Search Results (2,712)

The development of patient-derived organoids (PDOs) has substantially advanced the study of gastrointestinal diseases by providing three-dimensional human models that faithfully recapitulate the structural, molecular, and functional characteristics of native tissues. Unlike conventional two-dimensional cultures and animal models, intestinal organoids preserve epithelial architecture, cellular heterogeneity, and patient-specific genetic features, enabling more physiologically relevant investigations of gastrointestinal physiology and disease. Recent technological advances, including co-culture systems, organoid-derived monolayers, and organ-on-chip platforms, have further expanded their ability to model epithelial interactions with immune cells, stromal components, and the gut microbiota. These developments have facilitated mechanistic studies of epithelial barrier function, host–microbiota communication, microbial metabolites, and endocrine signaling, while also supporting translational applications in inflammatory bowel disease, infectious disorders, inherited gastrointestinal diseases, and gastrointestinal cancers. Moreover, patient-derived organoids have emerged as promising platforms for drug screening, biomarker discovery, precision medicine, and regenerative therapies. Despite these advances, several challenges remain, including limited representation of the native tissue microenvironment, lack of standardized culture protocols, scalability, and regulatory issues that currently restrict routine clinical implementation. This review summarizes recent progress in gastrointestinal organoid technology, highlighting current applications, emerging experimental platforms, and future perspectives for integrating organoid-based models into translational research and personalized medicine. Full article

This review systematically summarizes the metabolic transformation patterns, bioavailability regulation mechanisms, and multi-target host health effects of honey phenolic compounds under the action of gut microbiota, based on literature from 1996 to 2026. It focuses on elucidating the “high efficacy in vitro, low exposure in vivo” paradox, the three-step cascade metabolic pathway (deglycosylation, C-ring cleavage, and reduction with secondary transformation), and the synergistic prebiotic effects of “oligosaccharides plus phenolics.” Current evidence indicates that the health benefits of honey are largely derived from microbiota-derived small-molecule metabolites rather than from the parent compounds, and these metabolites exert regulatory effects via the gut–liver, gut–brain, gut–immune, and gut–fat axes. However, the vast majority of evidence comes from in vitro fermentation, animal models, or ex vivo fecal cultures, with a severe shortage of high-quality human intervention studies, thereby limiting causal inference. Therefore, this review proposes a shift in honey quality evaluation from traditional qualitative chemical composition-based assessment toward precision functional evaluation based on metabolite profiles, and emphasizes the urgent need to establish standardized metabolite-based quality markers, develop enterotype-based stratified nutrition strategies, and conduct rigorous randomized controlled trials, so as to promote the transformation of honey from a traditional food into a targeted dietary intervention agent. Full article

The study evaluated the effects of dietary compound enzyme preparations (CEPs) supplementation on antioxidant capacity, immune response, and intestinal health of pigeons. A total of 288 White King parent pigeons were randomly assigned to four treatments, with six replications of 12 pigeons each. The control (CK) group received a basal diet, whereas the CEP groups were fed a basal diet with 0.25 g/kg (low compound enzyme preparation group, LCEP), 0.5 g/kg (middle compound enzyme preparation group, MCEP), and 1.0 g/kg (high compound enzyme preparation group, HCEP) CEPs. Results showed that supplementation with 0.25 g/kg of CEPs significantly increased duodenal crypt depth (CD), as well as jejunal villus height (VH) and the villus height-to-crypt depth ratio (VCR) (p < 0.05). It also increased the immunoglobulins of serum, such as IgA, IgG, and IgM, as well as enhanced antioxidant capacity by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities of serum (p < 0.05). Furthermore, we found that CEPs altered ileum content microbiota composition, increasing the relative abundance of p_Bacteroidota and g_Bifidobacterium (p < 0.05). In addition, untargeted metabolomics analysis identified 92 upregulated and 95 downregulated metabolites. Pathway enrichment analysis of these differential metabolites revealed that CEP supplementation altered the metabolomic profile of the ileum contents, with differential metabolites mainly enriched in alanine, aspartate and glutamate metabolism, fatty acid biosynthesis, and unsaturated fatty acid biosynthesis pathways. These results demonstrated that dietary supplementation with CEPs at different doses improved antioxidant capacity to varying degrees and maintained intestinal immune balance by modulating microbiota, which provides a theoretical basis for the rational application of compound enzyme preparations in breeding pigeon feed. Moreover, this study provides mechanistic evidence that CEPs can improve intestinal health, immunity, and antioxidant capacity. It also fills a key knowledge gap in pigeon nutrition by linking enzyme use with gut microbiota and metabolic regulation. Full article

