Metabolomics Reveals Anaerobic Bacterial Fermentation and Hypoxanthine Accumulation for Fibrinous Pleural Effusions in Children with Pneumonia

• Published in: Journal of proteome research Vol. 18; no. 3; pp. 1248 - 1254
• Main Authors: Chiu, Chih-Yung, Cheng, Mei-Ling, Wong, Kin-Sun, Lai, Shen-Hao, Chiang, Meng-Han, Tsai, Ming-Han, Lin, Gigin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.2019
• Subjects: 3-Hydroxybutyric Acid - metabolism; Adolescent; Anaerobiosis - genetics; Bacteria, Anaerobic - metabolism; Bacteria, Anaerobic - pathogenicity; Child; Child, Preschool; Cytokines - genetics; Cytokines - metabolism; Female; Fermentation; Fibrin - genetics; Fibrin - metabolism; Fibrinolysis - genetics; Glucose - metabolism; Humans; Hypoxanthine - metabolism; Infant; Lactic Acid - metabolism; Lung - diagnostic imaging; Lung - metabolism; Lung - pathology; Male; Metabolomics - methods; Pleural Effusion - metabolism; Pleural Effusion - microbiology; Pleural Effusion - pathology; Pneumonia - diagnostic imaging; Pneumonia - metabolism; Pneumonia - microbiology; Pneumonia - pathology; infectious parapneumonic effusion; fibrin; metabolomics; nuclear magnetic resonance; childhood pneumonia
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.8b00864

Fibrin formation in infectious parapneumonic effusion (IPE) characterizes complicated parapneumonic effusion and is important for providing guidelines for the management of IPEs that require aggressive interventions. We aim to identify metabolic mechanisms associated with bacterial invasion, inflammatory cytokines, and biochemical markers in cases of fibrinous infectious pleural effusions in children with pneumonia. Pleural fluid metabolites were determined by 1H nuclear magnetic resonance spectroscopy. Metabolites that contributed to the separation between fibrinous and nonfibrinous IPEs were identified using supervised partial least squares discriminant analysis (Q 2/R 2 = 0.84; P permutation < 0.01). IL-1β in the inflammatory cytokines and glucose in the biochemical markers were significantly correlated with 11 and 9 pleural fluid metabolites, respectively, and exhibited significant overlaps. Four metabolites, including glucose, lactic acid, 3-hydroxybutyric acid, and hypoxanthine, were significantly correlated with plasminogen activator inhibitor type 1 in the fibrinolytic system enzymes. Metabolic pathway analysis revealed that anaerobic bacterial fermentation with increased lactic acid and butyric acid via glucose consumption and adenosine triphosphate hydrolysis with increased hypoxanthine appeared to be associated with fibrinous IPE. Our results demonstrate that an increase in lactic acid anaerobic fermentation and hypoxanthine accumulation under hypoxic conditions are associated with fibrin formation in IPE, representing advanced pleural inflammatory progress in children with pneumonia.