Search Results (25)

Background/Objective: Among the inflammatory bowel illnesses, ulcerative colitis (UC) affects 5 million people worldwide. UC manifests as weight loss, rectal bleeding, persistent diarrhea, and abdominal pain. Experimental research focused into the potential benefits of atorvastatin for colitis, although the literature only has a small amount of clinical evidence. To examine atorvastatin’s protective effect in UC patients by assessing its impact on fecal myeloperoxidase, zonulin, and disease activity index (DAI). Methods: Two groups of patients with mild to moderate UC were randomly assigned. Over a six-month period, the control group (placebo group) received a placebo alongside mesalamine (1 g, three times daily [t.i.d.]). The atorvastatin group received atorvastatin (80 mg once daily) in addition to mesalamine (1 g t.i.d.). Disease severity was assessed by a gastroenterologist using the Disease Activity Index (DAI). Serum zonulin and fecal myeloperoxidase levels were measured before and after treatment to assess the biological efficacy of the interventions. Outcomes: Reduction in DAI and biomarker levels. Results: Both groups showed a significant decrease in DAI, zonulin, and fecal myeloperoxidase levels. However, the atorvastatin group (n = 23) demonstrated a significantly greater decrease in zonulin (p = 0.04), fecal myeloperoxidase (p = 0.03), and DAI (p = 0.001) compared to the placebo group (n = 24). In atorvastatin group, a significant correlation was observed between DAI and zonulin (p = 0.007, r = 0.4) and myeloperoxidase (p = 0.02, r = 0.36). Conclusions: The co-administration of atorvastatin may serve as a potential adjunct therapy for patients with UC. Full article

Background/Objectives: The aim of this study was to evaluate potential biomarkers of bacterial translocation (lipopolysaccharide-binding protein (LBP) and soluble CD14 subtype (sCD14-ST)) and intestinal wall damage (intestinal fatty acid binding protein (I-FABP), Zonulin, and regenerating islet-derived protein-3α (REG3α)) in patients with multiple organ dysfunction syndrome (MODS). Methods: The study involved 327 patients divided into two groups: Group 1 comprised 227 patients with MODS (main group), while Group 2 comprised 100 patients with identical pathologies but without MODS (control group). To examine these biomarkers in the blood, venous blood was taken in the control group on the day of admission to the hospital, in patients with MODS on the first day of MODS staging, and later on Days 3 and 7 of its development. Levels of these markers in blood serum were determined by enzyme-linked immunosorbent assays according to the manufacturers’ instructions. Results: In the control group, values of all the investigated markers were lower than in the group of MODS patients (p < 0.0001). In the main group, the mortality rate was 44.9% (n = 102). The values of sCD14-ST on Day 1 and of I-FABP and REG3α on Days 1 and 3 were higher in deceased MODS patients (p < 0.05), while LBP levels on Day 7 were conversely lower in the deceased patients (p = 0.006). SOFA and APACHE II scores were higher in the deceased patients (p < 0.0001). Conclusions: In MODS patients, the increased I-FABP, REG3α, and sCD14-ST but decreased LBP levels may indicate increased intestinal wall permeability and bacterial translocation, which may exacerbate the course of multiple organ dysfunction and increase the risk of mortality. Despite the limitations of this study, the studied potential biomarkers can be considered noteworthy candidates for identifying MODS patients at high risk of mortality. Full article

Background/Objectives: Cow’s milk allergy is one of the most common food allergies in children, and its pathomechanism is still under investigation. Recently, an increasing number of studies have linked food allergy to intestinal barrier dysfunction. The present study aimed to investigate changes in the intestinal microenvironment during the development of β-lactoglobulin (β-lg) allergy under conditions of early intestinal dysfunction. Methods: BALB/c mice received intraperitoneal β-lg with Freund’s adjuvant, followed by oral β-lg while receiving dextran sulphate sodium salt (DSS) in their drinking water (0.2% w/v). The immunized group without DSS and the groups receiving saline, oral β-lg, or DSS served as controls. Results: The study showed that the immunization effect was greater in mice with mild intestinal barrier dysfunction. Although DSS did not affect the mice’s humoral response to β-lg, in combination with β-lg, it significantly altered their cellular response, affecting the induction and distribution of T cells in the inductive and peripheral tissues and the activation of immune mediators. Administration of β-lg to sensitized mice receiving DSS increased disease activity index (DAI) scores and pro-inflammatory cytokine activity, altered the distribution of claudins and zonulin 1 (ZO-1) in the colonic tissue, and negatively affected the balance and activity of the gut microbiota. Conclusions: The research model used appears attractive for studying food allergen sensitization, particularly in relation to the initial events leading to mucosal inflammation and the development of food hypersensitivity. Full article

Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation. Full article

Cancer patients face increased susceptibility to invasive infections, primarily due to ulcerative lesions on mucosal surfaces and immune suppression resulting from chemotherapy. Pseudomonas aeruginosa (P. aeruginosa) bacteremia is notorious for its rapid progression into fatal sepsis, posing a significant threat to cancer patients, particularly those experiencing chemotherapy-induced neutropenia. This bacterial infection contributes significantly to morbidity and mortality rates among such individuals. Our latest report showed the mutually beneficial effects of postbiotic butyrate on 1,25-dihydroxyvitamin D3 (1,25D3)-controlled innate immunity during Salmonella colitis. Hence, we investigated the impact of butyrate and 1,25D3 on chemotherapy-induced gut-derived P. aeruginosa sepsis in mice. The chemotherapy-induced gut-derived P. aeruginosa sepsis model was established through oral administration of 1 × 10⁷ CFU of the P. aeruginosa wild-type strain PAO1 in C57BL/6 mice undergoing chemotherapy. Throughout the infection process, mice were orally administered butyrate and/or 1,25D3. Our observations revealed that the combined action of butyrate and 1,25D3 led to a reduction in the severity of colitis and the invasion of P. aeruginosa into the liver and spleen of the mice. This reduction was attributed to an enhancement in the expression of defensive cytokines and antimicrobial peptides within the cecum, coupled with decreased levels of zonulin and claudin-2 proteins in the mucosal lining. These effects were notably more pronounced when compared to treatments administered individually. This study unveils a promising alternative therapy that involves combining postbiotics and 1,25D3 for treating chemotherapy-induced gut-derived P. aeruginosa sepsis. Full article

Broiler chickens in livestock production face numerous challenges that can impact their health and welfare, including mycotoxin contamination and heat stress. In this study, we aimed to investigate the combined effects of two mycotoxins, deoxynivalenol (DON) and fumonisins (FBs), along with short-term heat stress conditions, on broiler gut health and endotoxin translocation. An experiment was conducted to assess the impacts of mycotoxin exposure on broilers, focusing on intestinal endotoxin activity, gene expression related to gut barrier function and inflammation, and the plasma concentration of the endotoxin marker 3-OH C14:0 either at thermoneutral conditions or short-term heat stress conditions. Independently of heat stress, broilers fed DON-contaminated diets exhibited reduced body weight gain during the starter phase (Day 1–12) compared to the control group, while broilers fed FB-contaminated diets experienced decreased body weight gain throughout the entire trial period (Day 1–24). Furthermore, under thermoneutral conditions, broilers fed DON-contaminated diets showed an increase in 3-OH C14:0 concentration in the plasma. Moreover, under heat stress conditions, the expression of genes related to gut barrier function (Claudin 5, Zonulin 1 and 2) and inflammation (Toll-like receptor 4, Interleukin-1 beta, Interleukin-6) was significantly affected by diets contaminated with mycotoxins, depending on the gut segment. This effect was particularly prominent in broilers fed diets contaminated with FBs. Notably, the plasma concentration of 3-OH C14:0 increased in broilers exposed to both DON- and FB-contaminated diets under heat stress conditions. These findings shed light on the intricate interactions between mycotoxins, heat stress, gut health, and endotoxin translocation in broiler chickens, highlighting the importance of understanding these interactions for the development of effective management strategies in livestock production to enhance broiler health and welfare. Full article

Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of nosocomial infections associated with a high mortality rate and represents a serious threat to human health and the increasing frequency of antimicrobial resistance. Cancer patients are more vulnerable to invasive infection due to ulcerative lesions in mucosal surfaces and immune suppression secondary to chemotherapy. In our in vitro study, we observed that probiotics have the potential to yield beneficial effects on intestinal epithelial cells infected with P. aeruginosa. Additionally, probiotics were found to confer advantageous effects on the innate immunity of mice suffering from Salmonella-induced colitis. As a result, we sought to investigate the impact of probiotics on gut-derived P. aeruginosa sepsis induced by chemotherapy. Following chemotherapy, gut-derived P. aeruginosa sepsis was induced in female C57BL/6 mice aged 6–8 weeks, which were raised under specific-pathogen-free (SPF) conditions in an animal center. Prior to the induction of the sepsis model, the mice were administered 1 × 10⁸ colony-forming units (CFU) of the probiotics, namely Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) via oral gavage. We observed that LGG or BL amplified the inflammatory mRNA expression in mice undergoing chemotherapy and suffering from gut-derived P. aeruginosa sepsis. This led to a heightened severity of colitis, as indicated by histological examination. Meanwhile, there was a notable decrease in the expression of antimicrobial peptide mRNA along with reduced levels of zonulin and claudin-2 protein staining within mucosal tissue. These alterations facilitated the translocation of bacteria to the liver, spleen, and bloodstream. To our astonishment, the introduction of probiotics exacerbated gut-derived P. aeruginosa sepsis in mice undergoing chemotherapy. Conclusively, we must be prudent when using probiotics in mice receiving chemotherapy complicated with gut-derived P. aeruginosa sepsis. Full article

Background: A few studies on pediatric Celiac Disease (CD) are available from Central Asia. Recent immunogenetic research has highlighted that the HLA-DQ2/8 genetic predisposition to CD as well as the dietary intake of gluten in this geographical area, are comparable to other regions of the world where CD prevalence is known to be 1% or higher. Methods: This is a prospective and cross-sectional study investigating the prevalence and clinical characteristics of CD in symptomatic children referred to the pediatric gastroenterology department of a tertiary hospital in Uzbekistan from 1 September 2021, until 31 July 2022. In addition to collecting the relevant information related to clinical manifestations and laboratory analyses from the clinical files, a specific survey was also administered to patients’ guardians. Serological, histopathological, and immunogenetic parameters specific to CD, fecal zonulin, and pancreatic elastases were assessed in CD patients. Results: The study population consisted of 206 children. Overall, almost all of them (n = 192; 93.2%) were referred because of gastrointestinal manifestations, which were associated with extra-gastrointestinal manifestations in most cases (n = 153; 74.3%); a minority (n = 14; 6.8%) was mainly referred due short stature and/or growth failure only. Among all of these study participants, CD was diagnosed in 11 children (5.3%). Notably, although diarrhea was similarly reported in CD and non-CD patients, watery diarrhea (type 7 according to the Bristol stool scale) was much more frequently and significantly observed in the former group. All of these CD patients showed anti-tTG IgA 10 times higher than the upper normal limit, except one child with lower serum levels of total IgA; however, all of them received a diagnostic confirmation by histopathological analysis due to the lack of EMA testing in the country. Notably, most CD children (82%) showed a Marsh III histological grading. Around half patients (54.5%) showed zonulin values above the reference range, whereas none showed insufficient levels of pancreatic elastase. However, no correlation or association between zonulin and clinical, laboratory, histopathological, and immunogenetic parameters was found. Conclusions: This study may further suggest a relevant prevalence of CD in Uzbek children, based on this partial picture emerging from symptomatic patients only. Additionally, we highlighted the prevalence of typical CD forms with watery diarrhea, which should strongly support a full diagnostic work-up for CD in the local clinical setting. The high levels of anti-tTG IgA and high Marsh grade might also lead us to speculate a significant diagnostic delay despite the classical clinical expression of CD. Full article

