Search Results (1,433)

Bacillus velezensis-based probiotics are increasingly recognized for their potential to enhance intestinal health in companion animals, yet their mechanisms of action in canine epithelial systems remain incompletely defined. This study aimed to evaluate whether a live Bacillus velezensis probiotic consortia (BC) modulates epithelial barrier integrity, immune signaling, apoptosis-renewal pathways, and metabolic activity in canine-relevant intestinal and macrophage cell models. MCA-B1 proximal gastrointestinal epithelial cells and DH82 macrophage-like cells were exposed to BC cultures, followed by quantification of tight-junction expression, permeability (FITC-Dextran), cytokine responses, phagocytic activity, apoptosis-related markers, and metabolomic profiles. BC treatment significantly strengthened the epithelial barrier, inducing a marked upregulation of Claudin 1 (CLDN1) (11.3 fold), CLDN4 (2.4 fold), Occludin (OCLN, 1.7 fold), and increasing key proteins including ZO-2 and cingulin while reducing LPS-induced FITC-Dextran permeability to 94.5%. BC concurrently modulated innate immune signaling, increasing MyD88 (33.2%), IL-8 (14.6 fold), IL-18 (2.6 fold), and IFNB1 protein levels, while enhancing anti-inflammatory regulation, including a robust rise in DH82-derived IL-10. Apoptosis-renewal markers shifted toward physiological turnover, with increased BCL2 (1.9 fold) and reduced BAK1. Metabolomic profiling of BC activity revealed elevated AMP, abundant Peptide Transporter 1 (PEPT1)-transportable peptides, increased γ-glutamyl metabolites, and lower Glutathione disulfide (GSSG), consistent with AMPK-linked tight-junction assembly and glutathione-supported redox buffering. Together, these data indicate that Bacillus velezensis-derived metabolites positively influence barrier-related, immunological, and metabolic responses in a canine proximal intestinal epithelial system and modulate functional responses in macrophage-like cells. These in vitro findings contribute to the mechanistic understanding of host cellular responses to Bacillus-associated metabolites. Full article

Functional feed additives can improve growth, health, and fillet quality in farmed fish, but their stability during feed processing is limited. This study evaluated the effects of dietary microencapsulated rosemary essential oil (REO), astaxanthin (AX), and butyric acid (BA) on growth, oxidative response, and fillet quality in juvenile rainbow trout (7.9 ± 0.3 g; 90 days). Growth parameters, intestinal and liver health, oxidative status, and fillet pH and color, together with proximate composition and fatty acid profile, were measured. All supplemented groups exhibited higher growth performance compared to controls. Histology and stress/inflammatory markers indicated no adverse effects on tissue health. Regarding fillet quality, REO maintained protein content, AX enhanced lipid content and color stability, and BA promoted a leaner fillet with higher protein deposition. Fillet pH remained more stable in REO and BA groups after frozen storage, suggesting improved product stability. Fatty acid profiles were moderately altered, with REO increasing C18:1n7 and AX enhancing polyunsaturated fatty acids, whereas BA had minimal effects. Plasma antioxidant enzyme activities were lower in supplemented fish, indicating improved redox balance. Overall, microencapsulation preserved the bioactive properties of REO, AX, and BA, supporting their practical use as targeted functional feed additives in rainbow trout aquaculture. Full article

