Allergy Asthma Respir Dis.  2016 Sep;4(5):321-327. 10.4168/aard.2016.4.5.321.

Current status of microbiome research in asthma and chronic obstructive pulmonary disease

• Kim BK
• Rhee CK
• Jung JY
• Kang HR
• Cho SH

• KMID: 2391921
• DOI: http://doi.org/10.4168/aard.2016.4.5.321

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation resulting in airflow limitation. They include various phenotypes and endotypes in their disease entities. For that reason, they lack proper biomarkers and epoch-making progresses in treatment nowadays. Healthy airway has been believed to be sterile traditionally. However, with the help of nonculture sequencing techniques, researchers discovered that it is full of the commensal and symbiotic microbial flora. Therefore, microbiome has emerged as a possible biomarker and a clue to understand the pathogenesis of airway disease. Microbiome research in asthma has focused on the association between characteristics of microbiome, such as composition and diversity. However, now it refers to the role of microbiome, including Proteobacteria, in the development and pathogenesis of asthma and allergic diseases. Microbiome research in COPD has revealed its different composition according to the existence and severity of the disease. Also, differences in microbiome composition according to exacerbation state or specific treatment of COPD are reported. Therefore, many researchers pay attention to the possible role of microbiome as a biomarker or a treatment target in asthma and COPD. Herein, we review recent studies on microbiome research in asthma and COPD.

Keyword

Microbiome; Asthma; Chronic obstructive lung disease

MeSH Terms

Asthma*
Biomarkers
Inflammation
Microbiota*
Phenotype
Proteobacteria
Pulmonary Disease, Chronic Obstructive*
Research Design
Biomarkers

Figure

• 

  Fig. 1 Role of microbiome in the pathogenesis of chronic obstructive pulmonary disease (COPD).

• 

  Fig. 2 Development of asthma and early-life airway microbial exposure.

• 

  Fig. 3 Role of Lactobacillus in the pathogenesis of chronic obstructive pulmonary disease (COPD). GD1, glycerol dehydratase 1.

Reference

1. Park HW, Tantisira KG, Weiss ST. Pharmacogenomics in asthma therapy: where are we and where do we go? Annu Rev Pharmacol Toxicol. 2015; 55:129–147.

2. Sim DW, Lee JH. Biomarkers of adult asthma and personalized medicine. Allergy Asthma Respir Dis. 2016; 4:4–13.

3. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010; 181:315–323.

4. Cookson W. The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol. 2004; 4:978–988.

5. Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, et al. Disordered microbial communities in asthmatic airways. PLoS One. 2010; 5:e8578.

6. Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS, Liu J, et al. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol. 2011; 127:372–381.e1-3.

7. Goleva E, Jackson LP, Harris JK, Robertson CE, Sutherland ER, Hall CF, et al. The effects of airway microbiome on corticosteroid responsiveness in asthma. Am J Respir Crit Care Med. 2013; 188:1193–1201.

8. Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014; 44:842–850.

9. Sze MA, Hogg JC, Sin DD. Bacterial microbiome of lungs in COPD. Int J Chron Obstruct Pulmon Dis. 2014; 9:229–238.

10. Park H, Shin JW, Park SG, Kim W. Microbial communities in the upper respiratory tract of patients with asthma and chronic obstructive pulmonary disease. PLoS One. 2014; 9:e109710.

11. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989; 299:1259–1260.

12. Brooks C, Pearce N, Douwes J. The hygiene hypothesis in allergy and asthma: an update. Curr Opin Allergy Clin Immunol. 2013; 13:70–77.

13. Strachan DP. Allergy and family size: a riddle worth solving. Clin Exp Allergy. 1997; 27:235–236.

14. Webley WC, Aldridge KL. Infectious asthma triggers: time to revise the hygiene hypothesis? Trends Microbiol. 2015; 23:389–391.

15. Aaby P, Shaheen SO, Heyes CB, Goudiaby A, Hall AJ, Shiell AW, et al. Early BCG vaccination and reduction in atopy in Guinea-Bissau. Clin Exp Allergy. 2000; 30:644–650.

16. Matricardi PM, Rosmini F, Ferrigno L, Nisini R, Rapicetta M, Chionne P, et al. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ. 1997; 314:999–1003.

17. Shaheen SO, Aaby P, Hall AJ, Barker DJ, Heyes CB, Shiell AW, et al. Cell mediated immunity after measles in Guinea-Bissau: historical cohort study. BMJ. 1996; 313:969–974.

18. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008; 178:667–672.

