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Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1ß, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota's diversity and balance.

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Introduction: Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development. Methods: In this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence. Results: The study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24-28) weeks, postmenstrual age at diagnosis 28 (26-31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41-50) U/g of protein] compared to controls [115 (76-144), P = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0-0.1)] than in controls [0.3 (0.2-0.5), P = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens. Conclusion: This study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts.

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Interest to the tissue-specific intestinal isoenzyme of alkaline phosphatase (IAP) has increased in recent years due to eating disorders that have led to widespread obesity and diet-related diseases. Obesity is considered as an inflammation of low intensity, which is accompanied by the manifestation of various metabolic complications and a disturbance of intestinal homeostasis. IAP is one of the participants in the mechanism of the macroorganism protection against inflammatory and infectious processes, carrying out enzymatic detoxification of bacterial lipopolysaccharide (the trigger of the inflammatory process). Deficiency of IAP activity contributes to the risk of obesity, inflammatory diseases. The objective of the research was to summarize the current understanding of the role of IAP involved in the molecular mechanism of diet-induced obesity and to evaluate the impact of dietary components - fats and dietary fiber on IAP activity. Material and methods. A literature search on the role of IAP in the development of obesity was carried out using PubMed, Scopus, Web of Science, Google Scholar, ResearchGate, RSCI databases. Results. IAP prevents the development of the inflammatory process by participating in the detoxification of toxic bacterial products, limiting the translocation of pathogenic bacteria from the intestine to various tissues and organs of the macroorganism. The enzyme maintains the integrity of the intestinal barrier, influencing the synthesis and proper localization of tight junction's proteins between intestinal epithelial cells, promotes changes in the composition of the microbiota, decreasing pathogenic bacteria and increasing the population of the community of beneficial microorganisms. IAP is involved in the regulation of fatty acid absorption and influences on the adipogenesis. Monitoring the activity of IAP present in human stool can predict the early development of such complications associated with obesity as metabolic syndrome and diabetes mellitus, Some nutrients modulate IAP activity. Depending on the amount, type, composition of fats and the duration of their consumption, either an increase or decrease in the IAP activity are observed, while dietary fibers stimulate the activity of the enzyme. Conclusion. IAP activity can be considered as an early predictor of the risk of obesity. Deficiency of IAP activity contributes to the development of obesity caused by high-fat diet. The high activity of the enzyme contributes to the support of intestinal homeostasis and limits transepithelial movement of bacteria, weakening the inflammatory process induced by lipopolysaccharides, the excess concentration of which is detected in obesity. Stimulating enzyme activity through dietary intervention reduces the risk of obesity and metabolic complications.

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Intestinal alkaline phosphatase (IAP) is an enzyme that plays a protective role in the gut. This study investigated the effect of IAP treatment on experimental colitis in mice subjected to forced exercise on a high-fat diet. C57BL/6 mice with TNBS colitis were fed a high-fat diet and subjected to forced treadmill exercise with or without IAP treatment. Disease activity, oxidative stress, inflammatory cytokines, and gut microbiota were assessed. Forced exercise exacerbated colitis in obese mice, as evidenced by increased disease activity index (DAI), oxidative stress markers, and proinflammatory adipokines and cytokines. IAP treatment significantly reduced these effects and promoted the expression of barrier proteins in the colonic mucosa. Additionally, IAP treatment altered the gut microbiota composition, favoring beneficial Verrucomicrobiota and reducing pathogenic Clostridia and Odoribacter. IAP treatment ameliorates the worsening effect of forced exercise on murine colitis by attenuating oxidative stress, downregulating proinflammatory biomarkers, and modulating the gut microbiota. IAP warrants further investigation as a potential therapeutic strategy for ulcerative colitis.

