The Role of the Gut Microbiota in the Metabolism of Polyphenols as Characterized by Gnotobiotic Mice

Abstract

A growing body of experimental data suggests that microbes in the gut influence behavior and can alter brain physiology and neurochemistry. Although promising, researchers are only starting to understand the potential of the gut microbiota for use in neurological disease. Recent evidence demonstrated that gastrointestinal activities are linked to mood disorders such as anxiety, depression, and most recently, cognitive functions in age-related neurodegenerative disorders. Studies from our group and others are uncovering new evidence suggesting that the gut microbiota plays a crucial role in the metabolism and bioavailability of certain dietary compounds and synthetic drugs. Based on this evidence, this review article will discuss the implications of the gut microbiota in mechanisms of bioavailability and biotransformation with an emphasis on dietary polyphenol compounds. This will be followed by a survey of ongoing innovative research identifying the ability of individual gut bacteria to enhance the bioavailability of gut-derived, brain-penetrating, bioactive polyphenol metabolites that ultimately influence mechanisms associated with the promotion of resilience against psychological and cognitive impairment in response to stress. Lastly, current research initiatives aimed at promoting the generation of brain bioactive polyphenol metabolites by specialized gut microbes will be discussed, specifically the use of gnotobiotic mice to develop bioengineered second generation probiotics. We propose that leveraging the gut microbial ecosystem to generate brain targeted bioactive metabolites from dietary polyphenols can attenuate lifestyle risk factors and promote resilience against age-related cognitive decline.

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

“…Moreover, healthy gut microbiota may be fundamental for the transformation of dietary nutrients into active compounds exerting beneficial effects on the brain. Polyphenols represent a prototype of this possible mechanism 118. In fact, red raspberry-derived anthocyanins and ellagitannins need specific gut microbiota metabolism to be transformed into urolithins,119 which may exert important neuroprotective effects 80,81.…”

Variation in the pH of experimental diets affects the performance of Lymantria dispar asiatica larvae and its gut microbiota

“…Many diseases or conditions associated with suboptimal health are proved to be related with intestinal microbiota, such as depression (Cheung et al, 2019), chronic constipation (Ohkusa, Koido, Nishikawa, & Sato, 2019), and nonalcoholic liver disease (Ding et al, 2019). Similarly, numerous investigations have been devoted to elucidating the role of intestinal microflora in mammals (Pasinetti et al, 2018;Roselli et al, 2017) and fishes (Gómez & José Luis, 2010;Zhou, Ringø, Olsen, & Song, 2018). Although studying entomic intestinal microflora remains relatively novel, its development and metabolism, even behavior is shown to be similar to the gut microbiota of the other animals (Ayayee, Muñoz-Garcia, & Keeney, 2018;Qiao, Keesey, Hansson, & Knaden, 2019;Xia et al, 2018).…”

Activation of Nrf2 signaling by sitagliptin and quercetin combination against β‐amyloid induced Alzheimer's disease in rats

“…Nrf2 then translocates to the nucleus and ties to the antioxidant response element (N. Singh et al, ). This coupling causes downstream actuation of HO‐1 (Gupta et al, ; Pasinetti et al, ; Wang et al, ). The present examination expressed higher nuclear aggregation of Nrf2 by triptolide in the event of the Aβ‐infused brain.…”