An Observational Study to Evaluate the Association between Intestinal Permeability, Leaky Gut Related Markers, and Metabolic Health in Healthy Adults

We explored whether metabolic health is linked to intestinal permeability, using a multi-sugar (MS) permeability test, and whether intestinal permeability is correlated with the leaky gut-related markers (LGM) zonulin, LBP, and sCD14. Metabolically healthy (n = 15) and unhealthy subjects (n = 15) were recruited based on waist circumference, fasting glucose, and high-density lipoprotein cholesterol levels. Participants underwent an MS permeability test that assessed site-specific permeabilities of the gastroduodenum and small and large intestines. The test was performed with/without an acetylsalicylic acid challenge to measure and correlate the gut permeability, LGM, and metabolic health. At baseline, metabolic health showed no correlation with gut permeability. Significant correlations were found between the metabolic health parameters and LGM. In the acetylsalicylic acid challenged MS permeability test, low-density lipoprotein cholesterol was correlated with the sucralose/erythritol ratio, reflecting the whole intestinal permeability. Correlations between most metabolic health parameters and LGM during the acetylsalicylic acid challenge were less pronounced than at baseline. In both MS permeability tests, no significant correlations were found between LGM (plasma and serum) and gut permeability. Thus, correlations between LGM and metabolic health might not be linked with paracellular gut permeability. Transcellular translocation and/or lipoprotein-related transportation is a more likely mechanism underlying the association between LGM and metabolic health.

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Exploring the Link between Leaky-Gut-Related Markers and Metabolic Health in a Large Dutch Adult Population

Metabolites ◽

10.3390/metabo11120877 ◽

2021 ◽

Vol 11 (12) ◽

pp. 877

Author(s):

Hiroyuki Hoshiko ◽

Edith J. M. Feskens ◽

Els Oosterink ◽

Renata M. C. Ariens ◽

Jurriaan J. Mes ◽

...

Keyword(s):

Chronic Inflammation ◽

Metabolic Diseases ◽

Inflammatory Marker ◽

Adult Population ◽

Large Population ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Metabolic Health ◽

Leaky Gut ◽

Health Parameters

A leaky gut can trigger chronic inflammation and poses a primary risk for metabolic diseases. This study established a relationship between intestinal integrity (leaky gut) and metabolic health in a general population. Leaky-gut markers (LGMs) were studied in a large population of Dutch adults with a broad spectrum of metabolic health. This study enrolled 500 individuals selected within the NQplus cohort study (n = 2048) by stratified randomization, based on waist circumference, fasting glucose, and high-density lipoprotein (HDL) cholesterol to obtain a representative and balanced population in terms of metabolic health parameters, sex (male/female), and age (<54/≥54 years). LGMs—zonulin, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14)—were measured in EDTA plasma or serum. Zonulin was most strongly associated with metabolic health. Zonulin and LBP were most strongly associated with the inflammatory marker C-reactive protein (CRP). The quartile analysis for zonulin and LBP showed that most metabolic health parameters and CRP levels increased from Q1 to Q4, with significant differences between quartiles, except for markers related to glucose homeostasis (glucose and glycated hemoglobin A1c (HbA1c)). Associations between LGMs and metabolic health parameters in this large Dutch adult population indicate that LGMs are valuable markers for identifying people at risk of a leaky gut and subsequent chronic inflammation linked to metabolic disorders.

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Dysmetabolic features of the overweight patients receiving antipsychotic drugs: A comparison with normal weight and obese subjects

European Psychiatry ◽

10.1016/j.eurpsy.2012.12.001 ◽

2014 ◽

Vol 29 (3) ◽

pp. 179-182 ◽

Cited By ~ 3

Author(s):

P. Manu ◽

C.-U. Correll ◽

M. Wampers ◽

R. van Winkel ◽

W. Yu ◽

...

Keyword(s):

Metabolic Syndrome ◽

Antipsychotic Drugs ◽

Hemoglobin A1c ◽

Density Lipoprotein ◽

Tolerance Test ◽

Normal Weight ◽

Metabolic Health ◽

Lipoprotein Cholesterol ◽

Oral Glucose ◽

Post Challenge

AbstractBackground:Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI = 25–29.9) without metabolic syndrome or diabetes has not been thoroughly investigated.Objective:To assess the metabolic health of overweight patients receiving antipsychotic drugs.Methods:We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes.Results:Compared with the normal weight subjects (n = 286), overweight patients (n = 212) had higher fasting insulin resistance as assessed with the homeostatic model (P = 0.023), insulin secretion during the oral glucose tolerance test (P = 0.0037), triglycerides (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0089), and lower levels of high-density lipoprotein cholesterol (P = 0.0014). The obese (n = 50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P = 0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups.Conclusions:Overweight (BMI = 25–29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.

