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BACKGROUND: Alcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PURPOSE: We explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. METHODS: Firstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. RESULTS: Ten main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. CONCLUSION: In this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

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The management of dysfunctional intestinal epithelium by promoting mucosal healing and modulating the gut microbiota represents a novel therapeutic strategy for inflammatory bowel disease (IBD). As a convenient and well-tolerated method of drug delivery, intrarectal administration may represent a viable alternative to oral administration for the treatment of IBD. Here, a biomimetic supramolecular assembly of hyaluronic acid (HA) and ß-cyclodextrin (HA-ß-CD) for the delivery of the C domain peptide of insulin-like growth factor-1 (IGF-1C), which gradually releases IGF-1C, is developed. It is identified that the supramolecular assembly of HA-ß-CD enhances the stability and prolongs the release of IGF-1C. Furthermore, this biomimetic supramolecular assembly potently inhibits the inflammatory response, thereby restoring intestinal barrier integrity. Following HA-ß-CD-IGF-1C administration, 16S rDNA sequencing reveals a significant increase in the abundance of the probiotic Akkermansia, suggesting enhanced intestinal microbiome homeostasis. In conclusion, the findings demonstrate the promise of the HA-based mimicking peptide delivery platform as a therapeutic approach for IBD. This biomimetic supramolecular assembly effectively ameliorates intestinal barrier function and intestinal microbiome homeostasis, suggesting its potential for treating IBD.

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BACKGROUND: PM2.5, a known public health risk, is increasingly linked to intestinal disorders, however, the mechanisms of its impact are not fully understood. PURPOSE: This study aimed to explore the impact of chronic PM2.5 exposure on intestinal barrier integrity and to uncover the underlying molecular mechanisms. METHODS: C57BL/6 J mice were exposed to either concentrated ambient PM2.5 (CPM) or filtered air (FA) for six months to simulate urban pollution conditions. We evaluated intestinal barrier damage, microbial shifts, and metabolic changes through histopathology, metagenomics, and metabolomics. Analysis of the TLR signaling pathway was also conducted. RESULTS: The mean concentration of PM2.5 in the CPM exposure chamber was consistently measured at 70.9 ± 26.8 µg/m³ throughout the study period. Our findings show that chronic CPM exposure significantly compromises intestinal barrier integrity, as indicated by reduced expression of the key tight junction proteins Occludin and Tjp1/Zo-1. Metagenomic sequencing revealed significant shifts in the microbial landscape, identifying 35 differentially abundant species. Notably, there was an increase in pro-inflammatory nongastric Helicobacter species and a decrease in beneficial bacteria, such as Lactobacillus intestinalis, Lactobacillus sp. ASF360, and Eubacterium rectale. Metabolomic analysis further identified 26 significantly altered metabolites commonly associated with intestinal diseases. A strong correlation between altered bacterial species and metabolites was also observed. For example, 4 Helicobacter species all showed positive correlations with 13 metabolites, including Lactate, Bile acids, Pyruvate and Glutamate. Additionally, increased expression levels of TLR2, TLR5, Myd88, and NLRP3 proteins were noted, and their expression patterns showed a strong correlation, suggesting a possible involvement of the TLR2/5-MyD88-NLRP3 signaling pathway. CONCLUSIONS: Chronic CPM exposure induces intestinal barrier dysfunction, microbial dysbiosis, metabolic imbalance, and activation of the TLR2/5-MyD88-NLRP3 inflammasome. These findings highlight the urgent need for intervention strategies to mitigate the detrimental effects of air pollution on intestinal health and identify potential therapeutic targets.

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Intestinal barrier hyperpermeability, which is characterised by impaired tight junction proteins, is associated with a variety of gastrointestinal and systemic diseases. Therefore, maintaining intestinal barrier integrity is considered one of the effective strategies to reduce the risk of such disorders. This study aims to investigate the potential benefits of two probiotic strains (Lactiplantibacillus plantarum ST-III and Lacticaseibacillus rhamnosus KF7) on intestinal barrier function by using a physiologically relevant in vitro model of the intestinal epithelium. Our results demonstrate that both strains increased transepithelial electrical resistance, a measure of intestinal barrier integrity. Immunolocalisation studies indicated that this improvement in barrier function was not due to changes in the co-localisation of the tight junction (TJ) proteins ZO-1 and occludin. However, we observed several modifications in TJ-related genes in response to the probiotics, including the upregulation of transmembrane and cytosolic TJ proteins, as well as TJ signalling proteins. Gene expression modulation was strain- and time-dependent, with a greater number of differentially expressed genes and higher fold-change being observed in the L. plantarum ST-III group and at the latter timepoint. Further studies to investigate how the observed gene expression changes can lead to enhanced barrier function will aid in the development of probiotic foods to help improve intestinal barrier function.

