The interplay between functional food nutrients and neurosteroids has garnered significant attention for its potential to enhance stress resilience in health and/or disease. Several bioactive nutrients, including medicinal herbs, flavonoids, and bioavailable polyphenol-combined nanoparticles, as well as probiotics, vitamin D and omega-3 fatty acids, have been shown to improve blood–brain barrier (BBB) dysfunction, endogenous neurosteroid homeostasis and brain function. These nutrients can inhibit oxidative stress and neuroinflammation, which are linked to the pathogenesis of various neurological disorders. Interestingly, flavonoids exhibit dose-dependent effects, activating the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway at the physiological/low dose (neurohormesis). This leads to the upregulation of antioxidant phase II genes and proteins such as heme oxygenase-1 (HO-1) and sirtuin-1 (Sirt1), which are activated by curcumin and resveratrol, respectively. These adaptive neuronal response mechanisms help protect against reactive oxygen species (ROS) and neurotoxicity. Impaired Nrf2 and neurosteroid hormone signaling in the brain can exacerbate selective vulnerability to neuroinflammatory conditions, contributing to the onset and progression of neurodegenerative and psychiatric disorders, including Alzheimer’s disease, anxiety and depression and other neurological disorders, due to the vulnerability of neurons to stress. This review focuses on functional food nutrients targeting Nrf2 antioxidant pathway and redox resilience genes to regulate the neurosteroid homeostasis and BBB damage associated with altered GABAergic neurotransmission. By exploring the underlying molecular mechanisms using innovative technologies, we aim to develop promising neuroprotective strategies and personalized nutritional and neuroregenerative therapies to prevent or attenuate oxidative stress and neuroinflammation, ultimately promoting brain health.

Neuronutrition to improve brain resilience to stress and human health has received considerable attention. The use of specific nutrients is effective in preventing and slowing neurodegenerative and neuropsychiatric disorders. Selective neuronutrients, including polyphenols, short-chain fatty acids (SCFAs), tryptophan, tyrosine, and sulfur metabolites, can modulate the dysregulated nuclear factor erythroid 2 (Nrf2) pathway through neuroepigenetic modifications and altered levels of neurotransmitters such as serotonin, melatonin, and dopamine. In particular, abnormal epigenetic alterations in the promoter function of the NFE2L2/Nrf2 gene may contribute to the onset and progression of various diseases by disrupting cellular homeostasis. Recent evidence has documented that polyphenols are capable of modulating Nrf2 signaling; to do this, they must reverse hypermethylation in the CpG islands of the NFE2L2 gene. This process is achieved by modifying the activity of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Furthermore, a diverse group of polyphenolic metabolites can be identified and quantified using innovative mass spectrometry platforms in both in vitro models and human urine samples to investigate redox metabolic homeostasis under physiological and pathophysiological conditions. This review aims to deepen the current understanding of the role of nutrient-derived secondary metabolites. It highlights innovative strategies to effectively prevent, slow, or potentially reverse neuroinflammation and oxidative stress, key drivers of neuronal damage. The targeted application of these metabolites can be considered a novel, personalized neuronutritional approach to promote brain health and neuronal adaptation.

