Search Results (1,204)

Bioactive peptides (BPs) are increasingly recognized for modulating the gut microbiome, metabolome, and brain function via the gut–brain axis. Kapi-pla, a traditional Thai fermented freshwater fish paste rich in proteins and peptides, is widely consumed in Southern Thailand. This study profiled the peptides of Phatthalung Kapi-pla (PK) and Songkhla Kapi-pla (SK) and investigated their impacts on gut microbiota and metabolome using a simulated colonic fermentation model with fecal samples from patients with Alzheimer’s disease (AD). Microbial composition and metabolites were assessed by 16S rRNA sequencing and LC–MS/MS, respectively. After 24 h fermentation, PK modestly increased Shannon diversity relative to the unsupplemented control, with richness indices unchanged, reduced Proteobacteria abundance and opportunistic pathogens such as Escherichia–Shigella and Klebsiella, and selectively increased short- and branched-chain fatty acids, including acetate, propionate, butyrate, and iso-valerate. PK further enhanced neuroactive metabolites relevant to AD pathology, underscoring its potential as a functional food ingredient to ameliorate AD-associated dysbiosis and support gut–brain axis health. 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

Lonicera japonica Thunb. (honeysuckle), a traditional herb with “food-medicine homology” status in Chinese medicine, is valued for its antipyretic and detoxifying properties. This review systematically summarizes its chemical composition—over 507 identified compounds, including phenylpropanoids, flavonoids, triterpenoids, saponins, and the plant-specific miR2911—as well as its multi-target pharmacological mechanisms and emerging translational applications, with particular emphasis on the gut–brain axis-mediated neuroprotective effects. Despite low oral bioavailability, honeysuckle polysaccharides and chlorogenic acid have been shown to exert significant neuroprotection in Alzheimer’s disease models by modulating gut microbiota composition, increasing short-chain fatty acid production, and restoring intestinal barrier integrity—a mechanism that challenges conventional direct-action paradigms. We also outline the applications of honeysuckle in functional foods, pharmaceuticals, animal husbandry, and cosmetics, and propose future directions including precision fermentation and mechanism-driven clinical trials. By integrating phytochemistry, pharmacology, and biotechnology, this review provides a roadmap for the evidence-based development of honeysuckle as a precise medicinal and edible resource. Full article

Autism spectrum disorder (ASD) and epilepsy are complex, frequently co-occurring neurodevelopmental and neurological disorders that share key mechanisms, such as altered neurotransmission, oxidative stress, neuroinflammation, and gut–brain axis disruption. Despite pharmacological advances, current treatments often provide only partial relief and are associated with significant side effects. The comorbidity of ASD and epilepsy, affecting millions worldwide, remains under-recognised and poorly addressed, imposing a profound burden on patients, families, and healthcare systems through reduced quality of life, increased caregiving demands, and substantial social and economic costs. This review highlights the convergent pathways shared between ASD and epilepsy, including immune dysregulation, synaptic dysfunction, and metabolic imbalance, which create opportunities for unified therapeutic strategies. Marine algae have emerged as a sustainable source of bioactive compounds offering a unique potential to address these overlapping pathologies. Algal polyunsaturated fatty acids, carotenoids, polyphenols, polysaccharides, and vitamins have antioxidant, anti-inflammatory, neuroprotective, and microbiota-modulating activities. By addressing both the biological underpinnings and clinical burden of ASD–epilepsy comorbidity, algae-based strategies represent a novel and ecologically sustainable direction for mitigating ASD–epilepsy comorbidity and advancing marine-inspired neurotherapeutics. Full article

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder in which systemic pathophysiological alterations significantly contribute to disease progression and non-motor manifestations, such as depression and anxiety. The microbiota–gut–brain axis represents a critical bidirectional pathway in which intestinal dysbiosis and epithelial barrier disruption catalyze central neuroinflammation. This scoping review synthesizes evidence from 43 empirical and analytical studies across 28 countries and maps the findings under the WHO International Classification of Functioning (ICF) framework. Pathophysiological data reveal a profound taxonomic shift in patients with ALS, characterized by severe depletion of neuroprotective, butyrate-producing genera (Akkermansia and Prevotella) and enrichment of pro-inflammatory Enterobacteriaceae. This dysbiotic state leads to structural damage to the intestinal mucosa, alteration of Paneth cells, and downregulation of tight junction proteins (zonulin), triggering a “leaky gut” phenomenon. Subsequent systemic translocation of lipopolysaccharides (LPS) induces TLR4-mediated endotoxemia, microglial hyperactivation, and accelerated motor neuron apoptosis. Conversely, therapeutic modulation via Fecal Microbiota Transplantation (FMT), psychobiotics, and metabolic interventions (ketogenic or Mediterranean diets) has demonstrated significant efficacy in restoring epithelial integrity, mitigating mitochondrial hypermetabolism, and reducing emotional distress. This review identifies a critical research gap in the microstructural characterization of the enteric nervous system in ALS. Incorporating microbiome-targeted biomarkers into clinical protocols is crucial for implementing a stratified, multi-systemic therapeutic strategy aimed at enhancing patient prognosis and psychological well-being. 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

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

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

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

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

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/Objectives: Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition for which current therapies remain inadequate. Probiotics acting on the microbiota–gut–brain axis are a promising preventive strategy, but their benefits are strain-specific. Here we examined whether Lacticaseibacillus paracasei LP36 alleviates lipopolysaccharide (LPS)-induced depression-like behavior in mice, and we characterized its metabolic actions using serum untargeted metabolomics. Methods: Sixty male C57BL/6J mice were randomized into eight groups (58 completed the study and were analyzed) and received saline or LP36 (1 × 10⁸, 1 × 10⁹, or 1 × 10¹⁰ colony-forming units (CFU)/mL) by gavage for 28 days, with LPS (0.5 mg/kg, i.p.) or saline given during the last 10 days. Results: LP36 pretreatment alleviated LPS-induced depression-like behavior in the sucrose preference, forced swimming, and tail suspension tests. Of 2867 annotated serum metabolites, 404 differed between the LPS and control groups, and 601 between the LP36 (10¹⁰)-treated and LPS groups. Among 180 shared differential metabolites, 172 (95.6%) changed in opposite directions, indicating that LP36 mainly reverses LPS-induced metabolic perturbations. KEGG enrichment localized these effects to lipid-related pathways, with lower relative signal intensities of polyunsaturated fatty acids and sphingolipids under LPS and higher relative signal intensities after LP36. In addition, the relative signal intensities of several microbiota-derived metabolites, including indoles, kynurenines, and secondary bile acids, shifted toward control-group values after LP36 intervention, which might reflect a contribution of the gut microbiota. Conclusions: LP36 is thus a candidate psychobiotic that may alleviate depression by reshaping gut microbiota-related metabolism and the associated lipid remodeling. Full article