The gut microbiota is a key regulatory hub linking environmental exposure, the mucosal barrier, and joint inflammation, and plays an important role in the pathogenesis and progression of rheumatoid arthritis (RA). Mechanistic studies in this field mainly address two interrelated questions: how RA-associated gut microbiota modulate mucosal immunity and systemic autoimmunity through strain-level variation, niche competition, and metabolic remodeling; and how disease stage, host immune status, and drug exposure reciprocally reshape gut microbial structure and function. Accordingly, this review follows the framework of “anti-inflammatory/pro-inflammatory microbial niches—microbiota-derived metabolites—immune cell homing and migration” to summarize recent advances in the role of gut microbiota and their derivatives in RA onset, progression, and therapeutic response. Focusing on disease-stage-specific remodeling of gut functional ecology, we discuss how short-chain fatty acids, tryptophan-derived indoles, bile acids, succinate, and other microbial effector molecules regulate RA immunopathology through regulatory T cells (Treg), regulatory B cells (Breg), type 17 T helper cells (Th17), and IL-17-producing T follicular helper cells (Tfh17), dendritic cells, fibroblast-like synoviocytes, and osteoclasts. We also highlight intestinal antigen sampling, autoantibody generation, immune cell trafficking, and synovial reactivation as key links in the gut–joint axis. This review aims to shift RA microbiome research from taxonomic profiling toward stage-specific functional ecological analysis, providing a basis for risk stratification, therapeutic response prediction, and microbiota-based adjunctive interventions. Full article

Cardiac senescence is not an isolated organ decline but a systemic consequence driven by pathological crosstalk between the heart and its peripheral metabolic organs. In this review, we discard the traditional organ–centric perspective and construct an integrated framework around multi-organ crosstalk axes, including the epicardial adipose tissue–heart axis, the skeletal muscle–heart axis, the gut–heart axis, and the kidney–heart axis. For each axis, we dissect the local molecular mediators—inflammatory cytokines, lipotoxic metabolites, microbiota-derived compounds such as trimethylamine N-oxide (TMAO), renin-angiotensin-aldosterone system (RAAS) effectors, and extracellular vesicle (EV) cargoes—and illustrate how they converge onto common pathways of oxidative stress, impaired autophagy, and cellular senescence. Importantly, we emphasize that these signals do not operate in isolation; they act synergistically through the circulation, converting local organ dysfunction into systemic cardiac aging via convergence onto shared senescence pathways. By redefining aging as a potentially modifiable multi-organ crosstalk, we propose emerging nodal points—senolytics, myokine mimetics, gut microbiota modulation, RAAS/sodium–glucose cotransporter 2 (SGLT2) inhibitors, and integrated lifestyle strategies—to block pathological crosstalk and delay cardiovascular aging. This framework shifts the research focus from isolated organs to systemic multi-organ crosstalk, providing new insights into cardiometabolic aging. 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

Ageing is characterized by progressive metabolic and inflammatory dysregulation, in which methylglyoxal (MGO), a highly reactive dicarbonyl by-product of glycolysis, is involved in the formation of advanced glycation end products (AGEs). This review provides an integrated overview of the bidirectional relationship between MGO-derived carbonyl stress and the gut microbiota, focusing on its implications for ageing and age-related diseases. We summarize current evidence on MGO production, clearance, tissue distribution, and reactivity, with particular attention to the intestinal lumen as a site where dietary compounds, host metabolism, and microbial activity converge. Age-related dysbiosis may impair intestinal barrier integrity, alter microbial metabolite production, and promote chronic low-grade inflammation, thereby reinforcing metabolic dysfunction and favoring free MGO accumulation. Conversely, MGO and AGEs can reshape microbial communities, compromise epithelial tight junctions, and amplify inflammatory signalling through receptor-dependent and independent mechanisms. Evidence from in vitro, animal, and clinical studies supports a role for the MGO–microbiota axis in metabolic, cardiovascular, gastrointestinal, neurodegenerative, and frailty-related conditions. Targeting microbiota composition, intestinal barrier function, and MGO scavenging pathways may therefore represent a promising strategy to mitigate carbonyl stress and preserve health during ageing. Full article

