Urolithins at the Crossroads of Gut Inflammation and Cancer-A Narrative Review

Chronic inflammation and the associated dysbiosis of the gut microbiota are increasingly recognized as key factors contributing to the development of inflammatory bowel disease (IBD) and colorectal cancer (CRC). The diet-gut microbiota-immune system-cancer axis is considered a key regulator of these processes. Among the bioactive compounds found in the diet, ellagitannins have garnered significant scientific interest due to their conversion by the gut microbiota into biologically active metabolites known as urolithins. Urolithin A (UroA), one of the best characterized compounds, exhibits broad anti-inflammatory, antioxidant, immunomodulatory, and anticancer properties. It modulates signaling pathways associated with inflammation, oxidative stress, mitochondrial dysfunction, and cell proliferation. Furthermore, UroA has been shown to improve intestinal barrier integrity, regulate immune cell activity, and induce mitophagy, thereby contributing to the restoration of mitochondrial and cellular homeostasis. A growing body of evidence also suggests that UroA may inhibit cancer cell proliferation, induce apoptosis, and disrupt the molecular pathways involved in colorectal carcinogenesis. This review summarizes the current state of knowledge regarding the biosynthesis and bioavailability of UroA, its molecular mechanisms of action in IBD, and its potential role in the prevention and treatment of CRC. Furthermore, the limitations of UroA-based therapies and future research directions are discussed. Although further, well-designed clinical trials are necessary, current findings suggest that UroA may represent a promising microflora-targeted therapeutic strategy in chronic inflammatory and CRC diseases.