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Introduction: BTBD8 has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of BTBD8 in normal development and IBD pathogenesis remains unknown. Methods: We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and Btbd8 knockout (KO) mice for seven consecutive days to induce IBD. Subsequently, we further examined whether Btbd8 KO affects intestinal barrier and inflammation. Results: We demonstrated that Btbd8 deficiency partially protects mice from DSS-induced IBD, even though no obvious phenotypes were observed in Btbd8 KO mice. Btbd8 deletion leads to strengthened tight junctions between intestinal epithelial cells, elevated intestinal stem cell activity, and enhanced mucus layer. All these three mechanisms work together to improve the intestinal barrier integrity in Btbd8 KO mice. In addition, Btbd8 deficiency mitigates inflammation by reducing the expression of IL-1ß and IL-6 by macrophages. Discussion: Our studies validate the crucial role of Btbd8 in IBD pathogenesis, and reveal that Btbd8 deficiency may ameliorate DSS-induced IBD through improving the intestinal barrier integrity, as well as suppressing inflammatory response mediated by macrophages. These findings suggest that Btbd8 could be a promising therapeutic target for the treatment of IBD.

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Ulcerative colitis is a common type of inflammatory bowel disease that affects millions of individuals around the world. Traditional UC treatment has focused on suppressing immune responses rather than treating the underlying causes of UC, which include oxidative stress, inflammation, and microbiota dysbiosis. Diosmin (DIO), a naturally occurring flavonoid, possesses antioxidant and anti-inflammatory properties. This study aimed to assess the efficacy of DIO in treating dextran-sulfate sodium (DSS)-induced colitis, and to investigate some of its underlying mechanisms, with an emphasis on Akkermansia muciniphila abundance, inflammatory markers, and intestinal barrier function. C57BL/6 mice were given 4% (w/v) DSS to induce colitis. DSS-induced mice were administered DIO (100 and 200 mg/kg) or sulfasalazine orally for 7 days. Every day, the disease activity index (DAI) was determined by recording body weight, diarrhea, and bloody stool. Changes in fecal A. muciniphila abundance, colonic MUC1 and MUC2 expression, as well as oxidative stress and inflammatory markers were all assessed. Histopathological changes, colonic PIK3PR3 and ZO-1 levels, and immunohistochemical examinations of occludin and claudin-1, were investigated. DIO administration resulted in a dose-dependent decrease in DAI, as well as increase in A. muciniphila abundance and MUC2 expression while decreasing MUC1 expression. DIO also dramatically reduced colonic oxidative stress and inflammation by regulating the NF-κB and Nrf2 cascades, restored intestinal barrier integrity by inhibiting PIK3R3 and inducing ZO-1, and improved occludin/claudin-1 gene expression and immunostaining. This study provides the first evidence that DIO preserves intestinal barrier integrity and increases A. muciniphila abundance in DSS-induced colitis. However, more research is required to explore the impact of DIO on the overall composition and diversity of the gut microbiota. Likewise, it will be important to fully understand the molecular mechanisms by which A. muciniphila maintains intestinal barrier function and its potential use as an adjuvant in the treatment of UC.

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Human milk oligosaccharides (HMOs) can modulate the intestinal barrier and regulate immune cells to favor the maturation of the infant intestinal tract and immune system, but the precise functions of individual HMOs are unclear. To determine the structure-dependent effects of individual HMOs (representing different structural classes) on the intestinal epithelium as well as innate and adaptive immune cells, we assessed fucosylated (2'FL and 3FL), sialylated (3'SL and 6'SL) and neutral non-fucosylated (LNT and LNT2) HMOs for their ability to support intestinal barrier integrity, to stimulate the secretion of chemokines from intestinal epithelial cells, and to modulate cytokine release from LPS-activated dendritic cells (DCs), M1 macrophages (MØs), and co-cultures with naïve CD4+ T cells. The fucosylated and neutral non-fucosylated HMOs increased barrier integrity and protected the barrier following an inflammatory insult but exerted minimal immunomodulatory activity. The sialylated HMOs enhanced the secretion of CXCL10, CCL20 and CXCL8 from intestinal epithelial cells, promoted the secretion of several cytokines (including IL-10, IL-12p70 and IL-23) from LPS-activated DCs and M1 MØs, and increased the secretion of IFN-γ and IL-17A from CD4+ T cells primed by LPS-activated DCs and MØs while reducing the secretion of IL-13. Thus, 3'SL and 6'SL supported Th1 and Th17 responses while reducing Th2 responses. Collectively, our data show that HMOs exert structure-dependent effects on the intestinal epithelium and possess immunomodulatory properties that confer benefits to infants and possibly also later in life.