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The intestinal barrier is critical for maintaining intestinal homeostasis, and its dysfunction is associated with various diseases. Recent findings have revealed the multifunctional role of intestinal alkaline phosphatase (IAP) in diverse biological processes, including gut health maintenance and function. This review summarizes the protective effects of IAP on intestinal barrier integrity, encompassing the physical, chemical, microbial, and immune barriers. We discuss the results and insights from in vitro, animal model, and clinical studies as well as the available evidence regarding the impact of diet on IAP activity and expression. IAP can also be used as an indicator to assess intestinal-barrier-related diseases. Further research into the mechanisms of action and long-term health effects of IAP in maintaining overall intestinal health is essential for its future use as a dietary supplement or functional component in medical foods.

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BACKGROUND: Recent evidence suggests that measures of maternal gut enteropathy are associated with unfavorable fetal outcomes. It is, therefore, crucial to identify and treat the features of intestinal enteropathy among reproductive-age women living in areas where enteropathy is highly prevalent. However, there is a lack of non-invasive diagnostic tests to determine EED, making it difficult to identify the disease in field settings. In this study, we tested the potential of fecal pH as a biomarker of gut enteropathy and investigated its relationship with fecal biomarkers of intestinal enteropathy in reproductive-age women living in resource-limited environments. METHODS: Data on socio-demographic information, anthropometry, and biological samples were collected from 78 apparently healthy women aged between 20 and 27 years from November 2018 to December 2019. The association of stool pH with two fecal biomarkers of gut enteropathy (i.e., intestinal alkaline phosphatase [IAP] and fecal lipocalin-2 [LCN-2] was investigated using multiple linear regression models after adjusting for relevant covariates. RESULTS: In the adjusted models, alkaline stool pH (pH > 7.2) was found to be significantly associated with a decrease in the fecal IAP level by 1.05 unit (95% CI: -1.68, -0.42; p < 0.001) in the log scale, and acidic stool pH (pH < 6) was found to be significantly associated with an increase in the fecal LCN-2 level by 0.89 units (95% CI: 0.12, 1.67; p < 0.025) in the log scale. CONCLUSIONS: The study findings demonstrated an association of fecal pH with biomarkers of gut enteropathy indicating its applicability as a simple tool for understanding intestinal enteropathy among reproductive-age women living in resource-limited settings.

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Objective: Heatstroke (HS) is a severe acute disease related to gastrointestinal barrier dysfunction, systemic inflammation and multiple organ injury. Many of the functions of Intestinal alkaline phosphatase (IAP) have been linked to gut homeostasis, gut barrier function and inflammation. However, the protective effect of IAP on heatstroke is not fully elucidated. This study aims to explore the protective effect of IAP on heatstroke by maintaining intestinal barrier and improving permeability. Methods: Male C57BL/6 mice were placed in a controlled climate chamber (ambient temperature: 40.0 ± 0.5 °C; humidity: 60 ± 5 %) until the maximum core temperature (Tc, max) reached 42.7 °C (the received criterion of HS). Then heat exposed mice (n = 195) were divided into three groups: 0.2 mL of 0.9 % physiological saline (HS) or vehicle (HS + Vehicle) or 300 IU IAP (HS + IAP) by gavage at 0, 24, and 48 h after onset. Control group mice (Con) (n = 65) were not exposed to heat and were gavaged with 0.9 % physiological saline of the same volume at the same time. Results: IAP treatment significantly reduced the levels of endotoxin, FD4, and D-lactate in the blood of heatstroke mice, reduced intestinal permeability and maintained the integrity of the intestinal barrier by increasing the expression of tight junction proteins. Meanwhile, IAP treatment alleviated liver and kidney damage caused by heatstroke, reduced serum levels of inflammatory cytokines, and thus improved survival rate of mice after heatstroke. Conclusion: This study indicates that IAP can improve the intestinal barrier function and intestinal permeability by increasing intestinal tight junctions, reduce systemic inflammation and multiple organ injury and improving the survival rate of heatstroke. Therefore, we consider IAP may be added to enteral nutrition formulas as a potential means for diseases characterized by intestinal permeability disorders, including heatstroke.

