Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Respiratory Microbiome in Children

소아의 호흡기 미생물군 유전체

  • Kim, Dong Hyun (Department of Pediatrics, Inha University School of Medicine)
  • 김동현 (인하대학교 의과대학 소아과학교실)
  • Received : 2019.07.14
  • Accepted : 2019.12.09
  • Published : 2019.12.25
Download PDF
⟨ Previous Next ⟩

Abstract

The human respiratory tract hosts both pathogenic and commensal bacteria. The development of well-conserved 16S rRNA sequencing and culture-independent techniques has enabled many achievements in the study of the human microbiome. Microbial composition of the respiratory tract in early childhood has been shown to correlate to respiratory health in later stages of life. This review highlights current understandings of respiratory microbiota development in healthy children, examples of microbial interactions, impacts on the host immune system, and the relationship between respiratory tract microbiome and respiratory health.

사람의 호흡기계는 감염 질환을 일으키는 세균과 집락균이 복잡하게 공존하는 기관이다. 세균이 배양되지 않아도 분석이 가능한 16S 리보좀 RNA 유전자 서열분석 기법이 도입된 이래 사람의 미생물군 유전체에 대한 많은 연구 성과들이 보고되었다. 출생 후 영아기 호흡기 내의 미생물총 구조는 이후의 호흡기계 건강과 연관이 있음이 관찰되었다. 본 종설에서는 건강한 어린이의 호흡기 미생물총의 발달, 미생물 간 상호 작용, 숙주의 면역에 미치는 영향, 미생물군 유전체와 호흡기 건강의 연관성에 대하여 지금까지 알려진 내용들을 알아보고자 한다.

