The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids

Abstract

Dietary polyphenols promote memory in models of sleep deprivation (SD), stress, and neurodegeneration. The biological properties of dietary polyphenols greatly depend upon the bioavailability of their phenolic metabolites derivatives, which are modulated by gut microbiota. We recently demonstrated that supplementation with grape-derived bioactive dietary polyphenol preparation (BDPP) improves SD-induced cognitive impairment. This study examined the role of the gut microbiota in the ability of BDPP to prevent memory impairment in response to SD. C57BL6/J mice, treated with antibiotics mix (ABX) or BDPP or both, were sleep-deprived at the end of a fear conditioning training session and fear memory was assessed the next day. Gut microbiota composition was analyzed in fecal samples and BDPP-driven phenolic acid metabolites extraction was measured in plasma. We report that the beneficial effect of BDPP on memory in SD is attenuated by ABX-induced dysbiosis. We identified specific communities of fecal microbiota that are associated with the bioavailability of BDPP-derived phenolic acids, which in turn, are associated with memory promotion. These results suggest the gut microbiota composition significantly affects the bioavailability of phenolic acids that drive the dietary polyphenols’ cognitive resilience property. Our findings provide a preclinical model with which to test the causal association of gut microbiota-polyphenols, with the ultimate goal of potential developing dietary polyphenols for the prevention/treatment of cognitive impairment.

Whole Blueberry and Isolated Polyphenol-Rich Fractions Modulate Specific Gut Microbes in an In Vitro Colon Model and in a Pilot Study in Human Consumers

“…Importantly, in older age groups anthocyanins appear to lower the risk of cognitive decline [32]. However, there is a lack of human studies investigating the consumption of polyphenol-rich berries, metabolic improvement, and the microbiota, with the majority of relevant data derived from animal studies [27,[89][90][91][92]. Importantly, we recognize critics of FRAP assays and that, according to the literature, more oxidative damage markers should be added to allow robust conclusions to be drawn [88].…”

Biologically Active Compounds of Plants: Structure-Related Antioxidant, Microbiological and Cytotoxic Activity of Selected Carboxylic Acids

“…Despite the passage of years, this group of compounds is still the subject of much research on their unique antibacterial, cardioprotective, anti-inflammatory, and anti-cancer properties. Recent studies also focus on explaining the relationship between dietary polyphenols and phenolic acids and memory impairment [ 7 ], antidepressant effects [ 8 ], and retinal degeneration [ 9 ]. Last year’s reports described several interesting new properties of the analysed acids, including inhibiting the activity of p -coumaric acid on interbacterial quorum-sensing communication, which may be an innovative solution in the preservation of perishable food such as meat [ 10 ].…”

Improving natural product research translation: From source to clinical trial

“…139,140 Nonabsorbed polymeric polyphenols may, for example, modulate absorption of polyphenol monomers in humans, such that history of exposure significantly influences pharmacokinetics. [141][142][143][144][145][146] Gastrointestinal microbiota have been shown in many cases to be required for the generation of bioactive metabolites of NPs. [141][142][143][144][145][146] Gastrointestinal microbiota have been shown in many cases to be required for the generation of bioactive metabolites of NPs.…”