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INTRODUCTION: Geese can naturally obtain dietary fiber from pasture, which has anti-inflammatory and antioxidant properties. This study aimed to investigate the inhibitory impacts of pasture on ameliorating LPS-ROS-induced gut barrier dysfunction and liver inflammation in geese. Materials and methods. The lipopolysaccharides (LPS), alkaline phosphatase (ALP), reactive oxygen species (ROS), tight junction proteins, antioxidant enzymes, immunoglobulins, and metabolic syndrome were determined using ELISA kits. The Kelch-like-ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) and inflammatory cytokines were determined using the quantitative reverse transcription PCR (RT-qPCR) method. The intestinal morphology was examined using the Hematoxylin and Eosin (H&E) staining method in ileal tissues. Results. Pasture significantly influences nutrient absorption (p < 0.001) by ameliorating LPS and ROS-facilitated ileal permeability (p < 0.05) and systemic inflammation (p < 0.01). Herein, the gut permeability was paralleled by liver inflammation, which was significantly mimicked by ALP-dependent Nrf2 (p < 0.0001) and antioxidant enzyme activation (p < 0.05). Indeed, the correlation analysis of host markers signifies the importance of pasture in augmenting geese's health and production by averting gut and liver inflammation. Conclusions. Our results provide new insight into the mechanism of the pasture-induced ALP-dependent Nrf2 signaling pathway in limiting systemic inflammation in geese.

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Necrotizing enterocolitis (NEC) is a devastating neonatal disease that affects neonates worldwide and often leads to high morbidity and mortality rates. Despite extensive research, the cause of NEC remains unclear, and current treatment options are limited. An important novel finding is the potential role of intestinal Alkaline Phosphatase (IAP) in both pathogenesis and treatment of NEC. IAP can play a vital role in detoxifying liposaccharides (LPS), a key mediator of many pathological processes, thereby reducing the inflammatory response associated with NEC. Furthermore, IAP can help prevent dysbiosis, improve intestinal perfusion, and promote autophagy. In this comprehensive review, we present evidence of the possible connection between IAP and the LPS/Toll-like receptor 4 (TLR4) pathway, impaired gut immunity, and dysbiosis in the preterm gut. Based on these findings, the administration of exogenous IAP might provide promising preventive and therapeutic avenues for the management of NEC.

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BACKGROUND: Intestinal alkaline phosphatase (iAP) is an intestinal brush border enzyme that is one of the factors involved in the pathogenesis of inflammatory bowel disease (IBD). The aim of the study was to investigate the relationship between iAP enzyme and histological inflammatory activity in patients with IBD. METHODS: A total of 44 children were enrolled in this study including IBD patients (n=24; 12 Crohn`s disease [CD] and 12 ulcerative colitis [UC]) and controls (n=20). Anti-human iAP antibody stained ileocolonoscopic biopsy specimens were graded for the terminal ileum and each section of the colon. Hematoxylin-eosin stained sections were used to determine inflammatory activity. Histopathological findings were compared in pre- and post-treatment biopsies of each group and with the control group (CG). RESULTS: A low grade of iAP staining was detected in IBD patients compared to the CG (p=0.02). iAP was remarkably concentrated in the terminal ileum (TI) and especially in region 1, which involved the apical surface, brush border, and epithelial cells. A significant negative correlation was found between the grade of iAP staining and inflammatory activity both in pre- and post-treatment biopsies (p=0.02, p=0.008, respectively) in the terminal ileum of CD patients. Likewise, pre-treatment biopsies of UC and CD patients and biopsies of the CG were compared with each other according to the grade of iAP staining. There were significant negative correlations for CD patients compared to UC and the CG in region1 of TI, and regions 1 and 2 (lamina propria and goblet cells) of the colon (p= 0.015, p= 0.006, p < 0.001, respectively). CONCLUSIONS: As a histological marker, iAP can be of value in monitoring the histological activity of IBD, particularly in remarkable inflammation in the small intestine.

