Search Results (734)

Nutrient-sensing nuclear receptors (NSNRs), including PPARs, FXR, LXRs, RAR/RXR, VDR, and related orphan receptors, integrate a molecular interface that allows diet to communicate directly with the genome. By binding fatty acids, bile acids, sterols, vitamins, polyphenols, and other food-derived metabolites, NSNRs translate qualitative and quantitative features of the diet into coordinated transcriptional programmes across metabolically active organs. This ligand-dependent signalling network integrates dietary information to orchestrate inter-organ lipid and glucose metabolism, mitochondrial function, thermogenesis, and immune response, thereby enabling the organism to adapt dynamically to fasting–feeding cycles. In this review, we synthesise current evidence on the integrated roles of major NSNRs in the liver, skeletal muscle, white and brown adipose tissue, and kidney, emphasising how receptor networks within and between metabolic organs collectively govern energy expenditure, substrate partitioning, and systemic metabolic flexibility. We propose a conceptual framework in which diet functions as an “external endocrine organ”, acting as the primary source of chemically diverse NSNR ligands, while metabolic tissues serve as secondary signal amplifiers and integrators. Through circulating lipid species, bile acids, oxysterols, and other metabolites, these organs engage in continuous bidirectional communication that reprograms NSNR activity across tissues. We then examine how the global shift from minimally processed, nutrient-rich foods to nutrient-poor, energy-dense ultra-processed diets leads to a reduction in NSNR ligand diversity, promoting hepatic steatosis, muscle metabolic inflexibility, adipose tissue dysfunction, renal lipotoxicity, and chronic low-grade inflammation, ultimately causing obesity, type 2 diabetes, and cardiometabolic disease. Finally, we explore strategies to restore NSNR function, including Mediterranean and plant-based dietary patterns, as well as diets enriched with ω-3 polyunsaturated fatty acids, monounsaturated fats, and polyphenols. By integrating molecular, physiological, and clinical evidence, this review aims to clarify how NSNR networks translate dietary cues into coordinated inter-organ metabolism and how nutrient-poor diets lead to metabolic diseases trough a loss of metabolic information, rather than merely by energy excess. This framework supports a paradigm shift from calorie-centred nutrition to diet quality as the main therapeutic target for preventing metabolic diseases and promoting health. Full article

Background: Chronic kidney disease (CKD) is characterized by irreversible structural damage and functional deterioration of the kidneys. Esculetin (ES), with its anti-inflammatory, antioxidant, and immunomodulatory activities, shows potential in delaying renal function decline. This study aimed to investigate the protective effect of ES on adenine-induced CKD in mice and its underlying molecular mechanism, with a focus on its role in preventing the transition from acute kidney injury (AKI) to CKD. Methods: A AKI-to-CKD transition mice model was established by feeding mice a 0.2% adenine diet, and ES (30, 60 mg/kg) was co-administered for 4 weeks as a prophylactic intervention. Serum creatinine (SCr), blood urea nitrogen (BUN), and renal histopathology (HE, Masson, IHC) were evaluated to assess renal injury. Network pharmacology and transcriptomics were combined to screen the targets, and Western blot was used to verify the signaling pathways. Results: ES significantly reduced SCr and BUN levels in CKD mice and alleviated renal tubular dilation and inflammatory infiltration. ES decreased pro-inflammatory factors (IL-1β, IL-6, TNF-α) and MDA levels and enhanced SOD activity. Additionally, ES inhibited renal interstitial collagen deposition and reversed epithelial–mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA levels. Mechanism studies confirmed that ES significantly inhibited the phosphorylation levels of p-EGFR, p-SRC, p-PI3K, p-AKT, and p-p65 in renal tissues. Conclusions: ES effectively inhibits inflammation, oxidative stress, and fibrosis by modulating the EGFR/SRC/PI3K/AKT/NF-κB signaling axis, thereby preventing the AKI-to-CKD transition in the adenine-induced renal injury model and alleviating the progression of chronic renal damage. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the most common underlying cause of chronic kidney disease in pediatric populations. Maternal hypovitaminosis D links to mesoderm-related birth defects, leading to our hypothesis that maternal vitamin D deficiency (VDD) impairs renal development (a mesoderm-derived process) and induces offspring CAKUT. To investigate whether a low-vitamin D level can cause CAKUT, we used vitamin D-free diets to induce a maternal vitamin D deficiency mice model. The maternal vitamin D deficiency (VDD) mice models and normal vitamin D status (CON) were successfully established by administering a vitamin D-free or vitamin D-sufficient diet for 4 weeks prior to pregnancy. The overall incidence of CAKUT was significantly increased in VDD neonatal mice (19.4% vs. 2.44%; p = 0.0006), with a higher incidence of early duplicated budding in E11.5. E11.5 ureteric bud tissue revealed significantly increased activity of Gdnf-Ret-p-Erk1/2 signaling in the VDD group. In vivo intervention with the p-Erk1/2 antagonist U0126 in the pregnant VDD mice model at E10.5 improved CAKUT occurrence in offspring with p-Erk1/2 expression decreasing toward normal levels. Early metanephric ureteric bud H3K4me3 CUT&TAG analysis at E12.5 revealed chromatin activation patterns, which revealed that the downregulation of Hnf1β promoter region peaks was accompanied by reduced Hnf1β expression, and Robo2 promoter region peak was upregulated with increased Robo2 expression in the VDD group. Maternal vitamin D deficiency in mice significantly increased offspring CAKUT incidence. This phenotype was mediated by enhanced Gdnf-Ret-p-Erk1/2 signaling and reversed by p-Erk1/2 inhibition, with VDD inducing epigenetic remodeling of Hnf1β and Robo2 promoters. Full article

Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article

The high concentration of the inflammatory cytokine IL-36 in the serum of patients with type 2 diabetes mellitus (T2DM), along with the reduced renal damage observed in IL-36R knockout mice following ischemia–reperfusion-induced acute kidney injury, suggests a significant association between IL-36 activity and diabetic complications such as diabetic nephropathy (DN). It is also known that minor structural alterations in glomerular tissues can lead to changes in blood vessel pressure, potentially contributing to the development of DN, with inflammation acting as a triggering factor. However, further studies are needed to confirm this relationship. In this study, we observed that mesangial (MES-SV40) cells cultured under high-glucose conditions produced IL-36α in a dose-dependent manner. This cytokine production was also detected in mesangial cells from the glomerular tissues of mice with a high-calorie diet-induced T2DM, whereas healthy mice did not show such expression. In addition, we observed that mouse endothelial cells (SVECs) showed increased tubule formation in co-culture with MES-SV40 cells that had been previously exposed to 30 mmol/L glucose, as well as with the supernatant from these cells. IL-36R expression was confirmed in endothelial cells, as well as the angiogenic effect of IL-36α. Given that elevated VEGF levels have been reported in patients with DN by other authors, our results suggest that IL-36 produced by mesangial cells under high-glucose conditions may promote angiogenesis in glomerular tissues, potentially initiating the development of diabetic nephropathy. Full article

Background: Hyperuricemia (HUA) is a metabolic disorder that severely threatens human health. Chronic uric acid (UA) overload promotes the progression of tubulointerstitial fibrosis (TIF), leading to impaired UA excretion. Our previous studies identified HIPK2 inhibitor XRF-1021, which exhibits robust anti-TIF activity and lowers UA levels in vivo. This study aimed to elucidate its UA-lowering mechanism and therapeutic potential for HUA. Methods: Uricase and xanthine oxidase (XOD) assays were performed to assess effects on UA degradation/production. HEK293T cells transiently expressing UA transporters and gene-knockdown rats were used to evaluate transporter inhibition, while HK-2 cells were analyzed by Western blot. Pharmacokinetics were characterized in rats. Efficacy was tested in potassium oxonate-induced acute HUA rats, diet/adenine-induced chronic HUA quails, and adenine-induced mice with HUA secondary to TIF. Maximum tolerated dose and long-term toxicity were assessed in rats. Results: XRF-1021 neither activated uricase nor inhibited XOD, indicating no direct effect on UA catabolism or synthesis. Instead, XRF-1021 inhibited URAT1 and GLUT9, reducing renal UA reabsorption, while sparing OAT3, OAT4, and ABCG2 activity and upregulating OAT3 and NPT4, suggesting minimal risk of disrupting drug or uremic toxin handling. XRF-1021 showed dose-dependent systemic exposure in rats, lowered serum UA, and provided renal protection in vivo. LD₅₀ values were 2345.4 mg/kg (male) and 1078.9 mg/kg (female), with no obvious toxicity after long-term dosing. Conclusions: XRF-1021 lowers UA by inhibiting URAT1 and GLUT9 to enhance renal UA excretion and provides kidney protection, supporting XRF-1021 as a promising candidate for HUA therapy. Full article