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SCOPE: Manno-oligosaccharides from cassia seed gum (CMOS) have demonstrated anti-inflammatory and regulatory effects on cholesterol metabolism. However, their protective effects against the progression of atherosclerosis (AS) and underlying molecular mechanisms have not been investigated. This study investigates the anti-atherosclerotic effects of CMOS on ApoE-/- mice. METHODS AND RESULTS: CMOS are supplemented in atherosclerotic male ApoE-/- mice fed with a high-fat-high-cholesterol diet (HFHCD). After the 12-week intervention, CMOS at 1200 mg kg-1 ·bw d-1 significantly decrease the atherosclerotic lesion area by 0.63-fold and the aortic arch lesion size by 0.63-fold when compared to the HFHCD group. Moreover, inflammation in atherosclerotic lesions is reduced by CMOS intervention, and the levels of serum lipids and inflammatory cytokines are decreased. The number of goblet cells and the expression of intestinal epithelial tight junction proteins in the H-CMOS group increase, thus indicating that CMOS can restore intestinal barrier integrity in atherosclerotic mice. Furthermore, CMOS reshape the unbalanced gut microbiota in ApoE-/- mice caused by HFHCD, and reduce the relative abundance of Desulfovibrio and Faecalibaculum that exhibits positive relationships with inflammation. CONCLUSION: CMOS inhibit inflammation, alter intestinal barrier integrity, and regulate gut microbiota to attenuate AS in ApoE-/- mice.

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Oxidative stress and intestinal inflammation are main pathological features of ulcerative colitis (UC). Ferroptosis, characterized by iron accumulation and lipid peroxidation, is closely related to the pathologic process of UC. 16S rRNA sequencing for intestinal microbiota analysis and gas chromatography-mass spectrometry (GC-MS) for short-chain fatty acid (SCFA) contents clearly demonstrated lower amounts of butyrate-producing bacteria and butyrate in colitis mice. However, the precise mechanisms of sodium butyrate (NaB) in treating UC remain largely unclear. We found that ferroptosis occurred in colitis models, as evidenced by the inflammatory response, intracellular iron level, mitochondria ultrastructural observations and associated protein expression. NaB inhibited ferroptosis in colitis, significantly rescued weight loss and colon shortening in mice and reduced inflammatory lesions and mitochondrial damage. Furthermore, NaB improved intestinal barrier integrity and markedly suppressed the expression of pro-ferroptosis proteins. Conversely, the protein expression of anti-ferroptosis markers including nuclear factor erythroid-related Factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4), was significantly upregulated with NaB treatment. Moreover, the knockdown of Nrf2 reversed the anti-colitis effect of NaB. Taken together, NaB exhibited a protective effect by ameliorating ferroptosis in experimental colitis through Nrf2/GPX4 signaling and improving intestinal barrier integrity, which provides a novel mechanism for NaB prevention of UC.

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Parameters correlated with age and mortality in Drosophila melanogaster include decreased negative geotaxis and centrophobism behaviors, decreased climbing and walking speed, and darkened pigments in oenocytes and eye. Cessation of egg laying predicts death within approximately 5 days. Endogenous green fluorescence in eye and body increases hours prior to death. Many flies exhibit erratic movement hours before death, often leading to falls. Loss of intestinal barrier integrity (IBI) is assayed by feeding blue dye ("Smurf" phenotype), and Smurf flies typically die within 0-48 h. Some studies report most flies exhibit Smurf, whereas multiple groups report most flies die without exhibiting Smurf. Transgenic reporters containing heat shock gene promoters and innate immune response gene promoters progressively increase expression with age, and partly predict remaining life span. Innate immune reporters increase with age in every fly, prior to any Smurf phenotype, in presence or absence of antibiotics. Many flies die on their side or supine (on their back) position. The data suggest three mechanisms for death of Drosophila. One is loss of IBI, as revealed by Smurf assay. The second is nervous system malfunction, leading to erratic behavior, locomotor malfunction, and falls. The aged fly is often unable to right itself after a fall to a side-ways or supine position, leading to inability to access the food and subsequent dehydration/starvation. Finally, some flies die upright without Smurf phenotype, suggesting a possible third mechanism. The frequency of these mechanisms varies between strains and culture conditions, which may affect efficacy of life span interventions.

