Pediatric lung transplantation: Dynamics of the microbiome and bronchiolitis obliterans in cystic fibrosis

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:39

Article

Metwally, Ahmed A.^1,2,3  Ascoli, Christian²  Turturice, Benjamin^2,4  Rani, Asha²  Ranjan, Ravi²  Chen, Yang^2,5  Schott, Cody^2,4  Faro, Albert^6,7  Ferkol, Thomas W.^7,8  Finn, Patricia W.^1,2,4  Perkins, David L.^1,9,10 

[1] Univ Illinois, Dept Bioengn, Chicago, IL USA

[2] Univ Illinois, Dept Med, Div Pulm Crit Care Sleep & Allergy, Chicago, IL USA

[3] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[4] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA

[5] Univ Illinois, Dept Biol Sci, Chicago, IL 60680 USA

[6] Cyst Fibrosis Fdn, Bethesda, MD USA

[7] Washington Univ, Sch Med, Dept Pediat, Div Pediat Allergy Immunol & Pulm Med, St Louis, MO 63110 USA

[8] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

[9] Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA

[10] Univ Illinois, Dept Surg, Chicago, IL 60680 USA

关键词: cystic fibrosis;    bronchiolitis obliterans;    lung transplantation;    microbiome;    longitudinal studies;   

DOI  :  10.1016/j.healun.2020.04.016

来源: Elsevier

【 摘 要 】

BACKGROUND: Compositional changes in the microbiome are associated with the development of bronchiolitis obliterans (BO) after lung transplantation (LTx) in adults with cystic fibrosis (CF). The association between the lower airway bacterial community and BO after LTx in children with CF remains largely unexplored and is possibly influenced by frequent antibiotic therapy. The objectives of this study were to examine the relationship between bacterial community dynamics and the development of BO and analyze antibiotic resistance trends in children after LTx for CF. METHODS: For 3 years from the time of transplant, 12 LTx recipients were followed longitudinally, with 5 subjects developing BO during the study period. A total of 82 longitudinal bronchoalveolar lavage samples were collected during standard of care bronchoscopies. Metagenomic shotgun sequencing was performed on the extracted microbial DNA from bronchoalveolar lavage specimens. Taxonomic profiling was constructed using WEVOTE pipeline. The longitudinal association between development of BO and temporal changes in bacterial diversity and abundance were evaluated with MetaLonDA. The analysis of antibiotic resistance genes was performed with the ARGs-OAP v2.0 pipeline. RESULTS: All recipients demonstrated a Proteobacteria-predominant lower airways community. Temporal reduction in bacterial diversity was significantly associated with the development of BO and associated with neutrophilia and antibiotic therapy. Conversely, an increasing abundance of the phylum Actinobacteria and the orders Neisseriales and Pseudonocardiales in the lower airways was significantly associated with resilience to BO. A more diverse bacterial community was related to a higher expression of multidrug resistance genes and increased proteobacterial abundance. CONCLUSIONS: Decreased diversity within bacterial communities may suggest a contribution to pediatric lung allograft rejection in CF. J Heart Lung Transplant 2020;39:824-834 (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

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