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Open Access 01-12-2017 | Review

Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients

Authors: Sébastien Boutin, Alexander H. Dalpke

Published in: Molecular and Cellular Pediatrics | Issue 1/2017

Abstract

Cystic fibrosis (CF) is a genetic disease in which bacterial infections of the airways play a major role in the long-term clinical outcome. In recent years, a number of next-generation sequencing (NGS)-based studies aimed at deciphering the structure and composition of the airways’ microbiota. It was shown that the nasal cavity of CF patients displays dysbiosis early in life indicating a failure in the first establishment of a healthy microbiota. In contrast, within the conducting and lower airways, the establishment occurs normally first, but is sensitive to future dysbiosis including chronic infections with classical pathogens in later life. The objective of this mini-review is to give an update on the current knowledge about the development of the microbiota in the early life of CF patients. Microbial acquisition in the human airways can be described by the island model: Microbes found in the lower airways of CF patients represent “islands” that are at first populated from the upper airways reflecting the “mainland.” Colonization can be modeled following the neutral theory in which the most abundant bacteria in the mainland are also frequently found in the lower airways initially. At later times, however, the colonization process of the lower airways segregates by active selection of specific microbes. Future research should focus on those processes of microbial and host interactions to understand how microbial communities are shaped on short- and long-term scales. We point out what therapeutic consequences arise from the microbiome data obtained within ecological framework models.

Elborn JS (2016) Cystic fibrosis. Lancet Lond Engl. 388:2519–2531. doi:10.1016/S0140-6736(16)00576-6

Mall MA, Hartl D (2014) CFTR: cystic fibrosis and beyond. Eur Respir J 44:1042–1054. doi:10.1183/09031936.00228013 CrossRefPubMed

Cox MJ, Allgaier M, Taylor B et al (2010) Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One 5:e11044. doi:10.1371/journal.pone.0011044 CrossRefPubMedPubMedCentral

Burns JL, Gibson RL, McNamara S et al (2001) Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis 183:444–452. doi:10.1086/318075

Marchandin H, Michon AL and Jumas-Bilak E (2012). Atypical Bacteria in the CF Airways: Diversity, Clinical Consequences, Emergence and Adaptation, Cystic Fibrosis - Renewed Hopes Through Research, D Sriramulu (Ed.), InTech, doi:10.5772/30253

Foweraker J (2009) Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br Med Bull 89:93–110. doi:10.1093/bmb/ldn050 CrossRefPubMed

Hauser AR, Jain M, Bar-Meir M, McColley SA (2011) Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev 24:29–70. doi:10.1128/CMR.00036-10 CrossRefPubMedPubMedCentral

Beringer PM, Appleman MD (2000) Unusual respiratory bacterial flora in cystic fibrosis: microbiologic and clinical features. Curr Opin Pulm Med 6:545–550CrossRefPubMed

Rogers GB, Hart CA, Mason JR et al (2003) Bacterial diversity in cases of lung infection in cystic fibrosis patients: 16S ribosomal DNA (rDNA) length heterogeneity PCR and 16S rDNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol 41:3548–3558. doi:10.1128/JCM.41.8.3548-3558.2003 CrossRefPubMedPubMedCentral

10.

Boutin S, Graeber SY, Weitnauer M et al (2015) Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis. PLOS ONE 10:e0116029. doi:10.1371/journal.pone.0116029 CrossRefPubMedPubMedCentral

11.

Zhao J, Schloss PD, Kalikin LM et al (2012) Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci 109:5809–5814. doi:10.1073/pnas.1120577109 CrossRefPubMedPubMedCentral

12.

Etherington C, Naseer R, Conway SP et al (2014) The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation. J Cyst Fibros 13:49–55. doi:10.1016/j.jcf.2013.06.004 CrossRefPubMed

13.

Willger SD, Grim SL, Dolben EL et al (2014) Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis. Microbiome 2:40. doi:10.1186/2049-2618-2-40 CrossRefPubMedPubMedCentral

14.

Madan JC, Koestler DC, Stanton BA, et al (2012) 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. doi:10.1128/mBio.00251-12

15.

Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB (2016) The microbiome and the respiratory tract. Annu Rev Physiol 78:481–504. doi:10.1146/annurev-physiol-021115-105238 CrossRefPubMed

16.

Sibley CD, Grinwis ME, Field TR et al (2011) Culture enriched molecular profiling of the cystic fibrosis airway microbiome. PLoS ONE 6:e22702. doi:10.1371/journal.pone.0022702 CrossRefPubMedPubMedCentral

17.

Tunney MM, Field TR, Moriarty TF et al (2008) Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 177:995–1001. doi:10.1164/rccm.200708-1151OC CrossRefPubMed

18.

Whiteson KL, Bailey B, Bergkessel M et al (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. doi:10.1164/rccm.201312-2129PP CrossRefPubMedPubMedCentral

19.

Dickson RP, Erb-Downward JR, Freeman CM et al (2015) Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann Am Thorac Soc 12:821–830. doi:10.1513/AnnalsATS.201501-029OC CrossRefPubMedPubMedCentral

20.

Charlson ES, Bittinger K, Haas AR et al (2011) Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med 184:957–963. doi:10.1164/rccm.201104-0655OC CrossRefPubMedPubMedCentral

21.

Venkataraman A, Bassis CM, Beck JM, et al (2015) Application of a neutral community model to assess structuring of the human lung microbiome. mBio 6:e02284-14. doi: 10.1128/mBio.02284-14

22.

Morris A, Beck JM, Schloss PD et al (2013) Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med 187:1067–1075. doi:10.1164/rccm.201210-1913OC CrossRefPubMedPubMedCentral

23.

Li L, Ma ZS (2016) Testing the Neutral Theory of Biodiversity with Human Microbiome Datasets. Sci Rep. 6:31448. doi:10.1038/srep31448

24.

Cohen NA (2006) Sinonasal mucociliary clearance in health and disease. Ann Otol Rhinol Laryngol Suppl 196:20–26CrossRefPubMed

25.

Kluytmans JA, Wertheim HFL (2005) Nasal carriage of Staphylococcus aureus and prevention of nosocomial infections. Infection 33:3–8. doi: 10.1007/s15010-005-4012-9

26.

Mika M, Korten I, Qi W et al (2016) The nasal microbiota in infants with cystic fibrosis in the first year of life: a prospective cohort study. Lancet Respir Med. 4:627-35. doi:10.1016/S2213-2600(16)30081-9

27.

Biesbroek G, Tsivtsivadze E, Sanders EAM et al (2014) Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med 190:1283–1292. doi:10.1164/rccm.201407-1240OC CrossRefPubMed

28.

Wos-Oxley ML, Chaves-Moreno D, Jáuregui R et al (2016) Exploring the bacterial assemblages along the human nasal passage. Environ Microbiol 18:2259–2271. doi:10.1111/1462-2920.13378 CrossRefPubMed

29.

Zhou Y, Mihindukulasuriya KA, Gao H et al (2014) Exploration of bacterial community classes in major human habitats. Genome Biol 15:R66. doi:10.1186/gb-2014-15-5-r66 CrossRefPubMedPubMedCentral

30.

Prevaes SMPJ, de Winter-de Groot KM, Janssens HM et al (2016) Development of the nasopharyngeal microbiota in infants with cystic fibrosis. Am J Respir Crit Care Med 193:504–515. doi:10.1164/rccm.201509-1759OC CrossRefPubMed

31.

Folkesson A, Jelsbak L, Yang L et al (2012) Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol 10:841–851. doi:10.1038/nrmicro2907 CrossRefPubMed

32.

Bonestroo HJC, de Winter-de Groot KM, van der Ent CK, Arets HGM (2010) Upper and lower airway cultures in children with cystic fibrosis: do not neglect the upper airways. J Cyst Fibros 9:130–134. doi:10.1016/j.jcf.2010.01.001 CrossRefPubMed

33.

Taylor CJ, McGaw J, Howden R et al (1990) Bacterial reservoirs in cystic fibrosis. Arch Dis Child 65:175–177. doi:10.1136/adc.65.2.175 CrossRefPubMedPubMedCentral

34.

