1887

Journal of Medical Microbiology logo

Volume 71, Issue 2

and in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis Open Access

Abstract

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV change. The presence of and were associated with a greater annual rate of FEV change; −52.3 ml yr (95 % CI-87.7;−16.9), –67.9 ml yr (95 % CI-115.6;−20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV decline of −3.7 ml yr (95 % CI: −6.1 to −1.3, =0.003) and −5.3 ml yr (95 % CI: −8.7 to −1.9, =0.002) for each log increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): anaerobic infection , cystic fibrosis and microbiology
Funding
This study was supported by the:
  • The National Biofilms Innovation Centre (Award BB/R012415/1)
    • Principle Award Recipient: PaulWilliams
  • The National Biofilms Innovation Centre (Award BB/R012415/1)
    • Principle Award Recipient: MiguelCámara
  • Medical Research Council (Award G0801558/1)
    • Principle Award Recipient: NotApplicable
  • National Institute for Health Research (Award Nottingham Biomedical Research Centre)
    • Principle Award Recipient: NotApplicable
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001481
2022-02-03
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jmm/71/2/jmm001481.html?itemId=/content/journal/jmm/10.1099/jmm.0.001481&mimeType=html&fmt=ahah

References

  1. Ellaffi M, Vinsonneau C, Coste J, Hubert D, Burgel P-R et al. One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis. Am J Respir Crit Care Med 2005; 171:158–164 [View Article] [PubMed]
     [Google Scholar]
  2. Chmiel JF, Aksamit TR, Chotirmall SH, Dasenbrook EC, Elborn JS et al. Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi. Ann Am Thorac Soc 2014; 11:1298–1306 [View Article]
     [Google Scholar]
  3. Zemanick ET, Sagel SD, Harris JK. The airway microbiome in cystic fibrosis and implications for treatment. Curr Opin Pediatr 2011; 23:319–324 [View Article] [PubMed]
     [Google Scholar]
  4. Huang YJ, LiPuma JJ. The microbiome in cystic fibrosis. Clin Chest Med 2016; 37:59–67 [View Article] [PubMed]
     [Google Scholar]
  5. Tunney MM, Field TR, Moriarty TF, Patrick S, Doering G et al. Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 2008; 177:995–1001 [View Article] [PubMed]
     [Google Scholar]
  6. Chmiel JF, Aksamit TR, Chotirmall SH, Dasenbrook EC, Elborn JS et al. Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi. Ann Am Thorac Soc 2014; 11:1298–1306 [View Article]
     [Google Scholar]
  7. Mall MA, Danahay H, Boucher RC. Emerging concepts and therapies for mucoobstructive lung disease. Ann Am Thorac Soc 2018; 15:S216–S226 [View Article] [PubMed]
     [Google Scholar]
  8. Fodor AA, Klem ER, Gilpin DF, Elborn JS, Boucher RC et al. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS One 2012; 7:e45001 [View Article] [PubMed]
     [Google Scholar]
  9. Zhao J, Schloss PD, Kalikin LM, Carmody LA, Foster BK et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A 2012; 109:5809–5814 [View Article] [PubMed]
     [Google Scholar]
  10. Carmody LA, Zhao J, Kalikin LM, LeBar W, Simon RH et al. The daily dynamics of cystic fibrosis airway microbiota during clinical stability and at exacerbation. Microbiome 2015; 3:12 [View Article] [PubMed]
     [Google Scholar]
  11. Jones AM. Anaerobic bacteria in cystic fibrosis: pathogens or harmless commensals?. Thorax 2011; 66:558–559 [View Article]
     [Google Scholar]
  12. Nocker A, Sossa-Fernandez P, Burr MD, Camper AK et al. Use of propidium monoazide for live/dead distinction in microbial ecology. Appl Environ Microbiol 2007; 73:5111–5117 [View Article] [PubMed]
     [Google Scholar]
  13. Barr HL, Halliday N, Barrett DA, Williams P, Forrester DL et al. Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study. J Cyst Fibros 2017; 16:230–238 [View Article] [PubMed]
     [Google Scholar]
  14. UK Cystic Fibrosis Registry Https://www.cysticfibrosis.org.uk/the-work-we-do/uk-cf-registry. n.d
