REVIEW
Lower Respiratory Tract Microbiome
 
More details
Hide details
1
Center for Respiratory Failure, Thoracic Diseases General Hospital “Sotiria”, Athens
2
Bioanalytica-Genotype SA, Athens, Greece
CORRESPONDING AUTHOR
Aliki Korkontzelou   

Center for Respiratory Failure, “Sotiria” General Hospital for Chest Diseases, 152 Mesogeion Av., 11527 Athens, Greece
 
Pneumon 2017;30(3):165–174
 
KEYWORDS
ABSTRACT
Given the fact that the hypothesis of respiratory microbe sterility is being degraded, researchers are currently studying healthy lung microbiota homeostasis as well as its disturbance in case of illness. Taking into consideration the thorough understanding of diseases that gut microbiota studies offered, one cannot but anticipate that respiratory microbiome research would reveal further insight to the pathogenesis of lung disorders but mostly to healthy respiratory physiology. In this article, we review published studies with a view to summarizing important terms and definitions in human microbiome studies, obstacles in lung microbiota research, microbial diversity of lower respiratory tract in health state and major lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease (ILD), lung cancer and cystic fibrosis.
 
REFERENCES (100)
1.
Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroen 2015;31:69-75.
 
2.
Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol 2011;9:244-53.
 
3.
Martin DH. The Microbiota of the Vagina and Its Influence on Women’s Health and Disease. Am J Med Sci 2012;343:2-9.
 
4.
Wage WG. The oral microbiome in health and disease. Pharmacol Res 2013;69:137-43.
 
5.
Segal LN, Blaser MJ. A Brave new world the lung microbiota in an era of change. Ann Am Thorac Soc 2014; 11(Suppl 1):S21-7.
 
6.
Dickson RP, Erb-Downward JR, Freeman CM, 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.
 
7.
Proctor LM. The Human Microbiome Project in 2011 and beyond. Cell Host Microbiome 2014;10:287-91.
 
8.
Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the Human Microbiome. Nutrition Reviews 2012;70(Suppl1):S38–S44.
 
9.
van Leeuwenhoek A. An abstract of a Letter from Antonie van Leeuwenhoek: About Animals in the scrurf of the Teeth. Philos Trans R Soc Lond. 1684;14:568–74.
 
10.
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett C, Knight R, Gordon JI. The human microbiome project: exploring the microbial part of ourselves in a changing world. Nature, 2007;449(7164):804–10.
 
11.
Morgan XC, Huttenhower C. Chapter 12: Human Microbiome Analysis. PLoS Comput Biol 2012;8:e1002808.
 
12.
Rogers GB, Carroll MP, Bruce KD. Studying bacterial infections through cultureindependent approaches. Journal of Medical Microbiology 2009;58:1401–18.
 
13.
Batt CA. Encyclopedia of Food Microbiology. Academic Press; 2014.
 
14.
Fakruddin M, Mannan KS, Mzumdar RM, Chowdhury A, Hossain MN. Identification and characterization of microorganisms: DNA-fingerprinting methods. Songklanakarin J Sci Tech 2013;35:397-404.
 
15.
Restrepo MI, Mortensen EM, Velez JA, Frei C, Anzueto A. A comparative study of communityacquired pneumonia patients admitted to the ward and the ICU. Chest J 2008;133:610–17.
 
16.
Woese CR, Stackebrandt E, Macke TJ, Fox GE. A phylogenetic definition of the major eubacterial taxa. Syst Appl Microbiol 1985;6:143-51.
 
17.
Clarridge JE. Impact of 16S rRNA Gene Sequence Analysis for Identification of Bacteria on Clinical Microbiology and Infectious Diseases. Clin Microbiol Rev 2004;17:840–62.
 
18.
Tian RM, Cai L, Zhang WP, Cao HL, Qian PY. Rare Events of Intragenus and Intraspecies Horizontal Transfer of the 16S rRNA Gene. Genome Biol Evol 2015;7:2310-20.
 
19.
Chakravorty S, Helb D, Burday M, Connell N, Alland D. A detailed analysis of 16S ribosomal RNA gene segments for the diagnosis of pathogenic bcteria. J Microbiol Methods 2007;69:330-9.
 
20.
Choi Y, Hong SR, Jeon BY, et al. Conventional and real-time PCR targeting 16S ribosomal RNA for the detection of Mycobacterium tuberculosis complex. Int J Tuberc Lung D 2015;19:1102-8.
 
21.
Wade W. Unculturable bacteria—the uncharacterized organisms that cause oral infections. J R Soc Med 2002;95:81–3.
 
22.
Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 1975;94:81-3.
 
