Upper versus lower airway microbiome and metagenome in children with cystic fibrosis and their correlation with lung inflammation
Autoři:
Mariana E. Kirst aff001; Dawn Baker aff002; Eric Li aff001; Mutasim Abu-Hasan aff002; Gary P. Wang aff001
Působiště autorů:
Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida College of Medicine, Gainesville, FL, United States of America
aff001; Department of Pediatrics, Division of Pediatric Pulmonology, University of Florida College of Medicine, Gainesville, FL, United States of America
aff002; Medical Service, Infectious Disease Section, North Florida/South Georgia Veterans Health System, Gainesville, FL, United States of America
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222323
Souhrn
Objective
Airways of children with cystic fibrosis (CF) harbor complex polymicrobial communities which correlates with pulmonary disease progression and use of antibiotics. Throat swabs are widely used in young CF children as a surrogate to detect potentially pathogenic microorganisms in lower airways. However, the relationship between upper and lower airway microbial communities remains poorly understood. This study aims to determine (1) to what extent oropharyngeal microbiome resembles the lung microbiome in CF children and (2) if lung microbiome composition correlates with airway inflammation.
Method
Throat swabs and bronchoalveolar lavage (BAL) were obtained concurrently from 21 CF children and 26 disease controls. Oropharyngeal and lung microbiota were analyzed using 16S rRNA deep sequencing and correlated with neutrophil counts in BAL and antibiotic exposure.
Results
Oropharyngeal microbial communities clustered separately from lung communities and had higher microbial diversity (p < 0.001). CF microbiome differed significantly from non-CF controls, with a higher abundance of Proteobacteria in both upper and lower CF airways. Neutrophil count in the BAL correlated negatively with the diversity but not richness of the lung microbiome. In CF children, microbial genes involved in bacterial motility proteins, two-component system, flagella assembly, and secretion system were enriched in both oropharyngeal and lung microbiome, whereas genes associated with synthesis and metabolism of nucleic acids and protein dominated the non-CF controls.
Conclusions
This study identified a unique microbial profile with altered microbial diversity and metabolic functions in CF airways which is significantly affected by airway inflammation. These results highlight the limitations of using throat swabs as a surrogate to study lower airway microbiome and metagenome in CF children.
Klíčová slova:
Biology and life sciences – Microbiology – Medical microbiology – Microbiome – Microbial genomics – Microbial control – Antimicrobials – Antibiotics – Genetics – Genomics – Metagenomics – Developmental biology – Fibrosis – Anatomy – Neck – Throat – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – Neutrophils – Immune cells – Cellular structures and organelles – Biochemistry – Nucleic acids – RNA – Non-coding RNA – Ribosomal RNA – Ribosomes – Organisms – Bacteria – Medicine and health sciences – Clinical genetics – Genetic diseases – Autosomal recessive diseases – Cystic fibrosis – Pulmonology – Pharmacology – Drugs – Immunology
Zdroje
1. O'Sullivan BP, Freedman SD. Cystic fibrosis. Lancet. 2009;373: 1891–1904. doi: 10.1016/S0140-6736(09)60327-5 19403164
2. Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352: 1992–2001. 352/19/1992 [pii]. doi: 10.1056/NEJMra043184 15888700
3. MacKenzie T, Gifford AH, Sabadosa KA, Quinton HB, Knapp EA, Goss CH, et al. Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry. Ann Intern Med. 2014;161: 233–241. doi: 10.7326/M13-0636 25133359
4. Armstrong DS, Hook SM, Jamsen KM, Nixon GM, Carzino R, Carlin JB, et al. Lower airway inflammation in infants with cystic fibrosis detected by newborn screening. Pediatr Pulmonol. 2005;40: 500–510. doi: 10.1002/ppul.20294 16208679
5. Nixon GM, Armstrong DS, Carzino R, Carlin JB, Olinsky A, Robertson CF, et al. Early airway infection, inflammation, and lung function in cystic fibrosis. Arch Dis Child. 2002;87: 306–311. doi: 10.1136/adc.87.4.306 12244003