The ABE classification is crucial for the management of stable chronic obstructive pulmonary disease (COPD), reflecting disease symptom burden and exacerbation risk. Although gut microbiota is intimately linked to COPD pathogenesis, associations among the gut microbiota, its derived metabolites, and exacerbation risk in stable COPD patients remain poorly understood. We recruited 74 stable COPD patients (Group A, n = 18; Group B, n = 26; Group E, n = 30) for cross-sectional multi-omics profiling via fecal metagenomic sequencing and untargeted serum metabolomic analyses. Group E exhibited a decreasing trend in alpha diversity compared to Groups A and B. In addition, Group A displayed the most complex bacterial cooperative network, showing lower complexity and connectivity as symptom burden and risk of exacerbations increased. Taxonomically, the family Prevotellaceae was significantly enriched in Group A, while Streptococcaceae and Lactobacillaceae were more abundant in Groups B and E. Among 51 species displaying progressive trends with increasing exacerbation risk, 35 increased (e.g., Clostridium ljungdahlii) and 16 decreased (e.g., Prevotella dentalis). Furthermore, metabolomics analysis revealed that serum O-phosphoethanolamine levels were markedly elevated in Group E and showed a positive correlation with the COPD Assessment Test and modified Medical Research Council dyspnea scale scores. Exploratory mediation analysis suggested that elevated systemic O-phosphoethanolamine levels partially mediated the association between Clostridium ljungdahlii and COPD exacerbation risk. This study establishes significant associations between gut microbiota and phenotypic stratification in stable COPD patients. The identified Clostridium ljungdahlii/O-phosphoethanolamine axis may be associated with symptom burden and COPD exacerbation risk, provide a basis for further mechanistic studies. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Growing evidence implicates the gut microbiome in AD-related pathways through microbial metabolites, intestinal barrier function, and systemic immune signaling. This narrative review synthesizes current evidence on gut microbial alterations in AD, with particular attention to short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, intestinal permeability, gut–skin microbiome interactions, and microbiota-targeted interventions. Human studies have reported associations between AD and altered abundance of selected microbial taxa, metabolite profiles, and markers of intestinal barrier dysfunction, whereas animal and in vitro studies provide complementary mechanistic evidence. However, findings remain heterogeneous across age groups, disease phenotypes, geographic populations, analytical platforms, and treatment exposures, and causality is incompletely established. Probiotic and synbiotic interventions have shown strain-specific and context-dependent effects, while postbiotics, fecal microbiota transplantation, washed microbiota transplantation, and metabolite-directed approaches remain investigational. AI-assisted multi-omics methods may improve biological stratification and hypothesis generation, but current applications are limited by small sample sizes, cohort heterogeneity, overfitting, insufficient external validation, and limited clinical implementation. Current evidence therefore supports the gut microbiome as a mechanistically plausible contributor, potential biomarker, and therapeutic target in AD while underscoring the need for longitudinal, phenotype-aware, and externally validated studies before routine clinical translation. 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: Inflammatory bowel disease is a complex intestinal inflammatory disorder linked to immune dysregulation, oxidative stress, and an imbalance in the gut microbiota. Grape seed flour (GSF), a winemaking by-product rich in polyphenols and fibres, displays antioxidant and anti-inflammatory properties and may help maintain gut homeostasis. Methods: The phenolic composition and antioxidant capacity of our GSF were evaluated. We assessed whether a diet containing 10% (w/w) GSF protects against dextran sulphate sodium (DSS)-induced acute colitis in BALB/c mice. Animals received either a standard diet or a GSF-supplemented diet before and during DSS exposure. Body weight and disease activity index were monitored. At sacrifice, colon length and colonic histology scoring were measured. The study of the faecal microbiota and predicted genome was performed using PICRUSt. Caecal metabolites, including short-chain fatty acids, were also quantified. Results: GSF is rich in fibres (64%) and exhibits a very high polyphenolic content and high antioxidant capacity. GSF supplementation attenuated DSS-induced weight loss and disease activity and limited colonic shortening and histological damage. It also improved biomarkers of colon, mesenteric lymph nodes (MLNs), and liver injury. At the molecular level, GSF downregulated key pro-inflammatory mediators in the colon and liver, while enhancing anti-inflammatory (e.g., IL-10) and antioxidant markers, indicating reinforcement of regulatory and redox-protective pathways along the gut–liver axis. At the gut microbiota level, GSF supplementation modulated α-diversity. Further analysis demonstrated that GSF reshaped the GM profile by preventing the blooming of some taxa, including UBA1819, Akkermansia, and Bacteroides caecimuris, and enriching butyrate-producing bacteria, such as Muribaculaceae and Ruminococcus. These shifts were accompanied by lower acetone and ethyl acetate levels and higher indole levels, which are known to support epithelial barrier integrity and mucosal homeostasis. Conclusions: Overall, GSF mitigates DSS-induced colitis through combined actions on inflammatory signalling, oxidative stress, immune regulation, microbiota composition and microbiota-derived metabolites, supporting its potential as a functional prebiotic ingredient for intestinal health. Full article

