Search Results (353)

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by impaired social interaction and repetitive stereotyped behaviors, with pathogenic mechanisms that remain incompletely understood. The gut microbiota has emerged as a key regulator of ASD; however, its impact on hippocampal proteomic and phosphoproteomic signatures has not been fully characterized. In this study, we performed fecal microbiota transplantation (FMT) by transferring fecal samples from children with ASD and typically developing controls into antibiotic-treated mice. Gut microbiota from children with ASD induced several ASD-like behaviors in recipient mice, accompanied by aberrant activation of microglia, astrocytes, and neurons, as well as impaired neurogenesis. Phosphoproteomic profiling combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that differentially phosphorylated proteins were predominantly enriched in synapse-related pathways. ASD-derived microbiota markedly reduced synaptic density, downregulated the synaptic proteins SYP and PSD-95, and inhibited the expression of blood–brain barrier (BBB) tight junction proteins. In silico structural simulations using AlphaFold3 (AF3) and HADDOCK further supported that ASD-FMT may promote abnormal phosphorylation, potentially remodeling SHANK3 and SRRM2 conformations and weakening the binding affinity of SHANK3. Integrative proteomic and phosphoproteomic screening identified FNDC3A as a potential susceptibility-associated protein upregulated by gut microbiota from children with ASD, which was verified in mouse hippocampal tissues and plasma samples from children with ASD using Western blotting and ELISA, respectively. Mechanistically, ASD pathogenesis may be attributable not only to the dysregulation of classical ASD susceptibility genes but also to gut microbiota-driven post-translational phosphorylation remodeling of multiple protein structures. Importantly, this study established an innovative research framework that integrates in silico analyses with wet-lab experiments, yielding novel insights into ASD pathogenesis from the perspective of gut microbiota-induced alterations in the hippocampal phosphoproteome and revealing a plausible molecular mechanism underlying ASD. Full article

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

Plastic contamination (plastamination) has become a pervasive environmental threat with growing implications for human health. Among plastic-derived contaminants, micro- and nano-plastics (MNPs) are of particular concern due to their persistence, widespread distribution, and capacity to interact with biological systems. Humans are exposed to MNPs through ingestion, inhalation, dermal contact, and maternal transfer, and these particles can cross biological barriers, including the blood–brain barrier, reaching the central nervous system. MNPs disrupt cellular homeostasis by inducing oxidative stress, mitochondrial dysfunction, and inflammation. In the brain, these processes drive glial activation and chronic neuroinflammation, which are closely associated with neuronal damage and neurological disorders, including Parkinson’s disease (PD). MNPs can also affect systemic pathways such as the gut–brain axis (GBA) and neuroendocrine regulation, suggesting broader physiological consequences. This narrative review synthesizes current evidence on the neurotoxic and pro-inflammatory potential of MNPs. Since MNPs may promote the aggregation of proteins implicated in neurodegeneration, such as alpha-synuclein, their possible role in PD is discussed. Despite several knowledge gaps, MNPs may be emerging environmental risk factors for brain health and neurodegenerative diseases such as PD. Nevertheless, there is a need for further studies in the field, standardized methodologies and longitudinal studies to implement effective mitigation strategies. 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

The intricate interplay between the gut microbiome and the enteric nervous system remains a paramount focus in understanding the multifactorial pathogenesis of disorders of gut–brain interaction (DGBI), most notably irritable bowel syndrome (IBS). While the clinical entity of post-infectious IBS is well-established, the independent, long-term pathophysiological impact of iatrogenic antibiotic exposure is garnering critical attention within neurogastroenterology. This narrative review provides a comprehensive synthesis of current epidemiological and mechanistic evidence positioning antibiotic-induced microbial depletion as a potential predisposing factor for incident IBS. By evaluating recent literature, we highlight epidemiological trends demonstrating a consistent, dose-dependent relationship between cumulative antibiotic courses, particularly broad-spectrum agents, and an elevated risk of developing IBS, independent of prior acute enteric infections. Furthermore, we explore the mechanistic underpinnings of this association, focusing on how systemic antibiotics induce persistent, detrimental alterations in commensal diversity. This resulting dysbiosis initiates a proposed cascade of downstream consequences, including compromised epithelial barrier integrity, persistent low-grade mucosal inflammation, and altered bile acid metabolism. These localized disruptions serve as established triggers for visceral hypersensitivity and dysregulated gastrointestinal motility communicated via the gut–brain axis. Ultimately, this review underscores that antibiotic exposure may act as a significant, modifiable risk factor for IBS pathogenesis. Recognizing this substantial iatrogenic risk reinforces an urgent clinical imperative for stringent antimicrobial stewardship and emphasizes the necessity for future research directed toward prophylactic, microbiome-sparing strategies to mitigate the escalating global burden of DGBIs. 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

