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Adipose Tissue-Derived Biomarkers of Intestinal Barrier Functions for the Characterization of Diarrhoea-Predominant IBS.

ABSTRACT: Background:Alterations of the small-intestinal permeability (s-IP) might play an essential role in a subgroup of diarrhoea-predominant IBS (D-IBS) patients. Goals:(a) To analyse in D-IBS patients the symptom profile in relation to the altered (+) or not (-) s-IP using the Gastrointestinal Symptom Rating Scale (GSRS). (b) To assess the circulating levels of the adipokines IL-6, IL-8, TNF-?, leptin, and adiponectin, along with LPS, TLR-4, neurotensin, and brain-derived neurotrophic factor (BDNF). The frequency distribution of SNPs at the loci for the investigated molecules and leptin receptor was evaluated. Study:The study included 34 D-IBS patients and 17 healthy controls (HC). s-IP permeability was assayed by high-performance liquid chromatography determination in the urine of the lactulose to mannitol ratio. Concentrations of IL-6, IL-8, TNF-?, LPS, TLR-4, leptin, adiponectin, neurotensin, and BDNF were assayed by ELISA. Screening of genetic variants was done employing the restriction fragment length polymorphism-polymerase chain reaction method. Results:D-IBS(-) patients had a significantly higher GSRS cluster pain and diarrhoea profile than D-IBS(+) ones. Significant correlations were found between the symptoms clusters and immune activation and inflammation markers. The levels of adipo(cyto)kines in D-IBS(+) patients were higher than those of controls, and IL-6 levels correlated with those of LPS. Leptin and BDNF were significantly higher, and neurotensin levels were significantly lower in D-IBS(+) than in controls. No differences were found in the frequency distribution of genotypes among the study groups. Conclusions:Results from this study could be of some help in the characterization of the D-IBS and highlight the contribution of an altered intestinal barrier in the pathogenesis of this syndrome. Besides, a role could be ascribed to molecules secreted by the visceral adipose tissue that can impact on barrier functions.

SUBMITTER: Russo F

PROVIDER: S-EPMC6304194 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Adipose Tissue-Derived Biomarkers of Intestinal Barrier Functions for the Characterization of Diarrhoea-Predominant IBS.

Russo Francesco F Chimienti Guglielmina G Riezzo Giuseppe G Linsalata Michele M D'Attoma Benedetta B Clemente Caterina C Orlando Antonella A

Disease markers 20181128

<h4>Background</h4>Alterations of the small-intestinal permeability (s-IP) might play an essential role in a subgroup of diarrhoea-predominant IBS (D-IBS) patients.<h4>Goals</h4>(<i>a</i>) To analyse in D-IBS patients the symptom profile in relation to the altered (+) or not (-) s-IP using the Gastrointestinal Symptom Rating Scale (GSRS). (<i>b</i>) To assess the circulating levels of the adipokines IL-6, IL-8, TNF-<i>α</i>, leptin, and adiponectin, along with LPS, TLR-4, neurotensin, and brain- ...[more]

PMID: 30622656

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Project description:BACKGROUND:Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(-)] increased s-IP according to normal or altered La/Ma ratio. METHODS:The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann-Whitney or the Kruskal-Wallis with Dunn's post-test was used to assess differences among the groups. RESULTS:As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(-) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(-) ones. CONCLUSIONS:The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population. TRIAL REGISTRATION:NCT01574209 . Registered March 2012. First recruitment started in April 2012.

Project description:BackgroundIrritable bowel syndrome (IBS) is characterised by gastrointestinal (GI) and psychological symptoms (e.g., depression, anxiety, and somatization). Depression and anxiety, but not somatization, have already been associated with altered intestinal barrier function, increased LPS, and dysbiosis. The study aimed to investigate the possible link between somatization and intestinal barrier in IBS with diarrhoea (IBS-D) patients.MethodsForty-seven IBS-D patients were classified as having low somatization (LS = 19) or high somatization (HS = 28) according to the Symptom Checklist-90-Revised (SCL-90-R), (cut-off score = 63). The IBS Severity Scoring System (IBS-SSS) and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were administered to evaluate GI symptoms. The intestinal barrier function was studied by the lactulose/mannitol absorption test, faecal and serum zonulin, serum intestinal fatty-acid binding protein, and diamine oxidase. Inflammation was assessed by assaying serum Interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-α. Dysbiosis was assessed by the urinary concentrations of indole and skatole and serum lipopolysaccharide (LPS). All data were analysed using a non-parametric test.ResultsThe GI symptoms profiles were significantly more severe, both as a single symptom and as clusters of IBS-SSS and GSRS, in HS than LS patients. This finding was associated with impaired small intestinal permeability and increased faecal zonulin levels. Besides, HS patients showed significantly higher IL-8 and lowered IL-10 concentrations than LS patients. Lastly, circulating LPS levels and the urinary concentrations of indole were higher in HS than LS ones, suggesting a more pronounced imbalance of the small intestine in the former patients.ConclusionsIBS is a multifactorial disorder needing complete clinical, psychological, and biochemical evaluations.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03423069 .

Dataset Information

Adipose Tissue-Derived Biomarkers of Intestinal Barrier Functions for the Characterization of Diarrhoea-Predominant IBS.

Publications

Adipose Tissue-Derived Biomarkers of Intestinal Barrier Functions for the Characterization of Diarrhoea-Predominant IBS.

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