Metabolic Signatures of Pancreatic Drain Fluid and Serum in Severe Acute Pancreatitis Revealed by High-Resolution ¹H NMR Metabolomics

Introduction: Acute pancreatitis (AP) is characterized by pancreatic necroinflammation, systemic inflammation, and profound metabolic dysregulation, resulting high mortality and morbidity. The early phase of severe acute pancreatitis (SAP) is accompanied by systemic inflammatory response syndrome (SIRS), multi-organ failure often requiring insensitive support of cardiopulmonary system. Respiratory failure is one of the major complications of AP and most patients with this extremely needed ventilatory support. Although serum metabolomics has been widely explored in SAP, the metabolomic profile of pancreatic drain fluid remains poorly characterized. This study compared the metabolomic signatures of serum and pancreatic drain fluid in SAP using high-resolution ¹H NMR spectroscopy.

Methods: Serum samples of SAP patients were collected within 48 hrs of ICU admission, and pancreatic drain fluid samples were obtained within 1-7 days of admission following percutaneous drainage of infected pancreatic collections. A total of 60 samples (30 serum and 30 drain fluid) were analysed using an 800 MHz ¹H NMR spectrometer. All the statistical analysis and pathway analysis was carried out using MetaboAnalyst 6.0. Untargeted metabolomic profiling and metabolite identification was done using Chenomx software.

Results: ¹H NMR metabolomics identified a different concentration metabolic fingerprint in pancreatic drain fluid compared with serum. Elevated arginine, tyrosine, phenylalanine, histidine, and formate, together with reduced glucose, delineated a compartment-specific metabolic phenotype, underscoring localized metabolic dysregulation associated with severe acute pancreatitis.

Conclusion: Pancreatic drain fluid metabolomics identifies localized metabolic perturbations with the potential to advance biomarker discovery and support precision medicine through improved clinical decision-making in severe acute pancreatitis.