Search Results (1,274)

Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut–brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by impaired glucose metabolism, mitochondrial dysfunction, inflammation, oxidative stress, and progressive cognitive decline. Because currently available pharmacological therapies provide only modest symptomatic benefit, nutrition-based interventions are increasingly being explored as complementary strategies for supporting brain metabolism and cognitive resilience. The KetoFLEX 12/3 dietary pattern, developed within the ReCODE (Reversal of Cognitive Decline) program, is a plant-rich, mildly ketogenic nutrition and lifestyle framework that integrates low-glycemic nutrition, time-restricted eating, and personalized metabolic optimization. The diet emphasizes deeply pigmented non-starchy vegetables, extra-virgin olive oil, nuts and seeds, omega-3-rich seafood, and minimally processed foods while limiting refined carbohydrates, sugars, processed foods, and selected grains and dairy products. Emerging mechanistic and clinical evidence suggests that KetoFLEX 12/3 may influence several pathways relevant to AD pathophysiology, including insulin signaling, mitochondrial bioenergetics, neuroinflammation, oxidative stress, autophagy, detoxification pathways, and gut–brain axis function. Observational findings from ReCODE-related studies have reported improvements in metabolic parameters, mood-related outcomes, cognitive measures, and brain volumetrics in participants adhering to multimodal precision-medicine interventions incorporating the KetoFLEX principles. Compared with traditional dietary models such as the Mediterranean or MIND diets, KetoFLEX 12/3 places greater emphasis on mild nutritional ketosis, meal timing, and metabolic personalization based on factors such as ApoE genotype and insulin sensitivity. The objective of this Perspective is to examine the mechanistic rationale, emerging evidence, limitations, and future research priorities for KetoFLEX 12/3 as a precision-nutrition framework for cognitive health in AD. Although much of the current evidence remains mechanistic, observational, or derived from multimodal intervention studies, the framework offers a biologically plausible precision-nutrition model that may inform future research and clinical investigation in cognitive decline. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder traditionally characterized by the extracellular accumulation of amyloid-beta (Abeta) plaques and the formation of intracellular neurofibrillary tau tangles; however, the prevailing scientific paradigm has shifted toward an integrative model of pathogenesis that recognizes neuroinflammation as a critical, self-perpetuating driver of cognitive attrition. This multifaceted interplay is mediated by the brain–body axis, wherein chronic systemic inflammation—stemming from metabolic dysfunction, cardiovascular disease, or environmental stressors such as fine particulate matter PM_2.5—compromises the structural integrity of the blood–brain barrier. Such environmental insults serve as priming agents for the innate immune system, shifting peripheral immune populations toward a pro-inflammatory phenotype that is further exacerbated by the stabilization of hypoxia-inducible factors (HIFs) through oxidative stress-induced pseudohypoxia, even under normoxic conditions. The subsequent activation of microglia and astrocytes transitions the cerebral microenvironment from a homeostatic, neurosupportive state into a neurotoxic milieu that actively promotes synaptic loss and neuronal death. Consequently, contemporary research has pivoted from broad-spectrum anti-inflammatory interventions toward targeted immune modulation, emphasizing that a comprehensive understanding of how systemic dysfunction perpetuates neuroinflammatory cascades is essential for developing efficacious therapies capable of attenuating AD progression and mitigating its global health burden. Full article

Background/Objectives: Major Depressive Disorder is a serious mental disorder that negatively affects an individual’s health and quality of life. The diagnosis of this disease is based on clinical interviews, questionnaires, and the patient’s self-reports. The objective of this study is to develop a biological diagnostic system based on the analysis of EEG signals and brain regions, rather than relying on self-reports. Methods: In this study, the EEG signals in the Multimodal Open Mental Disorder Analysis (MODMA) dataset were divided into six anatomical regions: prefrontal, frontal, central, parietal, temporal, and occipital. Empirical Wavelet Transform and Empirical Mode Decomposition methods were applied separately to the channels in each region, resulting in three IMF components. A total of 23 features, including statistical, nonlinear, spectral, and model-based (AR) features, were extracted from each IMF component. In addition to these features, asymmetry features between the left and right hemispheres were also included. Feature dimensions ranging from 10 to 40 were selected via the mRMR method, and the extracted feature sets were classified using SVM, k-NN, RUSBoost, Random Forest, and Meta-Ensemble machine learning models with Leave-One-Subject-Out (LOSO) validation. Results: According to the analysis results, the highest accuracy rate in Major Depressive Disorder (MDD) diagnosis was achieved by classifying features extracted from the frontal and prefrontal regions. The EMD signal processing method demonstrated superior performance compared to the EWT method. An accuracy rate of 98.11% was achieved using Random Forest and Meta-Ensemble models. Conclusions: In the proposed method, Explainable Artificial Intelligence (XAI) based SHAP analysis was applied to provide reliable and interpretable features for MDD diagnosis based on brain regional analysis. Full article