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Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), can affect the entire gastrointestinal tract and mucosal layer and lead to intestinal damage and intestinal dysfunction. IBD is an inflammatory disease of the gastrointestinal tract that significantly impacts public health development. Monoclonal antibodies and other synthetic medications are currently used to treat IBD, but they are suspected of producing serious side effects and causing a number of other problems with long-term use. Numerous in vitro and in vivo studies have shown that organic macromolecules from plants and animals have an alleviating effect on IBD-related problems, and many of them are also capable of altering enzymatic function, reducing oxidative stress, and inhibiting the production of cytokines and release of proinflammatory transcriptional factors. Thus, in this paper, the natural products with potential anti-IBD activities and their mechanism of action were reviewed, with a focus on the protective effects of natural products on intestinal barrier integrity and the regulation of tight junction protein expression and remodeling. In conclusion, the insights provided in the present review will be useful for further exploration and development of natural products for the treatment of IBD.

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Bacteroides as potential probiotics has several health benefits to the host, but its practical application faces many challenges due to its inherent properties. In this study, Bacteroides strains isolated from human feces alleviated colonic inflammation in mice, as evidenced by increased colon length and reduced tissue damage. Further study showed that anti-inflammation activity of Bacteroides strains was disturbed by dietary fiber deficiency (FD), which disrupted the balance between gut microbiota and colonic mucus layer, leading to a thinning of colonic mucus layer. A combination of Bacteroides strains and Undaria pinnatifida fucoidan (UPF) better alleviated colonic inflammation than either of them, including increases in the densities of goblet cells and glycoproteins and reduction in intestinal epithelial damage, pro-inflammatory cytokines and oxidative stress. The underlying mechanisms can be attributed to that UPF-induced alterations of mucosal microbiota cannot only directly benefit host health but also create an ecological condition that facilitates Bacteroides strains exert their healthy properties. In addition, both Bacteroides strains and UPF improved FD-induced lipid metabolism abnormality, mainly involving glycerophospholipid metabolism pathway. This study suggests that the application of Bacteroides has certain limitations, and UPF can be developed as a probiotic adjuvant for Bacteroides to enhance human health.

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BACKGROUND: Ventricular remodeling is the adaptive process in which the heart undergoes changes due to stress, leading to heart failure (HF). The progressive decline in cardiac function is considered to contribute to intestinal barrier impairment. LuQi Formula (LQF) is a traditional Chinese medicine preparation widely used in the treatment of ventricular remodeling and HF. However, the role of LQF in the impairment of intestinal barrier function induced by ventricular remodeling remains unclear. MATERIALS AND METHODS: Ventricular remodeling was induced in rats by permanently ligating the left anterior descending branch coronary artery, and cardiac function indexes were assessed using echocardiography. Heart and colon tissue morphology were observed by hematoxylin-eosin, Masson's trichrome and Alcian Blue Periodic acid Schiff staining. Myocardial cell apoptosis was detected using TUNEL and immunohistochemistry. Circulatory levels of brain natriuretic peptide (BNP), intestinal permeability markers endotoxin, D-lactate and zonulin, as well as inflammatory cytokines tumor necrosis factor alpha and interleukin-1 beta were measured by Enzyme-linked immunosorbent assay. Expression levels of tight junction (TJ) proteins and hypoxia-inducible factor-1 alpha (HIF-1α) in colon tissue were detected by immunofluorescence, immunohistochemistry and western blotting. Cardiac function indexes and intestinal permeability markers of patients with HF were analyzed before and after 2-4 months of LQF treatment. RESULTS: LQF protected cardiac function and alleviated myocardial fibrosis and apoptosis in rats with ventricular remodeling. LQF protected the intestinal barrier integrity in ventricular remodeling rats, including maintaining colonic tissue morphology, preserving the number of goblet cells and normal expression of TJ proteins. Furthermore, LQF upregulated the expression of HIF-1α protein in colon tissue. Intervention with a HIF-1α inhibitor weakened the protective effect of LQF on intestinal barrier integrity. Moreover, a reduction of HIF-1α aggravated ventricular remodeling, which could be alleviated by LQF. Correspondingly, the circulating levels of intestinal permeability markers and BNP in HF patients were significantly decreased, and cardiac function markedly improved following LQF treatment. CONCLUSIONS: We demonstrated that LQF effectively protected cardiac function by preserving intestinal barrier integrity caused by ventricular remodeling, at least partially through upregulating HIF-1α expression.

