Role of Bile Acids and Bile Salts in Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is one of the most common gastroenterological disorders leading to hospitalization. It has long been debated whether biliary AP, about 30% to 50% of all cases, is induced by bile acids (BAs) when they reach the pancreas via reflux or via the systemic blood circulation. Besides their classical function in digestion, BAs have become an attractive research target because of their recently discovered property as signaling molecules. The underlying mechanisms of BAs have been investigated in various studies. Bile acids are internalized into acinar cells through specific G-protein–coupled BA receptor 1 and various transporters. They can further act via different receptors: the farnesoid X, ryanodine, and inositol triphosphate receptor. Bile acids induce a sustained Ca 2+ influx from the endoplasmic reticulum and release of Ca 2+ from acidic stores into the cytosol of acinar cells. The overload of intracellular Ca 2+ results in mitochondrial depolarization and subsequent acinar cell necrosis. In addition, BAs have a biphasic effect on pancreatic ductal cells. A more detailed characterization of the mechanisms through which BAs contribute to the disease pathogenesis and severity will greatly improve our understanding of the underlying pathophysiology and may allow for the development of therapeutic and preventive strategies for gallstone-inducedAP.

The association between parenteral nutrition and pancreatic injury in adult patients: a retrospective observational study

“…They found significant increases in bile acids after PN initiation. Bile acids could have harmful effects on pancreatic duct cells [30,31]. Consistent with above-mentioned studies, we also observed that serum bile acids were significantly associated with serum level of pancreatic enzymes, which indicated that bile acids might play an important role in PN related pancreatic injury.…”

Based on multi omics analysis of gut microbiota characteristics in patients with acute pancreatitis and exploring the possible mechanism of its exacerbation trend from the level of microbiota and its metabolites

“…A number of differentially expressed metabolites were identified in patients with different severity (M vs. S) AP, including isoproterenol, muricholic acid, and cis-Aconitic acid.Previous studies have shown that bile acids and their metabolites have been associated with the cytopathological process of pancreatitis in some studies [27][28].Muricholic acid is a specific type of bile acids. Studies have found that bile acids play a role as signal molecules by targeting receptors, regulating a variety of pathophysiological processes such as metabolism, inflammation and immunity downstream [29][30][31].Prof.…”

Investigation of the potential role of TGR5 in pancreatic cancer by a comprehensive molecular experiments and the liquid chromatography mass spectrometry (LC–MS) based metabolomics

“…Morphologically, PANC-1 and BXPC3 cells treated with SBI-115 exhibited unregulated-shaped bodies and more visible vacuoles, and the transmission electron microscopy showed the mitochondria in SBI-115-treated cells exhibited decreased mitochondrial cristae, swollen-shaped body and ruptured mitochondrial membranes. Mitochondria are important organelles for cellular physiology and homeostasis in most eukaryotic organisms, and bile acids could directly act on the mitochondria [ 39 ]. TGR5 ablation did influence the mitochondrial biogenetic pathway [ 40 ].…”