OBJECTIVE: Metformin (MTF) shows promise in protecting against physical decline in osteoarthritis (OA), but how it works remains unclear. We studied MTF\'s effects on gut permeability and its link to physical performance in OA patients.
METHODS: We studied four groups: control (n = 72), OA non-diabetic (n = 58), OA diabetic on MTF (n = 55), and OA diabetic on other anti-diabetics (n = 57). We measured zonulin levels, as intestinal permeability marker, hand-grip strength (HGS), Oxford knee scoring (OKS) to determine OA severity, and short performance physical battery (SPPB) to determine physical functions.
RESULTS: Patients suffering from OA showed a reduction in HGS and SPPB scores with raised plasma zonulin than controls, irrespective of disease severity. MTF decreased plasma zonulin levels and improved OKS, gait speed, HGS, and SPPB scores in OA patients. However, OA patients taking other anti-diabetic medications demonstrated higher levels of plasma zonulin, reduced HGS, and SPPB scores. Furthermore, a robust correlation of plasma zonulin and HGS, OKS, gait speed, and SPPB scores in OA patients on MTF was observed. Moreover, we found reduced oxidative stress and inflammation associated with these alterations in OA patients treated with MTF.
CONCLUSIONS: MTF improves HGS and physical performance by lowering zonulin levels, preserving gut permeability in OA patients.

Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition-CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC-Cerebral Palsy Controls) and 24 healthy children (HC-healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group (p = 0.012, p = 0.025). When comparing the CPG (n = 53) with the HC group (n = 24), statistically significant differences were observed for calprotectin (p = 0.000018, higher in the CPG) and IFABP (p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin.

BACKGROUND: Gut dysbiosis leading to increased intestinal barrier permeability and translocation of lipopolysaccharide (LPS) in the circulation has been demonstrated in patients with acute myocardial infarction and pulmonary embolism.
OBJECTIVE: We investigated changes in circulating LPS concentrations in acute ischemic stroke (AIS) and their consequences, including prognosis.
METHODS: We studied 98 AIS patients, aged 74±12 years, including 74 (75.5%) thrombolysed individuals. We determined serum LPS and zonulin, a marker of gut permeability, along with protein carbonylation (PC), fibrin clot properties, and thrombin generation on admission, at 24 hours and 3 months. Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke functional outcome using modified Rankin Scale (mRS) and stroke-related mortality were evaluated at 3 months.
RESULTS: Serum LPS and zonulin on admission were associated with time since symptom onset (r=0.57, p<0.0001 and r=0.40, p<0.0001). Baseline LPS correlated with PC (r=0.51, p<0.0001) but not with coagulation and fibrinolysis markers. LPS levels increased at 24 hours in thrombolysed patients (p<0.001) and correlated with the NIHSS score (r=0.31, p=0.002) and PC (r=0.32, p=0.0057). Both LPS and zonulin levels measured at 24 hours increased the odds of having unfavorable mRS (OR=1.22, 95%CI, 1.04-1.42 and 2.36, 95%CI, 1.24-4.49 per unit). Elevated LPS, but not zonulin, was associated with stroke-related mortality (OR=1.26, 95%CI, 1.02-1.55 per unit).
CONCLUSIONS: In AIS patients intestinal permeability is mainly driven by increasing time since the symptom onset. Our findings suggest that LPS with a trend toward its further rise following thrombolysis adversely affect neurological functional outcomes and 3-month mortality.