Lyczak JB, Cannon CL, Pier GB (2000) Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist1. Microbes Infect 2:1051–1060. doi:10.1016/S1286-4579(00)01259-4 CrossRefPubMed

35.

Kosorok MR, Jalaluddin M, Farrell PM et al (1998) Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis. Pediatr Pulmonol 26:81–88.

36.

Rosenfeld M, Emerson J, McNamara S et al (2012) Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort. J Cyst Fibros 11:446–453. doi:10.1016/j.jcf.2012.04.003 CrossRefPubMedPubMedCentral

37.

Ciofu O, Johansen HK, Aanaes K et al (2013) P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs. J Cyst Fibros Off J Eur Cyst Fibros Soc 12:729–736. doi:10.1016/j.jcf.2013.02.004 CrossRef

38.

Twomey KB, Alston M, An S-Q et al (2013) Microbiota and metabolite profiling reveal specific alterations in bacterial community structure and environment in the cystic fibrosis airway during exacerbation. PLoS ONE 8:e82432. doi:10.1371/journal.pone.0082432 CrossRefPubMedPubMedCentral

39.

Venkataraman A, Rosenbaum MA, Perkins SD et al (2011) Metabolite-based mutualism between Pseudomonas aeruginosaPA14 and Enterobacter aerogenes enhances current generation in bioelectrochemical systems. Energy Environ Sci 4:4550–4559. doi:10.1039/C1EE01377G CrossRef

40.

Venkataraman A, Rosenbaum MA, Werner JJ et al (2014) Metabolite transfer with the fermentation product 2,3-butanediol enhances virulence by Pseudomonas aeruginosa. ISME J 8:1210–1220. doi:10.1038/ismej.2013.232 CrossRefPubMedPubMedCentral

41.

Whiteson KL, Meinardi S, Lim YW et al (2014) Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2,3-butanedione fermentation. ISME J 8:1247–1258. doi:10.1038/ismej.2013.229 CrossRefPubMedPubMedCentral

42.

Armbruster CR, Wolter DJ, Mishra M, et al (2016) Staphylococcus aureus Protein A mediates interspecies interactions at the cell surface of Pseudomonas aeruginosa. mBio 7:e00538-16. doi: 10.1128/mBio.00538-16

43.

Mashburn LM, Jett AM, Akins DR, Whiteley M (2005) Staphylococcus aureus serves as an iron source for Pseudomonas aeruginosa during in vivo coculture. J Bacteriol 187:554–566. doi:10.1128/JB.187.2.554-566.2005 CrossRefPubMedPubMedCentral

44.

Korgaonkar AK, Whiteley M (2011) Pseudomonas aeruginosa enhances production of an antimicrobial in response to N-acetylglucosamine and Peptidoglycan. J Bacteriol 193:909–917. doi:10.1128/JB.01175-10 CrossRefPubMed

45.

Filkins LM, Graber JA, Olson DG et al (2015) Coculture of Staphylococcus aureus with Pseudomonas aeruginosa drives S. aureus towards fermentative metabolism and reduced viability in a cystic fibrosis model. J Bacteriol 197:2252–2264. doi:10.1128/JB.00059-15 CrossRefPubMedPubMedCentral

46.

Billings N, Millan MR, Caldara M et al (2013) The extracellular matrix component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog 9:e1003526. doi:10.1371/journal.ppat.1003526 CrossRefPubMedPubMedCentral

47.

Pernet E, Guillemot L, Burgel P-R et al (2014) Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity. Nat Commun 5:5105. doi:10.1038/ncomms6105 CrossRefPubMed

48.

Limoli DH, Yang J, Khansaheb MK et al (2016) Staphylococcus aureus and Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis 35:947–953. doi:10.1007/s10096-016-2621-0 CrossRefPubMed

49.

Segata N, Haake SK, Mannon P et al (2012) Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol 13:R42. doi:10.1186/gb-2012-13-6-r42 CrossRefPubMedPubMedCentral

50.

Klepac-Ceraj V, Lemon KP, Martin TR et al (2010) Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa. Environ Microbiol 12:1293–1303. doi:10.1111/j.1462-2920.2010.02173.x CrossRefPubMed

51.

