Biomarker Of Intestinal Permeability Research Articles

Study of fatty acid-binding protein and Bacteroidetes and Firmicutes levels in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus and small intestinal bacterial overgrowth syndrome

The aim of the study was to examine serum levels of liver and intestinal fatty acid-binding proteins (L-FABP and I-FABP), fecal numbers of Bacteroidetes (B) and Firmicutes (F) in patients with metabolic-associated fatty liver disease (MAFLD) in combination with type 2 diabetes mellitus (Т2DM) and small intestinal bacterial overgrowth (SIBO) syndrome. Materials and methods. The prospective, interventional, randomized study included 51 patients with MAFLD in combination with Т2DM, who were examined and divided into 2 groups. Group 1 consisted of 24 patients with MAFLD and Т2DM without SIBO. Group 2 was comprised of 27 patients with MAFLD in combination with Т2DM and SIBO. The control group included 20 apparently healthy individuals. Serum levels of L-FABP and I-FABP were measured by ELISA method using the Human L-FABP and I-FABP ELISA Kit test systems, respectively (Elabscience, USA). Fecal numbers of B and F were determined by real-time PCR. Bacterial DNA was detected in a thermal cycler Rotor-Gene 6000 (QIAGEN, Germany) using DNA 16S rRNA primers and NanoDrop ND-8000 reagents (Thermo Scientific, USA). Results. To assess the state of intestinal permeability, serum levels of L-FABP and I-FABP were examined and numbers of phylum F and В as well as their ratio were calculated. Patients of both groups have been found to have increased serum levels of L-FABP, I-FABP, numbers of B in fecal samples and decreased numbers of F and F/B ratio. Conclusions. The study results obtained have revealed increased intestinal permeability and demonstrated an important diagnostic value of serum L-FABP and I-FABP as a biomarker of intestinal permeability in diabetic MAFLD patients with or without SIBO. Increased fecal numbers of Bacteroidetes, decreased numbers of Firmicutes and F/B ratio have been detected in diabetic MAFLD patients with or without SIBO.

Dark Chocolate Intake Positively Modulates Gut Permeability in Elite Football Athletes: A Randomized Controlled Study.

Gut barrier disruption can lead to enhanced intestinal permeability, which allows endotoxins, pathogens, and other proinflammatory substances to move through the intestinal barrier into circulation. Intense exercise over a prolonged period increases intestinal permeability, which can be further worsened by the increased production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The aim of this study was to assess the degree of intestinal permeability in elite football players and to exploit the effect of cocoa polyphenols on intestinal permeability induced by intensive physical exercise. Biomarkers of intestinal permeability, such as circulating levels of zonulin, a modulator of tight junctions, occludin, a tight junction protein, and LPS translocation, were evaluated in 24 elite football players and 23 amateur athletes. Moreover, 24 elite football players were randomly assigned to either a dark chocolate (>85% cocoa) intake (n = 12) or a control group (n = 12) for 30 days in a randomized controlled trial. Biochemical analyses were performed at baseline and after 30 days of chocolate intake. Compared to amateur athletes, elite football players showed increased intestinal permeability as indicated by higher levels of zonulin, occludin, and LPS. After 30 days of dark chocolate intake, decreased intestinal permeability was found in elite athletes consuming dark chocolate. In the control group, no changes were observed. In vitro, polyphenol extracts significantly improved intestinal damage in the human intestinal mucosa cell line Caco-2. These results indicate that chronic supplementation with dark chocolate as a rich source of polyphenols positively modulates exercise-induced intestinal damage in elite football athletes.

Assessing the diagnostic value of zonulin as a biomarker for intestinal permeability in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus

