Search Results (601)

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 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

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

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

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

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

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops many years before clinical symptoms appear. The biological changes involved in the earliest stages remain poorly understood, particularly during the preclinical stage. Our previous work has identified gradual gut microbial and metabolic changes during this stage, suggesting these may represent early biological shifts that precede disease progression. Recent studies suggest that the gut microbiome may contribute to early AD processes through its effects on immune regulation, metabolism, and gut–brain communication. Changes in gut microbial composition, including reduced levels of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium, Roseburia, and Eubacterium, have been reported in individuals with AD and mild cognitive impairment. These microbial alterations have also been linked to disrupted metabolic activity, impaired gut barrier function, and increased neuroinflammatory responses. Diet is an important factor influencing gut microbial composition and metabolic activity. Mediterranean, DASH, and prudent dietary patterns are generally associated with beneficial microbial profiles and increased SCFA production, whereas Western dietary patterns are linked to lower microbial diversity and increased pro-inflammatory taxa. This review summarises the current evidence linking gut microbiota, SCFAs, microbial metabolism, and dietary patterns with early AD pathology, while highlighting important gaps in the existing literature. 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

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

Population aging is a growing problem. This process is driven not only by genetic factors but also by environmental factors, such as diet. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide, characterized by cognitive decline, synaptic dysfunction, and neuronal loss. Despite extensive research, effective disease-modifying therapies remain limited. Increasing evidence indicates that oxidative stress plays a central role in AD pathogenesis, acting as a key link between β-amyloid accumulation, tau hyperphosphorylation, mitochondrial dysfunction, and neuroinflammation. Accordingly, dietary strategies have been proposed to mitigate these pathological processes and may represent an important component of Alzheimer’s disease prevention. Moreover, emerging evidence on the gut–brain axis highlights the critical role of gut microbiota in regulating neuroinflammation and oxidative stress. Dysbiosis has been associated with increased permeability of the intestinal barrier, systemic inflammation, and accelerated neurodegeneration. Dietary patterns such as the Mediterranean, DASH, and MIND diets may exert beneficial effects by simultaneously influencing antioxidant status and microbial composition. This review aims to provide a comprehensive overview of the role of oxidative stress in Alzheimer’s disease and evaluate the potential of dietary interventions in modulating mechanisms involved in Alzheimer’s disease pathogenesis and supporting cognitive health. Particular attention is given to the neuroprotective effects of dietary antioxidants, including vitamins, polyphenols, and polyunsaturated fatty acids, which act through the reduction in reactive oxygen species, modulation of inflammatory pathways, and support of neuronal survival. Although current findings are promising, inconsistencies in clinical data indicate the need for further well-designed studies. Future research should focus on personalized nutritional strategies integrating dietary, genetic, and microbiome-related factors. Targeting oxidative stress through diet and microbiota modulation represents a promising complementary strategy for Alzheimer’s disease prevention and supportive management, although further clinical studies are required to establish disease-modifying effects. 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: Multiple sclerosis and periodontal disease are chronic inflammatory conditions that may share immune-mediated mechanisms, including cytokine activation, oral dysbiosis, oxidative stress, and systemic inflammatory burden. This systematic review aimed to synthesize recent evidence on common inflammatory pathways linking periodontal disease and multiple sclerosis. Methods: The review was conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE, Cochrane Library, and Scopus were searched for English-language studies published between June 2020 and June 2026. Eligible studies addressed multiple sclerosis, periodontal disease, oral microbiome alterations, systemic inflammation, or neuroinflammatory outcomes. Study selection and data extraction were performed independently by three reviewers. Risk of bias was assessed using AMSTAR 2, the Newcastle–Ottawa Scale, and the Joanna Briggs Institute checklist, according to study design. Results: Seventeen studies were included in the qualitative synthesis. The main shared mechanisms were cytokine-mediated inflammation involving TNF-α, IL-1β, IL-6, and IL-17; NF-κB signaling; Th17/Treg imbalance; blood–brain barrier disruption; oxidative stress; matrix metalloproteinase activity; complement activation; and oral–gut–brain axis dysregulation. The evidence suggests that periodontal inflammation may contribute to systemic immune activation and may amplify neuroinflammatory processes in multiple sclerosis. Conclusions: Current evidence supports a biologically possible association between periodontal disease and multiple sclerosis through shared inflammatory and microbial pathways. However, causality remains unproven, and further longitudinal and interventional studies are needed. Full article

