1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Lung Microbiota and Its Impact on the Mucosal Immune Phenotype

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Benjamin G. Wu1, Leopoldo N. Segal2
  • Editors: Robert Allen Britton3, Patrice D. Cani4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Medicine, NYU Division of Pulmonary, Critical Care, & Sleep Medicine, New York City, NY 10016; 2: Department of Medicine, NYU Division of Pulmonary, Critical Care, & Sleep Medicine, New York City, NY 10016; 3: Baylor College of Medicine, Houston, TX; 4: Université catholique de Louvain, Brussels, Belgium
  • Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0005-2016
  • Received 26 September 2016 Accepted 13 October 2016 Published 23 June 2017
  • Benjamin G. Wu, wub02@nyumc.org
image of Lung Microbiota and Its Impact on the Mucosal Immune Phenotype
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Lung Microbiota and Its Impact on the Mucosal Immune Phenotype, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/5/3/BAD-0005-2016-1.gif /docserver/preview/fulltext/microbiolspec/5/3/BAD-0005-2016-2.gif
  • Abstract:

    The use of culture-independent techniques has allowed us to appreciate that the upper and lower respiratory tract contain a diverse community of microbes in health and disease. Research has only recently explored the effects of the microbiome on the host immune response. The exposure of the human body to the bacterial environment is an important factor for immunological development; thus, the interaction between the microbiome and its host is critical to understanding the pathogenesis of disease. In this article, we discuss the mechanisms that determine the composition of the airway microbiome and its effects on the host immune response. With the use of ecological principles, we have learned how the lower airways constitute a unique niche subjected to frequent microbial migration (e.g., through aspiration) and constant immunological pressure. The discussion will focus on the possible inflammatory pathways that are up- and downregulated when the immune system is challenged by dysbiosis. Identification of potential markers and microbial targets to address the modulation of inflammation in early disease, when changes may have the most effect, will be critical for future therapies.

  • Citation: Wu B, Segal L. 2017. Lung Microbiota and Its Impact on the Mucosal Immune Phenotype. Microbiol Spectrum 5(3):BAD-0005-2016. doi:10.1128/microbiolspec.BAD-0005-2016.

Key Concept Ranking

Tumor Necrosis Factor alpha
0.43426618
0.43426618

References

1. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. 2007. The human microbiome project. Nature 449:804–810. http://dx.doi.org/10.1038/nature06244 [PubMed]
2. Ivanov II, Frutos RL, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, Finlay BB, Littman DR. 2008. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4:337–349. http://dx.doi.org/10.1016/j.chom.2008.09.009
3. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341. http://dx.doi.org/10.1126/science.1198469
4. Wright EK, Kamm MA, Teo SM, Inouye M, Wagner J, Kirkwood CD. 2015. Recent advances in characterizing the gastrointestinal microbiome in Crohn’s disease: a systematic review. Inflamm Bowel Dis 21:1219–1228. [PubMed]
5. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. 2004. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101:15718–15723. http://dx.doi.org/10.1073/pnas.0407076101 [PubMed]
6. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. 2011. Human nutrition, the gut microbiome and the immune system. Nature 474:327–336. http://dx.doi.org/10.1038/nature10213
7. Turnbaugh PJ, Gordon JI. 2009. The core gut microbiome, energy balance and obesity. J Physiol 587:4153–4158. http://dx.doi.org/10.1113/jphysiol.2009.174136
8. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. 2009. A core gut microbiome in obese and lean twins. Nature 457:480–484. http://dx.doi.org/10.1038/nature07540 [PubMed]
9. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19:576–585. http://dx.doi.org/10.1038/nm.3145
10. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 368:1575–1584. http://dx.doi.org/10.1056/NEJMoa1109400 [PubMed]
11. Tang WH, Wang Z, Shrestha K, Borowski AG, Wu Y, Troughton RW, Klein AL, Hazen SL. 2015. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Card Fail 21:91–96. http://dx.doi.org/10.1016/j.cardfail.2014.11.006 [PubMed]
12. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63. http://dx.doi.org/10.1038/nature09922
13. Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young VB. 2008. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis 197:435–438. http://dx.doi.org/10.1086/525047
14. Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, Goulding D, Rad R, Schreiber F, Brandt C, Deakin LJ, Pickard DJ, Duncan SH, Flint HJ, Clark TG, Parkhill J, Dougan G. 2012. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog 8:e1002995. http://dx.doi.org/10.1371/journal.ppat.1002995
15. Qin J, et al. 2012. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60. http://dx.doi.org/10.1038/nature11450
16. Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Krogh Pedersen H, Arumugam M, Kristiansen K, Voigt AY, Vestergaard H, Hercog R, Igor Costea P, Kultima JR, Li J, Jørgensen T, Levenez F, Dore J, MetaHIT Consortium, Nielsen HB, Brunak S, Raes J, Hansen T, Wang J, Ehrlich SD, Bork P, Pedersen O. 2015. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:262–266. http://dx.doi.org/10.1038/nature15766
17. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J. 2006. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55:205–211. http://dx.doi.org/10.1136/gut.2005.073817
18. Morgan XC, Kabakchiev B, Waldron L, Tyler AD, Tickle TL, Milgrom R, Stempak JM, Gevers D, Xavier RJ, Silverberg MS, Huttenhower C. 2015. Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol 16:67. http://dx.doi.org/10.1186/s13059-015-0637-x
19. Metzker ML. 2010. Sequencing technologies—the next generation. Nat Rev Genet 11:31–46. http://dx.doi.org/10.1038/nrg2626
20. Wu J, Peters BA, Dominianni C, Zhang Y, Pei Z, Yang L, Ma Y, Purdue MP, Jacobs EJ, Gapstur SM, Li H, Alekseyenko AV, Hayes RB, Ahn J. 2016. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J 10:2435–2446. http://dx.doi.org/10.1038/ismej.2016.37
21. Segal LN, Rom WN, Weiden MD. 2014. Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs. Ann Am Thorac Soc 11:108–116. http://dx.doi.org/10.1513/AnnalsATS.201310-339FR
22. Segal LN, Blaser MJ. 2014. A brave new world: the lung microbiota in an era of change. Ann Am Thorac Soc 11(Suppl 1):S21–S27. http://dx.doi.org/10.1513/AnnalsATS.201306-189MG
23. Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, Chen H, Berger KI, Goldring RM, Rom WN, Blaser MJ, Weiden MD. 2013. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome 1:19. http://dx.doi.org/10.1186/2049-2618-1-19
24. Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. 2016. The microbiome and the respiratory tract. Annu Rev Physiol 78:481–504. http://dx.doi.org/10.1146/annurev-physiol-021115-105238
25. Fujimura KE, Demoor T, Rauch M, Faruqi AA, Jang S, Johnson CC, Boushey HA, Zoratti E, Ownby D, Lukacs NW, Lynch SV. 2014. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proc Natl Acad Sci USA 111:805–810. http://dx.doi.org/10.1073/pnas.1310750111
26. Noverr MC, Falkowski NR, McDonald RA, McKenzie AN, Huffnagle GB. 2005. 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. http://dx.doi.org/10.1128/IAI.73.1.30-38.2005 [PubMed]
27. Noverr MC, Noggle RM, Toews GB, Huffnagle GB. 2004. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun 72:4996–5003. http://dx.doi.org/10.1128/IAI.72.9.4996-5003.2004
28. Sze MA, Dimitriu PA, Suzuki M, McDonough JE, Campbell JD, Brothers JF, Erb-Downward JR, Huffnagle GB, Hayashi S, Elliott WM, Cooper J, Sin DD, Lenburg ME, Spira A, Mohn WW, Hogg JC. 2015. Host response to the lung microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 192:438–445. http://dx.doi.org/10.1164/rccm.201502-0223OC [PubMed]
29. Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, Boushey H. 2015. The airway microbiome in patients with severe asthma: associations with disease features and severity. J Allergy Clin Immunol 136:874–884. http://dx.doi.org/10.1016/j.jaci.2015.05.044
30. Segal LN, Clemente JC, Tsay JCJ, Koralov SB, Keller BC, Wu BG, Li Y, Shen N, Ghedin E, Morris A, Diaz P, Huang L, Wikoff WR, Ubeda C, Artacho A, Rom WN, Sterman DH, Collman RG, Blaser MJ, Weiden MD. 2016. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol 1:16031. doi:10.1038/nmicrobiol.2016.31.
31. Twigg HL III, Morris A, Ghedin E, Curtis JL, Huffnagle GB, Crothers K, Campbell TB, Flores SC, Fontenot AP, Beck JM, Huang L, Lynch S, Knox KS, Weinstock G, Lung HIV Microbiome Project. 2013. Use of bronchoalveolar lavage to assess the respiratory microbiome: signal in the noise. Lancet Respir Med 1:354–356. http://dx.doi.org/10.1016/S2213-2600(13)70117-6
32. Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, Bushman FD, Collman RG. 2011. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med 184:957–963. http://dx.doi.org/10.1164/rccm.201104-0655OC
33. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, Littmann E, van den Brink MR, Jenq RR, Taur Y, Sander C, Cross JR, Toussaint NC, Xavier JB, Pamer EG. 2015. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517:205–208. http://dx.doi.org/10.1038/nature13828 [PubMed]
34. Charlson ES, Bittinger K, Chen J, Diamond JM, Li H, Collman RG, Bushman FD. 2012. Assessing bacterial populations in the lung by replicate analysis of samples from the upper and lower respiratory tracts. PLoS One 7:e42786. http://dx.doi.org/10.1371/journal.pone.0042786
35. Charlson ES, Chen J, Custers-Allen R, Bittinger K, Li H, Sinha R, Hwang J, Bushman FD, Collman RG. 2010. Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS One 5:e15216. http://dx.doi.org/10.1371/journal.pone.0015216
36. Shaker R, Hogan WJ. 2000. Reflex-mediated enhancement of airway protective mechanisms. Am J Med 108(Suppl 4a):8S–14S. http://dx.doi.org/10.1016/S0002-9343(99)00289-2
37. Kronenberger MB, Meyers AD. 1994. Dysphagia following head and neck cancer surgery. Dysphagia 9:236–244. http://dx.doi.org/10.1007/BF00301917
