Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Undseth, Ragnhild; Berstad, Arnold; Valeur, Jørgen

doi:10.3892/mmr.2016.5878

Cited by 8 publications

(11 citation statements)

References 29 publications

(33 reference statements)

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“…Available reports in the literature are contrasting. Recently, some authors tried to correlate the circulating levels of LPS, the LPS coreceptor soluble cluster of differentiation (sCD), monocyte chemoattractant protein 1 (MCP 1), intestinal fatty acid binding protein (IFABP), and calprotectin with the symptom scores calculated by the IBS Severity Scoring System, but they failed in identifying any associations [25]. In fact, in agreement with this report, we found no correlation between LPS and symptoms.…”

Section: Discussionsupporting

confidence: 83%

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

et al. 2018

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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-α, 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-α, 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.

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Section: Discussionsupporting

confidence: 83%

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

et al. 2018

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“…Based on the theory of increased gut permeability and low-grade inflammation as a central contributor to IBS etiology, several studies have compared a broad range of gut integrity markers and inflammatory markers in IBS patients to healthy controls, aiming to identify possible biomarkers. To date, the findings have been inconsistent, but a reported tendency has been altered levels of gut integrity markers [24,26,38] and higher levels of pro-inflammatory cytokines [39,40,41] in IBS patients compared to healthy controls. Interestingly, of the analyzed cytokines, only IL-8 showed values within a detectable range at baseline, suggesting that neither IL-4, IL-6, IL-10, TNF-α or INF-γ are relevant as inflammatory markers for our IBS population with predominant diarrhea or mixed bowel habits.…”

Section: Discussionmentioning

confidence: 99%

“…A chronic low-grade mucosal inflammation and increased intestinal permeability have been assumed to contribute to symptom generation in IBS patients, and several gut integrity markers have been investigated as potential biomarkers. These include zonulin, a physiologic regulator of intercellular tight junctions and suggested as a marker for impaired gut-barrier function [24]; lipopolysaccharide-binding protein (LBP), an acute phase protein suggested as a marker of bacterial translocation [25] and an intestinal fatty acid binding protein (iFABP), a marker for intestinal epithelial cell damage [26]. The clinical implications of these gut integrity markers in IBS have not been established.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome

et al. 2019

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Peptides from fish may beneficially affect several metabolic outcomes, including gut health and inflammation. The effect of fish peptides in subjects with irritable bowel syndrome (IBS) has not previously been investigated, hence this study aimed to evaluate the effect of a cod protein hydrolysate (CPH) supplement on symptom severity, gut integrity markers and fecal fermentation in IBS-patients. A double-blind, randomized parallel-intervention with six weeks of supplementation with 2.5 g CPH (n = 13) or placebo (n = 15) was conducted. The outcomes were evaluated at baseline and the end of the study. The primary outcomes were symptom severity evaluated by the IBS severity scoring system (IBS-SSS) and quality of life. The secondary outcomes included gut integrity markers and pro-inflammatory cytokines in serum, fecal fermentation measured by concentration of short-chain fatty acids (SCFAs) and fecal calprotectin. The groups were comparable at baseline. The total IBS-SSS-scores were reduced in both the CPH-group (298 ± 69 to 236 ± 106, p = 0.081) and the placebo-group (295 ± 107 to 202 ± 103, p = 0.005), but the end of study-scores did not differ (p = 0.395). The concentrations of serum markers and SCFAs did not change for any of the groups. The baseline measures for the whole group showed that the total SCFA concentrations were inversely correlated with the total IBS-SSS-score (r = −0.527, p = 0.004). Our study showed that a low dose of CPH taken daily by IBS-patients for six weeks did not affect symptom severity, gut integrity markers or fecal fermentation when compared to the placebo group.

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“…24 Undseth et al found a significantly lower level of I-FABP in patients with IBS compared with HC, but the study was again limited by small sample size (67 subjects). 25 To address these gaps in our knowledge of the role of altered IP in IBS, we compared serum zonulin and I-FABP levels in patients with IBS-D and IBS-C with that in HC and patients with increased permeability due to active celiac disease.…”

Section: Introductionmentioning

confidence: 99%

Serum zonulin is elevated in IBS and correlates with stool frequency in IBS‐D

et al. 2019

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Background: Studies have shown increased intestinal permeability in irritable bowel syndrome. Validating serum biomarkers for altered intestinal permeability in irritable bowel syndrome will facilitate research and pathophysiology-based therapy. Objective: To measure serum zonulin and intestinal fatty acid binding protein levels in diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome and compare with healthy controls and celiac disease. Methods: Serum zonulin and intestinal fatty acid binding protein levels were measured using enzyme-linked immunosorbent assays in constipation-predominant irritable bowel syndrome (n ¼ 50), diarrhea-predominant irritable bowel syndrome (n ¼ 50), celiac disease (n ¼ 53) and healthy controls (n ¼ 42). Irritable bowel syndrome symptom severity was measured using the irritable bowel syndrome-symptom severity scale. Results: Patients with constipation-predominant irritable bowel syndrome and diarrhea-predominant irritable bowel syndrome had higher zonulin levels compared with healthy controls (p ¼ 0.006 and 0.009 respectively), which was comparable to those with active celiac disease. Although zonulin levels did not correlate with the overall irritable bowel syndrome symptom severity scale, it positively correlated with stool frequency per week (p ¼ 0.03) and dissatisfaction with bowel habits (p ¼ 0.007) in diarrhea-predominant irritable bowel syndrome. Patients with diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome had lower intestinal fatty acid binding protein levels compared with celiac patients (p ¼ 0.005 and p ¼ 0.047 respectively). Conclusion: Serum zonulin is upregulated in irritable bowel syndrome and the levels are comparable to those in celiac disease. Zonulin levels correlated with severity of bowel habits in diarrhea-predominant irritable bowel syndrome. Intestinal fatty acid binding protein levels in irritable bowel syndrome patients were not increased suggesting no significant increase in enterocyte death.

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Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Cited by 8 publications

References 29 publications

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

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

Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome

Serum zonulin is elevated in IBS and correlates with stool frequency in IBS‐D

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