https://orcid.org/0000-0002-5813-3194
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Abstract
Purpose
To assess the metabolites associated with Pseudomonas aeruginosa infection by analyzing the microbial diversity and metabolomics in lower respiratory tract of bronchiectasis patients and to explore the therapeutic approaches for Pseudomonas aeruginosa infection.
Methods
Bronchoalveolar lavage fluid samples from bronchiectasis patients and controls were analyzed by 16S rRNA and ITS sequencing, and metabolomic analysis was performed by liquid chromatography/mass spectrometry. A co-culture model of air-liquid interface cultured human bronchial epithelial cell with Pseudomonas aeruginosa was constructed to verify the correlation between sphingosine metabolism, acid ceramidase expression, and Pseudomonas aeruginosa infection.
Results
After screening, 54 bronchiectasis patients and 12 healthy controls were included. Sphingosine levels in bronchoalveolar lavage fluid were positively correlated with lower respiratory tract microbial diversity and negatively correlated with the abundance of Pseudomonas spp. Moreover, sphingosine levels in bronchoalveolar lavage fluid and acid ceramidase expression levels in lung tissue specimens were significantly lower in bronchiectasis patients than in healthy controls. Sphingosine levels and acid ceramidase expression levels were also significantly lower in bronchiectasis patients with positive Pseudomonas aeruginosa cultures than in bronchiectasis patients without Pseudomonas aeruginosa infection. Acid ceramidase expression in air-liquid interface cultured human bronchial epithelial cell had significantly increased after 6 h of Pseudomonas aeruginosa infection, while it had decreased significantly after 24 h of infection. In vitro experiments showed that sphingosine had a bactericidal effect on Pseudomonas aeruginosa by directly disrupting its cell wall and cell membrane. Furthermore, adherence of Pseudomonas aeruginosa on bronchial epithelial cells was significantly reduced after sphingosine supplementation.
Conclusion
Down-regulation of acid ceramidase expression in airway epithelial cells of bronchiectasis patients leads to insufficient metabolism of sphingosine, which has a bactericidal effect, and consequently weakens the clearance of Pseudomonas aeruginosa; thus, a vicious circle is formed. Exogenous supplementation with sphingosine aids bronchial epithelial cells in resisting Pseudomonas aeruginosa infection.
Abbreviations
P. Aeruginosa, Pseudomonas aeruginosa; BALF, bronchoalveolar lavage fluid; LC-MS, liquid chromatography coupled with mass spectrometry; BSI, bronchiectasis severity index; HE, hematoxylin and eosin; CFU, colony forming unit; ELISA, enzyme-linked immunosorbent assay; TSB, trypticase soy broth; PLS-DA, partial least squares discriminant analysis; ANOSIM, analysis of similarities; CCA, canonical correspondence analysis.
Data Sharing Statement
All data generated or analysed during this study are included in this published article and its Supplementary Material.
Ethics Approval and Informed Consent
This study was approved by the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital ethics committee [2021 (S402)] and Qilu Hospital of Shandong University ethics committee [2019 (147)], and all study participants provided informed consent.
Author Contributions
QQ, XJW and WYJ acquired and analyzed the data, and drafted the work. ZJ, GMX and LY provided specimens for bronchoscopy of patients and were contributors in writing the manuscript. DL designed the work and substantively revised it. All authors reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. All authors agree to take responsibility and are accountable for the contents of the article. All authors approved the final manuscript and agreed on the journal to which the article will be submitted.
Disclosure
The authors declare that they have no competing interests.