UNASSIGNED: The aim of this study is to determine whether the levels of zonulin and occludin, tight junctions (TJ) proteins in the intestinal epithelium, will differ between obsessive compulsive disorder (OCD) patients and healthy controls. We also intended to investigate whether these would vary in OCD patients with and without major depressive disorder (MDD) comorbidity and in comparison with healthy controls.
UNASSIGNED: Sixty patients diagnosed with OCD and 30 healthy controls were included in the study. The cases were administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HDRS). The patients were divided into two subgroups based on their HDRS scores and presence of MDD comorbidity. Zonulin and occludin levels were measured using the ELISA method. The research was carried out between April 2021 and October 2021.
UNASSIGNED: Zonulin and occludin levels were significantly higher in the OCD patient group than in the control group (p<0.001). The levels of both were also significantly higher in the OCD patients with MDD comorbidity (OCD+MDD) compared to those without MDD (OCD-MDD) (p<0.001). Zonulin and occludin levels also rose significantly as disease severity increased in the OCD patient group (respectively; p<0.001, p=0.001). The levels of both increased in line with the severity of depression based on HDRS scores in the OCD+MDD group (p<0.001). A positive correlation was determined between the duration of OCD and zonulin and occludin levels. Evaluation of the entire OCD group revealed a moderate positive correlation between Y-BOCS and HDRS scores and zonulin and occludin.
UNASSIGNED: Zonulin and occludin levels in this research were significantly higher in the patients with OCD than in the healthy controls. That elevation was positively correlated with disease duration and severity, and the increase was significantly more pronounced in OCD with MDD comorbidity. These findings point to a possible disorder in the intestinal barrier and blood-brain barrier in OCD patients.

UNASSIGNED: There is a link between cardiovascular diseases and intestinal permeability, but it is not clear. This review aimed to elucidate intestinal permeability in cardiovascular diseases by meta-analysis.
UNASSIGNED: Multidisciplinary electronic databases were searched from the database creation to April 2023. All included studies were assessed for risk of bias according to the Joanna Briggs Institute Critical Appraisal Checklist. The heterogeneity of each study was estimated using the I2 statistic, and the data were analyzed using Review Manager 5.3 and Stata 16.0.
UNASSIGNED: In total, studies in 13 pieces of literature were included in the quantitative meta-analysis. These studies were conducted among 1,321 subjects mostly older than 48. Patients had higher levels of intestinal permeability markers (lipopolysaccharide, d-lactate, zonulin, serum diamine oxidase, lipopolysaccharide-binding protein, intestinal fatty acid binding protein, and melibiose/rhamnose) than controls (standard mean difference SMD = 1.50; 95% CI = 1.31-1.88; p < 0.00001). Similarly, lipopolysaccharide levels were higher in patients than in controls (SMD = 1.61; 95% CI = 1.02-2.21; p < 0.00001); d-lactate levels were higher in patients than in controls (SMD = 1.16; 95% CI = 0.23-2.08; p = 0.01); zonulin levels were higher in patients than in controls (SMD = 1.74; 95% CI = 1.45-2.03; p < 0.00001); serum diamine oxidase levels were higher in patients than in controls (SMD = 2.51; 95% CI = 0.29-4.73; p = 0.03).
UNASSIGNED: The results of the meta-analysis verified that the intestinal barrier was damaged and intestinal permeability was increased in patients with cardiovascular diseases. These markers may become a means of the diagnosis and treatment of cardiovascular diseases.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=414296, identifier CRD42023414296.

Diabetes mellitus, as a chronic metabolic disorder, significantly impacts the pancreas and among other organs, affects duodenal function. Emerging evidence suggests that probiotics can exert beneficial effects on gut health and metabolism. In our previous research, we evaluated the probiotic Lactobacillus paraplantarum BGCG11 primarily for its protective properties against diabetic rats\' damaged liver and kidneys. In this work, we further examined the effects of probiotic strain BGCG11 on the function of the duodenum and pancreas in diabetic rats. We explored the potential mechanisms underlying the probiotic\'s effects, focusing on general indicators of diabetes, the architecture and morphology of pancreatic islets, duodenal integrity (measuring the transfer of fluid and serum zonulin level), and the modulation of gut microbiota composition. Our findings reveal the protective and regulatory roles of L. paraplantarum BGCG11 in mitigating diabetes-induced pancreatic and duodenal dysfunction regardless of its application time (pre- or post-treatment), highlighting its therapeutic potential in managing diabetes-related gastrointestinal complications.

