Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome

Area of Science:

• Microbiology
• Metabolomics
• Immunology

Background:

• Cystic fibrosis (CF) lungs harbor thick mucus, promoting chronic infections, notably by Pseudomonas aeruginosa.
• Pseudomonas aeruginosa produces toxins, but its behavior in the CF lung environment is poorly understood.
• Current methods may not accurately reflect bacterial activity in vivo.

Purpose of the Study:

• Investigate the chemical composition of CF sputum using molecular networking-based metabolomics.
• Assess the relationship between detected microbial molecules, the microbiome, and clinical culture data.
• Identify host and microbial metabolites contributing to CF pathogenesis.

Main Methods:

• Employed molecular networking-based metabolomics on CF sputum samples.
• Analyzed detected metabolites, including xenobiotics, P. aeruginosa metabolites, and host sphingolipids.
• Compared metabolomic data with clinical culture and microbiome profiles.

Main Results:

• Detected xenobiotics, P. aeruginosa metabolites, and host sphingolipids in CF sputum.
• Found discrepancies between P. aeruginosa metabolites in sputum and those from laboratory cultures.
• Observed absence of Pseudomonas Quinolone Signal (PQS) in sputum despite precursor presence.
• Identified sphingolipids (sphingomyelins, ceramides, lactosylceramide) as highly abundant and differentially abundant in CF sputum.

Conclusions:

• CF sputum is a complex mixture of host, microbial, and xenobiotic molecules.
• Bacterial detection via culturing or 16S rRNA profiling may not indicate active metabolite production in sputum.
• Host sphingolipids, particularly ceramides, may play a significant role in CF-associated hyperinflammation.
• In vivo P. aeruginosa metabolite production may differ from in vitro findings due to the lung environment.