Search Results (1,896)

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

Background: Postpartum depression (PPD) is a prevalent and debilitating disorder, with increasing evidence implicating the gut microbiota–brain axis. However, integrated alterations in gut microbiota and circulating metabolites in PPD remain insufficiently characterized. Methods: Fecal and serum samples were collected from patients with PPD and healthy controls (HC). Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17). Gut microbiota was analyzed by 16S rRNA sequencing, and serum metabolites were profiled using untargeted LC–MS-based metabolomics. Spearman correlation and receiver operating characteristic (ROC) analyses were performed. Results: A total of 63 participants (42 PPD, 21 HC) were included. Significant alterations in gut microbial composition were observed in PPD, including decreased Faecalibacterium and Akkermansia and increased Ralstonia and Fusobacterium. Candidate differential serum metabolic features, including LPE-related and energy-metabolism-related features, were identified. Exploratory correlation analyses suggested distinct microbiota–metabolite association patterns, and several microbial taxa and serum metabolic features were associated with HAMD-17 scores. ROC analysis showed that several taxa and metabolic features exhibited preliminary discriminative performance with this cohort, although further validation is required. Conclusions: PPD was associated with alterations in gut microbiota composition and exploratory circulating metabolite profiles, potentially involving lipid dysregulation, neuroinflammation, steroid-related metabolism, and neurotoxicity-related pathways. The identified taxa and putatively annotated metabolites should be regarded as exploratory PPD-associated candidates rather than validated biomarkers or mechanistic mediators. Further validation in larger, independent cohorts is warranted. These findings may also inform future microbiota- and nutrition-oriented strategies for postpartum mental health management. Full article

Gamma (γ)-aminobutyric acid (GABA) is a non-proteinogenic amino acid recognized for its primary function as the main inhibitory neurotransmitter in the mammalian central nervous system and its role as a stress-responsive metabolite in various microorganisms. This review critically examines the biosynthesis of GABA by lactic acid bacteria (LAB) via the glutamate decarboxylase (GAD) system and evaluates its potential applications in food and health sectors. The mechanistic details of the GAD pathway are analyzed, focusing on the integrated roles of gadA/gadB decarboxylases, the gadC antiporter, and pyridoxal−5′-phosphate (PLP) dependency in relation to acid resistance, metabolic flux, and strain variability. Taxonomic and strain-level diversity among GABA-producing LAB is assessed, with emphasis on the highly strain-specific nature of GABA production rather than broad species or genus generalizations. Fermentation optimization parameters (pH, temperature, substrate loading, and cofactor management) and scale-up challenges, including techno-economic feasibility and downstream recovery efficiency, are critically evaluated. Integration of LAB-derived GABA into fermented food matrices is discussed with attention to sensory compromises, stability, regulatory factors, and clean-label considerations. Evidence from clinical and preclinical studies is synthesized to assess the physiological significance of dietary GABA, distinguishing between purified GABA supplementation, GABA-enriched fermented foods, and probiotic effects of live LAB, while addressing the GABA paradox and gut–brain axis interactions. Significant research gaps are identified, including the need for standardized quantification methodologies, multi-omics-guided strain engineering, predictive bioprocess modeling, and rigorously designed human trials in realistic food matrices. This review provides a systems-oriented, critical framework to promote scalable and evidence-based advancement of GABA-enriched functional foods. Full article

Alcohol consumption has been increasingly associated with alterations in the gut microbiota and its metabolic activity; however, evidence regarding microbiota-derived metabolites remains fragmented. This systematic review aimed to synthesize current evidence on the effects of alcohol consumption on gut microbiota-derived metabolites in humans and non-human primates. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included studies published between 2012 and 2026. Searches were performed in PubMed, Web of Science, Scopus, and ScienceDirect. Study quality was assessed using the Newcastle–Ottawa Scale for human studies and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias tool for non-human primate studies. Twelve studies met the inclusion criteria, comprising four non-human primate studies and eight human studies. Alcohol exposure was consistently associated with metabolomic alterations across multiple biological matrices. Recurrent findings included reductions in short-chain fatty acids, alterations in tryptophan-derived metabolites, changes in phenolic and aromatic amino acid-related compounds such as hippuric acid, and disturbances in bile acid and purine metabolism. Findings regarding microbial diversity and taxonomic composition were more heterogeneous, with several studies reporting reduced abundances of Faecalibacterium and related butyrate-producing taxa. Studies evaluating abstinence suggested partial recovery of both microbial and metabolomic alterations. Overall, the available evidence suggests that alcohol consumption is associated with alterations across several microbiota-related metabolic pathways, highlighting candidate metabolites that may contribute to alcohol-related pathophysiology and serve as potential translational biomarkers. Full article