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BACKGROUND: Intestinal barrier dysfunction plays a central role in the pathological onset of Crohn's disease. We identify the cadherin superfamily member protocadherin 20 (PCDH20) as a crucial factor in Crohn's disease. Here we describe the function of PCDH20 and its mechanisms in gut homeostasis, barrier integrity, and Crohn's disease development. RESULTS: PCDH20 mRNA and protein expression is significantly downregulated in the colonic epithelium of Crohn's disease patients and mice with induced colitis compared with controls. In mice, intestinal-specific Pcdh20 knockout causes defects in enterocyte proliferation and differentiation, while causing morphological abnormalities. Specifically, the deletion disrupts barrier integrity by unzipping adherens junctions via ß-catenin regulation and p120-catenin phosphorylation, thus aggravating colitis in DSS- and TNBS-induced colitis mouse models. Furthermore, we identify activating transcription factor 6 (ATF6), a key chaperone of endoplasmic reticulum stress, as a functional downstream effector of PCDH20. By administering a selective ATF6 activator, the impairment of intestinal barrier integrity and dysregulation of CHOP/ß-catenin/p-p120-catenin pathway was reversed in Pcdh20-ablated mice with colitis and PCDH20-deficient colonic cell lines. CONCLUSIONS: PCDH20 is an essential factor in maintaining intestinal epithelial homeostasis and barrier integrity. Specifically, PCDH20 helps to protect against colitis by tightening adherens junctions through the ATF6/CHOP/ß-catenin/p-p120-catenin axis.

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BACKGROUND: The elevated circulating toxins secondary to the impairment of intestinal barrier integrity commonly elicit a chronic inflammatory response and finally contribute to multiple diseases. These toxins, including bacterial by-products and heavy metals, are the potent risk factors for the development of recurrent spontaneous abortion (RSA). Preclinical evidence suggests that several dietary fibers can restore intestinal barrier function and decrease the accumulation of heavy metals. However, it is uncertain whether treatment with a newly developed blend of dietary fibers product (Holofood) benefits patients with RSA. METHODS: In this trial, we enrolled 70 adult women with RSA, who were randomly assigned into the experiment group and the control group in a 2:1 ratio. Upon the basis of conventional therapy, subjects in the experiment group (n = 48) received 8 weeks oral administration with Holofood three times daily at a dose of 10 g each time. Subjects without Holofood consumption were set as the control (n = 22). Blood samples were collected for the determinations of metabolic parameters, heavy mental lead, and the indices related to intestinal barrier integrity (D-lactate, bacterial endotoxin, and diamine oxidase activity). RESULTS: The reduction amplitude in blood lead from baseline to week 8 was 40.50 ± 54.28 (µg/L) in the experiment group as compared with 13.35 ± 36.81 (µg/L) in the control group (P = 0.037). The decreased level of serum D-lactate from baseline to week 8 was 5.58 ± 6.09 (mg/L) in the experiment group as compared with - 2.38 ± 8.90 (mg/L, P < 0.0001) in the control group. The change in serum DAO activity from baseline to week 8 was 3.26 ± 2.23 (U/L) in the experiment group as compared with - 1.24 ± 2.22 (U/L, P < 0.0001) in the control group. Participants who received Holofood had a greater decline in blood endotoxin from baseline to week 8 than those in the control group. Moreover, by comparing with the self-baseline, Holofood consumption significantly decreased the blood levels of lead, D-lactate, bacterial endotoxin, and DAO activity. CONCLUSION: Our results suggest that Holofood affords a clinically relevant improvements in blood lead level and intestinal barrier dysfunction in patients with RSA.