Introduction: B. animalis subsp. lactis HN019 is a commercially available well-characterized probiotic with documented effects on human health, such as the ability to enhance the immune function and to balance the intestinal microbiome. Therefore, optimizing the manufacturing process to improve sustainability, increasing biomass yields and viability, and avoiding animal -derived nutrients in the medium to meet vegan consumer\'s needs, is currently of interest. Besides the established use of live probiotic cells, alternative supplements indicated as postbiotics, like non-viable cells and/or probiotics derived bioactive molecules might be considered as potential next generation biotherapeutics. In fact, advantages of postbiotics include fewer technological limitations, such as easier production processes and scale-up, and even higher specificity. Methods: In this work, medium design together with different fermentation strategies such as batch, fed-batch and in situ product removal on lab-scale bioreactors were combined. Medium pretreatment by ultrafiltration and protease digestion was performed to reduce polysaccharidic contaminants and facilitate the purification of secreted exopolysaccharides (EPS). The latter were isolated from the fermentation broth and characterized through NMR, GC-MS and SEC-TDA analyses. The expression of TLR-4, NF-kb and IL-6 in LPS challenged differentiated CaCo-2 cells treated with EPS, live and heat-killed B. lactis cells/broth, was evaluated in vitro by western blotting and ELISA. Zonulin was also assessed by immunofluorescence assays. Results and Discussion: The titer of viable B. lactis HN019 was increased up to 2.9 ± 0.1 x 1010 on an animal-free semidefined medium by applying an ISPR fermentation strategy. Medium pre-treatment and a simple downstream procedure enriched the representativity of the EPS recovered (87%), the composition of which revealed the presence of mannuronic acid among other sugars typically present in polysaccharides produced by bifidobacteria. The isolated EPS, live cells and whole heat inactivated broth were compared for the first up to date for their immunomodulatory and anti-inflammatory properties and for their ability to promote intestinal barrier integrity. Interestingly, EPS and live cells samples demonstrated immune-stimulating properties by downregulating the expression of TLR-4 and NF-kb, and the ability to promote restoring the integrity of the intestinal barrier by up-regulating the expression of zonulin, one of the tight junctions forming proteins. Postbiotics in the form of heat killed broth only reduced NF-kb expression, whereas they did not seem effective in the other tested conditions.

Given the growing global threat and rising prevalence of type 2 diabetes mellitus (T2DM), addressing this metabolic disease is imperative. T2DM is preceded by prediabetes (PD), an intermediate hyperglycaemia that goes unnoticed for years in patients. Several studies have shown that gut microbial diversity and glucose homeostasis in PD or T2DM patients are affected. Therefore, this review aims to synthesize the existing literature to elucidate the association between high-calorie diets, intestinal permeability and their correlation with PD or T2DM. Moreover, it discusses the beneficial effects of different dietary interventions on improving gut health and glucose metabolism. The primary factor contributing to complications seen in PD or T2DM patients is the chronic consumption of high-calorie diets, which alters the gut microbial composition and increases the translocation of toxic substances from the intestinal lumen into the bloodstream. This causes an increase in inflammatory response that further impairs glucose regulation. Several dietary approaches or interventions have been implemented. However, only a few are currently in use and have shown promising results in improving beneficial microbiomes and glucose metabolism. Therefore, additional well-designed studies are still necessary to thoroughly investigate whether improving gut health using other types of dietary interventions can potentially manage or reverse PD, thereby preventing the onset of T2DM.

OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) frequently exhibit an inability to maintain postural balance. However, the contribution of increased intestinal permeability or leaky gut to the postural imbalance in COPD is not known.
METHODS: We measured plasma zonulin, a marker of leaky gut, with relevance to postural balance in male controls (n = 70) and patients with mild (n = 67), moderate (n = 66), and severe (n = 58) COPD. We employed a short physical performance battery to evaluate postural balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), gait speed, plasma c-reactive proteins (CRP), and 8-isoprostanes as potential mechanistic connections between postural imbalance and leaky gut.
RESULTS: COPD patients demonstrated higher plasma zonulin, CRP, and 8-isoprostanes levels and lower balance, HGS, and gait speed than controls (all p < 0.05). These findings were more robust in patients with moderate and severe than mild COPD. In addition, plasma zonulin exhibited significant potential in diagnosing poor balance, low HGS, and gait speed in COPD patients (all p < 0.05). We also found significant correlations of plasma zonulin with CRP and 8-isoprostanes, providing heightened inflammation and oxidative stress as mechanistic connections between leaky gut and postural imbalance.
CONCLUSIONS: Plasma zonulin may be helpful in evaluating postural imbalance in COPD patients. Repairing intestinal leaks can be a therapeutic target to improve postural control in COPD.

Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.