Diabetic nephropathy (DN) is a serious complication in diabetic patients, leading to kidney dysfunction and ultimately end-stage renal disease. Although several pharmacological agents have been developed, treating DN remains challenging due to its complex and multifaceted pathogenesis. Endoplasmic reticulum (ER) stress plays a crucial role in DN pathology; however, the molecular mechanisms underlying reduced ER stress remain poorly understood. This study investigated the protective effects of 4-phenylbutyrate (4-PBA), an ER stress inhibitor, on DN and the related regulatory molecules through gene expression network analysis. A C57BL/6 mouse model of DN was used in combination with a high-fat diet and streptozotocin after unilateral nephrectomy and treated with 4-PBA by intraperitoneal injection for 6 weeks. The 4-PBA treatment effectively improves DN-induced renal structural and functional abnormalities by reducing albuminuria, podocyte loss, glomerular and tubular injury, and renal inflammation and cell death. These changes induced by 4-PBA were associated with decreased expression of ER stress markers and increased autophagy activities in diabetic kidneys. Importantly, 4-PBA reduced components of the complement C1q pathway, the NADPH oxidase complex, and chemokines, thereby attenuating chronic renal dysfunction. Conclusively, inhibition of ER stress is a promising pharmacological target for treating patients with DN. Full article

Background/Objectives: Chronic kidney disease (CKD) is a global public health concern, posing significant diagnostic and management challenges in primary care. Estimated glomerular filtration rate (eGFR) is central to CKD staging, yet different estimating equations may yield substantially different stage classifications when applied to the same population. This study aims to compare the eGFR-based CKD stage classification and stage distribution obtained using the Chronic Kidney Disease: Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations in a large primary care cohort, and to explore the implications of these classification differences for routine use in primary healthcare (PHC). Methods: A cross-sectional analysis was conducted using standardized electronic health records from 117,055 PHC patients in the Matosinhos Health Unit, Portugal, spanning 22 years (2000–2022). CKD staging followed KDIGO guidelines and focused on stages G3–G5, based on the most recent available serum creatinine value. CKD-EPI and MDRD equations were compared overall and across age strata, BMI categories, albuminuria categories (when available), and major comorbidity subgroups, including heart failure, diabetes, and hypertension. Results: Using CKD-EPI, a higher proportion of individuals were classified as CKD stages G3–G5 (9042; 7.73%) compared with MDRD (7686; 6.57%). Classification differences were most pronounced in advanced stages (relative increase with CKD-EPI: G3b +29.4%, G4 +23.6% and G5 +34.4%). Among individuals aged ≥80 years, equation-related classification differences were particularly marked in advanced stages (G5). Similarly, CKD-EPI was associated with higher CKD stage classification rates in high-risk subgroups, including patients with heart failure. Conclusions: Compared with MDRD, CKD-EPI yields a higher proportion of individuals classified into CKD stages, particularly advanced stages and among older adults and high-risk comorbidity subgroups. These findings highlight the substantial impact of equation choice on CKD stage classification in primary care and support the use of CKD-EPI for standardized eGFR reporting, while emphasizing that observed differences reflect classification rather than confirmed CKD diagnosis. Full article

