Metabolomic signatures of early pathway disruptions and clinical outcomes in community-acquired pneumonia: a prospective case-control study
Abstract
The 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.
We 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
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transformation, normalization and scaling, 93 GC-MS metabolites were retained from the initial 300 metabolites. Principal component analysis was done for unsupervised clustering, which was then followed by OPLS-DA for supervised group discrimination. Model performance was assessed using R²Y and cross-validation-derived Q² values, and model robustness and overfitting exclusion was further evaluated using permutation testing. Discriminatory metabolites were identified using VIP scores, fold change, log₂ fold change and…
How strong is the evidence?
Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 105 participants or records.
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