Homeostasis and Its Disruption in the Lung Microbiome

Overview

Journal Am J Physiol Lung Cell Mol Physiol

Publisher American Physiological Society

Specialties Cell Biology
Molecular Biology
Physiology
Pulmonary Medicine

Date 2015 Oct 4

PMID 26432870

Citations 80

Authors

Robert P Dickson

John R Erb-Downward

Gary B Huffnagle

Affiliations

Soon will be listed here.

Abstract

The disciplines of physiology and ecology are united by the shared centrality of the concept of homeostasis: the stability of a complex system via internal mechanisms of self-regulation, resilient to external perturbation. In the past decade, these fields of study have been bridged by the discovery of the lung microbiome. The respiratory tract, long considered sterile, is in fact a dynamic ecosystem of microbiota, intimately associated with the host inflammatory response, altered in disease states. If the microbiome is a "newly discovered organ," ecology is the language we use to explain how it establishes, maintains, and loses homeostasis. In this essay, we review recent insights into the feedback mechanisms by which the lung microbiome and the host response are regulated in health and dysregulated in acute and chronic lung disease. We propose three explanatory models supported by recent studies: the adapted island model of lung biogeography, nutritional homeostasis at the host-microbiome interface, and interkingdom signaling and the community stress response.

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References

Goddard A, Staudinger B, Dowd S, Joshi-Datar A, Wolcott R, Aitken M . Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota. Proc Natl Acad Sci U S A. 2012; 109(34):13769-74. PMC: 3427132. DOI: 10.1073/pnas.1107435109. View

Amberson J . A clinical consideration of abscesses and cavities of the lung. Bull Johns Hopkins Hosp. 1954; 94(5):227-37. View

Kanangat S, Meduri G, Tolley E, Patterson D, Meduri C, Pak C . Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infect Immun. 1999; 67(6):2834-40. PMC: 96589. DOI: 10.1128/IAI.67.6.2834-2840.1999. View

Segal L, Alekseyenko A, Clemente J, Kulkarni R, Wu B, Gao Z . Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2014; 1(1):19. PMC: 3971609. DOI: 10.1186/2049-2618-1-19. View

Dickson R, Erb-Downward J, Huffnagle G . Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis. Lancet Respir Med. 2014; 2(3):238-46. PMC: 4004084. DOI: 10.1016/S2213-2600(14)70028-1. View

Kaza S, McClean S, Callaghan M . IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteria. Int J Med Microbiol. 2010; 301(1):26-33. DOI: 10.1016/j.ijmm.2010.06.005. View

Willner D, Haynes M, Furlan M, Schmieder R, Lim Y, Rainey P . Spatial distribution of microbial communities in the cystic fibrosis lung. ISME J. 2011; 6(2):471-4. PMC: 3260497. DOI: 10.1038/ismej.2011.104. View

Freestone P, Hirst R, Sandrini S, Sharaff F, Fry H, Hyman S . Pseudomonas aeruginosa-catecholamine inotrope interactions: a contributory factor in the development of ventilator-associated pneumonia?. Chest. 2012; 142(5):1200-1210. DOI: 10.1378/chest.11-2614. View

Plotkin B, Roose R, Erikson Q, Viselli S . Effect of androgens and glucocorticoids on microbial growth and antimicrobial susceptibility. Curr Microbiol. 2004; 47(6):514-20. DOI: 10.1007/s00284-003-4080-y. View

10.

Zaborina O, Lepine F, Xiao G, Valuckaite V, Chen Y, Li T . Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa. PLoS Pathog. 2007; 3(3):e35. PMC: 1828698. DOI: 10.1371/journal.ppat.0030035. View

11.

Morris A, Beck J, Schloss P, Campbell T, Crothers K, Curtis J . Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013; 187(10):1067-75. PMC: 3734620. DOI: 10.1164/rccm.201210-1913OC. View

12.

Gunther A, Siebert C, Schmidt R, Ziegler S, Grimminger F, Yabut M . Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema. Am J Respir Crit Care Med. 1996; 153(1):176-84. DOI: 10.1164/ajrccm.153.1.8542113. View

13.

Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C . Disordered microbial communities in asthmatic airways. PLoS One. 2010; 5(1):e8578. PMC: 2798952. DOI: 10.1371/journal.pone.0008578. View

14.

Porat R, Clark B, Wolff S, Dinarello C . Enhancement of growth of virulent strains of Escherichia coli by interleukin-1. Science. 1991; 254(5030):430-2. DOI: 10.1126/science.1833820. View

15.

Zhang X, Essmann M, BURT E, LARSEN B . Estrogen effects on Candida albicans: a potential virulence-regulating mechanism. J Infect Dis. 2000; 181(4):1441-6. DOI: 10.1086/315406. View

16.

Poroyko V, Meng F, Meliton A, Afonyushkin T, Ulanov A, Semenyuk E . Alterations of lung microbiota in a mouse model of LPS-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2015; 309(1):L76-83. PMC: 4491514. DOI: 10.1152/ajplung.00061.2014. View

17.

Monton C, Torres A, Filella X, Xaubet A, de la Bellacasa J . Cytokine expression in severe pneumonia: a bronchoalveolar lavage study. Crit Care Med. 1999; 27(9):1745-53. DOI: 10.1097/00003246-199909000-00008. View

18.

Andersson S, Zomorodipour A, Andersson J, Sicheritz-Ponten T, Alsmark U, Podowski R . The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature. 1998; 396(6707):133-40. DOI: 10.1038/24094. View

19.

Dickson R, Martinez F, Huffnagle G . The role of the microbiome in exacerbations of chronic lung diseases. Lancet. 2014; 384(9944):691-702. PMC: 4166502. DOI: 10.1016/S0140-6736(14)61136-3. View

20.

Lozupone C, Cota-Gomez A, Palmer B, Linderman D, Charlson E, Sodergren E . Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med. 2013; 187(10):1110-7. PMC: 3734615. DOI: 10.1164/rccm.201211-2145OC. View