To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD).
Caecal biopsies were ...collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grade inflammation was evaluated by counting cells, including intraepithelial lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and protein expression of tumour necrosis factor (TNF)-α in biopsies and culture supernatants.
IBS-like symptoms were present in 35.4 and 38% of CD and UC patients, respectively. Paracellular permeability was significantly increased in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01, respectively). Significantly lower expression of ZO-1 and α-catenin was detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-α were significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS.
In quiescent IBD, IBS-like symptoms related to persistent subclinical inflammation associated with increased colonic paracellular permeability. A persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects associated with abdominal pain in quiescent IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered in quiescent IBD with IBS-like symptoms.
Growing evidence suggests that patients with irritable bowel syndrome (IBS) have increased intestinal permeability. In addition, mucosal soluble mediators are involved in the pathophysiology of pain ...in IBS. We aimed to investigate (1) paracellular permeability in colonic biopsies of patients with IBS; and (2) the ability of soluble factors from colonic biopsies to reproduce these alterations in vitro.
Paracellular permeability in colonic biopsies of healthy subjects and patients with IBS was measured by mounting the biopsies in Ussing chambers. Cleared supernatant (SUP) of the culture from colonic biopsies was collected and applied to Caco-2 cells for 48 h. Paracellular permeability and transepithelial resistance (TER) were evaluated. mRNA expression of the tight junction proteins, zonula occludens (ZO)-1 and occludin, was assessed in colonic biopsies. Abdominal pain was assessed using a validated questionnaire.
Permeability of colonic biopsies was significantly higher in patients with IBS compared to healthy subjects. These changes were associated with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy subjects. SUP-induced increased paracellular permeability correlated with the severity of abdominal pain.
Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS patients. These findings might pave the way both to identify novel biomarkers as well as new therapeutic targets in IBS.
Recent evidence suggests a role for increased colonic permeability and mucosal mast cell (MC) mediators on symptoms related to the irritable bowel syndrome (IBS). Whether allergic factors (AFs) are ...involved in the pathophysiology of IBS is unclear. We addressed the question of the possible influence of an allergic background on IBS symptoms.
We assessed paracellular permeability, mucosal MCs counts, and spontaneous release of tryptase of colonic biopsy specimens in 34 IBS patients and 15 healthy subjects. The severity of IBS was assessed through self-reported questionnaires. All individuals were tested for the presence of AF, including self-perception of adverse reaction to food, personal and familial history of atopic disease, elevated total or specific immunoglobulin E against food/inhalant antigens, blood eosinophilia, and skin tests.
IBS patients had significant enhanced colonic permeability, higher number of MCs, and spontaneous release of tryptase than healthy subjects. The severity of IBS was significantly correlated with colonic permeability (r=0.48, P=0.004), MCs counts (r=0.36, P=0.03), and tryptase (r=0.48, P=0.01). In 13 IBS patients (38.2%) having at least three AFs, symptoms scores, colonic permeability, MCs counts, and tryptase release by colonic biopsies were significantly higher than in those with less than three AFs. IBS patients with at least three AFs were more prone to diarrhea or alternating symptoms. None AF was found to be predictive of IBS severity.
In IBS patients, the presence of an allergic background correlates with a more severe disease and diarrhea predominance, possibly by enhancing mucosal MC activation and paracellular permeability.
Background Patients with irritable bowel syndrome (IBS) and Crohn disease (CD) have impaired quality of life (Qol) associated with fatigue. Whether IBS‐like symptoms have a similar impact on Qol and ...fatigue in quiescent CD than in IBS is currently unknown. Our aims were (i) to evaluate the prevalence of IBS‐like symptoms in quiescent CD and (ii) to compare the impact of IBS‐like symptoms on Qol and fatigue in both diseases.
Methods A total of 92 quiescent CD, 40 IBS and 20 healthy subjects similar in age were included prospectively in five French academic centers. IBS symptoms were evaluated through the Rome III criteria. The severity of IBS symptoms, Qol, fatigue, depression and anxiety was measured using questionnaires (Francis Score, Likert scales, Fatigue Impact Scale, short‐form Beck and Hospital Anxiety and Depression Scale).
Key Results Irritable bowel syndrome‐like symptoms were found in 42/92 (45.6%) patients with quiescent CD. The presence of IBS‐like symptoms was associated with significant more profound alterations of Qol, high scores of fatigue, depression, but similar levels of anxiety. Compared to CD patients with IBS‐like symptoms, IBS patients had more severe gastrointestinal symptoms and alterations of Qol, but similar scores of fatigue, depression and anxiety. In quiescent CD patients, fatigue was independently associated with the presence of IBS‐like symptoms (OR = 1.018, 95% CI: 1.002–1.034, P = 0.02).
Conclusions & Inferences The prevalence of IBS‐like symptoms is elevated in quiescent CD. The presence of IBS‐like symptoms in quiescent CD is probably associated with the range of fatigue/depression disorders. The mechanism underlying the occurrence of IBS‐like symptoms in quiescent CD needs to be further explored.