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

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

Background: Irritable bowel syndrome (IBS) is a chronic disorder of brain–gut interaction closely linked to psychological stress and highly prevalent among university student populations, yet data from Bahrain remain scarce. This study estimated the frequency of self-reported IBS-like symptoms among university students in Bahrain and examined their associations with sex, age, qualification level, body mass index (BMI), psychological stress, and lifestyle behaviors. Methods: A cross-sectional, online questionnaire-based survey was conducted among 310 students at the University of Bahrain in October 2021. A self-administered 16-item instrument, based on the Rome III symptom domains and used as a symptom-screening rather than a diagnostic tool (face validity only; no formal psychometric validation was performed), assessed sociodemographic characteristics, self-reported IBS-like symptoms, stress and anxiety, and lifestyle behaviors. Data were analyzed using chi-square tests and one-way ANOVA; effect sizes were quantified using Cramér’s V (chi-square) and partial eta-squared (η², ANOVA); the significance threshold was α = 0.05 (two-tailed). Results: Self-reported IBS-like symptoms were common: 52.9% (95% CI 47.3–58.4) reported recurrent abdominal pain, 58.1% (95% CI 52.5–63.4) abdominal bloating, and 80.3% (95% CI 75.5–84.4) reported interference with academic activities. Most participants perceived their mental state (84.8%) and examinations (73.2%) to worsen symptoms, yet only 48.7% correctly identified IBS. Exploratory subgroup analyses suggested differences by qualification level, with diploma-level students reporting higher rates of abdominal pain (p < 0.001; Cramér’s V = 0.22), bloating (p < 0.05; Cramér’s V = 0.13), and perceived psychological impact on symptom severity (p < 0.001; Cramér’s V = 0.19) compared with bachelor- and master-level counterparts. The substantial female over-representation (79%) precluded formal sex-based inference; all findings should be interpreted in this context. Conclusions: Self-reported IBS-like symptoms were commonly endorsed, and participants frequently perceived psychological stress to worsen symptoms. Diploma-level students may represent a previously unrecognized potentially at-risk subgroup warranting further investigation and, if confirmed, targeted stress-focused health-promotion strategies, particularly through brief psychoeducation modules integrated within diploma-program curricula, and dedicated prospective research. Future studies should incorporate validated Rome IV diagnostic criteria, multivariable regression modeling, and biomarker assessment to elucidate underlying brain–gut mechanisms. Full article

Seasonal affective disorder (SAD) is a recurrent mood disorder associated with reduced photoperiod exposure and circadian disruption during autumn and winter. Emerging evidence links SAD to alterations in serotonergic signaling, neuroimmune activity, metabolism, and the microbiota–gut–brain axis; however, the causal relationships among these systems remain incompletely understood. A structured search of PubMed, Web of Science, and Scopus identified relevant publications from 2000 to 2025, with clinical and preclinical evidence evaluated separately. Proposed links between circadian misalignment, inflammatory signaling, and tryptophan metabolism toward the kynurenine pathway are based largely on associative and preclinical findings rather than confirmed mechanisms in SAD. The microbiota–gut–brain axis in SAD is likely bidirectional, as seasonal changes in feeding behavior, physical activity, and circadian phase may themselves influence gut microbial composition and function. Accordingly, microbiome alterations in affective disorders may reflect both potential upstream modulators and downstream consequences of disease-related behavior. Psychobiotics have been proposed as modulators of gut–brain communication in affective disorders. Among candidate strains, Lacticaseibacillus rhamnosus GG (formerly Lactobacillus rhamnosus GG; LGG) has shown effects on intestinal barrier function, immune signaling, and host tryptophan metabolism in preclinical studies. However, evidence derives largely from animal or non-seasonal depression models, and direct evidence in SAD is lacking. Thus, LGG should be considered a mechanistically plausible candidate for future investigation rather than an established therapy. This review synthesizes evidence on circadian regulation, serotonergic and tryptophan metabolism, and microbiota–gut–brain interactions in SAD, and highlights mechanistic gaps for future studies. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and a leading cause of dementia worldwide, yet effective disease-modifying therapies remain elusive. Rodent models have been indispensable for elucidating key pathological mechanisms, including amyloid-beta (Aβ) deposition, tau pathology, neuroinflammation, and synaptic dysfunction. However, despite decades of preclinical success, the translation of therapeutic findings from rodent studies to clinical efficacy in humans has been largely unsuccessful, highlighting critical limitations in current modelling approaches. This narrative review provides a comprehensive and critical evaluation of rodent models of AD, encompassing transgenic, chemically induced, metabolic, inflammatory, and lesion-based paradigms. Rather than presenting these models in isolation, we propose a systems-level framework that categorizes them based on their ability to recapitulate distinct domains of AD pathology, including genetic, environmental, and systemic contributors. By synthesising existing research, highlighting critical gaps, and proposing a tiered minimum-criteria framework for the development of next-generation models, we offer a definitive operational roadmap instead of merely a list of deficiencies. We highlight that most existing models predominantly reflect familial and reductionist aspects of the disease, while failing to capture the complexity of sporadic AD, aging processes, vascular dysfunction, and whole-body interactions. Importantly, we emphasize emerging dimensions that are underrepresented in current rodent models, including glymphatic dysfunction, cerebral small vessel disease, and the microbiota–gut–brain axis, all of which play crucial roles in AD pathogenesis. We further discuss how integrating these factors into next-generation models may improve translational relevance and therapeutic predictability. By synthesizing current evidence and identifying key gaps, we provide a strategic roadmap for the development of more physiologically relevant and translationally robust rodent models. Advancing toward integrative, systems-based approaches will be essential for bridging the persistent gap between preclinical discoveries and clinical success in AD. Full article

Growing evidence indicates a bidirectional relationship between the gut microbiota and sleep disturbances in children, with the microbiota–gut–brain axis (MGBA) mediating this interaction. Sleep, circadian rhythms, and the gut microbiota form an interdependent and developmentally dynamic network that plays a crucial role in neurodevelopment during infancy and childhood. Although the mechanisms underlying this complex interaction have not yet been fully elucidated, emerging evidence suggests that multiple dimensions of sleep—including duration, quality, timing, and regularity—are closely associated with gut microbial composition and function. These findings support the rationale for nutritional and microbiota-targeted interventions during critical developmental windows. However, most mechanistic and taxonomic evidence derives from adult or mixed-age cohorts, while methodological heterogeneity, geographic bias, and the predominance of cross-sectional studies limit causal inference. This review provides an overview of the recent literature investigating the role of the gut microbiota in sleep and sleep disorders in children and summarizes potential microbiota-based therapeutic strategies. Full article