This review examines the structural variety, distribution, and physicochemical properties of chlorogenic acids (CGAs), identifying coffee and green coffee as the leading dietary sources of these compounds. Preclinical studies indicate that plant-derived phenolic compounds exhibit strong antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and antidiabetic effects across various disease models. The biological effectiveness of CGAs is attributed to their modulation of cellular signaling pathways, particularly by activating the erythroid 2-related factor 2 antioxidant defense mechanism and inhibiting the pro-inflammatory nuclear factor kappa B pathway. The regulation of the energy-sensing Sirtuin 1 and AMP-activated protein kinase pathways further enhances these therapeutic effects. In the gastrointestinal tract, CGAs serve as key modulators of the microbiota–gut–brain axis by exerting prebiotic-like effects, lowering the Firmicutes/Bacteroidetes ratio, promoting the production of short-chain fatty acids, and preserving gut barrier integrity. Some preclinical studies with coffee, Ilex paraguariensis, Eugenia uniflora, and other CGAs-rich extracts are also discussed. However, despite strong preclinical evidence, translating these findings into human clinical settings remains inconsistent due to significant individual differences in gut microbiota metabolism and the confounding effects of other components in dietary supplements, such as caffeine. Considering this, the review will first explore the molecular mechanisms supporting the potential development of CGAs as preventive interventions, while also discussing current human trials demonstrating selective improvements in neurological, cardiovascular, and metabolic functions. It will also highlight a historical limitation: the lack of studies on the bioavailability, bioactivity, and efficacy of isolated CGAs. The review will conclude by addressing the constraints of clinical studies, emphasizing the urgent need for future precision nutrition frameworks that employ standardized CGAs formulations to enhance potential therapeutic outcomes. 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

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by dysregulated host–microbiota interactions, epithelial barrier dysfunction, and aberrant immune activation. Despite advances in biologic and small-molecule therapies, a substantial proportion of patients exhibit incomplete response, loss of response, or treatment-related adverse effects, underscoring the need for novel adjunctive therapeutic approaches. The vagus nerve exerts a pivotal effects on immune homeostasis through the cholinergic anti-inflammatory pathway, thereby integrating peripheral immune sensing with central autonomic regulation. Within the context of IBD, a diminution in vagal tone has been observed to correlate with persistent mucosal inflammation and immune dysregulation. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique that may activate vagal circuits and modulate neuroimmune signaling without surgical intervention. This review endeavors to critically evaluate the potential efficacy of ta-VNS in the context of IBD, with particular emphasis on its discernible effects on immune, epithelial barrier, microbiota-related, and autonomic biomarkers. Emerging evidence, stemming from preliminary investigations, suggests that ta-VNS may exert an influence on inflammatory cytokine profiles, epithelial tight junction integrity, gut microbial composition, and systemic autonomic balance, warranting further elucidation. In addition, the review discusses differential responses between Crohn’s disease and ulcerative colitis, summarizes current preclinical and clinical evidence, and highlights biomarker-based strategies for evaluating therapeutic response in future randomized controlled trials. Although current evidence remains preliminary and stimulation parameters are not yet standardized, ta-VNS represents a promising adjunctive neuroimmune modulation strategy in IBD. Full article

Cirrhosis, accounting for 2.4% of global mortality in 2019, represents a leading cause of death in chronic liver disease. Hepatic encephalopathy (HE), a decompensated complication of cirrhosis, is associated with a median survival of only 0.92 years post-diagnosis. Current screening methods relying on neuropsychological tests (e.g., Psychometric Hepatic Encephalopathy Score, PHES) have limitations such as time-consuming procedures and subjective interpretation, potentially delaying diagnosis. To address this, we integrated four cirrhotic transcriptomic cohorts (GSE41919, GSE57193, GSE139602, and GSE15654) and employed an integrated algorithm (LASSO [Least Absolute Shrinkage and Selection Operator]–RFE [Recursive Feature Elimination]–random forest) to identify HE-specific biomarker genes. Ultimately, we developed an HE risk-prediction system centered on eight HE-specific marker genes, namely, PRB2, TUBA1C, NPC2, LRRC32, TLN1, SOX9, SERPINA3 and RNASE4. Based on these genes, an XGBoost (eXtreme Gradient Boosting)-based HE risk stratification model was constructed, and SHAP (SHapley Additive exPlanations) analysis was further introduced to address the “black-box” limitation of conventional machine learning models and to improve the interpretability. The finalized eight-gene system enables accurate, efficient, and interpretable HE risk assessment in patients with cirrhosis. Functional characterization through gene set enrichment analysis and structural equation modeling further revealed that these marker genes converge on four interconnected biological processes, namely, metabolic homeostasis, synaptic and neural transmission, immune inflammatory signaling, and hepatic detoxification, which collectively reflect the gut–liver–brain axis disruption central to HE pathogenesis. This dual-model system, incorporating both cirrhosis progression and survival prognosis, provides a reliable and clinically applicable tool for early HE risk warning and stratification, reducing the limitations of traditional neuropsychological screening and offering a translational foundation for timely intervention and prognostic optimization in high-risk cirrhotic patients. Full article