Transcranial magnetic stimulation-electroencephalography (TMS–EEG) biomarkers have recently become available as a means to obtain new understanding of the causal chains of neuronal signaling in the brain. This is a key piece in the puzzle of how the brain is organized and how it works. Using dMRI tractography, we can map the circuit beneath a chosen cortical target; TMS can then stimulate it, and EEG records responses that reflect—and may even be caused by—activity in that structural circuit. The chain of events after stimulus delivery can be observed and quantified using current neuroimaging and TMS–EEG technology, a matter of tremendous relevance on how to approach novel therapeutic approaches in clinical conditions. Herein, we elaborate upon a perspective of how groundbreaking multi-locus TMS (mTMS) technology associated with EEG and multimodal neuroimaging can be applied to modulate the flow dynamics of the glymphatic system (GS). The enhancement of the GS waste clearance functionality has been shown to improve significantly symptom severity in neurodegenerative disorders such as Alzheimer’s (AD) and Parkinson’s disease (PD) or long COVID. In this perspective paper, we consider that next-generation therapeutics using versatile technologies such as noninvasive neuromodulation and neuroimaging will provide important benefits in public health and in how society can address the management of these difficult-to-deal-with ailments more effectively. Full article

Cardiovascular disease is the leading cause of death in women, yet prevention and management have historically relied on male-centered models. Sex and gender critically influence risk, clinical presentation, and outcomes. Depression, anxiety, and psychosocial stress, more prevalent in women, act as key amplifiers of cardiovascular risk. We conducted a clinically oriented narrative review based on a broad, non-systematic search of major databases, integrating evidence selected for relevance and methodological robustness to clarify biological and psychosocial mechanisms linking mental health and cardiovascular disease in women. Affective disorders and stress contribute to cardiovascular risk through interconnected pathways, including hormonal fluctuations, autonomic and neuroendocrine dysregulation, inflammation, endothelial dysfunction, and heightened platelet reactivity. These mechanisms interact with gender-related exposures such as caregiving burden, occupational stress, and interpersonal violence. Stress-related phenotypes, including mental stress, induced ischemia and takotsubo syndrome, exemplify the heart-brain axis and its clinical implications. Incorporating mental health into cardiovascular risk assessment is essential for precision prevention in women. A women-centered approach should include systematic psychosocial evaluation, multidisciplinary care, and tailored strategies to improve risk control, adherence, and outcomes. Full article

Introduction: Functional gastrointestinal disorders (FGIDs), conceptualized as disorders of gut–brain interaction, are among the most common chronic or recurrent conditions in childhood, affecting approximately 20–30% of children worldwide across community and clinical settings. FGIDs are associated with substantial impairments in quality of life, frequent school absences, and high levels of psychological comorbidity, contributing to a considerable burden for families and healthcare systems. Despite their high prevalence, the pathophysiology remains incompletely understood, with evidence pointing to a multifactorial interplay of biological, psychological, and environmental factors. Given their frequency across healthcare settings and their significant psychosocial and economic impact, a better characterization of FGIDs in real-world pediatric populations is needed. This retrospective chart review aimed to examine patterns of FGIDs and their associations with gender, temporal factors, geographic setting, and hospitalization burden in a Swiss pediatric cohort within a biopsychosocial framework. Methods: This retrospective chart review study included 1445 patients aged 0–18 years. Patients were selected based on having received an ICD-10 diagnosis attributed to FGID. The frequency and distribution of the aforementioned factors were determined, as well as their associations with each other. Results: A male predominance of FGIDs in newborns (p < 0.001), a female predominance in adolescents (p < 0.001), and sex-based differences in subtype distribution (p < 0.001) was found in this cohort of patients. A higher proportion of FGID cases were found among children in urban areas than in rural and suburban areas. Infants were hospitalized for significantly longer periods on average than older children and males were hospitalized for longer periods on average than females. Discussion and Conclusions: These findings highlight the importance of early, integrated, interdisciplinary care pathways. Given the growing mental health issues affecting adolescent girls and the well-documented bidirectional relationship between emotional stress and FGID symptoms, it is suggested that early psychological screening and family-based interventions could reduce the chronicity of symptoms, prevent unnecessary hospitalizations and improve long-term health outcomes. Full article

