Search Results (459)

The gut–immune–metabolic axis has emerged as a central regulator of human health, with growing evidence indicating that microbiota-derived metabolites improve gut microbial ecology, enhance intestinal barrier integrity, reduce systemic inflammation, and maintain metabolic homeostasis. This review synthesizes current mechanistic and clinical evidence on the role of postbiotics in regulating intestinal barrier integrity, immune responses, oxidative stress, and metabolic–endocrine homeostasis. The literature was identified through the PubMed/MEDLINE, Scopus, and Web of Science, integrating evidence from experimental, mechanistic, animal and clinical studies on the therapeutic potential of postbiotics to modulate the gut–immune–metabolic axis. Preclinical studies suggest that postbiotics may enhance epithelial barrier function by improving tight junction integrity through multiple pathways such as PI3K/Akt signaling, stimulating mucin-2 (MUC2) production, and reducing intestinal permeability. They modulate immune responses through interactions with Toll-like receptors, nucleotide-binding oligomerization domain receptors, and G-protein-coupled receptors (GPR41/43), influencing key signaling pathways, including NF-κB and Nrf2, and altering cytokine profiles, such as IL-10, TNF-α, and IFN-γ. Similarly, preclinical investigations have demonstrated that short-chain fatty acids (SCFAs) and other microbial metabolites may improve insulin sensitivity, regulate hepatic gluconeogenesis, stimulate glucagon-like peptide 1 (GLP-1) secretion, and modulate lipid metabolism through the FXR and TGR5 signaling pathways. Emerging human studies suggest potential benefits of postbiotics in regulating gut, immune, and metabolic health; nevertheless, clinical evidence remains limited and is influenced by variability in postbiotic composition, dosage, formulation, and metabolite profiles. Therefore, standardized production approaches and well-designed large-scale randomized clinical trials are required to confirm therapeutic efficacy and establish evidence-based applications of postbiotics. Full article