23.
Hunkapiller T, Kaiser RJ, Koop BF, Hood L. Large-scale and automated DNA sequence determination. Science 1991; 254(5028):59-67.
 
24.
Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol 2008; 26:1135-45.
 
25.
Reis-Filho JS. Next-generation sequencing. Breast Cancer Res 2009; 11:S12.
 
26.
Behjati S, Tarpey PS. What is next generation sequencing? Archives of disease in childhood. Arch Dis Child Educ Pract Ed 2013; 98:236–8.
 
27.
Johansson N, Kalin M, Tiveljung-Lindell A, Giske CG, Hedlund J. Etiology of Community-Acquired Pneumonia: Increased Microbiological Yield with New Diagnostic Methods. Clin Infect Dis 2010; 50:202-9.
 
28.
Hogan DA, Willger SD, Dolben EL, et al. Analysis of lung microbiota in BAL, protected brush and sputum samples from subjects with mild and cystic fibrosis lung disease. PLoS One 2016; 11:e0149998.
 
29.
Huse SM, Ye Y, Zhou Y, Fodor AA. A Core Human Microbiome as Viewed through 16S rRNA Sequence Clusters. PLoS ONE 2012; 7:e34242.
 
30.
Charlson ES, Bittinger K, Haas AR, et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med 2011; 184:957–63.
 
31.
Cui L, Morris A, Huang L, et al. The Microbiome and the Lung. Ann Am Thorac Soc 2014; 11(Suppl4):S227–S32.
 
32.
Knights D, Kuczynski J, Charlson ES, et al. Bayesian communitywide culture-independent microbial source tracking. Nat Methods 2011; 8:761–3.
 
33.
Eddens T, Kolls JK. Host defenses against bacterial lower respiratory tract infection. Curr Opin Immunol 2012; 24:424–30.
 
34.
Pezzulo AA, Kelly PH, Nassar BS, et al. Abundant DNase I-sensitive bacterial DNA in healthy porcine lungs and its implications for the lung microbiome. Appl Environ Microbiol 2013; 279:5936-41.
 
35.
Venkataraman A, Bassis CM, Beck JM, et al. Application of a neutral community model to assess structuring of the human lung microbiome. mBio 2015; 6:e02284–14.
 
36.
Marsland BJ. Influences of the Microbiome on the Early Origins of Allergic Asthma. Ann Am Thorac Soc 2013; 10:S165-S69.
 
37.
Dickson RP, Huffnagle GB. The Lung Microbiome: New Principles for Respiratory Bacteriology in Health and Disease. PLoS Pathog 2015; 11:e1004923.
 
38.
Erb-Downward JR, Thompson DL, Han MK, et al. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PloS one 2011; 6:e16384.
 
39.
Morris A, Beck JM, Schloss PD, et al. Comparison of the Respiratory Microbiome in Healthy Nonsmokers and Smokers. Am J Respir Crit Care Med 2013;187:1067-75.
 
40.
Hilty M, Burke C, Pedro H, et al. Disordered microbial communities in asthmatic airways. PLoS One 2010; 5:e8578.
 
41.
Lozupone C, Cota-Gomez A, Palmer E, Linderman DJ, Charlson ES, Sadergren E. Widespread colonization of the lung by Tropheryma Whipplei in HIV infection. ATS J 2013; 187:1110-7.
 
42.
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.
 
43.
Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature 2012; 486:222-7.
 
44.
Stressmann FA, Rogers GB, Klem ER, et al. Analysis of the bacterial communities present in lungs of patients with cystic fibrosis from American and British centers. J Clin Microbiol 2011;49:281-91.
 
45.
West JB. Regional difference in the lung. Chest 1978;74:426-37.
 
46.
Ingenito EP, Solway J, McFadden ER Jr, et al. Indirect assessment of mucosal surface temperatures in the airways: theory and tests. J Appl Physiol 1987;632075-83.
 
47.
Dickson RP, Erb-Downward JR, Prescott HC, et al. Analysis of Culture-Dependent versus Culture-Independent Techniques for Identification of Bacteria in Clinically Obtained Bronchoalveolar Lavage Fluid. J Clin Microbiol 2014; 52:3605–13.
 
48.
Willner D, Haynes MR, Furlan M, et al. Spatial distribution of microbial communities in the cystic fibrosis lung. ISME J 2012;b6:471-4.
 
49.
Stuart-Harris CH, Pownall M, Scothorne CM, Franks Z. The factor of infection in chronic bronchitis. The Quarterly journal of medicine 1953; 22:121–32.
 
50.
Di Stefano A, Turato G, Maestrelli P, et al. Airflow limitation in chronic bronchitis is associated with T-lymphocyte and macrophage infiltration of the bronchial mucosa. American Journal of Respiratory Critical Care Medicine 1996; 153:629–32.
 
