Search Results (380)

Pediatric disorders of gut–brain interaction (DGBIs) comprise chronic or recurrent symptom-based gastrointestinal conditions that cannot be fully explained by identifiable structural, biochemical, or organic abnormalities after appropriate clinical evaluation. The term DGBI is used throughout this review in accordance with current terminology, whereas the historical term “functional gastrointestinal disorders” (FGIDs) is retained only when referring to studies that used earlier Rome classifications. This review examines the impact of four modifiable factors—sleep, psychological stress, circadian rhythm, and diet—on their development and severity in children and adolescents. Relevant literature was identified through PubMed, with emphasis on recent pediatric studies, systematic reviews, and meta-analyses. Sleep disturbances are associated with greater abdominal pain, functional disability, and impaired daytime functioning. Stress may exacerbate symptoms through hypothalamic–pituitary–adrenal axis activation, autonomic imbalance, altered motility, and visceral hypersensitivity. Circadian disruption may affect gastrointestinal motility, barrier function, enteroendocrine signaling, and microbial rhythmicity, although pediatric evidence remains limited. Diet influences fermentation, microbiota, intestinal permeability, and symptom expression, with regular meals, adequate hydration, and appropriate fiber intake representing important initial measures. These factors interact bidirectionally through shared neuroendocrine, autonomic, immune, and microbial pathways. Clinical management should therefore adopt a biopsychosocial, multidisciplinary approach combining symptom management with modification of sleep, stress, circadian habits, and dietary patterns. Further prospective pediatric studies are needed to clarify causality and support personalized interventions. Full article

Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary components. Prolonged exposure can nevertheless result in gradual tissue accumulation. This review summarises current evidence on dietary aluminium exposure, factors influencing its bioavailability, toxicokinetics, biological effects, gut microbiota interactions, and population-level health risk. Methods: A comprehensive narrative literature review was conducted using publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles, review papers, and reports issued by international organisations were critically evaluated with particular emphasis on dietary sources, drinking water, food additives, food contact materials, gastrointestinal absorption, toxicokinetics, biological mechanisms, gut microbiota, and health risk assessment. Results: Food represents the principal source of aluminium exposure in the general population, while drinking water usually contributes a smaller but continuous fraction of total oral intake. Dietary exposure varies substantially between populations and is influenced by food composition, processing practices, the use of aluminium-containing additives, and migration from food contact materials. Aluminium bioavailability is modified by chemical speciation and dietary constituents, including citrate, phosphates, silicates, phytates, polyphenols, and essential minerals. Despite limited absorption, prolonged exposure can lead to gradual aluminium accumulation, particularly in bone tissue and the central nervous system. Proposed biological mechanisms include oxidative stress, mitochondrial dysfunction, disruption of mineral homeostasis, and inflammatory signalling. Emerging evidence also indicates that aluminium may alter the gut microbiota, impair intestinal barrier integrity, and influence the gut–brain axis. Population exposure assessments show considerable regional variation, with some groups approaching or exceeding established tolerable weekly intake values. Conclusions: Dietary aluminium exposure represents a relevant issue in nutritional toxicology and food safety. Although current evidence does not establish that typical dietary exposure directly causes chronic disease, long-term exposure, differences in bioavailability, and the possibility of elevated intake in selected population groups justify continued monitoring and further prospective human studies. Future research should integrate dietary intake, aluminium speciation, nutritional status, biomarkers of internal exposure, and long-term health outcomes to improve risk assessment and support effective exposure-reduction strategies. Full article