6. Rosenfeld M, Gibson RL, McNamara S, Emerson J, Burns JL, Castile R, et al. Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol. 2001;32: 356–366. 11596160
7. Balough K, McCubbin M, Weinberger M, Smits W, Ahrens R, Fick R. The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis. Pediatr Pulmonol. 1995;20: 63–70. 8570304
8. Paugam A, Baixench MT, Demazes-Dufeu N, Burgel PR, Sauter E, Kanaan R, et al. Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France. Med Mycol. 2010;48 Suppl 1: S32–6. doi: 10.3109/13693786.2010.503665 21067327
9. Giron RM, Maiz L, Barrio I, Martinez MT, Salcedo A, Prados C. Nontuberculous mycobacterial infection in patients with cystic fibrosis: a multicenter prevalence study. Arch Bronconeumol. 2008;44: 679–684. S0300-2896(08)75777-6 [pii]. 19091237
10. Esther CR, Henry MM, Molina PL, Leigh MW. Nontuberculous mycobacterial infection in young children with cystic fibrosis. Pediatr Pulmonol. 2005;40: 39–44. doi: 10.1002/ppul.20222 15858802
11. Ronne Hansen C, Pressler T, Hoiby N, Gormsen M. Chronic infection with Achromobacter xylosoxidans in cystic fibrosis patients; a retrospective case control study. J Cyst Fibros. 2006;5: 245–251. S1569-1993(06)00064-6 [pii]. doi: 10.1016/j.jcf.2006.04.002 16777495
12. De Baets F, Schelstraete P, Van Daele S, Haerynck F, Vaneechoutte M. Achromobacter xylosoxidans in cystic fibrosis: prevalence and clinical relevance. J Cyst Fibros. 2007;6: 75–78. S1569-1993(06)00086-5 [pii]. doi: 10.1016/j.jcf.2006.05.011 16793350
13. Hansen CR, Pressler T, Nielsen KG, Jensen PO, Bjarnsholt T, Hoiby N. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients. J Cyst Fibros. 2010;9: 51–58. doi: 10.1016/j.jcf.2009.10.005 19939747
14. Frangolias DD, Mahenthiralingam E, Rae S, Raboud JM, Davidson AG, Wittmann R, et al. Burkholderia cepacia in cystic fibrosis. Variable disease course. Am J Respir Crit Care Med. 1999;160: 1572–1577. doi: 10.1164/ajrccm.160.5.9805046 10556123
15. Ledson MJ, Gallagher MJ, Jackson M, Hart CA, Walshaw MJ. Outcome of Burkholderia cepacia colonisation in an adult cystic fibrosis centre. Thorax. 2002;57: 142–145. doi: 10.1136/thorax.57.2.142 11828044
16. Whiteford ML, Wilkinson JD, McColl JH, Conlon FM, Michie JR, Evans TJ, et al. Outcome of Burkholderia (Pseudomonas) cepacia colonisation in children with cystic fibrosis following a hospital outbreak. Thorax. 1995;50: 1194–1198. doi: 10.1136/thx.50.11.1194 8553277
17. Esther CR, Esserman DA, Gilligan P, Kerr A, Noone PG. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J Cyst Fibros. 2010;9: 117–123. doi: 10.1016/j.jcf.2009.12.001 20071249
18. Qvist T, Taylor-Robinson D, Waldmann E, Olesen HV, Hansen CR, Mathiesen IH, et al. Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis. J Cyst Fibros. 2016;15: 380–385. doi: 10.1016/j.jcf.2015.09.007 26482717
19. Bryant JM, Grogono DM, Rodriguez-Rincon D, Everall I, Brown KP, Moreno P, et al. Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium. Science. 2016;354: 751–757. doi: 10.1126/science.aaf8156 27846606
20. Paganin P, Fiscarelli EV, Tuccio V, Chiancianesi M, Bacci G, Morelli P, et al. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function. PLoS One. 2015;10: e0124348. doi: 10.1371/journal.pone.0124348 25898134
21. Flight WG, Smith A, Paisey C, Marchesi JR, Bull MJ, Norville PJ, et al. Rapid Detection of Emerging Pathogens and Loss of Microbial Diversity Associated with Severe Lung Disease in Cystic Fibrosis. J Clin Microbiol. 2015;53: 2022–2029. doi: 10.1128/JCM.00432-15 25878338
22. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Bruce KD. characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16s ribosomal DNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol. 2004;42: 5176–5183. doi: 10.1128/JCM.42.11.5176-5183.2004 [pii]. 15528712
23. Rogers GB, van der Gast C J, Cuthbertson L, Thomson SK, Bruce KD, Martin ML, et al. Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition. Thorax. 2013;68: 731–737. doi: 10.1136/thoraxjnl-2012-203105 23564400
24. Harris JK, De Groote MA, Sagel SD, Zemanick ET, Kapsner R, Penvari C, et al. Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. Proc Natl Acad Sci U S A. 2007;104: 20529–20533. 0709804104 [pii]. doi: 10.1073/pnas.0709804104 18077362
