title: Fate of microbial metabolites of dietary polyphenols in rats: is the brain their target destination?
abstract: Different polyphenol compounds are ingested when consuming a serving of fruits rich in polyphenols, spanning from one-phenol hydroxybenzoic acid to more complex polymeric compounds. Only a minor quantity of the polyphenols (5-10%) is absorbed. The remainder reaches the colon and is extensively metabolized by gut microbiota to low-molecular weight metabolites. Their subsequent tissue distribution is still undefined, although these microbial metabolites are currently believed to play a role in human health and disease states. To fill this knowledge gap, we performed a pharmacokinetics experiment in which a single bolus of 23 polyphenol microbial metabolites (total 2.7 μmol) was administered intravenously to rats to reliably reproduce a physiological postabsorption situation. Tissues and urine were collected shortly thereafter (15 s to 15 min) and were analyzed by UHPLC-MS/MS to quantitatively track these compounds. Remarkably, the brain was found to be a specific target organ for 10 of the 23 polyphenol metabolites injected, which significantly increased in the treated animals. In most cases, their appearance in the brain was biphasic, with an early wave at 2 min (4 compounds) and a second wave starting at 5 min; at 15 min, 9 compounds were still detectable. Most compounds were excreted into the urine. The concentrations in the brain of the treated animals were compared against those of the control group by Student's t test, with p-values < 0.1 considered to be statistically significant. These findings provide new perspectives for understanding the role of diet on brain chemistry. Our experimental approach has enabled us to obtain rich metabolomics information from a single experiment involving a limited number of animals.
authors.affiliation: †Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), via E. Mach 1, 38010 San Michele all'Adige, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Gasperotti
authors.affiliation: ‡Department of Life Sciences, University of Trieste, via L. Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Passamonti
authors.affiliation: ‡Department of Life Sciences, University of Trieste, via L. Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tramer
authors.affiliation: †Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), via E. Mach 1, 38010 San Michele all'Adige, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Masuero
authors.affiliation: §Department of Physics, University of Trento, via Sommarive 14, 38123 Trento, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Guella
authors.affiliation: †Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), via E. Mach 1, 38010 San Michele all'Adige, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mattivi
authors.affiliation: †Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), via E. Mach 1, 38010 San Michele all'Adige, Italy.
authors.forename: Urska
authors.initials: U
authors.lastname: Vrhovsek
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002264:Carboxylic Acids / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D005638:Fruit / Q000737:chemistry; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism; D059808:Polyphenols / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D002264:Carboxylic Acids; D059808:Polyphenols
keywords: Polyphenols; brain; fruit consumption; gut microbiota; mass spectrometry; target metabolomics