Metabolomics profiles show elevated phenylalanine and lactate alongside depleted sphingosine 1-phosphate and citrulline in ARDS patients

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe condition with high mortality, despite the absence of metabolomics biomarkers validated for its pathophysiological features. This systematic review and meta-analysis aim to identify robust metabolic ARDS signatures. METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, OVID, and Cochrane Library up to March 2025. Case-control studies comparing metabolomics profiles between patients with ARDS and those without ARDS were included. Study quality and risk of bias were assessed using the Newcastle-Ottawa Scale and the NTP/OHAT tool. Random-effects meta-analyses of standardized mean differences were performed with subgroup and sensitivity analyses, while pathway enrichment was conducted as a separate component of the biological evaluation. RESULTS: Phenylalanine and lactate levels were elevated in ARDS patients, whereas sphingosine 1-phosphate and citrulline were depleted. Pathway analysis reveals eight disrupted networks, including arginine biosynthesis and glyoxylate metabolism, with "amino acids/peptides" driving the predominant alterations. CONCLUSION: This study illustrates metabolic reprogramming as a hallmark of ARDS pathogenesis, linking amino acid and lipid imbalances to inflammation and vascular dysfunction. The findings emphasise the importance of platform harmonization and the potential of biomarker research.