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Effect of Jianpi Qinghua Decoction on Gut Microbiota, Intestinal Permeability and Glycolipid Metabolism in Newly Diagnosed T2DM Patients: Study Protocol for a Randomized, Double-blind, Placebo-controlled Clinical Trial

10.21203/rs.3.rs-633298/v1 ◽

2021 ◽

Author(s):

Shenyi Jin ◽

Sheng Zhang ◽

Qingguang Chen ◽

Xu Han ◽

Yahua Liu ◽

...

Keyword(s):

Clinical Trial ◽

Gut Microbiota ◽

Intestinal Permeability ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Postprandial Blood Glucose ◽

Controlled Clinical Trial ◽

Newly Diagnosed ◽

Double Blind ◽

Double Blind Placebo

Abstract BackgroundThe gut microbiome is a key target for traditional Chinese medicines (TCM) to ameliorate type 2 diabetes mellitus (T2DM). Patients with T2DM have quite distinct gut microbiota in comparisons with normal individuals, and it directly influences intestinal permeability. This study aims to investigate the underlying effects of Jianpi Qinghua Decoction on gut microbiota and intestinal permeability in newly diagnosed T2DM patients.Methods / designThis study is a single-center, randomized, double-blind, placebo-controlled clinical trial in 120 subjects with newly diagnosed T2DM. The patients will be randomized in a 1:1 ratio into placebo group (1/10 Jianpi Qinghua Decoction + maltodextrin twice daily, n = 60) and treatment group (Jianpi Qinghua Decoction twice daily, n = 60). The study drugs will be double blinded to both investigators and participants. The visits will be done at baseline (visit 0), 1 month (visit 1), 2 months (visit 2), 3 months (visit 3). Measures include: anthropometric measures, blood pressure, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG) and serum insulin, total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL), safety indexs (including blood routine examination, clinical urine tests, liver/renal profile), identifying intestinal permeability used ELISA testing serum LPS, serum intestinal fatty acid binding protein (IFABP), serum Zonulin concentrations and fecal sample collection for gut microbiota profiling through 16S rRNA gene sequencing. Data will be analyzed using SPSS version 26. DiscussionWe describe a clinical research protocol evaluating the impact of Jianpi Qinghua Decoction on gut microbiota and intestinal permeability in newly diagnosed T2DM patients. We assume that adminstration of Jianpi Qinghua Decoction will correct gut microbial dysbiosis and intestinal permeability, leading to improved glycemic control.Trial registrationChinese clinical trial registry, identifier: ChiCTR2000039423（http://www.chictr.org.cn/edit.aspx?pid=62537&htm=4.）.Registered on 27 October 2020.

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Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666181115100610 ◽

2018 ◽

Vol 18 (19) ◽

pp. 1641-1655 ◽

Cited By ~ 13

Author(s):

Denitsa Simeonova ◽

Mariya Ivanovska ◽

Mariana Murdjeva ◽

Andre F. Carvalho ◽

Michael Maes

Keyword(s):

Intestinal Permeability ◽

Clinical Chemistry ◽

Bacterial Overgrowth ◽

Chronic Fatigue ◽

Secretory Iga ◽

Leaky Gut ◽

Gut Permeability ◽

Gut Dysbiosis ◽

Medical Disorders ◽

Molecular Immunology

Background: Increased intestinal permeability with heightened translocation of Gramnegative bacteria, also known as “leaky gut”, is associated with the pathophysiology of neuroimmune disorders, such as Major Depressive Disorder (MDD), Chronic Fatigue Syndrome (CSF) and (deficit) schizophrenia, as well as with general medical disorders, including irritable bowel syndrome. This review aims to summarize clinical biochemistry and molecular immunology tests that may aid in the recognition of leaky gut in clinical practice. <p> Methods: We searched online libraries, including PubMed/MEDLINE, Google Scholar and Scopus, with the key words “diagnosis” or “biomarkers” and “leaky gut”, “bacterial translocation”, and “intestinal permeability” and focused on papers describing tests that may aid in the clinical recognition of leaky gut. <p> Results: To evaluate tight junction barrier integrity, serum IgG/IgA/IgM responses to occludin and zonulin and IgA responses to actomyosin should be evaluated. The presence of cytotoxic bacterial products in serum can be evaluated using IgA/IgM responses to sonicated samples of common Gram-negative gut commensal bacteria and assays of serum lipopolysaccharides (LPSs) and other bacterial toxins, including cytolethal distenting toxin, subunit B. Major factors associated with increased gut permeability, including gut dysbiosis and yeast overgrowth, use of NSAIDs and alcohol, food hypersensitivities (IgE-mediated), food intolerances (IgG-mediated), small bacterial overgrowth (SIBO), systemic inflammation, psychosocial stressors, some infections (e.g., HIV) and dietary patterns, should be assessed. Stool samples can be used to assay gut dysbiosis, gut inflammation and decreased mucosal defenses using assays of fecal growth of bacteria, yeast and fungi and stool assays of calprotectin, secretory IgA, β-defensin, α- antitrypsin, lysozyme and lactoferrin. Blood and breath tests should be used to exclude common causes of increased gut permeability, namely, food hypersensitivities and intolerances, SIBO, lactose intolerance and fructose malabsorption. <p> Discussion: Here, we propose strategies to recognize “leaky gut” in a clinical setting using the most adequate clinical chemistry and molecular immunology assays.

