Search Results (1,043)

Cardiac surgery induces systemic stress responses that may compromise intestinal homeostasis in animal patients, yet the underlying mechanisms remain poorly understood. This study investigated postoperative intestinal pathophysiology in a porcine model, focusing on the activation of the NF-κB pathway and its impact on intestinal stem cell function. Thirty-two large white pigs (40–50 kg) were randomized into control and model groups; the model group underwent simulated cardiac procedures involving aortotomy and left ventricular outflow tract exposure under standardized anesthesia. Our findings revealed significant NF-κB pathway activation and upregulation of matrix metalloproteinases (MMPs) in the intestine following surgery. Intestinal stem cells isolated from crypts showed downregulated expression of key barrier proteins. Notably, organoids derived from the model group exhibited impaired early proliferative capacity and delayed morphogenesis, despite preserved differentiation potential upon extended culture. This suggests a stress-induced state that favors the maintenance of stemness over commitment to differentiation. These results delineate an NF-κB/MMP-mediated mechanism linking surgical stress to intestinal barrier dysfunction and stem cell dysregulation in this large animal model. Crucially, the study provides insights that may help improve perioperative care and reduce gastrointestinal complications in animal patients undergoing major surgeries, thereby enhancing animal welfare. The identified pathways offer potential targets for developing supportive therapies in veterinary practice. Full article

Micro- and nanoplastics (MNPs) are pervasive in food-contact environments and the human diet, positioning the gastrointestinal (GI) tract as the primary portal of entry and a plausible site of early biological effects. Human exposure is supported by detection of microplastics in stool and colon tissue, and emerging clinical studies report associations between fecal microplastic burden and GI disease states, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Preclinical studies provide mechanistic plausibility, reporting that ingested MNPs can modulate microbial ecology, alter mucus membrane integrity, increase intestinal permeability through changes in cellular tight junction biology, and induce inflammatory gene expression. These effects can vary by MNP polymer type, particle size/shape, aging state, and exposure dose. Human-relevant experimental platforms increasingly demonstrate size- and concentration-dependent uptake and host responses while revealing substantial inter-individual variability. We synthesize current evidence on dietary sources and key physiochemical properties as they relate to mechanistic pathways connecting MNP exposure to dysbiosis–immune activation–neoplasia axes, in addition to methodological limitations that constrain current clinical utility. Further research including standardized biomonitoring and exposure protocols, environmentally realistic chronic low-dose mixtures, longitudinal human cohorts, and interventional designs that test whether exposure reduction modifies GI inflammation biomarkers and cancer-relevant pathways are critical to clarifying causality. Full article

This review examines the functional role of lactic acid bacteria (LAB) and Bifidobacteria in modulating host physiology through interconnected metabolic, immune, and neuroendocrine pathways. These effects are particularly relevant in gastrointestinal diseases, where dysbiosis is associated not only with local intestinal dysfunction but also with systemic conditions, including metabolic syndrome, infections and complications in immunocompromised individuals. LAB and Bifidobacteria play key roles through the production of short-chain fatty acids, which contribute to maintaining intestinal barrier integrity, regulating lipid and glucose metabolism, improving insulin sensitivity, and exerting anti-inflammatory effects that may reduce the risk of metabolic disorders. Beyond metabolic regulation, the review explores the emerging concept of psychobiotics, focusing on how probiotic bacteria modulate host physiology through integrated metabolic, immune and neuroendocrine mechanisms. Current evidence suggests that these effects are highly strain-specific and influenced by dosage and study design, and host-related factors, often arising indirectly through complex host-microbe interactions rather than direct neurotransmitter activity. Although increasing evidence links these microorganisms to stress regulation, mood, and cognitive function, findings from human studies remain inconsistent. Therefore, well-designed clinical trials, combined with multi-omics approaches, are needed to clarify underlying mechanisms and substantiate clinical efficacy. Overall, probiotics-based strategies offer a promising and practical approach to supporting metabolic health and general psychological well-being through functional foods. Full article