Keywords

References

  1. Savage DC. Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 1977;31:107-33. https://doi.org/10.1146/annurev.mi.31.100177.000543
  2. Woese CR, Fox GE. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc Natl Acad Sci U S A 1977;74:5088-90. https://doi.org/10.1073/pnas.74.11.5088
  3. Stahl DA, Lane DJ, Olsen GJ, Pace NR. Analysis of hydrothermal vent-associated symbionts by ribosomal RNA sequences. Science 1984;224:409-11. https://doi.org/10.1126/science.224.4647.409
  4. Woese CR, Olsen GJ. Archaebacterial phylogeny: perspectives on the urkingdoms. Syst Appl Microbiol 1986;7:161-77. https://doi.org/10.1016/S0723-2020(86)80001-7
  5. Giovannoni SJ, Britschgi TB, Moyer CL, Field KG. Genetic diversity in Sargasso Sea bacterioplankton. Nature 1990;345:60-3. https://doi.org/10.1038/345060a0
  6. Schmidt TM, DeLong EF, Pace NR. Analysis of a marine picoplankton community by 16S rRNA gene cloning and sequencing. J Bacteriol 1991;173:4371-8. https://doi.org/10.1128/JB.173.14.4371-4378.1991
  7. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921. https://doi.org/10.1038/35057062
  8. NIH HMP Working Group, Peterson J, Garges S, Giovanni M, McInnes P, Wang L, et al. The NIH Human Microbiome Project. Genome Res 2009;19:2317-23. https://doi.org/10.1101/gr.096651.109
  9. Rogers GB, Shaw D, Marsh RL, Carroll MP, Serisier DJ, Bruce KD. Respiratory microbiota: addressing clinical questions, informing clinical practice. Thorax 2015;70:74-81. https://doi.org/10.1136/thoraxjnl-2014-205826
  10. Huang YJ, Charlson ES, Collman RG, Colombini-Hatch S, Martinez FD, Senior RM. The role of the lung microbiome in health and disease. A National Heart, Lung, and Blood Institute workshop report. Am J Respir Crit Care Med 2013;187:1382-7. https://doi.org/10.1164/rccm.201303-0488WS
  11. Relman DA, Falkow S. The meaning and impact of the human genome sequence for microbiology. Trends Microbiol 2001;9:206-8. https://doi.org/10.1016/S0966-842X(01)02041-8
  12. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science 2005;308:1635-8. https://doi.org/10.1126/science.1110591
  13. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol 2007;5:e177. https://doi.org/10.1371/journal.pbio.0050177
  14. Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med 2016;8:51. https://doi.org/10.1186/s13073-016-0307-y
  15. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med 2014;6:237ra65. https://doi.org/10.1126/scitranslmed.3008599
  16. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep 2016;6:23129. https://doi.org/10.1038/srep23129
  17. Lauder AP, Roche AM, Sherrill-Mix S, Bailey A, Laughlin AL, Bittinger K, et al. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome 2016;4:29. https://doi.org/10.1186/s40168-016-0172-3
  18. Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, et al. The maternal microbiota drives early postnatal innate immune development. Science 2016;351:1296-302. https://doi.org/10.1126/science.aad2571
  19. Koch MA, Reiner GL, Lugo KA, Kreuk LS, Stanbery AG, Ansaldo E, et al. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. Cell 2016;165:827-41. https://doi.org/10.1016/j.cell.2016.04.055
  20. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 2010;107:11971-5. https://doi.org/10.1073/pnas.1002601107
  21. Bosch AATM, Levin E, van Houten MA, Hasrat R, Kalkman G, Biesbroek G, et al. Development of upper respiratory tract microbiota in infancy is affected by mode of delivery. EBioMedicine 2016;9:336-45. https://doi.org/10.1016/j.ebiom.2016.05.031
  22. 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
  23. 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
  24. Johnson CL, Versalovic J. The human microbiome and its potential importance to pediatrics. Pediatrics 2012;129:950-60. https://doi.org/10.1542/peds.2011-2736
  25. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006;118:511-21. https://doi.org/10.1542/peds.2005-2824
  26. 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
  27. Pettigrew MM, Laufer AS, Gent JF, Kong Y, Fennie KP, Metlay JP. Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children. Appl Environ Microbiol 2012;78:6262-70. https://doi.org/10.1128/AEM.01051-12
  28. Leibovitz E, Greenberg D, Piglansky L, Raiz S, Porat N, Press J, et al. Recurrent acute otitis media occurring within one month from completion of antibiotic therapy: relationship to the original pathogen. Pediatr Infect Dis J 2003;22:209-16. https://doi.org/10.1097/01.inf.0000066798.69778.07
  29. Bogaert D, Keijser B, Huse S, Rossen J, Veenhoven R, van Gils E, et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS One 2011;6:e17035. https://doi.org/10.1371/journal.pone.0017035
  30. Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rumke HC, et al. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 2004;363:1871-2. https://doi.org/10.1016/S0140-6736(04)16357-5
  31. 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
  32. Spijkerman J, Prevaes SM, van Gils EJ, Veenhoven RH, Bruin JP, Bogaert D, et al. Long-term effects of pneumococcal conjugate vaccine on nasopharyngeal carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis. PLoS One 2012;7:e39730. https://doi.org/10.1371/journal.pone.0039730
  33. Greenberg D, Givon-Lavi N, Broides A, Blancovich I, Peled N, Dagan R. The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers. Clin Infect Dis 2006;42:897-903. https://doi.org/10.1086/500935
  34. Liu CM, Price LB, Hungate BA, Abraham AG, Larsen LA, Christensen K, et al. Staphylococcus aureus and the ecology of the nasal microbiome. Sci Adv 2015;1:e1400216. https://doi.org/10.1126/sciadv.1400216
  35. Lim MY, Yoon HS, Rho M, Sung J, Song YM, Lee K, et al. Analysis of the association between host genetics, smoking, and sputum microbiota in healthy humans. Sci Rep 2016;6:23745. https://doi.org/10.1038/srep23745
  36. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature 2012;486:222-7. https://doi.org/10.1038/nature11053
  37. Stearns JC, Davidson CJ, McKeon S, Whelan FJ, Fontes ME, Schryvers AB, et al. Culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age. ISME J 2015;9:1246-59. https://doi.org/10.1038/ismej.2014.250