Background/Objectives: Gastrointestinal dysmotility (GID) is a frequent non-motor manifestation of Parkinson’s disease (PD). However, its peripheral electrophysiological characteristics, as well as the underlying neural mechanisms within the brain–gut axis, remain insufficiently understood. This study aimed to delineate spatiotemporal abnormalities in gastrointestinal pacing activity in PD and to explore their associations with cerebral functional connectivity (FC). Methods: Multichannel electrogastroenterography (EGEG) recordings, including both preprandial and postprandial states from gastric (leads 1–4) and intestinal (leads 5–8) regions, were obtained from patients with PD and healthy controls (HCs), alongside resting-state functional MRI (rs-fMRI). The striatal–thalamic circuit was selected as the seed region for FC analysis. Between-group differences in EGEG-derived spatiotemporal metrics were assessed using analysis of covariance (ANCOVA), while FC differences were examined using two-sample t-tests. Partial correlation analyses were conducted to evaluate associations among neuroimaging measures, aberrant gastrointestinal electrophysiological indices, and clinical variables. Regional specificity of correlations was further tested by comparing dependent correlation coefficients. In addition, multivariate brain–gut connectivity was assessed using partial canonical correlation analysis (pCCA) with 1000 permutation tests. Results: Relative to HCs, PD patients exhibited a significant reduction in the proportion of normal slow waves in both gastric and intestinal regions during preprandial and postprandial states (pFDR < 0.05). FC analysis revealed increased connectivity between the left thalamus and right insula in PD, whereas interhemispheric connectivity of the caudate nuclei and putamina was significantly reduced. Additionally, FC between the left pallidum and left precentral gyrus was attenuated in the PD group. Partial correlation analysis demonstrated a positive association between postprandial normal slow-wave fraction and interhemispheric caudate connectivity (r = 0.63, pFDR = 0.047). Furthermore, left thalamus–right insula connectivity correlated with both total Non-Motor Symptoms Scale (NMSS) scores (r = 0.57, pFDR = 0.042) and gastrointestinal subscale scores (r = 0.63, pFDR = 0.037). At the multivariate level, pCCA revealed a strong association between lentiform nucleus connectivity and preprandial gastric slow-wave rhythms (canonical r = 0.892, p = 0.004). Conclusions: In PD, caudate nucleus FC shows a preferential association with gastric rather than intestinal electrophysiological activity. Multivariate analyses further demonstrate a significant network-level association between lentiform nucleus connectivity and baseline gastric pacing rhythms, extending regional findings to a broader network interaction. Together, these results provide multimodal correlational evidence reflecting parallel central and peripheral alterations in PD, highlighting synchronized alterations in central networks and peripheral gastrointestinal rhythmicity. Full article

Age-related alterations in the gut microbiota contribute to chronic low-grade inflammation, immune dysregulation, metabolic dysfunction, frailty, sarcopenia, and cognitive decline. Dietary polyphenols and fermentable fiber modulate microbial composition and metabolism, promoting the production of bioactive metabolites, including short-chain fatty acids, secondary bile acids, indole derivatives, and urolithins, which regulate intestinal barrier integrity, immune homeostasis, mitochondrial function, and gut–organ communication. This narrative review critically synthesizes evidence from experimental studies, observational cohorts, randomized controlled trials, systematic reviews, and meta-analyses to examine microbiota-mediated mechanisms linking these dietary components to healthy aging within the geroscience framework. Although mechanistic evidence is compelling, translation into clinically meaningful aging outcomes remains limited because most intervention studies are small and heterogeneous and primarily rely on surrogate biomarkers. Current evidence supports polyphenol- and fiber-rich dietary patterns as biologically plausible strategies for promoting healthy aging through modulation of the gut microbiota; however, establishing causal relationships will require standardized microbiome methodologies, validated microbiome-derived biomarkers, integrated multi-omics approaches, and adequately powered longitudinal studies and randomized controlled trials. Full article