Background and Objectives: The concept of the gut–muscle–brain axis encompasses the intricate, multidirectional interactions between the gut microbiota (GM), physical exercise (PE), and the central nervous system. Within this framework, gut dysbiosis has been implicated in the pathogenesis of Alzheimer’s disease (AD). Given that cognitive functions in AD appear to benefit from PE, it is plausible to hypothesize that these improvements may be partially mediated by PE-induced alterations in GM taxonomy. Therefore, the objective of this study is to evaluate the potential effects of PE in the GM and their implications for AD. Methods: A systematic review was conducted in PubMed, Web of Science and Scopus following the PRISMA guidelines up to July 2025 for preclinical controlled trials that assessed the effects of PE on the GM of AD animal models. A random-effects model meta-analysis was performed to estimate the pooled effect of PE on GM frequency or composition. This study received no external funding. Results: Eight studies were included in the systematic review (sample size, n = 126), of which two could be meta-analyzed. We found that PE significantly reduced Actinobacteria abundance (MD = −0.005%; 95% CI, −0.008 to −0.002; p = 0.001) with no statistically significant evidence of heterogeneity (I² = 89.60%, Q = 0.102, p = 0.950) or publication bias observed (Begg’s test, p = 0.296), but no significant effects were found for other phylums or genera. Conclusions: PE appears capable of modulating the GM of animal models with AD in a selective and heterogeneous manner. Further studies are needed to clarify the mechanisms by which this is possible and to determinate its impact on the pathogenesis of the disease. Full article

Background/Objectives: Major depressive disorder (MDD) has been increasingly associated with alterations of the gut microbiome through the microbiota–gut–brain axis. However, published findings remain highly heterogeneous, limiting identification of reproducible microbial signatures associated with depression. This systematic review aimed to evaluate reproducible taxonomic and functional gut microbiome alterations in patients with MDD compared with healthy controls. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science Core Collection, and the Cochrane Library for studies published between January 2016 and December 2025. Observational human studies evaluating gut microbiome composition in adults with clinically diagnosed MDD and healthy control groups were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Due to substantial methodological heterogeneity, findings were synthesized using structured qualitative narrative analysis. Results: Sixteen observational studies were included in the qualitative synthesis. Findings related to alpha diversity were inconsistent across studies, whereas beta diversity alterations demonstrated greater reproducibility across independent cohorts. The most recurrent microbiome pattern involved depletion of short-chain fatty acid (SCFA)-producing bacteria, particularly Faecalibacterium and Roseburia, together with recurrent alterations affecting members of the Ruminococcaceae, Lachnospiraceae, and Clostridia groups. Functional microbiome alterations demonstrated greater consistency than higher-level taxonomic findings and included reduced butyrate synthesis pathways, dysregulated amino acid and tryptophan metabolism, increased lipopolysaccharide biosynthesis, and enrichment of pro-inflammatory microbial signatures. Antidepressant-naïve cohorts generally demonstrated more homogeneous dysbiosis patterns than mixed-treated populations. Conclusions: Current evidence suggests that functional gut microbiome dysregulation may represent a more reproducible biological feature of MDD than isolated taxonomic alterations alone. However, substantial heterogeneity in study design, participant characteristics, sequencing methodologies, and analytical approaches continues to limit clinical translation. Large-scale longitudinal multi-omics studies using standardized methodologies are required to clarify the role of the gut microbiome in depressive disorders and to evaluate the potential utility of microbiome-based biomarkers and interventions in mental health and public health practice. Full article