Background/Objectives: Obesity and type 2 diabetes are increasingly common among patients undergoing hip and knee arthroplasty and are associated with higher risks of prosthetic joint infection, impaired wound healing, and prolonged hospitalisation. Dietary carbohydrate restriction has demonstrated benefits in glycemic control and weight reduction, but its feasibility and safety in the perioperative arthroplasty population remain underexplored. This pilot study evaluated the safety, feasibility, and short-term metabolic effects of a low-carbohydrate diet supported by WhatsApp-based meal photo-logging in patients undergoing total hip or knee arthroplasty. Methods: A retrospective cohort analysis was performed on 43 patients enrolled in a carbohydrate-restricted dietary programme between 2021 and 2024. Patients submitted photographs of all meals via WhatsApp with a minimum contact frequency of four times daily, enabling real-time feedback and medication adjustment. Anthropometric and metabolic parameters, including weight, BMI, HbA1c, renal function, and lipid profile, were assessed before and after the intervention. Results: Participants (mean age 69.12 ± 7.51 years) demonstrated significant improvement across several metabolic markers. Mean weight decreased by 5.74 kg (p < 0.001), BMI by 2.26 kg/m² (p < 0.001), and HbA1c by 0.72% (p < 0.001). No episodes of severe hypoglycaemia or perioperative discharge delays related to glycemic instability were observed. Renal function remained stable, with no significant change in eGFR (p = 0.442). Among patients with available lipid data (n = 14), LDL-cholesterol and total cholesterol increased, while triglycerides showed a non-significant downward trend. Conclusions: A low-carbohydrate diet combined with high-frequency digital monitoring appears feasible and safe, achieving meaningful short-term improvements in weight and glycemic control without adverse renal or hypoglycemic events. The lipid changes observed, however, warrant cautious interpretation. These findings are hypothesis-generating, and larger prospective studies are needed to confirm the clinical impact of this approach and its relevance to perioperative optimisation. Full article

Despite the known association between calcium and magnesium in drinking water and stone risk, the difference in stone prevention of purified water remineralized with varying calcium-to-magnesium ratios (Ca:Mg) remains unclear. Objectives: This study investigates the impact of different Ca:Mg in the remineralization of purified water on calcium oxalate crystallization and renal injury. Methods: Sixty male Sprague-Dawley rats were induced calcium oxalate crystals by a sodium oxalate diet and divided into six groups, where they drank purified water with or without remineralized varying Ca:Mg (0.5, 3.4, 10, 20, 100). Serum and urine biomarkers of renal function, renal injury, mineral metabolism, bone metabolism, and urine calcium oxalate crystals were detected. Kidneys were isolated for pathological examination. Results: Findings showed that remineralization by 0.5 and 3.4 Ca:Mg significantly reduced urinary calcium oxalate crystallization, renal injury, and improved renal function, while extreme ratios (Ca:Mg over 10) showed no benefits. Conclusions: These results elucidate the pathophysiological effects of Ca:Mg in drinking water on renal health, particularly emphasizing the protective role of the 0.5 and 3.4 in inhibiting calcium oxalate crystallization and mitigating renal injury. It provides a quantifiable reference for purified water remineralization aimed at stone prevention. Full article