38. Bassis CM, Erb-Downward JR, Dickson RP, Freeman CM, Schmidt TM, Young VB, Beck JM, Curtis JL, Huffnagle GB. 2015. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio 6:e00037. http://dx.doi.org/10.1128/mBio.00037-15
39. Gleeson K, Eggli DF, Maxwell SL. 1997. Quantitative aspiration during sleep in normal subjects. Chest 111:1266–1272. http://dx.doi.org/10.1378/chest.111.5.1266 [PubMed]
40. Cvejic L, Harding R, Churchward T, Turton A, Finlay P, Massey D, Bardin PG, Guy P. 2011. Laryngeal penetration and aspiration in individuals with stable COPD. Respirology 16:269–275. http://dx.doi.org/10.1111/j.1440-1843.2010.01875.x [PubMed]
41. Morse CA, Quan SF, Mays MZ, Green C, Stephen G, Fass R. 2004. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin Gastroenterol Hepatol 2:761–768. http://dx.doi.org/10.1016/S1542-3565(04)00347-7
42. Teramoto S, Ohga E, Matsui H, Ishii T, Matsuse T, Ouchi Y. 1999. Obstructive sleep apnea syndrome may be a significant cause of gastroesophageal reflux disease in older people. J Am Geriatr Soc 47:1273–1274. http://dx.doi.org/10.1111/j.1532-5415.1999.tb05216.x
43. Field SK, Underwood M, Brant R, Cowie RL. 1996. Prevalence of gastroesophageal reflux symptoms in asthma. Chest 109:316–322. http://dx.doi.org/10.1378/chest.109.2.316
44. Scott RB, O’Loughlin EV, Gall DG. 1985. Gastroesophageal reflux in patients with cystic fibrosis. J Pediatr 106:223–227. http://dx.doi.org/10.1016/S0022-3476(85)80291-2
45. Koh WJ, Lee JH, Kwon YS, Lee KS, Suh GY, Chung MP, Kim H, Kwon OJ. 2007. Prevalence of gastroesophageal reflux disease in patients with nontuberculous mycobacterial lung disease. Chest 131:1825–1830. http://dx.doi.org/10.1378/chest.06-2280
46. Dickson RP, Erb-Downward JR, Prescott HC, Martinez FJ, Curtis JL, Lama VN, Huffnagle GB. 2014. Cell-associated bacteria in the human lung microbiome. Microbiome 2:28. http://dx.doi.org/10.1186/2049-2618-2-28
47. Beck JM, Schloss PD, Venkataraman A, Twigg H III, Jablonski KA, Bushman FD, Campbell TB, Charlson ES, Collman RG, Crothers K, Curtis JL, Drews KL, Flores SC, Fontenot AP, Foulkes MA, Frank I, Ghedin E, Huang L, Lynch SV, Morris A, Palmer BE, Schmidt TM, Sodergren E, Weinstock GM, Young VB, Lung HIV Microbiome Project. 2015. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am J Respir Crit Care Med 192:1335–1344. http://dx.doi.org/10.1164/rccm.201501-0128OC
48. Segal LN, Dickson RP. 2016. The lung microbiome in HIV. Getting to the HAART of the host-microbe interface. Am J Respir Crit Care Med 194:136–137. http://dx.doi.org/10.1164/rccm.201602-0280ED
49. Huxley EJ, Viroslav J, Gray WR, Pierce AK. 1978. Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am J Med 64:564–568. http://dx.doi.org/10.1016/0002-9343(78)90574-0
50. Simpson JL, Daly J, Baines KJ, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, Hugenholtz P, Willner D, Gibson PG. 2016. Airway dysbiosis: Haemophilus influenzae and Tropheryma in poorly controlled asthma. Eur Respir J 47:792–800. http://dx.doi.org/10.1183/13993003.00405-2015
51. Smits HH, Hiemstra PS, Prazeres da Costa C, Ege M, Edwards M, Garn H, Howarth PH, Jartti T, de Jong EC, Maizels RM, Marsland BJ, McSorley HJ, Müller A, Pfefferle PI, Savelkoul H, Schwarze J, Unger WW, von Mutius E, Yazdanbakhsh M, Taube C. 2016. Microbes and asthma: opportunities for intervention. J Allergy Clin Immunol 137:690–697. http://dx.doi.org/10.1016/j.jaci.2016.01.004
52. Huang YJ. 2015. The respiratory microbiome and innate immunity in asthma. Curr Opin Pulm Med 21:27–32. http://dx.doi.org/10.1097/MCP.0000000000000124
53. Huang YJ. 2013. Asthma microbiome studies and the potential for new therapeutic strategies. Curr Allergy Asthma Rep 13:453–461. http://dx.doi.org/10.1007/s11882-013-0355-y
54. Huang YJ, Boushey HA. 2015. The microbiome in asthma. J Allergy Clin Immunol 135:25–30. http://dx.doi.org/10.1016/j.jaci.2014.11.011
55. Huang YJ, Boushey HA. 2014. The microbiome and asthma. Ann Am Thorac Soc 11(Suppl 1):S48–S51. http://dx.doi.org/10.1513/AnnalsATS.201306-187MG [PubMed]
56. Huang YJ, Boushey HA. 2013. The bronchial microbiome and asthma phenotypes. Am J Respir Crit Care Med 188:1178–1180. http://dx.doi.org/10.1164/rccm.201309-1702ED [PubMed]
57. Huang YJ, Charlson ES, Collman RG, Colombini-Hatch S, Martinez FD, Senior RM. 2013. 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 187:1382–1387. http://dx.doi.org/10.1164/rccm.201303-0488WS
58. Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, Davies J, Ervine A, Poulter L, Pachter L, Moffatt MF, Cookson WO. 2010. Disordered microbial communities in asthmatic airways. PLoS One 5:e8578. http://dx.doi.org/10.1371/journal.pone.0008578
59. Lynch SV, Bruce KD. 2013. The cystic fibrosis airway microbiome. Cold Spring Harb Perspect Med 3:a009738. http://dx.doi.org/10.1101/cshperspect.a009738
60. Huang YJ, LiPuma JJ. 2016. The microbiome in cystic fibrosis. Clin Chest Med 37:59–67. http://dx.doi.org/10.1016/j.ccm.2015.10.003
61. Whelan FJ, Surette MG. 2015. Clinical insights into pulmonary exacerbations in cystic fibrosis from the microbiome. What are we missing? Ann Am Thorac Soc 12(Suppl 2):S207–S211. [PubMed]
