Hormetic Nutrition and Redox Regulation in Gut-Brain Axis Disorders

Dear Colleagues,

Growing interest is focusing on the antioxidant and anti-inflammatory effects of polyphenols for enhancing human stress resilience in health and disease. Recently, bidirectional crosstalk in the gut-brain axis (GBA) has gained attention for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics have been shown to improve gut bioavailability and blood-brain barrier (BBB) permeability, thus inhibiting oxidative stress, metabolic dysfunction and inflammation linked to gut dysbiosis and the consequent onset and progression of nervous system disorders. According to hormesis, phytochemicals exhibit biphasic dose-response effects, activating antioxidant signaling pathways at low doses, resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol to block ROS production, microbiota dysfunction and neurotoxic damage. Importantly, the modulation of the composition and function of gut microbiota through polyphenols increases the abundance of beneficial bacteria and can prevent and treat not only Alzheimer’s disease but also other neurological disorders. Interestingly, dysregulation of the Nrf2 pathway in the gut and brain can exacerbate selective susceptibility under neuroinflammatory conditions due to the high vulnerability of brain cells to oxidative stress. Herein, we aimed to discuss natural inducers 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 Special Issue, we mainly focus on the hormetic effects of polyphenols, summarizing their neuroprotective and anti-inflammatory properties as well as pharmacological interventions in gut-brain disorders.

Dr. Maria Concetta Scuto
Prof. Dr. Vittorio Calabrese
Prof. Dr. Angela Trovato
Prof. Dr. Edward J. Calabrese
Guest Editors

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• oxidative stress
• inflammation
• polyphenols
• gut–brain axis
• vitagenes
• hormesis