Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine

Abstract

Background: There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such "functional metabolites" in ARDS using metabolomics and in vivo experiments in a mouse model.Methods: Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for "functional metabolites", which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of "functional metabolites" in the lung injury and mortality caused by the respiratory disorder. Results: The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. Conclusion: Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine.

Phenylalanine and COVID-19: Tracking disease severity markers

“…Recently Xu et al showed that patients with acute respiratory distress syndrome (ARDS) have significantly different metabolomic profiles than healthy controls. [31] According to their results, phenylalanine, D-phenylalanine, and phenylacetylglutamine levels were higher among non-survivors. Phenylalanine metabolism was the most notably altered pathway among non-survivors and survivors.…”

Cluster analysis and profiling of airway fluid metabolites in pediatric acute hypoxemic respiratory failure

“…There are several studies that have compared the metabolic profiles of plasma, pulmonary edema fluid, bronchoalveolar lavage fluid (BALF), and non-bronchoscopic alveolar lavage (mini BALF or mBALF) in adults with acute respiratory distress syndrome (ARDS) to healthy controls using various untargeted and targeted techniques including 1 H-nuclear magnetic resonance (1-H NMR), gas chromatography-mass spectrometry (GC–MS) and liquid chromatography-mass spectrometry (LC–MS) 5,6,25,26 . Others have used metabolomic analyses to aid diagnosis, stratify ARDS patients by severity, and predict survival outcome 5 , 27 – 29 . Pathways distinguishing survivors from non-survivors with ARDS included glutamine and glutamate metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and phenylalanine metabolism 6 , 29 .…”

“…Others have used metabolomic analyses to aid diagnosis, stratify ARDS patients by severity, and predict survival outcome 5 , 27 – 29 . Pathways distinguishing survivors from non-survivors with ARDS included glutamine and glutamate metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and phenylalanine metabolism 6 , 29 . Adult endotyping studies using mBALF showed differences in lysine, arginine, tyrosine, threonine, and branched chain amino acids 6 .…”

Accurate virus identification with interpretable Raman signatures by machine learning

“…We also included surface protein-related functional groups and individual amino acids, such as amide, phenylalanine and tyrosine. Phenylalanine and tyrosine are chosen because of reports that they are present and important in respiratory viruses (29)(30)(31)(32)(33). RNA is also included because all viruses tested here have RNA genomes.…”