51.
Sethi S, Evans N, Grant BJ, Murphy TF. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002; 347:465–71.
 
52.
Hilty M, Burke C, Pedro H. Disordered Microbial Communities in Asthmatic Airways. Neyrolles O, ed. PLoS ONE. 2010; 5:e8578. doi:10.1371/journal.pone.0008578.
 
53.
Sze MA, Dimitriu PA, Hayashi S, et al. The lung tissue microbiome in chronic obstructive pulmonary disease. American Journal of Respiratory Critical Care Medicine 2012; 185:1073-80.
 
54.
Zakharkina T, Heinzel E, Koczulla RA, et al. Analysis of the Airway Microbiota of Healthy Individuals and Patients with Chronic Obstructive Pulmonary Disease by T-RFLP and Clone Sequencing. PLoS ONE 2013; 8:e68302. doi:10.1371/journal. pone.0068302.
 
55.
Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoSOne 2012; 7:e47305. doi: 10.1371/ journal.pone.0047305.
 
56.
Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006; 368:804-13.
 
57.
Hahn DL, Dodge RW, Golubjatnikov R. Association of Chlamydia pneumonia~ (strain WAR) infection with wheenng, asthmatic bronchitis, and adult-onset asthma. JAMA 1991; 266:225-30.
 
58.
Yano T, Ichikawa Y, Komatu S, et al Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma. Am J Respir Crit Care Med 1994; 149:1348–53.
 
59.
Martin RJ, Chu HW, Honour JM, Harbeck RJ. Airway inflammation and bronchial hyperresponsiveness after Mycoplasma pneumoniae infection in a murine model. Am J Resp Cell Mol 2001; 24:577–82.
 
60.
Specjalski K, Jassem E. Chlamydophila pneumoniae, Mycoplasma pneumoniae infections, and asthma control. Allergy Asthma Proc 2011; 32:9–17.
 
61.
Bisgaard H, Hermansen MN, Bonnelykke K, et al. Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study. BMJ 2010; 341:c4978.
 
62.
Bisgaard H, Hermansen MN, Buchvald F, et al. Childhood asthma after bacterial colonization of the airways in neonates. N Eng J Med 2007; 357:1487-95.
 
63.
Kloepfer KM, Lee WM, Pappas TE, et al. Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. J Allergy Clin Immunol 2014; 133:1301–1307. 7 e1–7 e3.
 
64.
Huang YJ, Nariya S, Harris JM, et al. The airway microbiome in patients with severe asthma: associations with disease features and severity. J Allergy Clin Immunol 2015;136:874–84.
 
65.
Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. Asthmaassociated differences in microbial composition of induced sputum. J Allergy Clin Immunol 2013;131:346–52.
 
66.
Semenzato G, Adami F, Maschio N, Agostini C. Immune mechanisms in interstitial lung diseases. Allergy 2000; 55:1103–20. doi: 10.1034/j.1398-9995.2000.00127.
 
67.
Garzoni C, Brugger SD, Qi W, et al. Microbial communities in the respiratory tract of patients with interstitial lung disease. Thorax 2013; 68:1150-6. Doi:10.1136/thoraxjnl-2012-202917.
 
68.
Friaza V, La Horra C, Rodríguez-Domínguez MJ, et al. Metagenomic analysis of bronchoalveolar lavage samples from patients with idiopathic interstitial pneumonia and its antagonic relation with Pneumocystis jirovecii colonization. Journal of Microbiological Methods 2010;82:98–101.
 
69.
Han MK, Zhou Y, Murray S, et al.; COMET Investigators. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. Lancet Respiratory Medicine 2014; 2:548–56.
 
70.
Molyneaux PL, Cox MJ, Willis-Owen SAG, et al. The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine 2014; 190:906-13.
 
71.
Vogtmann E, Goedert J.J. Epidemiologic studies of the human microbiome and cancer. Br J Cancer 2016;114:237–42.
 
72.
Brenner DR, McLaughlin JR, Hung RJ. Previous lung diseases and lung cancer risk: a systematic review and meta-analysis. PLOS 2011; doi.org/10.1371/journal.pone.0....
 
73.
Senn L, Entenza JM, Greub G, et al. Bloodstream and endovascular infectionsb due to Abiotrophia defectiva and Granulicatella species. BMC Infect Dis 2006;6:9. Doi.org/10.1186/1471-2334-6-9.
 
74.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74.
 
75.
Wu BJ, Cahaney CF, Tsay JJ, et al. Evaluation of The Microbiome Associated with Lung Cancer. American Journal of Respiratory and Critical Care Medicine 2015; DOI: 10.1164/ajrccm-conference.2015.191.1_MeetingAbstracts.A5164.
 