A subset of patients with irritable bowel syndrome (IBS) have an increased number of mast cells (MCs) in the colonic mucosa. Psychological factors are believed to contribute to the course of IBS.
To ...examine associations between fatigue, depression and MCs of the colonic mucosa in IBS.
Colonic biopsies were taken from 50 Rome II IBS patients, 21 healthy controls and 11 depressed/fatigued patients without IBS. The cellularity of the lamina propria was determined as the number of inflammatory cells per high power field (hpf) through a 400x microscope. The Fatigue Impact Scale (FIS) and the short form Beck Depression Inventory (BDI) evaluated the severity of fatigue and depression.
IBS patients had a significant increase in the cellularity of the lamina propria compared with controls or with depressed patients (mean (SD) 94.5 (48-110) vs 68 (58-82) and 78 (87-90) cells per hpf, p = 0.005 and p = 0.05, respectively), in particular of MCs (9.3 (5.6-11.7) vs 4.0 (2.7-6.8) and 4.3 (2.8-7.8) cells per hpf, p = 0.001 and p = 0.005, respectively). Both the FIS and BDI scores were significantly higher in IBS or in depressed patients than in controls (p<0.001). In IBS, the FIS score correlated significantly with the cellularity of the lamina propria (r = 0.51, p<0.0001) and MCs (r = 0.64, p<0.0001). In IBS, the BDI score correlated significantly with MCs (r = 0.29, p = 0.03).
Elevated MCs counts are a key feature of the low-grade inflammatory infiltrate in the caecal mucosa of IBS. Fatigue and depression are associated with mucosal cell counts, in particular MCs, suggesting that psychological factors are associated with the low-grade inflammatory infiltrate in IBS.
Background: Patients describe that body posture may affect their abdominal bloating, distension, and flatulence, but whether changes in position have objectively demonstrable effects, either ...beneficial or deleterious, has not been investigated. Aim: To determine the effect of body posture, upright versus supine, on intestinal transit of gas loads. Subjects: Eight healthy subjects without gastrointestinal symptoms. Methods: In each subject a gas mixture was continuously infused into the jejunum (12 ml/min) for three hours, and gas evacuation, clearance of a non- absorbable gaseous marker, perception, and abdominal girth were measured. Paired studies were randomly performed in each subject on separate days in the upright and supine positions. Results: In the upright position, intestinal gas retention was much smaller than when supine (13 (52) ml v 146 (75) ml retention at 60 minutes, respectively; p<0.05), and clearance of the gas marker was expedited (72 (10)% clearance v 49 (16)% at 60 minutes, respectively; p<0.05). The gas challenge test was well tolerated both in the upright and supine positions without abdominal distension. Conclusion: Body posture has a significant influence on intestinal gas propulsion: transit is faster in the upright position than when supine.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of "intestinal" food allergies or intolerance. The aim of this study was to characterize the clinical ...features of IBS patients suspected of suffering from adverse reactions to food.
The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation at our outpatient clinic. A detailed medical history was recorded, paying particular attention to any allergies and reported intolerance to food. Each patient was screened for allergies; intestinal permeability tests was performed in randomly selected patients from different groups. Findings were analyzed using the chi2 test.
Adverse reactions to one or more foods were reported by 80 patients (62.5%); skin prick tests (SPT) were positive in 67 patients (52.3%) with no significant differences between patients complaining of different symptoms. Patients who reported a food intolerance had more positive SPTs than those who did not (47 of 80 58.7% vs 20 of 48 41.7%); this difference was not statistically significant, although it suggests a trend (p < 0.0610). There was little consistency between the specific foods reported to cause intolerance and those resulting from the tests (11 of 80 patients, 13.7%). The intestinal permeability test was normal in 29 of 33 patients (87.9%).
More than 50% of IBS patients were found sensitized to some food or inhalant without any typical clinical signs. Patients were unable to identify potentially offending foods. The lack of a correlation between SPT results and reported food allergies needs further investigation to clarify the pathophysiology and improve the diagnosis of intestinal food allergies.
To determine the effects of mild physical activity on intestinal gas transit and clearance.
In 8 healthy adults, a gas mixture was infused continuously into the jejunum (12 mL/min) for 120 minutes ...with simultaneous duodenal lipid perfusion (1 kcal/min). Gas evacuation, perception of abdominal sensations (on a scale of 0 none to 6 pain), and abdominal girth were measured at 15-minute intervals during rest and intermittent pedalling, with subjects in a supine position.
Mean (± SD) intestinal gas retention was lower during exercise than at rest (−84 ± 303 mL vs. 143 ± 219 mL,
P <0.05). Gas retention during rest was associated with significant abdominal distension (8 ± 6 mm,
P <0.01 vs. basal), which was decreased with exercise (3 ± 7 mm,
P <0.05 vs. rest). The gas challenge test was well tolerated both during exercise and rest (perception score: 0.6 ± 0.5 vs. 0.9 ± 0.4,
P = 0.25).
In healthy subjects, gut transit of intraluminal gas is enhanced by mild physical activity.
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