Background: The development of Slow Transit Constipation (STC) is associated with intestinal barrier damage. Coreopsis tinctoria Nutt. (CT) is effective in treating STC, but the mechanisms are unclear. Methods: We investigated three CT extracts—traditional aqueous extract, and an aqueous extract from supercritical fluid extraction, with or without lipophilic components—on intestinal transit in a loperamide-induced STC rat model. The potential therapeutic targets of CT for STC were initially predicted using an integrated approach of network pharmacology and molecular docking. The therapeutic effect of CT was evaluated in a STC rat model by assessing defecation parameters (fecal count, water content, intestinal transit), colon histology (H&E and AB-PAS staining), inflammatory markers (ELISA), and target protein expression (Western blotting and immunohistochemistry). In parallel, an LPS-induced IEC-6 cell injury model was used to investigate intestinal barrier protection, analyzing cell viability (CCK-8), apoptosis (flow cytometry and Western blotting), migration (scratch assay), and protein expression (Western blotting). Results: Docking and enrichment analysis highlighted hub targets (TNF, AKT1, Caspase3, STAT3, and BCL-2) and the PI3K/AKT pathway. In vivo, CT treatment improved defecation function, reduced colonic damage, and decreased markers of inflammation and apoptosis in STC rats. It also up-regulated ZO-1 and Occludin, lowered serum markers of intestinal permeability D-lactate (D-LA) and Diamine oxidase (DAO), and restored intestinal barrier function. Furthermore, CT reduced Caspase3 expression and increased the expression of proteins such as BCL-2, PI3K, and P-AKT/AKT. These findings were further supported by in vitro experiments. Conclusions: CT improves STC and its associated intestinal barrier damage by activating the PI3K/AKT pathway and suppressing inflammation and apoptosis, among which the aqueous extract from supercritical fluid extraction combined with the lipophilic fraction exhibits the best efficacy. Full article

Taurine supplementation has been shown to promote growth, but the underlying mechanisms remain incompletely understood. Here, we investigated the effects of taurine on intestinal health in mice under both normal and LPS-induced inflammatory conditions. Thirty-six male C57BL/6J mice were first divided into control and 2% taurine groups for 42 days. On day 43, each group was split into PBS or LPS subgroups, resulting in four groups (Con, LPS, Tau, LPS+Tau). Twelve hours after LPS injection, all mice were euthanized for sample collection. The results demonstrated that taurine supplementation increased body weight gain (p < 0.05) without affecting feed intake, indicating improved feed efficiency. Mechanistically, taurine supplementation enhanced intestinal absorptive function through multiple convergent pathways: it increased the activities of digestive enzymes (trypsin, maltase, and sucrase), upregulated nutrient transporter gene expression (EAAT3, SGLT1, and FATP4), and improved villus and microvillus morphology. These functional improvements were confirmed by a 1.7-fold increase in serum D-xylose absorption and significant elevations in total protein and albumin levels (p < 0.05). Notably, taurine supplementation upregulated the gene expression of intestinal stem cell (ISC) proliferation markers (Lgr5 and Ki67) and differentiation markers, including Villin (enterocyte), Muc2 (goblet cell) and ChgA (enteroendocrine cell). Under LPS challenge, taurine supplementation significantly attenuated disease severity, preserved villus architecture, and reversed inflammation-induced declines in digestive enzymes and nutrient transporters. Collectively, these findings establish taurine as a multifunctional nutrient that enhances intestinal health by optimizing digestive and absorptive capacity while promoting epithelial renewal, thereby supporting its potential application to improve growth and counteract intestinal injury. Full article

Background: Intestinal acute radiation syndrome (IARS) represents a life-threatening component of acute radiation syndrome with limited effective countermeasures. Understanding molecular determinants governing intestinal epithelial resilience to ionizing radiation is critical for developing radiation toxicity mitigation strategies. Objectives: This study investigates the role of PIKfyve, a phosphoinositide kinase essential for endolysosomal homeostasis, in modulating radiation-induced intestinal toxicity. Methods: We utilized an inducible intestinal epithelial-specific PIKfyve-knockout mouse model (PIKfyve cKO) subjected to 10 Gy abdominal irradiation. Intestinal toxicity was assessed through histopathology, barrier permeability (FD4 assay), apoptosis markers, and transcriptomic profiling. Small intestinal organoids were employed for mechanistic validation. Results: PIKfyve deletion alone did not perturb normal gut architecture but precipitated severe post-irradiation toxicity, including villous atrophy, crypt hypoplasia, and massive crypt-cell apoptosis. Barrier dysfunction was evidenced by elevated serum FD4 and heightened systemic pro-inflammatory cytokines, culminating in markedly increased mortality. Transcriptomic analysis revealed potentiated DNA-damage signaling and amplified inflammatory cascades in PIKfyve-deficient intestines. Conclusions: These findings identify PIKfyve as a critical guardian of intestinal epithelial integrity against radiation toxicity. Given emerging PIKfyve inhibitors in cancer therapy, our results raise important safety considerations for clinical radiotherapy and position PIKfyve as a potential target for radiation toxicity mitigation. Full article