The aim of the study was to assess the diagnostic value of serum zonulin concentrations in patients with metabolic-associated fatty liver disease (МAFLD) in combination with type 2 diabetes mellitus (T2DM). Materials and methods. The study involved 93 patients with MAFLD in combination with T2DM, who were examined and allocated to two groups. Group 1 consisted of 48 patients with non-alcoholic steatohepatitis (NASH) in combination with T2DM without small intestinal bacterial overgrowth (SIBO) syndrome. Group 2 comprised 45 patients with NASH in combination with T2DM and SIBO. The control group consisted of 25 apparently healthy persons. The ELISA method was used for quantitative determination of serum zonulin. Results. When comparing parameters of liver functional activity and ultrasonographic findings of liver steatosis and fibrosis, a significant increase in the activity of ALT and AST was revealed in Group 1 – 67.22 ± 2.25 U/l and 52.97 ± 1.04 U/l (p < 0.001) and in Group 2 – 69.20 ± 1.52 U/l and 54.82 ± 1.10 U/l (p < 0.001) compared to those in the control group – 18.00 ± 1.01 U/l and 18.96 ± 0.82 U/l (p < 0.001) respectively, as well as an increase in the ultrasound attenuation coefficient (UAC) in patients of Groups 1 and 2 amounting to 2.94 ± 0.03 dB/cm and 2.92 ± 0.04 dB/cm, respectively, and also the liver stiffness (LS) in Group 1 – 8.06 ± 0.07 kPa and in Group 2 – 8.00 ± 0.06 kPa compared to those in the control group (p < 0.001). When measuring the level of serum zonulin, a significant increase was revealed in patients of Group 1 – 61.69 ± 1.04 ng/ml and Group 2 – 89.39 ± 1.30 ng/ml compared to that in the control group – 16.76 ± 1.47 ng/ml (p < 0.001). Analyzing correlation coefficients in patients of Groups 1 and 2, a positive linear moderate association was found between the serum zonulin concentration and the activity of ALT, AST and UAC and LS. Conclusions. The study resultsobtained have demonstrated the great diagnostic value of serum zonulin as a biomarker of intestinal permeability in NASH patients in combination with T2DM, and with or without SIBO.

Serum Zonulin and Claudin-5 but not Interferon-Gamma and Interleukin-17A Levels Increased in Children with Specific Learning Disorder: A Case-Control Study.

Gut-blood and blood-brain barrier permeabilty (gut-brain axis) has been attracting increased attention in the etiology of neurodevelopmental disorders. In this study, we aimed to investigate serum levels of zonulin (a biomarker of intestinal permeability), claudin-5 (a biomarker of blood-brain barrier permeability), and interferon-gamma and interleukin-17A in children with specific learning disorder. Forty-three children with DSM-5 diagnosis of specific learning disorder and 43 healthy children were included in this study. Serum levels of zonulin, claudin-5, interferon-gamma, and interleukin-17A were measured using commercial enzyme-linked immunosorbent assay kits. Serum zonulin and claudin-5 levels of the study group were significantly higher than the control group according to the multivariate analysis of covariance test while controlling for age, gender, and body mass index. However, serum interferon-gamma and interleukin-17A levels were not significantly different between the two groups. There was no correlation either between zonulin and interferon-gamma and interleukin-17A or claudin-5 and interferon-gamma and interleukin-17A. Gut-blood and blood-brain barrier permeability may be disrupted in subjects with special learning disorder. Further research is needed to determine whether zonulin and claudin-5 may be biomarkers, and some dietary interventions or specific agents such as zonulin or claudin-5 inhibitors could be used in the management of neurodevelopmental disorders including special learning disorder.

Biomarkers of intestinal permeability and blood-brain barrier permeability in adolescents with major depressive disorder

BackgroundThe etiology in major depressive disorder (MDD) has not been fully understood. Accumulating evidence suggests an association between altered intestinal and blood-brain barrier (BBB) permeability and psychiatric disorders, while its changes in adolescent MDD populations have been received less attention. In this study, our aim was to explore the differences in plasma levels of intestinal and blood-brain barrier permeability markers in adolescents with MDD compared with healthy controls (HCs). MethodsWe enrolled MDD (n = 50), and HCs (n = 40) with the age of 13–18 years old. The plasma level of zonulin, I-FABP, LPS, and claudin-5 were quantified. The Hamilton Depression Scale 17 items (HAMD-17) and Hamilton Anxiety Scale 14 items (HAMA-14) were used for symptom assessments. ResultsThe plasma levels of zonulin, I-FABP, LPS, and claudin-5 in the MDD group were significantly higher than those in the HCs. Plasma I-FABP levels in MDD with moderate to severe anxiety were significantly higher than those in MDD without moderate to severe anxiety and HCs. In addition, these four biomarkers (alone or combined) can be used as diagnostic markers for MDD in adolescents. LimitationsThe key limitation of this study is the blood measurements at a single time point with a relatively small sample size. ConclusionsThese findings advance our understanding of the pathophysiology of intestinal barrier injury, bacterial translocation, and blood-brain barrier injury involved in adolescents with MDD.

Preliminary evaluation of serum zonulin in canine chronic enteropathies.