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Introduction: Diet strongly affects gut microbiota composition, and gut bacteria can influence the intestinal barrier functions and systemic inflammation through metabolic endotoxemia. In-house feeding system (IHF, a low dietary fiber source) may cause altered cecal microbiota composition and inflammatory responses in meat geese via increased endotoxemia (lipopolysaccharides) with reduced intestinal alkaline phosphatase (ALP) production. The effects of artificial pasture grazing system (AGF, a high dietary fiber source) on modulating gut microbiota architecture and gut barrier functions have not been investigated in meat geese. Therefore, this study aimed to investigate whether intestinal ALP could play a critical role in attenuating reactive oxygen species (ROS) generation and ROS facilitating NF-κB pathway-induced systemic inflammation in meat geese. Methods: The impacts of IHF and AGF systems on gut microbial composition via 16 sRNA sequencing were assessed in meat geese. The host markers analysis through protein expression of serum and cecal tissues, hematoxylin and eosin (H&E) staining, localization of NF-қB and Nrf2 by immunofluorescence analysis, western blotting analysis of ALP, and quantitative PCR of cecal tissues was evaluated. Results and Discussion: In the gut microbiota analysis, meat geese supplemented with pasture showed a significant increase in commensal microbial richness and diversity compared to IHF meat geese demonstrating the antimicrobial, antioxidant, and anti-inflammatory ability of the AGF system. A significant increase in intestinal ALP-induced Nrf2 signaling pathway was confirmed representing LPS dephosphorylation mediated TLR4/MyD88 induced ROS reduction mechanisms in AGF meat geese. Further, the correlation analysis of top 44 host markers with gut microbiota showed that artificial pasture intake protected gut barrier functions via reducing ROS-mediated NF-κB pathway-induced gut permeability, systemic inflammation, and aging phenotypes. In conclusion, the intestinal ALP functions to regulate gut microbial homeostasis and barrier function appear to inhibit pro-inflammatory cytokines by reducing LPS-induced ROS production in AGF meat geese. The AGF system may represent a novel therapy to counteract the chronic inflammatory state leading to low dietary fiber-related diseases in animals.

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Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 ± 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho ≥ 0.415, p ≤ 0.009) and negatively associated with the relative abundance of Sutterella genus (Proteobacteria phylum; rho ≥ -0.270, p ≤ 0.041), respectively. Moreover, plasma levels of omega-6 derived oxylipins were negatively associated with the relative abundance of Acidaminococcus and Phascolarctobacterium genera (Firmicutes phylum; all rho ≥ -0.263, p ≤ 0.024), as well as Sutterella, Succinivibrio, and Gemmiger genera (Proteobacteria phylum; all rho ≥ -0.263, p ≤ 0.024). Lastly, the ratio between omega-6 and omega-3 oxylipins plasma levels was negatively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho = -0.334, p = 0.004) and Butyricimonas genus (Bacteroidetes phylum; rho = -0.292, p = 0.014). In conclusion, our results show that the plasma levels of omega-3 and omega-6 derived oxylipins are associated with the relative abundance of specific fecal bacteria genera.

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Background and Purpose: Emerging studies have shown that gut-derived endotoxins might play a role in intestinal and systemic inflammation. Although the significance of intestinal permeability in modulating the pathogenesis of Schizophrenia (SCZ) is recognized, not much data on the specific role of intestinal permeability biomarkers, viz., zonulin, lipopolysaccharide-binding protein (LBP), and intestinal alkaline phosphatase (IAP) in SCZ is available. Therefore, we measured the plasma levels of zonulin, LBP, and IAP and its correlation with neutrophil-to-lymphocyte ratio (NLR); a marker of systemic inflammation in patients with SCZ. Methods: We recruited 60 individuals, patients with SCZ (n = 40) and healthy controls (n = 20), from a large tertiary neuropsychiatry center. Plasma levels of zonulin, IAP, and LBP were quantified by enzyme-linked immunosorbent assay. Results: Plasma levels of both LBP and zonulin were significantly increased (P <0.05), whereas the IAP levels (P <0.05) were significantly decreased in patients with SCZ compared to healthy controls. Pearson correlation analysis revealed that zonulin and LBP had a significant positive correlation with NLR, and IAP negatively correlated with NLR. Individuals with SCZ had higher independent odds of zonulin [odds ratio (OR): 10.32, 95% CI: 1.85-57.12], LBP [OR: 1.039, 95% CI: 1.02-1.07], and IAP [OR: 0.643, 95% CI: 0.471-0.879], even after adjusting for potential confounders. Conclusion: Our study demonstrates an association of zonulin, LBP, and IAP in Asian Indian SCZ patients and correlates with NLR. Our results indicate that low-grade inflammation induced by metabolic endotoxemia might be implicated in the pathoetiology of SCZ.

