Biological Significance of Urolithins, the Gut Microbial Ellagic Acid-Derived Metabolites: The Evidence So Far

Bacchus-Biological significance of urolithinsJuan Carlos Espín and colleagues from CEBAS-CSIC (ES) have reviewed literature describing urolithin metabolites production by gut microbiota, their absorption, tissue distribution and pharmacokinetics, and cell and molecular mechanisms for their biological effects as determined using different models in vitro, and in animals and humans.

Health benefits attributed to pomegranate are associated with its high polyphenols content, particularly ellagitannins, which is also true for other ellagitannin-rich fruits and nuts including strawberry, raspberry, blackberry, walnuts, and Muscadine grapes.

The bioavailability of ellagitannins and ellagic acid, however, from these foods is very low because of extensive metabolism by gut microbiota to produce urolithins. It is, therefore, conceivable that the health benefits of ellagitannin-containing foods are related to these gut microbiota-produced urolithins, meaning evaluation of their biological effects is essential.

More recent research, based on testing in vitro, suggests evidence of anti-inflammatory, anti-carcinogenic, anti-glycative, antioxidant, and antimicrobial effects, supporting the potential of urolithinsin health effects attributed to pomegranate and other ellagitannin-rich foods.

The review describes how urolithins can reach significant concentrations in the human body, after intake of ellagitannin-containing products. However, there is very little work on the direct biological activity of urolithins,and future studies should use physiologically relevant metabolites (e.g. urolithins in gut models and conjugated derivatives in systemic models) at concentrations that can be achieved in vivo.

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Highlights:

  1. Mechanistic and studies in vivo are necessary to clarify the health effects of urolithins.
  2. Pomegranate extract and urolithin A modulated favourably gut microbiota in healthy rats, which could contribute to the health benefits associated with pomegranate juice and intake of urolithin A from ellagitannin-rich fruits and nuts.
  3. Studies in vitro with specific cell models and metabolites (i.e. urolithin and conjugates, such as glucuronides or sulphates) couldbeuseful to unravel mechanisms of action.