In humans, serum zonulin, a biomarker of intestinal permeability, correlates with underlying enteropathies and has potential application as a therapeutic target. The aim of this study was to evaluate serum zonulin as a biomarker for canine chronic enteropathy. Prospective enrolment of twenty-one client-owned dogs with at least 1 of the following gastrointestinal (GI) signs for at least 3 weeks duration: anorexia, hyporexia, dysrexia, vomiting, weight loss or diarrhea. 21 control dogs, age and breed matched, were also enrolled. Dogs with gastrointestinal signs were diagnosed with chronic enteropathy based on a complete blood count, serum chemistry, specific canine pancreatic lipase, cobalamin, resting cortisol, abdominal ultrasound and gastrointestinal endoscopy with histopathology. Enrolled control dogs had an unremarkable physical examination, complete blood count, serum chemistry and no clinical signs of gastrointestinal disease. Dogs were ineligible if antibiotics or immunosuppressive medications were administered within 1 month of enrolment. Blood samples were analysed using a commercial canine serum zonulin quantitative ELISA. Dogs with chronic enteropathies had median serum zonulin values of 0.28 ng/mL (interquartile range: 0.04-2.59), while control dogs of 0.27 ng/mL (0.05-3.67). There was no significant difference in canine serum zonulin levels between these populations. The estimated difference in the median concentrations was -0.01 ng/mL (95% CI: -0.23 to 0.89). In this study, using a commercial canine zonulin ELISA, serum zonulin levels did not differentiate between dogs with chronic enteropathies and control dogs.

"Leaky Gut" as a Keystone of the Connection between Depression and Obstructive Sleep Apnea Syndrome? A Rationale and Study Design.

Obstructive sleep apnea (OSA) and depression are highly comorbid. Immune alterations, oxidative stress or microbiota dysfunction have been proposed as some mechanisms underlying this association. The aim of the proposed study is to assess the severity and profile of OSA and depressive symptoms in the context of serum microbiota metabolites, biomarkers of intestinal permeability, inflammation and oxidative stress in adult patients diagnosed with OSA syndrome. The study population consists of 200 subjects. An apnoea-hypopnoea index ≥ 5/hour is used for the diagnosis. Depressive symptoms are assessed with Beck Depression Inventory. Measured serum markers are: tumour necrosis factor–alpha and interleukin-6 for inflammation, total antioxidant capacity and malondialdehyde concentration for oxidative stress, zonulin, calprotectin, lipopolisaccharide-binding protein and intestinal fatty acids-binding protein for intestinal permeability. All of the above will be measured by enzyme-linked immunosorbent assay (ELISA). Associations between clinical symptoms profile and severity and the above markers levels will be tested. It would be valuable to seek for overlap indicators of depression and OSA to create this endophenotype possible biomarkers and form new prophylactic or therapeutic methods. The results may be useful to establish a subpopulation of patients sensitive to microbiota therapeutic interventions (probiotics, prebiotics, and microbiota transplantation).

Stress and the gut-brain axis: Cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability following severe physical and psychological stress

BackgroundPhysical and psychological stress alter gut-brain axis activity, potentially causing intestinal barrier dysfunction that may, in turn, induce cognitive and mood impairments through exacerbated inflammation and blood brain barrier (BBB) permeability. These interactions are commonly studied in animals or artificial laboratory environments. However, military survival training provides an alternative and unique human model for studying the impacts of severe physical and psychological stress on the gut-brain axis in a realistic environment. PurposeTo determine changes in intestinal barrier and BBB permeability during stressful military survival training and identify relationships between those changes and markers of stress, inflammation, cognitive performance, and mood state. Materials and methodsSeventy-one male U.S. Marines (25.2 ± 2.6 years) were studied during Survival, Evasion, Resistance, and Escape (SERE) training. Measurements were conducted on day 2 of the 10-day classroom phase of training (PRE), following completion of the 7.5-day field-based simulation phase of the training (POST), and following a 27-day recovery period (REC). Fat-free mass (FFM) was measured to assess the overall physiologic impact of the training. Biomarkers of intestinal permeability (liposaccharide-binding protein [LBP]) and BBB permeability (S100 calcium-binding protein B [S100B]), stress (cortisol, dehydroepiandrosterone sulfate [DHEA-S] epinephrine, norepinephrine) and inflammation (interleukin-6 [IL-6], high-sensitivity C-reactive protein [hsCRP]) were measured in blood. Cognitive performance was assessed by psychomotor vigilance (PVT) and grammatical reasoning (GR) tests, and mood state by the Profile of Mood States (total mood disturbance; TMD), General Anxiety Disorder-7 (GAD-7), and Patient Health (PHQ-9) questionnaires. ResultsFFM, psychomotor vigilance, and LBP decreased from PRE to POST, while TMD, anxiety, and depression scores, and S100B, DHEA-S, IL-6, norepinephrine, and epinephrine concentrations all increased (all p ≤ 0.01). Increases in DHEA-S were associated with decreases in body mass (p = 0.015). Decreases in FFM were associated with decreases in LBP concentrations (p = 0.015), and both decreases in FFM and LBP were associated with increases in TMD and depression scores (all p < 0.05) but not with changes in cognitive performance. Conversely, increases in S100B concentrations were associated with decreases in psychomotor vigilance (p < 0.05) but not with changes in mood state or LBP concentrations. ConclusionsEvidence of increased intestinal permeability was not observed in this military survival training-based model of severe physical and psychological stress. However, increased BBB permeability was associated with stress and cognitive decline, while FFM loss was associated with mood disturbance, suggesting that distinct mechanisms may contribute to decrements in cognitive performance and mood state during the severe physical and psychological stress experienced during military survival training.