  38. Jakobsson HE, Jernberg C, Andersson AF, Sjolund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One 2010;5:e9836. https://doi.org/10.1371/journal.pone.0009836
  39. Charlson ES, Chen J, Custers-Allen R, Bittinger K, Li H, Sinha R, et al. Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS One 2010;5:e15216. https://doi.org/10.1371/journal.pone.0015216
  40. Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, et al. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med 2013;187:1067-75. https://doi.org/10.1164/rccm.201210-1913OC
  41. Marsh RL, Kaestli M, Chang AB, Binks MJ, Pope CE, Hoffman LR, et al. The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx. Microbiome 2016;4:37. https://doi.org/10.1186/s40168-016-0182-1
  42. Bassis CM, Erb-Downward JR, Dickson RP, Freeman CM, Schmidt TM, Young VB, et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio 2015;6:e00037-15.
  43. 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
  44. 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
  45. Lohmann P, Luna RA, Hollister EB, Devaraj S, Mistretta TA, Welty SE, et al. The airway microbiome of intubated premature infants: characteristics and changes that predict the development of bronchopulmonary dysplasia. Pediatr Res 2014;76:294-301. https://doi.org/10.1038/pr.2014.85
  46. Payne MS, Goss KC, Connett GJ, Kollamparambil T, Legg JP, Thwaites R, et al. Molecular microbiological characterization of preterm neonates at risk of bronchopulmonary dysplasia. Pediatr Res 2010;67:412-8. https://doi.org/10.1203/PDR.0b013e3181d026c3
  47. Mourani PM, Harris JK, Sontag MK, Robertson CE, Abman SH. Molecular identification of bacteria in tracheal aspirate fluid from mechanically ventilated preterm infants. PLoS One 2011;6:e25959. https://doi.org/10.1371/journal.pone.0025959
  48. Huitzil S, Sandoval-Motta S, Frank A, Aldana M. Modeling the role of the microbiome in evolution. Front Physiol 2018;9:1836. https://doi.org/10.3389/fphys.2018.01836
  49. Mashima I, Nakazawa F. The influence of oral Veillonella species on biofilms formed by Streptococcus species. Anaerobe 2014;28:54-61. https://doi.org/10.1016/j.anaerobe.2014.05.003
  50. Cook LC, LaSarre B, Federle MJ. Interspecies communication among commensal and pathogenic streptococci. MBio 2013;4:e00382-13.
  51. Armbruster CE, Hong W, Pang B, Weimer KE, Juneau RA, Turner J, et al. Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling. MBio 2010;1:e00102-10.
  52. 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
  53. Ramsey MM, Freire MO, Gabrilska RA, Rumbaugh KP, Lemon KP. Staphylococcus aureus shifts toward commensalism in response to Corynebacterium species. Front Microbiol 2016;7:1230.
  54. Deasy AM, Guccione E, Dale AP, Andrews N, Evans CM, Bennett JS, et al. Nasal inoculation of the commensal Neisseria lactamica inhibits carriage of Neisseria meningitidis by young adults: a controlled human infection study. Clin Infect Dis 2015;60:1512-20. https://doi.org/10.1093/cid/civ098
  55. Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 2010;465:346-9. https://doi.org/10.1038/nature09074
  56. Zipperer A, Konnerth MC, Laux C, Berscheid A, Janek D, Weidenmaier C, et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 2016;535:511-6. https://doi.org/10.1038/nature18634
  57. Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. Corynebacterium accolens releases antipneumococcal free fatty acids from human nostril and skin surface triacylglycerols. MBio 2016;7:e01725-15.
  58. van den Broek MF, De Boeck I, Kiekens F, Boudewyns A, Vanderveken OM, Lebeer S. Translating recent microbiome insights in otitis media into probiotic strategies. Clin Microbiol Rev 2019;32:e00010-18.
  59. Sajjan US, Jia Y, Newcomb DC, Bentley JK, Lukacs NW, LiPuma JJ, et al. H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression. FASEB J 2006;20:2121-3. https://doi.org/10.1096/fj.06-5806fje
  60. Blanken MO, Rovers MM, Molenaar JM, Winkler-Seinstra PL, Meijer A, Kimpen JL, et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013;368:1791-9. https://doi.org/10.1056/NEJMoa1211917
  61. Zomer-Kooijker K, van der Ent CK, Ermers MJ, Uiterwaal CS, Rovers MM, Bont LJ, et al. Increased risk of wheeze and decreased lung function after respiratory syncytial virus infection. PLoS One 2014;9:e87162. https://doi.org/10.1371/journal.pone.0087162
  62. Ni K, Li S, Xia Q, Zang N, Deng Y, Xie X, et al. Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection. PLoS One 2012;7:e41104. https://doi.org/10.1371/journal.pone.0041104
  63. Boase S, Jervis-Bardy J, Cleland E, Pant H, Tan L, Wormald PJ. Bacterial-induced epithelial damage promotes fungal biofilm formation in a sheep model of sinusitis. Int Forum Allergy Rhinol 2013;3:341-8. https://doi.org/10.1002/alr.21138
  64. Briard B, Heddergott C, Latge JP. Volatile compounds emitted by Pseudomonas aeruginosa stimulate growth of the fungal pathogen Aspergillus fumigatus. MBio 2016;7:e00219-16.
  65. Dickson RP, Erb-Downward JR, Freeman CM, McCloskey L, Beck JM, Huffnagle GB, et al. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann Am Thorac Soc 2015;12:821-30. https://doi.org/10.1513/AnnalsATS.201501-029OC
  66. Uehara A, Fujimoto Y, Fukase K, Takada H. Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol 2007;44:3100-11. https://doi.org/10.1016/j.molimm.2007.02.007
  67. Wang J, Li F, Sun R, Gao X, Wei H, Li LJ, et al. Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages. Nat Commun 2013;4:2106. https://doi.org/10.1038/ncomms3106
  68. Rice TA, Brenner TA, Percopo CM, Ma M, Keicher JD, Domachowske JB, et al. Signaling via pattern recognition receptors NOD2 and TLR2 contributes to immunomodulatory control of lethal pneumovirus infection. Antiviral Res 2016;132:131-40. https://doi.org/10.1016/j.antiviral.2016.06.002
  69. Almada G, Haro C, Vintini E, Medina M. Safety of a nasal vaccine against Streptococcus pneumoniae using heat-killed Lactobacillus casei as adjuvant. Immunobiology 2015;220:109-16. https://doi.org/10.1016/j.imbio.2014.08.013
  70. Ranucci G, Buccigrossi V, de Freitas MB, Guarino A, Giannattasio A. Early-life intestine microbiota and lung health in children. J Immunol Res 2017;2017:8450496.