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

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 that require intensification of therapy with enhanced airway clearance and int...

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Autores principales: Muhlebach, Marianne S., Sha, Wei, MacIntosh, Beth, Kelley, Thomas J., Muenzer, Joseph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424819/
https://www.ncbi.nlm.nih.gov/pubmed/32812947
http://dx.doi.org/10.1016/j.metop.2019.100010
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author Muhlebach, Marianne S.
Sha, Wei
MacIntosh, Beth
Kelley, Thomas J.
Muenzer, Joseph
author_facet Muhlebach, Marianne S.
Sha, Wei
MacIntosh, Beth
Kelley, Thomas J.
Muenzer, Joseph
author_sort Muhlebach, Marianne S.
collection PubMed
description 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 that require intensification of therapy with enhanced airway clearance and intravenous (IV) antibiotics. OBJECTIVES: In an observational study we tested if the profile of metabolites in serum distinguished the pre-from post-exacerbation state and which systemically measurable pathways were affected during the process to recovery. METHODS: Serum collected within 48 h of start and completion, respectively of IV antibiotics was collected from people with CF ages 6–30 years. Three day food records were collected prior to each sample. To reduce variation between subjects only subjects who had pancreatic insufficiency, had similar CF mutations, and did not have CF liver disease or diabetes were included. Metabolomic profiling was conducted by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy with metabolites being identified based on retention time/index, mass to charge ratio and comparison to known compounds. Biostatistical analyses used paired t-test with correction for multiple comparisons and orthogonal partial least square discriminant analysis. RESULTS: Thirty subjects (20 male) with a mean ± SEM age of 15.3 ± 1.2 years participated, 17 of whom had matched food-records. Lung function was significantly improved post-therapy compared to pre-therapy, (mean ± SEM) 75 ± 4% vs. 68 ± 4% predicted (n = 26). Serum metabonomics showed distinction of the pre-vs. post-therapy groups with 123 compounds contributing to the differentiation pre-versus post-antibiotics by multiple biostatistical analyses. Compounds and pathways affected included bile acids and microbial derived amino acid metabolites, increases in lipid classes of the glycerophospholipid, glycerolipids, cholesterol, phopsholipids, and most pronounced, the class of sphingolipids. Changes in n6/n3 fatty acids, decreased polyamines but increased metabolites in the nitric oxide pathway, and changes in the tryptophan-kynurenine pathway indicated decreased inflammation at resolution of exacerbation. CONCLUSIONS: Changes in serum metabolites that distinguished CF pulmonary exacerbation vs. resolution of symptoms showed evidence of decreased inflammation and improvement from a catabolic state.
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spelling pubmed-74248192020-08-17 Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation Muhlebach, Marianne S. Sha, Wei MacIntosh, Beth Kelley, Thomas J. Muenzer, Joseph Metabol Open Original Research Paper 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 that require intensification of therapy with enhanced airway clearance and intravenous (IV) antibiotics. OBJECTIVES: In an observational study we tested if the profile of metabolites in serum distinguished the pre-from post-exacerbation state and which systemically measurable pathways were affected during the process to recovery. METHODS: Serum collected within 48 h of start and completion, respectively of IV antibiotics was collected from people with CF ages 6–30 years. Three day food records were collected prior to each sample. To reduce variation between subjects only subjects who had pancreatic insufficiency, had similar CF mutations, and did not have CF liver disease or diabetes were included. Metabolomic profiling was conducted by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy with metabolites being identified based on retention time/index, mass to charge ratio and comparison to known compounds. Biostatistical analyses used paired t-test with correction for multiple comparisons and orthogonal partial least square discriminant analysis. RESULTS: Thirty subjects (20 male) with a mean ± SEM age of 15.3 ± 1.2 years participated, 17 of whom had matched food-records. Lung function was significantly improved post-therapy compared to pre-therapy, (mean ± SEM) 75 ± 4% vs. 68 ± 4% predicted (n = 26). Serum metabonomics showed distinction of the pre-vs. post-therapy groups with 123 compounds contributing to the differentiation pre-versus post-antibiotics by multiple biostatistical analyses. Compounds and pathways affected included bile acids and microbial derived amino acid metabolites, increases in lipid classes of the glycerophospholipid, glycerolipids, cholesterol, phopsholipids, and most pronounced, the class of sphingolipids. Changes in n6/n3 fatty acids, decreased polyamines but increased metabolites in the nitric oxide pathway, and changes in the tryptophan-kynurenine pathway indicated decreased inflammation at resolution of exacerbation. CONCLUSIONS: Changes in serum metabolites that distinguished CF pulmonary exacerbation vs. resolution of symptoms showed evidence of decreased inflammation and improvement from a catabolic state. Elsevier 2019-06-08 /pmc/articles/PMC7424819/ /pubmed/32812947 http://dx.doi.org/10.1016/j.metop.2019.100010 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Paper
Muhlebach, Marianne S.
Sha, Wei
MacIntosh, Beth
Kelley, Thomas J.
Muenzer, Joseph
Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
title Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
title_full Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
title_fullStr Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
title_full_unstemmed Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
title_short Metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
title_sort metabonomics reveals altered metabolites related to inflammation and energy utilization at recovery of cystic fibrosis lung exacerbation
topic Original Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424819/
https://www.ncbi.nlm.nih.gov/pubmed/32812947
http://dx.doi.org/10.1016/j.metop.2019.100010
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