Scoffield JA, Wu H (2015) Oral Streptococci and nitrite-mediated interference of Pseudomonas aeruginosa. Infect Immun 83:101–107. doi:10.1128/IAI.02396-14 CrossRefPubMed

52.

Whiley RA, Fleming EV, Makhija R, Waite RD (2015) Environment and colonisation sequence are key parameters driving cooperation and competition between Pseudomonas aeruginosa cystic fibrosis strains and oral commensal Streptococci. PLoS ONE 10:e0115513. doi:10.1371/journal.pone.0115513

53.

Garzoni C, Brugger SD, Qi W et al (2013) Microbial communities in the respiratory tract of patients with interstitial lung disease. Thorax 68:1150–1156. doi:10.1136/thoraxjnl-2012-202917 CrossRefPubMedPubMedCentral

54.

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. doi:10.1016/S2213-2600(14)70028-1 CrossRefPubMedPubMedCentral

55.

O’Neill K, Bradley JM, Johnston E et al (2015) Reduced bacterial colony count of anaerobic bacteria is associated with a worsening in lung clearance index and inflammation in cystic fibrosis. PLoS ONE 10:e0126980. doi:10.1371/journal.pone.0126980 CrossRefPubMedPubMedCentral

56.

Brown PS, Pope CE, Marsh RL et al (2014) Directly sampling the lung of a young child with cystic fibrosis reveals diverse microbiota. Ann Am Thorac Soc 11:1049–1055. doi:10.1513/AnnalsATS.201311-383OC CrossRefPubMedPubMedCentral

57.

Willner D, Haynes MR, Furlan M et al (2012) Spatial distribution of microbial communities in the cystic fibrosis lung. ISME J 6:471–474. doi:10.1038/ismej.2011.104 CrossRefPubMed

58.

Winstanley C, O’Brien S, Brockhurst MA (2016) Pseudomonas aeruginosa evolutionary adaptation and diversification in cystic fibrosis chronic lung infections. Trends Microbiol 24:327–337. doi:10.1016/j.tim.2016.01.008 CrossRefPubMedPubMedCentral

59.

Jorth P, Staudinger BJ, Wu X et al (2015) Regional isolation drives bacterial diversification within cystic fibrosis lungs. Cell Host Microbe 18:307–319. doi:10.1016/j.chom.2015.07.006 CrossRefPubMedPubMedCentral

60.

Renwick J, McNally P, John B et al (2014) The microbial community of the cystic fibrosis airway is disrupted in early life. PLoS ONE 9:e109798. doi:10.1371/journal.pone.0109798 CrossRefPubMedPubMedCentral

61.

Coburn B, Wang PW, Diaz Caballero J et al (2015) Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 5:10241. doi:10.1038/srep10241 CrossRefPubMedPubMedCentral

62.

Goddard AF, Staudinger BJ, Dowd SE et al (2012) Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota. Proc Natl Acad Sci 109:13769–13774. doi:10.1073/pnas.1107435109 CrossRefPubMedPubMedCentral

63.

Magalhães AP, Azevedo NF, Pereira MO, Lopes SP (2016) The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy. Appl Microbiol Biotechnol 100:1163–1181. doi:10.1007/s00253-015-7177-x CrossRefPubMed

64.

Palmer KL, Mashburn LM, Singh PK, Whiteley M (2005) Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology. J Bacteriol 187:5267–5277. doi:10.1128/JB.187.15.5267-5277.2005 CrossRefPubMedPubMedCentral

65.

O’Dwyer DN, Dickson RP, Moore BB (2016) The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol Baltim Md 196:4839–4847. doi:10.4049/jimmunol.1600279, 1950

66.

Zemanick ET, Harris JK, Wagner BD et al (2013) Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS ONE 8:e62917. doi:10.1371/journal.pone.0062917 CrossRefPubMedPubMedCentral

67.

Sherrard LJ, Bell SC, Tunney MM (2016) The role of anaerobic bacteria in the cystic fibrosis airway. Curr Opin Pulm Med. 22:637–643. doi:10.1097/MCP.0000000000000299

68.

Worlitzsch D, Rintelen C, Böhm K et al (2009) Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients. Clin Microbiol Infect 15:454–460. doi:10.1111/j.1469-0691.2008.02659.x CrossRefPubMed

69.