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In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR in vivo, and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation in vitro. Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice. We found that an IAP + IAP enhancer significantly ameliorated blood glucose, insulin, low-density lipoprotein, gut barrier function, inflammatory markers, and lipopolysaccharide (LPS) in serum. IAP could dephosphorylate LPS and nucleoside triphosphate in a pH-dependent manner in vitro. Firstly, LPS is inactivated by IAP and IAP reduces LPS-induced inflammation. Secondly, adenosine, a dephosphorylated product of adenosine triphosphate, elicited anti-inflammatory effects by binding to the A2A receptor, which inhibits NF-κB, TNF, and PI3K-Akt signalling pathways. Hence, IAP can be used as a natural anti-inflammatory agent to reduce intestinal inflammation-induced IR.

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Type 1 diabetes is associated with increased intestinal inflammation and decreased abundance of butyrate-producing bacteria. We investigated the effect of butyrate on inflammation, kidney parameters, HbA1c, serum metabolites and gastrointestinal symptoms in persons with type 1 diabetes, albuminuria and intestinal inflammation. We conducted a randomized placebo-controlled, double-blind, parallel clinical study involving 53 participants randomized to 3.6 g sodium butyrate daily or placebo for 12 weeks. The primary endpoint was the change in fecal calprotectin. Additional endpoints were the change in fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins, serum lipopolysaccharide, CRP, albuminuria, kidney function, HbA1c, metabolites and gastrointestinal symptoms. The mean age was 54 ± 13 years, and the median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. The median fecal calprotectin in the butyrate group was 48 [26:100] µg/g at baseline, and the change was -1.0 [-20:10] µg/g; the median in the placebo group was 61 [25:139] µg/g at baseline, and the change was -12 [-95:1] µg/g. The difference between the groups was not significant (p = 0.24); neither did we find an effect of butyrate compared to placebo on the other inflammatory markers, kidney parameters, HbA1c, metabolites nor gastrointestinal symptoms. Twelve weeks of butyrate supplementation did not reduce intestinal inflammation in persons with type 1 diabetes, albuminuria and intestinal inflammation.

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Tight junctions (TJs) are essential components of intestinal barrier integrity and protect the epithelium against passive paracellular flux and microbial translocation. Dysfunctional TJ leads to leaky gut, a condition associated with diseases including inflammatory bowel disease (IBD). Sulfate-Reducing Bacteria (SRB) are minor residents of the gut. An increased number of Desulfovibrio, the most predominant SRB, is observed in IBD and other diseases associated with leaky gut. However, it is not known whether Desulfovibrio contributes to leaky gut. We tested the hypothesis that Desulfovibrio vulgaris (DSV) may induce intestinal permeability in vitro. Snail, a transcription factor, disrupts barrier function by affecting TJ proteins such as occludin. Intestinal alkaline phosphatase (IAP), a host defense protein, protects epithelial barrier integrity. We tested whether DSV induced permeability in polarized Caco-2 cells via snail and if this effect was inhibited by IAP. Barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and by 4kDa FITC-Dextran flux to determine paracellular permeability. We found that DSV reduced TEER, increased FITC-flux, upregulated snail protein expression, caused nuclear translocation of snail, and disrupted occludin staining at the junctions. DSV-induced permeability effects were inhibited in cells knocked down for snail. Pre-treatment of cells with IAP inhibited DSV-induced FITC flux and snail expression and DSV-mediated disruption of occludin staining. These data show that DSV, a resident commensal bacterium, can contribute to leaky gut and that snail may serve as a novel therapeutic target to mitigate DSV-induced effects. Taken together, our study suggests a novel underlying mechanism of association of Desulfovibrio bloom with diseases with increased intestinal permeability. Our study also underscores IAP as a novel therapeutic intervention for correcting SRB-induced leaky gut via inhibition of snail.

