Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Urolithin A (Uro A) is a dietary metabolite of the intestinal microbiota following the ingestion of plant-based food ingredients ellagitannins and ellagic acid in mammals. Accumulating studies have reported its multiple potential health benefits in a broad range of diseases, including cardiovascular disease, cancer, cognitive impairment, and diabetes. In particular, Uro A is safe via direct oral administration and is non-genotoxic. The pancreas plays a central role in regulating energy consumption and metabolism by secreting digestive enzymes and hormones. Numerous pathophysiological factors, such as inflammation, deficits of mitophagy, and endoplasmic reticulum stress, can negatively affect the pancreas, leading to pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes mellitus. Recent studies showed that Uro A activates autophagy(definition) and inhibits endoplasmic reticulum stress in the pancreas, thus decreasing oxidative stress, inflammation, and apoptosis. In this review, we summarize the knowledge of Uro A metabolism and biological activity in the gut, as well as the pathological features and mechanisms of common pancreatic diseases. Importantly, we focus on the potential activities of Uro A and the underlying mechanisms in ameliorating various pancreatic diseases via inhibiting inflammatory signaling pathways, activating autophagy, maintaining the mitochondrial function, and improving the immune microenvironment. It might present a novel nutritional strategy for the intervention and prevention of pancreatic diseases.