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The aim of this research was to investigate potential new biomarkers which could be used in the clinical practice of ulcerative colitis (UC). Given the crucial role of intestinal barrier integrity and inflammation in the pathogenesis of UC, the serum profile of proteins linked to intestinal barrier and pro-inflammatory neutrophil products may be useful in diagnosing and monitoring the activity of the disease. We measured serum levels of proguanylin (pro-GN), S100A12, and pentraxin 3 (PTX3) in 31 patients with UC before and after a year of biological treatment, as well as in 20 healthy individuals. Significant differences in the serum profiles of pro-GN (5.27 vs. 11.35, p < 0.001), S100A12 (39.36 vs. 19.74, p < 0.001) and PTX3 (3197.05 vs. 1608.37, p < 0.001) were observed between pre-treatment patients with UC and healthy individuals. Furthermore, in UC patients prior to treatment, the levels of S100A12 (p < 0.0005; r = 0.628) and PTX3 (p < 0.05; r = 0.371) were correlated with disease activity as measured by the Mayo scale. Following a year of biological treatment with adalimumab, the concentration of pro-GN significantly increased (5.27 vs. 6.68, p < 0.005) in the blood of UC patients, while the level of PTX-3 decreased (3197.05 vs. 1946.4, p < 0.0001). Our study demonstrates the usefulness of pro-GN, S100A12, and PTX3 measurements in diagnosing and monitoring the activity of UC.

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Velvet antler is a precious traditional Chinese medicine used for thousands of years. This study investigated the anti-colitis effects of water extracts of Formosan sambar deer (SVAE) and red deer (RVAE) to identify the possible mechanisms and the bioactive compounds using a dextran sulfate sodium (DSS)-induced colitis mouse model. The mechanism of action and the ameliorating effects of SVAE and RVAE on DSS-induced colitis were evaluated using a mouse model. Ultra-high performance liquid chromatography-mass/mass and gas chromatography-mass/mass were applied to identify the bioactive components of the SVAE and RVAE water extracts. The results revealed that both high-dose SVAE and RVAE could ameliorate the symptoms of colitis due to reduced systemic inflammatory responses, enhanced intestinal barrier integrity by restoration of tight junction proteins, and improved gut dysbiosis. The potentially bioactive components of SVAE and RVAE were identified as small molecules (<3 kDa). Further identification by untargeted metabolomics analysis suggested that l-carnitine, hypoxanthine, adrenic acid, creatinine, gamma-aminobutyric-lysine, oleic acid, glycine, poly-γ-glutamic acid, and eicosapentaenoic acid in VAWEs might be involved in ameliorating the symptoms of colitis. This study provided evidence for the potential usage of SVAE and RVAE as anti-colitis agents.

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Complementary and alternative medicine has the potential to enrich conventional therapy to improve the treatment of various diseases. Patients that suffer from inflammatory bowel disease, which requires a constant need for medication, have to deal with the adverse effects of repeated application. Natural products such as Epigallocatechin-3-gallate (EGCG) possess the potential to improve symptoms of inflammatory diseases. We investigated the efficacy of EGCG on an inflamed co-culture model simulating IBD and compared it to the efficacies of four commonly applied active pharmaceutical ingredients. EGCG (200 µg/mL) strongly stabilized the TEER value of the inflamed epithelial barrier to 165.7 ± 4.6% after 4 h. Moreover, the full barrier integrity was maintained even after 48 h. This corresponds to the immunosuppressant 6-Mercaptopurin and the biological drug Infliximab. The EGCG treatment significantly decreased the release of the pro-inflammatory cytokines IL-6 (to 0%) and IL-8 (to 14.2%), similar to the effect of the corticosteroid Prednisolone. Therefore, EGCG has a high potential to be deployed as complementary medicine in IBD. In future studies, the improvement of EGCG stability is a key factor in increasing the bioavailability in vivo and fully harnessing the health-improving effects of EGCG.