Marine-derived collagen peptides exhibit potent intestinal barrier protection; however, their gastrointestinal fate and molecular targets remain unclear, limiting their practical applications. This study investigated the digestive stability and transepithelial transport of GPSGPQGSR, a mucoprotective peptide from Alaska pollock (Gadus chalcogrammus) skin, using simulated gastrointestinal digestion, a Caco-2 cell transport model, and an UPLC-QTOF-MS/MS. The results showed that GPSGPQGSR was a digestion-resistant peptide that reached the intestinal epithelium intact. Although brush border membrane enzymes partially hydrolysed the peptide, 42.16% of intact GPSGPQGSR remained in the luminal compartment after 2 h of incubation. No intact peptide was detected in the basolateral compartment. Molecular docking and 100 ns molecular dynamics simulations identified TLR2 (−14.936 kcal/mol) and PAR2 (−10.154 kcal/mol) as high-affinity extracellular targets of GPSGPQGSR, with stable peptide–receptor interactions and extensive hydrogen bonding networks between the peptide and each receptor (RMSD of 1.8 Å and 2.2 Å, respectively). Pharmacological blockade of TLR2 or PAR2 abolished the protective effects of GPSGPQGSR. These findings demonstrate that GPSGPQGSR acts as a digestion-resistant extracellular signalling peptide that reaches the intestinal epithelium intact and protects barrier function through apical TLR2 and PAR2, providing a mechanistic basis for the rational development of marine collagen peptides for improving intestinal health. Full article

In ulcerative colitis (UC), the therapeutic efficacy of nanoparticle (NP)-based drug delivery systems is limited by premature drug release, uptake or degradation of NPs during their passage through the harsh gastrointestinal tract (GIT) environment, poor colon targeting, and rapid NP clearance caused by diarrhea symptoms. This study focused on designing an advanced spatiotemporally controlled nanohybrid hydrogel drug delivery system to overcome these challenges. We developed a pH- and temperature-responsive polysaccharide-based hydrogel composed of chitosan (CS), β-glycerol phosphate disodium salt pentahydrate (GP), hydroxypropyl cellulose (HPC), and collagen type I (Col I), designated as CS/HHPC/Col I-GP. The hydrogel exhibited a dense and uniform porous reticular structure, with an average pore diameter of 127.45 ± 2.22 μm. The equilibrium swelling ratio of the CS/HHPC/Col I-GP was determined to be 32.10 ± 1.11 g/g, indicating excellent swelling capacity and sustained structural stability over 6 h—making it suitable for sustained drug release in the intestinal tract. Then, the prepared curcumin nanoparticles (CurNPs) were encapsulated into the CS/HHPC/Col I-GP hydrogel to form the CS/HHPC/Col I-GP-CurNPs composite. The polysaccharide-based hydrogel shell of the formulation withstood harsh gastrointestinal conditions, enabled targeted adhesion to the colon, and was specifically degraded by colonic enzymes. The CurNPs released in the colon benefit from their negatively charged characteristics, enabling accumulation at the positively charged inflamed sites and achieving sustained Cur release. The results of the gastrointestinal digestion simulation experiment showed that the cumulative release of CS/HHPC/Col I-GP-CurNPs was only 12.33 ± 2.17% in simulated gastric fluid (SGF) and reached 96.91 ± 1.98% in simulated colonic fluid (SCF) after 60 h. Cell and animal experimental data confirmed that the formulation significantly alleviated colitis symptoms by modulating the repolarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes and deactivating the TLR4/MyD88/NF-κB pathway. Furthermore, the integrity of the intestinal mucosal barrier and the gut microbiota were enhanced. This study provides a promising strategy for the oral drug treatment of UC. Full article

Visceral pain is a central feature of chronic gastrointestinal disorders, yet the epithelial sensory mechanisms that shape afferent input before it enters pain-relevant neural pathways remain insufficiently integrated into current models. This review advances the concept that the intestinal epithelium is not only a barrier or endocrine interface, but also an active neuroepithelial regulatory layer positioned upstream of visceral sensory signaling. Neuropod-cell studies established that specialized epithelial cells can communicate rapidly with vagal neurons and preserve luminal stimulus identity through transmitter-selective coding. Enterochromaffin cells extend this framework as polymodal epithelial sensory transducers that detect chemical, microbial, neurohumoral, and mechanical cues, convert them into serotonergic afferent signaling, and can causally amplify visceral hypersensitivity in experimental models. Complementing these amplifying pathways, GUCY2C^high (guanylate cyclase C-enriched) neuropod-like epithelial cells reveal a pain-restraining mechanism that regulates dorsal root ganglion excitability and preserves linaclotide-responsive suppression of nociceptive output in preclinical systems. Together, these findings support an integrative model in which epithelial sensory circuits may act as filters of biological meaning, amplifiers of afferent gain, and brakes on aberrant nociceptive escalation. This framework does not replace neural, immune, or central mechanisms of visceral pain, but adds an upstream epithelial tier that may shape pain vulnerability, persistence, or treatment responsiveness in selected contexts. Defining the cellular logic, molecular mediators, and human relevance of these circuits will be essential for advancing neuroepithelial pain biology toward disease-relevant and therapeutic applications. Full article

