Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms

Abstract

The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.

Keywords: Caenorhabditis elegans; Drosophila; Saccharomyces cerevisiae; human; microbiota; neurodegeneration; phytochemicals; rodents; zebrafish.

Figure 1

Diets rich in (poly)phenols originate large amounts of flavonoids and flavonoid conjugates reaching the digestive system. (1) In the small intestine, epithelial and bacterial enzymes remove sugar conjugates while absorption occurs. (2) The majority of flavonoids travel to the lower part of the gut where microbiota catabolizes flavonoids into LMWPM that will be absorbed into enterohepatic circulation. (3) LMWPM will enter systemic circulation intact or will undergo phase I and II metabolic reactions by intestinal and liver cells before reaching the circulation. LMWPM—low molecular weight (poly)phenol metabolites. L.I.—large intestine.

Figure 2

Chemical structures of low molecular weight (poly)phenol metabolites resulting from gut microbiota catabolism of flavonoids or enterohepatic phase I and II metabolic conversions. The nomenclature used followed recent recommendations [32]. Sulf—sulfate; Gluc—glucuronide; Me—methyl group.

Figure 3

Main hallmarks of neurodegeneration and neurodegenerative diseases—protein misfolding, neuroinflammation, neuronal degeneration and oxidative stress—shared between the major cellular types present in the brain such as neurons, astrocytes and microglia. UPS: ubiquitin—proteosome system, ROS: reactive oxygen species, RNS: reactive nitrogen system, AD: Alzheimer’s disease, PD: Parkinson’s disease, HD: Huntington’s disease, ALS: amyotrophic lateral sclerosis.