62. Caverly LJ, Zhao J, LiPuma JJ. 2015. Cystic fibrosis lung microbiome: opportunities to reconsider management of airway infection. Pediatr Pulmonol 50(Suppl 40):S31–S38. http://dx.doi.org/10.1002/ppul.23243
63. Twigg HL III, Knox KS, Zhou J, Crothers KA, Nelson DE, Toh E, Day RB, Lin H, Gao X, Dong Q, Mi D, Katz BP, Sodergren E, Weinstock GM. 2016. Effect of advanced HIV infection on the respiratory microbiome. Am J Respir Crit Care Med 194:226–235. http://dx.doi.org/10.1164/rccm.201509-1875OC [PubMed]
64. Lozupone C, Cota-Gomez A, Palmer BE, Linderman DJ, Charlson ES, Sodergren E, Mitreva M, Abubucker S, Martin J, Yao G, Campbell TB, Flores SC, Ackerman G, Stombaugh J, Ursell L, Beck JM, Curtis JL, Young VB, Lynch SV, Huang L, Weinstock GM, Knox KS, Twigg H, Morris A, Ghedin E, Bushman FD, Collman RG, Knight R, Fontenot AP, Lung HIV Microbiome Project. 2013. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med 187:1110–1117. http://dx.doi.org/10.1164/rccm.201211-2145OC
65. Sze MA, Dimitriu PA, Hayashi S, Elliott WM, McDonough JE, Gosselink JV, Cooper J, Sin DD, Mohn WW, Hogg JC. 2012. The lung tissue microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 185:1073–1080. http://dx.doi.org/10.1164/rccm.201111-2075OC
66. Sze MA, Hogg JC, Sin DD. 2014. Bacterial microbiome of lungs in COPD. Int J Chron Obstruct Pulmon Dis 9:229–238. [PubMed]
67. Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AW. 2014. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol 12:87. http://dx.doi.org/10.1186/s12915-014-0087-z
68. Venkataraman A, Bassis CM, Beck JM, Young VB, Curtis JL, Huffnagle GB, Schmidt TM. 2015. Application of a neutral community model to assess structuring of the human lung microbiome. mBio 6:e02284-14. http://dx.doi.org/10.1128/mBio.02284-14 [PubMed]
69. Knights D, Kuczynski J, Charlson ES, Zaneveld J, Mozer MC, Collman RG, Bushman FD, Knight R, Kelley ST. 2011. Bayesian community-wide culture-independent microbial source tracking. Nat Methods 8:761–763. http://dx.doi.org/10.1038/nmeth.1650
70. Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, Darveau RP, Curtis MA. 2011. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe 10:497–506. http://dx.doi.org/10.1016/j.chom.2011.10.006
71. Pop M, Paulson JN, Chakraborty S, Astrovskaya I, Lindsay BR, Li S, Bravo HC, Harro C, Parkhill J, Walker AW, Walker RI, Sack DA, Stine OC. 2016. Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment. BMC Genomics 17:440. http://dx.doi.org/10.1186/s12864-016-2777-0
72. Schwartz DA, Quinn TJ, Thorne PS, Sayeed S, Yi AK, Krieg AM. 1997. CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract. J Clin Invest 100:68–73. http://dx.doi.org/10.1172/JCI119523
73. Riley RL. 1957. Aerial dissemination of pulmonary tuberculosis. Am Rev Tuberc 76:931–941. [PubMed]
74. Riley RL, Mills CC, O’Grady F, Sultan LU, Wittstadt F, Shivpuri DN. 1962. Infectiousness of air from a tuberculosis ward. Ultraviolet irradiation of infected air: comparative infectiousness of different patients. Am Rev Respir Dis 85:511–525. [PubMed]
75. Adams RI, Bateman AC, Bik HM, Meadow JF. 2015. Microbiota of the indoor environment: a meta-analysis. Microbiome 3:49. http://dx.doi.org/10.1186/s40168-015-0108-3
76. Meadow JF, Altrichter AE, Bateman AC, Stenson J, Brown GZ, Green JL, Bohannan BJ. 2015. Humans differ in their personal microbial cloud. PeerJ 3:e1258. http://dx.doi.org/10.7717/peerj.1258
77. Stephenson MF, Mfuna L, Dowd SE, Wolcott RD, Barbeau J, Poisson M, James G, Desrosiers M. 2010. Molecular characterization of the polymicrobial flora in chronic rhinosinusitis. J Otolaryngol Head Neck Surg 39:182–187. [PubMed]
78. Boase S, Foreman A, Cleland E, Tan L, Melton-Kreft R, Pant H, Hu FZ, Ehrlich GD, Wormald PJ. 2013. The microbiome of chronic rhinosinusitis: culture, molecular diagnostics and biofilm detection. BMC Infect Dis 13:210. http://dx.doi.org/10.1186/1471-2334-13-210
79. Blaser MJ, Chen Y, Reibman J. 2008. Does Helicobacter pylori protect against asthma and allergy? Gut 57:561–567. http://dx.doi.org/10.1136/gut.2007.133462
80. Reibman J, Marmor M, Filner J, Fernandez-Beros ME, Rogers L, Perez-Perez GI, Blaser MJ. 2008. Asthma is inversely associated with Helicobacter pylori status in an urban population. PLoS One 3:e4060. http://dx.doi.org/10.1371/journal.pone.0004060
81. Rosen R, Hu L, Amirault J, Khatwa U, Ward DV, Onderdonk A. 2015. 16S community profiling identifies proton pump inhibitor related differences in gastric, lung, and oropharyngeal microflora. J Pediatr 166:917–923. http://dx.doi.org/10.1016/j.jpeds.2014.12.067
82. Souza DG, Vieira AT, Soares AC, Pinho V, Nicoli JR, Vieira LQ, Teixeira MM. 2004. The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J Immunol 173:4137–4146. http://dx.doi.org/10.4049/jimmunol.173.6.4137
83. Silvestri L, van Saene HK, Zandstra DF, Marshall JC, Gregori D, Gullo A. 2010. Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: systematic review of randomized controlled trials. Crit Care Med 38:1370–1376. http://dx.doi.org/10.1097/CCM.0b013e3181d9db8c [PubMed]
84. Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, Young VB, Toews GB, Curtis JL, Sundaram B, Martinez FJ, Huffnagle GB. 2011. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS One 6:e16384. http://dx.doi.org/10.1371/journal.pone.0016384 [PubMed]
85. Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, Flores SC, Fontenot AP, Ghedin E, Huang L, Jablonski K, Kleerup E, Lynch SV, Sodergren E, Twigg H, Young VB, Bassis CM, Venkataraman A, Schmidt TM, Weinstock GM, Lung HIV Microbiome Project. 2013. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med 187:1067–1075. http://dx.doi.org/10.1164/rccm.201210-1913OC [PubMed]
86. Lomolino MV, Brown JH. 2009. The reticulating phylogeny of island biogeography theory. Q Rev Biol 84:357–390. http://dx.doi.org/10.1086/648123
87. Dickson RP, Erb-Downward JR, Freeman CM, McCloskey L, Beck JM, Huffnagle GB, Curtis JL. 2015. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann Am Thorac Soc 12:821–830. http://dx.doi.org/10.1513/AnnalsATS.201501-029OC [PubMed]
88. Dickson RP, Erb-Downward JR, Huffnagle GB. 2014. Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis. Lancet Respir Med 2:238–246. http://dx.doi.org/10.1016/S2213-2600(14)70028-1
89. Dickson RP, Martinez FJ, Huffnagle GB. 2014. The role of the microbiome in exacerbations of chronic lung diseases. Lancet 384:691–702. http://dx.doi.org/10.1016/S0140-6736(14)61136-3
90. Whiteson KL, Bailey B, Bergkessel M, Conrad D, Delhaes L, Felts B, Harris JK, Hunter R, Lim YW, Maughan H, Quinn R, Salamon P, Sullivan J, Wagner BD, Rainey PB. 2014. The upper respiratory tract as a microbial source for pulmonary infections in cystic fibrosis. Parallels from island biogeography. Am J Respir Crit Care Med 189:1309–1315. http://dx.doi.org/10.1164/rccm.201312-2129PP
91. Veldhuizen R, Nag K, Orgeig S, Possmayer F. 1998. The role of lipids in pulmonary surfactant. Biochim Biophys Acta 1408:90–108. http://dx.doi.org/10.1016/S0925-4439(98)00061-1
92. West JB. 2012. Respiratory Physiology: The Essentials, 9th ed. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, PA.
93. Lieberman TD, Flett KB, Yelin I, Martin TR, McAdam AJ, Priebe GP, Kishony R. 2014. Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures. Nat Genet 46:82–87. http://dx.doi.org/10.1038/ng.2848
94. Rogan MP, Geraghty P, Greene CM, O’Neill SJ, Taggart CC, McElvaney NG. 2006. Antimicrobial proteins and polypeptides in pulmonary innate defence. Respir Res 7:29. http://dx.doi.org/10.1186/1465-9921-7-29
95. Richmond BW, Brucker RM, Han W, Du RH, Zhang Y, Cheng DS, Gleaves L, Abdolrasulnia R, Polosukhina D, Clark PE, Bordenstein SR, Blackwell TS, Polosukhin VV. 2016. Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency. Nat Commun 7:11240. http://dx.doi.org/10.1038/ncomms11240
96. Costerton JW, Lewandowski Z, DeBeer D, Caldwell D, Korber D, James G. 1994. Biofilms, the customized microniche. J Bacteriol 176:2137–2142. http://dx.doi.org/10.1128/jb.176.8.2137-2142.1994
97. Whitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS. 2002. Extracellular DNA required for bacterial biofilm formation. Science 295:1487. http://dx.doi.org/10.1126/science.295.5559.1487
98. Costerton JW, Stewart PS, Greenberg EP. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322. http://dx.doi.org/10.1126/science.284.5418.1318 [PubMed]
99. Twigg HL III. 1998. Pulmonary host defenses. J Thorac Imaging 13:221–233. http://dx.doi.org/10.1097/00005382-199810000-00003
100. Renshaw SA, Parmar JS, Singleton V, Rowe SJ, Dockrell DH, Dower SK, Bingle CD, Chilvers ER, Whyte MK. 2003. Acceleration of human neutrophil apoptosis by TRAIL. J Immunol 170:1027–1033. http://dx.doi.org/10.4049/jimmunol.170.2.1027 [PubMed]
101. Chmiel JF, Davis PB. 2003. State of the art: why do the lungs of patients with cystic fibrosis become infected and why can’t they clear the infection? Respir Res 4:8. http://dx.doi.org/10.1186/1465-9921-4-8
102. Klemm P, Schembri MA. 2000. Bacterial adhesins: function and structure. Int J Med Microbiol 290:27–35. http://dx.doi.org/10.1016/S1438-4221(00)80102-2
103. Deslée G, Mal H, Dutau H, Bourdin A, Vergnon JM, Pison C, Kessler R, Jounieaux V, Thiberville L, Leroy S, Marceau A, Laroumagne S, Mallet JP, Dukic S, Barbe C, Bulsei J, Jolly D, Durand-Zaleski I, Marquette CH, REVOLENS Study Group. 2016. Lung volume reduction coil treatment vs usual care in patients with severe emphysema: the REVOLENS randomized clinical trial. JAMA 315:175–184. http://dx.doi.org/10.1001/jama.2015.17821 [PubMed]
104. Oliver A, Cantón R, Campo P, Baquero F, Blázquez J. 2000. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–1254. http://dx.doi.org/10.1126/science.288.5469.1251
105. Rello J, Ausina V, Ricart M, Castella J, Prats G. 1993. Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 104:1230–1235. http://dx.doi.org/10.1378/chest.104.4.1230
106. Poroyko V, Meng F, Meliton A, Afonyushkin T, Ulanov A, Semenyuk E, Latif O, Tesic V, Birukova AA, Birukov KG. 2015. Alterations of lung microbiota in a mouse model of LPS-induced lung injury. Am J Physiol Lung Cell Mol Physiol 309:L76–L83. http://dx.doi.org/10.1152/ajplung.00061.2014 [PubMed][CrossRef]
107. Dickson RP, Erb-Downward JR, Huffnagle GB. 2015. Homeostasis and its disruption in the lung microbiome. Am J Physiol Lung Cell Mol Physiol 309:L1047–L1055.
108. Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis-Owen SA, Homola D, Trujillo-Torralbo MB, Elkin S, Kon OM, Cookson WO, Moffatt MF, Johnston SL. 2013. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 188:1224–1231. http://dx.doi.org/10.1164/rccm.201302-0341OC [PubMed]
109. Twigg H, Knox KS, Zhou J, Crothers K, Nelson D, Toh E, Day RB, Lin H, Gao X, Dong Q, Mi D, Katz BP, Sodergren E, Weinstock G. 2016. Effect of advanced HIV infection on the respiratory microbiome. Am J Respir Crit Care Med 194:226–235. doi:10.1164/rccm.201509-1875OC.
110. Cui L, Lucht L, Tipton L, Rogers MB, Fitch A, Kessinger C, Camp D, Kingsley L, Leo N, Greenblatt RM, Fong S, Stone S, Dermand JC, Kleerup EC, Huang L, Morris A, Ghedin E. 2015. Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease. Am J Respir Crit Care Med 191:932–942. http://dx.doi.org/10.1164/rccm.201409-1583OC [PubMed]
111. Gohy ST, Detry BR, Lecocq M, Bouzin C, Weynand BA, Amatngalim GD, Sibille YM, Pilette C. 2014. Polymeric immunoglobulin receptor down-regulation in chronic obstructive pulmonary disease. Persistence in the cultured epithelium and role of transforming growth factor-β. Am J Respir Crit Care Med 190:509–521. http://dx.doi.org/10.1164/rccm.201311-1971OC [PubMed]
112. Polosukhin VV, Cates JM, Lawson WE, Zaynagetdinov R, Milstone AP, Massion PP, Ocak S, Ware LB, Lee JW, Bowler RP, Kononov AV, Randell SH, Blackwell TS. 2011. Bronchial secretory immunoglobulin a deficiency correlates with airway inflammation and progression of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 184:317–327. http://dx.doi.org/10.1164/rccm.201010-1629OC
113. Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantragoon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Van Sinderen D, Mak JY, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J. 2014. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 509:361–365. http://dx.doi.org/10.1038/nature13160 [PubMed]
114. Gapin L. 2014. Check MAIT. J Immunol 192:4475–4480. http://dx.doi.org/10.4049/jimmunol.1400119 [PubMed]
115. Hinks TS, Wallington JC, Williams AP, Djukanovič R, Staples KJ, Wilkinson TM. 2016. Steroid-induced deficiency of mucosal-associated invariant T cells in the COPD lung: implications for NTHi infection. Am J Respir Crit Care Med 194:1208–1218. http://dx.doi.org/10.1164/rccm.201601-0002OC
116. Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. 2012. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One 7:e47305. http://dx.doi.org/10.1371/journal.pone.0047305
117. Huang YJ, Kim E, Cox MJ, Brodie EL, Brown R, Wiener-Kronish JP, Lynch SV. 2010. A persistent and diverse airway microbiota present during chronic obstructive pulmonary disease exacerbations. OMICS 14:9–59. [PubMed]
118. Segal LN, Clemente JC, Wu BG, Wikoff WR, Gao Z, Li Y, Ko JP, Rom WN, Blaser MJ, Weiden MD. 2016. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung. Thorax 72:13–22. 10.1136/thoraxjnl-2016-208599. [PubMed]
119. Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS, Liu J, Woyke T, Allgaier M, Bristow J, Wiener-Kronish JP, Sutherland ER, King TS, Icitovic N, Martin RJ, Calhoun WJ, Castro M, Denlinger LC, Dimango E, Kraft M, Peters SP, Wasserman SI, Wechsler ME, Boushey HA, Lynch SV, National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network. 2011. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol 127:372–381.e1-3. [PubMed]
120. Fujimura KE, Johnson CC, Ownby DR, Cox MJ, Brodie EL, Havstad SL, Zoratti EM, Woodcroft KJ, Bobbitt KR, Wegienka G, Boushey HA, Lynch SV. 2010. Man’s best friend? The effect of pet ownership on house dust microbial communities. J Allergy Clin Immunol 126:410–412.e1-3. [PubMed]
121. Ege MJ, Mayer M, Normand AC, Genuneit J, Cookson WO, Braun-Fahrländer C, Heederik D, Piarroux R, von Mutius E, GABRIELA Transregio 22 Study Group. 2011. Exposure to environmental microorganisms and childhood asthma. N Engl J Med 364:701–709. http://dx.doi.org/10.1056/NEJMoa1007302 [PubMed]
122. Bisgaard H, Hermansen MN, Buchvald F, Loland L, Halkjaer LB, Bønnelykke K, Brasholt M, Heltberg A, Vissing NH, Thorsen SV, Stage M, Pipper CB. 2007. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 357:1487–1495. http://dx.doi.org/10.1056/NEJMoa052632 [PubMed]
123. Huang EY, Inoue T, Leone VA, Dalal S, Touw K, Wang Y, Musch MW, Theriault B, Higuchi K, Donovan S, Gilbert J, Chang EB. 2015. Using corticosteroids to reshape the gut microbiome: implications for inflammatory bowel diseases. Inflamm Bowel Dis 21:963–972. http://dx.doi.org/10.1097/MIB.0000000000000332 [PubMed]
124. Gilligan PH. 2014. Infections in patients with cystic fibrosis: diagnostic microbiology update. Clin Lab Med 34:197–217. http://dx.doi.org/10.1016/j.cll.2014.02.001 [PubMed]
125. Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. 2010. Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA 303:2386–2392. http://dx.doi.org/10.1001/jama.2010.791
126. Martiniano SL, Nick JA. 2015. Nontuberculous mycobacterial infections in cystic fibrosis. Clin Chest Med 36:101–115. http://dx.doi.org/10.1016/j.ccm.2014.11.003 [PubMed]
127. van der Gast CJ, Walker AW, Stressmann FA, Rogers GB, Scott P, Daniels TW, Carroll MP, Parkhill J, Bruce KD. 2011. Partitioning core and satellite taxa from within cystic fibrosis lung bacterial communities. ISME J 5:780–791. http://dx.doi.org/10.1038/ismej.2010.175
128. Willner D, Haynes MR, Furlan M, Schmieder R, Lim YW, Rainey PB, Rohwer F, Conrad D. 2012. Spatial distribution of microbial communities in the cystic fibrosis lung. ISME J 6:471–474. http://dx.doi.org/10.1038/ismej.2011.104 [PubMed]
129. Coburn B, Wang PW, Diaz Caballero J, Clark ST, Brahma V, Donaldson S, Zhang Y, Surendra A, Gong Y, Elizabeth Tullis D, Yau YC, Waters VJ, Hwang DM, Guttman DS. 2015. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 5:10241. http://dx.doi.org/10.1038/srep10241
130. Goddard AF, Staudinger BJ, Dowd SE, Joshi-Datar A, Wolcott RD, Aitken ML, Fligner CL, Singh PK. 2012. Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota. Proc Natl Acad Sci USA 109:13769–13774. http://dx.doi.org/10.1073/pnas.1107435109
131. Ghorbani P, Santhakumar P, Hu Q, Djiadeu P, Wolever TM, Palaniyar N, Grasemann H. 2015. Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth. Eur Respir J 46:1033–1045. http://dx.doi.org/10.1183/09031936.00143614
132. Clark JA, Coopersmith CM. 2007. Intestinal crosstalk: a new paradigm for understanding the gut as the “motor” of critical illness. Shock 28:384–393. http://dx.doi.org/10.1097/shk.0b013e31805569df
133. Klingensmith NJ, Coopersmith CM. 2016. The gut as the motor of multiple organ dysfunction in critical illness. Crit Care Clin 32:203–212. http://dx.doi.org/10.1016/j.ccc.2015.11.004
134. Ownby DR, Johnson CC, Peterson EL. 2002. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963–972. http://dx.doi.org/10.1001/jama.288.8.963
135. von Mutius E, Vercelli D. 2010. Farm living: effects on childhood asthma and allergy. Nat Rev Immunol 10:861–868. http://dx.doi.org/10.1038/nri2871 [PubMed]
136. Bazett M, Bergeron ME, Haston CK. 2016. Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model. Sci Rep 6:19189. http://dx.doi.org/10.1038/srep19189
137. Bazett M, Honeyman L, Stefanov AN, Pope CE, Hoffman LR, Haston CK. 2015. Cystic fibrosis mouse model-dependent intestinal structure and gut microbiome. Mamm Genome 26:222–234. http://dx.doi.org/10.1007/s00335-015-9560-4 [PubMed]
138. Segal LN, Blaser MJ. 2015. Harnessing the early-life microbiota to protect children with cystic fibrosis. J Pediatr 167:16–18.e11. [PubMed]
139. Hoen AG, Li J, Moulton LA, O’Toole GA, Housman ML, Koestler DC, Guill MF, Moore JH, Hibberd PL, Morrison HG, Sogin ML, Karagas MR, Madan JC. 2015. Associations between gut microbial colonization in early life and respiratory outcomes in cystic fibrosis. J Pediatr 167:138–147.e1-3. [PubMed]
140. Harris B, Morjaria SM, Littmann ER, Geyer AI, Stover DE, Barker JN, Giralt SA, Taur Y, Pamer EG. 2016. Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation. Am J Respir Crit Care Med 194:450–463. http://dx.doi.org/10.1164/rccm.201507-1491OC
141. Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, O’Leary CE, Oliver PM, Kolls JK, Weiser JN, Worthen GS. 2014. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med 20:524–530. http://dx.doi.org/10.1038/nm.3542 [PubMed]
142. Caballero S, Pamer EG. 2015. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu Rev Immunol 33:227–256. http://dx.doi.org/10.1146/annurev-immunol-032713-120238
143. Schuijt TJ, van der Poll T, de Vos WM, Wiersinga WJ. 2013. The intestinal microbiota and host immune interactions in the critically ill. Trends Microbiol 21:221–229. http://dx.doi.org/10.1016/j.tim.2013.02.001
144. Schuijt TJ, Lankelma JM, Scicluna BP, de Sousa e Melo F, Roelofs JJ, de Boer JD, Hoogendijk AJ, de Beer R, de Vos A, Belzer C, de Vos WM, van der Poll T, Wiersinga WJ. 2016. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut 65:575–583. http://dx.doi.org/10.1136/gutjnl-2015-309728
145. Kumar P, Monin L, Castillo P, Elsegeiny W, Horne W, Eddens T, Vikram A, Good M, Schoenborn AA, Bibby K, Montelaro RC, Metzger DW, Gulati AS, Kolls JK. 2016. Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity 44:659–671. http://dx.doi.org/10.1016/j.immuni.2016.02.007
146. Tanabe S. 2013. The effect of probiotics and gut microbiota on Th17 cells. Int Rev Immunol 32:511–525. http://dx.doi.org/10.3109/08830185.2013.839665
147. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498. http://dx.doi.org/10.1016/j.cell.2009.09.033