19. Hahn DL, Dodge RW, Golubjatnikov R. Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma. JAMA. 1991; 266:225–230.

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

21. Liu AH. Revisiting the hygiene hypothesis for allergy and asthma. J Allergy Clin Immunol. 2015; 136:860–865.

22. Bager P, Wohlfahrt J, Westergaard T. Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy. 2008; 38:634–642.

23. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol. 2012; 9:565–576.

24. van Nimwegen FA, Penders J, Stobberingh EE, Postma DS, Koppelman GH, Kerkhof M, et al. Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J Allergy Clin Immunol. 2011; 128:948–955.e1-3.

25. Kalliomäki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001; 107:129–134.

26. Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol. 2011; 31:Suppl 1. S29–S34.

27. Russell SL, Gold MJ, Hartmann M, Willing BP, Thorson L, Wlodarska M, et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 2012; 13:440–447.

28. Mommers M, Thijs C, Stelma F, Penders J, Reimerink J, van Ree R, et al. Timing of infection and development of wheeze, eczema, and atopic sensitization during the first 2 yr of life: the KOALA Birth Cohort Study. Pediatr Allergy Immunol. 2010; 21:983–989.

29. Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan-Müller G, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol. 2011; 128:646–652.e1-5.

30. Herbst T, Sichelstiel A, Schär C, Yadava K, Bürki K, Cahenzli J, et al. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am J Respir Crit Care Med. 2011; 184:198–205.

31. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011; 331:337–341.

32. Karimi K, Inman MD, Bienenstock J, Forsythe P. Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med. 2009; 179:186–193.

33. 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; 108:5354–5359.

34. Yasui H, Kiyoshima J, Hori T. Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota. Clin Diagn Lab Immunol. 2004; 11:675–679.

35. Fujimura KE, Demoor T, Rauch M, Faruqi AA, Jang S, Johnson CC, et al. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proc Natl Acad Sci U S A. 2014; 111:805–810.

36. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014; 20:159–166.

37. Huang YJ, Boushey HA. The microbiome in asthma. J Allergy Clin Immunol. 2015; 135:25–30.

38. Panzer AR, Lynch SV. Influence and effect of the human microbiome in allergy and asthma. Curr Opin Rheumatol. 2015; 27:373–380.

39. Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. Asthma-associated differences in microbial composition of induced sputum. J Allergy Clin Immunol. 2013; 131:346–352.e1-3.

40. Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V, Lau L, et al. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS One. 2014; 9:e100645.

41. Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, et al. The airway microbiome in patients with severe asthma: Associations with disease features and severity. J Allergy Clin Immunol. 2015; 136:874–884.

42. Pérez-Losada M, Castro-Nallar E, Bendall ML, Freishtat RJ, Crandall KA. Dual transcriptomic profiling of host and microbiota during health and disease in pediatric asthma. PLoS One. 2015; 10:e0131819.

43. Castro-Nallar E, Shen Y, Freishtat RJ, Pérez-Losada M, Manimaran S, Liu G, et al. Integrating microbial and host transcriptomics to characterize asthma-associated microbial communities. BMC Med Genomics. 2015; 8:50.

44. Cardenas PA, Cooper PJ, Cox MJ, Chico M, Arias C, Moffatt MF, et al. Upper airways microbiota in antibiotic-naïve wheezing and healthy infants from the tropics of rural Ecuador. PLoS One. 2012; 7:e46803.

45. 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; 17:704–715.

46. Simpson JL, Daly J, Baines KJ, Yang IA, Upham JW, Reynolds PN, et al. Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma. Eur Respir J. 2016; 47:792–800.

47. 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.

48. Tomosada Y, Chiba E, Zelaya H, Takahashi T, Tsukida K, Kitazawa H, et al. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol. 2013; 14:40.

49. Gollwitzer ES, Saglani S, Trompette A, Yadava K, Sherburn R, McCoy KD, et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat Med. 2014; 20:642–647.

50. Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, et al. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One. 2011; 6:e16384.

51. Garcia-Nuñez M, Millares L, Pomares X, Ferrari R, Pérez-Brocal V, Gallego M, et al. Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease. J Clin Microbiol. 2014; 52:4217–4223.

52. Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 2012; 7:e47305.

53. Sze MA, Utokaparch S, Elliott WM, Hogg JC, Hegele RG. Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD. BMJ Open. 2015; 5:e006677.

54. Sze MA, Dimitriu PA, Suzuki M, McDonough JE, Campbell JD, Brothers JF, et al. Host response to the lung microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015; 192:438–445.

55. Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis-Owen SA, Homola D, et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013; 188:1224–1231.

56. Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J Clin Microbiol. 2014; 52:2813–2823.

57. Wang Z, Bafadhel M, Haldar K, Spivak A, Mayhew D, Miller BE, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016; 47:1082–1092.