  15. Rogers GB, Marsh P, Stressmann AF, Allen CE, Daniels TVW et al. The exclusion of dead bacterial cells is essential for accurate molecular analysis of clinical samples. Clin Microbiol Infect 2010; 16:1656–1658 [View Article] [PubMed]
     [Google Scholar]
  16. Rogers GB, Carroll MP, Zain NMM, Bruce KD, Lock K et al. Complexity, temporal stability, and clinical correlates of airway bacterial community composition in primary ciliary dyskinesia. J Clin Microbiol 2013; 51:4029–4035 [View Article] [PubMed]
     [Google Scholar]
  17. Lee TWR, Brownlee KG, Conway SP, Denton M, Littlewood JM et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003; 2:29–34 [View Article] [PubMed]
     [Google Scholar]
  18. Muhlebach MS, Zorn BT, Esther CR, Hatch JE, Murray CP et al. Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children. PLoS Pathog 2018; 14:e1006798 [View Article] [PubMed]
     [Google Scholar]
  19. Brown PS, Pope CE, Marsh RL, Qin X, McNamara S et al. Directly sampling the lung of a young child with cystic fibrosis reveals diverse microbiota. Ann Am Thorac Soc 2014; 11:1049–1055 [View Article] [PubMed]
     [Google Scholar]
  20. Worlitzsch D, Rintelen C, Böhm K, Wollschläger B, Merkel N et al. Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients. Clin Microbiol Infect 2009; 15:454–460 [View Article] [PubMed]
     [Google Scholar]
  21. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G et al. Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with cystic fibrosis. J Clin Microbiol 2006; 44:2601–2604 [View Article] [PubMed]
     [Google Scholar]
  22. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G et al. Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with cystic fibrosis. J Clin Microbiol 2006; 44:2601–2604 [View Article] [PubMed]
     [Google Scholar]
  23. Sherrard LJ, Bell SC, Tunney MM. The role of anaerobic bacteria in the cystic fibrosis airway. Curr Opin Pulm Med 2016; 22:637–643 [View Article] [PubMed]
     [Google Scholar]
  24. Sibley CD, Duan K, Fischer C, Parkins MD, Storey DG et al. Discerning the complexity of community interactions using a Drosophila model of polymicrobial infections. PLoS Pathog 2008; 4:e1000184 [View Article] [PubMed]
     [Google Scholar]
  25. Line L, Alhede M, Kolpen M, Kühl M, Ciofu O et al. Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum. Front Microbiol 2014; 5:554 [View Article] [PubMed]
     [Google Scholar]
  26. Pallett R, Leslie LJ, Lambert PA, Milic I, Devitt A et al. Anaerobiosis influences virulence properties of Pseudomonas aeruginosa cystic fibrosis isolates and the interaction with Staphylococcus aureus. Sci Rep 2019; 9:6748 [View Article] [PubMed]
     [Google Scholar]
  27. Sherrard LJ, McGrath SJ, McIlreavey L, Hatch J, Wolfgang MC et al. Production of extended-spectrum β-lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota. Int J Antimicrob Agents 2016; 47:140–145 [View Article] [PubMed]
     [Google Scholar]
  28. Keravec M, Mounier J, Guilloux C-A, Fangous M-S, Mondot S et al. Porphyromonas, a potential predictive biomarker of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis. BMJ Open Respir Res 2019; 6:e000374 [View Article] [PubMed]
     [Google Scholar]
  29. Bernarde C, Keravec M, Mounier J, Gouriou S, Rault G et al. Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation. PLoS One 2015; 10:e0124124 [View Article] [PubMed]
     [Google Scholar]
  30. Zemanick ET, Harris JK, Wagner BD, Robertson CE, Sagel SD et al. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS One 2013; 8:e62917 [View Article] [PubMed]
     [Google Scholar]
  31. Mac Aogáin M, Narayana JK, Tiew PY, Ali NABM, Yong VFL et al. Integrative microbiomics in bronchiectasis exacerbations. Nat Med 2021; 27:688–699 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001481
Loading
Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis
J. Med. Microbiol. 71, 001481 (2022); https://doi.org/10.1099/jmm.0.001481
/content/journal/jmm/10.1099/jmm.0.001481
/content/journal/jmm/10.1099/jmm.0.001481
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error