Maintenance of gut homeostasis is critical for overall health, as the gut microbiota plays a central role in regulating host metabolism, immune responses, and intestinal barrier integrity. Dysbiosis is closely associated with gastrointestinal disorders and inflammatory diseases, yet the ability of probiotics to preserve microbial resilience under inflammatory stress remains incompletely understood. In this study, we evaluated the protective effects of a multi-strain probiotic formulation, Neuralli^TM-CORE (CORE), using a dextran sulfate sodium (DSS)-induced colitis mouse model. Mice were pre-supplemented with CORE for two weeks prior to DSS exposure. CORE supplementation significantly reduced disease activity index, increased body weight, and partially recovered the colonic histopathological damage in DSS-treated mice. Cytokine profiling showed that CORE reduced circulating PTX2, CHI3L1, CXCL13, and MMP-2 levels, suggesting attenuation of inflammation and tissue remodeling. Microbiota analysis revealed that CORE did not fully prevent DSS-induced dysbiosis but attenuated the early decline in α-diversity and promoted re-emergence of specific microbial taxa, including Duncaniella and Muribaculum, members of the Muribaculaceae family, which are inversely associated with inflammation. Correlation analysis further linked these taxa to reduced colitis severity. Collectively, CORE attenuates DSS-induced colitis by improving inflammatory resolution, supporting mucosal recovery, and enhancing microbiota resilience. Full article

Ginseng (Panax ginseng C. A. Mey.) is a classic traditional Chinese herbal medicine with a history of clinical use that spans millennia. Its utilisation has long been established in the regulation of physical and mental equilibrium, in addition to the amelioration of conditions pertaining to the heart, spleen, and brain. Recent studies have indicated that the core biological activity of the substance under investigation is mediated by key active components such as ginsenosides, polysaccharides, and polyphenols. These components are closely associated with the regulation of the gut-brain axis (GBA). However, extant reviews have predominantly concentrated on individual diseases or specific mechanisms, thereby lacking a thorough investigation into the comprehensive analysis of how ginseng components exert systemic effects via the GBA. This review systematically searched and analyzed published studies in major databases regarding the regulation of the GBA by ginseng bioactive components, summarizing the latest advances in its role as a multifactorial disease intervention regulator targeting the GBA. It has been demonstrated that ginseng components exert a multifaceted GBA regulatory effect through interconnected mechanisms, including modulation of the gut microbiota, protection of the intestinal barrier, anti-inflammatory actions, and regulation of neurotransmitters, showing promising preclinical therapeutic potential in neurodegenerative diseases, mood disorders, metabolic diseases, and gastrointestinal disorders. Contrary to previous reviews, which focused on the description of individual ginseng components or specific diseases, this study provides a comprehensive analysis of how various bioactive components of ginseng modulate the gut-brain axis in relation to multiple disease categories through a systematic review. However, the preponderance of extant evidence derives from preclinical studies and necessitates further validation through clinical trials. This review provides pivotal directions and theoretical underpinnings for the clinical translation of ginseng’s bioactive components and the development of disease intervention strategies targeting the gut-brain axis. Full article

