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Host–microorganism interactions in lung diseases

Nature Reviews Immunology volume 14, pages 827–835 (2014)Cite this article

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Abstract

Until recently, the airways were thought to be sterile unless infected; however, a shift towards molecular methods for the quantification and sequencing of bacterial DNA has revealed that the airways harbour a unique steady-state microbiota. This paradigm shift is changing the way that respiratory research is approached, with a clear need now to consider the effects of host–microorganism interactions in both healthy and diseased lungs. We propose that akin to recent discoveries in intestinal research, dysbiosis of the airway microbiota could underlie susceptibility to, and progression and chronicity of lung disease. In this Opinion article, we summarize current knowledge of the airway microbiota and outline how host–microorganism interactions in the lungs and other tissues might influence respiratory health and disease.

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Figure 1: The composition of the bacterial, fungal and viral microbiota at distinct body sites.
Figure 2: Heterogeneous microbial habitats within the lungs.
Figure 3: Microbial influences on immune status and lung disease.
Figure 4: Bacterial dysbiosis during chronic lung disorders.

References

  1. Erb-Downward, J. R. et al. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS ONE 6, e16384 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hilty, M. et al. Disordered microbial communities in asthmatic airways. PLoS ONE 5, e8578 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Charlson, E. S. et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am. J. Respir. Crit. Care Med. 184, 957–963 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sze, M. A. et al. The lung tissue microbiome in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 185, 1073–1080 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  5. van der Gast, C. J. et al. Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities. ISME J. 5, 780–791 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Charlson, E. S. et al. Assessing bacterial populations in the lung by replicate analysis of samples from the upper and lower respiratory tracts. PLoS ONE 7, e42786 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Salter, S. Reagent contamination can critically impact sequence-based microbiome analyses. BioRxiv http://dx.doi.org/10.1101/007187 (2014).

  8. Grice, E. A. & Segre, J. A. The skin microbiome. Nature Rev. Microbiol. 9, 244–253 (2011).

    Article  CAS  Google Scholar 

  9. Frank, D. N. et al. The human nasal microbiota and Staphylococcus aureus carriage. PLoS ONE 5, e10598 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lazarevic, V. et al. Metagenomic study of the oral microbiota by Illumina high-throughput sequencing. J. Microbiol. Methods 79, 266–271 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kim, T. K. et al. Heterogeneity of vaginal microbial communities within individuals. J. Clin. Microbiol. 47, 1181–1189 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Maldonado-Contreras, A. et al. Structure of the human gastric bacterial community in relation to Helicobacter pylori status. ISME J. 5, 574–579 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cho, I. & Blaser, M. J. The human microbiome: at the interface of health and disease. Nature Rev. Genet. 13, 260–270 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Charlson, E. S. et al. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am. J. Respir. Crit. Care Med. 186, 536–545 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Madan, J. C. et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. MBio 3, e00251-12 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Scupham, A. J. et al. Abundant and diverse fungal microbiota in the murine intestine. Appl. Environ. Microbiol. 72, 793–801 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hoffmann, C. et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS ONE 8, e66019 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ghannoum, M. A. et al. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 6, e1000713 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Findley, K. et al. Topographic diversity of fungal and bacterial communities in human skin. Nature 498, 367–370 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Drell, T. et al. Characterization of the vaginal micro- and mycobiome in asymptomatic reproductive-age Estonian women. PLoS ONE 8, e54379 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Underhill, D. M. & Iliev, I. D. The mycobiota: interactions between commensal fungi and the host immune system. Nature Rev. Immunol. 14, 405–416 (2014).

    Article  CAS  Google Scholar 

  23. Dollive, S. et al. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PLoS ONE 8, e71806 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. Ott, S. J. et al. Fungi and inflammatory bowel diseases: Alterations of composition and diversity. Scand. J. Gastroenterol. 43, 831–841 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, E. et al. Characterization of the skin fungal microbiota in patients with atopic dermatitis and in healthy subjects. Microbiol. Immunol. 55, 625–632 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Noverr, M. C., Falkowski, N. R., McDonald, R. A., McKenzie, A. N. & Huffnagle, G. B. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13. Infect. Immun. 73, 30–38 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Erb Downward, J. R., Falkowski, N. R., Mason, K. L., Muraglia, R. & Huffnagle, G. B. Modulation of post-antibiotic bacterial community reassembly and host response by Candida albicans. Sci. Rep. 3, 2191 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wylie, K. M., Weinstock, G. M. & Storch, G. A. Emerging view of the human virome. Transl. Res. 160, 283–290 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Breitbart, M. & Rohwer, F. Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing. Biotechniques 39, 729–736 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Abeles, S. R. et al. Human oral viruses are personal, persistent and gender-consistent. ISME J. 8, 1753–1767 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mallia, P. et al. Exacerbations of asthma and chronic obstructive pulmonary disease (COPD): focus on virus induced exacerbations. Curr. Pharm. Des. 13, 73–97 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl. Med. 6, 237ra265 (2014).

