Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation

Dschietzig, Thomas; Boschann, Felix; Ruppert, Jana; Armbruster, Franz Paul; Meinitzer, Andreas; Banković, Dragić; Mitrović, Veselin; Melzer, Christoph

doi:10.7754/clin.lab.2016.160512

Cited by 13 publications

(17 citation statements)

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“…Furthermore we detected a significantly positive correlation between renal function, measured as eGFR, and the zonulin concentration and were thus able to confirm the finding recently reported by Dschietzig et al 14 In this study, which was conducted in a special group of patients with an auto matic implantable cardioverter/ defibrillator, the authors had described such a correlation for the first time, deducing that the low zonulin concentration associated with impaired renal function results from the depletion of zonulin with the urine. We were indeed able to determine a significantly nega tive correlation between the serum zonulin concentration and the extent of proteinuria measured as UACR in the urine.…”

Section: Discussionsupporting

confidence: 91%

Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function

Hasslacher¹

2018

JDMDC

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Background: The raised permeability of the intestinal barrier (IB) is a factor of major pathogenetic relevance for the development of type-1 and type-2 diabetes. Little is known about the extent to which an impaired function of the IB is still detectable even after a relatively long duration of diabetes and which correlations are present between such an impairment and clinical parameters. We investigated these correlations by measuring serum zonulin levels as a parameter of the IB function in people with a longer history of type-2 diabetes. Methods: In 63 diabetic patients (mean history of diabetes 13 years) and 19 non diabetic controls, the serum zonulin concentrations were measured alongside metabolism parameters (HbA1c, insulin resistance, lipids) and renal function (estimated glomerular filtration rate [eGFR], urinary albumin/creatinine ratio [UACR]). In addition, we also re¬corded the patients' demographic parameters and drug therapy details. Results: More than one half of diabetic patients (58%) exhibited elevated serum zonulin levels compared to nondiabetic controls. Regression analyses showed a significant positive correlation of zonulin concentrations to BMI and HbA1c, but not to insulin resistance or lipids. A significant positive correlation was found between zonulin and eGFR, alongside a significantly negative correlation to proteinuria (UACR). Taking several confounders into consideration, UACR remained an independent factor of influence on the zonulin concentration. Conclusion: An impaired IB was found in the majority of the diabetic patients even after a long-term duration of the disorder. Whether the detected positive associations between the zonulin concentration and HbA1c as well as BMI are reasons or consequences of the impaired IB must be investigated further in longitudinal studies. The correlations between circulating zonulin and parameters of kidney function demonstrated here for the first time may indicate that zonulin has effects in other organs too that have to be clarified in further studies.

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Section: Discussionsupporting

confidence: 91%

Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function

Hasslacher¹

2018

JDMDC

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“…Zonulin is considered to be a valid biomarker of tight junction integrity of the gut in various diseases 22 , 23 . In ESRD elevated serum zonulin levels have been demonstrated by others and linked to inflammation and metabolic diseases 24 , 25 . No data on faecal zonulin or calprotectin levels in ESRD could be found in literature.…”

Section: Discussionmentioning

confidence: 89%

Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis

Stadlbauer

Horvath

Ribitsch

et al. 2017

Sci Rep

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Complications of end-stage renal disease (ESRD) are critically related to inflammation. The gut microbiome is a key driver of inflammation. Since dialysis modalities may differently influence the gut microbiome, we aimed to compare the effects of haemodialysis (HD) and peritoneal dialysis (PD) on patients’ gut microbiome composition and function. We therefore studied faecal microbiome composition and function as well as inflammation and gut permeability in 30 patients with ESRD (15 HD, 15 PD) and compared to 21 healthy controls. We found an increase in potentially pathogenic species and a decrease in beneficial species in patients on HD and to a lesser extend in patients on PD when compared to controls. These changes in taxonomic composition also resulted in differences in predicted metagenome functions of the faecal microbiome. In HD but not in PD, changes in microbiome composition were associated with an increase in c-reactive protein (CRP) but not with intestinal inflammation or gut permeability. In conclusion microbiome composition in ESRD differs from healthy controls but also between modes of dialysis. These differences are associated with systemic inflammation and cannot completely be explained by dialysis vintage. The mode of renal replacement therapy seems to be an important driver of dysbiosis in ESRD.

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“…A previous study had shown a positive relationship between LPS and zonulin in T2DM [ 42 ]. Thus, increased zonulin levels allow more gut bacterial endotoxins and metabolites to cross the gut–membrane blood barrier into the circulatory system [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD

Al‐Obaide

Singh

Datta

et al. 2017

JCM

161

134

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Trimethylamine-N-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). The purpose of our study was to investigate the gut microbiota associated with trimethylamine (TMA) production, the precursor of TMAO, and the serum levels of TMAO and inflammatory biomarkers associated with type 2 diabetes mellitus (T2DM) and CKD. Twenty adults with T2DM and advanced CKD and 20 healthy adults participated in the study. Analyses included anthropometric and metabolic parameters, characterization of TMA producing gut microbiota, and concentrations of TMAO, lipopolysaccharides (LPS) endotoxin, zonulin (Zo) gut permeability marker, and serum inflammatory and endothelial dysfunction biomarkers. Diversity of the gut microbiota was identified by amplification of V3–V4 regions of the 16S ribosomal RNA genes and DNA sequencing. TMAO was quantified by Mass Spectrometry and serum biomarkers by ELISA. The significance of measurements justified by statistical analysis. The gut microbiome in T2DM-CKD patients exhibited a higher incidence of TMA-producing bacteria than control, p < 0.05. The serum levels of TMAO in T2DM-CKD patients were significantly higher than controls, p < 0.05. TMAO showed a positive correlation with Zo and LPS, inflammatory and endothelial dysfunction biomarkers. A positive correlation was observed between Zo and LPS in T2DM-CKD subjects. An increased abundance of TMA-producing bacteria in the gut microbiota of T2DM-CKD patients together with excessive TMAO and increased gut permeability might impact their risk for cardiovascular disease through elevation of chronic inflammation and endothelial dysfunction.

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Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation

Cited by 13 publications

References 0 publications

Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function

Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function

Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis

Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD

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