148. Suzuki K, Meek B, Doi Y, Muramatsu M, Chiba T, Honjo T, Fagarasan S. 2004. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc Natl Acad Sci USA 101:1981–1986. http://dx.doi.org/10.1073/pnas.0307317101 [PubMed]
149. Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R. 2011. UniFrac: an effective distance metric for microbial community comparison. ISME J 5:169–172. http://dx.doi.org/10.1038/ismej.2010.133
150. Yadava K, Pattaroni C, Sichelstiel AK, Trompette A, Gollwitzer ES, Salami O, von Garnier C, Nicod LP, Marsland BJ. 2016. Microbiota promotes chronic pulmonary inflammation by enhancing IL-17A and autoantibodies. Am J Respir Crit Care Med 193:975–987. http://dx.doi.org/10.1164/rccm.201504-0779OC [PubMed]
151. McDermott AJ, Huffnagle GB. 2014. The microbiome and regulation of mucosal immunity. Immunology 142:24–31. http://dx.doi.org/10.1111/imm.12231 [PubMed]
152. Byrd AL, Segre JA. 2016. Infectious disease. Adapting Koch’s postulates. Science 351:224–226. http://dx.doi.org/10.1126/science.aad6753
153. Koch R. 1952. Tuberculosis etiology. Dtsch Gesundheitsw 7:457–465. (In German.) [PubMed]
154. Fredricks DN, Relman DA. 1996. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin Microbiol Rev 9:18–33. [PubMed]
155. Wommack KE, Ravel J. 2013. Microbiome, demystifying the role of microbial communities in the biosphere. Microbiome 1:1. http://dx.doi.org/10.1186/2049-2618-1-1
156. Dickson RP. 2016. The microbiome and critical illness. Lancet Respir Med 4:59–72. http://dx.doi.org/10.1016/S2213-2600(15)00427-0
microbiolspec.BAD-0005-2016.citations
cm/5/3
content/journal/microbiolspec/10.1128/microbiolspec.BAD-0005-2016
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.BAD-0005-2016
2017-06-23
2017-09-22

Abstract:

The use of culture-independent techniques has allowed us to appreciate that the upper and lower respiratory tract contain a diverse community of microbes in health and disease. Research has only recently explored the effects of the microbiome on the host immune response. The exposure of the human body to the bacterial environment is an important factor for immunological development; thus, the interaction between the microbiome and its host is critical to understanding the pathogenesis of disease. In this article, we discuss the mechanisms that determine the composition of the airway microbiome and its effects on the host immune response. With the use of ecological principles, we have learned how the lower airways constitute a unique niche subjected to frequent microbial migration (e.g., through aspiration) and constant immunological pressure. The discussion will focus on the possible inflammatory pathways that are up- and downregulated when the immune system is challenged by dysbiosis. Identification of potential markers and microbial targets to address the modulation of inflammation in early disease, when changes may have the most effect, will be critical for future therapies.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Conceptual model: signal-to-noise ratio. Healthy gastrointestinal microbiome, where there is an organ of healthy biomass and background “noise” or signal amplified by background (e.g., background microbiota present in the colonoscope) that does not represent the gut microbiome. This background microbiome is overwhelmed by the large biomass present the sample. Healthy lung microbiome, where there is relatively low biomass and background signals tend to overwhelm the lung microbiome signal. Diseased gastrointestinal microbiome, where the pathogenic signal (dysbiosis) will eventually overcome the high underlying biomass. The pathogenic signal will overpower the background microbiome and be apparent given the high amount of biomass present in the gut. Diseased lung microbiome. Unlike the diseased gut microbiome, the pathogenic signal may be confounded by the background noise and may not be apparent until sufficient progression of disease supports the altered dysbiosis.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0005-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Host-microbiota interaction in the lung. This schema represents the normal lung microbiome and its dysbiosis. In this model, enrichment with background taxa (represented as blue bacteria) in pneumotype occurs in a lung with preserved mucociliary clearance of microorganisms and minimal inflammatory signals within the lung. In the presence of enrichment of the lower airway microbiome with oral taxa (represented as red bacteria) in pneumotype, there will be upregulation of the Th17 inflammatory phenotype and recruitment of neutrophils and lymphocytes. PMN, polymorphonuclear leukocyte.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.BAD-0005-2016
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error