Background/Objectives: Diabetes mellitus (DM) is associated with a doubled prevalence of elevated intraocular pressure (IOP) caused by trabecular meshwork (TM) dysfunction. Chronic hyperglycaemia leads to oxidative stress and fibrotic remodeling of the TM. We previously identified the Sigma-1 receptor (S1R) as a novel anti-fibrotic target by demonstrating that its agonist, fluvoxamine (FLU), is protective in diabetes-related renal fibrosis. Here, we investigate its potential to mitigate ocular fibrosis. Methods: First, we wanted to verify in different in vivo models (high-fat diet/streptozotocin (HFD/STZ) rats, db/db mice) that type 2 DM (T2DM) leads to fibrotic remodeling of the TM. Then, in vitro, we assessed the effect of FLU (15 µM) on hyperglycaemia-induced (HG, 25 µM) fibrosis, oxidative stress and endogenous nitric oxide (NO) production. Results: In T2DM models, excessive accumulation of collagen, α-smooth muscle actin (αSMA), fibronectin (Fn) and F-actin was observed in the eyes. Ocular fibrosis was accompanied by IOP elevation (13.7 vs. 18.7 mmHg) in db/db mice. In human TM cells (HTM5), FLU decreased HG-induced cell proliferation (14% vs. 24%) and upregulated S1R protein expression. Furthermore, FLU suppressed the expressions of key fibrotic elements, including transforming growth factor-β2 (TGF-β2) by 37%, Fn by 49%, collagen type 1 (COL1A1) and type 4 (COL4A1) by 24% and 45%, respectively. FLU also reversed HG-induced F-actin accumulation by 39% and enhanced intracellular NO levels by 34%. Crucially, FLU decreased ROS generation by half, demonstrating its protective effect against HG-induced oxidative stress. Conclusions: These findings highlight the potential of S1R activation as a promising therapeutic target to alleviate hyperglycaemia-induced injury to the TM by modulating multiple molecular pathways. Full article

We studied the expression of connexin 43 (Cx43) and pannexin 1 (PANX1) in different cellular populations of the kidneys of diabetic mice and diabetic and non-diabetic patients, to evaluate their role as potential therapeutic targets in diabetic kidney disease (DKD). A combination of a low dose of streptozotocin and a high-fat diet (HFD) was used to induce a type 2 diabetes model (DM2) in mice. Kidney tissues from diabetic (n = 9) and control patients (n = 11) who underwent nephrectomy were collected. Tissues from mice and humans were processed for double immunofluorescence, using antibodies against Cx43, phosphorylated Cx43 (pCx43) or PANX1 and markers for specific cell populations: endothelium (CD31/PECAM1); pericytes/mesangium (PDGFRB); podocytes (nephrin/synaptopodin); proximal tubules and collecting ducts (aquaporin 2). The results showed a significant decrease in the expression of pCx43 in PDGFRB-immunoreactive mesangium in diabetic patients compared to the control group (p < 0.0001). This contrasted with an increase in pCx43 in pericytes of diabetic mice (p = 0.1). However, we found a general decrease in Cx43 protein expression in diabetic mouse kidneys (p < 0.05). We also found a decrease in the expression of PANX1 in endothelial cells of diabetic patients (p < 0.05) and a significant increase in PANX1 expression in cells expressing PDGFRB (p < 0.05). Expression of PANX1 in endothelium (r = −0.50; p < 0.05) and pCx43 in the mesangium (r = −0.65; p < 0.01) correlated negatively with the percentage of sclerotic glomeruli. The expression and activation of Cx43 and the expression of PANX1 are altered in distinct populations of renal cells during long-term type 2 diabetes mellitus, especially cells of the vascular wall. This may indicate their role in the pathophysiological processes of DKD. Therefore, connexin and pannexin channels could be considered as possible therapeutic targets in the prevention and treatment of diabetic kidney disease. Full article

Dromedary camels possess unique anatomical, physiological, and metabolic adaptations that enable survival in arid environments; however, these same adaptations make them highly sensitive to nutritional imbalance under modern feeding conditions. This review synthesizes current knowledge on nutritional pathologies and metabolic disorders in camels, emphasizing the links between diet composition, foregut fermentation, mineral status, and systemic health. Imbalances in energy and carbohydrates predispose camels to subacute and acute acidosis, negative energy balance, and ketosis-like syndromes, particularly when rapidly fermentable feeds are introduced without adequate fiber or water. Protein and nitrogen disorders, including ammonia toxicity and impaired urea recycling, arise from mismatches between degradable protein, fermentable energy, hydration, and mineral availability. Widespread deficiencies of phosphorus, copper, cobalt, zinc, selenium, and vitamins A and E remain major constraints, leading to pica, poor microbial fermentation, oxidative stress, immunosuppression, reproductive failure, and skeletal disorders. Nutritional disturbances frequently extend beyond the gastrointestinal tract, forming a gut–liver–kidney metabolic axis characterized by hepatic dysfunction, renal compromise, and systemic oxidative stress. The review also addresses gastrointestinal impaction, foreign-body ingestion, toxic plant consumption, and feeding on human food waste as emerging nutritional challenges, particularly in peri-urban systems. Advances in diagnostic ultrasonography, feed evaluation techniques, probiotics, mineral–vitamin supplementation, and omics-based approaches are discussed as tools for improving early diagnosis and precision nutrition. Despite growing research interest, the lack of camel-specific feeding standards and reliance on cattle-based recommendations remain critical gaps. This review highlights the need for species-specific nutrient requirement models, sustainable rangeland management, and integrative research to support the health, resilience, and productivity of camels under changing environmental and production systems. Full article