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Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and kidney tissues. Beyond the well-known effects on bone mineralization, the bone ALP (BALP) isoforms (B/I, B1, B1x, and B2) are also involved in the pathogenesis of ectopic calcification. This narrative review summarizes the recent clinical investigations and mechanisms that link ALP and BALP to inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality. The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed. Recent advances in different pharmacological strategies are highlighted, with the potential to modulate the expression of ALP directly and indirectly in CKD-mineral and bone disorder (CKD-MBD), e.g., epigenetic modulation, phosphate binders, calcimimetics, vitamin D, and other anti-fracture treatments. We conclude that the significant evidence for ALP as a pathogenic factor and risk marker in CKD-MBD supports the inclusion of concrete treatment targets for ALP in clinical guidelines. While a target value below 120 U/L is associated with improved survival, further experimental and clinical research should explore interventional strategies with optimal risk-benefit profiles. The future holds great promise for novel drug therapies modulating ALP.

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Intestinal alkaline phosphatase (IALP) has recently assumed a special relevance, being the subject of study in the prevention and treatment of certain diseases related to leaky gut. This brush border enzyme (ecto-enzyme) plays an important role in the maintenance of intestinal microbial homeostasis and intestinal barrier function through its ability to dephosphorylate lipopolysaccharide (LPS). This review addresses how IALP and intestinal barrier dysfunction may be implicated in the pathophysiology of specific diseases such as inflammatory bowel disease, necrotizing enterocolitis, and metabolic syndrome. The use of IALP as a possible biomarker to assess intestinal barrier function and strategies to modulate IALP activity are also discussed.

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Inflammatory bowel diseases (IBD) are commonly considered as Crohn's disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.

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The effect of sodium butyrate (SB) and taurine on rat intestinal alkaline phosphatase (RIA) and the effect of the interaction of taurine and/or SB with bacterial lipopolysaccharides on ALP activity were investigated. In vitro analysis of the activity of RIA was carried out using various concentrations of SB and/or taurine. Substrate concentration-dependent kinetic study was performed at 1-10 mM of taurine and SB at 5.17 mM of p-nitrophenyl phosphate (p-NPP). The in vivo effect of lipopolysaccharide (LPS) in the presence and absence of taurine and SB on the activity of RIA was also evaluated. LPS was administered to rats intraperitoneally and 20 min after; this was followed by oral administration of SB and/or taurine. The hydrolysis of p-NPP by RIA was enhanced by taurine and SB at different concentrations. The in vivo kinetic study revealed that RIA activity was greater (588.23 × 10-3  µmol/min/ml) when taurine and SB were co-administered with bacterial LPS, yielding a low Km (0.12 mM) value. This suggested an increased affinity for the substrate by the enzyme. The degree of activation was highest when SB and taurine were administered together with LPS. The study concluded that SB and taurine are activators of RIA and their positive synergistic interaction in the presence of bacterial LPS may further emphasize the role of both activators in attenuating bacterial LPS-mediated diseases. PRACTICAL APPLICATIONS: The development and progression of a myriad of diseases such as inflammatory bowel disease, atherosclerosis, sepsis, multiple sclerosis, and rheumatoid arthritis have been linked to bacterial endotoxin. Taurine is an amino acid derived from cysteine, while sodium butyrate is a short-chain fatty acid. Consumption of food and food supplement rich in taurine and sodium butyrate can help protect against endotoxemic injury and aid tissue repair in the small intestine, digestibility, growth, and overall health of animals.

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