otitis media with effusion. Laryngoscope 2016;126:2844-51. https://doi.org/10.1002/lary.26128
  43. Stapleton AL, Shaffer AD, Morris A, Li K, Fitch A, Methe BA. The microbiome of pediatric patients with chronic rhinosinusitis. Int Forum Allergy Rhinol 2021;11:31-9. https://doi.org/10.1002/alr.22597
  44. Bassis CM, Tang AL, Young VB, Pynnonen MA. The nasal cavity microbiota of healthy adults. Microbiome 2014;2:27. https://doi.org/10.1186/2049-2618-2-27
  45. Drago L, Pignataro L, Torretta S. Microbiological aspects of acute and chronic pediatric rhinosinusitis. J Clin Med 2019;8:149. https://doi.org/10.3390/jcm8020149
  46. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004;2:95-108. https://doi.org/10.1038/nrmicro821
  47. Brook I. The role of bacterial interference in otitis, sinusitis and tonsillitis. Otolaryngol Head Neck Surg 2005;133:139-46. https://doi.org/10.1016/j.otohns.2005.03.012
  48. Wood AJ, Fraser JD, Swift S, Patterson-Emanuelson EA, Amirapu S, Douglas RG. Intramucosal bacterial microcolonies exist in chronic rhinosinusitis without inducing a local immune response. Am J Rhinol Allergy 2012;26:265-70. https://doi.org/10.2500/ajra.2012.26.3779
  49. Peerbooms PG, Engelen MN, Stokman DA, van Benthem BH, van Weert ML, Bruisten SM, et al. Nasopharyngeal carriage of potential bacterial pathogens related to day care attendance, with special reference to the molecular epidemiology of Haemophilus influenzae. J Clin Microbiol 2002;40:2832-6. https://doi.org/10.1128/JCM.40.8.2832-2836.2002
  50. Simell B, Auranen K, Kayhty H, Goldblatt D, Dagan R, O'Brien KL, et al. The fundamental link between pneumococcal carriage and disease. Expert Rev Vaccines 2012;11:841-55. https://doi.org/10.1586/erv.12.53
  51. McDaniel LS, Swiatlo E. Should pneumococcal vaccines eliminate nasopharyngeal colonization? mBio 2016;7:e00545-16.
  52. Lee EK, Jun JK, Choi UY, Kwon HJ, Kim KH, Kang JH. Nasopharyngeal carriage rate and serotypes of streptococcus pneumoniae and antimicrobial susceptibility in healthy Korean children younger than 5 years old: focus on influence of pneumococcal conjugate vaccination. Infect Chemother 2013;45:76-84. https://doi.org/10.3947/ic.2013.45.1.76
  53. Choe YJ, Lee HJ, Lee H, Oh CE, Cho EY, Choi JH, et al. Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea. Vaccine 2016;34:4771-6. https://doi.org/10.1016/j.vaccine.2016.08.030
  54. Cho EY, Choi EH, Kang JH, Kim KH, Kim DS, Kim YJ, et al. Early changes in the serotype distribution of invasive pneumococcal isolates from children after the introduction of extended-valent pneumococcal conjugate vaccines in Korea, 2011-2013. J Korean Med Sci 2016;31:1082-8. https://doi.org/10.3346/jkms.2016.31.7.1082
  55. Lee J, Kim KH, Jo DS, Ma SH, Kim JH, Kim CS, et al. A longitudinal hospital-based epidemiology study to assess acute otitis media incidence and nasopharyngeal carriage in Korean children up to 24 months. Hum Vaccin Immunother 2020;16:3090-7. https://doi.org/10.1080/21645515.2020.1748978
  56. Syrjanen RK, Herva EE, Makela PH, Puhakka HJ, Auranen KJ, Takala AK, et al. The value of nasopharyngeal culture in predicting the etiology of acute otitis media in children less than two years of age. Pediatr Infect Dis J 2006;25:1032-6. https://doi.org/10.1097/01.inf.0000241097.37428.1d
  57. Xu Q, Casey JR, Chang A, Pichichero ME. When co-colonizing the nasopharynx haemophilus influenzae predominates over Streptococcus pneumoniae except serotype 19A strains to cause acute otitis media. Pediatr Infect Dis J 2012;31:638-40. https://doi.org/10.1097/inf.0b013e31824ba6f7