Integrated rice–fish farming is increasingly promoted as a sustainable aquaculture model, yet its effects on flesh quality and gut microbial assembly in Pelteobagrus fulvidraco remain insufficiently understood. Here, we compared pond-cultured (PP) and rice-field-cultured (PR) individuals using growth measurements, muscle amino acid and fatty acid profiling, untargeted LC-MS/MS metabolomics and 16S rRNA gene sequencing. Body weight and length did not differ significantly between groups, whereas PP fish showed greater body width and height. PR fish contained higher levels of Ser, Val, Ile and total essential amino acids, together with amino acid and energy-related metabolites. In contrast, PP fish showed higher concentrations of saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, total fatty acids and lipid-associated metabolites. The gut microbiota also differed markedly between culture systems. PP fish exhibited higher α-diversity and enrichment of Proteobacteria, Firmicutes, Pseudomonas and Ralstonia, whereas PR fish were characterized by Verrucomicrobiota, Fusobacteriota, Akkermansia and Cetobacterium. Predicted functions suggested enhanced carbohydrate and energy metabolism in PR fish and stronger environmental-response-related functions in PP fish. These findings indicate that pond and rice-field culture promote distinct quality-forming pathways in yellow catfish, providing a basis for optimizing rice–yellow catfish co-culture toward quality-oriented production. 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

Background: Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonists have substantially improved the management of obesity and cardiometabolic disease, providing significant benefits on weight reduction, glycemic control, and cardiovascular outcomes. Despite these advances, gastrointestinal (GI) adverse events remain a major cause of dose reduction, treatment interruption, and poor long-term adherence. Increasing evidence suggests that interactions between incretin-based therapies and the intestinal microenvironment may contribute to GI tolerability and influence treatment persistence. Methods: We conducted a narrative review of the literature examining the relationship between incretin-based therapies, gut microbiota, intestinal barrier function, and microbial metabolites. Evidence from randomized clinical trials, observational studies, systematic reviews, and mechanistic investigations was evaluated to explore potential gut-directed supportive strategies during incretin-based treatment. Results: Preclinical and mechanistic evidence suggests possible bidirectional interactions between incretin pharmacology and the intestinal microenvironment, whereas direct human evidence remains limited and inconsistent. Alterations in gastrointestinal motility induced by GLP-1 receptor agonists could theoretically influence microbial composition and fermentation dynamics, although human studies have not consistently demonstrated significant microbiota changes. Based on these observations, we propose the Incretin–Microbiota Tolerance Axis (IMTA) as a conceptual framework linking gut homeostasis, GI tolerability, and treatment adherence. Among potential supportive interventions, partially hydrolyzed guar gum (PHGG) may promote SCFA-producing microbiota and improve bowel function, whereas simethicone may provide symptomatic relief of gas-related discomfort during dose escalation. SCFA-supportive nutritional approaches may further contribute to maintenance of intestinal homeostasis. Conclusions: Optimization of the intestinal microenvironment may represent a complementary strategy to improve GI tolerability and support long-term adherence during incretin-based therapy. Although the IMTA framework is supported by biological plausibility and emerging evidence, prospective clinical studies are required to determine whether microbiota-targeted interventions improve treatment persistence and cardiometabolic outcomes in patients receiving GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists. Full article