Stroke remains one of the leading causes of death and long-term neurological disability worldwide, while currently available therapeutic strategies are limited by narrow treatment windows and incomplete neuroprotection. In this context, plant-derived polyphenols have attracted increasing attention as potential adjunctive agents because of their multimodal biological activity. This review focuses on resveratrol and curcumin, two of the most extensively investigated polyphenols, and evaluates their potential role in the prevention and treatment of ischaemic and haemorrhagic stroke. Evidence from in vitro studies, animal models, and early clinical trials indicates that both compounds may attenuate key mechanisms involved in stroke-related brain injury, including oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, autophagy dysregulation, blood–brain barrier disruption, and microglial activation. Emerging evidence further suggests that interactions with the gut microbiota and modulation of the gut–brain axis may contribute to their biological effects by influencing intestinal barrier integrity, microbial metabolite production, systemic inflammation, and vascular risk. Preclinical studies show that resveratrol and curcumin can reduce infarct volume, limit cerebral oedema, preserve neuronal viability, promote angiogenesis and neurogenesis, and improve neurological and cognitive outcomes. Their beneficial effects have been reported both when administered before stroke onset and after cerebral injury, suggesting potential relevance for both prevention and post-stroke therapy. However, interpretation of these findings requires consideration of the translational limitations of experimental stroke models, which do not fully reproduce the heterogeneity, comorbidities, age profile, and variable reperfusion patterns characteristic of human stroke. Although commonly used models such as middle cerebral artery occlusion provide important mechanistic and therapeutic insights, preclinical efficacy should therefore not be regarded as a direct predictor of clinical benefit. Resveratrol and curcumin may also complement established and emerging treatment strategies, including thrombolysis, endovascular interventions, antihypertensive therapy, and stem cell-based approaches. Nevertheless, their clinical translation remains limited by poor solubility, low bioavailability, rapid metabolism, and insufficient clinical evidence. Novel formulations, including nanoparticles, exosome-based delivery systems, and structurally modified analogues, may help overcome these barriers by improving brain targeting and therapeutic efficacy. Overall, resveratrol and curcumin represent promising but still investigational candidates for adjunctive stroke therapy, requiring further well-designed clinical trials to define their optimal dosing, timing, safety, and clinical value. Full article

Background: Microbiome-based mechanisms have emerged as a key area of investigation in epilepsy, given the growing recognition that gut microbial communities can modulate central nervous system (CNS) function through the gut–brain axis. Epilepsy is a common chronic neurological disorder affecting more than 65 million people worldwide, and despite the availability of anti-seizure medications (ASMs), approximately 30% of patients develop drug-resistant epilepsy. Current ASMs primarily suppress seizures rather than prevent disease progression, highlighting the need for alternative therapeutic strategies. In this context, increasing evidence supports a role for microbiota-dependent pathways in modulating seizure activity and treatment responsiveness. However, the mechanistic basis of these interactions remains incompletely understood. Methods: This narrative review synthesizes findings from the existing literature to examine the role of microbiota-derived metabolites, including neurotransmitters, vitamins, and the polyphenol metabolite S-equol, in gut–brain communication relevant to epilepsy. Evidence was drawn from both preclinical animal models and clinical studies to provide an integrated, mechanistic perspective on how these pathways may influence central nervous system function and seizure susceptibility. Emphasis was placed on studies describing molecular, metabolic, and signaling mechanisms linking the gut microbiome to epileptogenesis and treatment response. Results: Current evidence indicates that communication between the gut and CNS occurs through neural pathways, such as the vagus nerve, as well as through circulating microbial metabolites. These metabolites can cross the intestinal barrier and, in some cases, the blood–brain barrier (BBB), serving as key mediators of host–microbiota signaling. Emerging studies suggest that while some microbial metabolites may directly influence neuronal hyperexcitability and seizure susceptibility, others likely exert secondary or modulatory effects through broader metabolic and immune pathways. However, the precise mechanisms underlying these interactions remain incompletely understood. Conclusions: Some microbial-derived metabolites may serve as promising biomarkers and mechanistic mediators of epilepsy; however, further investigation is needed to define the molecular and cellular pathways through which these metabolites influence seizure susceptibility and epileptogenesis. Full article

Background/Objectives: Dietary modifiers of the gut ecosystem may influence intestinal and host responses associated with psychological stress. However, it remains unclear whether sucralose, a widely consumed non-nutritive sweetener, alters host–microbiota interactions following chronic stress exposure. We investigated the effects of short-term experimental sucralose exposure in mice previously subjected to chronic restraint stress (CRS). Methods: Following completion of the CRS protocol, mice received 0.03% or 0.1% sucralose in drinking water for 12 days. Intestinal phenotypes, cecal microbial community structure, microbial metabolites, colonic epithelial gene expression, and epithelial serotonergic responses following allyl isothiocyanate (AITC)-induced visceral stimulation were evaluated. Results: Colon length was significantly reduced in the 0.1% sucralose group, whereas intestinal permeability remained unchanged. Sucralose selectively altered colonic epithelial gene expression and was associated with changes in cecal microbial community structure without marked changes in alpha diversity. The relative abundance of Bacteroides acidifaciens was significantly reduced, particularly in the 0.1% sucralose group. Fecal acetate and cecal tryptophan concentrations were decreased following sucralose exposure. Following AITC-induced visceral stimulation, the CRS + 0.1% sucralose group exhibited reduced immobility behavior together with increased epithelial serotonin and 5-hydroxyindoleacetic acid concentrations. Conclusions: In mice previously exposed to CRS, short-term sucralose exposure was associated with colon shortening, differences in cecal microbial community structure, reduced Bacteroides acidifaciens abundance, decreased fecal acetate and cecal tryptophan concentrations, and altered epithelial serotonergic responsiveness following visceral stimulation. The behavioral and epithelial serotonergic findings suggest that prior stress exposure may influence selected host responses to sucralose. These findings provide a basis for future studies examining how dietary sweeteners modify host–microbiota interactions following chronic stress exposure. Full article

