Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders

Abstract

The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience and overall human health have received much attention. Recently, the gut–brain axis has attracted prominent interest for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics have shown to improve gut bioavailability and blood–brain barrier (BBB) permeability, thus inhibiting the oxidative stress, metabolic dysfunction and inflammation linked to gut dysbiosis and ultimately the onset and progression of central nervous system (CNS) disorders. In accordance with hormesis, polyphenols display biphasic dose–response effects by activating at a low dose the Nrf2 pathway resulting in the upregulation of antioxidant vitagenes, as in the case of heme oxygenase-1 upregulated by hidrox® or curcumin and sirtuin-1 activated by resveratrol to inhibit reactive oxygen species (ROS) overproduction, microbiota dysfunction and neurotoxic damage. Importantly, modulation of the composition and function of the gut microbiota through polyphenols and/or probiotics enhances the abundance of beneficial bacteria and can prevent and treat Alzheimer’s disease and other neurological disorders. Interestingly, dysregulation of the Nrf2 pathway in the gut and the brain can exacerbate selective susceptibility under neuroinflammatory conditions to CNS disorders due to the high vulnerability of vagal sensory neurons to oxidative stress. Herein, we aimed to discuss hormetic nutrients, including polyphenols and/or probiotics, targeting the Nrf2 pathway and vitagenes for the development of promising neuroprotective and therapeutic strategies to suppress oxidative stress, inflammation and microbiota deregulation, and consequently improve cognitive performance and brain health. In this review, we also explore interactions of the gut–brain axis based on sophisticated and cutting-edge technologies for novel anti-neuroinflammatory approaches and personalized nutritional therapies.

The Involvement of Antioxidants in Cognitive Decline and Neurodegeneration: Mens Sana in Corpore Sano

“…Converging and recent evidence is suggestive of the central role of the GBA as a crucial substrate involved in the process of neurodegeneration [ 31 ]. Specifically, gut microbiota composition perturbations lead to increased oxidative stress, neuronal death, and neuroinflammation, culminating in the development of disorders such as Alzheimer’s disease [ 32 , 33 ] and Parkinson’s disease [ 34 , 35 ].…”

“…The consumption of antioxidants fosters neuroprotective effects and can modulate gut microbiota composition, increasing beneficial bacteria and reducing pathogenic species, also improving gut barrier integrity and blood–brain barrier permeability [ 31 ]. Crucially, a series of antioxidants have been found in lower concentrations in frail and cognitively impaired individuals compared to healthy controls [ 37 ].…”

Dietary Curcumin Intake and Its Effects on the Transcriptome and Metabolome of Drosophila melanogaster

“…Nevertheless, deterrent effects have been also shown in response to curcumin [ 30 , 31 ], specifically, decreasing the lifespan, larval development, and egg laying. Hormesis is a process in which the consumption of a substance, e.g., curcumin, can have priming and inhibitory effects in a dose-dependent manner [ 32 , 33 ], an effect that has been previously discussed in curcumin [ 34 ], and can be a reason for these discrepant results, as well as divergent physiological and genomic structure characteristics between vertebrates and invertebrates [ 35 ].…”