  58. Siegel SJ, Weiser JN. Mechanisms of bacterial colonization of the respiratory tract. Annu Rev Microbiol 2015;69:425-44. https://doi.org/10.1146/annurev-micro-091014-104209
  59. Wolter N, Tempia S, Cohen C, Madhi SA, Venter M, Moyes J, et al. High nasopharyngeal pneumococcal density, increased by viral coinfection, is associated with invasive pneumococcal pneumonia. J Infect Dis 2014;210:1649-57. https://doi.org/10.1093/infdis/jiu326
  60. Short KR, Habets MN, Hermans PW, Diavatopoulos DA. Interactions between Streptococcus pneumoniae and influenza virus: a mutually beneficial relationship? Future Microbiol 2012;7:609-24. https://doi.org/10.2217/fmb.12.29
  61. Hanage WP, Auranen K, Syrjanen R, Herva E, Makela PH, Kilpi T, et al. Ability of pneumococcal serotypes and clones to cause acute otitis media: implications for the prevention of otitis media by conjugate vaccines. Infect Immun 2004;72:76-81. https://doi.org/10.1128/IAI.72.1.76-81.2004
  62. Shouval DS, Greenberg D, Givon-Lavi N, Porat N, Dagan R. Site-specific disease potential of individual Streptococcus pneumoniae serotypes in pediatric invasive disease, acute otitis media and acute conjunctivitis. Pediatr Infect Dis J 2006;25:602-7. https://doi.org/10.1097/01.inf.0000220231.79968.f6
  63. Pelton SI. Deconstructing pneumococcal progression from colonization to disease. Infect Immun 2018;86:e00225-18. https://doi.org/10.1128/IAI.00225-18
  64. Lal D, Keim P, Delisle J, Barker B, Rank MA, Chia N, et al. Mapping and comparing bacterial microbiota in the sinonasal cavity of healthy, allergic rhinitis, and chronic rhinosinusitis subjects. Int Forum Allergy Rhinol 2017;7:561-9. https://doi.org/10.1002/alr.21934
  65. Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 2015;17:704-15. https://doi.org/10.1016/j.chom.2015.03.008
  66. Choi CH, Poroyko V, Watanabe S, Jiang D, Lane J, deTineo M, et al. Seasonal allergic rhinitis affects sinonasal microbiota. Am J Rhinol Allergy 2014;28:281-6. https://doi.org/10.2500/ajra.2014.28.4050
  67. Chung KF. Potential role of the lung microbiome in shaping asthma phenotypes. Ann Am Thorac Soc 2017;14(Supplement_5):S326-31. https://doi.org/10.1513/AnnalsATS.201702-138AW
  68. Perez-Losada M, Crandall KA, Freishtat RJ. Two sampling methods yield distinct microbial signatures in the nasopharynges of asthmatic children. Microbiome 2016;4:25. https://doi.org/10.1186/s40168-016-0170-5
  69. Perez-Losada M, Alamri L, Crandall KA, Freishtat RJ. Nasopharyngeal microbiome diversity changes over time in children with asthma. PLoS One 2017;12:e0170543. https://doi.org/10.1371/journal.pone.0170543
  70. Perez-Losada M, Authelet KJ, Hoptay CE, Kwak C, Crandall KA, Freishtat RJ. Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas. Microbiome 2018;6:179. https://doi.org/10.1186/s40168-018-0564-7
  71. Vissing NH, Chawes BL, Bisgaard H. Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates. Am J Respir Crit Care Med 2013;188:1246-52. https://doi.org/10.1164/rccm.201302-0215OC
  72. Rubin K, Glazer S. The pertussis hypothesis: bordetella pertussis colonization in the etiology of asthma and diseases of allergic sensitization. Med Hypotheses 2018;120:101-15. https://doi.org/10.1016/j.mehy.2018.08.006
  73. Fazlollahi M, Lee TD, Andrade J, Oguntuyo K, Chun Y, Grishina G, et al. The nasal microbiome in asthma. J Allergy Clin Immunol 2018;142:834-43.e2. https://doi.org/10.1016/j.jaci.2018.02.020
  74. Ishida Y, Nakamura F, Kanzato H, Sawada D, Hirata H, Nishimura A, et al. Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis: a double-blind, placebo-controlled study. J Dairy Sci 2005;88:527-33. https://doi.org/10.3168/jds.S0022-0302(05)72714-4
