Advancing Clinical and Pathophysiological Insights into Pancreatitis Using Lipidomics and Metabolomics

Acute pancreatitis (AP) and chronic pancreatitis (CP) are distinct inflammatory conditions with significant clinical burden, including associated complications and mortality. These pancreatic conditions share overlapping pathophysiologic features. Although AP can be followed by recurrent episodes (recurrent acute pancreatitis, RAP), most CP does not follow a simple linear progression from AP; rather, CP reflects sustained processes causing injury to the pancreas (e.g., toxic-metabolic, genetic, obstructive), leading to fibrosis and organ dysfunction. Lipidomics and metabolomics can provide insights into the pathophysiology of the disease. Although researchers have extensively explored lipids and metabolites to better understand disease mechanisms, comprehensive detailed insights into the pathways and intricate roles these molecules play in pancreatitis remain unidentified. This gap can be partially attributed to limited availability of human samples from disease subgroups in pancreatitis, and current technological constraints in analytical methods, particularly regarding complete lipid and metabolite detection, identification, and quantification. In this review, we summarize lipidomic and metabolomic workflows in the context of understanding pancreatitis pathophysiology, including their design and analytical strategies. We also highlight clinical studies on pancreatitis, utilizing lipidomics and metabolomics as a tool to identify altered or dysregulated lipids or metabolites, and their association with the disease state and its progression.