Chronic kidney disease (CKD), a progressive disorder leading to renal dysfunction, remains a significant global health issue. This study investigated whether Lactiplantibacillus plantarum HY7718 modulates gut–kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in a mouse model of adenine-induced chronic kidney disease. We examined fibrosis- and inflammation-related gene expression in mouse tissues and analyzed the gut microbiota via next-generation sequencing. HY7718 supplementation was associated with reduced expression of genes related to renal fibrosis (Col1a1, Acta2) and vascular inflammation (Icam-1, Vcam-1). Further, HY7718 suppressed intestinal inflammatory responses, including downregulation of pro-inflammatory cytokines (Tnf, Il-1β, Il-6) and TLR4/MyD88/NF-κB signaling pathway genes in the colon tissues. Gastrointestinal function was also improved, with significant upregulation of gastric motility-related genes and increased digestive enzyme activity. The gut microbiota composition was altered by HY7718, with reduced abundance of pro-inflammatory taxa such as Mucispirillum and Deferribacterota, whereas beneficial genera like Lactiplantibacillus were enriched. These microbial shifts were associated with reduced intestinal inflammatory and renal fibrosis-related markers. Overall, the findings indicate that HY7718 supplementation modulates gut–kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in adenine-induced CKD mice and supports further investigation of this strain in CKD-related settings. Full article

Background/Objectives: Aging is characterized by progressive functional decline associated with alterations in gut microbiota, epithelial barrier dysfunction, and cellular senescence. Although quercetin has been proposed as a potential anti-aging compound, its clinical application is limited by poor bioavailability. In this study, we investigated whether enhancing quercetin bioavailability using EubioQuercetin (EQN) modulates aging-related phenotypes through the gut microbiota–intestinal barrier axis. Methods: Male C57BL/6J mice were treated with EQN or conventional quercetin (CQN) for 12 weeks. External aging phenotypes were assessed using a composite aging score based on hair glossiness, hair loss, and the presence of white hair. Gut microbiota composition was analyzed via 16S rRNA sequencing with centered log-ratio transformation, and intestinal gene expression was assessed by quantitative reverse transcription-polymerase chain reaction. Results: EQN significantly reduced the aging score compared with the control group (median 4.5 vs. 8, p < 0.01), while CQN also showed a moderate reduction. Microbiota analysis identified taxa positively associated with aging (Lactobacillus, Romboutsia, Desulfovibrio, and Lachnoclostridium) and negatively associated taxa (Akkermansia and Christensenellaceae). EQN suppressed aging-associated taxa and partially increased taxa linked to a healthier microbiota profile. At the intestinal level, EQN downregulated senescence-associated genes (p21, PCNA, and Lgr5) and upregulated the tight junction gene claudin-1. In contrast, systemic inflammatory markers and short-chain fatty acids were not significantly associated with the aging score. Conclusions: These findings indicate that enhancing quercetin bioavailability attenuates externally assessed aging phenotypes in aged mice and is associated with coordinated changes in gut microbiota and intestinal gene expression. Modulation of the gut microbiota–intestinal barrier axis may represent a potential mechanism underlying these effects. Full article