Global plastic production and inadequate waste management have led to widespread environmental contamination with microplastics (MPs), now detected in food, water, and air. Their small size, diverse polymer composition, and capacity to carry chemical additives and co-pollutants facilitate intestinal uptake and raise concerns about their potential impact on gut microbiota. This review synthesizes current evidence on how MPs influence gut microbial composition and function, gut barrier integrity, and associated inflammatory and metabolic pathways. We conducted a narrative review of in vivo animal studies, in vitro simulated gut systems, and human observational studies that assessed MP exposure, gut microbiota profiles, and downstream toxicological outcomes. MPs originate from primary and secondary sources and can act as vectors for metals and organic pollutants. Following ingestion, they may cross the intestinal barrier via endocytic and persorption routes, acquire a protein corona, and be recognized by immune cells, activating TLR/NF-κB, and MAPK pathways alongside oxidative stress. In these models, MP exposure induces dysbiosis, characterized by loss of beneficial SCFA-producing bacteria (e.g., Bifidobacterium, Lactobacillus, Bacteroides) and expansion of pathobionts (e.g., Escherichia/Shigella, Staphylococcus, Enterobacteriaceae), accompanied by altered bile acid metabolism. These microbiota and metabolic alterations are linked to increased gut permeability, intestinal inflammation, metabolic dysfunction, and, in some studies, reproductive and neurobehavioral effects. Current evidence supports MPs as emerging modulators of gut microbial and intestinal homeostasis. However, heterogeneity across experimental models, reliance on high exposure doses, and lack of standardized MP characterization limit robust risk assessment. These limitations underscore the need for harmonized methodologies, longitudinal large-scale human studies, and the development of targeted mitigation strategies. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by Aβ deposition, tau hyperphosphorylation, and neuroinflammation. No effective drugs can slow disease progression. Polysaccharides from traditional Chinese medicine (TCM) exhibit neuroprotective activities (e.g., antioxidant, anti-inflammatory) with good safety. However, their clinical application is limited by low oral bioavailability, poor blood–brain barrier (BBB) permeability, and a pharmacokinetic–pharmacodynamic paradox. The emerging role of the microbiota–gut–brain axis in AD offers a strategy to overcome this paradox. This review summarizes the structural features and classification of TCM polysaccharides (from plants, fungi, and roots/rhizomes) and highlights their anti-AD mechanisms via the gut–brain axis. Acting as prebiotics, these polysaccharides escape upper digestion and are fermented by gut microbiota into short-chain fatty acids (SCFAs) and other metabolites, which enter circulation, cross the BBB, and alleviate AD pathology through metabolic, immune, and neuronal pathways. Outcomes include reduced Aβ deposition and tau phosphorylation, suppressed neuroinflammation, restored synaptic function, and improved cognition. This review provides a theoretical framework for TCM polysaccharide intervention in AD via the gut–brain axis and a pharmacological basis for developing natural product-based AD therapies. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Current treatments, including anti-inflammatory drugs and biologics, often have limited efficacy and significant side effects, highlighting the need for novel therapeutic approaches. Phellodendrine (PHE) is a characteristic ingredient of Phellodendri chinensis, yet its effects and mechanisms on IBD remain elusive. The present study evaluated the potential of PHE for preventing dextran sulfate sodium-induced IBD in zebrafish. PHE effectively reduced inflammatory cell infiltration and modulated polarized macrophages. The qPCR results further confirmed the down-regulation of pro-inflammatory genes and up-regulation of anti-inflammatory factors. Consequently, PHE promoted the resolution of IBD inflammation. PHE also restored intestinal barrier integrity by enhancing MUC2 expression, increasing goblet cell counts, and reducing intestinal permeability of both chemical and physical barriers. In addition, PHE was associated with alterations in the gut microbiome, including a reduction in potentially pathogenic microbes and an increase in beneficial microbial populations. PHE also alleviated oxidative stress. Network pharmacology suggested the potential involvement of the IL-17 signaling pathway, the lipid and atherosclerosis pathway, and the TNF signaling pathway in the preventive effects of PHE against intestinal inflammation in the zebrafish model. In vivo gene expression analysis suggested that JUN, PTGS2, IL1B, DRD2, CALM1, and HSP90AA1 may serve as putative targets of PHE. Collectively, our results indicate that PHE demonstrates potential anti-inflammatory and barrier-protective activities in a zebrafish model of intestinal inflammation. The pharmacological mechanisms by which PHE restores intestinal barriers (microbial, chemical, physical, and immune barriers) include resolving inflammation, decreasing ROS production, and enhancing lipid accumulation in the lumen overlying the intestinal mucus barrier. This study provides novel insights into the preventive effects of PHE against intestinal inflammation in a zebrafish model, suggesting its potential as a candidate for further investigation. 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 complex and heterogeneous condition characterized by the coexistence of obesity, type 2 diabetes mellitus (T2DM), hypertension, chronic low-grade inflammation, and metabolic dysfunction. Increasing evidence suggests that the gut microbiota plays a central role in the development and progression of MetS by influencing host metabolism, intestinal barrier integrity, immune activation, endocrine signaling, and vascular homeostasis. This narrative review summarizes current evidence regarding gut microbiota alterations across major obesity-related metabolic phenotypes, including obesity alone, obesity complicated by T2DM, and obesity associated with hypertension. Obesity is generally characterized by reduced microbial diversity, depletion of beneficial taxa such as Faecalibacteriumprausnitzii and Akkermansia muciniphila, impaired short-chain fatty acid (SCFA) signaling, increased intestinal permeability, and metabolic endotoxemia. The coexistence of T2DM is associated with a more pronounced depletion of butyrate-producing bacteria, altered bile acid metabolism, impaired incretin signaling, and enhanced inflammatory activation that may contribute to insulin resistance and hyperglycemia. In hypertensive obesity, gut dysbiosis appears to preferentially involve disturbances within the gut–vascular axis, including reduced SCFA-producing taxa, increased trimethylamine N-oxide production, endothelial dysfunction, oxidative stress, and vascular inflammation. Although microbial signatures partially overlap among metabolic phenotypes, functional alterations in microbial metabolites and host–microbiota interactions may better explain disease heterogeneity than isolated taxonomic changes. Current evidence supports the potential role of microbiota-targeted interventions and integrated multi-omics approaches in future precision medicine strategies for cardiometabolic disease prevention and management. Full article