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Elevated high density lipoprotein cholesterol and low grade systemic inflammation is associated with increased gut permeability in normoglycemic men

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/j.numecd.2018.07.006 ◽

2018 ◽

Vol 28 (12) ◽

pp. 1296-1303 ◽

Cited By ~ 4

Author(s):

M.D. Robertson ◽

C. Pedersen ◽

P.J. Hinton ◽

A.S.J.R. Mendis ◽

P.D. Cani ◽

...

Keyword(s):

High Density Lipoprotein ◽

Systemic Inflammation ◽

High Density Lipoprotein Cholesterol ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Low Grade ◽

Gut Permeability

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Identification of leaky gut-related markers as indicators of metabolic health in Dutch adults: The Nutrition Questionnaires plus (NQplus) study

PLoS ONE ◽

10.1371/journal.pone.0252936 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252936

Author(s):

Hiroyuki Hoshiko ◽

Edith J. M. Feskens ◽

Els Oosterink ◽

Renata M. C. Ariens ◽

Jurriaan J. Mes ◽

...

Keyword(s):

Cohort Study ◽

Bacterial Translocation ◽

Metabolic Diseases ◽

Metabolic Health ◽

Leaky Gut ◽

C Reactive Protein ◽

Gamma Glutamyl Transpeptidase ◽

Protein Levels ◽

Reactive Protein ◽

Health Parameters

Background and aim Chronic inflammation is a primary risk factor for chronic metabolic disease and may be triggered by a “leaky gut.” Several biomarkers have been recognized to indicate intestinal permeability (i.e., leaky gut) and bacterial translocation. Nonetheless, which of these biomarkers exhibit the highest correlation with metabolic health parameters remains unclear. Hence, this study aimed to explore the correlation between leaky gut-related markers and metabolic health. Methods Based on waist circumference, plasma fasting glucose, plasma gamma-glutamyl transpeptidase (GGT), and plasma LDL cholesterol, two groups of 40 subjects with the most extreme metabolic health profiles were selected from the NQplus cohort study (n = 2048), which was previously conducted by the Wageningen University’s Division of Human Nutrition. Eight potential leaky gut-related markers were selected from the literature and measured in serum or EDTA plasma samples of these selected individuals. These samples were also obtained from the NQplus cohort study. Results From the leaky gut markers, levels of zonulin, lipopolysaccharide-binding protein, soluble CD14, bactericidal/permeability-increasing protein, and peptidoglycan were significantly higher in individuals with unhealthy metabolic profiles (p<0.05). No differences in EndoCAb IgM, EndoCAb IgA, and EndoCAb IgG were observed between healthy and unhealthy individuals. Stepwise regression analysis revealed that zonulin was substantially associated with metabolic health parameters such as BMI, blood glucose, triglyceride, GGT, and C-reactive protein levels. C-reactive protein, an inflammation marker, showed the most pronounced association with zonulin. Conclusions Biomarkers that link a leaky gut and subsequent bacterial translocation to metabolic health were identified in this study. Especially zonulin may aid in monitoring a leaky gut and detecting individuals at risk for developing chronic metabolic diseases.

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Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽

10.1024/0301-1526/a000348 ◽

2014 ◽

Vol 43 (3) ◽

pp. 189-197 ◽

Cited By ~ 10

Author(s):

Yiqiang Zhan ◽

Jinming Yu ◽

Rongjing Ding ◽

Yihong Sun ◽

Dayi Hu

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

High Density Lipoprotein Cholesterol ◽

Ankle Brachial Index ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Cholesterol Ratio ◽

Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

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