Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota

Abstract

Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin‐rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so‐called urolithin metabotypes (UM‐A, UM‐B, and UM‐0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.

Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome: Results From a European Two-Center Study

“…Considering their microbial origin, this variability could be mainly due to changes in the gut microbiota composition over the study year, but also to other phenotypic (e.g., weight changes) and environmental (e.g., changes in dietary habits) factors ( 34 ). In particular, it should be noted the existence of inter-individual variability factors related to the incapacity of some individuals to produce specific microbiota derivatives, i.e., the so-called “metabotypes.” This is of particular importance for urolithin production, for which three metabotypes have been described ( 35 ), and could be, at least in part, behind the variability reported in the present study. Altogether, our results suggest that microbial-derived metabolites could be better indicators of healthy dietary habits than the corresponding parent polyphenol species.…”

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

“…Urolithin metabotypes (UMs) can be divided into three phenotypes (UM-A, UM-B, and UM-0) based on the different abilities of human subjects to excrete urolithins. UM-A produced Uro A; UM-B mainly produced iso-Uro A and Uro-B; and UM-0 did not produce Uro-A, iso-Uro A, or Uro B [13]. The distribution of UM-A and UM-B was affected by aging, with UM-A decreasing from 85% to 55% after adulthood [14].…”

Urolithins and intestinal health

“…ETs and EA are polyphenols present in a variety of fruits, vegetables, nuts and medicinal plants, with a variety of biological activities. Most of EA is metabolized by intestinal flora to produce a series of urolithins that are more easily absorbed, and their concentrations in different tissues ranging from 0.003 to 50 μM (40). Therefore, urolithins may be the real bioactive substances rich in ETs in organisms.…”