Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis
Department of Chemistry, Missouri University of Science and Technology, Rolla, MO 65409, USA
Department of Veteran’s Affairs Medical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA
Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA
Author to whom correspondence should be addressed.
Microorganisms 2020, 8(2), 199; https://doi.org/10.3390/microorganisms8020199
Received: 20 December 2019 / Revised: 25 January 2020 / Accepted: 28 January 2020 / Published: 31 January 2020
(This article belongs to the Special Issue Microbiota-Gut-Brain Axis)
Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.