The relationship between dysbiosis and central nervous diseases has been proved in the last 10 years. Microbial alterations cause increased intestinal permeability, and the penetration of bacterial fragment and toxins induces local and systemic inflammatory processes, affecting distant organs, including the brain. Therefore, the integrity of the intestinal epithelial barrier plays a central role in the microbiota–gut–brain axis. In this review, we discuss recent findings on zonulin, an important tight junction regulator of intestinal epithelial cells, which is assumed to play a key role in maintaining of the blood–brain barrier function. In addition to focusing on the effect of microbiome on intestinal zonulin release, we also summarize potential pharmaceutical approaches to modulate zonulin-associated pathways with larazotide acetate and other zonulin receptor agonists or antagonists. The present review also addresses the emerging issues, including the use of misleading nomenclature or the unsolved questions about the exact protein sequence of zonulin. Full article

Rodent models may help investigations on the possible link between autism spectrum disorder (ASD) and gut microbiota since autistic patients frequently manifested gastrointestinal troubles as co-morbidities. Thirty young male rats were divided into five groups: Group 1 serves as control; Group 2, bee pollen and probiotic-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism; Group 4 and Group 5, the protective and therapeutic groups were given bee pollen and probiotic combination treatment either before or after the neurotoxic dose of PPA, respectively. Serum occludin, zonulin, lipid peroxides (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX), catalase, and gut microbial composition were assessed in all investigated groups. Recorded data clearly indicated the marked elevation in serum occludin (1.23 ± 0.15 ng/mL) and zonulin (1.91 ± 0.13 ng/mL) levels as potent biomarkers of leaky gut in the PPA- treated rats while both were normalized to bee pollen/probiotic-treated rats. Similarly, the high significant decrease in catalase (3.55 ± 0.34 U/dL), GSH (39.68 ± 3.72 µg/mL), GST (29.85 ± 2.18 U/mL), and GPX (13.39 ± 1.54 U/mL) concomitant with a highly significant increase in MDA (3.41 ± 0.12 µmoles/mL) as a marker of oxidative stress was also observed in PPA-treated animals. Interestingly, combined bee pollen/probiotic treatments demonstrated remarkable amelioration of the five studied oxidative stress variables as well as the fecal microbial composition. Overall, our findings demonstrated a new approach to the beneficial use of bee pollen and probiotic combination as a therapeutic intervention strategy to relieve neurotoxic effects of PPA, a short-chain fatty acid linked to the pathoetiology of autism. Full article

Our recent report illustrated the unitedly advantageous effects of postbiotic butyrate on active vitamin D3 (VD3)-orchestrated innate immunity in Salmonella colitis. There is growing awareness that aryl hydrocarbon receptor (AhR) can regulate intestinal immunity and barrier function, through modulating cecal inflammation and junction proteins expression. Hence, we researched the participation of AhR-regulated tight junction functions on the united effects of butyrate and VD3 on intestinal defense to Salmonella infection. Salmonella colitis model were elicited by oral gavage with 1 × 10⁸ CFU of a S. typhimurium wild-type strain SL1344 in C57BL/6 mice. Before and after the colitis generation, mice were fed with butyrate and/or VD3 by oral gavage in the absence or presence of intraperitoneal injection of AhR inhibitor for 4 and 7 days, respectively. We observed that butyrate and VD3 could concert together to reduce the invasion of Salmonella in colitis mice by enhancing cecal cytokines and antimicrobial peptides expression and reducing zonulin and claudin-2 protein expressions in mucosal stain, compared to single treatment, which were counteracted by AhR inhibitor. It implies that AhR is involved in the united effects of butyrate and VD3 on the intestinal defense to Salmonella infection in colitis mice. This study discloses the promising alternative therapy of combining postbiotic and VD3 for invasive Salmonellosis and the pivotal role of AhR pathway. Full article

Helichrysum italicum (Roth) G. Don (HI) and Helichrysum arenarium (L.) Moench (HA) are rich in polyphenols and their infusions have beneficial effects for patients with metabolic syndrome. To investigate whether these effects are mediated by the gut microbiota, we analysed the effects of daily consumption of HI or HA infusion on the composition of gut microbiota, inflammatory status, and zonulin, a marker of gut barrier permeability. The study was a randomized, double-blind comparative trial. Thirty participants were randomly assigned to two groups and received either HA or HI tea filter bags, each containing 1 g of dried plant material, for daily consumption lasting 4 weeks. The results show that consumption of both infusions resulted in a reduction of some genera belonging to Firmicutes and in a slight but significant reduction in Shannon diversity index. Consumption of HI infusion significantly reduced serum levels of proinflammatory markers and zonulin alongside with the observed trend of Proteobacteria reduction. It can therefore be concluded that the HI and HA infusions could act as prebiotics and thus improve the intestinal environment. In addition, HI infusion has a positive impact on microbial dysbiosis and gut barrier dysfunction that occur in obesity and metabolic syndrome. Full article