Highly pathogenic avian influenza (HPAI) A/H5N1 has emerged as a cause of severe disease in domestic cats, but clinical data from field outbreaks remain limited. We retrospectively reviewed medical records, laboratory results, and ancillary examinations from 22 domestic cats with RT-qPCR-confirmed A/H5N1 infection diagnosed in Poland in June 2023. To the best of our knowledge, we report the first comprehensive retrospective case series from the 2023 Polish outbreak, combining 22 laboratory-confirmed cats with detailed clinical timelines and laboratory findings. For each cat, the temporal progression of clinical signs, hematology, serum biochemistry, and, when available, imaging findings were evaluated. Post-mortem examination data were not systematically available in this retrospective cohort. Notably, six of these cats were strictly indoor cats that received raw poultry meat as part of their diet. Disease onset was acute, with fever, lethargy, and anorexia rapidly progressing to severe dyspnea and neurological signs, including ataxia, seizures, and paraplegia; case fatality was 100%, with a typical interval of ≤3 days from first signs to death or euthanasia. Hematologic changes were dominated by thrombocytopenia, lymphopenia, and marked eosinopenia, consistent with a systemic inflammatory/stress leukogram. Biochemistry indicated marked tissue injury, with increased AST, LDH, and CK activities, whereas creatinine and urea remained largely within reference intervals, arguing against primary renal failure. Imaging supported the presence of interstitial to diffuse pneumonia. These data characterize the clinical and laboratory phenotypes of feline A/H5N1 infection and underscore its importance as a rapidly fatal respiratory and neurological disease with One Health implications. Full article

Hyperuricemia is a metabolic disorder characterized by elevated serum uric acid levels and is increasingly linked to alterations in intestinal mucosal condition and gut microbiota composition. Probiotics have been proposed as safe, non-pharmacological approaches for managing hyperuricemia, but strain-specific evidence remains limited. This study aimed to evaluate the anti-hyperuricemic potential of Limosilactobacillus reuteri MBHC10138, isolated from human breast milk, and to examine its association with purine metabolism–related parameters, renal morphological features, intestinal barrier-associated markers, and gut microbiota composition. In vitro, MBHC10138 effectively degraded purine nucleosides that are metabolized into uric acid, suggesting its potential to reduce uric acid production in the host. In a mouse model of diet- and oxonate-induced hyperuricemia, oral administration of MBHC10138 significantly lowered serum uric acid levels to a level comparable with allopurinol treatment, while improving renal morphology. Histological and molecular analyses demonstrated restoration of the tight junction proteins zonula occludens-1 and occludin, indicative of enhanced intestinal barrier integrity. Furthermore, MBHC10138 administration modulated the gut microbiota by restoring microbial α-diversity and significantly increasing the relative abundances of the Clostridia vadinBB60 group and Oscillospiraceae, taxa associated with butyrate production, compared with the allopurinol-treated group. Collectively, these findings indicate that MBHC10138 exerts dual actions against hyperuricemia and intestinal barrier dysfunction through the regulation of purine metabolism, promotion of renal urate excretion, and modulation of gut microbial composition. MBHC10138 may thus represent a promising probiotic candidate for the prevention and adjunctive management of hyperuricemia-related metabolic disorders. Full article