    Google Scholar 

  35. Gollwitzer, E. S. et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nature Med. 20, 642–647 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Deshmukh, H. S. et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nature Med. 20, 524–530 (2014).

    Article  CAS  PubMed  Google Scholar 

  37. Lohmann, P. et al. The airway microbiome of intubated premature infants: characteristics and changes that predict the development of bronchopulmonary dysplasia. Pediatr. Res. 76, 294–301 (2014).

    Article  CAS  PubMed  Google Scholar 

  38. Gillilland, M. G. 3rd et al. Ecological succession of bacterial communities during conventionalization of germ-free mice. Appl. Environ. Microbiol. 78, 2359–2366 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nature Med. 20, 159–166 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. Gollwitzer, E. S. & Marsland, B. J. Microbiota abnormalities in inflammatory airway diseases — Potential for therapy. Pharmacol. Ther. 141, 32–39 (2014).

    Article  CAS  PubMed  Google Scholar 

  41. Ege, M. J. et al. Exposure to environmental microorganisms and childhood asthma. N. Engl. J. Med. 364, 701–709 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Fanaro, S., Chierici, R., Guerrini, P. & Vigi, V. Intestinal microflora in early infancy: composition and development. Acta Paediatr. Suppl. 91, 48–55 (2003).

    CAS  PubMed  Google Scholar 

  43. Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Woodmansey, E. J. Intestinal bacteria and ageing. J. Appl. Microbiol. 102, 1178–1186 (2007).

    Article  CAS  PubMed  Google Scholar 

  45. Abrahamsson, T. R. et al. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin. Exp. Allergy 44, 842–850 (2014).

    Article  CAS  PubMed  Google Scholar 

  46. Power, S. E., O'Toole, P. W., Stanton, C., Ross, R. P. & Fitzgerald, G. F. Intestinal microbiota, diet and health. Br. J. Nutr. 111, 387–402 (2014).

    Article  CAS  PubMed  Google Scholar 

  47. Stevens, V., Dumyati, G., Fine, L. S., Fisher, S. G. & van Wijngaarden, E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin. Infect. Dis. 53, 42–48 (2011).

    Article  PubMed  Google Scholar 

  48. Sullivan, A., Edlund, C. & Nord, C. E. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect. Dis. 1, 101–114 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Jernberg, C., Lofmark, S., Edlund, C. & Jansson, J. K. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 1, 56–66 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4554–4561 (2011).

    Article  CAS  PubMed  Google Scholar 

  51. Russell, S. L. et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 13, 440–447 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Russell, S. L. et al. Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases. J. Allergy Clin. Immunol. http://dx.doi.org/10.1016/j.jaci.2014.06.027 (2014).

  53. Brusselle, G. G. & Joos, G. Is there a role for macrolides in severe asthma? Curr. Opin. Pulm Med. 20, 95–102 (2014).

    Article  CAS  PubMed  Google Scholar 

  54. Pragman, A. A., Kim, H. B., Reilly, C. S., Wendt, C. & Isaacson, R. E. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS ONE 7, e47305 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Goleva, E. et al. The effects of airway microbiome on corticosteroid responsiveness in asthma. Am. J. Respir. Crit. Care Med. 188, 1193–1201 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Habibzay, M., Weiss, G. & Hussell, T. Bacterial superinfection following lung inflammatory disorders. Future Microbiol. 8, 247–256 (2013).

    Article  CAS  PubMed  Google Scholar 

  57. Abt, M. C. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37, 158–170 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Goulding, J. et al. Lowering the threshold of lung innate immune cell activation alters susceptibility to secondary bacterial superinfection. J. Infect. Dis. 204, 1086–1094 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mallia, P. et al. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 186, 1117–1124 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Molyneaux, P. L. et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 188, 1224–1231 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Dicksved, J. et al. Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Appl. Environ. Microbiol. 73, 2284–2289 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. von Mutius, E. & Vercelli, D. Farm living: effects on childhood asthma and allergy. Nature Rev. Immunol. 10, 861–868 (2010).

    Article  CAS  Google Scholar 

  63. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).

    Article  PubMed  Google Scholar 

  64. Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15, 382–392 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Michail, S. et al. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm. Bowel Dis. 18, 1799–1808 (2012).

    Article  PubMed  Google Scholar 

  66. Kong, H. H. et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Fahlen, A., Engstrand, L., Baker, B. S., Powles, A. & Fry, L. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch. Dermatol. Res. 304, 15–22 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Huang, Y. J. & Lynch, S. V. The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications. Expert Rev. Respir. Med. 5, 809–821 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Dickson, R. P., Martinez, F. J. & Huffnagle, G. B. The role of the microbiome in exacerbations of chronic lung diseases. Lancet 384, 691–702 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sze, M. A., Hogg, J. C. & Sin, D. D. Bacterial microbiome of lungs in COPD. Int. J. Chron. Obstruct Pulmon Dis. 9, 229–238 (2014).