Динамика уровня зонулина в стуле при инфекции COVID-19 и в постковидный период у детей

Fecal zonulin is currently used as a biomarker of intestinal permeability. Objective. To assess the state of intestinal permeability in a novel coronavirus infection (COVID-19) in children based on the determination of fecal zonulin levels. Patients and methods. Fecal zonulin levels were assessed in 35 children with COVID-19, which was mild in most of them. Fecal sampling was performed at the time of diagnosis and 14 days after the start of observation. Patients were then randomized into two groups. Group 1 (study, n = 19) received Maxilac® Baby synbiotic (2 sachets once a day) for 1 month, group 2 (control, n = 16) did not receive any probiotics, prebiotics, and adsorbents for a month; the third stool sampling was performed 1 month after the second. The study was carried out by enzyme immunoassay using the IDK Zonulin ELISA test system (Immundiagnostik AG, Germany). Results. Fecal zonulin levels were 77.38 ± 12.59 ng/mL at the beginning of the disease, 76.26 ± 13.10 ng/mL on day 14, and 82.64 ± 11.99 ng/mL after one month (p1–2 = 0.75; p1–3 = 0.04; p2–3 = 0.04). Children who received Maxilac® Baby for a month did not have significant increases in zonulin levels (76.26 ± 13.10 ng/mL and 79.02 ± 11.87 ng/mL; p = 0.40), while the control group demonstrated significantly elevated zonulin levels (76.26 ± 13.10 ng/mL and 87.95 ± 10.96 ng/mL; p = 0.048). Conclusion. A month after the coronavirus infection, the intestinal permeability in children increases significantly, whereas it does not change during the course of the disease. Administration of Maxilac® Baby synbiotic in children who had a mild-tomoderate coronavirus infection and did not receive antibiotics effectively prevents intestinal permeability disorders in them. Key words: children, SARS-CoV-2, zonulin, coronavirus infection, intestinal permeability, COVID-19

Relationship Of Zonulin Levels With Thyroid Function And Metabolic Parameters In Hashimoto’s Thyroiditis

Aim: Intestinal permeability is one of the factors responsible for the pathogenesis of many immune-related diseases, one of which is Hashimoto's-thyroid (HT). We used zonulin as a biomarker of intestinal permeability in this cross-sectional study. We aimed to determine serum zonulin levels in individuals diagnosed with HT and to investigate the relationship between zonulin and autoimmunity biomarkers, thyroid function and metabolic parameters. Materials and Methods: The study was conducted with 43 women newly diagnosed with HT and a control group of 30 matched with them. The evaluated parameters were thyroperoxidase-antibody (TPO-AB), thyroglobulin-antibody (Tg-AB), thyroid hormone profile, metabolic parameters and zonulin levels. Results: Higher levels of TSH, TPO-AB, Tg-AB, TG and TC were measured in the HT group compared to controls (P&lt;0.005). The means of zonulin in HT.patients were significantly higher than in the control group (P&lt;0.005). Conclusion: The correlations between zonulin levels and TSH and TPO-AB among all subjects in this study support the idea that intestinal permeability is a distinguishing feature in the conditions causing the formation of immunological hypersensitivity in HT. More studies are needed to prove that impaired intestinal permeability is among the causes of decreased thyroid function.