The enteric nervous system (ENS) can function semi-autonomously from the central nervous system (CNS) in regulating complex gastrointestinal processes and exhibits substantial developmental, epigenetic, neuroimmune, and adaptive plasticity. We propose the concept of Stress-Induced Long-term Epigenetic Implicit Memory (SLEIM) as a hypothesis-generating theoretical framework suggesting that prenatal maternal stress may contribute to persistent biological alterations within ENS-related pathways through interacting epigenetic, neuroimmune, neuronal, glial, and microbiota-associated mechanisms. The precise biological substrates and mechanisms underlying this proposed framework remain unknown. Through the microbiota–gut–brain axis (MGBA), such stress-related biological alterations may influence physiological communication between the ENS and CNS and in turn affect stress-response systems, including HPA axis activity, immune signalling, cortisol regulation, mast-cell activation, and cytokine balance. The frequent comorbidity of fibromyalgia (FM) and irritable bowel syndrome (IBS) suggests the existence of shared pathogenic mechanisms involving central sensitisation, neuroimmune processes, and MGBA dysfunction. In this study, we therefore also address dependency-related characteristics and autonomy vulnerabilities reported in some patients with FM and consider how developmental, psychological, neurobiological, and illness-related factors may contribute to these patterns. Within the proposed SLEIM framework, prenatal stress-related biological influences may represent a potential developmental pathway that contributes to vulnerability to IBS, FM, and related functional disorders later in life. However, these relationships remain hypothetical and require future empirical investigation. Full article

Liposomes are among the most extensively studied delivery systems owing to their biocompatibility, structural versatility, and ability to improve the stability and bioavailability of bioactive compounds. Meanwhile, edible fungal polysaccharides (EFPs), particularly β-glucans and heteropolysaccharides, have attracted increasing interest because of their antioxidant, immunomodulatory, prebiotic, and health-promoting properties. The integration of EFPs with liposomal systems has emerged as a promising strategy for developing multifunctional nanocarriers with enhanced physicochemical stability and biological performance. However, current research remains fragmented, and the mechanisms by which EFP molecular structures influence liposome assembly, stability, gastrointestinal fate, and delivery efficiency are poorly understood. Moreover, existing reviews primarily focus on liposomes or fungal polysaccharides independently, without systematically addressing their interfacial interactions, structure-function relationships, and translational applications. This review provides a comprehensive and critical overview of EFP liposomes, highlighting the interactions between fungal polysaccharides and lipid bilayers, including hydrogen bonding, electrostatic interactions, hydrophobic association, and surface conjugation. The effects of EFPs on liposomal physicochemical properties, encapsulation performance, membrane stability, gastrointestinal protection, mucoadhesion, cellular uptake, and biological activity are further discussed. Emerging applications in targeted delivery, oral delivery, gut microbiota modulation, gut–brain axis regulation, and functional foods are also critically evaluated. Importantly, this review identifies key research gaps, including the lack of quantitative structure-function relationships, limited understanding of biological transport mechanisms, insufficient investigation of microbiota-mediated effects, and challenges in scalable manufacturing. By integrating glycobiology, nanotechnology, and food science, this review establishes a unified framework for the rational design and future development of EFP-based liposomal delivery systems. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

Vascular cognitive impairment (VCI) is a major form of dementia with a complex pathogenesis. Emerging evidence indicates a strong interaction between intestinal mucosal barrier integrity and neuroinflammation, which has been proposed as a candidate contributor in VCI progression. This review comprehensively reviews the initiation and amplification of neuroinflammation in chronic cerebral ischemia. It highlights how impairment of the intestinal mucosal barrier, gut microbiota dysbiosis, and translocation of microbial metabolites contribute to central neuroinflammation via circulatory and neural pathways, suggesting a potential self-sustaining pathological cycle within the gut–brain axis. Furthermore, we analyze the underlying molecular mechanisms, critique current limitations, and suggest promising directions for future research. Full article