    PubMed  PubMed Central  Google Scholar 

  71. Craven, M. et al. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn's disease. PLoS ONE 7, e41594 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).

    Article  CAS  PubMed  Google Scholar 

  73. Herbst, T. et al. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respir. Crit. Care Med. 184, 198–205 (2011).

    Article  CAS  PubMed  Google Scholar 

  74. Hagner, S. et al. Farm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice. Allergy 68, 322–329 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Nembrini, C. et al. Bacterial-induced protection against allergic inflammation through a multicomponent immunoregulatory mechanism. Thorax 66, 755–763 (2011).

    Article  PubMed  Google Scholar 

  76. Thavagnanam, S., Fleming, J., Bromley, A., Shields, M. D. & Cardwell, C. R. A meta-analysis of the association between Caesarean section and childhood asthma. Clin. Exp. Allergy 38, 629–633 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl Acad. Sci. USA 107, 11971–11975 (2010).

    Article  PubMed  Google Scholar 

  78. von Mutius, E. Environmental factors influencing the development and progression of pediatric asthma. J. Allergy Clin. Immunol. 109, S525–S532 (2002).

    Article  PubMed  Google Scholar 

  79. Olszak, T. et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336, 489–493 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cahenzli, J., Koller, Y., Wyss, M., Geuking, M. B. & McCoy, K. D. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 14, 559–570 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. West, J. B. Regional differences in the lung. Chest 74, 426–437 (1978).

    CAS  PubMed  Google Scholar 

  82. Ingenito, E. P. et al. Indirect assessment of mucosal surface temperatures in the airways: theory and tests. J. Appl. Physiol. 63, 2075–2083 (1987).

    Article  CAS  PubMed  Google Scholar 

  83. Duncan, S. H., Louis, P., Thomson, J. M. & Flint, H. J. The role of pH in determining the species composition of the human colonic microbiota. Environ. Microbiol. 11, 2112–2122 (2009).

    Article  PubMed  Google Scholar 

  84. Lardner, A. The effects of extracellular pH on immune function. J. Leukoc. Biol. 69, 522–530 (2001).

    CAS  PubMed  Google Scholar 

  85. Wolak, J. E., Esther, C. R. Jr & O'Connell, T. M. Metabolomic analysis of bronchoalveolar lavage fluid from cystic fibrosis patients. Biomarkers 14, 55–60 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Palmer, K. L., Aye, L. M. & Whiteley, M. Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J. Bacteriol. 189, 8079–8087 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Moreau-Marquis, S., Stanton, B. A. & O'Toole, G. A. Pseudomonas aeruginosa biofilm formation in the cystic fibrosis airway. Pulm Pharmacol. Ther. 21, 595–599 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Spor, A., Koren, O. & Ley, R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nature Rev. Microbiol. 9, 279–290 (2011).

    Article  CAS  Google Scholar 

  89. Abeles, S. R. & Pride, D. T. Molecular bases and role of viruses in the human microbiome. J. Mol. Biol. http://dx.doi.org/10.1016/j.jmb.2014.07.002 (2014).

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Acknowledgements

This work was supported by Swiss National Science Foundation grant 310030_146983 (awarded to B.J.M.). B.J.M. is part of the European Cooperation in Science and Technology (COST) action BM1201, which is entitled “Developmental Origins of Chronic Lung Disease”.

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  1. Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, CLE D02-206, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland

    Benjamin J. Marsland & Eva S. Gollwitzer

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Correspondence to Benjamin J. Marsland.

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Supplementary information

Supplementary information S1 (table)

Constituents of the airway microbiota in health and disease. (PDF 613 kb)

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Glossary

Bronchoalveolar lavage fluid

Fluid containing bronchoalveolar cells that is obtained by infusing and extracting saline during bronchoscopy.

Chronic obstructive pulmonary disease

(COPD). A chronic lung disorder that is particularly associated with cigarette smoking and is characterized by the presence of emphysema and chronic bronchitis.

Cystic fibrosis

A genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator that leads to recurrent respiratory infections and a progressive loss of lung function.

Short-chain fatty acids

(SCFAs). Fatty acids with aliphatic tails of less than six carbons in length that are produced during bacterial fermentation of dietary fibres.

Systemic metabolome

The complete set of small-molecule chemicals (metabolites) found within the bloodstream.

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Marsland, B., Gollwitzer, E. Host–microorganism interactions in lung diseases. Nat Rev Immunol 14, 827–835 (2014). https://doi.org/10.1038/nri3769

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