Influence of Diet and Levels of Zonulin, Lipopolysaccharide and C-Reactive Protein on Cardiometabolic Risk Factors in Young Subjects.

A western diet and increased intestinal permeability may contribute to systemic inflammation and the development of cardio-metabolic alterations. The aim of this study was to assess the relationship between diet, biomarkers of intestinal permeability, and chronic low-grade inflammation on the cardiometabolic profile. A cross-sectional study was carried out in 238 young subjects aged 18–29 years, divided into two groups: with <3 cardiometabolic risk factors (CRF) and ≥3 risk factors. Anthropometric parameters, biochemical profile, and serum levels of zonulin, lipopolysaccharide (LPS), and high-sensitivity C-reactive protein (hs-CRP) were measured, and the macronutrient intake was evaluated. Interaction models showed elevated glucose levels in the presence of high biomarker levels: zonulin ≥51.6 ng/mL plus LPS ≥ 1.35 EU/mL (β = 1.1, p = 0.006), and LPS ≥1.35 EU/mL plus hs-CRP ≥ 4.3 mg/L (β = 1.2, p = 0.007). In addition, triglyceride levels increased in the presence of LPS ≥ 1.35 EU/mL and hs-CRP ≥ 4.3 mg/L (β = 3.9, p = 0.01). Despite having increased biomarker levels, a higher consumption of water (≥2100 mL), polyunsaturated fatty acids (≥6.0 g), or fiber (≥30 g) decreased triglyceride (β = −9.6, p = 0.03), total cholesterol (β = −5.1, p = 0.01), and LDL-C levels (β = −7.7, p = 0.01). These findings suggest that the increased consumption of water, PUFA and fiber may improve lipid profile in subjects with intestinal permeability dysfunction or low-grade systemic inflammation.

Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects.

Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively affect the gut microbiota-immune system-intestinal barrier (IB) axis. In this context, we tested the hypothesis that a PR-dietary intervention would affect the presence of bacterial factors in the bloodstream of older adults. We collected blood samples within a randomized, controlled, crossover intervention trial in which older volunteers (n = 51) received a polyphenol-enriched and a control diet. We quantified the presence of bacterial DNA in blood by qPCR targeting the 16S rRNA gene (16S; bacterial DNAemia). Blood DNA was taxonomically profiled via 16S sequencing. Higher blood 16S levels were associated with higher BMI and markers of IP, inflammation, and dyslipidemia. PR-intervention did not significantly change bacterial DNAemia in the older population (P = 0.103). Nonetheless, the beneficial changes caused by the polyphenol-enriched diet were greatest in participants with higher bacterial DNAemia, specifically in markers related to IP, inflammation and dyslipidemia, and in fecal bacterial taxa. Finally, we found that the bacterial DNA detected in blood mostly belonged to γ-Proteobacteria, whose abundance significantly decreased after the polyphenol-rich diet in subjects with higher bacterial DNAemia at baseline. This study shows that older subjects with higher bacterial DNAemia experienced a beneficial effect from a polyphenol-rich diet. Bacterial DNAemia may be a further relevant marker for the identification of target populations that could benefit more from a protective dietary treatment. This trial was retrospectively registered at www.isrctn.org (ISRCTN10214981) on April 28, 2017.

Association of Emulsifier and Highly Processed Food Intake with Circulating Markers of Intestinal Permeability and Inflammation in the Cancer Prevention Study-3 Diet Assessment Sub-Study

Compelling animal studies report increased intestinal permeability, inflammation, and colorectal carcinogenesis with exposure to certain emulsifiers commonly added to processed foods, but human data are lacking. Highly processed food consumption is also associated with obesity and higher risk of chronic diseases. We cross-sectionally examined the association of emulsifier and highly processed food consumption estimated from six 24-h dietary recalls among 588 U.S. men and women over one year, with biomarkers of intestinal permeability and inflammation measured from two fasting blood samples collected six months apart. In multivariable-adjusted generalized linear models, greater emulsifier intake (g/d) was not associated with antibodies to flagellin (P-trend = 0.88), lipopolysaccharide (LPS) (P-trend = 0.56), or the combined total thereof (P-trend = 0.65) but was positively associated with an inflammatory biomarker, glycoprotein acetyls (GlycA) (P-trend = 0.02). Highly processed food intake (% kcal/d) was associated with higher anti-LPS antibodies (P-trend = 0.001) and total anti-flagellin and anti-LPS antibodies (P-trend = 0.005) but not with other biomarkers, whereas processed food intake expressed as % g/d was associated with higher GlycA (P-trend = 0.02). Our findings suggest that, broadly, highly processed food consumption may be associated with intestinal permeability biomarkers, and both emulsifier and highly processed food intakes may be associated with inflammation. Additional studies are warranted to further evaluate these relationships. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1957947

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.

