title: Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease β-amyloid oligomerization.
abstract: METHODS
  Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age-related neurodegenerative disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE-derived phenolic acid in the brain.
  
  
  RESULTS
  We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3-hydroxybenzoic acid and 3-(3´-hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3-hydroxybenzoic acid and 3-(3´-hydroxyphenyl)propionic acid potently interfere with the assembly of β-amyloid peptides into neurotoxic β-amyloid aggregates that play key roles in AD pathogenesis.
  
  
  CONCLUSIONS
  Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.
authors: Center of Nutrition and Food Sciences, ARC center of Excellence in Plant Cell Walls, The University of Queensland, Brisbane, Queensland, Australia.
authors: Dongjie
authors: D
authors: Wang
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
authors: Lap
authors: L
authors: Ho
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
authors: Jeremiah
authors: J
authors: Faith
authors: Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors: Kenjiro
authors: K
authors: Ono
authors: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
authors: Elsa M
authors: EM
authors: Janle
authors: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.
authors: Pamela J
authors: PJ
authors: Lachcik
authors: Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
authors: Bruce R
authors: BR
authors: Cooper
authors: Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
authors: Amber H
authors: AH
authors: Jannasch
authors: School of Agriculture and Food Sciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Bruce R
authors: BR
authors: D'Arcy
authors: Center of Nutrition and Food Sciences, ARC center of Excellence in Plant Cell Walls, The University of Queensland, Brisbane, Queensland, Australia.
authors: Barbara A
authors: BA
authors: Williams
authors: Department of Nutrition Science, Purdue University, West Lafayette, IN, USA.|Department of Food Science, Purdue University, West Lafayette, IN, USA.
authors: Mario G
authors: MG
authors: Ferruzzi
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
authors: Samara
authors: S
authors: Levine
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
authors: Wei
authors: W
authors: Zhao
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.
authors: Lauren
authors: L
authors: Dubner
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NJ, USA.|Geriatric Research and Clinical Center, James J. Peter Veterans Affairs Medical Center, Bronx, NY, USA.
authors: Giulio M
authors: GM
authors: Pasinetti
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D005285:Fermentation; D000069196:Gastrointestinal Microbiome; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D062385:Hydroxybenzoates / Q000097:blood / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism; D059808:Polyphenols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011422:Propionates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C491266:3-hydroxyphenylpropionic acid; D016229:Amyloid beta-Peptides; D000872:Anthocyanins; D056604:Grape Seed Extract; D062385:Hydroxybenzoates; D010446:Peptide Fragments; D010636:Phenols; D059808:Polyphenols; D011422:Propionates; C075222:amyloid beta-protein (1-42); C032948:3-hydroxybenzoic acid; C017616:phenolic acid
keywords: Bioavailability; Grape seed polyphenol extract; Phenolic metabolites; Proanthocyanidins; β-Amyloid