76.
Yu G, Gail MH, Consonni D, et al. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome Biology. 2016;17:163. doi:10.1186/s13059-016-1021-1.
 
77.
Riordan JR 2008. CFTR function and prospects for therapy. Annu Rev Biochem 77: 701–726.
 
78.
Davies JC, Alton EWFW, Bush A. Cystic fibrosis. Br J Med 2007; 335:1255–9.
 
79.
Davies JC. Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respir Rev 2002; 3:128-34.
 
80.
Burns JL, Rolain J-M. Culture-based diagnostic microbiology in cystic fibrosis: Can we simplify the complexity? Journal of Cystic Fibrosis 2014; 13:1-9.
 
81.
Govan JR, Deretic V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Mol. Biol. Rev.September 1996; 60:3539-74.
 
82.
Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. Association between respiratory tract methicillinresistant Staphylococcus aureus and survival in cystic fibrosis. JAMA 2010;303:2386–92.
 
83.
Marzuillo C, De Giusti M, Tufi D, et al. Molecular characterization of Stenotrophomonas maltophilia isolates from cystic fibrosis patients and the hospital environment. Infect Control Hosp Epidemiol 2009; 30:753–8.
 
84.
Hill UG, Andres Floto R, Haworth CS. Non-tuberculous mycobacteria in cystic fibrosis. Journal of the Royal Society of Medicine 2012; 105(Suppl 2):S14–S18. http://doi.org/10.1258/jrsm.20....
 
85.
Nielsen SM, Nørskov-Lauritsen N, Bjarnsholt T, Meyer RL. Achromobacter Species Isolated from Cystic Fibrosis Patients Reveal Distinctly Different Biofilm Morphotypes. Microorganisms 2016; 4:33. http://doi.org/10.3390/microor....
 
86.
Grinwis ME, Sibley CD, Parkins MD, Eshaghurshan CS, Rabin HR, Surette MG. Characterization of Streptococcus milleri Group Isolates from Expectorated Sputum of Adult Patients with Cystic Fibrosis. J Clin Microbiol 2010; 48:395-401.
 
87.
Rogers G, Carroll M, Serisier D, Hockey P, Jones G, Bruce K. Characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16s ribosomal DNA terminal restriction fragment length polymorphism profiling. Journal of Clinical Microbiology 2004; 42:5176–83.
 
88.
Sherrard LJ, Bell SC, Tunney MM. The role of anaerobic bacteria in the cystic fibrosis airway. Curr Opin Pulm Med 2016; 22:637-43.
 
89.
Coburn B, Wang PW, Diaz Caballero J, et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 2015; 5:10241. doi: 10.1038/srep10241.
 
90.
Huang YJ, LiPuma JJ. The Microbiome in Cystic Fibrosis. Clinics in Chest Medicine 2016; 37:59–67. http://doi.org/10.1016/j. ccm.2015.10.003.
 
91.
Zhao J, Schloss PD, Kalikin LM, et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A. 2012; 109:5809–14.
 
92.
Fodor AA, Klem ER, Gilpin DF, et al. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS One 2012; 7:e45001. doi: 10.1371/journal.pone.0045001.
 
93.
Chow J, Lee SM, Shen A, Khosravi A, Mazmanian SK. Hostbacterial symbiosis in health and disease. Adv Immunol 2010; 107:243-74.
 
94.
Gent AE, Hellier MD, Grace RH, Swarbrick ET, Coggon D. Inflammatory bowel disease and domestic hygiene in infancy. Lancet 1994; 343:766-7.
 
95.
Guarner F, Bourdet-Sicard R, Brandtzaeg P, et al. Mechanisms of disease: the hygiene hypothesis revisited. Nat Rev Gastroenterol Hepatol 2006; 3:275-84.
 
96.
Ege MJ, Mayer M, Normand AC, et al. Exposure to Environmental Microorganisms and Childhood Asthma. N Eng J Med 2011; 364:701-9.
 
97.
Arumugan M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature 2011; 473:174-180.
 
98.
Knights DTL, Ward TL, McKinlay CE, et al. Rethinking «Enterotypes». Cell Host Microbe 2014; 16:433-7.
 
99.
Sze MA, Hogg JC, Sin DD. Bacterial microbiome of lungs in COPD. Int J Chron Obstruct Pulmon Dis 2014; 9:229-238.
 
100.
Riiser A. The human microbiome, asthma, and allergy. Allergy Asthma Clin Immunol 2015; 11:35.
 
eISSN:1791-4914
ISSN:1105-848X