Congenital heart disease (CHD) is the most common congenital anomaly worldwide and is associated with substantial infant morbidity and mortality. This narrative review synthesizes evidence linking CHD to alterations in the gut microbiome across neonatal, perioperative, and chronic stages and highlights a gut–heart–immune framework in which microbial imbalance, intestinal barrier dysfunction, and systemic inflammation may interact to influence clinical outcomes. Early infancy represents a potential window for microbiome and immune development, shaped by delivery mode and feeding, with many breastfed infants developing a Bifidobacterium-dominant community supported by human milk oligosaccharides. In CHD, abnormal splanchnic perfusion and hypoxemia, together with intensive care and perioperative exposures (fasting, delayed enteral feeding, antibiotics, acid suppression), may predispose to dysbiosis and impaired barrier function. Cardiac surgery with cardiopulmonary bypass can act as a “second hit,” with evidence of increased gut permeability, endotoxemia, inflammatory activation, and biomarker signals of enterocyte injury and tight-junction disruption. Clinically, these mechanisms align with gut-sensitive outcomes including necrotizing enterocolitis (especially in ductal-dependent lesions), feeding intolerance, and postoperative infection-risk phenotypes. Interventions show mixed evidence: human milk exposure appears protective for NEC risk, synbiotics demonstrated outcome benefits in a randomized trial of cyanotic CHD infants, while probiotics may modify dysbiosis without consistently preventing intestinal injury and require careful safety frameworks. Key research gaps include the need for longitudinal stage-based cohorts, integration of microbiome profiling with barrier injury and perfusion markers, and standardized safety monitoring in intervention trials. Full article

As aquaculture adopts more sustainable feed formulations, interest in functional feed additives has grown to help mitigate the health and performance challenges associated with low-marine-ingredient diets. This study evaluated the effects of dietary supplementation with a commercial blend of mono-, di-, and triglycerides of short- and medium-chain fatty acids (SCFAs and MCFAs; BalanGUT™ AQ P, BASF) on growth, health, and disease resistance to Vibrio anguillarum in juvenile gilthead sea bream (Sparus aurata) fed practical low fishmeal and fish oil diets. Over an 8-week trial, fish were fed diets containing 0.3%, 0.5%, or 1% of a glyceride blend of SCFAs and MCFAs (BalanGUT™ AQ P) or a Control diet without functional additive supplementation. Growth performance and feed utilization were not affected by the supplementation of SCFAs/MCFAs glycerides, although non-significant trends (p > 0.05) toward improved specific growth rate (up to 12%) and reduced feed conversion ratio (up to 17%) were observed in sea bream fed supplemented diets, particularly during the 4 initial weeks and at the highest inclusion level (1%). Moderate (0.5%) and high (1%) supplementation levels of SCFAs and MCFAs significantly improved survival following Vibrio anguillarum challenge, despite no significant changes being observed in general systemic innate immune markers, such as serum lysozyme or ACH50 activities. SCFAs/MCFAs supplementation, particularly at 0.3% or 0.5%, also modulated intestinal morphology, including thinner submucosa and smaller goblet cell area in the posterior intestine, suggestive of a more homeostatic mucosa and reduced basal inflammation when feeding a low-FM/FO-based diet. These results suggest that the protective effects of this SCFAs/MCFAs glyceride blend are mediated primarily through local rather than systemic immune modulation. Overall, this study supports the use of functional SCFAs and MCFAs glyceride blends as a functional strategy to promote resilience and health in fish fed sustainable, low-marine-ingredient diets. Full article

Inflammatory bowel disease (IBD) involves intestinal barrier dysfunction and chronic inflammation. Manna, derived from the solidified phloem sap of Fraxinus species, is rich in mannitol and polyphenols and valued for its laxative, antioxidant, and anti-inflammatory properties. In this study, manna was digested in vitro to obtain its bioaccessible fraction (BFM), whose anti-inflammatory activity was tested in a Caco-2/RAW264.7 co-culture model. Caco-2 cells were pretreated with BFM (1/20 v/v, 6 mg/mL) 90 min before LPS stimulation (1 µg/mL, 24 h) of macrophages, using budesonide (1 μM) as reference. BFM pretreatment significantly reduced IL-8 secretion (70.8%) in Caco-2 cells, and IL-6 (43.1%) and TNF-α (83.1%) in RAW264.7 macrophages. It also improved redox balance in Caco-2 cells by decreasing iNOS (48.2%), NOx (33.2%), and ROS (26.4%), while stabilizing tight junctions through occludin upregulation (18.3%). Mechanistically, BFM downregulated NF-κB-COX-2-PGE₂ signaling in macrophages, reducing NF-κB p65 nuclear translocation (65.6%), COX-2 levels (79.3%), and PGE₂ production (50.8%). Co-treatment with budesonide showed antagonism for most markers (Combination Index (CI), 0.41–0.76), but additive/synergistic effects on ROS (CI, 1.06 ± 0.06) and NOx (CI, 1.10 ± 0.04). These findings highlight manna’s strong anti-inflammatory activity at a low, non-laxative dose (3.8 g/day), supporting its nutraceutical potential in IBD management. Full article

