Microbiome Investigation of the Lower Airways of Bronchiectasis Patients with Serum Cytokine and Chemokine Content into the Pathogenesis of Bronchiectasis
Abstract
Bronchiectasis is a chronic respiratory condition characterized by persistent airway inflammation and recurrent infections, yet its underlying pathogenesis remains incompletely understood. This study aimed to investigate the roles of the lower respiratory tract microbiome and serum cytokine/chemokine profiles in the pathogenesis of bronchiectasis.
In this retrospective study, we enrolled 285 bronchiectasis patients admitted to our hospital between January 2024 and June 2025. Participants were categorized into an acute exacerbation group (n=158) and a clinically stable group (n=127). We compared the two groups in terms of respiratory pathogens, immune function indicators (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, white blood cell count, and neutrophil count), pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A), anti-inflammatory cytokines (interleukin-10 and interleukin-4), acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A), and chemokines (monocyte chemoattractant protein-1). The involvement of these factors in disease pathogenesis was analyzed.
Significant differences were observed between the groups in the rates of hypoalbuminemia, the presence of dyspnea and hemoptysis, and the oxygenation index in arterial blood gas analysis. Sputum cultures were positive in 103 (65.19%) patients in the acute exacerbation group, compared to 58 (45.67%) in the stable group. Immune markers CD3+, CD4+, CD8+, and the CD4+/CD8+ ratio were lower during acute exacerbation, while WBC and NEUT levels were elevated. Pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A) and acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A) were significantly higher during exacerbation, whereas anti-inflammatory cytokines (interleukin-10 and interleukin-4) were lower. Monocyte chemoattractant protein-1 levels were also elevated during exacerbation.
Dysbiosis of the lower respiratory tract microbiome, immune dysfunction, and exacerbated inflammatory responses are interrelated and collectively contribute to the pathogenesis of bronchiectasis.
2. De Angelis A, Johnson ED, Sutharsan S, Aliberti S. Exacerbations of bronchiectasis. Eur Respir Rev. 2024;33(173):230098.
3. Nigro M, Laska IF, Traversi L, Simonetta E, Polverino E. Epidemiology of bronchiectasis. Eur Respir Rev. 2024;33(174):230100.
4. Spinou A, Lee AL, O’Neil B, Oliveira A, Shteinberg M, Herrero-Cortina B, et al. Patient-managed interventions for adults with bronchiectasis. Eur Respir Rev. 2024;33(174):230102.
5. Perea L, Faner R, Chalmers JD, Sibila O. Pathophysiology and genomics of bronchiectasis. Eur Respir Rev. 2024;33(173):230094.
6. Choi H, Xu JF, Chotirmall SH, Chalmers JD, Morgan LC, Dhar R. Bronchiectasis in Asia. Eur Respir Rev. 2024;33(173):230096.
7. Cole PJ. Inflammation: a two-edged sword—the model of bronchiectasis. Eur J Respir Dis Suppl. 1986;147:6–15.
8. Chalmers JD, Chang AB, Chotirmall SH, Dhar R, McShane PJ. Bronchiectasis. Nat Rev Dis Primers. 2018;4(1):45.
9. Muñoz G, de Gracia J, Buxó M, Alvarez A, Vendrell M. Long-term benefits of airway clearance in bronchiectasis. Eur Respir J. 2018;51(1):1701926.
10. Chalmers JD, Boersma W, Lonergan M, Jayaram L, Crichton ML, Karalus N, et al. Long-term macrolide antibiotics in bronchiectasis. Lancet Respir Med. 2019;7(10):845–54.
11. Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis. Lancet. 2018;392(10150):880–90.
12. Cohen R, Shteinberg M. Diagnosis and evaluation of bronchiectasis. Clin Chest Med. 2022;43(1):7–22.
13. Chalmers JD, Elborn S, Greene CM. Bronchiectasis in adults. Eur Respir Rev. 2023;32(168):220168.
14. Xu JF, Gao YH, Song YL, Qu JM, Guan WJ. Bronchiectasis: Chinese perspective. ERJ Open Res. 2022;8(2):00193-2022.
15. Narayana JK, Mac Aogáin M, Hansbro PM, Chotirmall SH. The bronchiectasis microbiome. Curr Opin Pulm Med. 2025;31(2):135–44.
16. de la Rosa-Carrillo D, García-Clemente MM. Bronchiectasis exacerbations. Int J Tuberc Lung Dis. 2022;26(7):581–83.
17. Doumat G, Aksamit TR, Kanj AN. Bronchiectasis: inflammation review. Respir Med. 2025;244:108179.
18. Choi H, Ryu S, Keir HR, Giam YH, Dicker AJ, Perea L, et al. Inflammatory molecular endotypes in bronchiectasis. Am J Respir Crit Care Med. 2023;208(11):1166–76.
19. Bezzio C, Della Corte C, Vernero M, Di Luna I, Manes G, Saibeni S. Immune-mediated inflammatory diseases. Ther Adv Gastroenterol. 2022;15:17562848221115312.
20. Singh S, Anshita D, Ravichandiran V. MCP-1 in disease. Int Immunopharmacol. 2021;101(Pt B):107598.
21. Aliberti S, Goeminne PC, O’Donnell AE, Aksamit TR, Al-Jahdali H, Barker AF, et al. Diagnosis of bronchiectasis in adults. Lancet Respir Med. 2022;10(3):298–306.
22. Choi H, Chalmers JD. Bronchiectasis exacerbation. Ann Transl Med. 2023;11(1):25.
23. Narayana JK, Aliberti S, Mac Aogáin M, Jaggi TK, Ali N, Ivan FX, et al. Gut-lung axis in bronchiectasis. Am J Respir Crit Care Med. 2023;207(7):908–20.