(1) Background: The aim of this study was to assess the impact of multi-strain probiotic supplementation on the physical capacity and selected health indicators related to the exercise capacity of competitive road cyclists such as body composition, markers of intestinal permeability, pro- and anti-inflammatory markers, and anti-/pro-oxidant potential. (2) Methods: The group comprised 26 competitive road cyclists aged between 18 and 26. The study was a 4-month double-blind, random-assignment, parallel-group, and placebo-controlled trial. The measurements of physical capacity in the exercise tests of the anaerobic Wingate test (the level of total work volume, maximal anaerobic power, average power per revolution, mean time to achieve maximal anaerobic power, and time to maintain maximal anaerobic power) and the aerobic test using a cycle ergometer (maximum oxygen uptake, exercise duration, maximum load power, and maximal heart rate) were repeated after one, three, and four months. (3) Results: The probiotic supplementation resulted in increased levels of the relative magnitude of maximal oxygen uptake (65.28 vs. 69.18), the duration of training until failure (14.35 vs. 15.65), the load on the ergometer (5.11 vs. 5.36), and the degree of decrease in heart rate (193.3 vs. 188.6) together with a feeling of less discomfort during the exercise test (Borg scale) (19.38 vs. 18.43), confirming the beneficial effect of probiotics on the cyclists’ aerobic capacity during exercise. The probiotic supplementation produces no effects on the anaerobic capacity and body composition of the athletes, except for an observed increase in muscle mass. The concentration of zonulin in the stool mass decreased as a result of the probiotic therapy (81.2 vs. 25.21), and α1-atitrypsin was maintained at a similar level during the experiment (0.95 vs. 1.05), indicating a sealing of the intestinal barrier and beneficial changes in the cyclists’ intestinal function. The supplementation resulted in a reduction in the concentrations of: tumor necrosis factor TNF-α after the aerobic (13.88 vs. 9.75) and anaerobic tests (8.54 vs. 6.8), IL-6 before (1.2 vs. 0.86) and after the anaerobic test (1.47 vs. 0.97), IL-10 before the anaerobic test (0.70 vs. 0.44), and the total oxidative status (TOS) of the blood plasma before (663.7 vs. 484.6) and after the anaerobic test (643.1 vs. 435.9). (4) Conclusions: The probiotic supplementation resulted in increased levels of the cyclists’ aerobic capacity and their maintenance of anaerobic capacity and positively affected selected health indicators related to the exercise capacity of competitive road cyclists. Full article

(1) Background: The gut microbiota might play a part in affecting athletic performance and is of considerable importance to athletes. The aim of this study was to search the recent knowledge of the protagonist played by high-intensity and high-duration aerobic exercise on gut microbiota composition in athletes and how these effects could provide disadvantages in sports performance. (2) Methods: This systematic review follows the PRISMA guidelines. An exhaustive bibliographic search in Web of Science, PubMed, and Scopus was conducted considering the articles published in the last 5 years. The selected articles were categorized according to the type of study. The risk of bias was assessed using the Joanna Briggs Institute’s Critical Appraisal Tool for Systematic Reviews. (3) Results: Thirteen studies had negative effects of aerobic exercise on intestinal microbiota such as an upsurge in I-FABP, intestinal distress, and changes in the gut microbiota, such as an increase in Prevotella, intestinal permeability and zonulin. In contrast, seven studies observed positive effects of endurance exercise, including an increase in the level of bacteria such as increased microbial diversity and increased intestinal metabolites. (4) Conclusions: A large part of the studies found reported adverse effects on the intestinal microbiota when performing endurance exercises. In studies carried out on athletes, more negative effects on the microbiota were found than in those carried out on non-athletic subjects. Full article

Celiac disease (CD) comprises over 1% of the world’s population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines. Full article