Fate of microbial metabolites of dietary polyphenols in rats: is the brain their target destination?

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, though 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 post-absorption situation. Tissues and urine were collected shortly thereafter (15 sec 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 ten 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 Pvalues < 0.1 considered 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