Quinn RA, Whiteson K, Lim Y-W et al (2015) A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation. ISME J 9:1024–1038. doi:10.1038/ismej.2014.234 CrossRefPubMed

70.

Cuthbertson L, Rogers GB, Walker AW et al (2016) Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. ISME J 10:1081–1091. doi:10.1038/ismej.2015.198 CrossRefPubMed

71.

Sherrard LJ, Graham KA, McGrath SJ, et al (2013) Antibiotic resistance in Prevotella species isolated from patients with cystic fibrosis. J Antimicrob Chemother 68:2369–74. doi:10.1093/jac/dkt191

72.

Lim YW, Schmieder R, Haynes M et al (2013) Metagenomics and metatranscriptomics: windows on CF-associated viral and microbial communities. J Cyst Fibros Off J Eur Cyst Fibros Soc 12:154–164. doi:10.1016/j.jcf.2012.07.009 CrossRef

73.

Fouhy F, Stanton C, Cotter PD et al (2015) Proteomics as the final step in the functional metagenomics study of antimicrobial resistance. Antimicrob Resist Chemother 6:172. doi:10.3389/fmicb.2015.00172

74.

Bronstein MN, Sokol RJ, Abman SH et al (1992) Pancreatic insufficiency, growth, and nutrition in infants identified by newborn screening as having cystic fibrosis. J Pediatr 120:533–540CrossRefPubMed

75.

Flass T, Tong S, Frank DN et al (2015) Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis. PLoS ONE 10:e0116967. doi:10.1371/journal.pone.0116967 CrossRefPubMedPubMedCentral

76.

Li L, Somerset S (2014) The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies. Clin Nutr Edinb Scotl 33:571–580. doi:10.1016/j.clnu.2014.04.004 CrossRef

77.

Li L, Somerset S (2014) Digestive system dysfunction in cystic fibrosis: challenges for nutrition therapy. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver 46:865–874. doi:10.1016/j.dld.2014.06.011

78.

Rogers GB, Carroll MP, Hoffman LR et al (2010) Comparing the microbiota of the cystic fibrosis lung and human gut. Gut Microbes 1:85–93. doi:10.4161/gmic.1.2.11350 CrossRefPubMedPubMedCentral

79.

Hoen AG, Li J, Moulton LA, et al (2015) Associations between gut microbial colonization in early life and respiratory outcomes in cystic fibrosis. J Pediatr 167:138-147–3. doi: 10.1016/j.jpeds.2015.02.049

80.

Munck A (2014) Cystic fibrosis: evidence for gut inflammation. Int J Biochem Cell Biol 52:180–183. doi:10.1016/j.biocel.2014.02.005 CrossRefPubMed

81.

Lynch SV, Goldfarb KC, Wild YK et al (2013) Cystic fibrosis transmembrane conductance regulator knockout mice exhibit aberrant gastrointestinal microbiota. Gut Microbes 4:41–47. doi:10.4161/gmic.22430 CrossRefPubMedPubMedCentral

82.

Bazett M, Honeyman L, Stefanov AN et al (2015) Cystic fibrosis mouse model-dependent intestinal structure and gut microbiome. Mamm Genome 26:222–234. doi:10.1007/s00335-015-9560-4

83.

Duytschaever G, Huys G, Bekaert M et al (2013) Dysbiosis of bifidobacteria and Clostridium cluster XIVa in the cystic fibrosis fecal microbiota. J Cyst Fibros 12:206–215. doi:10.1016/j.jcf.2012.10.003

84.

Bruzzese E, Raia V, Spagnuolo MI et al (2007) Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr Edinb Scotl 26:322–328. doi:10.1016/j.clnu.2007.01.004 CrossRef

85.

Bruzzese E, Callegari ML, Raia V et al (2014) Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial. PLoS One 9:e87796. doi:10.1371/journal.pone.0087796 CrossRefPubMedPubMedCentral

Title: Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients
Authors: Sébastien Boutin
Alexander H. Dalpke
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Molecular and Cellular Pediatrics / Issue 1/2017
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-016-0067-1

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