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Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation

1
George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
2
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
*
Authors to whom correspondence should be addressed.
Metabolites 2019, 9(4), 78; https://doi.org/10.3390/metabo9040078
Received: 28 March 2019 / Revised: 16 April 2019 / Accepted: 17 April 2019 / Published: 19 April 2019
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Abstract

Increasing evidence supports the beneficial effects of polyphenol-rich diets, including the traditional Mediterranean diet, for the management of cardiovascular disease, obesity and neurodegenerative diseases. However, a common concern when discussing the protective effects of polyphenol-rich diets against diseases is whether these compounds are present in systemic circulation in their intact/parent forms in order to exert their beneficial effects in vivo. Here, we explore two common classes of dietary polyphenols, namely isoflavones and lignans, and their gut microbial-derived metabolites for gut and blood–brain barrier predicted permeability, as well as protection against neuroinflammatory stimuli in murine BV-2 microglia. Polyphenol microbial metabolites (PMMs) generally showed greater permeability through artificial gut and blood–brain barriers compared to their parent compounds. The parent polyphenols and their corresponding PMMs were evaluated for protective effects against lipopolysaccharide-induced inflammation in BV-2 microglia. The lignan-derived PMMs, equol and enterolactone, exhibited protective effects against nitric oxide production, as well as against pro-inflammatory cytokines (IL-6 and TNF-α) in BV-2 microglia. Therefore, PMMs may contribute, in large part, to the beneficial effects attributed to polyphenol-rich diets, further supporting the important role of gut microbiota in human health and disease prevention. View Full-Text
Keywords: polyphenol; gut microbial metabolites; permeability; equol; enterodiol; enterolactone; inflammation polyphenol; gut microbial metabolites; permeability; equol; enterodiol; enterolactone; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Johnson, S.L.; Kirk, R.D.; DaSilva, N.A.; Ma, H.; Seeram, N.P.; Bertin, M.J. Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation. Metabolites 2019, 9, 78.

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