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Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease
- Source :
- PeerJ, PeerJ, Vol 4, p e2174 (2016)
- Publication Year :
- 2016
- Publisher :
- PeerJ Inc., 2016.
-
Abstract
- Background.Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy.Methods.Longitudinal sputum samples were collected from 11 patients (n= 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics.Results.The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated toStenotrophomonasandPseudomonas, while ceramides and other lipids were correlated withStreptococcus,Rothia, and anaerobes.Conclusions.This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset.
- Subjects :
- 0301 basic medicine
Exacerbation
medicine.drug_class
Bioinformatics
Antibiotics
lcsh:Medicine
Disease
Biology
Cystic fibrosis
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Metabolomics
medicine
Metabolome
Respiratory Medicine
Mass spectrometry
business.industry
General Neuroscience
lcsh:R
General Medicine
medicine.disease
Personalized medicine
3. Good health
030104 developmental biology
Infectious Diseases
030228 respiratory system
Immunology
Sputum
medicine.symptom
General Agricultural and Biological Sciences
business
Subjects
Details
- Language :
- English
- ISSN :
- 21678359
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- PeerJ
- Accession number :
- edsair.doi.dedup.....13c3af7b575b707f14b81f1e62044b24