title: Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: A randomized clinical trial.
abstract: The pomegranate lipid-lowering properties remain controversial, probably due to the interindividual variability in polyphenol (ellagitannins) metabolism.
  
  
  
  We aimed at investigating whether the microbially derived ellagitannin-metabolizing phenotypes, i.e. urolithin metabotypes A, (UM-A), B (UM-B), and 0 (UM-0), influence the effects of pomegranate extract (PE) consumption on 18 cardiovascular risk biomarkers in healthy overweight-obese individuals.
  
  
  
  A double-blind, crossover, dose-response, randomized, placebo-controlled trial was conducted. The study (POMEcardio) consisted of two test phases (dose-1 and dose-2, lasting 3 weeks each) and a 3-week washout period between each phase. Forty-nine participants (BMI > 27 kg/m2) daily consumed one (dose-1, 160 mg phenolics/day) or four (dose-2, 640 mg phenolics/day) PE or placebo capsules. Notably, UM-B individuals showed the highest baseline cardiovascular risk. After dose-2, total cholesterol (-15.5 ± 3.7%), LDL-cholesterol (-14.9 ± 2.1%), small LDL-cholesterol (-47 ± 7%), non-HDL-cholesterol (-11.3 ± 2.5%), apolipoprotein-B (-12 ± 2.2%), and oxidized LDL-cholesterol -24 ± 2.5%) dose dependently decreased (P < 0.05) but only in UM-B subjects. These effects were partially correlated with urolithin production and the increase in Gordonibacter levels. Three (50%) nonproducers (UM-0) became producers following PE consumption.
  
  
  
  UM clustering suggests a personalized effect of ellagitannin-containing foods and could explain the controversial pomegranate benefits. Research on the specific role of urolithins and the microbiota associated with each UM is warranted.
authors.affiliation: Department of Food Science and Technology, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Sarrías
authors.affiliation: Department of Food Science and Technology, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Villalba
authors.affiliation: Department of Food Science and Technology, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Romo-Vaquero
authors.affiliation: TÜBİTAK Marmara Research Center, Food Institute, Gebze-Kocaeli, Turkey.
authors.forename: Cesarettin
authors.initials: C
authors.lastname: Alasalvar
authors.affiliation: Department of Biochemistry, Faculty of Medicine, , Karadeniz Technical University, Trabzon, Turkey.
authors.forename: Asim
authors.initials: A
authors.lastname: Örem
authors.affiliation: Department of Food Technology and Nutrition, Catholic University of San Antonio, Murcia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Zafrilla
authors.affiliation: Department of Food Science and Technology, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.affiliation: Department of Food Science and Technology, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
authors.forename: María V
authors.initials: MV
authors.lastname: Selma
authors.affiliation: Department of Food Science and Technology, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D003374:Coumarins / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000032:analysis / Q000494:pharmacology; D029561:Lythraceae / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D050177:Overweight / Q000097:blood*; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D003374:Coumarins; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D059808:Polyphenols; D002784:Cholesterol
keywords: Cardiometabolic; EFSA; Gut microbiota; Metabotype; Urolithins