Background/Objectives: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, Dendrobium huoshanense (DHS) modulates intestinal flora, maintains the intestinal mucosal barrier, and promotes gastrointestinal motility and digestive secretion. However, the role and mechanism of DHS in improving SD-induced intestinal injury have not been fully studied. Methods: The SD model was established by subjecting rats to complete SD using a specialised SD instrument. Hematoxylin and eosin (HE) staining was performed to evaluate pathological injury in ileal tissues. Enzyme-linked immunosorbent assay (ELISA) and biochemical methods were used to quantify the main inflammatory cytokines, oxidative stress markers, and hypothalamic–pituitary–adrenal (HPA) axis activity. The expression levels of E-cadherin and Occludin proteins in the ileum tissue were analyzed by Western blotting. Additionally, the pH value of ileal mucus, unit secretion, water content, and dry matter weight were measured. Differential metabolites in rat ileum mucus were profiled using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results: DHS alleviated the pathological injury of the ileum induced by SD. DHS reduced the levels of serotonin (5-HT), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), while increasing interleukin-10 (IL-10) levels, thereby attenuating systemic inflammatory responses. Furthermore, DHS decreased malondialdehyde (MDA) content and elevated glutathione (GSH) and superoxide dismutase (SOD) levels in ileal tissues. DHS also upregulated the protein expression of E-cadherin and Occludin in intestinal tissues. In addition, DHS decreased the pH of ileal mucus, promoted intestinal mucus secretion, and increased dry matter content, facilitating the restoration of the mucus barrier. DHS may alleviate SD-induced ileal injury by modulating steroid hormone biosynthesis. DHS decreased the levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), and corticotropin-releasing hormone (CRH), indicating that DHS suppresses the abnormal activation of the hypothalamic–pituitary–adrenal (HPA) axis. Conclusions: In this study, a comprehensive multi-index evaluation showed that DHS could significantly improve the ileal injury caused by SD in rats. The mechanism involved regulating the balance of serum neurotransmitters and inflammatory factors, reducing oxidative stress in tissues, and improving the physicochemical properties of intestinal mucus. Metabolomic analysis further revealed that these protective effects may be mediated via the regulation of steroid hormone biosynthesis pathways and are associated with the inhibition of abnormal HPA axis activation. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed type 2 diabetes mellitus (T2DM) and obesity care, with clinical trials demonstrating weight loss exceeding 15%. However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates. We characterize the global persistence gap and propose a framework integrating Medical Nutrition Therapy (MNT) to improve adherence. Methods: We conducted a narrative review of real-world evidence from North America, Europe, Asia, and Latin America, synthesized with physiological, nutritional, and behavioral data to distinguish established contributors to discontinuation from strategies that remain partly extrapolated from related populations. Results: Global persistence varies widely: from approximately 75–80% at 12 months in reimbursed T2DM cohorts (Sweden, Denmark) to below 10% in obesity-focused or high out-of-pocket-cost settings (Poland, Colombia), with intermediate rates in the United States and United Kingdom; in several cohorts, persistence falls below 15% by 24 months. The primary drivers are gastrointestinal intolerance and economic barriers. Meal size, dietary composition, and gastric-emptying effects influence gastrointestinal tolerability; inadequate protein intake during rapid weight loss raises concern for lean mass loss. Conclusions: Pharmacotherapy alone is unlikely to sustain long-term obesity management. Narrowing the persistence gap will require an integrated care model in which structured nutritional support—targeting protein intake, micronutrient density, and gastric-sparing feeding—is systematically offered rather than treated as an optional adjunct, while recognizing that most supporting evidence is extrapolated from primary trials in obesity and cardiometabolic disease rather than derived from GLP-1–specific randomized trials. Full article

Mitochondria are central regulators of cellular bioenergetics, redox balance, and signaling pathways that integrate metabolic and immune responses. Emerging evidence indicates that biological sex is an important determinant of mitochondrial function, in part through the regulatory effects of sex hormones on mitochondrial biogenesis, oxidative phosphorylation, reactive oxygen species production, and quality control mechanisms. Estrogen, testosterone, and progesterone differentially modulate mitochondrial dynamics, substrate utilization, antioxidant capacity, and immune signaling, resulting in distinct mitochondrial phenotypes that may influence disease susceptibility across the lifespan. In this review, we synthesize current knowledge on the mechanistic basis of sex differences in mitochondrial function and highlight mitochondria as key mediators linking endocrine signaling to immunometabolic regulation. We discuss how mitochondrial-derived signals, including mitochondrial reactive oxygen species, mitochondrial DNA release, and cardiolipin exposure, activate inflammatory pathways such as NF-κB, cGAS–STING, and NLRP3 inflammasome signaling. These pathways may contribute to chronic inflammation, gut barrier dysfunction, and systemic metabolic disruption. We further examine the impact of major endocrine transitions, including pregnancy, the postpartum period, menopause, and androgen imbalance in conditions such as polycystic ovary syndrome, on mitochondrial function and disease risk. Particular emphasis is placed on the gastrointestinal tract as a metabolically active and mitochondria-dependent interface, where mitochondrial dysfunction may contribute to epithelial barrier disruption, microbial dysbiosis, and systemic inflammation. Finally, we discuss emerging therapeutic strategies targeting mitochondrial function, including exercise, hormone-based therapies, mitochondria-targeted antioxidants, and interventions aimed at improving mitochondrial quality control. Understanding sex-specific mitochondrial regulation may provide a framework for improved endocrine stratification, mitochondrial phenotyping, and precision medicine approaches across diverse clinical contexts. Full article