Strenuous 12-h run elevates circulating biomarkers of oxidative stress, inflammation and intestinal permeability in middle-aged amateur runners: A preliminary study.

Given the solid evidence that prolonged strenuous exercise is a cause of metabolic stress, this study sought to determine whether a 12-h run would affect total oxidant status (TOS), total oxidant capacity (TOC), total antioxidant status (TAS), high-sensitivity C-reactive protein (hs-CRP) and the biomarkers of intestinal permeability (protein fatty acid-binding proteins (I-FABP) and zonulin) in middle-aged male subjects. Ten amateur long-distance runners (aged 52.0 ± 6.2 years, body height 176.9 ± 4.9 cm, body mass 73.9 ± 6.0 kg) were enrolled in the study. The venous blood samples were collected 1 hour before and right after the run and were analyzed for the levels of TAS, TOS/TOC, hs-CRP, I-FABP and zonulin. The post-run concentrations of TOS/TOC were significantly elevated (p < 0.001), but TAS changes were not significant. Pearson’s correlation coefficients calculated for the post run values of TAS and TOS/TOC were statistically significant and negative (r = -0.750, p < 0.05). Significant increases in the concentrations of hs-CRP (p < 0.001), I-FABP (p < 0.05) and zonulin (p < 0.01) were noted. The results indicate that a strenuous 12-h run disturbs the prooxidant-antioxidant balance in middle-aged men, as well as promoting inflammation and impairing intestinal permeability.

Assessment of Serum Level of Claudin‐3 and Its Association with Disease Severity in Patients with Psoriasis Vulgaris

Background: Psoriasis is a common inflammatory disorder of the skin. Psoriasis is a disease of multifactorial origin where certain environmental factors acting on individuals with specific genetic predisposition leads to an immune dysregulation. Claudins are transmembrane proteins, which participate in the formation of tight junctions by binding to the actin cytoskeleton. Claudin‐3 present in the blood is considered as a useful biomarker of intestinal permeability. Objective: To evaluate serum level of claudin-3 in patients with psoriasis in comparison to control group and correlate its levels with disease severity. Patients and methods: Fifty-three patients (32 males and 21 females) with psoriasis and forty normal healthy control (23 males and 17 females) who matched the cases group as regard age and sex were included in this work. They were randomly selected from the Dermatology Department outpatient clinic in Mansoura University Hospital. Results: Psoriasis group showed significantly higher level of claudin-3 when compared to control group (mean=58.3 versus 41.2; p 0.05 for each). Higher BMI, smoking and higher claudin-3 level were associated with prediction of higher PASI score in univariate analysis. While multivariate analysis revealed that only smoking and higher claudin-3 level were considered independent predictor of more severe psoriasis cases. Conclusion: Claudin-3 level was significantly higher in patients with psoriasis than healthy controls. PASI correlated with claudin-3 levels.

The Effects of Probiotic/Synbiotic on Serum Level of Zonulin as a Biomarker of Intestinal Permeability: A Systematic Review and Meta-Analysis.

Background:This systematic review and meta-analysis was conducted to obtain a conclusive result on the influence of probiotics/synbiotic on serum levels of zonulin. Data related to serum levels of zonulin were extracted to determine the effects of probiotic/synbiotic on intestinal permeability.Methods:The literature search was conducted across the Cochrane Central Register of Controlled Trials, Pub-Med, Scopus and ISI Web of Science, Search up to Nov 2018. Clinical trials evaluating the effect of probiotic/synbiotic on serum zonulin levels of all human subjects were included.Results:Nine studies (including 496 intervention and 443 control subjects) met the inclusion criteria for the meta-analysis. According to the meta-analysis, probiotic/synbiotic has a significant effect on serum zonulin reduction (WMD=−10.55 [95% CI: −17.76, −3.34]; P=0.004). However, the high level of heterogeneity was observed among the studies (I2=97.8, P<0.001). The subgroup analysis suggested study quality, blinding, study duration, Participants age, subject’s health status and supplement type as sources of heterogeneity.Conclusion:Probiotic/synbiotic have favorable effects on serum levels of zonulin as a measure of intestinal permeability. However, the results should be interpreted with caution due to the high heterogeneity and further evidence is required before definitive recommendations can be made.