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disorder and a major global health challenge. The traditional “one drug–one target” paradigm has shown limitations in addressing its multifactorial nature. Multitarget-directed ligands (MTDLs), designed to modulate multiple pathological pathways, have emerged as a promising therapeutic strategy. Objectives: To examine the structural, thematic, and temporal evolution of multitarget strategies for AD treatment between 2006 and 2025. Methods: A total of 1184 Web of Science-indexed articles were analyzed. Publication growth, h-index, author productivity, institutional and national contributions, and keyword co-occurrence networks were evaluated using VOSviewer. Bibliometric laws (Price, Bradford, Zipf, and Lotka) were applied to characterize productivity patterns and thematic organization. Results: Multitarget research shows exponential growth, suggesting a consolidation of the MTDL paradigm. China, India, the United States, Italy, and Spain were the most productive countries. Early studies focused on cholinesterase inhibition, particularly acetylcholinesterase-based hybrids. The field expanded to include β-amyloid aggregation, oxidative stress, metal chelation, and blood–brain barrier permeability. Recent trends emphasize integration of computational approaches, including molecular docking, molecular dynamics, virtual screening, and network pharmacology, alongside targets such as BACE1 and GSK-3β. Conclusions: Multitarget strategies have evolved toward a systems-oriented framework. Despite advances, challenges remain in reducing cholinesterase dependency and improving translational validation. This study provides a framework to interpret therapeutic evolution and guide future network-based drug design. Full article

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder increasingly discussed within the microbiota-gut–brain axis. This narrative review synthesizes evidence on bacterial and fungal dysbiosis in ADHD, with emphasis on Candida spp., diet, probiotics, synbiotics, and health-related quality of life. A structured narrative search of PubMed/MEDLINE, Scopus, and KoBSON-accessible sources was performed for studies addressing ADHD, gut microbiota, mycobiome, Candida, nutrition, microbiome-targeted interventions, and quality of life. Evidence was synthesized thematically because of methodological heterogeneity. Available studies suggest that ADHD may be associated with altered gut microbial diversity, changes in taxa such as Faecalibacterium, Blautia, Odoribacter, and Enterococcus, and immune–metabolic alterations. However, findings are heterogeneous and do not support a single ADHD-specific microbial signature. The fungal component remains insufficiently investigated, although evidence indicates increased Candida, particularly Candida albicans, in children with ADHD and a possible link with intestinal permeability. Dietary quality, micronutrient status, probiotics, and synbiotics may modulate microbiota–gut–brain pathways, but should be considered complementary and individualized, particularly in patients with gastrointestinal, dietary, immune, or metabolic vulnerability. Bacterial and fungal dysbiosis may represent biologically plausible, primarily associative components of ADHD-related pathophysiology. Evidence remains preliminary, exploratory, non-causal, and requires cautious interpretation in future research and clinical settings. Full article

The impact of diet on human health is constantly being researched. Nutrition is one of the most powerful tools for influencing gene expression, and dietary habits can promote the expression of genetic predisposition to obesity, diabetes, cardiovascular disease, cancer, and neurodegenerative diseases (NDs). The dietary inflammatory index (DII) is a numerical score that assesses the pro-or anti-inflammatory potential of a given diet. According to high DII scores, a Western diet or a standard American diet (SAD) has proinflammatory properties. By disrupting the gut microbiome, SAD creates an unfavorable environment in the intestine that is associated with a low-grade systemic inflammatory response and oxidative changes that may promote the development of NDs. An increased intestinal permeability and loss of blood–brain barrier (BBB) integrity play key roles in the pathomechanisms of diet-dependent NDs, leading to proinflammatory signaling via the gut–brain axis. The aim of this narrative review is to present in detail the current state of knowledge on the function of the gut–brain axis depending on the pro-/anti-inflammatory potential of the diet, measured by the DII, in the context of the contributions of intestinal and BBB permeability disorders to the development of NDs. Full article

Prenatal alcohol exposure (PAE) is recognized as a major public health concern due to its profound and lasting effects on the central nervous system (CNS) and its ability to induce fetal alcohol spectrum disorders (FASD), which encompass a wide range of cognitive, behavioural, and neuropsychiatric disorders that persist throughout life. Experimental and clinical studies have identified several mechanisms underlying ethanol impairing brain development, including apoptosis, oxidative stress, disruption of morphogen and growth factor signalling pathways, impaired neuronal proliferation and migration, neurotransmitter systems’ dysfunction, glial cells damage associated with deficient myelination, vascular and blood–brain barrier (BBB) alterations, and lasting epigenetic reprogramming. However, to date no widely accepted integrative framework explaining how these impairments underline the heterogeneous phenotype observed in FASD is available. The present brings together developmental neurobiology and computational neuroscience to conceptualize PAE as a disorder of emerging neural and functional architecture. Here, we summarize the pharmacokinetics of ethanol in pregnancy, critical windows of vulnerability, and the classical pathways of alcohol teratogenesis affecting neuronal survival, migration, synaptogenesis, myelination, and gene regulation. We have also reviewed MRI, diffusion imaging, and EEG/MEG evidence showing altered brain volumes, white matter microstructure, functional connectivity, and network organization in individuals with PAE. Finally, we propose a systems-level model that conceptualizes PAE as a disorder of emerging neuro-computational architecture, in which ethanol-induced cellular and molecular perturbations collectively alter the building blocks and self-organization rules of brain network assembly. Full article

Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, mitochondrial dysfunction, and oxidative stress. Despite recent advances, current therapies offer little benefit, and AD remains a significant challenge. Polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have attracted attention for their neuroprotective effects primarily through anti-inflammatory and antioxidant properties, but also for their ability to influence membrane fluidity and neuronal function. DHA is the predominant omega-3 PUFA in nerve cell membranes and is critical for synaptic plasticity and cognitive function. Some evidence has demonstrated that marine omega-3 supplementation reduces Aβ deposition, modulates microglial activation, and prevents cognitive decline in animal models. Even with heterogeneous results, preclinical and clinical studies suggest that long-term DHA/EPA supplementation can improve cognitive function in subjects with mild cognitive impairment (MCI) and reduce neuroinflammation markers. However, individual variability and brain bioavailability pose significant challenges. This review summarizes and discusses the current knowledge on the importance of PUFAs for human health, exploring novel mechanistic hypotheses, such as the effect of omega-3 fatty acids on brain iron homeostasis, the microbiota–gut–brain axis, the glymphatic system, and miRNAs. Furthermore, it focuses on the therapeutic potential of PUFAs in the treatment of AD and proposes future directions for translational research. Full article

Anxiety disorders pose an increasing challenge to the mental health of individuals, particularly in regions with limited healthcare access. This study investigated the potential of integrating a brain–computer interface for processing electroencephalography (EEG) data with deep learning models to accurately classify anxious and non-anxious states. In the first phase, a convolutional neural network (CNN) was developed and validated on the public GAMEEMO dataset, achieving a classification accuracy of 95.72%. In the second phase, we conducted a separate experimental validation with seven participants (aged 18–60 years) using a within-subjects design. The protocol comprised a custom Stroop test to elicit acute cognitive stress and anxiety-related arousal, followed by a guided 4–7–8 breathing exercise to induce relaxation. EEG data from this experiment were used to classify anxious versus non-anxious states with the same CNN architecture after domain adaptation. On this self-collected dataset, the CNN achieved an accuracy of 86.58%. These results demonstrate proof-of-concept transferability while highlighting the performance gap between controlled benchmark data and real-world, small-sample recordings. The deep learning model can subsequently be coupled with neurofeedback techniques to manage anxiety levels. Overall, the findings support the potential of the developed automated system for detecting stress-induced anxious states, with possible future integration into neurofeedback-based management systems. Full article

The gut–microbiota–brain axis (GMBA), an intricate network connecting the gastrointestinal (GI) tract and the brain, plays a pivotal role in maintaining overall health and influencing disease processes. The human gut microbiota, comprising over 3000 bacterial species, regulates immune responses, hormonal signals, and metabolite production, maintaining homeostasis under normal conditions. Dysbiosis, or microbial imbalance, has been linked to various central nervous system (CNS) disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). Given the growing interest in this topic and the limited effectiveness of current therapeutic strategies for managing patients with AD, the purpose of the current narrative review is to analyze the pathophysiological role of the GMBA in the pathogenesis of AD and assess potential therapeutic strategies targeting the GMBA, particularly the microbiome and its metabolites. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify clinical studies, experimental research, and review articles examining the GMBA in health and AD, as well as related therapeutic strategies. The search terms included “Alzheimer’s disease”, “neuroinflammation”, “amyloid-beta”, “tau”, “gut–brain axis”, “microbiome”, “short-chain fatty acids”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. In AD, altered gut microbiota composition is associated with neuroinflammation, neurodegeneration, and exacerbation of disease progression. Probiotics have shown potential in enhancing cognitive function and reducing neuroinflammation by modulating microbiota composition and influencing brain-derived neurotrophic factor (BDNF) levels. Prebiotics, through their impact on gut microbiota and metabolite production, also offer therapeutic promise by improving cognitive function and mitigating neuroinflammation. With its historical and modern applications, fecal microbiota transplantation (FMT) may represent a potential strategy for addressing dysbiosis and its neurological implications. This manuscript focuses on GMBA and its effects on neuroinflammation, neurodegeneration, and CNS health while emphasizing the need for further research into microbiome-based therapies and the gut–brain relationship in patients with AD. Full article