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Metabolites. 2019 Apr 19;9(4). pii: E78. doi: 10.3390/metabo9040078.

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

Author information

1
George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA. shelby_johnson@uri.edu.
2
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA. shelby_johnson@uri.edu.
3
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA. rileykirk@uri.edu.
4
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA. nickdasilva91@gmail.com.
5
George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA. Hang_ma@uri.edu.
6
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA. Hang_ma@uri.edu.
7
George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA. nseeram@uri.edu.
8
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA. nseeram@uri.edu.
9
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA. mbertin@uri.edu.

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.

KEYWORDS:

enterodiol; enterolactone; equol; gut microbial metabolites; inflammation; permeability; polyphenol

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