25. Cox MJ, Allgaier M, Taylor B, Baek MS, Huang YJ, Daly RA, et al. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One. 2010;5: e11044. doi: 10.1371/journal.pone.0011044 20585638
26. Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, 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. 2012;3: doi: 10.1128/mBio.00251-12 Print 2012. 10.1128/mBio.00251-12 [doi]. 22911969
27. Klepac-Ceraj V, Lemon KP, Martin TR, Allgaier M, Kembel SW, Knapp AA, et al. Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa. Environ Microbiol. 2010;12: 1293–1303. doi: 10.1111/j.1462-2920.2010.02173.x 20192960
28. Goddard AF, Staudinger BJ, Dowd SE, Joshi-Datar A, Wolcott RD, Aitken ML, et al. 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: 13769–13774. doi: 10.1073/pnas.1107435109 22872870
29. Zemanick ET, Wagner BD, Robertson CE, Stevens MJ, Szefler SJ, Accurso FJ, et al. Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods. Ann Am Thorac Soc. 2015;12: 221–229. doi: 10.1513/AnnalsATS.201407-310OC 25474078
30. Hoppe JE, Towler E, Wagner BD, Accurso FJ, Sagel SD, Zemanick ET. Sputum induction improves detection of pathogens in children with cystic fibrosis. Pediatr Pulmonol. 2015;50: 638–646. doi: 10.1002/ppul.23150 25565628
31. Rosenfeld M, Emerson J, Accurso F, Armstrong D, Castile R, Grimwood K, et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr Pulmonol. 1999;28: 321–328. 10536062
32. Armstrong DS, Grimwood K, Carlin JB, Carzino R, Olinsky A, Phelan PD. Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatr Pulmonol. 1996;21: 267–275. doi: 10.1002/(SICI)1099-0496(199605)21:5<267::AID-PPUL1>3.0.CO;2-K [pii]. 8726151
33. Avital A, Uwyyed K, Picard E, Godfrey S, Springer C. Sensitivity and specificity of oropharyngeal suction versus bronchoalveolar lavage in identifying respiratory tract pathogens in children with chronic pulmonary infection. Pediatr Pulmonol. 1995;20: 40–43. 7478780
34. Ramsey BW, Wentz KR, Smith AL, Richardson M, Williams-Warren J, Hedges DL, et al. Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients. Am Rev Respir Dis. 1991;144: 331–337. doi: 10.1164/ajrccm/144.2.331 1859056
35. Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013;31: 814–821. doi: 10.1038/nbt.2676 23975157
36. [Anonymous]. A language and environment for statistical computing. R: R Foundation for Statistical Computing.t http://www.R-project.org). 2008.
37. Magoc T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011;27: 2957–2963. doi: 10.1093/bioinformatics/btr507 21903629
38. Pruesse E, Quast C, Knittel K, Fuchs BM, Ludwig W, Peplies J, et al. SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res. 2007;35: 7188–7196. doi: 10.1093/nar/gkm864 17947321
39. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010.
40. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12: R60. doi: 10.1186/gb-2011-12-6-r60 21702898
41. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7: 335–336. doi: 10.1038/nmeth.f.303 20383131
42. Lozupone C, Hamady M, Knight R. UniFrac—an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics. 2006;7: 371. doi: 10.1186/1471-2105-7-371 16893466
43. Marsh RL, Kaestli M, Chang AB, Binks MJ, Pope CE, Hoffman LR, et al. The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx. Microbiome. 2016;4: 37–016. doi: 10.1186/s40168-016-0182-1 27388563
44. Kloepfer KM, Deschamp AR, Ross SE, Peterson-Carmichael SL, Hemmerich CM, Rusch DB, et al. In children, the microbiota of the nasopharynx and bronchoalveolar lavage fluid are both similar and different. Pediatr Pulmonol. 2018;53: 475–482. doi: 10.1002/ppul.23953 29405661
45. Zemanick ET, Wagner BD, Robertson CE, Ahrens RC, Chmiel JF, Clancy JP, et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J. 2017;50: doi: 10.1183/13993003.00832–2017 Print 2017 Nov. 1700832 [pii].
46. Pittman JE, Wylie KM, Akers K, Storch GA, Hatch J, Quante J, et al. Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis. Ann Am Thorac Soc. 2017;14: 1548–1555. doi: 10.1513/AnnalsATS.201702-121OC 28708417
47. Frayman KB, Armstrong DS, Carzino R, Ferkol TW, Grimwood K, Storch GA, et al. The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis. Thorax. 2017;72: 1104–1112. doi: 10.1136/thoraxjnl-2016-209279 28280235
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