title: Gastrointestinal stability of urolithins: an in vitro approach.
abstract: OBJECTIVE
  Urolithins are bioactive ellagitannin-derived metabolites showing a wide phenotypic variation in their production by the gut microbiota. This work represents a first in vitro step toward the development of new strategies focused on the oral supplementation of urolithins with the aim of overcoming their selective production and making their putative health benefits available for the whole population.
  
  
  METHODS
  In order to study their gastrointestinal stability, urolithin A, urolithin B, and urolithin B-glucuronide, as well as ellagic acid, were subjected to a simulated gastrointestinal digestion model consisting of oral, gastric, and pancreatic steps followed by a 24-h fecal fermentation. The effect of the entero-hepatic recirculation on urolithin B-glucuronide, a phase II metabolite, was also investigated.
  
  
  RESULTS
  Urolithin B was the molecule able to resist to a greater extent the conditions of the gastrointestinal tract, while urolithin A and ellagic acid were drastically unstable during the colonic step. Conjugation with glucuronic acid, ideally occurring in the liver, conferred to urolithin B an increased stability, which may be interesting in the framework of entero-hepatic recirculation.
  
  
  CONCLUSIONS
  This set of experiments lets hypothesize that orally supplemented urolithins may come into contact with the colonic epithelium and become accessible for uptake or exert local anti-inflammatory activity, overcoming the limitations of enterotypes unable to convert ellagitannins into these putatively beneficial metabolites.
authors.affiliation: The Laboratory of Phytochemicals in Physiology, LS9 InterLab Group, Department of Food Science, University of Parma, Parma, Italy. pedromiguel.menaparreno@unipr.it.|Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125, Parma, Italy. pedromiguel.menaparreno@unipr.it.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mena
authors.affiliation: The Laboratory of Phytochemicals in Physiology, LS9 InterLab Group, Department of Food Science, University of Parma, Parma, Italy.|Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125, Parma, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Dall'Asta
authors.affiliation: The Laboratory of Phytochemicals in Physiology, LS9 InterLab Group, Department of Food Science, University of Parma, Parma, Italy.|Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125, Parma, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Calani
authors.affiliation: Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125, Parma, Italy.
authors.forename: Furio
authors.initials: F
authors.lastname: Brighenti
authors.affiliation: The Laboratory of Phytochemicals in Physiology, LS9 InterLab Group, Department of Food Science, University of Parma, Parma, Italy.|Human Nutrition Unit, Department of Food Science, University of Parma, Via Volturno 39, 43125, Parma, Italy.|The Need for Nutrition Education/Innovation Programme (NNEdPro), University of Cambridge, Cambridge, UK.
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
mesh_terms: D055598:Chemical Phenomena; D003106:Colon / Q000378:metabolism / Q000382:microbiology; D003374:Coumarins / Q000378:metabolism*; D004063:Digestion; D004610:Ellagic Acid / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005285:Fermentation; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D003374:Coumarins; D020719:Glucuronides; D047348:Hydrolyzable Tannins; C000595064:urolithin B; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid
keywords: Bioaccessibility; Colonic fermentation; Ellagic acid; Ellagitannin; Gastrointestinal tract; Microbial metabolite