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This study was conducted to investigate the effects of supplementing different ratios of phytogenic feed additives (PFA) to weaned pigs challenged with pathogenic Escherichia coli on growth performance, nutrient digestibility, intestinal barrier integrity, and immune response, and to determine the optimal mixing ratio for post-weaning diarrhea (PWD) prevention. A total of 48 4-wk-old weaned pigs with initial body weight of 8.01 ± 0.39 kg were placed in individual metabolic cages, and then randomly assigned to eight treatment groups. The eight treatments were as follows: a basal diet without E. coli challenge (negative control, NC), a basal diet with E. coli challenge (positive control, PC), PC with supplementing 0.1% mixture of 20% bitter citrus extract (BCE), 10% microencapsulated blend of thymol and carvacrol (MEO), and 70% excipient (T1), PC with supplementing 0.1% mixture of 10% MEO, 20% premixture of grape seed and grape marc extract, green tea, and hops (PGE), and 60% excipient (T2), PC with supplementing 0.1% mixture of 10% BCE, 10% MEO, 10% PGE, and 70% excipient (T3), PC with supplementing 0.1% mixture of 20% BCE, 20% MEO, and 60% excipient (T4), PC with supplementing 0.1% mixture of 20% MEO, 20% PGE, and 60% excipient (T5), and PC with supplementing 0.1% mixture of 10% BCE, 20% MEO, 10% PGE, and 60% excipient (T6). The experiments progressed in 16 days, including 5 days before and 11 days after the first E. coli challenge (day 0). In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F 18 for three consecutive days from day 0 postinoculation (PI). Compared with the PC group, the PFA2 and PFA6 groups significantly increased (P < 0.05) feed efficiency and decreased (P < 0.05) diarrhea during the entire period. At day 11 PI, the PFA6 group significantly improved (P < 0.05) gross energy digestibility compared to the PFA1 group. The PFA6 group significantly decreased (P < 0.05) tumor necrosis factor α (TNF-α) and interleukin-6 in serum and increased (P < 0.05) the villus height to crypt depth ratio (VH:CD). The PFA2 significantly decreased (P < 0.05) the relative protein expression of calprotectin in the ileum. In conclusion, improvements in growth performance, diarrhea reduction, and immunity enhancement are demonstrated when 10% BCE, 20% MEO, 10% PGE, and 60% excipient are mixed.

Phytogenic feed additives (PFA) include various herbs and spices, such as essential oils and polyphenols. Flavonoids and polyphenols contained in PFA are generally known to have antioxidant and antibacterial actions and based on this, PFA is considered an alternative to antibiotics in the swine industry. Pathogenic Escherichia coli infection is one of the most important causes of post-weaning diarrhea (PWD) in pigs. PWD causes intestinal damage, which leads to severe diarrhea, reduced growth performance, and mortality in weaned pigs, resulting in significant financial loss to the swine industry. Therefore, this study was conducted to investigate the effects of supplementing different ratios of PFA to weaned pigs challenged with E. coli and determine the optimal mixing ratio for PWD prevention. Our study results showed that growth performance was improved when supplementing a mixture of 10% bitter citrus extract (BCE), 20% microencapsulated blend of thymol and carvacrol (MEO), 10% premixture of grape seed and grape marc extract, green tea, and hops (PGE), and 60% excipient. Also, the effect of improving the immune response and intestinal morphology was shown. In conclusion, a mixture of 10% BCE, 20% MEO, 10% PGE, and 60% excipients is considered the optimal mixing ratio.

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Grape pomace (GP) is a winemaking by-product particularly rich in (poly)phenols and dietary fiber, which are the main active compounds responsible for its health-promoting effects. These components and their metabolites generated at the intestinal level have been shown to play an important role in promoting health locally and systemically. This review focuses on the potential bioactivities of GP in the intestinal environment, which is the primary site of interaction for food components and their biological activities. These mechanisms include (i) regulation of nutrient digestion and absorption (GP has been shown to inhibit enzymes such as α-amylase and α-glucosidase, protease, and lipase, which can help to reduce blood glucose and lipid levels, and to modulate the expression of intestinal transporters, which can also help to regulate nutrient absorption); (ii) modulation of gut hormone levels and satiety (GP stimulates GLP-1, PYY, CCK, ghrelin, and GIP release, which can help to regulate appetite and satiety); (iii) reinforcement of gut morphology (including the crypt-villi structures, which can improve nutrient absorption and protect against intestinal damage); (iv) protection of intestinal barrier integrity (through tight junctions and paracellular transport); (v) modulation of inflammation and oxidative stress triggered by NF-kB and Nrf2 signaling pathways; and (vi) impact on gut microbiota composition and functionality (leading to increased production of SCFAs and decreased production of LPS). The overall effect of GP within the gut environment reinforces the intestinal function as the first line of defense against multiple disorders, including those impacting cardiometabolic health. Future research on GP's health-promoting properties should consider connections between the gut and other organs, including the gut-heart axis, gut-brain axis, gut-skin axis, and oral-gut axis. Further exploration of these connections, including more human studies, will solidify GP's role as a cardiometabolic health-promoting ingredient and contribute to the prevention and management of cardiovascular diseases.