An Observational Study to Evaluate the Association between Intestinal Permeability, Leaky Gut Related Markers, and Metabolic Health in Healthy Adults.
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ABSTRACT:
SUBMITTER: Hoshiko H
PROVIDER: S-EPMC8623210 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundOral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion.AimsThe aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D).MethodsSixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose.ResultsBaseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D.ConclusionsBaseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.
| S-EPMC8328885 | biostudies-literature
Project description:Background and aimsThe barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose.MethodsHealthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points.ResultsThe final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination.ConclusionsThis study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm our finding.
| S-EPMC5391961 | biostudies-literature
Project description:The pathogenesis of inflammatory bowel disease (IBD) is multifactorial with data suggesting the role of a disturbed interaction between the gut and the intestinal microbiota. A defective mucosal barrier may result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological response that promotes intestinal inflammation. IBD patients display several defects in the many specialized components of mucosal barrier, from the mucus layer composition to the adhesion molecules that regulate paracellular permeability. These alterations may represent a primary dysfunction in Crohn's disease, but they may also perpetuate chronic mucosal inflammation in ulcerative colitis. In clinical practice, several studies have documented that changes in intestinal permeability can predict IBD course. Functional tests, such as the sugar absorption tests or the novel imaging technique using confocal laser endomicroscopy, allow an in vivo assessment of gut barrier integrity. Antitumor necrosis factor-? (TNF-?) therapy reduces mucosal inflammation and restores intestinal permeability in IBD patients. Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction but their use is still limited and further studies are needed before considering permeability manipulation as a therapeutic target in IBD.
| S-EPMC4637104 | biostudies-other
Project description:Injuries and subclinical effects from exposure to blasts are of significant concern in military operational settings, including tactical training, and are associated with self-reported concussion-like symptomology and physiological changes such as increased intestinal permeability (IP), which was investigated in this study. Time-series gene expression and IP biomarker data were generated from "breachers" exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre-, post-, and follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and taking longer to think, dissipating ~16 h following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p = 0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n = 23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mild traumatic brain injury and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive functioning. These preliminary findings show for the first time within real-world military operational settings that exposures to blast can contribute to IP.
| S-EPMC10971443 | biostudies-literature
Project description:Background and aimChronic 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.MethodsBased 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.ResultsFrom 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.ConclusionsBiomarkers 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.
| S-EPMC8177645 | biostudies-literature
Project description:Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.
| S-EPMC4210345 | biostudies-literature
Project description: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.
| S-EPMC8706458 | biostudies-literature
Project description:Constant remodeling of tight junctions to regulate trans-epithelial permeability is essential in maintaining intestinal barrier functions and thus preventing diffusion of small molecules and bacteria to host systemic circulation. Gut microbiota dysbiosis and dysfunctional gut barrier have been correlated to a large number of diseases such as obesity, type 2 diabetes and inflammatory bowel disease. This led to the hypothesis that gut bacteria-epithelial cell interactions are key regulators of epithelial permeability through the modulation of tight junctions. Nevertheless, the molecular basis of host-pathogen interactions remains unclear mostly due to the inability of most in vitro models to recreate the differentiated tissue structure and components observed in the normal intestinal epithelium. Recent advances have led to the development of a novel cellular model derived from intestinal epithelial stem cells, the so-called organoids, encompassing all epithelial cell types and reproducing physiological properties of the intestinal tissue. We summarize herein knowledge on molecular aspects of intestinal barrier functions and the involvement of gut bacteria-epithelial cell interactions. This review also focuses on epithelial organoids as a promising model for epithelial barrier functions to study molecular aspects of gut microbiota-host interaction.
| S-EPMC7503654 | biostudies-literature
Project description:Abstract It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross-sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12-h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low-grade inflammation defined by high-sensitivity C-reactive protein ?1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P = 0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low-grade inflammation or presence of noninsulin-dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low-grade inflammation alone (P = 0.043) or type 2 diabetes alone (P = 0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low-grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier.
| S-EPMC4001874 | biostudies-literature
Project description:BackgroundMetabolic diseases have been related to gut microbiota, and new knowledge indicates that diet impacts host metabolism through the gut microbiota. Identifying specific gut bacteria associated with both diet and metabolic risk markers may be a potential strategy for future dietary disease prevention. However, studies investigating the association between the gut microbiota, diet, and metabolic markers in healthy individuals are scarce.ObjectiveWe explored the relationship between a panel of gut bacteria, dietary intake, and metabolic and anthropometric markers in healthy adults.DesignForty-nine volunteers were included in this cross-sectional study. Measures of glucose, serum triglyceride, total cholesterol, hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) were collected after an overnight fast, in addition to fecal samples for gut microbiota analyzes using a targeted approach with a panel of 48 bacterial DNA probes and assessment of dietary intake by a Food Frequency Questionnaire (FFQ). Correlations between gut bacteria, dietary intake, and metabolic and anthropometric markers were assessed by Pearson's correlation. Gut bacteria varying according to dietary intake and metabolic markers were assessed by a linear regression model and adjusted for age, sex, and BMI.ResultsOf the 48 gut bacteria measured, 24 and 16 bacteria correlated significantly with dietary intake and metabolic and/or anthropometric markers, respectively. Gut bacteria including Alistipes, Lactobacillus spp., and Bacteroides stercoris differed according to the intake of the food components, fiber, sodium, saturated fatty acids, and dietary indices, and metabolic markers (BP and total cholesterol) after adjustments. Notably, Bacteroides stercoris correlated positively with the intake of fiber, grain products, and vegetables, and higher Bacteroides stercoris abundance was associated with higher adherence to Healthy Nordic Food Index (HNFI) and lower diastolic BP after adjustment.ConclusionOur findings highlight the relationship between the gut microbiota, diet, and metabolic markers in healthy individuals. Further investigations are needed to address whether these findings are causally linked and whether targeting these gut bacteria can prevent metabolic diseases.
| S-EPMC9250133 | biostudies-literature