Gut barrier dysfunction and portal endotoxemia contribute to metabolic dysfunction-associated steatohepatitis (MASH) progression through activation of hepatic inflammatory signaling. Milk-derived extracellular vesicles (EVs) contain bioactive microRNAs and have recently attracted attention as modulators of intestinal homeostasis. This study investigated the effect of bovine milk-derived extracellular vesicles (B-mEVs) in ameliorating MASH by improving intestinal barrier function. C57BL/6J mice fed a choline-deficient amino acid-defined high-fat diet (CDA-HFD) were orally treated with B-mEVs, and therapeutic effects were evaluated. Liver histology, fibrosis, portal lipopolysaccharide (LPS) levels, intestinal permeability, and gut microbiota composition were evaluated. The direct effects of B-mEVs on intestinal barrier function were assessed using palmitic acid-stimulated Caco-2 cells. Small RNA sequencing and microRNA enrichment analyses were performed to characterize B-mEV cargo. B-mEV treatment attenuated hepatic steatosis, inflammation, and fibrosis in CDA-HFD-fed mice and reduced serum aminotransferase levels, portal LPS concentrations, hepatic macrophage accumulation, and hepatic TLR4/NF-κB signaling activation. Meanwhile, B-mEVs restored intestinal tight junction proteins, including ZO-1, occludin, and claudin-1, and improved intestinal permeability in vivo. In Caco-2 cells, B-mEVs attenuated palmitic acid-induced barrier dysfunction and suppressed myosin light chain kinase expression. Gut microbiota analysis revealed partial restoration of Akkermansia abundance after B-mEV administration. Furthermore, to explore the molecular basis of these protective effects, small RNA sequencing demonstrated enrichment of regulatory microRNAs, including let-7a-5p, and pathway analyses identified associations with intestinal barrier and inflammatory signaling pathways. B-mEVs ameliorated CDA-HFD-induced steatohepatitis by restoring intestinal barrier integrity and suppressing gut-derived LPS/TLR4 inflammatory signaling. These findings suggested that milk EVs may represent a novel gut–liver axis-targeted therapeutic strategy for MASH. Full article

Gut microbiota dysbiosis and metabolic disorders are key factors in inflammatory Bowel Disease (IBD) pathogenesis and progression. Although Artemisia rupestris water extract (AR) contains many anti-inflammatory compounds, its effects and mechanisms in colitis have not yet been explored. This study is the first to evaluate AR’s therapeutic efficacy in dextran sodium sulfate (DSS)-induced colitis and to investigate whether AR acts by modifying the gut microbiota and correcting metabolic imbalances. An acute inflammatory bowel disease model was established in mice using 3% DSS. Mice received AR at different doses, and clinical and pathological indices, histopathological scores, and blood concentrations of pro-inflammatory cytokines were evaluated. We explored AR; mechanisms in IBD using 16S rRNA sequencing and untargeted metabolomics. AR decreased concentrations of pro-inflammatory cytokines IL-6, CXCL-1, and TNF-α, and reduced MPO levels. It reduced intestinal permeability and mitigated IBD symptoms. Immunohistochemistry demonstrated that AR downregulated TLR4 and TLR9, while restoring Occludin (OCC) and Zonula Occludens-1 (ZO-1). AR modified the gut microbiota by reducing aberrant taxa such as HT002 and Erysipelatoclostridium, while increasing beneficial bacteria including Bacteroides, Alloprevotella, and Lachnospiraceae_NK4A136_group. AR also rectified metabolic disturbances by reducing 5OH-HIP, reversing decreases in metabolites such as 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoate and vanillin, and influencing amino acid and lipid metabolic pathways. AR treatment produces therapeutic effects distinct from other interventions by targeting inflammatory responses, restoring the gut microbiota and metabolism, suppressing TLR4 and TLR9 signaling, and repairing the mucosal barrier. Full article

Pediatric sarcopenic obesity (PSO) is an emerging conceptual framework characterized by the coexistence of excess visceral adiposity and impaired skeletal muscle accretion. Evidence suggests that this pathology is driven by systemic meta-inflammation rooted in the gut microbiota–immunometabolism axis. Dysbiosis, particularly the depletion of infant-type Bifidobacterium, compromises the intestinal barrier, potentially causing metabolic endotoxemia. In preclinical models, this triggers a pro-inflammatory, “Warburg-like” glycolytic shift in innate immune cells, releasing cytokines (IL-6, TNF-$\mathsf{\alpha }$) that heavily upregulate the ubiquitin–proteasome system in developing muscle. To address this cascade, we hypothesize that a targeted synbiotic approach utilizing dietary anthocyanins (e.g., cyanidin-3-O-galactoside) and prebiotic galacto-oligosaccharides (GOS) may offer metabolic benefits. This review clarifies the pharmacokinetic distinction between the systemic toxicity of high-dose injected galactose and the safety of dietary galactosides. Preclinical data suggest that ingested galactosides resist upper gastrointestinal digestion and undergo colonic cleavage by commensal $\mathsf{\beta }$-galactosidase, yielding short-chain fatty acids (SCFAs) that support intestinal permeability while releasing bioactive phenolic aglycones. Systemically, these aglycones may attenuate skeletal muscle catabolism by supporting PI3K/Akt signaling. Synthesizing current preclinical and adult-derived evidence, this review highlights the theoretical therapeutic potential of early-life synbiotic interventions as adjunctive therapies to support healthy muscle developmental trajectories in pediatric populations. Full article

