Cargando…
Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease
Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; c...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330610/ https://www.ncbi.nlm.nih.gov/pubmed/35892580 http://dx.doi.org/10.3390/cells11152283 |
_version_ | 1784758204364750848 |
---|---|
author | Arshad, Haroon Siokis, Anastasios Franke, Raimo Habib, Aamna Alfonso, Juan Carlos López Poliakova, Yuliya Lücke, Eva Michaelis, Katina Brönstrup, Mark Meyer-Hermann, Michael Bilitewski, Ursula Vila, Jordi Abel, Laurent Illig, Thomas Schreiber, Jens Pessler, Frank |
author_facet | Arshad, Haroon Siokis, Anastasios Franke, Raimo Habib, Aamna Alfonso, Juan Carlos López Poliakova, Yuliya Lücke, Eva Michaelis, Katina Brönstrup, Mark Meyer-Hermann, Michael Bilitewski, Ursula Vila, Jordi Abel, Laurent Illig, Thomas Schreiber, Jens Pessler, Frank |
author_sort | Arshad, Haroon |
collection | PubMed |
description | Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD. |
format | Online Article Text |
id | pubmed-9330610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93306102022-07-29 Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease Arshad, Haroon Siokis, Anastasios Franke, Raimo Habib, Aamna Alfonso, Juan Carlos López Poliakova, Yuliya Lücke, Eva Michaelis, Katina Brönstrup, Mark Meyer-Hermann, Michael Bilitewski, Ursula Vila, Jordi Abel, Laurent Illig, Thomas Schreiber, Jens Pessler, Frank Cells Article Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD. MDPI 2022-07-24 /pmc/articles/PMC9330610/ /pubmed/35892580 http://dx.doi.org/10.3390/cells11152283 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Arshad, Haroon Siokis, Anastasios Franke, Raimo Habib, Aamna Alfonso, Juan Carlos López Poliakova, Yuliya Lücke, Eva Michaelis, Katina Brönstrup, Mark Meyer-Hermann, Michael Bilitewski, Ursula Vila, Jordi Abel, Laurent Illig, Thomas Schreiber, Jens Pessler, Frank Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease |
title | Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease |
title_full | Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease |
title_fullStr | Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease |
title_full_unstemmed | Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease |
title_short | Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease |
title_sort | reprogramming of amino acid metabolism differs between community-acquired pneumonia and infection-associated exacerbation of chronic obstructive pulmonary disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330610/ https://www.ncbi.nlm.nih.gov/pubmed/35892580 http://dx.doi.org/10.3390/cells11152283 |
work_keys_str_mv | AT arshadharoon reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT siokisanastasios reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT frankeraimo reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT habibaamna reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT alfonsojuancarloslopez reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT poliakovayuliya reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT luckeeva reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT michaeliskatina reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT bronstrupmark reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT meyerhermannmichael reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT bilitewskiursula reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT vilajordi reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT abellaurent reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT illigthomas reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT schreiberjens reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease AT pesslerfrank reprogrammingofaminoacidmetabolismdiffersbetweencommunityacquiredpneumoniaandinfectionassociatedexacerbationofchronicobstructivepulmonarydisease |