Background: Inonotus obliquus, a fungus known for its edible and medicinal properties, has traditionally been used as a herbal tea to relieve gastrointestinal disorders. Melanin, a major active constituent of this fungus, exhibits antioxidant, anti-inflammatory, and immune-modulating effects. This study aimed to investigate the therapeutic potential and mechanisms of Inonotus obliquus crude melanin (IOM) in treating dextran sulfate sodium (DSS)-induced colitis in mice. Methods: The study assessed colonic inflammation, mucosal damage, and intestinal barrier integrity. It also measured the levels of proinflammatory cytokines and oxidative stress markers. Gut microbiota composition was analyzed using 16S rRNA gene sequencing following IOM treatment. Additionally, label-free quantitative proteomic analysis was performed to explore the underlying mechanisms. Results: IOM administration significantly ameliorated colitis symptoms, strengthened the intestinal barrier, and reduced inflammation and oxidative stress in a dose-dependent manner. Furthermore, IOM modulated gut microbiota composition by increasing the relative abundance of Lactobacillus and Muribaculaceae, while reducing that of Bacteroides, Escherichia-Shigella, and Romboutsia. Proteomic analyses revealed that IOM treatment regulated the neutrophil pro-NETotic signaling pathway, which was further verified by immunohistochemistry or Western blot analysis of key pro-NETotic markers (e.g., PAD4, CitH3, MPO). Importantly, the relative abundances of these bacterial taxa were significantly correlated with the ulcerative colitis (UC) progression and neutrophil pro-NETotic activation. Conclusions: IOM mitigates DSS-induced colitis alongside the modulation of gut microbiota and the suppression of neutrophil pro-NETotic activation, suggesting its potential as a functional food ingredient for the management of UC. Full article

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery. Full article

Aims: The effects of two Lactiplantibacillus plantarum strains and their probiotics on loperamide-induced constipation in mice were compared, and the possible mechanisms of the two strains in alleviating constipation were explored. Methods: KM mice were divided into the normal group, model group, positive control group, LTJ53 group, LP11824 group, HK-LTJ53 group and HK-LP11824 group. Loperamide was used to induce constipation in the mice. The study examined changes in defecation time, intestinal propulsion rate, gastric emptying rate, gastrointestinal peptides, colon histology, expression of intestinal barrier function genes, gut microbiota, and short-chain fatty acids (SCFAs). Results: Both live and postbiotic forms of L. plantarum significantly shortened defecation time, improved gastric emptying and intestinal motility, increased the levels of 5-hydroxytryptamine (5-HT), gastrin (GAS) and motilin (MTL), decreased the level of vasoactive intestinal peptide (VIP), restored colon morphology, upregulated the expression of Zonula Occludens-1 (ZO-1), mucin 2 (MUC2) and aryl hydrocarbon receptor (AhR), and downregulated the expression of aquaporin 4 (AQP4). They can also regulate the composition of the gut microbiota and alter the levels of SCFAs. Strain-specific effects were observed: LTJ53 was more effective in improving weight loss and gastric emptying, while LP11824 showed stronger efficacy in promoting small intestinal motility. Conclusions: L. plantarum and its postbiotics can relieve constipation through regulating the intestinal flora, enhancing gastrointestinal motility, adjusting the levels of neurotransmitters, and improving the intestinal barrier function. The specific effects of the two strains can support the selection of function-oriented precise intervention. Full article

The role of zonulin as a biomarker of intestinal permeability in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting remains poorly understood. In this study, we aimed to evaluate serum zonulin dynamics, identify its predictors, and assess its prognostic significance in patients undergoing allo-HSCT. This multicenter, prospective cohort study was conducted across four Brazilian hospitals. Eligible participants were patients aged ≥12 years who provided at least one blood sample during the allo-HSCT course. A control group of 15 healthy adult individuals was also included. Serum zonulin levels were quantified using enzyme-linked immunosorbent assay multiple times over the allo-HSCT course. Outcomes included acute graft-versus-host disease, overall survival, and bloodstream infections. A total of 477 blood samples were collected from 140 patients. Compared with the control group, zonulin levels were persistently elevated at all evaluated time points throughout the allo-HSCT course. However, no significant differences were observed among the different time points assessed during transplantation. No clinical or transplantation-related characteristics were identified as significant predictors of elevated zonulin levels. Finally, zonulin did not demonstrate prognostic value for allo-HSCT-related outcomes. Future studies should investigate whether other intestinal permeability biomarkers have prognostic relevance in the allo-HSCT setting. Full article