Background/Objectives: Autism spectrum disorder (ASD) is often associated with gastrointestinal dysfunction and gut microbiota alterations. This study aimed to characterize the gut microbiota in children with ASD in relation to nutritional factors and to evaluate the effects of dietary interventions combined with probiotics. Methods: The study included 96 children with ASD and 39 neurotypical controls. Follow-up data after intervention were available for 60 children with ASD. Gut microbiota composition was assessed by 16S rRNA sequencing, and fecal calprotectin and zonulin were measured before and after intervention. Most children with ASD (n = 91) received a rotational or elimination diet for six months, and all participants with ASD received probiotics for 1.5 months. Results: Children with ASD showed significant microbiota changes compared with controls, including increased Prevotella, Sarcina, NK4A214 group, and RF39 taxon, along with reduced butyrate-producing bacteria, such as Roseburia, Eubacterium xylanophilum group, and Eubacterium ventriosum group. Formula feeding was associated with increased Odoribacter, whereas food selectivity was linked to higher Prevotella, Sarcina, Methanobrevibacter, and RF39. A rotational diet increased Erysipelotrichaceae UCG-003 and Streptococcus, while an elimination diet increased Butyricicoccus and reduced fecal calprotectin (p = 0.023). Fecal zonulin decreased significantly after intervention in the follow-up ASD subgroup (p = 0.018). Conclusions: The obtained data suggest that children with ASD may exhibit certain microbiota features associated with nutritional patterns. Dietary interventions combined with probiotics appear to be associated with microbiota modulation and a tendency toward improvement in markers of intestinal inflammation and barrier function. Full article

Microplastic (MP) pollution poses a threat to wild animals, but its toxicological impact on terrestrial passerines remains unclear. To address this gap, we conducted the first systematic study investigating how microplastic particle size and dosage jointly influence gut microbiota and multi-system physiological functions in a small terrestrial bird. Eurasian tree sparrows (Passer montanus) were exposed to polystyrene microplastics (PS-MPs) of two particle sizes (0.5 and 15 μm in diameter) and two dosages (100 and 500 μg/d) via oral ingestion for 21 days. After exposure, body status, peripheral blood cell profiles, organ indices, intestinal histomorphology, oxidative stress, and barrier integrity markers displayed no significant changes compared with the control group. In the gut microbiota, large PS-MP particles significantly enhanced microbial species richness and phylogenetic diversity, and their effect was more pronounced than that of small ones. Additionally, structural alterations and distinct community compositions emerged across groups. Both particle size and dosage affected gut microbial composition and taxa abundance, with particle size exhibiting a relatively stronger effect. However, the relative abundance of the top 10 dominant phyla and predicted microbial functional profiles exhibited no significant intergroup differences. In summary, short-term PS-MP exposure primarily impacts the gut microbial structure of Eurasian tree sparrows without disrupting their key physiological functions. This suggests that the birds possess a certain buffering capacity against short-term PS-MP stress, though their long-term ecological tolerance to complex, real-world MP mixtures remains to be further investigated. Full article