24. Wen B, Zhang G, Zhan C, Chen C, Yi H, et al. Declaration of Helsinki 2024 revision. Postgrad Med J. 2025;101(1194):371–82.
25. Kim N, Fischer AH, Dyring-Andersen B, Rosner B, Okoye GA. Statistical methods in clinical research. J Invest Dermatol. 2017;137(10):e173–8.
26. Konovalovas A, Armalytė J, Klimkaitė L, Liveikis T, Jonaitytė B, Danila E, et al. Microbiome and biomarkers in bronchiectasis. Microbiol Spectr. 2024;12(12):e04144-23.
27. Chang AB, Kantar A, Redding GJ, Hill AT. Reversibility of bronchiectasis. Arch Bronconeumol. 2023;59(4):199–200.
28. Vicendese D, Yerkovich S, Grimwood K, Valery PC, Byrnes CA, Morris PS, et al. Azithromycin in children with bronchiectasis. Chest. 2023;163(1):52–63.
29. Terpstra LC, van der Geest D, Bronsveld I, Heijerman H, Boersma WG. Inhaled antibiotics in bronchiectasis. Clin Respir J. 2023;17(8):748–53.
30. Conceição M, Shteinberg M, Goeminne P, Altenburg J, Chalmers JD. Pseudomonas eradication in bronchiectasis. Eur Respir Rev. 2024;33(171):230157.
31. Cedeño de Jesús S, Almadana Pacheco V, Valido Morales A, Muñíz Rodríguez AM, Ayerbe García R, Arnedillo-Muñoz A. Pulmonary rehabilitation in bronchiectasis. Int J Environ Res Public Health. 2022;19(17):10864.
32. Hill AR, Bedi P, Cartlidge MK, Turnbull K, Donaldson S, Clarke A, et al. Exacerbation relapse in asthma and bronchiectasis. Lung. 2023;201(1):17–23.
33. Mac Aogáin M, Tiew PY, Jaggi TK, Narayana JK, Singh S, Hansbro PM, et al. Targeting respiratory microbiomes. Expert Rev Respir Med. 2024;18(3–4):111–25.
34. Cheng M, Xu Y, Cui X, Wei X, Chang Y, Xu J, et al. Lower respiratory tract microbiome dynamics. Nat Commun. 2024;15(1):8361.
35. Hong R, Lin S, Zhang S, Yi Y, Li L, Yang H, et al. Respiratory microbiome via mNGS. Front Cell Infect Microbiol. 2024;14:1320831.
36. Cox MJ, Turek EM, Hennessy C, Mirza GK, James PL, Coleman M, et al. Sputum microbiome in bronchiectasis. PLoS One. 2017;12(2):e0170622.
37. Bertelsen A, Elborn JS, Schock BC. Prevotella–P. aeruginosa interaction. J Cyst Fibros. 2021;20(4):682–691.
38. Dufrénoy M, Luca L, Bironneau V, Meurice JC, Puyade M, Martin M. Primary immune deficiency screening. Rev Med Interne. 2024;45(9):537–42.
39. Arslan Arshad AS, Khan A, Ahmad W, Arshad I. Viral genomics. Adv Mod Biomed. 2025;1(1):1–16.
40. Perea L, Cantó E, Suarez-Cuartin G, Aliberti S, Chalmers JD, Sibila O, et al. Immune profile clustering. Chest. 2021;159(5):1758–67.
41. Jonckheere AC, Steelant B, Seys SF, Cremer J, Dilissen E, Boon L, et al. Regulatory T cell deficiency. J Immunol. 2022;209(8):1595–605.
42. Gao Y, Richardson H, Dicker AJ, Barton A, Kuzmanova E, Shteinberg M, et al. Exacerbation endotypes. Am J Respir Crit Care Med. 2024;210(1):77–86.
43. Lin HC, Hsieh MH, Lo YL, Huang HY, Huang SW, Huang CD, et al. IL-6 and TIMP-1 in bronchiectasis. J Inflamm Res. 2024;17:5701–5709.
44. Sagel SD, Kupfer O, Wagner BD, Davis SD, Dell SD, Ferkol TW, et al. Airway inflammation in PCD. Ann Am Thorac Soc. 2023;20(1):67–74.
45. He Q, Li M, Cao J, Zhang M, Feng C. Dectin-1 and IL-17 in aspergillosis. Front Cell Infect Microbiol. 2022;12:1018499.
46. Westhölter D, Beckert H, Straßburg S, Welsner M, Sutharsan S, Taube C, et al. Regulatory T cells in cystic fibrosis. J Cyst Fibros. 2021;20(6):1072–9.
47. Posadas T, Oscullo G, Zaldivar E, Villa C, Dobarganes Y, Girón R, et al. CRP prognostic value. Arch Bronconeumol. 2021;57(1):21–7.
48. Eklöf J, Alispahic IA, Armbruster K, Lapperre TS, Browatzki A, Overgaard RH, et al. Antibiotics for P. aeruginosa. Respir Res. 2024;25(1):236.
49. Shirata M, Nishioka K, Hamao N, Oi I, Hidaka Y, Ibi Y, et al. Facemask during exercise. Respir Med. 2023;220:107453.
50. Kok HC, McCallum GB, Yerkovich ST, Grimwood K, Fong SM, Nathan AM, et al. Antibiotic duration in pneumonia. Pediatr Infect Dis J. 2024;43(9):872–9.
51. Beyoglu MA, Sahin MF, Turkkan S, Yazicioglu A, Akbulut ED, Neselioglu S, et al. Thiol-disulfide homeostasis. Exp Clin Transplant. 2023;21(10):841–7.
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| Keywords | ||
| Bronchiectasis Bronchi Cellular Cytokines Immunity Inflammation Microbiota | ||
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