Emulsifier and Highly Processed Food Intake and Biomarkers of Intestinal Permeability and inflammation in the Cancer Prevention Study-3 Diet Assessment Sub-Study

Abstract Objectives Emulsifiers may increase intestinal permeability, inflammation, and colorectal carcinogenesis in animals. Highly processed foods are associated with obesity and may increase risk of chronic diseases, including cancer. We estimated intake of emulsifiers and highly processed foods in participants from the Cancer Prevention Study-3 Diet Assessment Sub-study and examined their association with biomarkers of gut permeability and inflammation. Methods This study included 657 men and women who completed six 24-hr dietary recalls and two fasting blood samples over one year. Antibodies (IgG and IgA) to flagellin and lipopolysaccharide (LPS) and glycoprotein acetyls (GlycA) were measured using enzyme-linked immunosorbent assay and nuclear magnetic resonance, respectively. Total flagellin and LPS were each calculated as the sum of IgG and IgA; total antibody comprised the sum of total flagellin and LPS. Foods containing ≥1 emulsifier were identified from ingredient lists; foods typically containing emulsifiers were coded as such if an ingredient list was not available. We estimated emulsifier intake as 0.5% of total food weight, per FDA guidance. Highly processed foods were defined using the NOVA and Poti et al. classification systems and calculated as % grams of total foods and % kcal of total energy. Multivariable-adjusted generalized linear models were used to estimate associations of emulsifier and processed food quartiles with continuous antibody or inflammatory biomarkers. Results Higher emulsifier intake (g/d) was not associated with total flagellin (P-trend = 0.48), total LPS (P-trend = 0.61), total antibody (P-trend = 0.49), or GlycA (P-trend = 0.16). Higher processed food intake (% kcal/d) was associated with higher total LPS (P-trend = 0.001) and total antibody (P-trend = 0.01) but not with other biomarkers, whereas processed food intake estimated as % g/d was only associated with higher GlycA (P-trend = 0.02). Conclusions Our results suggest highly processed food, but not emulsifier, intake may be associated with gut permeability biomarkers. Additional studies are needed to further understand the relationship between emulsifier and highly processed food intake and intestinal permeability and inflammation. Funding Sources The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-3 cohort.

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases.

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

Fontan protein-losing enteropathy is associated with advanced liver disease and a proinflammatory intestinal and systemic state.

Protein-losing enteropathy (PLE) after Fontan surgery carries significant morbimortality. Its pathophysiology and association with other Fontan complications are poorly understood. Our aims were to examine whether Fontan-PLE is associated with greater liver damage and to assess the presence of systemic and intestinal inflammation. Fontan patients with PLE and Fontan controls without PLE matched for age and Fontan surgery procedure were included. Data were prospectively compiled on blood and stool tests, liver imaging, elastography, cardiac-MRI and cardiac catheterization. Twenty-nine Fontan patients were enrolled (14 with PLE and 15 controls without PLE). Patients with PLE had more advanced liver disease estimated by non-invasive methods: blunt liver margins on ultrasonography (71.4% vs 26.7%, P=.027), greater median liver stiffness (25.4 vs 14.5kPa, P=.003) and higher FIB-4 (P=.016). Portal hypertension-related signs were more common in patients with PLE including ascites (P=.035), larger spleen size (P=.005), oesophageal varices/splanchnic collateral shunts (P=.03), higher liver stiffness-spleen size-to-platelet ratio risk score (P<.001) and lower platelet count (P=.01). Systemic proinflammatory cytokines (TNF-α, interleukin-6), biomarkers of intestinal permeability (intestinal fatty-acid binding protein) and faecal calprotectin concentrations were also significantly increased in Fontan-PLE (P<.05). Faecal calprotectin directly correlated with alpha-1 antitrypsin clearance and inversely with cardiac index, total serum proteins and body mass index. Fontan-PLE is associated with advanced liver disease and increased markers of systemic inflammation and intestinal permeability. Faecal calprotectin is elevated and correlates with Fontan-PLE severity. Liver assessment is mandatory in all Fontan patients, and especially in those with PLE.