This article delves into the intricate relationship between oral health, quality of life, and behavioral characteristics in individuals with autism spectrum disorder (ASD). Background/Objectives: Autism has been associated with various challenges, and this study seeks to elucidate the impact of ASD on oral health outcomes and overall well-being. The research focuses on assessing overall oral health by evaluating various parameters, such as the condition of lips, tongue, gums and tissues, natural teeth, dentures, oral hygiene, and dental pain in individuals with ASD. Additionally, the study explores the influence of age, sex, and certain variables, like basic daily living skills on oral health practices, aiming to identify potential correlations between these factors and oral health outcomes. Methods: We employed standardized instruments to quantitatively measure and analyze the impact of oral health status on the overall quality of life experienced by individuals with ASD. Results: The study found a statistically significant positive association between oral health, measured by the Oral Health Assessment Tool (OHAT), and quality of life, as indicated by EuroQol 5-Dimensions Youth version (EQ-5D-Y) total scores (β = 0.13045, p = 0.00271). This suggests that better oral health is linked to higher quality of life. When adjusting for age and sex in a multiple linear regression model, the association remained significant but with a slightly reduced effect size (β = 0.10536, p = 0.0167). Age also showed a marginally significant positive association with quality-of-life scores. ANOVA results indicated that participants with advanced oral health status reported significantly higher quality-of-life scores than those with poorer oral health (p = 0.00246). The study also found that intelligence quotient (IQ) does not substantially influence dental health status, while the “Autonomy” subscale of the EQ-5D-Y is positively related to the OHAT. Conclusions: Unhealthy oral conditions significantly impact the overall quality of life in individuals with ASD. Therefore, it is crucial to include regular dental assessments and treatments in therapeutic protocols for patients with ASD.

Microplastics (MPs), emerging contaminants of significant global concern, have a substantially increased environmental impact due to their biological persistence and accumulation in the body. Exposure to MPs has been associated with oxidative stress, systemic inflammation, and cellular dysfunction, notably affecting critical tissues such as the stomach, colon, and brain. This review explores the correlation between MPs and cancer risk along the gastric–colon–brain axis, identifying the signaling pathways altered by MP exposure. Furthermore, it highlights the role of functional nutrition and bioactive flavonoids—including chlorogenic acid, coumaric acid, and naringin—as well as the use of highly bioavailable combined polyphenol nanoparticles as potential detoxifying agents. Functional nutrients are effective in enhancing cellular resilience against reactive oxygen species (ROS) production and MP-induced toxicity, offering protective effects at the gastric, intestinal, and brain barriers. Activation of the Nrf2 pathway by bioactive compounds promotes the expression of detoxifying enzymes, suggesting a promising nutritional strategy to mitigate MP-related damage. This review underscores how functional nutrition may represent a viable therapeutic approach to reduce the harmful effects of MP exposure. The integration of advanced technologies—such as microfluidic systems, organ-on-a-chip platforms, and machine learning—and the identification of key molecular targets lay the foundation for developing preventive and personalized medicine strategies aimed at lowering the risk of environmentally induced carcinogenesis.

The therapeutic potential of functional nutrients has garnered considerable attention for enhancing resilience signaling and counteracting the damage to human health caused by microplastic pollutants. The intricate interactions between microplastics (MPs) and nanoplastics (NPs) and functional nutrients, including polyphenols, flavonoids, phenylpropanoids, phenolic acids, diterpenoids, and triterpenoids, have been shown to improve blood–brain barrier (BBB) homeostasis and brain function by inhibiting oxidative stress, ferroptosis, and inflammation linked to the pathogenesis of metabolic and brain disorders. Interestingly, nutrients exhibit biphasic dose–response effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and stress-resilience proteins at minimum doses, thereby preventing or blocking MP and NP-induced damage. Notably, chronic exposure to environmental pollutants causes aberrant regulation of NFE2L2 gene and related antioxidant signaling, which can exacerbate selective susceptibility to brain insulin resistance under inflammatory conditions. This, in turn, impairs glucose metabolism and facilitates β-amyloid (Aβ) plaque synthesis leading to the onset and progression of Alzheimer’s disease (AD), also known as “Type 3 diabetes”. This pathological process triggered by oxidative stress, inflammation, and ferroptosis creates a vicious cycle that ultimately contributes to neuronal damage and loss. The review aims to investigate the therapeutic potential of functional nutrients targeting the Nrf2 pathway and stress resilience proteins to regulate epigenetic alterations, and to explore the underlying molecular mechanisms using innovative in vitro platforms for the development of promising preventive strategies and personalized nutritional interventions to attenuate oxidative stress, ferroptosis, and inflammation, with the goal of ultimately improving clinical outcomes.