Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation.

摘要: Abstract Background Cystic fibrosis lung disease is characterized by chronic bacterial infections in the setting of mucus abnormalities. Patients experience periodic exacerbations that manifest with increased respiratory symptoms require intensification therapy enhanced airway clearance and intravenous (IV) antibiotics. Objectives In an observational study we tested if profile metabolites serum distinguished pre-from post-exacerbation state which systemically measurable pathways were affected during process to recovery. Methods Serum collected within 48 h start completion, respectively IV antibiotics was from people CF ages 6–30 years. Three day food records prior each sample. To reduce variation between subjects only who had pancreatic insufficiency, similar mutations, did not have liver or diabetes included. Metabolomic profiling conducted Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy being identified based on retention time/index, mass charge ratio comparison known compounds. Biostatistical analyses used paired t-test correction for multiple comparisons orthogonal partial least square discriminant analysis. Results Thirty (20 male) a mean ± SEM age 15.3 ± 1.2 years participated, 17 whom matched food-records. Lung function significantly improved post-therapy compared pre-therapy, (mean ± SEM) 75 ± 4% vs. 68 ± 4% predicted (n = 26). metabonomics showed distinction pre-vs. groups 123 compounds contributing differentiation pre-versus post-antibiotics biostatistical analyses. Compounds included bile acids microbial derived amino acid metabolites, increases lipid classes glycerophospholipid, glycerolipids, cholesterol, phopsholipids, most pronounced, class sphingolipids. Changes n6/n3 fatty acids, decreased polyamines but nitric oxide pathway, changes tryptophan-kynurenine pathway indicated inflammation at resolution exacerbation. Conclusions pulmonary exacerbation evidence improvement catabolic state.