Microplastics and nanoplastics (MNPs) are emerging environmental pollutants due to their persistence and bodily accumulation. Recently, functional foods have received much attention for their ability to reverse or block MNP damage for therapeutic purposes and the potential risk of developing oral–gut–brain axis disorders. Among these, artichoke, spirulina algae, Opuntia ficus-indica, pterostilbene, hydroxycinnamic acids, and quinic acid are rich sources of polyphenols. These bioactive ingredients, especially when combined with probiotics and prebiotics, exhibit significant antioxidant and anti-inflammatory potential by activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and cellular resilience enzymes. Nrf2 activation enhances cellular resilience response, and it may preserve oral epithelial barrier (OEB), intestinal epithelial barrier (IEB), and blood–brain barrier (BBB) integrity, while modulating oral pathogens, gut microbial dysbiosis, and neuroinflammatory processes. However, most of the available evidence supporting these mechanisms derives from in vitro and animal studies, whereas clinical evidence in humans remains limited. Perturbations of Nrf2 due to circulating MNPs may exacerbate selective susceptibility to oral, gut, and nervous system disorders, including Alzheimer’s disease (AD). Although these findings are biologically plausible, the causal relationships and their clinical relevance have not yet been fully established. This review discusses the role of functional foods in maintaining oral–gut–brain health through Nrf2-mediated mechanisms that may mitigate MNP-induced inflammation and reactive oxygen species (ROS). The review also examines emerging concepts in precision nutritional medicine, including individual variability in dietary responses, microbiome-related factors, and future personalized strategies for populations exposed to MNPs. Finally, current knowledge gaps, the scarcity of human studies, and the challenges in translating preclinical findings into clinical practice are highlighted, emphasizing the need for further translational and clinical research. Full article

Background: The Braak hypothesis proposes that α-synuclein (α-syn) pathology may originate in the gastrointestinal tract and propagate to the central nervous system along the gut–brain axis; however, the precise propagation routes and the factors influencing this process remain controversial. Methods: A gut-originating Parkinson’s disease model was established by injecting α-syn preformed fibrils (PFF) into the duodenal muscularis of C57BL/6J and A53T transgenic mice. Phosphorylated α-synuclein (p-α-syn) pathology, motor behavior, and gut microbiota were assessed, with truncal vagotomy included to evaluate its association with gut-to-brain propagation. Results: In C57BL/6J mice, at 4 months post-injection, p-α-syn deposition was observed in both the duodenal muscular layer and the striatum, accompanied by gut microbiota alterations and motor behavioral deficits. Truncal vagotomy was associated with reduced p-α-syn levels in the brain and alterations in the gut microbiota. In A53T transgenic mice, p-α-syn pathology and neurodegenerative changes were also observed following α-syn PFF injection, though the lack of a genetically matched wild-type control precludes definitive attribution of these phenotypes solely to the A53T transgene. Conclusions: These results align with the Braak hypothesis, showing that gut-derived p-α-syn pathology and associated functional impairments are intimately linked to vagal pathways during their propagation to the brain. Additionally, this gut-origin PD mouse model may serve as a useful tool for future mechanistic investigations. Full article

Dietary patterns increasingly influence research on neurodegenerative diseases, with attention shifting from isolated nutrients to integrative nutritional models. The Amazonian Diet, a biodiversity-based dietary pattern rich in native fruits, seeds, freshwater fish, and cassava-derived foods, is naturally enriched in bioactive compounds including polyphenols, anthocyanins, carotenoids, methylxanthines, selenium, vitamins, and unsaturated fatty acids. This review aimed to investigate the potential relevance of key foods derived from the Amazonian Diet to Parkinson’s disease (PD) by integrating compositional nutritional analysis, multivariate analytical approaches, and mechanistic evidence synthesis. In Stage 1, the composition of 36 Amazonian foods was analyzed using TBCA and FAO data, followed by hierarchical clustering analysis (Ward’s linkage, Euclidean distance). Distinct compositional patterns were identified, highlighting foods with high bioactive diversity, relevant lipid composition, and dietary fiber. In Stage 2, an integrative literature review (PubMed/MEDLINE, SciELO) of in vitro, in vivo, observational, and clinical studies suggested that açaí berry, guaraná, cocoa/cacao, camu-camu, and Brazil nuts contain nutrients and bioactive compounds that intersect with biological pathways implicated in PD, including oxidative stress, mitochondrial dysfunction, and neuroinflammation. However, this review does not evaluate the effects of the Amazonian Diet on PD incidence, progression, symptoms, levodopa response, or biomarkers. 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