Interactions among the gut, brain, and skin are increasingly understood as a systemic regulatory network connecting intestinal activity, neuroimmune communication, and cutaneous homeostasis. Microbiota-derived metabolites, immune mediators, and neuroendocrine pathways can influence central nervous system activity and subsequently regulate skin homeostasis. This review summarizes current evidence on how functional ingredients modulate the gut–brain–skin axis in the context of aging and skin health. Polyphenols, probiotics, and omega-3 fatty acids appear to act through overlapping biological routes, including reshaping microbial communities, supporting epithelial barrier function, regulating immune activity, and limiting oxidative stress. These gut-derived signals may affect the brain through neural, endocrine, and immune pathways, thereby modulating neuroinflammation, hypothalamic–pituitary–adrenal (HPA) axis activity, and neurotransmitter balance. Through brain–skin communication, these changes may influence inflammation, epidermal barrier integrity, collagen remodeling, and skin aging processes. Emerging clinical evidence suggests potential improvements in skin-related outcomes and systemic inflammatory markers; however, studies remain heterogeneous, and integrated assessments of gut, brain, and skin endpoints are limited. Further studies that integrate multi-omics profiling with carefully designed clinical trials will be required to define causal pathways and support the development of evidence-based nutritional approaches targeting this axis. Full article

Background: The oral microbiome plays a fundamental role in maintaining local and systemic health during childhood, a developmental period characterized by dynamic microbial, immune, and neuroendocrine maturation. Increasing evidence suggests that oral dysbiosis may influence gut microbiota composition, systemic inflammation, and neuroinflammatory pathways through the oral–gut–brain axis. Aim: This narrative review aimed to summarize and critically evaluate current evidence regarding the relationship between oral dysbiosis, gut microbial alterations, systemic inflammation, and neurodevelopmental processes in pediatric populations. Methods: A search of the literature was conducted using PubMed, Scopus, and Web of Science, including studies published between January 2016 and April 2026. Eligible studies included randomized controlled trials, observational studies, and reviews investigating at least one component of the oral–gut–brain axis in children or adolescents. Results: Current evidence supports a biological interaction between oral and gut microbiota through microbial translocation and immune-mediated mechanisms. Oral dysbiosis may contribute to gut microbial imbalance, intestinal barrier dysfunction, and systemic low-grade inflammation. Altered gut microbiota has been associated with neuroinflammatory signaling, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and adverse neurodevelopmental outcomes. Furthermore, pediatric randomized controlled trials suggest that probiotics and synbiotics can modulate oral and gut microbial composition, improve selected inflammatory and immune biomarkers, and reduce salivary cortisol levels. Conclusions: The oral–gut–brain axis represents a promising framework for understanding the systemic consequences of oral dysbiosis during childhood. However, direct evidence integrating oral, intestinal, immunological, and neurodevelopmental outcomes remains limited, highlighting the need for longitudinal and multidisciplinary pediatric studies. Full article

Epilepsy is increasingly recognized as a systemic disorder involving complex interactions between the brain and peripheral systems. Among these, the gut microbiota has emerged as a key regulator of host metabolism and immune homeostasis through the production of bioactive metabolites that mediate the communication between gut and brain. In recent years, growing evidence has linked gut dysbiosis to epilepsy, particularly in drug-resistant forms, and interventional studies targeting the gut microbiota in animal models suggest that microbiota-driven metabolic alterations may contribute to seizure generation and recurrence, as well as the associated neuropathology and cognitive deficits. In this review, we summarize current knowledge on the role of the gut microbiota–metabolome axis in acquired epilepsy, with a particular focus on short-chain fatty acids (SCFAs) and tryptophan-derived pathways. SCFAs represent major microbial products involved in energy metabolism, inflammation, blood–brain barrier integrity, neurotransmission and epigenetic mechanisms. In parallel, microbiota-dependent tryptophan metabolism represents a central hub linking intestinal microbial activity to brain function through serotonin, kynurenine, and indole pathways. Dysregulation of these pathways may influence neuronal excitability and contribute to seizures. Converging evidence supports the concept that epilepsy is associated with a coordinated alteration of gut microbial composition and host–microbiota metabolic interactions. However, further research is needed to elucidate the mutual communication between the gut and its microbiota and the metabolic flux, and their influence on brain function in neurological conditions. A better understanding of the underlying pathways and mechanisms may highlight novel therapeutic strategies and discover novel biomarkers of disease trajectory. Full article