  75. Lin WY, Fu LS, Lin HK, Shen CY, Chen YJ. Evaluation of the effect of Lactobacillus paracasei (HF.A00232) in children (6-13 years old) with perennial allergic rhinitis: a 12-week, double-blind, randomized, placebo-controlled study. Pediatr Neonatol 2014;55:181-8. https://doi.org/10.1016/j.pedneo.2013.10.001
  76. Jerzynska J, Stelmach W, Balcerak J, Woicka-Kolejwa K, Rychlik B, Blauz A, et al. Effect of Lactobacillus rhamnosus GG and vitamin D supplementation on the immunologic effectiveness of grass-specific sublingual immunotherapy in children with allergy. Allergy Asthma Proc 2016;37:324-34. https://doi.org/10.2500/aap.2016.37.3958
  77. Luoto R, Ruuskanen O, Waris M, Kalliomaki M, Salminen S, Isolauri E. Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. J Allergy Clin Immunol 2014;133:405-13. https://doi.org/10.1016/j.jaci.2013.08.020
  78. Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L, Chandel DS, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature 2017;548:407-12. https://doi.org/10.1038/nature23480
  79. De Grandi R, Drago L, Bidossi A, Bottagisio M, Gelardi M, De Vecchi E. Putative microbial population shifts attributable to nasal administration of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a. Probiotics Antimicrob Proteins 2019;11:1219-26. https://doi.org/10.1007/s12602-018-9488-6
  80. Yang Y, Jing Y, Yang J, Yang Q. Effects of intranasal administration with Bacillus subtilis on immune cells in the nasal mucosa and tonsils of piglets. Exp Ther Med 2018;15:5189-98. https://doi.org/10.3892/etm.2018.6093
  81. Kumpitsch C, Koskinen K, Schopf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol 2019;17:87. https://doi.org/10.1186/s12915-019-0703-z
  82. de Steenhuijsen Piters WA, Sanders EA, Bogaert D. The role of the local microbial ecosystem in respiratory health and disease. Philos Trans R Soc Lond B Biol Sci 2015;370:20140294. https://doi.org/10.1098/rstb.2014.0294
  83. Biesbroek G, Tsivtsivadze E, Sanders EA, Montijn R, Veenhoven RH, Keijser BJ, 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. https://doi.org/10.1164/rccm.201407-1240OC
  84. Biesbroek G, Bosch AA, Wang X, Keijser BJ, Veenhoven RH, Sanders EA, et al. The impact of breastfeeding on nasopharyngeal microbial communities in infants. Am J Respir Crit Care Med 2014;190:298-308. https://doi.org/10.1164/rccm.201401-0073OC
  85. Shilts MH, Rosas-Salazar C, Tovchigrechko A, Larkin EK, Torralba M, Akopov A, et al. Minimally invasive sampling method identifies differences in taxonomic richness of nasal microbiomes in young infants associated with mode of delivery. Microb Ecol 2016;71:233-42. https://doi.org/10.1007/s00248-015-0663-y
  86. Frayman KB, Armstrong DS, Grimwood K, Ranganathan SC. The airway microbiota in early cystic fibrosis lung disease. Pediatr Pulmonol 2017;52:1384-404. https://doi.org/10.1002/ppul.23782
  87. Dumas A, Bernard L, Poquet Y, Lugo-Villarino G, Neyrolles O. The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol 2018;20:e12966. https://doi.org/10.1111/cmi.12966
  88. Schenck LP, Surette MG, Bowdish DM. Composition and immunological significance of the upper respiratory tract microbiota. FEBS Lett 2016;590:3705-20. https://doi.org/10.1002/1873-3468.12455
  89. Prevaes SM, de Winter-de Groot KM, Janssens HM, de Steenhuijsen Piters WA, Tramper-Stranders GA, Wyllie AL, et al. Development of the nasopharyngeal microbiota in infants with cystic fibrosis. Am J Respir Crit Care Med 2016;193:504-15. https://doi.org/10.1164/rccm.201509-1759oc
