ArticleBMC pulmonary medicine2026
Metabolomic signatures of early pathway disruptions and clinical outcomes in community-acquired pneumonia: a prospective case-control study.
Article in BMC pulmonary medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe disruption of metabolic pathways in patients with community-acquired pneumonia (CAP) may provide insights into disease progression. We aim to identify early disruption in the serum metabolome of CAP patients using untargeted metabolic approaches.
methodsWe conducted a single-centre, prospective case-control study involving 105 participants (70 with CAP and 35 healthy controls), between January 2025 and November 2025. We also performed a subgroup exploratory metabolomic analysis among the 70 CAP patients, comparing 60 patients with severe CAP requiring ICU admission with the 10 non-severe CAP patients who did not require ICU admission. Untargeted serum metabolomics was performed using gas chromatography-mass spectrometry (GC-MS) to investigate metabolic dysregulation in patients with CAP. The analysis of the clinical data was performed using SPSS version 25.0. The data of metabolomics was analyzed using MetaboAnalyst version 6.0. After the preprocessing, log
resultsThe variable importance in projection (VIP) scores showed that out of 93 untargeted metabolites studied using GC-MS, the greatest differences between the CAP patients and healthy controls were about malic acid (VIP:3.374, fold change 2.591), 4-hydroxybenzeneacetic acid (VIP:2.459, fold change 27.97), 2-hydroxybutyric acid (VIP:2.059, fold change 4.779), and 4-hydroxyphenyllactic acid (VIP:1.882, fold change 20.67). Key disrupted pathways in CAP patients included propanoate, glyoxylate, and dicarboxylate; tricarboxylic acid cycle; nitrogen; tyrosine, cysteine, and methionine; and amino acid pathways. Comparison between the severe CAP patients (ICU admission required) and non-severe CAP patients (no-ICU admission), VIP analysis identified boric acid, ethylene glycol, ethanimidic acid, linoleic acid, oleic acid, cholesterol, 3-hydroxybutyrate, and α-tocopherol as the principal discriminating metabolites, while pathway analysis revealed perturbations in glutathione metabolism, amino acid metabolism, the tricarboxylic acid cycle, pyruvate metabolism, and arachidonic acid metabolism.
conclusionsCAP patients demonstrated early disruptions of key metabolic pathways compared with healthy controls, spanning energy metabolism, amino acid pathways, redox balance, lipid inflammatory signalling, and gut-host metabolic axes. These findings highlight the potential utility of metabolomic profiling as an adjunctive clinical tool for early risk stratification and biochemical phenotyping in CAP.
trial registrationClinical trials Registry of India (CTRI 2024/12/078631) registration was done 27.12.2024.
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