Depression and anxiety are increasingly understood to involve systemic biological processes, where chronic stress, immune dysregulation, and vascular dysfunction converge on brain-relevant symptoms. Fermented foods are widely studied as psychobiotic candidates, yet results remain inconsistent because products vary in chemistry, viability, sodium, and biogenic amines, and trials often rely on broad symptom outcomes without exposure verification. A major gap is the lack of a reusable, mechanism-first framework that links what a product delivers to barrier, endothelial, and neurovascular target engagement. As a narrative and conceptual review rather than a systematic review, the article integrates mechanistic evidence into a conceptual framework rather than undertaking quantitative evidence synthesis. It addresses that gap by treating fermented vegetables, dairy, soy, and selected Brazilian cassava ferments and artisanal cheeses as metabolite-engineering platforms mapped onto a tri-barrier remodeling axis from gut epithelium to endothelium and platelets to the blood–brain barrier. We synthesize dosing-resolved metabolite modules, including short-chain fatty acids, tryptophan-derived indoles, bile acids, neuroactive small molecules, and peptide and exopolysaccharide fingerprints, and align them with interpretable readouts for permeability, endotoxemia proxies, endothelial activation, immunothrombosis, and epigenetic aging pace. Here we highlight how this modular framework converts heterogeneous food studies into testable exposure hypotheses, guides comparator design and phenotype stratification, and clarifies why null results can be informative. To maintain a focused scope, the review uses selected fermented-food families as representative test platforms rather than attempting a complete survey of global fermented foods. The emphasis is therefore placed on mechanisms, exposure verification, and trial-design principles that can be transferred to other products. Full article

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with evolving pathogenesis. Biological barriers, especially intestinal and blood–brain barriers (BBBs) with their tight junctions (TJ), are gaining attention in recent years as key players in disease initiation and progression. Among natural products targeting these barriers, cinnamon is emerging as a multi-targeted modulator of TJ. This narrative review integrates current evidence about gut and brain barrier dysfunction in lupus pathogenesis and highlights, on the basis of animal studies, the potential of cinnamon as a therapeutic candidate to restore barrier integrity and attenuate immune and neuroinflammation associated with lupus. Experimental evidence from lupus models supports the role of TJ disruption in disease pathogenesis. The alteration of TJ protein distribution in the epithelial barrier is correlated with an increased permeability of the intestinal barrier and changes in the microbiota composition in lupus, with consequent alteration in the gut–liver axis, liver inflammation and oxidative stress. Pre-clinical studies have demonstrated the restorative effect of cinnamon on gut TJ and permeability, microbiota and the gut–liver axis. Moreover, accumulating data suggest BBB disruption in lupus, correlated with neuroinflammation and behavioral disturbances. A murine model demonstrates the protective effect of cinnamon on BBB, especially via TJ localization, with the alleviation of neuropsychiatric alterations. Future perspectives should focus on cinnamon’s effect on the gut–brain axis and translational studies. Full article