  90. Luna PN, Hasegawa K, Ajami NJ, Espinola JA, Henke DM, Petrosino JF, et al. The association between anterior nares and nasopharyngeal microbiota in infants hospitalized for bronchiolitis. Microbiome 2018;6:2. https://doi.org/10.1186/s40168-017-0385-0
  91. Moore HC, Jacoby P, Taylor A, Harnett G, Bowman J, Riley TV, et al. The interaction between respiratory viruses and pathogenic bacteria in the upper respiratory tract of asymptomatic aboriginal and non-aboriginal children. Pediatr Infect Dis J 2010;29:540-5. https://doi.org/10.1097/inf.0b013e3181d067cb
  92. van den Bergh MR, Biesbroek G, Rossen JW, de Steenhuijsen Piters WA, Bosch AA, van Gils EJ, et al. Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria. PLoS One 2012;7:e47711. https://doi.org/10.1371/journal.pone.0047711
  93. Chertow DS, Memoli MJ. Bacterial coinfection in influenza: a grand rounds review. JAMA 2013;309:275-82. https://doi.org/10.1001/jama.2012.194139
  94. Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci U S A 2011;108:5354-9. https://doi.org/10.1073/pnas.1019378108
  95. Borges LGDA, Giongo A, Pereira LM, Trindade FJ, Gregianini TS, Campos FS, et al. Comparison of the nasopharynx microbiome between influenza and non-influenza cases of severe acute respiratory infections: a pilot study. Health Sci Rep 2018;1:e47. https://doi.org/10.1002/hsr2.47
  96. Laufer AS, Metlay JP, Gent JF, Fennie KP, Kong Y, Pettigrew MM. Microbial communities of the upper respiratory tract and otitis media in children. mBio 2011;2:e00245-10.
  97. Lappan R, Imbrogno K, Sikazwe C, Anderson D, Mok D, Coates H, et al. A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera. BMC Microbiol 2018;18:13. https://doi.org/10.1186/s12866-018-1154-3
  98. Chonmaitree T, Jennings K, Golovko G, Khanipov K, Pimenova M, Patel JA, et al. Nasopharyngeal microbiota in infants and changes during viral upper respiratory tract infection and acute otitis media. PLoS One 2017;12:e0180630. https://doi.org/10.1371/journal.pone.0180630
  99. Bhattacharyya N, Kepnes LJ. Assessment of trends in antimicrobial resistance in chronic rhinosinusitis. Ann Otol Rhinol Laryngol 2008;117:448-52. https://doi.org/10.1177/000348940811700608
  100. Kingdom TT, Swain RE Jr. The microbiology and antimicrobial resistance patterns in chronic rhinosinusitis. Am J Otolaryngol 2004;25:323-8. https://doi.org/10.1016/j.amjoto.2004.03.003
  101. Coffey CS, Sonnenburg RE, Melroy CT, Dubin MG, Senior BA. Endoscopically guided aerobic cultures in postsurgical patients with chronic rhinosinusitis. Am J Rhinol 2006;20:72-6. https://doi.org/10.1177/194589240602000113
  102. Martensson A, Abolhalaj M, Lindstedt M, Martensson A, Olofsson TC, Vasquez A, et al. Clinical efficacy of a topical lactic acid bacterial microbiome in chronic rhinosinusitis: a randomized controlled trial. Laryngoscope Investig Otolaryngol 2017;2:410-6. https://doi.org/10.1002/lio2.93
  103. Kiryukhina NV, Melnikov VG, Suvorov AV, Morozova YA, Ilyin VK. Use of Corynebacterium pseudodiphtheriticum for elimination of Staphylococcus aureus from the nasal cavity in volunteers exposed to abnormal microclimate and altered gaseous environment. Probiotics Antimicrob Proteins 2013;5:233-8. https://doi.org/10.1007/s12602-013-9147-x
  104. Mukerji SS, Pynnonen MA, Kim HM, Singer A, Tabor M, Terrell JE. Probiotics as adjunctive treatment for chronic rhinosinusitis: a randomized controlled trial. Otolaryngol Head Neck Surg 2009;140:202-8. https://doi.org/10.1016/j.otohns.2008.11.020