Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Abstract

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 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.

Microbial Phenolic Metabolites in Urine Are Inversely Linked to Certain Features of Metabolic Syndrome in Spanish Adolescents

“…Urolithins are the final metabolites of ellagitannins, the main group of hydrolysable tannins [ 13 , 14 , 47 ], which are found in nuts and red fruits, including grapes, pomegranates, and some berries. Ellagitannins are broken down into ellagic acids, which are transformed into urolithins by the action of the gut microbiota [ 14 , 47 , 48 ]. Urolithins are metabolized in enterocytes and hepatocytes into glucuronide, sulfate, and methylated phase II metabolites and are excreted in breast milk and urine [ 13 , 49 ].…”

“…We also observed that higher urinary levels of urolithin B were associated with lower odds of presenting abdominal obesity, which could be attributed to its enhancing effects on thermogenesis, lipolysis, fatty oxidation, and inhibition of lipogenesis and adipogenesis [ 47 ]. Significant interindividual variation has been observed in urolithin production and excretion, with an effect on cardiometabolic health [ 14 , 17 , 18 , 48 ]. Based on urinary excretion, three urolithin metabotypes (UMs) have been identified: UM-A individuals produce only urolithin A, those with UM-B produce urolithin B and isourolithin A, and those with UM-0 are nonproducers [ 14 , 17 , 18 ].…”

The Potential Roles of Dietary Anthocyanins in Inhibiting Vascular Endothelial Cell Senescence and Preventing Cardiovascular Diseases

“…SCFA, as a fuel that can provide energy for epithelial cells, can reduce intestinal pH and inhibit the proliferation of pathogens, thereby improving intestinal barrier and avoiding the translocation of pathogens and antigens [ 72 ].

Figure 2 Scheme of anthocyanin absorption and metabolism [ 75 ]. Anthocyanins can interact with enzymes in the oral cavity after being ingested, resulting in enzymatic hydrolysis of anthocyanins.

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“…Figure 2. Scheme of anthocyanin absorption and metabolism[75]. Anthocyanins can interact with enzymes in the oral cavity after being ingested, resulting in enzymatic hydrolysis of anthocyanins.…”

Urolithin A induces protective autophagy to alleviate inflammation, oxidative stress, and endoplasmic reticulum stress in pediatric pneumonia

“…In addition, UA inhibits RANKL-induced osteoclast formation and postmenopausal osteoporosis through inhibition of inflammation and downstream NF-κBactivated pyroapoptotic pathway. 25 through protective autophagy. Collectively, these observations confirmed that UA could serve as a promising drug for treating pneumonia.…”