The mammalian respiratory system stands as a frontline barrier, constantly exposed to environmental insults, balancing defensive immunity with gas exchange. Historically considered sterile, the lung harbors a dynamic, low-biomass microbiome that evolves continuously in response to pulmonary pathologies. Accumulating evidence underscores that respiratory health and structural recovery are not autonomous but are critically integrated with distal microbial systems, especially the intestinal tract, through the gut–lung axis (GLA). This review characterizes the GLA as a bidirectional communication highway fueled by immune pathways, microbial metabolites, and direct microbial translocations. During acute or chronic injuries, such as COVID-19, COPD, asthma, idiopathic pulmonary fibrosis (IPF) and lung cancer, the gut microbiota serves as a remote metabolic “rheostat”. It delivers pivotal signaling molecules, such as short-chain fatty acids (SCFAs) and tryptophan metabolites (indoles), that could shape the local microenvironment in which the respiratory epithelium undergoes functional repair or maladaptive, fibrotic remodeling. Mechanistically, gut-derived butyrate enhances mitochondrial activity in alveolar epithelial cells, while resident progenitors, such as Alveolar Type 2 (AT2) cells, depend on intact mitochondrial fatty acid oxidation for proper regenerative differentiation. Conversely, critical lung illness disrupts this homeostasis via a “pathological circuit,” where severe pulmonary inflammation drives gut permeability, fecal dysbiosis, and the subsequent translocation of pathogen-associated molecular patterns (PAMPs, such as LPS) or gut-associated bacteria back into the pulmonary circulation. This review highlights the systemic nature of lung regeneration, which likely depends heavily on intestinal health through the GLA. Ultimately, leveraging these remote microbial networks through precision postbiotic supplementation, dietary priming, or microbiota transplantation represents a crucial frontier in precision medicine to promote definitive alveolar repair. Full article

Background: Food allergy is a heterogeneous pediatric disease involving IgE-mediated, non-IgE-mediated, and mixed immune mechanisms, with manifestations ranging from mild symptoms to life-threatening anaphylaxis. Current diagnostic tools, including clinical history, skin prick testing, serum-specific IgE measurement, and oral food challenge, have limitations in specificity, invasiveness, prognostic value, and ability to guide personalized management. Methods: This narrative review summarizes emerging biomarkers in pediatric food allergy and evaluates their diagnostic, prognostic, predictive, and therapeutic potential. A literature search was conducted in PubMed/MEDLINE and Cochrane Central for English-language studies published between December 2015 and March 2026. Eligible studies included original clinical or translational research involving children aged 0–18 years and assessing functional cellular assays, epithelial barrier markers, intestinal permeability, gut microbiota, metabolomics, transcriptomics, proteomics, epigenetics, and immune biomarkers. Findings were synthesized qualitatively according to biomarker category and biological function. Results: Functional cellular biomarkers, particularly the basophil activation test, show the greatest translational readiness, with high diagnostic specificity, utility in reaction threshold and severity assessment, and potential value for monitoring oral immunotherapy. Biomarkers of epithelial barrier dysfunction, including zonulin, tight junction proteins, epithelial injury markers, filaggrin variants, and epithelial-derived cytokines, provide mechanistic insight into allergic sensitization and gastrointestinal phenotypes but remain insufficiently validated. Microbiota-derived, metabolomic, transcriptomic, proteomic, epigenetic, and integrated multi-omics approaches offer promising tools for risk prediction, tolerance monitoring, endotype identification, and precision medicine. Conclusions: Emerging biomarkers may improve diagnosis, risk stratification, therapeutic monitoring, and personalized care in pediatric food allergy. However, standardized assays, large longitudinal pediatric studies, and external validation are required before routine clinical implementation. Full article

Low-molecular-weight collagen peptides from food processing byproducts offer a sustainable approach to mitigating intestinal inflammation, yet their mechanistic roles remain incompletely understood. We evaluated red fish scale collagen peptides-I (LSCP-I), a <3 kDa collagen peptide fraction derived from Lutjanus erythropterus scales, in cellular and murine models of colitis. In Caco-2 cells subjected to macrophage-mediated inflammatory injury, LSCP-I (50 µg/mL) increased proliferation by 35%, enhanced migration by 40%, preserved barrier integrity, reduced reactive oxygen species (ROS) by 45%, decreased lipid peroxidation by 30%, and restored glutathione (GSH) and superoxide dismutase (SOD) activity. In mice with dextran sulfate sodium (DSS)-induced colitis, oral administration of LSCP-I at 200, 400 and 800 mg/kg/day attenuated weight loss and diarrhea, lowered intestinal permeability by 38%, enhanced colon histology, and restored the balance between pro- and anti-inflammatory cytokines. Mechanistically, LSCP-I activated the Nrf2 antioxidant pathway and partially restored gut microbiota composition. These results demonstrate that LSCP-I reinforces intestinal barrier function, restores redox homeostasis, and modulates host–microbiota interactions, establishing its potential as a functional food ingredient for the prevention and management of inflammatory bowel disease. Full article

Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut–brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases. Full article