Microplastics and nanoplastics (MNPs) have been recognized as ubiquitous emerging global pollutants, which are extensively detectable in diverse environmental media and food matrices. Increasing evidence indicates that the intestine is a primary target of orally ingested MNPs and a critical initiating hub for systemic toxicity. Once ingested orally, MNPs can interact with the intestinal mucus layer and epithelial barrier, induce gut microbiota dysbiosis, remodel bile acid and short-chain fatty acid metabolism, and activate oxidative stress, inflammation, apoptosis, and immune imbalance. These gut-derived disturbances may subsequently propagate adverse signals to distal organs through the gut-liver, gut-brain, gut-kidney, gut-lung, gut-reproductive, and gut-mammary axes. Intestinal barrier dysfunction, endotoxin translocation, abnormal microbial metabolites, and microbiota-derived immune signals constitute common mediating pathways linking local intestinal injury to multi-organ toxicity. In addition, smaller particle size, surface oxidation, environmental aging, bio-corona/plastisphere formation, and co-exposure with other contaminants can further modulate the intensity and specificity of gut-organ axis disruption. Prior reviews are limited to separate analyses of single-organ toxicity or isolated gut-organ pathways. To fill this gap, this work synthesizes contemporary mechanistic and experimental evidence to establish a gut-initiated systemic toxicology framework for MNPs. We differentiate direct particle translocation from gut-derived indirect signaling, evaluate the varying robustness of supporting evidence for each gut-organ axis, and underscore nanoscale biointerface properties as key modulators of MNPs systemic toxic potency. Full article

Background/Objectives: Gut dysbiosis in children with autism spectrum disorder (ASD) has been associated with alterations in microbial ecology and metabolic function that may contribute to gastrointestinal dysfunction and the severity of clinical manifestations. Synbiotic and probiotic supplementation has emerged as a promising microbiome-targeted strategy for ASD; however, its effects on gut microbiome composition, functional potential, and clinical outcomes remain incompletely understood. We conducted a longitudinal study of Mexican children diagnosed with ASD to analyze changes in the composition, diversity, and functional potential of the gut microbiome during six months of multi-strain synbiotic supplementation. Methods: Stool samples were collected from 25 children with ASD at baseline and after 3 and 6 months of multi-strain synbiotic supplementation. Gut microbiome composition and diversity were analyzed by 16S rRNA gene sequencing, whereas whole metagenome sequencing (WMS) was performed in a subset of samples to evaluate the functional potential of the fecal microbiome. Gastrointestinal symptoms were assessed using the Rome IV criteria, and ASD severity was evaluated with the Childhood Autism Rating Scale (CARS). Results: Twenty-five children with ASD completed the 6 months of synbiotic supplementation. Overall, ASD severity decreased, reflected by a reduction in total CARS score, and improvements in several CARS domains. Gastrointestinal symptoms also decreased significantly. Longitudinal microbiome profiling revealed significant taxonomic and diversity changes over the supplementation period, while WMS identified changes in microbial metabolic potential, including enrichment of tryptophan biosynthesis pathways and reduced L-rhamnose degradation. Conclusions: This exploratory research provides proof-of-concept evidence supporting multi-strain synbiotic supplementation in children with ASD. Larger controlled studies are needed to confirm these findings and clarify their relevance to microbiota–gut–brain axis interactions. The observed concordance between clinical improvements and microbiome remodeling supports further investigation of microbiome-targeted interventions according to ASD severity and duration of supplementation. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and impaired glucose metabolism, significantly increasing the risk of type 2 diabetes and cardiovascular disease. Recent evidence highlights the important role of the gut–brain axis in the pathogenesis of MetS through complex interactions between the gut microbiota, immune system, endocrine signaling, and host genetics. This narrative review provides an integrative overview of the mechanisms linking dysbiosis to metabolic dysfunction, with particular emphasis on gut microbiota alterations, intestinal permeability, chronic low-grade inflammation, and microbial metabolites such as short-chain fatty acids and lipopolysaccharides. The review also discusses the neural, endocrine, and immune pathways involved in gut–brain communication, including the role of gut-derived neurotransmitters in metabolic regulation. In addition, the contribution of host genetic susceptibility and epigenetic regulation is explored, highlighting how gene–microbiome interactions influence individual metabolic responses and disease risk. Recent advances in multi-omics technologies and precision medicine suggest that personalized approaches targeting both microbial and genetic factors may improve prevention and treatment strategies for MetS. Furthermore, microbiota-targeted interventions, including dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation, are discussed as emerging therapeutic perspectives. Overall, this review emphasizes the importance of considering MetS as a systemic disorder driven by interconnected biological networks involving microbiota, metabolism, immunity, and genetics. Full article