Seed oils from Sicilian white (WGSO) and red grapes (RGSO) were examined for their possible cytotoxic effect on HepG2 liver and CaCo-2 colorectal cancer cells, the latter also induced to intestinal differentiation. Half maximal inhibitory dilution (ID₅₀) values were obtained from viability assays, excluding RGSO-treated HepG2 and differentiated CaCo-2 cells exposed to both oils, which were unresponsive. Cell morphology and cycle status, reactive oxygen species (ROS) production, and the levels of cytoprotection, regulated cell death (RCD), and autophagy markers were evaluated. No occurrence of canonical apoptosis was proven in any experimental condition. In HepG2 cells, WGSO ID₅₀ primarily triggered autophagy collapse, as evidenced by modulation of Beclin-1, p62 and LC3 markers, initiating a cascade of metabolic disturbances that led to oxidative stress reaction and mild inflammatory signaling. In CaCo-2 cells, WGSO ID₅₀ mainly elicited a strong ROS-mediated cell injury without major alterations in autophagy, with transient activation but incomplete execution of pyroptotic and necroptotic effectors (gasdermin-D, pMLKL and HMGB1). In the same cells, RGSO ID₅₀ induced a weaker metabolic perturbation with transient activation of multiple RCD pathways and concomitant autophagy inhibition. Research findings revealed distinct damage-inducing properties linked to oils’ chemical profiles, underscoring their prospective utilization as beneficial bioactive supplements. Full article

This study induced obesity in mice through a high-fat diet (HFD) to investigate the regulatory effects of Clostridium butyricum WL-53 (C. butyricum WL-53) on lipid metabolism and intestinal inflammation. Thirty 6-week-old male C57 mice were randomly divided into three groups: the normal diet group (ND), the high-fat diet group (HFD), and the HFD supplemented with Clostridium butyricum (CB, C. butyricum) group (HFD-CB). The experiment lasted for five weeks. The results demonstrated that mice in the HFD-CB group exhibited significantly alleviated weight gain, reduced fat mass, and decreased hepatic lipid deposition. C. butyricum WL-53 treatment improved serum and hepatic lipid markers (TC, TG), decreased the levels of pro-inflammatory factors (TNF-α, IL-1β), and increased those of anti-inflammatory factors (IL-10, IL-4). Gut microbiota analysis indicated that HFD reduced microbial diversity and increased the abundance of Firmicutes. Meanwhile, C. butyricum WL-53 intervention reversed these changes and enriched beneficial genera. Metabolomics analysis revealed that C. butyricum WL-53 regulated glycerophospholipid metabolism, arachidonic acid metabolism, and cAMP signaling pathways, reversing metabolites to ameliorate lipid deposition and inflammation. In summary, C. butyricum WL-53 alleviates HFD-induced obesity and inflammation via gut microbiota modulation and metabolic reprogramming. Full article

Introduction: Alterations of the microbiota–gut–brain axis, including increased intestinal permeability (IP), changes in microbial activity, and immune activation, are central to the pathophysiology of irritable bowel syndrome with diarrhea (IBS-D). The low-fermentable oligo-di-monosaccharides and polyols (FODMAP) diet (LFD) is an established therapy for IBS, yet its systemic effects, particularly in patients with elevated depressive symptoms, remain incompletely characterized. Methods: This single-arm pre–post study investigated associations between depressive symptom severity and markers of small IP (s-IP), endotoxin exposure, inflammation, and erythrocyte membrane polyunsaturated fatty acid (PUFA) composition in 43 IBS-D patients undergoing a 12-week personalized LFD. Patients were classified using the Symptom Checklist-90-Revised depression subscale into those with (d+, n = 23) and without (d−, n = 20) clinically elevated depressive symptoms. Results: At baseline, d+ patients exhibited higher s-IP, circulating lipopolysaccharide levels, inflammatory markers, and a more pro-inflammatory PUFA profile. Following LFD, significant improvements in symptoms and several biological parameters were observed in the overall cohort. Greater absolute changes in d+ patients were consistent with their higher baseline values rather than indicating differential responsiveness. Baseline depressive symptoms were not significantly associated with the magnitude of post-intervention changes in IP or inflammatory markers. Conclusions: These findings suggest that elevated depressive symptoms identify an IBS-D subgroup characterized by greater baseline biological burden. Results should be interpreted as associative given the single-arm design, absence of a control group, and the concurrent reduction in body weight, which may have influenced the observed changes. Randomized controlled studies are needed to clarify the role of dietary interventions in modulating gut–brain axis-related pathways in IBS-D. Full article